Captopril, an ACE inhibitor, for optimizing reperfusion after acute myocardial infarction (original) (raw)
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European Journal of Pharmacology, 1996
Myocardial infarction induced hypertrophy of non-infarcted myocardium, in parallel with interstitial and perivascular fibrosis and a decreased capillary density, could increase sensitivity to ischemia. The structural cardiac changes can be reversed by long-term captopril treatment. In the present study, ischemic sensitivity in relation to cardiac perfusion was studied in isolated, perfused hearts of untreated and captopril-treated infarcted rats. In chronically (8 weeks) infarcted hearts, maximal vasodilation in response to administered adenosine and nitroprusside, as well as to endogenously released vasodilators during reperfusion, was decreased, suggesting impaired cardiac perfusion. Ischemic release of purines and lactate was reduced in infarcted hearts, indicating decreased sensitivity to ischemia of the remodeled myocardium. Captopril treatment (3-8 weeks post myocardial infarction), which reversed hypertrophy without affecting the flow capacity of the coronary vascular bed, restored maximal cardiac perfusion. Ischemic ATP breakdown was not affected by captopril, whereas lactate release was even further reduced, suggesting alterations towards a more aerobic ATP production. These data indicate that despite the reduced maximal cardiac perfusion, the remodeled myocardium of infarcted hearts is less sensitive to ischemia. Reversal of hypertrophy by chronic captopril restored maximal cardiac perfusion and led to a better preservation of aerobic ATP production during ischemia.
Cardioprotection by ACE Inhibitors in Myocardial Ischaemia/Reperfusion
Drugs, 1997
Myocardial ischaemia, when severe and sustained for more than 40 minutes, results in irreversible damage , i.e. myocardial infarction. However, with early reperfusion , damage is reversible. Complete recovery of contractile function requires some time, despite fully or almost fully restored blood flow. This phenomenon has been termed myocardial stunning. There is experimental evidence showing that angiotensin converting enzyme (ACE) inhibitors limit the development of infarct size, reduce the incidence of ischaemic and reperfusion arrhythmias, and enhance the recovery of contractile function of stunned myocardium. These cardioprotective effects of ACE inhibitors are mediated by an attenuated degradation of bradykinin. There is overwhelming evidence that angiotensin converting enzyme (ACE) inhibitors exert beneficial effects in patients with arterial hypertension or chronic heart failure, and after myocardial infarction .U '<' This review focuses on the experimental evidence for a protective role of ACE inhibitors in instances of an abrupt reduction in myocardial perfusion leading to irreversible cellular damage, i.e. myocardial necrosis, to life-threatening ventricular arrhythmias and, after reperfusion, to reversibly depressed contractile function, i.e. stunned myocardium.
Circulation, 2002
Whereas the number of patients with reduced left ventricular function after myocardial infarction who need revascularization is increasing, the operative outcome is still inadequate. Consequently, drugs that increase myocardial perfusion and decrease oxygen consumption of the remodeled myocardium are of particular interest to cardiac surgeons. Angiotensin-converting enzyme inhibitors (ACE-I) provide this pharmacologic profile. This study tests the hypothesis whether acute ACE inhibition during cardioplegic arrest improves outcome in failing rat hearts. Male Wistar rats (260+/-15 g) underwent coronary ligation. Ten weeks later the rats had developed heart failure (HF). Hearts were harvested and studied on a red cell-perfused working heart: 60 minutes of ischemia, protected by cold blood cardioplegia (CP) every 20 minutes, and 45 minutes of reperfusion. Rats were randomly assigned to 2 groups, 1 group receiving the ACE-I quinaprilat with CP (QuinaMI, n=11), and 1 group receiving CP on...
The ACE-inhibitor captopril improves myocardial perfusion in spontaneously diabetic (BB) rats
Diabetologia, 1995
The aim of this study was to examine the influence of inhibition on angiotensin converting enzyme (ACE) of myocardial function and perfusion of the rat impaired by diabetes. Spontaneously diabetic rats were treated with the ACE-inhibitor captopril for 4 months. Cardiac performance was analysed in the isolated heart perfused at constant volume. Epicardial perfusion was determined by measuring changes in epicardial fluorescence after injection of a bolus of fluoresceinisothiocyanate-dextrane (3 kDa) as described previously. As compared to untreated diabetic controls, captopril prevented the increase of end diastolic pressure, coronary perfusion pressure and vascular resistance. The intravascular volume was enlarged and the epicardial perfusion rate increased in hearts of diabetic rats treated with captopril as compared to diabetic controls. Treat-ment of diabetic rats with the ACE-inhibitor captopril (1) increases the number of perfused capillaries, and (2) can partly prevent the development of cardiac dysfunction in diabetes. Together with morphological data demonstrating an inhibition of interstitial and perivascular fibrosis in hearts of diabetic rats treated with captopril, our data suggest that ACE-inhibition is cardioprotective in diabetes. These observations are also compatible with the assumption that an accelerated generation of angiotensin II may be involved in the pathophysiological chain of events leading to diabetic cardiopathy. [Diabetologia (1995) 38: 509-517]
1991
Captopril, an inhibitor of angiotensin-converting enzyme, has been suggested to have additional cardioprotective action because of its ability to act as an antioxidant. The rates of reaction of captopril with several biologically-relevant reactive oxygen species were determined. Captopril reacts slowly, if at all, with superoxide (rate constant < 108 M -1 s -1) or hydrogen peroxide (rate constant < 1 M-~ s-l). It does not inhibit peroxidation of lipids stimulated by iron ions and ascorbate or by the myoglobin]H202 system. Indeed, mixtures of ferric ion and captopril can stimulate lipid peroxidation. Captopril reacts rapidly with hydroxyl radical (rate constant > 109 M -1 s -1) but might be unlikely to compete with most biological molecules for "OH because of the low concentration of captopril that can be achieved in vivo during therapeutic use. Captopril did not significantly inhibit iron ion-dependent generation of hydroxyl radicals from hydrogen peroxide. By contrast, captopril is a powerful scavenger of hypochlorous acid: it was able to protect %-antiproteinase (%AP) against inactivation by this species and to prevent formation of chloramines from taurine. We suggest that the antioxidant action of captopril in vivo is likely to be limited, and may be restricted to protection against damage by hypochlorous acid derived from the action of neutrophil myeloperoxidase.
