A preclinical study offers molecular insight into how activated protein C (APC) may improve the tolerance of aging hearts to reperfusion injury — a potentially adverse effect of treatment for ischemic heart disease

The research, published online Dec. 21 in Circulation Research, suggests that drugs derived from APC may limit ischemia and reperfusion-induced heart damage (reperfusion injury for short) and thereby help preserve cardiac function in older hearts.

Advanced age is a major risk factor for ischemic heart disease, often caused by a buildup of plaques in coronary arteries that narrows the vessels and restricts the supply of oxygenated blood to the heart. This «hardening of the arteries» can eventually trigger a heart attack.

Blood thinners, clot-buster medications, and other drugs, as well as procedures such as coronary artery bypass surgery and balloon angioplasty, are commonly used to restore blood flow to oxygen-starved (ischemic) heart muscle tissue. Paradoxically, especially in older patients, these necessary revascularization treatments can worsen cellular dysfunction and death around the site already damaged by a heart attack, or coronary artery disease. No effective treatments currently exist to prevent age-related reperfusion injury.

«Our research focuses on trying to determine why older hearts are at greater risk for reperfusion injury than younger hearts,» said lead author Di Ren, PhD, a research associate in the Department of Surgery, USF Health Morsani College of Medicine. «Our goal is to find targeted therapeutic strategies to help older people improve their resistance to the pathological condition of ischemia and reperfusion stress.»

«The preliminary evidence in this paper suggests that treatment with activated protein C has the potential to strengthen the cardiac tolerance of aging patients to reperfusion injury from surgery, minimally invasive procedures, or drugs, and (thereby) increase heart attack prevention or survival,» said the study’s principal investigator Ji Li, PhD, a professor of surgery at the USF Health Heart Institute.

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Materials provided by University of South Florida (USF Health). Original written by Anne DeLotto Baier. Note: Content may be edited for style and length.