Fiber orientation across the left ventricular myocardial wall has been studied. Specimens were obtained from 18 dog hearts rapidly fixed in situ in systole, in diastole, and in dilated diastole. Fiber orientation was determined across the free wall at eight sites from a T-shaped specimen by measurements with light microscopy in serial paraffin sections. Results indicate: (1) The wall has a well-ordered distribution of fiber angles varying from about 60° (from the circumferential direction) at the inner surface to about -60° on the outer surface. The greatest change in angle with respect to wall thickness occurs at the two surfaces (endocardial and epicardial). (2) Fiber angles did not change significantly during the transition from diastole to systole, despite a 28% increase in wall thickness (except in the papillary muscle root region). (3) The proportion of fibers lying in the sector of fiber angles oriented circumferentially (0±22.5°) to those oriented longitudinally (67.5 to 90° and -67.5 to -90°) is approximately 10:1. This ratio increases toward the base and diminishes toward the apex of the left ventricle. (4) All fiber angles in the lateral wall of hearts in systole increased through the wall by approximately 7° near the base and 19° near the apex relative to their counterparts in diastole, indicating bending or torsion of the left ventricle during contraction.

Force-velocity relations were studied in the cat papillary muscle. As with skeletal muscle, a characteristic relation has been demonstrated between the velocity of shortening (V) and the force developed (Po). Two generalities have been shown to pertain. First, increasing initial muscle length increases the maximal developed force (Po) without a change in the maximal velocity of shortening (Vmax). Secondly, at any one muscle length, changes in frequency of contraction and chemical environment (increased calcium and norepinephrine) increase Vmax with a variable change in Po. Changes in Vmax thus help to characterize an inotropic intervention (altered contractility). Work and power, at any one muscle length, are functions of afterload, with maxima when the load is approximately 40% of isometric tension. With increasing initial muscle length, the work and power at any one afterload as well as the maximal work and power of the muscle are both increased. At constant initial length, positive inotropic interventions (increased frequency, increased calcium, and norepinephrine) increase the work at any one afterload as well as shift the maximal work potential to a higher afterload. Work performance thus depends on muscle length, the prevailing force-velocity curve, and the afterload at which the muscle is operating.

SUMMARY:To determine whether myocyte death and angiotensin II (AT II) formation are implicated in the development of diabetic cardiomyopathy, rats were injected with streptozotocin, and apoptosis and necrosis were measured at 3, 10, and 28 days. Expression of the components of the renin-angiotensin system (RAS) and AT II levels were assessed at 3 days. The percentage of AT II-labeled myocytes and the number and distribution of AT II sites in myocytes were measured at 3 and 10 days. The effects of AT 1 blockade on local RAS and cell death were examined at 3 days. Diabetes was characterized by myocyte apoptosis that peaked at 3 days and decreased at 10 and 28 days, in spite of high concentrations of blood glucose. Cell necrosis was absent throughout. Angiotensinogen, renin, and AT 1 receptor increased in myocytes from diabetic rat hearts, while angiotensin-converting enzyme and AT 2 remained constant. AT II quantity increased severalfold, as did the fraction of AT II positive cells and the number of AT II sites per myocyte. However, AT II labeling decreased at 10 days, which paralleled the reduction in myocyte death. AT 1 antagonist inhibited upregulation of this receptor and angiotensinogen, which prevented AT II synthesis and myocyte death at their peaks with diabetes. An aggregate 30% myocyte loss and a 14% increase in the volume of viable cells were found in diabetic rats at 28 days. Thus diabetic cardiomyopathy may be viewed as an AT II-dependent process in which that peptide plays a critical role in myocyte death and hypertrophy. (Lab Invest 2000, 80:513-527).

To determine the effects of age on the myocardium, the functional and structural characteristics of the heart were studied in rats at 4, 12, 20, and 29 months of age. Mean arterial pressure, left ventricular pressure and its first derivative (dP/dt), and heart rate were comparable in rat groups up to 20 months. During the interval from 20 to 29 months, elevated left ventricular end-diastolic pressure and decreased dP/dt indicated that a significant impairment of ventricular function occurred with senescence. In the period between 4 and 12 months, a reduction of nearly 19% in the total number of myocytes was measured in both ventricles. In the subsequent ages, similar decreases in myocyte cell number were found in the left ventricle, whereas in the right ventricle, the initial loss was fully reversed by 20 months. Moreover, from 20 to 29 months, a 59% increase in the aggregate number of myocytes occurred in the right ventricular myocardium. In the left ventricle, a 3% increment was also seen, but this small change was not statistically significant. These estimations of myocyte cellular hyperplasia, however, were complicated by the fact that cell loss continued to take place with age. The volume fraction of collagen in the tissue, in fact, progressively increased from 8% and 7% at 4 months to 16% and 22% at 29 months in the left and right ventricles, respectively. In conclusion, myocyte cellular hyperplasia tends to regenerate the ventricular mass being lost with age in the adult mammalian rat heart.