This Man Was Dead; He Isn't Anymore - Technology Partners

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This Man Was Dead; He Isn't Anymore - Technology Partners

THE GOP’S IRAQ REBELLION • MEN IN DRAG, AGAINJuly 23, 2007newsweek.comThis ManWas Dead.He Isn’tAnymore.How ScienceIs Bringing MoreHeart-AttackVictims BackTo LifePHOTOGRAPH BY ETHAN HILLBrian Duffield, 41, whose heart stopped after a swim in May 2006


to cardiologists as the widowmaker. Atiny clot lodging there would have senthis heart into a brief burst of the ineffectualrhythm known as fibrillation, beforeit stopped altogether. Within 20 secondsthe hundred billion neurons in Bondar’sbrain would have used up their residualoxygen, shutting down the ceaseless exchangeof electrical charges that we experienceas consciousness. His breathingstopped as he entered a quiescence beyondsleep.About 250,000 times a year in theUnited States, someone’s heart stopsbeating on the street, or at home or atwork. This can be the result of a heart attack,when a clot chokes off a coronaryartery, or a host of other conditions includingcongenital defects, abnormalblood chemistry, emotional stress andphysical exertion. Without CPR, theirwindow for survival starts to close inabout five minutes. Life or death is mostlya matter of luck; response time to a 911call varies greatly by location, but can exceed10 minutes in many parts of thecountry. In rough numbers, they have a95 percent chance of dying.How long has itbeen since you’ve readan article about heartattacks that didn’tmention saturatedfats? Our age is obsessedwith “health,”but when health fails, the last line of defenseis in the emergency room, wheredoctors patrol the border between lifeand death—a boundary that they havecome to see as increasingly uncertain,even porous. This is a story about whathappens when your heart stops: aboutnew research into how brain cells die andhow something as simple as loweringbody temperature may keep them alive—research that could ultimately save asmany as 100,000 lives a year. And it’sabout the mind as well, the visions peoplereport from their deathbeds and theage-old questions about what, if anything,outlives the body. It begins with achallenge to something doctors have alwaysbeen taught in medical school: thatafter about five minutes without a pulse,the brain starts dying, followed by heartmuscle—the two most voracious consumersof oxygen in the body, victims ofOxygen deprivation is merely thestart of a cascade. Dying turns out tobe almost as complicated as living.their own appetites. The emerging viewis that oxygen deprivation is merely thestart of a cascade of reactions within andoutside the cells that can play out overthe succeeding hours, or even days. Dyingturns out to be almost as complicateda process as living, and somehow, amongits labyrinthine pathways, Bondar founda way out.Monica tried to recall what shehad learned in a CPR class decades earlier.She bent over Bondar and beganpushing down on his chest, thenrushed back to the kitchen to dial 911.“My husband is dying!” she gasped tothe operator.Compressing Bondar’s chest wouldhave sent a trickle of blood to his brain,supplying a fraction of its normal oxygenconsumption, not enough to bringhim back to consciousness. But the WestDeptford police station was only threeblocks away, and within two minutes ofMonica’s call three officers arrived with adefibrillator. They placed the pads onBondar’s chest, delivered two jolts ofelectricity to his heart, and got a pulseback. Soon paramedics arrived with oxygenand rushed him to a nearby communityhospital. The report Monica receivedthere after an hour was equivocal:Bondar was “stable”—his heart rate andblood pressure back to near normal—buthe was still in a coma. It was then thatMonica made a decision that may havesaved his life. She asked that her husbandbe moved the 15 miles to Penn, theregion’s leading university hospital.Dr. Lance Becker, director of Penn’syear-old Center for Resuscitation Science,frequently dreams about mitochondria:tubular structures within cells, encasingconvoluted membranes whereoxygen and glucose combine to producethe energy the body uses in moving everythingfrom molecules across cell membranesto barbells. Recently