Effect of Growth and Maturation in a Hypoxic Environment on Maximum Coronary Flow Rates of Isolated Rabbit Hearts

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Abstract
This study was designed to determine the effect of growth and maturation of rabbits in a hypoxic (H) environment on the ability to perfuse myocardium. Rabbits were raised in either a normoxic (N) (Po2 = 19.7 kPa or 149 torr) or an H environment (Po2 = 8.6 kPa or 65 ± 3 mm Hg) and were studied at ages 5 wk (immature) and 12 wk (mature). Coronary flow (CF) was measured at baseline, during infusion of a maximally dilating concentration of adenosine (A), and at peak reactive hyperemic response to transient inflow occlusion in an isolated, non-blood-perfused heart preparation. Hearts were unloaded, paced at a constant rate (200 beats/min), and perfused at a constant inflow pressure (50 mm Hg). Regional CF was measured, using microspheres, in right ventricular, left ventricular, and atrial cardiac segments during vasodilation with A. H rabbits developed right ventricular but not left ventricular segment hypertrophy/hyperplasia. CF was greater in immature than mature hearts and higher in H than N hearts during baseline, vasodilation with A, and at peak reactive hyperemia (two-way analysis of variance, p ≤ 0.05). Regional CF during vasodilation with A was greater in immature than mature hearts, in both right and left ventricular segments, and higher in H than N hearts in all cardiac segments (two-way analysis of variance, p ≤ 0.05). Differences in total and regional CF between H and N hearts were present at both study ages (t test, p ≤ 0.05). The differences in CF at baseline show that, under conditions of reduced O2 availability (bloodless perfusate), myocardial perfusion was better in immature than mature hearts and was improved by growth in hypoxia. On the other hand, the differences in CF during infusion of A and at peak reactive hyperemia show that the maximum capacity for myocardial perfusion was also better in the immature hearts and further improved by growth in hypoxia, even in segments undergoing hypertrophy/hyperplasia. These findings suggest an important adaptation to environmental hypoxia in growing, maturing rabbits: an increased intrinsic vascular capacity to perfuse hypertrophied and nonhypertrophied myocardium.

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