okay so good morning everybody thank you for joining us again in our grand rounds and it’s a real pleasure for me to introduce Paul Paul’s become over the years a really good friend I have this long list you have titles of Paul which is very long I’ll give you some of them but Paul is he’s actually not a cardiologist he’s actually a biomedical engineer he one of the few biomedical Engineers who’s not just professor of biomedical engineering he’s also a professor in uh he’s a professor in integrated biology and Physiology and of the car School of man management at the University of Minnesota he serves on multiple boards um and his main research eras has really been translational systems speci physiology he’s trained over 200 graduate students post doctoral fellows and medical students authored almost 3 articles 100 book chapters five books um but maybe I’ll share something personal how I came to know Paul so I met Paul about 10 years ago and I traveled to his lab the University of Minnesota from I was living in in Italy and at that stage I was publishing Lots on coronary bations and stting and thought I I really understood the field really well and was a sort of thought leader in the field and then I went to Paul’s lab and for the first time I got to see what I actually did in patients I got to see inside an artery and how I was manipulating stance and putting Sten into a bation and that experience of spending a day in Paul’s lab impacted my clinical practice and I’ve always thought about that how someone who’s a biomedical engineer you know who I didn’t know about who is doing this work somewhere else that really affected what I do every day and since then I’ve gone to Paul’s lab multiple times I’ve taken some of our faculty and know Andrea manaf as we’ve all gone to work in P that to teach to to understand better how our devices interact with kic anatomy and Paul has really created a unique way that nobody else in the world has been able to do and recreate of how to visualize anatomy in a heart so for the Fells I would suggest you go online I sent you the link and see his his library of anatomy it for me whenever I want to understand how the mro Val works the TR Val I usually go look at one of Paul’s videos um but it’s not only impacted Interventional Cardiology if you in EP Luigi you know a lot of what you do now with leadless pacemakers with ablation and mapping comes from Paul’s lab because Paul works really closely with metronic and a lot of the work metronic does has done in’s that but he’s also done stuff on organ preservation and organ Transportation uh and maybe he’ll talk about that uh so for the fellas take one of the cards you with the visible hard lab there’s a QR code in the back and you can download some of the apps that Paul’s team have created I have them on my phone when I’m trying to understand te and different uh um positions of a te prob he has all these simulators that you can have on your phone and you can use them to really understand cardiac Anatomy they really incredible but Paul thank you for coming uh I haven’t really talked about your topic today because I learned about the black bears from you and I think this topic is really an area of great interest that I’m I’m GNA leave leave for you to tell our faculty about but once again thank you for taking the time it’s pleasure to have you thank you for the invite as well it’s been a pleasure to be here and it’s always fun to talk about the translational aspect of my work I’m actually a human physiologist by training and an animist uh but I do teach Environmental engineering and most the grand students in my lab are biomedical Engineers um but I have one of the coolest jobs on the planet because not all I do I get to do the reanimated hearts all the time actually do field work um couple weeks out of the year in middle of nowhere studying hibernating black beirs so I’m going to kind of try to combine both of those today I’m going to talk to you about the translational research I do and how that impacts what we do in in the lab and vice versa go back and forth talk about some hibernation physiology fairs are amazing animals and amazing hibernators and I’ll discuss some of that and they upregulate a whole bunch of hormones and burn fat during the winter and then we’re trying to make that translational back to uh clinical medicine and then you know study this pre- and post conditioning and how it could impact not only what we do in the lab hopefully clinical medicine so we do a lot of different things our lab it’s a large lab but basically we do things where we do our Target drug delivery we do preconditioning agents the parent cardial space um and that is done routinely in the lab we typically will do that for um every prep an hour before doing omega-3 fatty acids or um small flipid that’s based on the bear work and I’ll talk about that we do muscle Force studies and that’s I did muscle Force studies in hibernating BlackBerry as well as patients intensive care units do a lot of work on transplantation University of Minnesota it’s a rich history in transplantation medicine and research huge Outreach mission of the lab we do isolate tissue bath work biomechanics but still the centerpiece of the lab has been the visible Heart Project and we’ve collaborated with metronic on that for the last 27 plus years um all the different groups from you know Val stance um ablations pacing systems and see we are a preclinical research lab but we’re early we’re not a GP approved lab good laboratory practice so we get the early stuff try to I have a cool shop they bring me a novel concept or technology and I have to try to figure out how to do a study on it and to me that’s the fun part right and takes a lot of creativity and and intuition so the joke of the lab is I probably put in more cardiac devices than anybody in the world i’ probably broken more cardiac devices in the heart than anybody in the world because the early Concepts and you know we’ll try to clue them back together or weld them back together in the lab U but it’s really a team sport right so I have a huge lab uh we