SUBSTRATE METABOLISM, HORMONE INTERACTION, AND ANGIOTENSIN-CONVERTINGENZYME-INHIBITORS IN LEFT-VENTRICULAR HYPERTROPHY

Left ventricular hypertrophy is considered to be an independent risk f actor giving rise to ischemia, arrhythmias, and left ventricular dysfu nction. Slow movement of intracellular calcium contributes to the impa ired contraction and relaxation function of hypertrophied myocardium. Myofibril content may also be shifted to fetal-type isoforms with decr eased contraction and relaxation properties in left ventricular hypert rophy. Myocyte hypertrophy and interstitial fibrosis are regulated ind ependently by mechanical and neurohumoral mechanisms, In severely hype rtrophied myocardium, capillary density is reduced, the diffusion dist ance for oxygen, nutrients, and metabolites is increased, and the rati o of energy-production sites to energy-consumption sites is decreased. The metabolic state of severely hypertrophied myocardium is anaerobic , as indicated by the shift of lactate dehydrogenase marker enzymes. T herefore, the hypertrophied myocardium is more vulnerable to ischemic events. As a compensatory response to severe cardiac hypertrophy and c ongestive heart failure, the ADP/ATP carrier is activated and atrial n atriuretic peptide is released to increase high-energy phosphate produ ction and reduce cardiac energy consumption by vasodilation and sodium and fluid elimination. However, in severely hypertrophied and failing myocardium, vasoconstrictor and sodium- and fluid-retaining factors, such as the renin-angiotensin system, aldosterone, and sympathetic ner ve activity, play an overwhelming role. Angiotensin-converting enzyme inhibitors (ACEIs) are able to prevent cardiac hypertrophy and improve cardiac function and metabolism, Under experimental conditions, these beneficial effects can be ascribed mainly to bradykinin potentiation, although a contribution of the ACEI-induced angiotensin II reduction cannot be excluded.