1. The effects of diazepam (Valium) on coronary and systemic vascular resistance were studied in anaesthetized dogs on cardiopulmonary bypass under conditions of constant heart rate and aortic pressure.2. Pharmacological doses of diazepam uniformly produced coronary vasodilation lasting 30 min; systemic vascular resistance also decreased, but to lesser degree.3. When coronary blood flow was maintained constant at physiological levels, diazepam produced no changes in left ventricular contractility, as assessed by peak LV isovolumetric pressure, dp/dt max, force-velocity, and length-tension relations, whereas previous experiments had demonstrated a positive inotropic effect in a similar preparation in which coronary blood flow was responsive to alterations in coronary vascular resistance.4. In five dogs, complete separation of the coronary and systemic circulations was accomplished by a double pump-oxygenator system; direct intracoronary administration of diazepam produced coronary vasodilatation, but coronary pressure and flow were not altered by administration of diazepam to the systemic circulation.5. It is concluded that diazepam augments myocardial contractility by increasing coronary blood flow. This relationship is independent of extracardiac humoral mechanisms, and appears to require the delivery of diazepam to the coronary circulation.
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