have a number of Staff here currently there’s uh eight phc students three Master students a couple posts have over 15 undergrad and volunteers which make us one of the larger Labs on campus and to me this is really the most important part of my job the coolest part of my job is training individuals and watching you know laun their careers and where they’re going and you know it’s it’s really them that keep the they’re the the Brain Trust um and keep me still at the U and still active I guess um so the visible Heart Project really started in ’96 and uh we got funding from metronic and basically um we were doing isolated kinea pig hearts and then a group from metronic and was my brother-in-law and Tim lasi said hey that’d be cool but if you could do that with a large meman heart we could Pace that’ be even better so we said why not and we started doing it and you know it’s just using a cardi ple buffer to stop the heart ulate all the great best um and then you can do a langor profusion mode or a whole four chamber working mode full functional mode of the heart so um you know it’s we kind of published that and been doing that continuously and then this was first described by Oscar langendorf who was a German physiologist from rostock in the you know late 1800s so it’s nothing new except we have all the cool technology and video and equipment to be able to see all this and so this is just showing a video clip from many many years ago where basically we can have a langendorf mode which means the atic valves closed can push a button and it can go into a poor chamber functional mode um and we’re a little bit like Hollywood so we’ll line up all our cameras to get the views that we want um and so again a little bit more details on the procedure this is how we remove the hearts um I’ve watched in Jones this movie many many times um carefully studied this and this is the quickest way to remove a heart for reanimation um and you just you know go in there and I have super strong hands so don’t make me angry um because you know I I know this technique um no that’s that’s a you know that’s not true I don’t do that method but I do wear the every time and then I thought oh this is such an old joke I’ve been saying this for 20 years but then Indiana Jones 5 just came out so I feel I’m younger than Harrison f it forward so it’s okay for me to show this the video so you know we’ve reanimate um animal hearts on a typical basis large Mion hearts and typically it’s poring Hearts pig heart and you know a pig will live for five or six years uh you can pick the size heart from the size animal you want and typically we’re taking animals that are seven or to n months old and their hearts are 450 to 500 gram um and so they’re lung adolescence we do o wine mini pigs we’ve done some canine Hearts this is a canine heart with a qually implanted encapsulated lead in it this is the Philips spectronics laser we had in the lab and we’re just showing how that laser will cut through fibrotic growth um so that’s a a cool part of this is that you could create all these videos showing Technologies and educate people on them as well the lab is set up you know we have state-of-the-art equipment we’re actually just ordered a new Philips floral system we got a brand new 40 EOS system but we have endoscopes that you can put inside 2.4 mm scopes will fit down the coronaries we have ooc as well and so basically when we’re trying to get these images you’re like Hollywood right so you’re going to line up all your Imaging multimodal Imaging and then you’re going to start your procedure and you’re going to go um and so this is you know kind of the fun part of the lab and again it’s is a um a bazard area because we’ve also had the privilege to reanimate human hearts so we’ve actually done 98 Hearts uh since 2000 the last one was a month ago so these are Hearts from organ donors where the Hearts are not deemed viable for transplant they’re recovering other organs and just like a organ transplant we got to get the lab with four to six hours and it had to have a reasonable ejection fraction and it has not to be cut up so they couldn’t the liver team could have been aggressive and piing the whole right atum they can’t do a lung transplant there’s no left or right atrium and they can’t look for valve harvesting so it’s rare plus then I have to have that team of students available in the lab because I can’t do this myself um so it’s it’s a rare event that you’re going to do this um but when we do it um you know the hearts are card plach we’ll flush that out usually Atri will start Contracting and then you shock it and most of them go in a native sinus rhythm and they’ll stay viable for from 5 to 7even hours the first two hours are dedicated collect all the functional images that you’ll see on the atlas website because we feel that with with these gifted organs we have to gift all that knowledge back to everybody and that’s been a mission of the lab and then after that the grad students that are doing work on isolated swine Hearts can do it on human heart making their work translational and then after that metronic will bring in various devices uh because it’s a human heart the concept is that they have to be able to we have to be able to publish or present that publicly in a reasonable time period so this is the arrangement we we’ve made over the years and you’ll see some of those images um we’ve shown here as we go um and we’ve also done um you know heart lung blocks and basically so you basically have a visible lung in a way U but it’s fun to pull back in these pulmonary veins and you can actually see the native pulmonary vein o left atum and again describe a new Martin in the 1880s the difference is we’re doing this without blood um and we have all these great oxygenators and everything else and then the cam to go inside and so you can see me pulling the scope back out of the lungs now I’m coming back into that um left atrium and I can see all that Anatomy so we’ve done you know the cryo balloon ablations there anable watch it seat in there um and it’s you know collecting all these educational