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Sharaf B. L. MD; McKendall, G. R. MD; Bier, J. MD; Fedele, F. MD; Most, A. S. MD; Gewirtz, H. MD
Coronary Artery Disease: April 1991

We tested the hypothesis that more than one mediator of coronary arteriolar tone may be active under certain experimental conditions and that as a result, impairment of blood flow regulation may not occur unless the function of all active and potentially active mediators is inhibited. Studies were conducted in nine closed-chest, sedated domestic swine instrumented with an artificial stenosis (80% luminal diameter reduction) in the left anterior descending coronary artery. Approximately 1 hour after stenosis placement and subsequent regional α-and β-adrenergic receptor blockade, sequential measurements of hemodynamics and regional myocardial blood flow were made at baseline, 15 minutes after completion of an indomethacin infusion distal to the stenosis, at the end of 20 minutes of arterial hyperoxia, after 10 minutes of adenosine deaminase infusion distal to the stenosis with hyperoxia maintained, and after 10 minutes of a combined 0.5 M NaOH plus 5 mM theophylline infusion distal to the stenosis with hyperoxia. A second experimental group was prepared in the same fashion. In this group, hemodynamic, flow, and metabolic measurements were made at baseline, and at 10, 20, and 30 minutes of NaOH (0.5 M) plus theophylline (5 mM) infusion and after 20 minutes of hyperoxia. In the primary group, results indicate that cumulative blockade of metabolic dilators (ie, prostacyclin, adenosine, tissue pH, Pco2, and Po2) impairs arteriolar relaxation by roughly 30% in endocardial layers distal to the stenosis but probably has no effect on tone in epicardial layers. Data obtained in the second experimental group support this interpretation because 1) distal zone endocardial flow failed to decline versus control at any time during the study and 2) epicardial flow also was unchanged versus control during the initial 20 minutes of NaOH plus theophylline infusion. Thus, maintenance of reduced arteriolar tone in epicardial layers distal to a severe coronary artery stenosis appears to be independent of metabolic mediators tested (ie, prostacyclin, adenosine, tissue pH, Pco2, and Po2) and only partially dependent on such mediators in endocardial layers.

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