Exercise training induces coronary vascular adaptations. The goal of this study was to contrast the effects of training on capillary and arteriolar growth. Minipigs were trained for 1, 3, 8, and 16 wk and compared with controls. Maximal O2 consumption increased continuously throughout the study. Capillary and arteriolar densities and diameters, and proliferation of vascular cells in these vessels, were determined in perfusion-fixed tissue. The arterioles were subdivided into five groups according to diameter: 10-19.9, 20-30, 31-40, 41-70, and 71-120 microgram. The total vascular bed cross-sectional area increased by 37% at 16 wk, mainly because of an increase in the number of the small arterioles and an increase in the diameter of the larger vessels. Capillary density increased at 3 wk and then returned to control levels by 16 wk; concomitantly, the number of arterioles (20-30 microgram) increased at 16 wk. We speculate that the "extra" capillaries observed at 3 wk were the source of the new arterioles.

Background-We tested the hypothesis that intracoronary injection of a recombinant adenovirus encoding adenylyl cyclase type VI (AC VI ) would increase cardiac function in pigs. Methods and Results-Left ventricular (LV) dP/dt and cardiac output in response to isoproterenol and NKH477 stimulation were assessed in normal pigs before and 12 days after intracoronary delivery of histamine followed by intracoronary delivery of an adenovirus encoding lacZ (control) or AC VI (1.4ϫ10 12 vp). Animals that had received AC VI gene transfer showed increases in peak LV dP/dt (average increase of 1267Ϯ807 mm Hg/s; Pϭ0.0002) and cardiac output (average increase of 39Ϯ20 mL ⅐ kg Ϫ1 ⅐ min Ϫ1 ; PϽ0.0001); control animals showed no changes. Increased LV dP/dt was evident 6 days after gene transfer and persisted for at least 57 days. Basal heart rate, blood pressure, and LV dP/dt were unchanged, despite changes in cardiac responsiveness to catecholamine stimulation. Twenty-three hour ECG recordings showed no change in mean heart rate or ectopic beats and no arrhythmias. LV homogenates from animals receiving AC VI gene transfer showed increased AC VI protein content (Pϭ0.0007) and stimulated cAMP production (Pϭ0.0006), confirming transgene expression and function; basal LV AC activity was unchanged. Increased cAMP-generating capacity persisted for at least 18 weeks (PϽ0.0002). Conclusions-Intracoronary injection of a recombinant adenovirus encoding AC provides enduring increases in cardiac function.

IGF-1 plus growth hormone administered to rats with left ventricular failure starting 1 month after MI was associated with substantial body growth, decreased systemic vascular resistance, and increased cardiac output. The failing heart also underwent treatment-induced increases in left and right ventricular weights in proportion to body growth, but left ventricular remodeling was minor, and a decrease in the ratio of left ventricular end-diastolic volume to body weight reflected relatively less chamber dilation compared with controls. A significant interaction between size of the myocardial infarction and treatment was observed for several variables, and IGF-1 and growth hormone increased the cardia index (P < .035) in rats with a large myocardial infarction.

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)

Background Although left ventricular hypertrophy (LVH) is frequently associated with impaired coronary vasodilator reserve, it is uncertain whether this leads to myocardial ischemia under physiological conditions. The goal of the present study was to determine whether swine with moderate LVH exhibit metabolic evidence of ischemia when myocardial oxygen requirements are increased. Methods and Results Myocardial metabolism was evaluated in an open-chest anesthetized preparation at baseline and during dobutamine infusion in 13 adolescent pigs with moderate LVH induced by supravalvular aortic banding and 12 age-matched control pigs. Transmural myocardial blood flow was quantified with radioactive microspheres; the ratio of phosphocreatine to ATP (PCr/ATP) in the anterior LV free wall was measured by 31 P–nuclear magnetic resonance; and anterior wall lactate release was quantified from the arterial-coronary venous difference in 14 C- or 13 C-labeled lactate. In a subset of 5 animals from each group, the metabolic fate of exogenous glucose was determined from the transmyocardial difference in 6- 14 C-glucose and its metabolites 14 C-lactate and 14 CO 2 . Coronary reserve, as assessed by the ratio of blood flow during adenosine infusion to baseline blood flow, was significantly lower in the LVH pigs compared with controls (3.5±0.4 versus 5.5±0.4 mL/g · min, P <.05); however, transmural myocardial blood flow was similar in both groups of pigs, both at baseline and with dobutamine stimulation, probably reflecting the higher coronary perfusion pressure in the LVH pigs. At baseline, PCr/ATP tended to be lower in the LVH pigs ( P =.09) but decreased similarly with dobutamine infusion in both groups. Isotopically measured anterior wall lactate release did not differ between the groups at baseline, nor did the increase in lactate release differ during dobutamine stimulation. The uptake of glucose, lactate, and free fatty acids did not differ between the groups in the basal state. However, during dobutamine stimulation, glucose uptake was greater in the LVH group (0.84±0.09 μmol/g · min versus 0.59±0.08 μmol/g · min, P <.05). In a subset of animals, 14 C-glucose was used to assess glucose oxidation. These data showed that the LVH animals had a greater rate of glucose oxidation (0.60±0.10 versus 0.28±0.08 μmol/g · min, P <.05) and a greater rate of glucose conversion to lactate (0.20±0.04 versus 0.09±0.02 μmol/g · min, P <.05) compared with the control pigs. Conclusions These results suggest that despite their reduced coronary vasodilator reserve and the absence of a greater rise in myocardial blood flow to compensate for a substantially higher LV double product, pigs with this model of moderate LVH do not exhibit a greater susceptibility to myocardial ischemia during dobutamine stress. However, LVH pigs exhibit significantly greater use of exogenous glucose during dobutamine stress, as evidenced by increases in both glucose oxidation and anaerobic glycolysis.