In an advance that could improve battlefield and trauma care, scientists at University of California San Diego and Albert Einstein College of Medicine of Yeshiva University have used tiny particles called nanoparticles to improve survival after life-threatening blood loss. Nanoparticles containing nitric oxide (NO) were infused into the bloodstream of hamsters, where they helped maintain blood circulation and protect vital organs. The research was reported in the February 21 online edition of the journal Resuscitation.
The new nanomedicine, tested in this study in animal models, was developed to address the need for better field treatments for cases of massive blood loss, which can cause cardiovascular collapse, also known as hemorrhagic shock. This potentially fatal condition is best treated with infusions of allogeneic blood and other fluids. But such treatments are limited to emergency rooms or trauma centers.
“It is highly impractical to pack these supplies for use in rural emergencies, mass-casualty disasters or on the battlefield,” said coauthor Joel Friedman, M.D., Ph.D., professor of physiology & medicine and of medicine and the Young Men’s Division Chair in Physiology at Einstein. “Our nanoparticle therapy may offer the potential for saving lives in those situations. It’s lightweight and compact and doesn’t require refrigeration.”
The new therapy counters hemorrhagic shock by increasing the body’s levels of NO gas, which, among other physiological functions, relaxes blood vessels and regulates blood pressure.
The gas is generated inside microscopic-sized particles that were developed by the Einstein team. NO is so short-lived that delivering it in therapeutic amounts requires a method of sustained release. The therapy is created by adding the NO-containing nanoparticles to saline solution, which was then infused into the animals. Once in the body, the nanoparticles gradually release a sustained dose of NO to tissues.
The new nanomedicine was successfully tested at UC San Diego in hamsters that had lost half their blood volume.
“Animals given the nanoparticles exhibited better cardiac stability, stronger blood flow to tissues and other measures of hemorrhagic shock recovery compared to controls receiving saline solution minus the nanoparticles,” reported Dr. Friedman.
“The NO gas slows the fight-or-flight response to severe bleeding that restricts blood flow, causing hemorrhagic shock irreversibility. This is a significant step to establish the basis for new treatments for hemorrhagic shock; increasing the odds of survival when fluid resuscitation or definitive interventions are not available,” said paper coauthor Pedro Cabrales Ph.D., a professor in the Department of Bioengineering from the UC San Diego, Jacobs School of Engineering.
Decreasing vasoconstriction could make modern therapies for treating hemorrhagic shock more effective by allowing blood and other fluids to promptly reach the microcirculation.
Two previously published studies by Dr. Cabrales and Dr. Friedman and colleagues have demonstrated the beneficial effects of IV injected NO-containing nanoparticles for reversing blood substitute-induced hypertension, increasing tissue perfusion and reducing inflammation.
The paper, “Exogenous Nitric Oxide Prevents Cardiovascular Collapse During Hemorrhagic Shock,” appears in the Februrary 21, 2011 online edition of Resuscitation. Other Einstein authors of the study were Adam Friedman, M.D. and Parimala Nachuraju, Ph.D.CoauthorPedro Cabrales, Ph.D., of the University of California, San Diego, California, carried out the animal studies.