images and then you can go into the pulmonary arteries and pull back through that retrograde um and you can see all this beautiful branching of all these vessels and it gives you just a totally different perspective as a human anatomist or as a clinician um understanding how complex these uh tissues and organs really are um and you pull back here you’re going to see the the pulmonic valve and you know this is where we’ve done implants of the melody valve and oh couple weeks ago we did a Harmony valve in in a um swine heart and this just actually shows what you can do is you can have a view of the valve from above and below Echo and Flur simultaneously in there and typically we try to do the multimodal Imaging and all these specimens as we go um and this is from 98 um so this was a metatronic 55076 lead Dr Tim lasy and I were working on WE collected these images he brought to the FDA for edification FDA panels to get FDA approval so uh we hope it expedited it but I think they put in over three million of these leads now worldwide and again it’s kind of fun to be able to to be part of kind of things as well um so here’s Goran stankovich um he’s visited lab the same thing a would have done we can have function on there we can have the cameras inside the coronaries here’s both wires in we can watch the balloon inflate the stent uh we can have the fluro we can run octs you can be heavy on the floral pedal because basically it’s a isolated heart and so you can do as much contast um as you want for educational video collection and we’ve done live webcasts um so the live one we did was to europ PCR a couple weeks ago Dr sovich was in Paris we had Dr uh Randa Davies and um uh yorg rifart in the lab and they were our operators and we did live Cas fication Center um to Paris um to be able to visualize that so again when we’re doing all that we’re doing zoom and everything else but the heart better work right so you got a live audience like here and so we actually try to figure out how we’re going to get these Hearts to always work well um and so we’ve done a lot of preconditioning studies of these Hearts um you know then the other things we’ve done we’ve done you know the latest thing is Michael bki one of the PhD students were looking at you know all the commure alignments of the AIC valves we’re doing stent and stent we’re actually doing chimney and and snor procedures and then what we have in our lab we have our own microct so we can take these Hearts afterwards micro CM get down to a 15 Micon resolution of device tissue interface and then we can um do 3D computational models and 3D printing um so we come to the lab and I’ve given I think a z some of these 3D prints as well and now we have actually better materials so you don’t break them they’re not as fragile so I have to get you some new ones but again this is the so the the partnership is that the grad students are doing um areas of research that are anatomic and kind of State ofthe art in the field um at the same time as we’re partnering with metronic so human heart comes in you know the goal is to get all the function get 3D Echo do fluro do pressure volume Loops do electrical mapping we have mapping catheters we actually have the cardio Insight system the a fair system in the lab that we can actually reanimate the hearts in um and we are then we’ll fix the hearts we’ll make the computational models we um we can do a uh defuser tensor MRI get fiber orientation and then we’re doing with a collaboration with PL doski group in Manchester the whole conduction system of the heart so now we’re starting to create a library where we have all that from reanimated Hearts um and so then we can really understand if you’re putting an aortic Val where that left bundle branch is or if you’re doing left bundle branch pacing you know what’s the the orientations of that relative to the septum and so these are some of the latest things that we’re doing um in the lab um and we’ve done this with other organs so we have a visible kidney we have a reanimated lungs this is human lungs that were’re reanimating in the lab these on the organ Care Systems out of transmedics out of Boston and so we’ve been able to do a lot of research on that as you know this system is a half million dollars each cartridge is single use so we made our own uh more research test bed for so for two to $4,000 we can do a reanimated lung study in lab and start to look at post conditioning agents to how to better take these organs and preserve them or postcondition them uh again most organs that you’re recovering for transplantation are marginalized because they’re coming out of an donor that’s sick and marginalized and it’s hormonal mess and you know all all the different catacombs to keep profusions and pressures so then when you take those organs away flush it out you’re actually um look you can post condition them so you can take a marginal organ and say yes this is actually a good organ for transplantation so that’s been a focus of the research the lab um and you know for a long time I was doing muscle Force studies we still have collaborations going on that um Hankins in um um bosel Switzerland we just actually published a paper a couple weeks ago where we actually monitor patients were neuromuscular disorders and ICU for five years um and tracking you know their uh when they have recuring visits the I what their muscle forces are and so I’ve been doing that work as well um and then um all of a sudden I get a call out of the blue saying hey I heard your studying muscle force and patients ICU how would you like to study a population of individuals that don’t get weak even though they’re immobilized for four to six months and the call was from Hank Carlo and who’s a you know zoologist biologist at University of Wyoming I said that would be awesome he guess well I’m studying hibernating black bears and I’m like that’d be awesome I’m from Minnesota I love the outdoors um and then over the years the collaboration has continued and grown and and we’ve had a whole cast of characters uh that have participated in the black bear research