We examined the effects of
diltiazem, a
calcium-entry blocker, on exercise-induced
myocardial ischemia in nine conscious dogs with chronic
coronary stenoses. An
ameroid constrictor, Doppler flow probe, and hydraulic occluder were placed around the left circumflex coronary artery, and left ventricular pressure was measured (Konigsberg micromanometer). Pairs of ultrasonic crystals were implanted for measuring left ventricular systolic wall thickening (% delta WTh) in control (left ventricular anterior wall) and ischemic (left ventricular posterior wall) regions, and regional myocardial blood flow was measured with the
microsphere method. Eighteen days (average) after surgery mean coronary blood flow velocity had decreased and reactive hyperemic flow velocity after 10 sec of
coronary occlusion was markedly reduced, but % delta WTh at rest remained normal, indicating collateral development. Control treadmill exercise was performed for 3.7 min (average), and 2 hr later administration of 0.3 mg/kg
diltiazem was followed by an identical exercise bout. Control exercise increased % delta WTh in the normal region, while in the ischemic region % delta WTh decreased markedly and
ischemia was evident (subendocardial flow, 0.29 +/- 0.12[SD] ml/min/g). After
diltiazem hemodynamic and % delta WTh values at rest were not changed; during exercise the heart rate was significantly lower (204 +/- 24 vs 227 +/- 33 beats/min, p less than .01), but values for other hemodynamic measures were similar to those during the control run. % delta WTh in the control region was not changed during exercise after
diltiazem, but compared with control exercise in the ischemic zone there was less dysfunction and subendocardial flow was greater. Recovery from exercise-induced dysfunction in the ischemic region occurred within 5 min, compared with over 30 min after control exercise. Thus, in a preparation of chronic
coronary stenosis, the
calcium-entry blocker improved the relationship between regional myocardial flow and function during exercise and led to more rapid recovery of regional myocardial dysfunction.