Effect of AT1 receptor blockade on cardiovascular outcome after cardiorespiratory arrest: an experimental study in rats

Abstract

BackgroundAT1 angiotensin II receptor (ATI) antagonists are beneficial in focal ischemia/reperfusion (I/R) cases. However, in cases of global I/R, such as cardiorespiratory arrest (CRA), ATI blocker’s effects are still unknown.MethodsRats were allocated into four groups: Sham group (SG) – animals submitted to surgical interventions, without CRA; Control group (CG) – animals submitted to CRA and ventricular fibrillation; Group AT1 (GAT1) – like CG, plus 0.2 mg/kg of Candesartan; Vehicle Group (VG): animals equally induced to CRA, and administration of 0.2 ml/kg of dimethyl sulfoxide. The rate of return of spontaneous circulation (ROSC), survival, hemodynamic variables, histopathology, and markers of tissue injury were analyzed.ResultsCompared to CG, the GAT1 group had a higher rate of ROSC (62.5% vs. 42.1%, p<0.0001), survival (100% vs. 62.5%, CI: 0.014-0.034; p = 0.027), lower incidence of arrhythmia after 10 minutes of ROSC, (10% vs. 62.5%, p=0.000) and lower neuronal and cardiac injury scores (p=0.025 and p=0.021, respectively). The groups did not differ regarding CRA duration, number of adrenaline doses, or number of defibrillations.ConclusionATI receptor blockade was responsible for higher rates of ROSC and survival, in addition to demonstrating neuronal and myocardial protection.HighlightsAT1 receptor block was responsible per higher rates of ROSC and survival in intervention group.The AT1 receptor block can be neuroprotector in ischemic injury caused by CPR.The candesartan administration during CPR can contribute with reduction of ventricular arrythmias.