Regional redistribution of myocardial perfusion by UL-FS 49, a selective bradycardic agent

The effects of UL-FS 49, a specific bradycardic agent, on systemic hemodynamics, regional myocardial function (sonomicrometry, percentage of segment shortening), and regional coronary blood flow (radioactive microspheres) were studied in open-chest, anesthetized dogs with severe left circumflex coronary artery (LCX) stenosis. UL-FS 49 was administered as two sequential bolus injections of 0.25 mg/kg. Heart rate decreased from 149 +/- 13 beats/min to 102 +/- 6 and 77 +/- 4 beats/min after 0.25 and 0.5 mg/kg cumulative doses of UL-FS 49, respectively. The reduction in heart rate was not associated with any significant change in left ventricular pressure or mean arterial pressure, left ventricular dp/dt, or coronary vascular resistance. Similarly no hemodynamic changes occurred with atrial pacing to the initial heart rate. Application of an LCX stenosis of sufficient severity to produce a 50% reduction in mean LCX blood flow (44 +/- 4 to 22 +/- 2 ml/min) resulted in a significant reduction in the percentage of segment shortening in the ischemic zone (9.8 +/- 1.6% to 6.5 +/- 1.1%). The percentage of segment shortening in the ischemic zone progressively improved to 8.4 +/- 1.2% and 9.4 +/- 0.5% after 0.25 and 0.5 mg/kg UL-FS 49, respectively. Subepicardial perfusion in the ischemic zone was decreased and subendocardial perfusion was increased after administration of UL-FS 49. Consequently the ischemic zone endocardial/epicardial ratio increased from 0.43 +/- 0.08 to 1.12 +/- 0.22 and 1.48 +/- 0.32 with low and high doses of UL-FS 49.(ABSTRACT TRUNCATED AT 250 WORDS)