um but again what’s kind of interesting to put this in perspective um you know something on the order of 70 80% of all Health Care dollars in the US are spent in the last six months of a patients life a lot of that is spent in the ICU a lot of that is spent on patients on ventilation and there’s really difficult no good way to assess them or improve their function or lean them off of ventilator and so we’re thinking that maybe the work we’re doing on hyting black bears is the way to do that so we actually bring Force devices in the ICU so it can actually track their um muscle wasting or loss or regaining um of these patients in the ICU and just for a perspective you know this is a study we published and it was an N7 because um about 50% of the patients died while we’re trying to do the monitary um but basically they’ll lose anywhere from 25 to 75% of their muscle Force um in a you know six week period of time and it takes them 13 plus weeks to recover that to be able to wean them off the ventilator huge clinical problem so again phone call from Hank 1997 same year we’re starting the visible Heart Project he said you know I’d like to know more about your muscle Force assessment of patients so came out went out there and gave a talk and there’s Hank and one of the bear Den in Wyoming they’re actually in slash piles in rock so they are kind of like caves which is different than Minnesota so then uh went out there um and you know we started talking about hibernation in black bears and they’re really amazing unique models cuz they don’t lose any muscle mass even they’re mobilized for four to six weeks and what I mean if I opened up this table and that was a space underneath that would be a big enough Den for a 400 lb bear to be in there for to four to six months and we basically have collar with u GPS on there you know as well we have implantable devices we know how much they’re moving around they’re immobilized they’re not leaving that um as well um but what’s interesting they have an intact fight ORF flight response so um if you go a rouse of blackbear in Minnesota they will leave at the den and they look just as fast in December as they do in March um coming out of the D um so they don’t lose any of this flight or flight abilities as well um so this is you know University of Wyoming uh we did necropsies on the Bears um I actually did a grizzly bear too um I show this picture because I have a picture of myself dissecting a grizzly bear no one else does probably in the room um and then we went to fa Country USA and we did our pilot studies um and they were kind enough to anesthetize a bear and again we built the device we didn’t know how well it would work so we did our pilot studies before we went out in the field um and and tried to record this um muscle force in hybriding bears in the wild um and so this is some of the dens we went to so this is a rope we’re supposed to hold on as we climb up to the den and then they did use some pist um the Bears in Colorado Ling they you know they can stand up and come out at you the only place that come out is the entrance so they would use pistols there to Mize the bear so typically we’ll um use uh teol but what was amazing is that we recorded this we got funding from NSF and NASA um again that they really lost 25% of their muscle floor so these are your dorsal flexors these are not anti-gravity muscles these are postural muscles and they’ve lost minimal Force for this three to four month period of time that we studied now if you’re the Department of Defense and you want to look at these parameters they’re going to take volunteers you you and you are going to be immobilized for a month in a bed we’re going to give you food and drink and we’re going to attract your muscle Force loss and you’ll lose 7% per day per day and so again bears are not eating or drinking or defecating and urinating so you can go about three days without drinking water you drink your urine you can make it a week right is that the one climber that you know cut off his own arm that was trapped in a crevis in Colorado um and if you have a full drink you can go about 30 to 40 days without eating uh before you’ll die and they’re going you know uh four to 6 months so how we get the the Bears is we have Barrel traps um and then the doors will slam down as they pull the food out of the back you run your trap L you drug them and in the summer you use ketamine um and then you’re going to put a collar on them these are satellite collar and then you can use Google Maps and you we can track where they are we have about U 40 Bears collared in Minnesota right now and about 25 of those have cardiac blonders implanted in links and yep links as well and then basically you can you know watch the bear uh recover I think Jenna was there for that study um so again four to six months no food no water don’t urinate or defecate their core temp temperature rains near normal so the core temperature goes from 37 38° Centigrade down to 35 or 36° Cent um and so basically they can arous um and come out and there’s really no physical activity um of them in the dens um during that period of time amazing animals um you know this is a you know the advantage of putting a collar on a bear and ear tags um is there’s about 15,000 bears in Minnesota and this is the oldest documented bear anywhere in the world was it Minnesota it was 39 and a half years old um and basically um the DNR this is Dave garelis with her at age 37 tracked her for 32 years they called her at age seven took a tooth they actually just aged animal like he rings on a tree rings on the tooth um and they were able to get a mortality signal we were able to go to the uh D find the skull some of the vertebrae bring it back to the U scan it make computational models of it um so if this bear is 39 and a half years old what do you think the average age of a bear is in Minnesota 15 good guess it’s actually five or six years there’s an active hunting season and the DNR manages all this U Harvest um so we actually work with them to study their physiology reproduction VI viability as well um and there’s