mitochondriahave been in the news because theyhave their own DNA, which is inheritedexclusively down the female line of descent,making them a useful tool for geneticistsand anthropologists.But Becker is interested in mitochondriafor another reason: he believes theyare the key to his audacious goal oftripling the time during which a humanbeing can go without a heartbeat and stillbe revived. That the five-minute rule isnot absolute has been known for a longtime, and the exceptions seem to involvelow temperatures. Children who fallthrough ice may survive unexpectedlylong immersions in cold water. OnNapoleon’s Russian campaign, his surgeongeneral noticed that wounded infantrymen,left on the snowy ground torecover, had better survival rates than officerswho stayed warm near the campfire.Becker is hoping to harness this effectto save lives today.Becker is 53, slenderand boyish in a way thatbelies his thinning hair;his typical greeting to colleaguesis a jaunty “What’sup, guys?” For his lab hehas assembled a highpoweredteam from a wide range of specialties,including a brilliant youngneuroscientist, Dr. Robert Neumar; anemergency-medicine specialist, Dr. BenAbella; plus cardiologists, biochemists,bioengineers and a mouse-heart surgeon.His associate director, Dr. VinayNadkarni, comes from pediatrics. Beckerhas in effect re-created at Penn, on amore ambitious scale, the laboratory hefounded in 1995 at the University ofChicago, with a grant of $50,000 from thephilanthropist Jay Pritzker. Ten years earlierPritzker had walked into the emergencyroom at Chicago’s Michael ReeseHospital complaining of chest pains, andcrumpled to the floor. Becker resuscitatedhim, the beginning of both a rewardingfriendship (Pritzker lived for 14 moreyears) and a new direction for Becker’s career.“Every day since then,” he says, “Iwould go home and wonder why Jay


People have a hard time believing that something assimple as cooling the patient can make such a difference.Pritzker got a second chance and so manyother people didn’t.”Becker’s interest in mitochondria reflectsa new understanding about howcells die from loss of circulation, or ischemia.Five minutes without oxygen isindeed fatal to brain cells, but the actualdying may take hours, or even days. Doctorshave known for a long time that theconsequences of ischemia play out overtime. “Half the time in cardiac arrest, weget the heart going again, blood pressureis good, everything is going along,” saysDr. Terry Vanden Hoek, director of theEmergency Resuscitation Center at theUniversity of Chicago, “and within a fewhours everything crashes and the patientis dead.” It took some time, though, forbasic research to supply an explanation.Neumar, working with rats, simulatescardiac arrest and resuscitation, and thenexamines the neurons at intervals afterward.Up to 24 hours later they appearnormal, but then in the next 24 hours,something kicks in and they begin to deteriorate.And Dr. James R. Brorson of theUniversity of Chicago has seen somethingsimilar in neural cells grown in culture;deprive them of oxygen and watchfor five minutes, or even much longer,and not much happens. “If your car runsout of gas, your engine isn’t destroyed, itjust needs fuel,” he says.Cell death isn’t an event; it’s a process.And in principle, a process can be interrupted.The process appears to begin inthe mitochondria, which control the cell’sself-destruct mechanism, known asapoptosis, and a related process, necrosis.Apoptosis is a natural function, destroyingcells that are no longer needed or havebeen damaged in some way. Cancer cells,which might otherwise be killed by apoptosis,survive by shutting down their mitochondria;cancer researchers are lookingfor ways to turn them back on. Beckeris trying to do the opposite, preventingcells that have been injured by lack of oxygenfrom, in effect, committing suicide.It’s a daunting problem. “We’re askingthe questions,” says one leading researcher,Dr. Norm Abramson of the Universityof Pittsburgh. “We just haven’tfound the answers.” Until recently, theconventional wisdom was that apoptosiscouldn’t be stopped once it was underway.It proceeds by a complex sequence of reactions—includinginflammation, oxidationand cell-membrane