Our laboratory previously reported that the end-systolic force-length relationship of the left ventricle provides a better method of evaluating myocardial contractile properties than the left ventricular end-systolic pressure-volume relationship, because it avoids deficiencies of the latter parameter such as dependence of its slope (E(max)) on the volume intercept (V(0)). The slope (E(c)) of the left ventricular end-systolic force-length relationship represents the contractility of functioning myocardium, while its length intercept (L(0)) reflects the length of non-functioning myocardium. However, the effect of regional
myocardial ischemia on these parameters, as evaluated by the force-length relationship, remains unknown. To clarify the effects of regional
ischemia and
angiotensin-converting enzyme inhibition on the myocardium during
ischemia-reperfusion, the changes in E(c) and L(0) were determined in anesthetized open-chest dogs. (1) Control group (n=26): Before and after 15 min of complete coronary artery occlusion, as well as after 15 min of reperfusion, left ventricular pressure and volume were simultaneously recorded during inferior vena cava occlusion. The left ventricular force-length relationship was obtained from the pressure and volume of three cylindrical segments of the ventricle, and E(c) and L(0) were calculated. (2)
Imidapril group (n=14):
Imidaprilat (1 microg/kg/min) was continuously infused from 30 min before
ischemia to the end of the experiment, and the same procedures were followed as in the control group. Fourteen out of the 26 dogs (54%) in the control group died of reperfusion-induced ventricular arrhythmias, while only two of the 14 dogs (14%) in the
imidapril group did so (P<0.05). In the control group, E(c) was increased during
ischemia and remained at the same level after reperfusion. However, E(c) was not altered in the
imidapril group. Although L(0) was increased during
ischemia and decreased after reperfusion in both groups, the percent increase of L(0) in the
imidapril group was significantly smaller than in the control group (8% vs. 32%, P<0.05). With the improvement of these indices, the
bradykinin concentration of coronary venous blood increased in the
imidapril group (P<0.01). These findings suggest that regional
myocardial ischemia increased the average contractility of overall functioning myocardium despite the increased non-functioning myocardium. Moreover,
imidapril has a cardioprotective effect against
ischemia-reperfusion injury by decreasing
infarct size, and through the antiarrhythmic effect and the reversal of increased overall contractility.