Rethinking Heart Failure

Abstract

An increasing body of clinical observations and experimental evidence suggests that cardiac dysfunction results from autonomic dysregulation of the contractile output of the heart. Excessive activation of the sympathetic nervous system and a decrease in parasympathetic tone are associated with increased mortality. Elevated levels of circulating catecholamines closely correlate with the severity and poor prognosis in heart failure. Sympathetic over-stimulation causes increased levels of catecholamines, which induce excessive aerobic metabolism leading to excessive cardiac oxygen consumption. Resulting impaired mitochondrial function causes acidosis, which results in reduction in blood flow by impairment of contractility. To the extent that the excessive aerobic metabolism resulting from adrenergic stimulation comes to a halt the energy deficit has to be compensated for by anaerobic metabolism. Glucose and glycogen become the essential nutrients. Beta-adrenergic blockade is used successfully to decrease hyperadrenergic drive. Neurohumoral antagonists block adrenergic over-stimulation but do not provide the heart with fuel for compensatory anaerobic metabolism. The endogenous hormone ouabain reduces catecholamine levels in healthy volunteers, promotes the secretion of insulin, induces release of acetylcholine from synaptosomes and potentiates the stimulation of glucose metabolism by insulin and acetylcholine. Ouabain stimulates glycogen synthesis and increases lactate utilisation by the myocardium. Decades of clinical experience with ouabain confirm the cardioprotective effects of this endogenous hormone. The so far neglected sympatholytic and vagotonic effects of ouabain on myocardial metabolism clearly make a clinical re-evaluation of this endogenous hormone necessary. Clinical studies with ouabain that correspond to current standards are warranted.