Alterations of myocardial blood flow associated with experimental canine left ventricular hypertrophy secondary to valvular aortic stenosis.

Abstract

SUMMARY. Experimental renovascular hypertension or supravalvular aortic constriction results in left ventricular hypertrophy and impaired minimum coronary vascular resistance. However, these experimental models expose the coronary arteries to increased intra-arterial pressure, so that hypertensive vascular changes might be responsible for the impaired minimum coronary resistance. This study was performed to test the hypothesis that left ventricular hypertrophy in the absence of increased coronary pressure results in abnormalities of myocardial perfusion. Aortic valve stenosis was produced by plication of the noncoronary aortic cusp of 11 dogs at 6-8 weeks of age. Studies were carried out when the animals reached adulthood; mean left ventriculanbody weight ratio was 7.1 ± 0.4 as compared to 4.4 ± 0.3 g/kg in 11 normal dogs (P < 0.01). Under quiet resting conditions, myocardial blood flow measured with microspheres was significantly greater than normal in dogs with aortic stenosis. However, during maximum coronary vasodilation with adenosine, mean left ventricular blood flow in dogs with hypertrophy (3.29 ± 0.39) was substantially less than in normal dogs (6.19 ± 0.54 ml/min per g; P < 0.01), whereas minimum coronary resistance was increased from 14.1 ± 1.7 in normal dogs to 23.7 ± 5.4 mmHgmin-g/ml (P < 0.01). To examine the response of myocardial perfusion to cardiac stress, blood flow was measured during pacing at 200 and 250 beats/min. Compared with normal dogs, animals with hypertrophy had a subnormal increase in myocardial blood flow during tachycardia; this perfusion deficit was most marked in the subendocardium. These data demonstrate that left ventricular hypertrophy alone, without increased coronary artery pressure, is associated with impaired minimum coronary vascular resistance and with abnormalities of myocardial blood flow during pacing stress. (Circ Res 58: 47-57, 1986)

Functional Changes in Coronary Microcirculation After Valve Replacement in Patients With Aortic Stenosis

“…28 The effect of intraventricular pressure changes on MBF is also poorly understood, with conflicting evidence from animal models. 29,30 In our study there was a clear relationship between a reduction in hemodynamic workload, as demonstrated by the change in AVA, and increase in CVR, which, in the absence of epicardial stenosis, suggests an improvement in coronary microcirculatory function in these patients after AVR. 31 Shortened DPT in AS results in blunting of myocardial perfusion, 2,32 particularly during tachycardia.…”

Inhibition of Hypertrophy, Per Se, May Not Be a Good Therapeutic Strategy in Ventricular Pressure Overload: Other Approaches Could Be More Beneficial

“…53 The same abnormality was described during exercise 54,55 in a pressure overload model produced by aortic banding in puppies. This was attributed to a reduced subendocardial coronary reserve related in part to the larger compressive forces in the subendocardium where stress is larger.…”

Complete reversibility of physiological coronary vascular abnormalities in hypertrophied hearts produced by pressure overload in the rat.

“…Furthermore, at the higher level of coronary perfusion pressure the absolute value of coronary flow rate under control perfusion or maximal vasodilation did not decrease compared with sham-operated controls (Fig. 5, A (4,6,9) indicate that the physiological coronary vascular abnormalities do not always coexist with cardiac muscle hypertrophy. Therefore, it is possible that the abnormalities in coronary circulation persist even after complete regression of cardiac muscle hypertrophy produced by pressure overload with coronary arterial hypertension.…”

“…In hypertrophied hearts, abnormalities in coronary circulation such as decreased coronary blood flow per unit muscle mass (2), increased coronary vascular resistance during maximal vasodilation (3)(4)(5)(6)(7)(8)(9), impaired autoregulation (10), changes in transmural blood flow distribution (3, 9-13), or decreased coronary flow reserve (6)(7)(8)(9)(14)(15)(16)(17)(18)(19)(20)(21)(22) have been reported in clinical and animal studies. If the hemodynamic load is normalized, cardiac muscle hypertrophy regresses in patients and animals (1,(23)(24)(25)(26)(27)(28)(29)(30)(31).…”

“…The abnormalities in coronary circulation might be caused indirectly by the presence of cardiac muscle hypertrophy sur-rounding the coronary vascular system per se (9), directly by coronary vascular changes produced by coronary arterial hypertension with or without significant cardiac muscle hypertrophy (4,6), or by both. Therefore, the time course ofnormalization of physiological coronary vascular abnormalities in hypertrophied hearts in response to pressure overload with coronary arterial hypertension may differ from that in the regression process ofmyocardial hypertrophy, even ifthe coronary circulation abnormalities are reversible.…”