Reduction of exercise-induced regional myocardial dysfunction by propranolol. Studies in a canine model of chronic coronary artery stenosis.

Abstract

SUMMARY In 10 dogs, we placed a Doppler flow probe, an ameroid constrictor, and a hydraulic cuff occluder around the left circumflex coronary artery (CA). Ultrasonic dimension gauges were implanted in control segments (CS) and ischemic segments (IS) of the left ventricle (LV). A microtransducer was used to measure LV pressure (LVP). Sixteen to 35 days later, when CA occlusion was nearly complete and collaterals had developed, the dogs were studied by telemetry during exercise, while running behind a van (8-11 mph for 3.5 minutes). Control exercise and exercise after propranolol (P) (average dose 0.5 mg/kg, iv) were conducted on the same day 2 hours apart. During control exercise, significant increases occurred in heart rate (HR) (116-249 beats/min), LVP (124-163 mm Hg), end-diastolic pressure (EDP) (8.1-25.9 mm Hg), peak (+)dP/dt (3618-7348 mm Hg/sec), and percent shortening (%AL) of CS (19.7-28.8) (all P < 0.01), but percent systolic wall thickening (%AW) and %AL of IS decreased greatly [22.2 ± 3.8 to 5.1 ± 1.3% (P< 0.01) and 12.6 ± 2.1 to 7.1 ± 2.4% (P< 0.01), respectively]. During matched exercise periods after P, significantly less marked increases occurred in HR (101-182 beats /min), LVP (123-139 mm Hg), EDP (9.4-20.9 mm Hg), peak (+)dP/dt (2801-4312 mm Hg/sec), and %AL of CS (17.1-22.4%) (all P < 0.01). However, %AW and %AL of IS did not deteriorate [19.0 ± 3.6 to 14.3 ± 3.2% (NS) and 11.3 ± 3.1 to 11.5 ± 3.9% (NS)]; both were significantly different from control exercise (P < 0.01). It is concluded that amelioration by propranolol of an exercise-induced myocardial oxygen demand-supply imbalance in a collateral-dependent zone can markedly reduce regional ischemia and dysfunction at the same exercise level.

Adaptation to the stress of tachycardia in patients with coronary artery disease: insight into the mechanism of the warm-up phenomenon.

“…12 Furthermore, the degree to which shortening is impaired within any single segment may vary according to interventions that may modify ischemia. 13 Hence, in our investigation it is reasonable to consider that the ischemic zone was composed of segments demonstrating both severe and moderate impairment of contractile function during P1. During P2 segments that had previously demonstrated moderate impairment of systolic contractile function may have demonstrated more severe impairment.…”

Comparative effects of nitroglycerin, nifedipine and metoprolol on regional left ventricular function in patients with one-vessel coronary disease.

“…nifedipine, measurements were obtained immediately after 5-minute infusions at rest and separately during exercise to assure "maximal" drug effects. In this manner, the study could be completed in all patients within 28 hours, including a maximum 26 Despite the similar antiischemic effect of all three drugs, the underlying hemodynamic mechanisms were quite different. After nitroglycerin, left ventricular filling pressure, end-diastolic volume and diastolic blood pressure decreased significantly, implying that a reduction in preload and afterload were the predominant effects.8' 9 Afterload was reduced even more by the vasodilatory effect of nifedipine reflected in reductions of systemic vascular resistance, blood pressure and left ventricular filling pressure.…”

Persistence of regional left ventricular dysfunction after exercise-induced myocardial ischemia.

“…Variable durations of dysfunction min) have been noted after exercise in studies using this model (14,15,18,19) and may reflect differences in exercise intensity and duration, and extent of collateral flow during and after exercise. Regional myocardial blood flow post-exercise was not measured in these studies, however, and therefore the functional abnormalities observed in the postexercise period might have reflected continued hypoperfusion of deeper myocardial layers and not persistent functional abnormalities resulting from previous exercise-induced ischemia.…”