breakdown—none of which seems to respond totraditional therapies. Becker views celldeath in cardiac arrest as a two-step process,beginning with oxygen deprivation,which sets up the cell for apoptosis; thenthe heart starts up again and the patientgets a lungful of oxygen, triggering whatis called reperfusion injury. The very substancerequired to save the patient’s lifeends up injuring or killing him.Researchers have ransacked their arsenalof drugs looking for ways to interruptthis sequence. Over the years they havetried various techniques on nearly 100,000patients around the world. None hasshown any benefits, according to Dr. A.Michael Lincoff, director of cardiovascularresearch at the Cleveland Clinic. But onething does seem to work, something so obviousand low-tech that doctors have a hardtime accepting it. It’s hypothermia, the intentionallowering of body temperature,down to about 92 degrees Fahrenheit, or 33Celsius. Research by a European team in2002 reported favorable results from a controlledstudy of several hundred cardiacarrestpatients; subjects who were cooledboth had better survival rates and less braindamage than a control group. The first biginternational conference on cooling tookplace in Colorado this February. Despite favorablestudies and the endorsement of theAmerican Heart Association, “we wereconcerned that [hypothermia] still wasn’tcatching on,” says the conference organizer,Dr. Daniel Herr of Washington HospitalCenter in Washington, D.C. The two leadingmanufacturers of cooling equipment—Medivance, Inc., and Gaymar Industries—say only about 225 hospitals, out of morethan 5,700 in the United States, have installedmachines for inducing hypothermia.Herr says the treatment requires a“paradigm shift” by doctors. “People have ahard time believing that something as simpleas cooling can make such a big difference.”Perhaps that’s because no one quiteunderstands how cooling works. It appearsto work globally on apoptosis, rather thanon any of the individual biochemical pathwaysinvolved in it. “The short answer is,we don’t know,” says Neumar.Researchers have also been lookinginto the way patients get oxygen duringresuscitation, and afterward. The treatmentgoal in cardiac arrest has been torush oxygen to the heart and brain atmaximum concentration; the mask theparamedic pops on your mouth suppliesit at 100 percent. “The problem withthat,” says Dr. Ronald Harper of UCLA,“is it does some very nasty things to thebrain.” Harper believes a mixture containing5 percent carbon dioxide wouldbuffer those negative effects, but theidea is still controversial. At the Universityof Maryland, Dr. Robert Rosenthaland Dr. Gary Fiskum have been lookinginto whether oxygen concentrationsshould be dialed down much more aggressively.In their lab, dogs with inducedcardiac arrest recovered betterwhen they were taken off full oxygen afterjust 12 minutes, compared with anhour in the control group. Rosenthalsays in practice patients sometimes areleft on pure oxygen for much longerthan an hour—in one hospital he studied,for as much as 121 hours.At Penn, Becker’s Resuscitation Centercoordinates with the Emergency Departmenton a protocol for cooling patients incardiac arrest. “We look at their prior mentalstate,” says Dr. Dave Gaieski. “If someonewas in a coma in a nursing home, we’renot going to cool them.” The same goes forpatients whose hearts stopped for longerthan an hour. Since 2005 just 14 patientshave met Penn’s criteria for hypothermia.Eight survived, six of them with completerecovery. No one knows how many otherswere saved by cooling around the country.Bondar arrived at Penn at about 1:30a.m., still comatose, minutes ticking awaywhile he was evaluated for cooling. Oncethe decision was made, the team sprang intoaction, injecting him with an infusion ofJULY 23, 2007 NEWSWEEK


