Microvascular, flow and O2 consumption responses of ischemic myocardium to prazosin.
The effects of selective alpha 1-adrenoceptor blockade with prazosin were investigated in ischemic rabbit heart. Using labeled microspheres, regional coronary blood flow was measured before and 1 hr after occlusion of the circumflex coronary artery in controls and animals given 1 mg/kg of prazosin 10 min after ligation. Small artery and vein O2 saturations were obtained microspectrophotometrically from hearts of anesthetized rabbits. Fluorescein isothiocyanate-dextran (150 mg/kg) was administered to mark the perfused microvessels and alkaline phosphatase stain was used to locate the total microvasculature. Prazosin depressed the arterial blood pressure. Coronary flow and O2 consumption (10.9 +/- 4.5 and 6.1 +/- 1.8 ml O2/min/100 g, nonoccluded and occluded) were significantly lower in the occluded region in the control group, while O2 extraction (4.9 +/- 1.4 and 6.8 +/- 2.6 ml O2/100 ml) was locally elevated. The results of occlusion in the prazosin-treated group were similar for flow, O2 consumption (9.9 +/- 4.5 and 6.7 +/- 5.3 ml O2/min/100 g, nonoccluded and occluded) and O2 extraction (6.6 +/- 2.3 and 8.2 +/- 2.3 ml O2/100 ml). The per cent of perfused microvessels was not significantly altered by occlusion in the control group. In the prazosin group, the percentage of occluded region subendocardial capillaries and arterioles perfused was significantly greater than in the control group, e.g., 65 +/- 9% perfused capillaries/mm2 in control occluded subendocardium vs 78 +/- 9% perfused capillaries/mm2 in prazosin-treated occluded subendocardium. Thus, the slight increase in microvessel utilization with prazosin was not sufficient to improve the flow or the O2 consumption in the ischemic myocardium.
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Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635.
Joselevitz-Goldman
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Weiss
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HR
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001784:Blood Gas Analysis; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D006454:Hemoglobins / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects*; D008863:Microspheres; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology*; D011817:Rabbits
D003911:Dextrans; D006454:Hemoglobins; C015219:fluorescein isothiocyanate dextran; D000469:Alkaline Phosphatase; D016650:Fluorescein-5-isothiocyanate; D011224:Prazosin