a lot of other states but that have um black bears in them as well so then this is like this is a den in the winter or this is a den in the winter I mean last winter we had no snow really we were wet in the spring the year before we had snow up to my hip and so we had to have snowshoes on and you’re carrying all your equipment there and you’ll be walking around trying to find the opening and it’s just snow and all of a sudden you’re walking you’ll sink in and that’s probably the opening and you’ll take shovels and you’ll start pulling the snow back and then you might hear the animal and you know then you’re going to drug the animal um but they have all different types of den we’ve studied the different ecosystems from Conifer Forest to theous Forest to this is the great PLS in uh Northern Minnesota it’s a lot of farming they’re actually cornfed Bears some of the male bears were like 600 lb um up there as well and so um you know it’s kind of fun to go out if you go to the Dan um and they’re covered with snow or not they’re always facing out so you can use an infite camera to see see where they are in there um or just look in there with a you know flashlight um and that’s typically what they’re doing and basically they’re always facing out why yeah defend themselves against predators and in Minnesota the natural predators are wolves wolves don’t hibernate um Colorado Wyoming it’s wolves and cougars um um so they actually have to be able to mount defend themselves so this is Dave drugging an animal we always Flinch you Flinch no matter what all right fun to hear that this is another way to the animal or [Laughter] all right we don’t do it that way at all this is another video where we got a laser on there you put a a cover over so you make it dark in there um so you can see the bear oh jaw stamping scares off you’re a girly background it’s not a bad audio that’s the Cubs in there this is me going in there Tim Wy had a 360 camera so this is me you see the hip you’re trying to get basically you take a hypmic with the heels all and you carve out a stick and you stick your arm in there and then you’re going to do a jab hole and then you’ll wait like 10 minutes you’re trying to always under drug the animal because they’re mildly hypothermic which also is anesthetic and so then you go in there with a stick and poke them again to see if sleeping they’re not you got to redrug them uh but again this was a video from a couple years ago when I drugged the animal this is just another view of you know the whole thing if you had a 360 camera this would be the way to do it we don’t so you actually are sticking your head in the hole um as you’re doing that um it’s a drugged animal e so again they made in May June July there’s delay implantation of the fertilized egg until the end of November five six week gestation period they’re born in early January at w mother hibernating wow um and she’s in a deep hibernation because we’ve tracked all their behaviors with imputable devices so this is Tim uh we thought we would you know try to design data loggers to is before the link project we had defibrillator cans uh we built the devices they had in 200 96 megabytes of memory which was incredible right this was state of the art 2000 96 megabytes of memory and we had had do these cycle these and do all the programming to figure out when they were going to turn on and everything else we got them implanted however we did anticipate that the Bears would have a dramatic fore body resp response and reject the devices in a couple week period of time so if you put that in a human in a cal and a pig and a sheep and a dog the device will stay in until you pull it out the Bears had this massive for body response and then we put these in in December so the first year I put them up in the Scher region with a lead down I okay that’s typical implant Zone didn’t put the lead in the heart just did externally didn’t work so next year I’m going to Smart the bear so I’ll H hang it in the par Neo space with the lead coming up they marsupialized those cans and rejected them as well and then there’s yearlings in the dens and they thought it was a fun chew toy and shw them all up um but we were able to get data from them and bears have a dramatic respiratory sinus arhythmia so you all have one here your heart rates 60 beats per minute your Inspire goes up to 61 or 62 xir goes down to 60 a bear will have a rusting heart rate of five or 10 beats per minute when they uh take a breath in heart rate goes up to 60 70 beats per minute when they exhale it’ll pause that pause can be either five to 20 seconds long we’ve seen some up to 35 seconds and that’s consistently to the winter for that particular animal and so again if you have a heartbeat for five or six seconds you’ll pass out so these bears are more or less passing out after every U breath they take um and their their respiratory rate goes down to two or three breasts per minute huge conservation of energy again they had this incredible healing ability during hibernation these are some neck injuries that the animals have we had some with gunshot wounds and arrows um if this was um a C you put on and sometime you size the collar for the animal to gain like typically 70 80 pounds this animal gained 150 pounds in from you know April till October okay so you it the colar injured them I de breeded it I sewed it up and in three months it’s totally healed not only is it healed but there’s not just fibrotic inlay growth with starring they actually form new hair follicles around that area and if you shave them they don’t grow any regrow any of the hair so they can put their energy only where they really need it so I shave a bear to do a 12 Le EKG and we’ve done hundreds if I do it December I don’t have to reshave them again in March um and then we’ve done 12 Le kgs there’s no electrical remodeling of the heart at all we’ve done I’ve done you know hundreds and echos if not thousands there’s no loss of cardiac Mass um even though they’re basically in a state of starvation and immobilized versus a patient right patient ICU you’re going to lose 23% of