Effect of chronotropic and inotropic stimulation on the coronary pressure-flow relation in left ventricular hypertrophy

Left ventricular hypertrophy (LVH) secondary to chronic pressure overload is associated with increased susceptibility to myocardial hypoperfusion and ischemia during increased cardiac work. The present study was performed to study the effects of chronotropic and inotropic stimulation on the coronary pressure-flow relation of the hypertrophied left ventricle of dogs and to determine the individual contributions of increases in heart rate and contractility to the exaggerated exercise-induced increases in effective back pressure (pressure at zero flow; Pzf). Ascending aortic banding in seven dogs increased the LV to body weight ratio to 7.7±0.3 g/kg compared to 4.8±0.2 g/kg in 10 normal dogs (p≤0.01). Maximum coronary vasodilation was produced by intracoronary infusion of adenosine. During resting conditions maximum coronary blood flow in the pressure overloaded hypertrophied left ventricle was impaired by both an increase in Pzf (25.1±2.6 vs 13.8±1.2 mmHg in hypertrophied vs normal ventricles, respectively, p≤0.01) and a decrease in maximum coronary conductance (slope of the linear part of the pressure-flow relation, slopep≥linear) (8.6±1.1 vs 12.7±0.9 ml/min/mmHg, p≤0.01). Right atrial pacing at 200 and 250 beats/min resulted in similar rightward shifts of the pressure-flow relation in hypertrophied and normal hearts with 3.1±0.8 and 4.7±0.8 mmHg increases in Pzf in LVH and normal dogs, respectively; stepwise multivariate regression analysis indicated that the exaggerated decrease in filling pressure (10±2 vs 6±2 mmHg) and decrease in left ventricular systolic pressure (45±5 vs 3±3 mmHg, p≤0.01) may have blunted a greater rightward shift of the pressure-flow relation produced by atrial pacing in the hypertrophied hearts. Inotropic stimulation with dobutamine (10–20 μg/kg/min, iv) resulted in minimal flow changes in normal hearts but produced a 4.4±1.5 mmHg (p≤0.05) rightward shift of the pressure-flow relation in hypertrophied hearts, which correlated with a greater increase in left ventricular systolic pressure (83±16 vs 18±4 mmHg, p≤0.05). Exercise resulted in a rightward shift in both normal and hypertrophied left ventricles, but the increase in Pzf was significantly greater in the hypertrophied hearts (15.2±0.9 vs 10.3±0.9 mmHg, p≤0.05). Stepwise multivariate regression analysis indicated that not only increases in left ventricular filling pressure, but also increases in heart rate and LV systolic pressure contributed to the abnormally great increase in effective coronary back pressure which results in limitation of myocardial perfusion during exercise in the pressure overloaded hypertrophied left ventricle.