Effect of young age on coronary adaptations to left ventricular pressure overload hypertrophy in sheep
MF Flanagan,
T Aoyagi,
JJ Currier,
SD Colan,
and
AM Fujii
Department of Pediatric Cardiology, Dartmouth Medical School, Hanover, New Hampshire.
OBJECTIVES. This study attempted to determine the effect of young age on changes in coronary conductance and capillary density with left ventricular pressure overload hypertrophy. Mechanisms responsible for age differences in perfusion capacity were examined. BACKGROUND. Hypertension in adults causes alterations in the coronary vasculature, resulting in diminished coronary perfusion capacity and myocardial ischemia. These processes are worsened in adults by advanced age. Young age may provide advantages in coronary adaptation to hypertension. METHODS. Coronary conductance was examined in conscious chronically instrumented 10-week old lambs and adult sheep with progressive ascending aortic stenosis of 6-week's duration and age-matched control sheep by means of the microsphere technique and vasodilators. Capillary density was measured post-mortem. RESULTS: Adult sheep with aortic stenosis had a decrease in left ventricular subendomyocardial capillary density by 17% and maximal coronary conductance with adenosine by 67%. In the nonhypertrophied right ventricle, maximal coronary conductance was depressed by 47%, whereas capillary density was normal, implying an effect of coronary hypertension on resistance vessels. In contrast, lambs with aortic stenosis maintained normal left ventricular capillary density, maximal coronary conductance and coronary reserve and had relatively little impairment of conductance in the right ventricular coronary bed (-15%, p = NS). Similar responses were found with other vasodilators, isoproterenol and chromonar. CONCLUSIONS. Young age confers advantages to coronary adaptation to left ventricular pressure overload, including angiogenesis proportionate to hypertrophy, resulting in normal capillary density and coronary conductance. There is also less hypertension-induced impairment of coronary conductance distinct from the effects of hypertrophy.
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