cardiac mass in a three to four week period of time U that’s why you wanted your patients up in in cardiac rehab as soon as possible no remodeling at all of these bare hearts in the state of starvation um so then we went to the implantable uh reveal devices because we thought it was unethical to put the cans still in and then we were able to record a lot more data and so this is this pattern in intense respiratory sinus AR rmia then we put on our gold proos synchronized our watches and we started walking towards the dens and we could get 50 to 100 ft away and they sense we’re there we could be downwind maybe we smell bad from carrying all equipment or whatever but they could sense we’re there and they start huffing going which drives up their heart rate which then gets them ready for a fight ORF flight response um and then you give the drug and then basically you knock out the anomic nervous system so then they have a constant renovated heart the heart rates are somewhere between 90 to 100 beats per minute to the whole period of the anesthesia so then you can record data for years so this is just showing activity so this is the summer active period This Is hibernation this is the on Daytime Nighttime heart rates yeah there’s a funny Spike right here that’s when we visited the D which it’s really nice to know that the Tils all lasted for three to um four hours wore off and they go back right into that deep respiratory sinus they really so like we were never there so it’s always nice to know is a field researcher you had that this is one animal we tracked for six years this is a female bear so she gave birth to Cubs and what they’ll do is the Cubs will stay with the mother um as yings through the summer then they’ll hibernate back with the mother and then basically um the following May June July if she sees a good-looking male she chases off her yearlings and starts the process over again um so this last winter we went to a whole bunch of Yearling dens one den had um five yearlings uh their weights were again these are were born in January now they’re stopped feeding in October somewhere between 70 and 100 pounds and then a fale that was 300 lb so we had 700 lb of Bear in the stem uh that were drugging and pulling out and this is one of the studies where Mark dimer did we actually had the GP satellite colors could pick a drone fly over the bear the bear would look up at at the camera and its heart rate would go up two or three fold and that last the Drone would leave and it would last for 10 minutes so it’s a huge catacol main release um and basically uh we were able to show that if we we had a group of captive Bears same response but they habituated after tour free Drone flights so again the G&R is interested if they’re going to track natural behavior of animals you have to attract that same animal multiple times because you are affecting the behavior by that drone flight um we can actually Track Road Crossings um and they actually will stop at a road the heart rates would go up uh this one actually was hit by a car and we were able to get the device back showed by gy and then fibrillated died um from being hit by the car um and then now we’re doing the the link devices and Link two devices um and this is one of the things Tim and I figured out we had it these stations at Bear dens where basically we can’t put a device inside a patient monitor inside the den the Bears will eat it so you VAR antenna goes to a box sitting outside with a couple car batteries patient monitor um and basically um voltage regulators and timers hooked up to a a solar panel to charge it and a cell phone module to send out the data this was the quality of data we were getting at the metronic baring site um and we we’ve been able to do this for multiple years and again um these pauses just to think about it um they actually um don’t have any tromatic events at all um and deep gain T So St in the heart even though the heart’s static for that and we’ve done act studies they self anti coagulate the acts will be over 250 to 300 um it’s we don’t know if it’s the fatty acids or what or some of proteins that release and that’s a a lot of group in Scandinavia are trying to study that as well so again huge fat deposits um they’re only mildly hypothermic they’re still using tons of energy per day there’s protein turnover um and if you think of Ura formation from the crab cycle their kidneys are shut down they have a specialized bacteria in the gut that catabolizes all the Ura um of course NASA and everybody else is there’s groups um there’s group very groups around the world studying all that but again they’re they release these also hibernation induction triggers um as well and that’s thought to be you know opioid in nature the active subunit is a Delta opioid Agonist um we’ve actually done studies on using that to protect skull’s muscle of the heart um and basically it’s thought to really uh be mardio protective they PR prevent prolong organ preservation times per preserves muscle mass and it minimizes both fcal and Global ES schia um of the heart and other tissues so again we’ve been studying this for years in the lab and various pre-clinical protocols this is Daniel Sig who’s now a distinguished scientist at metronic but it’s all these um well defined early and late phases of preconditioning and this is through G protein Cascades affecting all the way down to potassium channel hpac in the mitochondria and free radical Scavenging so there’s a lot of you know basic work done on these mechanisms um and then they also upregulate the release of bile acids uh during hibernation that’s been used in eastern medicine for thousands of years for treating almost every disease is um bare bi and actually there’s um black markets for about bar gold bladders you can sell them for 20 to $30,000 um they actually do bare firing in uh Asia um for this but there are synthetic forms Toka that’s used for treating liver disease in the United States but basically they will release more of that during hibernation again so it’s this organic mechanisms here’s just another bear sleep uh so the