Shibano T, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Methods Find Exp Clin Pharmacol. 1989 Sep;11(9):567-75.
In Langendorff rat hearts, anoxia increased the coronary flow, concentration of adenosine in the coronary effluent and the tissue level of lactate, and decreased the intracellular oxygen, left ventricular pressure (LVP), heart rate and the tissue levels of adenosine triphosphate (ATP) and creatine phosphate (CrP). In the normoxic heart, an infusion of iodoacetic acid (IAA) (0.1 mg/min) increased the coronary flow, adenosine concentration in the effluent, and decreased ATP and CrP levels, without decreasing the intracellular oxygen. When glucose in the perfusate was substituted for pyruvate, IAA did not produce the pharmacological effects. In the normoxic heart, an infusion of 2,4-dinitrophenol (DNP) (50 micrograms/min) increased the coronary flow, adenosine concentration in the effluent and oxygen consumption, but decreased the intracellular oxygen, LVP and the tissue levels of ATP and CrP, without affecting the lactate level. There was no direct relationship between the coronary flow and the adenosine concentration in the effluent, but there was a close relationship between the increase in coronary flow and the total loss of myocardial ATP and CrP during anoxia, infusion of IAA, or infusion of DNP. These results indicate that the total loss of ATP and CrP from the myocardium (and hence energy state of the myocardium) may be responsible for regulation of coronary flow.
在Langendorff灌流的大鼠心脏中，缺氧增加了冠脉血流量、冠脉流出液中腺苷的浓度以及乳酸的组织水平，并降低了细胞内氧含量、左心室压力（LVP）、心率以及三磷酸腺苷（ATP）和磷酸肌酸（CrP）的组织水平。在常氧心脏中，输注碘乙酸（IAA）（0.1mg/min）可增加冠脉血流量、流出液中腺苷的浓度，并降低ATP和CrP水平，但不降低细胞内氧含量。当用丙酮酸替代灌注液中的葡萄糖时，IAA未产生药理作用。在常氧心脏中，输注2,4-二硝基苯酚（DNP）（50μg/min）可增加冠脉血流量、流出液中腺苷的浓度以及氧消耗，但降低细胞内氧含量、LVP以及ATP和CrP的组织水平，而不影响乳酸水平。冠脉血流量与流出液中腺苷浓度之间无直接关系，但在缺氧、输注IAA或输注DNP期间，冠脉血流量的增加与心肌ATP和CrP的总丢失之间存在密切关系。这些结果表明，心肌中ATP和CrP的总丢失（进而心肌的能量状态）可能是冠脉血流调节的原因。