Sciencechilled saline—two liters at about 40 degrees—thenwrapping him in plastic tubesfilled with chilled, circulating water. Beckerbelieves, based on animal work, thatcooling patients even sooner—ideally, ontheir way to the hospital—would be evenmore effective, and part of the work of hislab involves perfecting an injectable slurryof saline and ice that could be administeredby a paramedic. Bondar was kept at about92 degrees for about a day, then allowed togradually return to normal temperature.He remained stable, but unresponsive,over the next three days, while Monicastayed at his bedside. She finally wenthome Sunday evening, and was awakenedMonday by a call from the hospital that shewas sure meant bad news.“Guess what?” said the voice on theother end. “Bill’s awake.”Bondar’s first words were, “How did Iget here?” He had lost track of a full week,from about two days before his heart attackuntil he woke up. That’s not unusual;short-term memory is often the first casualtyof cardiac arrest. Neumar says certaincells in the hippocampus, the part of thebrain that forms new memories, are forunknown reasons especially sensitive toischemia. Another Penn patient, SeanQuinn, was 20 and a student at DrexelUniversity when he went into unexplainedcardiac arrest in 2005. He wasone of the earliest patients cooled at Penn,and there’s reason to believe that it savedhis life, but the continuing memorydeficit has prevented him from returningto college.Certainly, people do not form memorieswhile they’re in a coma. Exactly oneyear before Bondar had his heart attack,Brian Duffield, then 40, a salesman inTucson, collapsed in the shower after aswim. Luckily for him, he was on the campusof the University of Arizona, whosehospital uses a cooling protocol similar toPenn’s. “I was there one minute and thenext thing I know, it’s a few days later andpeople are telling me I was dead and cameback,” says Duffield. But Duffield’s memoryand intellect and personality all returnedintact from his brush with death,as did Bondar’s. This is, on some level,deeply mysterious. We experience consciousnessembedded in time, a successionof mental states continually re-createdin our brains, even during sleep. Butwhen the brain shuts down, where doesthe mind go?That is the crux of one of the oldest debatesin philosophy. The materialist viewis that Bondar’s memories resided in thephysical state of the cells and synapses ofhis brain, a state that is preserved for someperiod after the heart stops beating. Beckerhas pronounced perhaps a thousanddeaths in his career, but often with the feelingthat—despite the lack of pulse, breathingor discernible brain function—somethingvital remains in the body on the bed.He felt it most strongly when his own fatherdied of cardiac arrest at the very hospitalwhere Becker was working in 1993.When Becker saw him, he was alreadydead, but something seemed preserved. “Ijust had the sense he wasn’t really deadyet,” Becker says. “He was dead. He hadbeen pronounced. But he hadn’t left.”This is the belief motivating peoplewho pay to have their bodies frozen in liquidnitrogen after their deaths, in the hopethat they can someday be thawed and restoredto life. The Alcor Foundation, inScottsdale, Ariz., has signed up about 825prospective patients, and has preserved 76of them, including Ted Williams. Thesearen’t all whole bodies; some people optfor just their heads, which, apart from beingcheaper, freeze faster than an entirebody, reducing the danger of frost damageto the cells. Of course, we are a long wayfrom knowing how to reanimate a frozenbody, let alone just a head. One possibility,according to Tanya Jones, chief operatingofficer of Alcor, is to take a cell from thehead and clone a new body to attach it to.The other is to scan the entire three-dimensionalmolecular array of the brain intoa computer which could hypotheticallyreconstitute the mind, either as a physicalConsciousness is a series of mentalstates. But when the brain shutsdown, where does the mind go?entity or a disembodied intelligence in cyberspace.This, obviously, is not for theimpatient. The physicist Ralph Merkle, anAlcor board member, has used this idea topopularize a fourth definition of death:“information-theoretic” death, the point atwhich the brain has succumbed to the pullof entropy and the mind can no longer bereconstituted. Only then, he says, are youreally and truly dead.But there’s anotheranswer to the question ofwhere Bondar’s mind wasduring the last week ofMay. This is the view thatthe mind is more than thesum of the parts of thebrain, and can exist outside it. “We stillhave no idea how brain cells generatesomething as abstract as a thought,” saysDr. Sam Parnia, a British pulmonologistand a fellow at Weill Cornell Medical College.