Atrionatriuretic Peptide Improves Left Ventricular Function After Myocardial Global Ischemia-Reperfusion in Hypoxic Hearts

Abstract

Atrionatriuretic peptide (ANP) is reported to be useful for attenuating myocardial ischemia-reperfusion injury and improving left ventricular function after reperfusion. However, ANP may be either ineffectual or harmful in cases where the myocardium has been chronically hypoxic since birth. This can be a result of the concomitant high levels of cyclic guanosine monophosphate (cGMP) produced within the myocardium. This study aimed to verify the validity of using ANP to improve left ventricular function after myocardial ischemia-reperfusion injury. For this purpose, a cyanotic congenital disease model that was developed using isolated rat hearts was used. Hearts were obtained from Sprague-Dawley rats that were housed from birth until 6 weeks of age either in a hypoxic environment with 13-14% FiO(2) (hypoxic group) or in ambient air (normoxic group). These hearts were subjected to 30min of normothermic global ischemia followed by 30min of reperfusion using the Langendorff technique. Left ventricular functional recovery in hearts administered ANP (0.1µM) into the reperfusion solution was compared with those hearts that were not administered ANP in both hypoxic (without ANP: n=6, with ANP: n=6, with ANP and HS-142-1[an antagonist of ANP]: n=6) and normoxic hearts (without ANP: n =6, with ANP: n=6). In the hypoxic hearts, ANP administration improved the percent recovery of the left ventricular developed pressure (76.3±9.2% without ANP vs. 86.9±6.7% with ANP), maximum first derivative of the left ventricular pressure (82.4±1.1% without ANP vs. 95.8±6.5% with ANP), and heart rate (85.6±4.7% without ANP vs. 96.1±5.2% with ANP) after reperfusion. The improvement and recovery of these cardiac functions were closely related to significantly increased levels of postischemic cGMP release after ANP administration. The effect of ANP was blocked by HS-142-1. The improvements observed in the hypoxic group were similar to those found in the normoxic group. ANP administration during reperfusion improved left ventricular function after myocardial acute global ischemia-reperfusion equally in both the chronically hypoxic and age-matched normoxic groups.