A model for the study of coronary spasm induced changes in cardiac metabolism

Abstract

A model is described which permits the study of localized and generalized arterial spasm in the intact working perfused rabbit heart with a perfluorochemical (FC-43) as perfusate. Coronary arteries were visualized by intraatrial injection of Patent Blue Dye with gated photography. Localized spasm resulted from topical spray of histamine (40 mumols) on the epicardial surface overlying an obtuse marginal artery. Before and following topical administration of histamine, regional coronary flow was determined using radioisotope-labeled microspheres. Generalized arterial spasm was initiated by intraatrial injection of histamine (10 mumols). After topical administration, abtuse marginal artery diameter decreased by 57%; large vessel resistance rose 32 fold; 20% rise of total coronary resistance resulted in a slight reduction of total coronary flow (16%). Heart rate, cardiac output, dP/dtmax and myocardial oxygen consumption did not change. However, regional coronary flow in the myocardium supplied by the affected artery diminished 21% resulting in ischemic changes in redox pairs. After intraatrial injection of histamine, changes were more pronounced. Obtuse marginal artery diameter declined by 88% resulting in 3300-fold rise of large vessel resistance. Total coronary resistance increased 150%, coronary flow and cardiac output diminished (56% and 24%). Both heart rate and dP/dtmax increased (16% and 17%). Generalized coronary spasm after intraatrial histamine injection resulted in severe metabolic effects: Myocardial oxygen consumption (-48%); ATP (-29%); creatine phosphate (-34%); redox ratios, alpha-glycerophosphate/dihydroxyacetone phosphate and lactate/pyruvate, increased by 449% and 114%, respectively. The findings illustrate that localized and generalized coronary spasm can be produced and quantitated in a working heart model.