“If you look at a brain cell under a microscope,it can’t think. Why should twobrain cells think? Or 2 million?” The evidencethat the mind transcends the brain issaid to come from near-death experiences,the powerful sensation of well-being thathas been described by people like AnthonyKimbrough, a Tennessee real-estate agentwho suffered a massive coronary in 2005 atthe age of 44. Dying on the table in thecath lab during angioplasty, he sensedthe room going dark, then lighter, and“all of a sudden I could breathe. I wasn’tin pain. I felt the best I ever felt in mylife. I remember looking at the nurses’faces and thinking, ‘Folks, if you knewhow great this is, you wouldn’t be worriedabout dying.’” Kimbrough had theodd sensation of being able to see everythingin his room at once, and even intothe next room. He is one of about 1,200people who have registered their experienceswith a radiation oncologist namedDr. Jeffrey Long, who established theNear Death Experience Research Foundationin 1998 to investigate the mysteryof how unconscious people can formconscious memories.That’s also what motivates Parnia, whohas begun a study of near-death experiencesin four hospitals in Britain, aimingfor 30 by the year-end. The study will testthe frequently reported sensation of lookingdown on one’s body from above, byputting random objects on high shelvesN E W SWEEK JULY 23, 2007


Scienceabove the beds of patients who are likely todie. If they later claim to have been floatingnear the ceiling, he plans to ask them whatthey saw. Parnia insists he’s not interestedin validating anyone’s religious beliefs; hisidea is that death can be studied by scientists,as well as theologians.As for Bondar, his mind stayed put duringhis ordeal, which ended when he wenthome with Monica on June 1, nine days afterhe died. Gerstenfeld had given him animplantable defibrillator, cleared hisblocked artery and inserted a stent to keepit open. “He came back fully intact,” saysGerstenfeld. “He was dead, if only for afew minutes. But it could have been muchworse. He could have been dead-dead.”We are, Becker believes, at the forefrontof a revolution in emergency medicinedestined to save millions of lives inthe years ahead. This is doctoring at itsmost basic, wresting people back fromdeath. “I have been fighting with death for20 years,” he says. “And I’ll keep doing it, Ithink, until I meet him in person.”With MATTHEW PHILIPS, JOAN RAYMOND andJULIE SCELFOThere’s aNew CPRBY JOAN RAYMONDThe good news: millions of Americansknow how to perform CPR. The badnews: when confronted with an apparentvictim of cardiac arrest, mostbystanders won’t do it because it includesmouth-to-mouth breathing.Now Dr. Gordon Ewy, director of the Universityof Arizona’s Sarver Heart Center, ischampioning a new form of CPR called cardiocerebral resuscitation, or CCR, whichfocuses on rapid, forceful chest compressions,about 100 per minute, minus themouth to mouth. “Mouth to mouth inflatesthe lungs, but it’s not the lungs that needoxygen, it’s the heart and the brain,” saysEwy. “Chest compressions alone will helpsave those organs.”The Sarver researchers have developedtwo separate CCR protocols. Bystanders whowitness a cardiac arrest are urged to performchest compressions until help arrives. Paramedicsare to attempt CCR for two minutes,before they use a defibrillator. Several Arizonafire departments have adopted the new approach.An analysis of that data shows survivalrates have nearly tripled.Current American Heart Association andAmerican Red Cross guidelines do recommendcompression-only CPR for anyone who isunwilling or unable to provide mouth tomouth. The AHA also encourages emergencydispatchers to give instructions for compression-onlyCPR to bystanders at the scene of apresumed cardiac arrest. “People want to dothe right thing,” says Ewy, “and we are givingthem an easier way to do the right thing.”(#14747) NEWSWEEK JULY 23, 2007 © 2007 NEWSWEEK, INC. REPRINTS@NEWSWEEK.COM6740 Top Gun StreetSan Diego, CA 92121Phone: 858-677-6390FAX: 858-671-6391Toll Free: 866-682-COOL

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