Left ventricular failure induced by myocardial infarction. I. Myocyte hypertrophy.

To determine whether left ventricular failure after acute myocardial infarction is associated with a growth response of the myocytes that tends to compensate for the loss of muscle mass and function, the left coronary artery in rats was ligated near its origin, and the animals were killed 3 days later. Elevated left ventricular end-diastolic pressure and decreased first derivative of left ventricular pressure and systolic arterial pressure indicated significant impairment of ventricular function. Absolute infarct size, determined morphometrically by measurement of the fraction of myocyte nuclei lost, averaged 57%. Hypertrophy of surviving left ventricular myocytes was 28%, involving a 14% increase in cell length and a 6% increase in diameter. Right ventricular myocyte volume per nucleus increased 21% by a 10% enlargement of cellular diameter with no change in length. These results show on a cellular basis that myocardial hypertrophy in the left ventricle is accomplished by cellular shape changes characteristic of a combination of pressure and volume overload hypertrophy, whereas cellular growth in the right ventricle is consistent with pressure overload hypertrophy.

Left ventricular failure induced by myocardial infarction. II. Tissue morphometry.

Three days after myocardial infarction involving 57% of the left ventricle in rats, the viable tissue of the left ventricle expanded 29%, whereas myocardial hypertrophy in the right ventricle was 19%. To determine whether tissue oxygenation in the hypertrophied ventricles was supported by a proportional growth of the capillary network, morphometric analysis was used to measure capillary luminal volume and surface densities and the diffusion distance for O2. The volume fraction of capillary lumen and the luminal surface of capillaries, related to O2 availability and diffusion, were altered by -21 and -19%, respectively, in the left ventricle and by -23 and -20%, respectively, in the right ventricle. The path length for O2 transport was found to be increased by 12 and 15% in the left and right ventricle, respectively. In contrast, myocyte mass expanded in proportion to tissue growth in the left ventricle and exceeded tissue growth by 5% in the right ventricle. Myocyte mitochondria and myofibrils both grew in proportion to the cells, so that their volume ratio was not changed in either ventricle. The relatively inadequate adaptation of the capillary vasculature suggests that hypertrophy after severe myocardial infarction may initially leave the heart more vulnerable to additional ischemic episodes.

Effects of strenuous exercise on the quantitative morphology of left ventricular myocardium in the rat.

The adaptation of the structural components in the myocardium of the left ventricle to strenuous exercise was studied morphometrically in rats following a treadmill running program. The response of the left ventricle was evaluated separately in the interventricular septum and in the left ventricular free wall. Exercise produced a 24% growth of the septum without altering free wall volume. The hypertrophic expansion of the septum was characterized by a decrease in the volume fraction of capillary lumen in the myocardium (-20%), a reduction in the capillary luminal surface per unit volume of myocytes (-17%) and by an increase in the maximum distance from the capillary wall to the mitochondria of myocytes (9%). Although none of these changes were demonstrable on a statistical basis in the left ventricular free wall, similar results were obtained in the whole left ventricle by combining the data from the septum and free wall. Since the septum constitutes a functional unit with the free wall, it was concluded that the effect of excessive physical activity on the capillary parameters responsible for oxygen availability and diffusion could lead to a local reduction in the oxygenation potential of ventricular myocardium.

Morphometry of right ventricular hypertrophy induced by myocardial infarction in the rat.

The growth response of the right ventricle was studied in rats following ligation of the left coronary artery, which produced infarcts comprising approximately 40% of the left ventricle. A month after surgery the weight of the right ventricle was increased 30%, and this hypertrophic change was characterized by a 17% wall thickening, consistent with the 13% greater diameter of myocytes. Myocardial hypertrophy was accompanied by an inadequate growth of the microvasculature that supports tissue oxygenation. This was seen by relative decreases in capillary luminal volume density (-27%) and capillary luminal surface density (-21%) and by an increase in the average maximum distance from the capillary wall to the mitochondria of myocytes (19%). In contrast, measurements of the mean myocyte volume per nucleus showed a proportional enlargement of these cells (32%), from 16,300 cu mu in control animals to 21,500 cu mu in experimental rats. Quantitative analysis of the right coronary artery revealed a 33% increase in its luminal area, commensurate with the magnitude of ventricular hypertrophy.

