Article ID Journal Published Year Pages File Type
5999204 Resuscitation 2011 7 Pages PDF
Abstract

Study aimsCardiac arrest mortality is significantly affected by failure to obtain return of spontaneous circulation (ROSC) despite cardiopulmonary resuscitation (CPR). Severe myocardial dysfunction and cardiovascular collapse further affects mortality within hours of initial ROSC. Recent work suggests that enhancement of nitric oxide (NO) signaling within minutes of CPR can improve myocardial function and survival. We studied the role of NO signaling on cardiovascular outcomes following cardiac arrest and resuscitation using endothelial NO synthase knockout (NOS3−/−) mice.MethodsAdult female wild-type (WT) and NOS3−/− mice were anesthetized, intubated, and instrumented with left-ventricular pressure-volume catheters. Cardiac arrest was induced with intravenous potassium chloride. CPR was performed after 8 min of untreated arrest. ROSC rate, cardiac function, whole-blood nitrosylhemoglobin (HbNO) concentrations, heart NOS3 content and phosphorylation (p-NOS3), cyclic guanosine monophosphate (cGMP), and phospho-troponin I (p-TnI) were measured.ResultsDespite equal quality CPR, NOS3−/− mice displayed lower rates of ROSC compared to WT (47.6% [10/21] vs. 82.4% [14/17], p < 0.005). Among ROSC animals, NOS3−/− vs. WT mice exhibited increased left-ventricular dysfunction and 120 min mortality. Prior to ROSC, myocardial effectors of NO signaling including cGMP and p-TnI were decreased in NOS3−/− vs. WT mice (p < 0.05). Following ROSC in WT mice, significant NOS3-dependent increases in circulating HbNO were seen by 120 min. Significant increases in cardiac p-NOS3 occurred between end-arrest and 15 min post-ROSC, while total NOS3 content was increased by 120 min post-ROSC (p < 0.05).ConclusionsGenetic deletion of NOS3 decreases ROSC rate and worsens post-ROSC left-ventricular function. Poor cardiovascular outcomes are associated with differences in NOS3-dependent myocardial cGMP signaling and circulating NO metabolites.

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