All fibers in three normal, four dilated, and two ischemic human ventricles were classified according to their myosin content using three sets of monoclonal antibodies each specific for one myosin heavy chain isoform (alpha, beta and beta'). Numerous fibers contained only beta myosin heavy chain (denoted as beta fibers), others contained either alpha and beta, or beta and beta' myosin heavy chain (denoted as alpha beta and beta beta' fibers, respectively). The percentages of alpha beta fibers were systematically determined along the walls of seven homologous regions of the ventricular myocardium. In all ventricles, there was an alpha beta-fiber transmural gradient, with less alpha beta fiber in the subendocardium than in the subepicardium. More alpha beta fibers were found in the right than in the left ventricular wall but there was no difference between the mid-portion and the apex of the free wall of each ventricle. The diseased ventricles contained a lower alpha beta fiber percentage than the normal hearts. beta beta' fibers were very rare in the normal ventricles (less than 5%) and almost inexistent in pathological hearts. The correlation between the mean alpha beta fiber percentages of the diseased hearts and their cardiac indices (r = 0.88, P less than 0.05) suggests that the small amount of alpha myosin distributed in a large number of ventricular fibers could play a role in the contractile performance of the heart. In conclusion, this study provides evidence for 1) an alpha beta fiber transmural gradient, and 2) a lower alpha myosin ratio in diseased than in normal human ventricle.

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A study was performed to assess whether plasma and myocardial concentrations of amiodarone correlated with changes on the surface electrocardiogram. Nine patients--seven with angina and two with paroxysmal ventricular tachycardia--were treated with oral amiodarone (200-400 mg daily) for at least nine months before undergoing cardiac surgery. QT intervals were measured from lead II of the surface electrocardiograms recorded before amiodarone treatment and immediately before surgery. Patients with prominent U waves after taking amiodarone were excluded from the study. Plasma and myocardial samples were collected at the beginning of the surgical procedure for estimating plasma and myocardial concentrations using the high performance liquid chromatographic technique. Amiodarone caused a significant lengthening of the QTc interval. There was a good correlation between plasma and myocardial concentrations, and both correlated well with the percentage increase in the QTc interval. Although there was a strong correlation between the dosage given (mg/kg/day) and both plasma and myocardial concentrations, the correlation with the percentage increase in the QTc interval was weaker but still highly significant. Despite previous reports to the contrary, the findings indicate that the plasma concentration of amiodarone does correlate well with the myocardial concentration. The degree of lengthening of the QTc interval may be used clinically to estimate the myocardial concentration of amiodarone.

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