title: Persistent coronary vasodilation during long-term, supramaximal doses of adenosine.
abstract: Active and reactive hyperemias have been observed in the skeletal muscle circulation tachyphylactic to exogenous adenosine following 3-h supramaximal doses of the vasodilator. These findings failed to support a need for adenosine in metabolic control of skeletal muscle blood flow. The present study was conducted to determine if the coronary circulation also develops tachyphylaxis to adenosine while remaining sensitive to other metabolically linked vasodilator mechanisms. Experiments were conducted in eight pentobarbital-anesthetized, open-chest dogs whose blood flow in the left anterior descending coronary artery (LAD) was measured electromagnetically during 3-h infusion of adenosine into the LAD. Measurements of regional myocardial blood flow (radioactive microspheres), myocardial O2 consumption (Fick principle), and percent segment shortening (ultrasonic crystals) were also obtained. Adenosine was infused into the LAD at a rate of 27.0-72.0 mumol/min, depending on blood flow rate. Calculated concentration of adenosine in LAD blood averaged 0.484 +/- 0.111 mumol/ml, which was well in excess of that required for maximal coronary vasodilation. LAD blood flow averaged 21.5 +/- 2.2 ml/min during the preadenosine control condition. LAD blood flow after 3 h adenosine (123.3 +/- 23.0 ml/min) was not significantly different from that after 1-3 min adenosine (105.8 +/- 17.9 ml/min). There was no significant transmural variation in LAD blood flow during adenosine infusion. Adenosine had no significant effect on myocardial O2 consumption or percent segment shortening. Our results demonstrate persistent transmural vasodilation in the canine coronary circulation during long-term, supramaximal doses of adenosine and are consistent with a role for endogenous adenosine in maintenance of coronary vasodilation during sustained elevations in myocardial energy demands.
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D008863:Microspheres; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011868:Radioisotopes; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D011868:Radioisotopes; D000241:Adenosine