Morphometry of exercise-induced right ventricular hypertrophy in the rat.

In our morphometric study of the effects of exercise on the heart, male Wistar-Kyoto rats at 5 weeks of age were subjected daily to a moderate treadmill running program that lasted for 7 weeks. The heart responded to physical conditioning by different magnitudes of tissue growth of the right (22%) and left (7%) ventricular myocardium, the latter change not statistically significant. The increase in right ventricular volume was associated with a 25% enlargement of ventricular area, a 26% average lengthening of the myocytes, and no change in sarcomere length and in ventricular midwall thickness. Exercise produced significant alterations in the quantitative parameters of the microvasculature of the right ventricle, but no appreciable changes in the left ventricle. Right ventricular hypertrophy was characterized by an absolute 44% growth of the endothelial luminal surface brought about through a 16% increase in capillary numerical density, and a 41% augmentation of the total length of the capillary network. Maximum diffusion distance from the capillary wall to the mitochondria of myocytes decreased 10% as a result of capillary proliferation and the lack of lateral expansion of myocyte cross-sectional area. Evaluation of the subcellular constituents of myocytes showed no change in the mitochondria:myofibrils volume ratio, indicating a growth of these components proportional to each other and to the growth of the myocyte population as a whole. It was concluded that, as a result of running exercise, right ventricular growth is analogous to eccentric hypertrophy in which the structural adaptations of the capillary bed can be expected to improve the diffusion and transport of oxygen within the tissue.

Morphometry of right ventricular hypertrophy induced by strenuous exercise in rat.

Effects on the myocardium, particularly those structural properties of the capillary network relevant to tissue oxygenation, were studied morphometrically in rats subjected to a severe running program. Physical conditioning produced a 31% increase in right ventricular weight and only a 12% increase in the weight of the left ventricle. Quantitative analysis of right ventricular myocardium demonstrated relative decreases in capillary luminal volume density (-27%) and capillary luminal surface density (-20%) and an increase in the average maximum distance from the capillary wall to the mitochondria of myocytes (14%). In contrast, the contractile mass expanded in proportion to the growth of the ventricle through augmentation of the cross-sectional area (17%) and length (19%) of the average myocyte. Evaluation of the subcellular constituents of myocytes showed no change in the mitochondria-to-myofibril volume ratio. In conclusion, the capillary bed controlling oxygen availability, diffusion, and transport suggests that excessive physical activity may be detrimental to the myocardium.

Elastic tissue and smooth muscle volume in elastic and muscular type arteries in the dog.

1. Relative elastic tissue and smooth muscle volumes were determined by a stereological point-counting method in arteries with a progressively diminishing diameter, from the aorta towards the periphery. 2. The volume relationship between the smooth muscle cell and its nucleus was determined by the same method. Mean nuclear volume amounted to 6.9% of total smooth muscle cell volume. 3. Relative elastic tissue volume fell from the aorta towards the peripheral arteries, from 22.6% in the ascending aorta to 4--6% in the smallest arteries examined. 4. Relative smooth muscle volume was practically the same and differences between the individual values in the vast majority of arteries examined were non-significant. Total smooth muscle volume, calculated from the volume of the smooth muscle cell nuclei, varied mostly from 45 to 55%. 5. It can be concluded from these results that the ability of small and medium muscular type arteries to change their diameter actively by muscular contraction (as against elastic type arteries, in which this ability is less expressed) is facilitated not only by the organization of the structural components of the arterial wall, but also by the lower elastic tissue volume, which is compensated by the volume of the other passive components of the vascular wall, while relative smooth muscle volume remains the same.