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

Abstract

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 beatslmin), 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 5 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 5 0.05). Differences in total and regional CF between H and N hearts were present at both study ages (t test, p 5 0.05). The differences in CF at baseline show that, under conditions of reduced Oz 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. Supported by an American Heart Association-Florida Affiliate Clinician Scientist Award (CS89/1) (G.H.). 5Acclimation of immature rodents to environmental hypoxia is associated with development of increased capillary density and capillary to myofiber ratios in both hypertrophied right and nonhypertrophied left ventricular myocardium (1-3). As a result of these increases in myocardial vascularity, intramyocardial diffusion distance for O2 is believed to be reduced, and ability to oxygenate myocardium is thought to be improved to some extent (2, 3). There is, however, a current paucity of data regarding the potential consequences of hypoxia-related changes in myocardial vascularity on myocardial perfusion.Turek et al. (4) studied the effect of raising rats at simulated altitude of 3500 m (hypobaric hypoxia) on regional coronary flow responses to ventilation with a gas mixture containing 1 ...

Chronic hypoxia increases the NO contribution of acetylcholine vasodilation of the fetal guinea pig heart

“…Previous studies have reported that chronic exposure to HPX increases maximal flow responses due to increased vessel growth in the newborn rabbit heart (14) and the fetal sheep heart (24,25). In the fetal guinea pig heart, HPX increased the NO contribution of acetylcholine-induced vasodilation but not the magnitude of vasodilation.…”