Chronic Administration of Nicardipine Attenuates Myocardial Stunning in Isolated Rabbit Hearts

The purpose of this study was to evaluate the effects of the chronic administration of a calcium channel blocker, nicardipine, on systolic and diastolic alterations occurring during myocardial stunning in isolated rabbit hearts. Rabbits were presented with nicardipine 20 mg (O.I.D.) for 30 days. Then hearts were isolated (group II) and compared with control hearts (group I) in their response to 20 min of global ischemia and 30 min of reperfusion. Coronary flow and heart rate were kept constant. Left ventricular isovolumic developed pressure (LVDP), its first derivative (dP/dt), and end diastolic pressure (LVEDP) were measured. After isolation, no statistically significant changes were detected in LVDP, + dP/dt_max, LVEDP, or coronary resistance in hearts of rabbits with or without the pharmacological intervention. Early after the onset of reperfusion, LVDP and + dP/dt_max partially recovered in a similar way in groups I and II. Late in reperfusion LVDP stabilized at 48 ± 7% in group I and 71 ± 6% in group II (P < 0.05) and + dP/dt_max stabilized at 56 ± 7% and 79 ± 6% (P < 0.05), respectively. Diastolic dysfunction was manifested by a 217 ± 39% increase in LVEDP (P < 0.05) in group I, and 140 ± 31% in group II (P < 0.05). The isovolumic relaxation time constant (τ, tau) increased from 70 ± 5 to 151 ± 27 ms (P < 0.05) and from 66 ± 6 to 97 ± 10 ms (NS) in groups I and II, respectively at 5 min of reperfusion. This relaxation parameter returned to normal values in the late reperfusion. Pretreating rabbits with nicardipine appears to protect the heart from the systolic and the diastolic dysfunction of stunning without evidence of prior decrease in contractile state or changes in coronary resistance.