Mechanism of inducible regional dysfunction during dipyridamole stress.

Abstract

We hypothesized that increased myocardial oxygen demand resulting from hypotension and reflex tachycardia unmasking a reduced endocardial myocardial blood flow (MBF) reserve is the mechanism of dipyridamole-induced regional dysfunction in chronic coronary artery disease. Ameroid constrictors were placed around the proximal coronary arteries and their major branches in 15 dogs to create chronic coronary stenosis. Seven days later, radiolabeled microsphere-derived MBF and 2-dimensional echocardiography-derived percent wall thickening (%WT) were measured at rest and after 0.56 mg/kg dipyridamole. Dipyridamole caused an increase (mean, 21%) in the rate-pressure product secondary to reflex tachycardia resulting from mild systemic hypotension. %WT in myocardial segments with an endocardial MBF reserve (dipyridamole/resting MBF) of 1.5 to 2.5 (n=35) did not change after dipyridamole, whereas it decreased in segments with an endocardial MBF reserve of <1.5 (n=30) and increased in those with an endocardial MBF reserve of > or =2.5 (n=45) (P<0.05). Most (80%) segments with endocardial MBF reserve of <1.5 and 14% with an endocardial MBF reserve of 1.5 to 2.5 showed inducible dysfunction after dipyridamole, whereas none of the segments with an endocardial MBF reserve of > or =2.5 showed this finding. A sigmoid relation (y=-6.74/[1+exp (19.9. [x-1.84])]+1.35. x, r=0.93, P<0.0001) was noted between endocardial MBF reserve and Delta%WT. In contrast, neither the epicardial MBF reserve nor the endocardial/epicardial MBF ratio during hyperemia was associated with inducible regional dysfunction. Increased myocardial oxygen demand resulting from hypotension and reflex tachycardia unmasking a reduced endocardial MBF reserve is the primary mechanism of dipyridamole-induced regional dysfunction in chronic coronary artery disease.