Journal of Molecular and Cellular Cardiology, 1991
but not Immediate Captopril Therapy Improves Cardiac Function in Conscious Rats, Following Myocardial Infarction. foumal of A4olccular and Cellular Cardiology (1991) '23, 187-197. After myocardial infarction, the reninangiotensin system is found to be activated. While this response may be beneficial in acute failure, it could be detrimental in chronic stages. Therefore effects of captopril therapy were investigated during early and later phases after myocardial infarction in conscious rats, chronically instrumented for hemodynamic measurements. Hemodynamics were measured at baseline and after stimulating the heart by a volume load (cardiac function curve). Myocardial infarction decreased baseline cardiac output and impaired cardiac function, without effects on baseline mean arterial pressure, central venous pressure and heart rate. Captopril given 3 to 5 weeks after infarction improved cardiac function in a dose-dependent manner by increasing stroke volume, whereas stroke work was not affected. In contrast, captopril given from 1 to 21 days after infarction did not lead to improved cardiac function; instead, tachycardia together with a decreased stroke volume suggested deterioration, rather than improvement, of cardiac function. These data indicate that captopril therapy in chronically infarcted conscious rats improved cardiac function when treatment was started after completion of the healing process, but that early treatment not only failed to improve ventricular function, but may have a deleterious effect of the heart.
Effects of captopril on myocardial protection during cardioplegia
International Journal of Cardiology, 1993
The study aimed at checking effects exerted by captopril (C) on human myocardial ACE system as well as the role played by tissue ACE inhibition in reducing reperfusion damage. A human experimental model was used during cardioplegia due to aorto-coronary-by-pass (CABG). Fifty-four patients with coronary artery disease affecting 3 vessels having suffered from acute myocardial infarction anterior (AMI-ant), homogeneous as far as ejection fraction (35-55%). number of grafts (3), clamping time, age and sex, were randomised in a double blind experiment, and were given captopril or placebo (P). A total of 4 mg/I Captopril was mixed into the cardioplegic solution with blood according to the method of Buckberg (Buckberg GD. J Thorac Cardiovasc Surg 1987; 93: 127-139). Eight samples (blood/perfusate) were obtained from each patients and norepinephrine (NE). epinephrine (E) were assayed using an HPLC technique. Angiotensin 1 was assayed by RIA. CK was also assayed (units/ml). Bloodiperfusate samples were taken during CABG: (I) pre-pump; (2) pump sample; (3) pump preclamping; (4) coronary sinus; (5) coronary sinus sample during reperfusion; (6) coronary sinus during warm reperfusion; (7) after clamping sample; after decanulation; Results: Captopril group (29 patients): angiotensin I: () 399; pg/ml (P < 0.01). CK, captopril group: (I) 79; (2) 95; (3) 100; (4) 94; (5) 104; (6) 94; (7) 108; (8) 108; vs. placebo: (I) 76; (2) 120; (3) 135; (4) 152 (5) 225; (6) 272; (7) 247; (8) 228; units/ml. (P < 0.01).
Basic Research in Cardiology, 2010
Brief periods (a few seconds) of cyclic coronary occlusions applied early in reperfusion induce a cardioprotection against infarct size, called postconditioning (PostC) in which B 2 -bradykinin receptors play a pivotal role. Since angiotensin-converting enzyme (ACE) inhibitors reduce degradation of kinins, we studied the effects of PostC on infarct size and postischemic myocardial dysfunction in both normotensive (WKY) and spontaneously hypertensive rats (SHR) acutely or chronically treated with the ACE inhibitor Captopril. Isolated hearts from SHR and WKY rats were subjected to the following protocols: (a) ischemia for 30-and 120-min reperfusion (