Exercise-induced cardiac hypertrophy: a correlation of blood flow and microvasculature.

The effects of exercise conditioning on the myocardium were studied in seven instrumented pigs strenuously exercised for 12 wk by treadmill running. Data were compared with eight instrumented untrained pigs. O2 consumption measured during maximum exercise effort was significantly elevated in the trained pigs (71.7 +/- 4.0 vs. 56.3 +/- 3.0 ml X ml-1 X kg-1). Absolute right and left ventricular mass increased by 20 and 13%, respectively, in response to exercise. Myocyte cross-sectional area increased by 21% in the trained hearts compared with the untrained hearts. Transmural left ventricular myocardial blood flow (ml X min-1 X g-1) was not significantly different at rest, during maximum exercise, or during exercise with adenosine infusion. However, training caused an elevation of the regional epicardial blood flow noted during exercise and exercise with adenosine. In the trained pigs mean aortic pressure during maximum exercise with adenosine infusion was not significantly different compared with untrained pigs. Coronary resistance during exercise with adenosine infusion was the same in both animal groups. In the trained group capillary numerical (no./mm2) and length (mm/mm3) densities were reduced, whereas arteriolar numerical and length densities were significantly increased compared with the untrained group. Measurements of capillary luminal surface density (mm2/mm3) in the trained group were unchanged compared with the untrained group. These results suggest that strenuous exercise does not stimulate the production of new capillaries, but this is modified by the ability of existing capillaries to increase their luminal surface area to parallel increases in myocyte growth. The arteriolar data suggest that exercise promotes the formation of new arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac vasculature and flow during pressure-overload hypertrophy.

The effects of pressure-overload hypertrophy (H) on myocardial blood flow and microvasculature were studied in the porcine left ventricle. Hypertrophy was produced in nine adult pigs by an aortic cuff constriction of the ascending aorta. Eight pigs served as controls. After 30 days the aortic cuff was released, and the hypertrophy group was studied 1 day postrelease. The degree of hypertrophy, determined by left ventricular-to-body weight ratio, was 45%. With hypertrophy, left ventricular blood flows were normal at rest. During exercise with adenosine infusion, myocardial blood flow to the endomyocardium was reduced compared with the control (C) group (H = 4.02 +/- 0.35, P less than 0.05; C = 5.33 +/- 0.41 ml X min-1 X g-1). Minimal coronary vascular resistance in the endomyocardium was increased during exercise with adenosine in the hypertrophy group compared with the control group. Anatomic studies revealed that hypertrophy causes a reduction in the endomyocardial capillary density (H = 1,654 +/- 168, P less than 0.025; C = 2,168 +/- 106, no./mm2) with a similar trend noted for the transmural arteriolar density. Arteriolar media wall cross-sectional area was unaffected by the pressure overload. These results indicate that changes in the vascular bed do not parallel myocyte growth during pressure-overload hypertrophy. The resultant anatomic imbalance compromises endomyocardial flow, making this region vulnerable to ischemia.

Regional capillary and myocyte distribution in normal and exercise trained male and female rat hearts.

Adult Sprague-Dawley male and female rats were exercise trained for five months by either treadmill running or swimming. Significant differences in left ventricular regional capillary density and myocyte cross-sectional area were found. In control rats the epicardial regions had greater capillary density than endocardial regions. Endocardial myocyte cross-sectional areas were greater than those of epicardial myocytes in both sexes. Male rats had larger endocardial myocytes and larger hearts than females. After exercise training, myocyte size increased in the epicardial region but not in the endocardial region, while capillary density increased significantly only in the endocardial region. Similar changes were seen in both male and female rats with comparable degrees of exercise induced hypertrophy. These data suggest that exercise training "normalizes" the distribution of capillaries in the myocardium. Capillary density increased only in the regions where myocyte cross-sectional area did not increase. Further, the effects of exercise on male and female rat hearts is not different when the degree of exercise induced hypertrophy is similar.

Gene expression in a swine model of right ventricular hypertrophy: intercellular adhesion molecule, vascular endothelial growth factor and plasminogen activators are upregulated during pressure overload.

We have investigated the molecular changes which occur during pressure overload hypertrophy of the RV in swine. Animals were banded on the pulmonary artery so that right ventricular pressure was increased two-fold. The heart was harvested at 3, 7, 24 and 72 h after surgery. Between 7 and 72 h there was evidence of muscle damage and inflammation. Northern blot experiments showed that pressure overload induced a transient increase in the expression of the immediate early genes and in the developmentally regulated atrial natriuretic factor and skeletal muscle alpha actin genes. Consistent with the histological observations of inflammation, increases in the expression of the gene for intercellular adhesion molecule, which encodes a protein involved in the binding of leukocytes by endothelial cells and myocytes, was observed between 3 and 24 h. In addition, the expression of vascular endothelial growth factor, a growth and permeability factor specific for endothelial cells was increased at 3 and 7 h of pressure overload. An increase in the expression of urokinase plasminogen activator and its inhibitors, plasminogen activator inhibitors I and II, was also observed between 3 and 24 h. This was associated with an increase in urokinase activity in the myocardial tissue. These results indicate that hypertrophy in a large mammal such as swine induces a program of gene expression similar to that previously described in rodents and suggests that up-regulation of a variety of other genes is an early response to pressure overload.