Force-length relationship in dogs as a measure of protective effect of imidapril on regional myocardial ischemia and reperfusion injury.
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.
Hosoya
K
K
Department of Medicine, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan.
Takeda
K
K
Nishikimi
T
T
Ishimitsu
T
T
Matsuoka
H
H
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000378:metabolism; D004285:Dogs; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D048289:Imidazolidines; D007262:Infusions, Intravenous; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D018727:Muscarinic Antagonists; D009569:Nitric Oxide; D001285:Atropine; D011433:Propranolol; C065166:imidapril; D001920:Bradykinin