Cubs are kind of tucked under her she’s protecting them she will not leave this Den she will protect her Cubs uh there’s no snow on this one but we’ve gone around to many dens where there’s wolf prints all the way around circling um the DS um and she’s protecting her tubs down inside so again you know have blizzard conditions and I’m doing these implants and everything else we’ve had you know 20 below temperatures 25 30 below windchills snowing and you’re trying to do this field research um at that period of time so that’s can be challenging some of the Delta opioid and research we’ve done also the fatty acids we’ve done infar models uh Daniel Sig and James Kohl’s did that where basically we would look at the area at risk we would um pre-treat the either IV or in the paracardial space and we could reduce infar size by over 50% and a athm is doing reperfusion by over 50% so this is schic reperfusion model uh it’s been well defined in the literature so this is just with these agents which is really kind of exciting um and so you can do this actually um in a pericardial space we’ve done that with other anti- rythmic agents and it’s a Target site and you can have the benefits of that agent in the Target without its systemic capis um so we’ve been you know again then looking at putting bare bi acids in the paric cardio space fatty acids Delta opioids or combinations today or you know last week we put in um a megaan um in the paracardial space for an hour prior to to the isolation reanimation reduces aymas it reduces Global esmia so the hearts will last longer once we have them on the apparatus and reduces the the defib shock thresholds so fewer shocks to get that heart back in the native sinus rhythm so minimizing my cardial stunning um with a fewer shocks and and then we’re trying to apply this to you know all the things we’re doing the lab the this is another set of the isolated lungs the organ Care Systems um where they’re looking at that as post conditioning agents there we’re doing that in the bench toop and the heart and the lungs we’ve done post conditioning the lungs so a human heart comes in now um it takes me about an hour to culate it set it all up and as we’re warming it we have actually give the Omega ban in the perfusate um and we can do high levels um you can’t go too high in a patient IB because there’s hemolytic properties of the um fatty acids on red blood cells so you minimize that but a Target organ or in a acellular perfusate we can go ahead and do that we’ve actually showed improved function we’ve have hearts come in ascribed to be and AF and they actually come in some of them have actually gone into a native sinus rhythm for a while until we’ve washed out that delto the omega3 fatty acids so just kind of to summarize and our laboratory really focuses on translational research cardiac Anatomy organ preservation scheme of protection and we’ve been studying hibernan black bears this amazing animals and world to hibernation they don’t lose any skeletal cardiac masks state of total starvation intact fight or flight responses can come out and defend themselves at any time and we’re actually um you know using this in the lab routinely so we reanimate a heart in the lab it’s not trivial we’re spending probably 10 to 15,000 a day so anything we can do to optimize that is Advantage for us and we actually have a um planned clinical trial where they going to do cabbage procedures and they’re going to actually do the paracardial delivery prior doing the whole cabbage to see if we can um reduce improve outcomes and time in the ICU of patients and uh do that acutely in the lab so last true vid fun videos here for you another bear in the spring this is a bear that hasn’t uh eat and or drink and a urinate or move for four to six months that looks pretty pretty capable there fit the camera um then we have Den cans um and so these are bear with earings they’re emerging um then in the spring and they’re actually pulling dry uh grass back in because there’s moisture in there as that things melt out and my hypothesis is it takes a the Bears several weeks to leave not because there’s not enough food and energy out there it’s because they actually have to sleep they’re sleep deprived because they didn’t have a natural Rim sleep or any sleep for four to six months and so we’re trying to collect the data from our devices and everything else to be able to show this emergence from this deep respiratory sinus rhythmia takes several weeks as well and we’ collected the data and we’re synchron in it with our videos we’re collaborating with the University of Washington we’ve got Link and Link two devices this Charlie Robbins um he’s basically looking at oxygen consumption they got grizzly bears train they’re feeding honey to a tube and the bear will then just walk on the treadmill um and we’re trying to work with them to put the devices in to see if we could do this in a while so we’re working with the um the wildlife groups at Yellowstone and Alaska Wildlife I’m trying to get these devices and collars um so we can do field work so we’ve actually made prototype devices there that have Bluetooth links to the devices and plant the animals we can collect data for several weeks we just don’t have the battery capacity yet we’re working on that but they’ve done Tim LA’s done this on elephants now in Thailand they have plenty of room for batteries um they’re just having problems with the communications now signal so we’re continuing to work on that but that’s maybe kind of the future direction as well so again now you’re taking human clinical devices and you’re applying it to Wildlife Research and actually um Dr Alena katinsky um who a electrophysiologist and Chicago area basically is doing that and the Apes great apes and all across the US um because they do show heart disease when they get into their 20s and 30s um so again it’s going the other direction now and then this is just some more um this is my sterile technique for implanting the Link and Link two devices um this is the data quality that we can get right in the field um and this last winter I I