Many myocardial proteins undergo programmed isoform change during fetal and neonatal development. Although post-developmental, non-programmed isoform change has also been shown in some myocardial proteins, isoenzymatic changes in myocardial creatine kinase(CK), lactate dehydrogenase(LD), and aspartate aminotransferase(AST)due to envilonmental stimuli have not been fully investigated yet. Therefore, in this study, we investigated myocardial isoenzyme redistribution of CK, LD, and AST in adult animals with catecholamine, hereditary, or diabetic cardiomyopathy, heart failure, or myocardial reperftision. Effects of calcium channel blockers(diltiazem, verapamil)and an angiotensin converting enzyme inhibitor(enalapril)on isoenzyme redistribution were also observed.
(1)In rats with chronic isoproterenol administration, Bio 14.6 hamsters, and rats with chronic left or right heart failure, significant depression of myocardial total CK activity as well as isoenzyme redistribution of CK and LD occ
urred. MM CK, mitochondrial CK, and LD1 activities decreased, and both CK-B and LD-M subunits(activity or %)increased. These changes positively correlated with the degree of myocardial injury or failure. Simultaneous MM and mitochondrial CK decrease in the myocardium indicates suppression of "phosphocreatine energy shuttle". Increases in CK-B, the affinity of which to creatine phophate is higher than CK-M, and LD-M, which favors anerobic metabolism than LD-H, may be metabolic compexisations of the ischemic or failing heart. Preliminary study showed that enalapril improved right heart failure, mortality rate, and myocardial isoenzyme redistribution without reducing pulmonary arterial pressure in rats with monocrotaline-induced pulmonary hypertension.
(2)In streptozocin-induced diabetic(IDDM)rats, myocardial total, MM and mitochondrial CK activities were all depressed just like the animals described in(1). However, in contrast with them, myocardial LDi activity increased and both CKB and LD-M(activity or %)decreased in the diabetic heart suggesting lack of compensation to myocardial ischemia or failure, or absence of ischemia or failure per se. These changes were not normalized by diltiazem or verapamil at all, but almost completely recovered by insulin indicating that isoenzyme redistribution in the diabetic heart may not be related to intracellular calcium overload, but to insulin deficiency.
(3)In the reperfused myocardium in awake rat model of 90 min ischemia followed by 24 h reperfusion, myocardial LD_1 activity was significantly(and LD-H subunit activity tended to be)restored suggesting the recovery of aerobic metabolism and/or the cessation of the infiltrafion of inflammatory cells. Less