Effects of ACE inhibition and β-receptor blockade on energy metabolism in rats postmyocardial infarction

Abstract

Chronic treatment with beta-receptor blockers or angiotensin-converting enzyme (ACE) inhibitors in heart failure can reduce mortality and improve left ventricular function, but the mechanisms involved in their beneficial action remain to be fully defined. Our hypothesis was that these agents prevent the derangement of cardiac energy metabolism. Rats were subjected to myocardial infarction (MI) or sham operation. Thereafter, animals were treated with bisoprolol, captopril, or remained untreated. Two months later, cardiac function was measured in the isolated heart by a left ventricular balloon (pressure-volume curves), and energy metabolism of residual intact myocardium was analyzed in terms of total and isoenzyme creatine kinase (CK) activity, steady-state levels (ATP, phosphocreatine), and turnover rates (CK reaction velocity) of high-energy phosphates (31P nuclear magnetic resonance) and total creatine content (HPLC). Bisoprolol and partially captopril prevented post-MI hypertrophy and partially prevented left ventricular contractile dysfunction. Residual intact failing myocardium in untreated, infarcted hearts showed a 25% decrease of the total, a 26% decrease of MM-, and a 37% decrease of the mitochondrial CK activity. Total creatine was reduced by 15%, phosphocreatine by 21%, and CK reaction velocity by 41%. Treatment with bisoprolol or captopril largely prevented all of these changes in infarcted hearts. Thus the favorable functional effects of beta-receptor blockers and ACE inhibitors post-MI are accompanied by substantial beneficial effects on cardiac energy metabolism.

Effects of Angiotensin-converting Enzyme Inhibition on Changes in Left Ventricular Myocardial Creatine Kinase System After Myocardial Infarction: Their Relation to Ventricular Remodeling and Function

“…These changes were in agreement with previous findings in experimental heart failure 5,6,8,9,[12][13][14] and in end-stage human heart failure, 15,16) and were characterized by a significant shift of cardiac CK isoenzymes towards the fetal BB-and MB-CK isoenzymes. This suggests a compensatory mechanism towards a more efficient cardiac CK system to improve cardiac energy metabolism in the LV dysfunctional condition.…”

“…23) A number of investigators reported changes in the cardiac CK system in chronic heart failure after experimental MI in rats, usually at 8 weeks after coronary ligation. 5,6,8,[10][11][12] These included reductions in total CK and mitochondrial CK activities and decreased total CR levels, as shown at 12 weeks after MI in the present study. In addition, a decreased mitochondrial CK fraction and increased MB-and BB-CK fractions were also characterized.…”

“…5,6) In general, alterations of energy metabolism in the chronically failing heart are characterized by diminished energy reserve of the noninfarcted left ventricular (LV) myocardium in association with a marked decrease in creatine phosphate (CP), total creatine (CR), total creatine kinase (CK), and mitochondrial CK isoenzyme activity and shifts of CK isoenzymes and lactate dehydrogenase isoenzymes. [5][6][7][8][9][10][11][12][13][14] In human heart failure, it has been reported that alterations of the myocardial CK system are associated with a depressed total enzyme activity and changes in isoenzyme distribution and contribute to the pathogenesis of heart failure. 15,16) However, there have been no detailed reports on the changes in myocardial energy metabolism after MI and their relation to LV remodeling and function in heart failure.…”

Chronic Phosphocreatine Depletion by the Creatine Analogue β-Guanidinopropionate Is Associated With Increased Mortality and Loss of ATP in Rats After Myocardial Infarction

“…15 Furthermore, in residual intact myocardium, PCr levels are reduced by up to 30% 15 and Flux CK up to 50%, 15 but ATP and P i levels remain constant. This HF model is well suited to study the effects of pharmacological intervention: eg, ACE inhibitors 18,22 and ␤-receptor blockers 22 have been found to preserve cardiac structure, function, and energetics, whereas the Ca 2ϩ channel blocker anipamil 23 exerted detrimental effects in this model.…”

The Effects of Biological Sex and Diet on the Development of Heart Failure

“…3,4 In contrast, the finding that estradiol-treated female rodents have a greater post-MI rate of death argues against a protective role. 5,6 Recent human studies on hormone replacement therapy similarly question the cardioprotective role of estrogen. 7,8 Clearly, the role of estrogen in cardiovascular disease (CVD) is complex, and further study is necessary.…”