Role of heart rate reduction in the treatment of exercise-induced myocardial ischaemia

The role of bradycardia in reducing exercise-induced ischaemia and wall dysfunction was examined in dogs with single vessel chronic coronary artery stenosis created using an ameroid constrictor. Treadmill exercise produced significant regional myocardial ischaemia (blood flow measured using microspheres) and contractile dysfunction (systolic wall thickening measured with sonomicrometers). Dogs were initially studied during a control run before and during a second identical run after administration of the cardioselective beta-adrenergic blocker atenolol, which improved regional ischaemic function from 4.4 +/- 3.7% to 8.5 +/- 2.8% and subendocardial perfusion from 0.43 +/- 0.23 to 0.55 +/- 0.29 ml min-1 g-1. In another group of dogs during a run with atenolol, the heart rate was paced to match the rate observed in the control run. During the atenolol run with pacing, all beneficial effects of atenolol observed at the reduced exercise heart rate were lost. A third group of dogs received the bradycardic agent UL-FS 49 (1.0 mg kg-1, i.v.) prior to exercise. UL-FS 49 produced a heart rate reduction during exercise from 230 +/- 19 to 139 +/- 10 beats min-1; this was associated with an increase in systolic wall thickening from 9.3 +/- 5.0% (during the control run) to 21.5 +/- 8.4%, thereby eliminating the exercise-induced contractile dysfunction. Transmural myocardial blood flow per beat to the poststenotic myocardium was improved significantly from 4.8 X 10(-3) +/- 1.9 X 10(-3) ml beat-1 to 9.8 X 10(-3) +/- 1.7 X 10(-3). Atrial pacing to match heart rate to the control exercise rate during the UL-FS 49 run did not eliminate all of the improvement in systolic wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)