Role of Propranolol in Improvement of the Relationship between O2 Supply and Consumption in an Ischemic Region of the Dog Heart

Abstract

A B S T R A C T Several aspects of the myocardial 02 supply/consumption relationship were determined after coronary artery occlusion and subsequent /l-adrenergic blockade in 16 anesthetized open-chest dogs. Small artery and vein 02 saturations, and hence extraction, were obtained microspectrophotometrically and combined with radioactive microsphere blood flow determinations to calculate regional myocardial 02 consumption. Eight dogs remained untreated after coronary artery ligation while another group was given 2 mg/kg propranolol, 10 min after occlusion. Untreated occlusion resulted in decreased arterial and especially venous 02 saturations, indicating an increased 02 extraction. Ischemic 02 consumption was reduced and the subendocardial/subepicardial consumption ratio was reversed (1.26 vs. 0.37) due to the pattern of occluded area flow. Calculated 02 supply/ consumption also decreased. Propranolol produced no significant changes in volume or distribution of flow within the ischemic region while reducing flow, extraction, and consumption in the unoccluded region. The heterogeneity of arterial and particularly venous 02 saturations within the ischemic region decreased dramatically. Venous 02 saturations were elevated relative to the control group resulting in a reduced 02 extraction. The decrease in heterogeneity of arterial and venous 02 saturations suggest that propranolol eliminates microregions of relatively high 02 extraction, consumption, and/or a majority of vessels with extremely low flow. This leads to a significant improvement in the 02 supply/consumption ratio in the ischemic myocardium of the dog. This may be due to a reduction in the heterogeneity and level of nj-adrenergic receptor activity within the heart.

Effect of complement depletion on O2 supply and consumption in ischemic dog myocardium

“…This mechanism may also be important with complement depletion as decreased microvascular obstruction may decrease microregional flow heterogeneity. As performed previously, changes in flow distribution may be estimated by measuring changes in microregional SvO2 distribution as measured by microspectrophotometry (4). In the present study no changes in SvO 2 distribution were observed though this does not totally eliminate the possibility of an altered flow distribution within the ischemic zone.…”

“…Previous studies from our laboratory have shown that a decreased microregional heterogeneity of flow to an ischemic region can be associated with a decreased severity of ischemia, even when the total ischemic regional flow is constant (4). This mechanism may also be important with complement depletion as decreased microvascular obstruction may decrease microregional flow heterogeneity.…”

REGIONAL O2 SUPPLY/CONSUMPTION IN NORMAL AND ISCHAEMIC RABBIT MYOCARDIUM: EFFECT OF NIFEDIPINE

“…The extensive collateral network in the rabbit heart was determined by Weiss (1982), where LAD occlusion decreased coronary blood flow by approximately 50%, as was observed also in the present study. This is in contrast to the 70-75% reductions in blood flow in the dog occlusion model (Gorman & Sparks 1980;Conway & Weiss 1982). Rabbits also have a high degree of noncollateral overlap flow, comprising approximately 21% of the blood flow to an occluded region (Weiss 1982).…”

Mechanism of beneficial effect of beta-adrenergic blockade on exercise-induced myocardial ischemia in conscious dogs.

“…In addition, it has been suggested that when myocardial oxygen consumption of the ischemic myocardium is reduced by /3-adrenergic blockade (slowed heart rate and reduced arterial pressure), the discrepancy between the demand for blood flow and the limited supply to the ischemic tissue is attenuated, which may result in improved regional function. 9 Finally, reduced left ventricular pressure (LVP) during exercise following /3-blockade 1 may contribute to the improvement in regional myocardial function in the ischemic myocardium. Thus, a variety of mechanisms potentially have a role in reducing exercise-induced regional myocardial ischemia and dysfunction.…”