implanted um six uh I don’t have a all right you have the M back there anybody that’s sorry um pretty much done um and again cancel all right so again you got also have to have fun in research every time we had a bear back in we do The Safety Dance um and then basically you know we some of the vehicles this is how much snow I have my snowshoes on timed in so this is challenging we take all our equipment out there our paths are weighing 50 60 pounds so you feel like you’re in in a you know natural geographic film every time you go out there and it’s super cool but then the think about that of how can bring it back to your pre-clinical research or human trials is you know fun you know things to think about and try to apply and get to so thank you very much for your well it was incredible thank you so much for sharing your Insight I think from for many of us we didn’t realize how interesting black bears are and how much we can learn that we can apply to our I know if there any questions um thank you for an absolutely spectacular lecture in your paars that are sleeping or hibernating with a mark sinus arhythmia do you see R cardi dependent arhythmia is atrial tribulation anything of that nothing which is amazing and then some of these animals are again that we are tracking with the ear tags and collars are 20 25 years old and they basically have no Aria so go from this pause right into consistent native sinus arhythmia um and we’ve really seen no electrical changes there was a couple that might have a a double Peak funny C curus complex but it was a rare case so it’s it’s mind B actually any any any clue to why the Lipan is so short I know that in the wild many of them are predated but but let’s say kept in captivity what is the natural C of that how long they live why yeah I have no idea um I just supposed be the natural course of their DNA and everything else and you know it’s just like why you pigs only live five or six years right um and it’s just I don’t know they’re mostly healthy um we haven’t seen any real disease per se like any cancers or anything else that sometimes they are with ticks so they might have Lyme disease and things like that but they don’t seem to present with anything like that um so yeah I have no clue lot to learn still yeah two bears held in captivity like do they hibernate um they that’s a great question no and I see there’s black bears in Florida and black bears in Florida do not hibernate unless their pregnant females the pregnant females with the will go in and hibernate during that period of gestation and when the cups are born so this five six weeks um she’s kind of hibernating and then basically while these cups are nursing and every else she’s she doesn’t want to do any work um they said they hibernating I’m just an adonal from what I’ve heard from the biologist down in Florida but yeah it depends on there so the ones the Grizz Bears some hibernaculum have access to water and food if they want and so they don’t really hibernate in these hibern yeah absolutely inspirational I’m almost speechless um two questions vascular aging you don’t see that in the Bears and the other question is we use the transmatics here for Trans L this may be too clinical question I’m just curious uh maybe aware that there’s more or primary graph dysfunction after the transplant when you have used the device which is probably what you’re targeting with the yeah these agents you have any uh hypotheses about why that might be and how that can be how are you fixing that yeah I mean there’s a lot of research so I’m looking at using different agents as well even they want to do some molecular kind of modulations of it um but again this is I think it’s you know you’re you’re putting pack red blood cells in most of these cases and if you look at these packed red blood cells they do degrade over time um so either they’re going to have to come up a system replenishing na or adding additional agents um but we actually did research on this um organ Care Systems with whole blood we’re able to take the lungs out of a pig and keep them viable for 24 hours with whole blood we took some of the lungs out of those animals five animals took one off the device 24 hours later implanted another animal and it was viable for 5 six hours we’re able to get um 10 sets of human lungs and a liter half of blood from the um upper body because the transplant abdominal team didn’t want us to take any blood from below we able to get a liter and a half of blood and get that blood and organ to the lab within two hours on ice and we were able to keep Bible function for 24 hours in these so there’s these other factors in the plasma and everything else that need to be investigated and looked at and I think they’re actually removing that and they’re actually maybe hurting causing some grass dysfunction because they’re removing too much um out of their preparations so are research hasn’t got anywhere no one’s adopting that because logistically it’s hard to think about you would do that right so you would actually have to have an orgon that you put on there with the whole blood and then that you’re thinking you’re going to go beyond so the next step of that preclinical research is super tricky how you going to justify putting lungs on with whole blood for 24 hours and then transplanting so that’s where with the roadblock right so sometimes in research you hit these um Road Lo in in your clinical research great um M were there any questions online from anybody online anybody has access to the online thing M’s not here oh well um no other questions well once again incredible I think we all learned so much thank you for taking the time to come uh to New York and yeah we look forward to having you again in the future all right perfect thank you and in a while [Music] doped by this great experience [Music] [Music] in that meeting I didn’t have any here either maybe for sure great [Music] job that’s the whole thing you know there always [Music] than for coming [Music] [Applause] okay thank you so much [Music] [Music] what
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