R. A. Gerren

The distribution of functional impairment across the lateral border of acutely ischemic myocardium.

To evaluate the degree and lateral extent of dysfunction in nonischemic myocardium adjacent to ischemic muscle, we measured systolic wall thickening with sonomicrometers during circumflex coronary occlusion in 12 anesthetized, open-chest dogs. The locations of the wall thickness measurements relative to the perfusion boundary were determined with myocardial blood flow (microspheres) maps constructed from multiple, small tissue samples. Five minutes after circumflex occlusion, systolic wall thickening in the central ischemic zone decreased from 3.00 ± 0.61 (mean ± SD) mm to −0.61 ± 0.36 mm (P < 0.01). In nonischemic myocardium greater than 10 mm from the perfusion boundary, systolic wall thickening increased from 2.56 ± 0.57 to 3.24 ± 0.72 mm (P < 0.01). In nonischemic myocardium within 10 mm of the perfusion boundary, systolic wall thickening was slightly but significantly reduced compared with control (2.72 ± 0.80 to 2.44 ± 0.79 mm, P < 0.05), supporting the concept of regional dysfunction in nonischemic myocardium at the lateral borders of an ischemic area. Sigmoid curves were fitted to the data to model changes in wall thickening as a continuous function of distance from the perfusion boundary. This allowed estimation of the extent of dysfunction into nonischemic myocardium which averaged less than 8 mm (approximately 30 degrees of endocardial circumference) at one border. The level of functional impairment in this zone was relatively modest, and systolic wall thickening in the immediate border area was reduced more than 50% from control only in tissue characterized by a blood supply of mixed ischemic and nonischemic origin. We conclude that a functional border zone exists lateral to an acutely ischemic area, but measurement of regional function produces relatively small exaggeration of the size of the acutely ischemic zone if severe reduction in mechanical performance is used to define the extent of the ischemic area.

Coronary Vasodilator Reserve in Young Dogs with Moderate Right Ventricular Hypertrophy

The effects of experimental right ventricular (RV) pressure overload and RV hypertrophy on coronary vasodilator reserve in young animals is not well established. Therefore, we measured coronary vasodilator reserve in the right ventricle of dogs from 7 to 12 months old with moderate RV hypertrophy due to pulmonary artery banding performed 3 to 7 days after birth. In the 5 dogs with pulmonary artery banding, substantial RV hypertension developed (RV pressure at rest, 73 +/- 11 mm Hg) as did RV hypertrophy (ratio of RV free wall/left ventricular free wall weight, 1.86 +/- 0.41 gm/kg). The reactive hyperemic response following brief coronary occlusions was used as an index of coronary vasodilator reserve. The ratios of peak reactive hyperemic response to resting flow, however, were not significantly different in the 5 banded dogs compared with 7 control animals (3.6 +/- 1.0 versus 2.6 +/- 0.6); this implies that the extent of vasodilator reserve was similar with or without moderate RV hypertrophy. In addition, myocardial blood flow, as determined using radioactive microspheres, was not significantly different at rest: 0.57 +/- 0.09 ml/min per gram in the banded dogs versus 0.48 +/- 0.12 ml/min per gram in the controls. Uniform transmural distribution of blood flow was maintained during infusion of isoproterenol, which was used to increase myocardial oxygen requirements in both groups. Minimum coronary vascular resistance was significantly lower in the banded than the control dogs (1.5 +/- 0.6 versus 6.2 +/- 2.3; p less than 0.01). This difference suggests that the cross-sectional area of the right coronary vascular bed increased with the development of RV hypertrophy.

Norepinephrine plus Phentolarnine Improves Regional Blood Flow during Experimental Low Cardiac Output Syndrome

A complication of cardiac surgical procedures is postoperative low cardiac output syndrome. Treatment with norepinephrine plus phentolamine (N + P) is beneficial, but the effect of these agents on regional organ blood flow has not been evaluated. Therefore, in 6 dogs with long-term instrumentation, pentobarbital was infused to simulate low cardiac output (32 + 10% of the conscious control level). Infusions of N + P at 0.2, 0.5, and 1.0 microgram/kg/min restored cardiac pump performance to conscious control levels. Regional blood flows, determined with tracer-labeled microspheres, were substantially reduced in the low cardiac output state but increased to values not markedly different from control levels in all organs studied except stomach fundus during infusion of N + P. The pressure-work index, an indirect measure of myocardial oxygen consumption, did not increase to more than the conscious level except at the highest dose. The data demonstrate that simultaneous infusion of N and P is capable of successfully improving cardiac pump performance with restoration of vital organ perfusion and without evidence of excessive myocardial oxygen consumption.

Changes in contractility fail to alter the size of the functional border zone in anesthetized dogs.

The functional border zone is nonischemic myocardium that exhibits reduced function adjacent to an ischemic area. To determine if the functional border zone can be modified by pharmacologic interventions that alter contractility, we infused isoproterenol (0.04-0.10 micrograms/kg/min) or administered propranolol (2 mg/kg) during circumflex coronary occlusion in nine anesthetized, open-chest dogs. We measured systolic wall thickening on both sides of the perfusion boundary, which was delineated with myocardial blood flow (microsphere) maps constructed from small tissue samples. By fitting sigmoid curves to the composite systolic wall thickening data after coronary occlusion, we modeled the distribution of functional impairment across the perfusion boundary. Defined as the distance from the perfusion boundary to 97.5% of the nonischemic asymptote of the sigmoid fits, the functional border zone was 31 degrees of circumference after coronary occlusion alone. Isoproterenol increased +dP/dt by 58% and augmented nonischemic systolic wall thickening without changing the lateral extent of the functional border zone (32 degrees). Propranolol reduced +dP/dt by 24% and depressed nonischemic systolic wall thickening, but the size of the functional border zone remained limited to 28 degrees. Within the functional border zone, wall thickening was significantly but only moderately reduced (-28%) compared with thickening in nonischemic myocardium more than 10 mm away from the perfusion boundary. The ratio of nonischemic border zone to central nonischemic area wall thickening remained the same with each intervention. We conclude that the dimensions of the functional border zone are fixed early after coronary occlusion and that inotropic interventions do not modify the extent or relative severity of nonischemic regional dysfunction.