Adult cardiac myocytes are incapable of mitosis. Dead cells are replaced by connective tissue so that after myocardial infarction (MI), function can only be restored by compensatory hypertrophy of the surviving myocardium. In physiological hypertrophy in response to exercise, high altitude, or mild hypertension, additional myoplasm expands cell diameter in an orderly fashion; Z-lines are in register and the normal ratio of volume densities of contractile elements, mitochondria, and capillaries is conserved. In hypertrophy induced by aortic or pulmonary artery banding or by experimental or congenital hypertension, the borderline between physiological and pathological hypertrophy may be crossed, causing disorganization of fibers and an unfavourable contractile element to capillary ratio. There was, therefore, a need for a graded model of hypertrophy, which involves simulating an altitude of 6,000 m at sealevel by supplying rabbits with appropriate nitrogen/oxygen mixtures. In this environment, 50% right ventricular hypertrophy can be achieved without alteration of left ventricular weight or hematocrit. Longer exposures produced 100% right ventricular hypertrophy, with only moderate increases in hematocrit and left ventricular weight. It is well known that adrenergic stimulation causes cardiac hypertrophy, and it has been suggested that release of a trophic factor from sympathetic nerves, either noradrenaline or a protein, might be a necessary stimulus for growth. If so, long-term treatment of post-MI patients with β-adrenergic blocking agents could inhibit a desirable compensatory hypertrophy of the surviving myocardium. In the above model it has been found, however, that neither β-blockade nor chemical sympathectomy with guanethidine or 6-hydroxydopamine had any effect on the hypertrophy, nor did treatment with verapamil or nifedipine. All the hypertrophied cardiac tissues studied had increased action potential durations (APD), but other electrophysiological parameters were little changed. During periods of acute exposure to hypoxia in vitro, APD shortened less in the hypertrophied hearts than in the controls. During intervals of normoxia, interposed between the periods of acute hypoxia, recovery of contractions and of all electrophysiological changes was complete. It is concluded that the hypertrophy did not cause associated electrical alterations likely to increase the risk of arrhythmias.
Address correspondence and reprint requests to E. M. Vaughan Williams, at Hertford College, Oxford University, Oxford OX1, U.K.
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