Hyperthyroidism is known to alter both systolic and diastolic cardiac function, as well as induce left ventricular hypertrophy. To investigate the cellular basis for these phenomena rats were rendered hyperthyroid and single left ventricular myocytes were isolated via collagenase perfusion of the intact heart. Contractile waves in the absence of stimulation as well as stimulated twitches were measured. Isolated hyperthyroid myocytes, when compared to their euthyroid controls, were found to maintain many of the contractile properties found in bulk preparation, thus validating the model and indicating that at lease some of the changes in cardiac function seen in the hyperthyroid state are intrinsic to the myocardium, and not secondary to altered loading conditions or heart rate. Using contractile waves in the absence of stimulation as an indication of the frequency of spontaneous calcium-induced calcium release from the sarcoplasmic reticulum, we find that hyperthyroid myocytes have more frequent spontaneous sarcoplasmic reticulum calcium release than euthyroid myocytes. Under some conditions these waves diminish twitch amplitude to a greater extent in hyperthyroid than in euthyroid myocytes. This may provide a basis for the hyperthyroid cardiomyopathy. Hyperthyroid myocytes are also more sensitive to both the inotropic and toxic effects of digitalis glycosides than euthyroid myocytes. Glycoside augmentation of contractile waves and induction of aftercontractures seen in single myocytes may reflect the cellular basis of afterdepolarizations and aftercontractures seen in bulk muscle. Studies are in progress to analyze photomicrographs of hyperthyroid myocytes so that functional changes which we have characterized on the cellular level may be extrapolated to the level of the sarcomere, the fundamental contractile unit.
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