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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2022-08-16T00:00:00-04:00" class="date-display-single">August 16, 2022</span></p><div class='syndicate'><h1>Restoring cell and organ function after the heart stops</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>Researchers restored cellular function in a pig’s organs more than an hour after its heart stopped.</li>
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<li>Such technology could eventually help repair organ damage from heart attacks or strokes, or be used to preserve organs for transplantation.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Perfused kidneys">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2022/20220816-kidney-blue.jpg?itok=wttfo3pE&timestamp=1660594192 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2022/20220816-kidney-blue.jpg?itok=054PoEgK&timestamp=1660594192 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2022/20220816-kidney-blue.jpg?itok=dd74_4OW&timestamp=1660594192 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2022/20220816-kidney-blue.jpg?itok=gvf3U6-F&timestamp=1660594192 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2022/20220816-kidney-blue.jpg?itok=hV9kFn-i&timestamp=1660594192 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2022/20220816-kidney-blue.jpg?itok=054PoEgK&timestamp=1660594192" alt="Small blood vessels appear after treatment with OrganEx, but not with the standard machine" title="Perfused kidneys" />
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||
</picture><span class="caption">Pig kidneys after 3 hours of perfusion with a conventional heart-lung perfusion machine (top) and OrganEx (bottom). The black shows where fluid has reached. </span><span class="credit">Andrijevic et al., Nature</span></div>
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||
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||
</div><p>Without a steady supply of oxygen from the blood, processes leading to cell death in mammals begin within minutes. Recent studies have shown that cells can still recover even hours after interrupting blood flow. But such recovery has so far only been demonstrated in isolated organs.</p>
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||
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||
<p>An NIH-funded team of researchers led by Dr. Nenad Sestan at Yale School of Medicine developed a system to promote cellular recovery and preserve tissue integrity in the intact body after loss of blood flow. The system, called OrganEx, is based on the team’s previous work restoring circulation and cell function in a pig brain that was removed after the animal’s death.</p>
|
||
|
||
<p>OrganEx uses a device like the heart-lung machines that take over the functions of the heart and lungs during surgery. The device pumps a mix of the pig’s own blood and a protective fluid throughout the body’s blood vessels in a process called perfusion. This fluid contains oxygen and a synthetic form of hemoglobin—the oxygen-carrying protein in red blood cells. It also contains electrolytes and compounds designed to protect cells and prevent blood clots.</p>
|
||
|
||
<p>The researchers tested OrganEx in pigs undergoing cardiac arrest. Perfusion of pigs began one hour after cardiac arrest and continued for another six hours. Results appeared in <em>Nature </em>on August 3, 2022.</p>
|
||
|
||
<p>OrganEx was able to circulate the fluid throughout the body and deliver adequate oxygen to tissues. It also prevented electrolyte imbalances that normally occur when blood flow stops. The researchers compared OrganEx with a conventional heart-lung perfusion machine that pumped the pig’s own blood back through its body.</p>
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||
|
||
<p>OrganEx perfusion for six hours preserved cell and tissue integrity and reduced cell death in various organs. These included the brain, heart, liver, and kidneys. In the brain, OrganEx preserved all three major cell types: neurons, astrocytes, and microglia. Cells in the heart, liver, and kidneys had less damage than corresponding cells after treatment with the standard device. </p>
|
||
|
||
<p>The researchers also found signs of restored organ function in the perfused pigs. They observed glucose uptake in brain, heart, and kidneys. They found electrical activity and contraction in the heart, and protein synthesis in the liver and brain. Several organs activated genes associated with cellular repair processes and preventing cell death.</p>
|
||
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||
<p>These findings suggest the potential for organs to recover up to an hour after blood flow stops. OrganEx technology could leverage this potential to prolong the life of human donor organs. This could make more organs available for transplants. It might also help damaged organs to recover following heart attacks or strokes. Yet the researchers stress that further research will be needed. It remains to be seen how much organ function can be recovered and how long it can be maintained. Because of the ethical implications of brain recovery after death, this and future work will continue to require rigorous ethical review.</p>
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||
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||
<p>“There are numerous potential applications of this exciting new technology,” says study co-author Dr. Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics. “However, we need to maintain careful oversight of all future studies, particularly any that include perfusion of the brain.”</p>
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||
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<p>—by Brian Doctrow, Ph.D.</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/life-support-machine-helps-cardiac-arrest-patients-survive" target="_top">Life Support Machine Helps Cardiac Arrest Patients Survive</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/extending-preservation-time-donated-livers" target="_top">Extending Preservation Time for Donated Livers</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/preserving-livers-transplantation" target="_top">Preserving Livers for Transplantation</a></li><li><a href="https://newsinhealth.nih.gov/2011/03/organ-donation-pass-it" target="_top">Organ Donation: Pass it On</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/35922506/">Cellular recovery after prolonged warm ischaemia of the whole body.</a> Andrijevic D, Vrselja Z, Lysyy T, Zhang S, Skarica M, Spajic A, Dellal D, Thorn SL, Duckrow RB, Ma S, Duy PQ, Isiktas AU, Liang D, Li M, Kim SK, Daniele SG, Banu K, Perincheri S, Menon MC, Huttner A, Sheth KN, Gobeske KT, Tietjen GT, Zaveri HP, Latham SR, Sinusas AJ, Sestan N. <em>Nature</em>. 2022 Aug 3. doi: 10.1038/s41586-022-05016-1. Online ahead of print. PMID: 35922506.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of Mental Health (NIMH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of General Medical Sciences (NIGMS), and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Schmidt Futures.</p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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