Acetaminophen and Myocardial Stunning after Transient Ischemia in Rabbit Hearts

Abstract

Myocardial stunning is a lingering contractile dysfunction that occurs after brief ischemia, even in the absence of necrosis. Recent studies have shown that acetaminophen may have some benefit on the return of left ventricular function after brief global ischemia in an in vitro model. This study was conducted to determine whether treatment with acetaminophen results in enhanced myocardial tolerance to transient ischemia-reperfusion by improving left ventricular function and decreasing stunning in an in vivo model. Anesthetized, open-chest rabbits were randomized to receive acetaminophen (37 mg/kg, n = 13) or saline (n = 11) 15 minutes before a series of transient coronary artery occlusions followed by reperfusion (three 10-minute periods of ischemia with 5 minutes reperfusion between). Hemodynamics and maximal and minimal values of developed pressure velocity (dP/dt) were measured at baseline, during ischemia, and throughout 2 hours of reperfusion. To assess myocardial stunning, echocardiography was used to determine regional systolic wall thickening fractions and global indices of function such as LV cavity dimensions and ejection fraction. Hemodynamic variables, including left ventricular systolic pressure and positive and negative dP/dt, were similar in both groups throughout the study. Left ventricular end-diastolic pressure was significantly lower in the acetaminophen group during occlusion and early reperfusion. The repeated short periods of ischemia in the free wall of the heart caused myocardial stunning in both groups. During ischemia, contractile function in the free wall was severely reduced, and although it improved during reperfusion, dysfunction persisted in the postischemic free wall after 2 hours of reflow, recovering to less than 52% of preischemic values (P < .01). The degree of dysfunction was similar in both groups. During ischemia, the end-diastolic left ventricular cavity area increased from 1.14 +/- 0.05 cm2 at baseline to 1.33 +/- 0.08 cm2 (P < .05) in controls, but had recovered after 2 hours of reflow. The end-diastolic area in acetaminophen-treated hearts increased from 1.13 +/- 0.08 cm2 at baseline to 1.35 +/- 0.08 cm2 during ischemia and also recovered 2 hours later. No significant differences in LV cavity areas were noted between the groups. Acetaminophen had no effect on changes in ejection fraction, which decreased similarly in both groups during ischemia to approximately 75% of baseline values. Although ejection fraction improved, it remained depressed at the end of reflow in both groups. Data from this study show that in a rabbit model of myocardial stunning, acetaminophen has a neutral effect on hemodynamics, recovery of fractional thickening, and on indices of global recovery such as left ventricular cavity dimensions or ejection fraction. Thus in the setting of experimental myocardial stunning, treatment with acetaminophen was safe but not cardioprotective.