Myocardial metabolism in toxin-induced heart failure and therapeutic implications

Background. Under normal conditions, myocardial metabolism is 60-80% reliant on the oxidation of fatty acids. This can be modified by conditions such as ischemia or poisoning with specific drugs, with the myocardium becoming more dependent on carbohydrate metabolism for energy. Acute poisoning with cardiotoxic drugs may be complicated by heart failure that is at present usually treated by inotropic drugs and vasopressors. However, changes in metabolic processes in poisoning may offer an opportunity for novel therapies. Current evidence. The scientific evidence obtained from ischemia-reperfusion models and the preservation of myocardial metabolism when myocardial blood flow is restored after a brief coronary occlusion (a theory known as "myocardial stunning") support this concept. Generalized or localized myocardial stunning may develop in patients who do not present with acute myocardial ischemia secondary to coronary artery disease, a condition referred to as takotsubo cardiomyopathy. This is characterized by the preservation of myocardial blood flow, associated with a depressed myocardial contractility, lasting from hours to weeks. Therapeutic implications. Several factors have been associated with takotsubo cardiomyopathy:- excessive sympathetic stimulation, either from exogenous or endogenous origin; drug poisoning or drug withdrawal. The metabolism of both glucose and fatty acids appears to be reduced in the hypocontractile areas. One of the hypotheses is that the catecholamine-mediated myocardial insulin resistance may be responsible for reduced glucose uptake. Among the drugs taken in overdose, calcium channel blockers and beta-blockers have been shown to influence myocardial metabolism, with a shift from fatty acids to glucose utilization. This is the rationale for the administration of insulin in order to stimulate glucose myocardial uptake. In addition, insulin at high doses seems also to have inotropic effects, which are independent from its effects on myocardial substrate handling. Conclusion. Better understanding of the relationship between the receptor interactions of myocardial toxins and their effects on myocardial metabolism is likely to result in the development of new targeted therapies aimed specifically at optimising metabolic processes in poisoning.