Theophylline increases coronary vascular tone in humans: evidence for a role of endogenous adenosine in flow regulation

Abstract

To elucidate the role of adenosine in coronary vasoregulation, we studied the effects of adenosine antagonism (by theophylline) on coronary blood flow at different levels of adenosine formation (stimulated by hypoxia and exercise). Six healthy subjects were studied. Coronary sinus (CS) blood flow (thermodilution) and cardiac oxygen extraction [(A-CS)O2D] were determined while breathing room air at rest, and 12% oxygen, both at rest and during light exercise, on two occasions. One of the experiments was performed during infusion of theophylline. The basal CS flow was 118 (67-168) mL min-1 (mean and 95% confidence interval), and the (A-CS)O2D was 125 (111-142) mL L-1. Inhalation of 12% O2 decreased the arterial haemoglobin oxygen saturation to 83 (80-86)% at rest and to 77 (73-81)% during exercise. CS flow increased to 167 (93-214) and 261 (179-343) mL min-1, respectively, and (A-CS)O2D decreased to 102 (85-119) and 94 (77-111) mL L-1, respectively. Theophylline, at a dose lacking effects on myocardial work, markedly attenuated the coronary flow response to exogenous adenosine, and decreased CS flow to 89 (58-119), 120 (79-161) and 190 (162-218) mL min-1 at normoxic rest, hypoxic rest and hypoxic exercise, respectively. The overall decrease amounted to 23% (P < 0.05). The calculated coronary vascular conductance also decreased by 23% (P < 0.05) and (A-CS)O2D increased by 15% (P < 0.001). In conclusion, the data support the hypothesis that endogenous adenosine is involved in regulation of human coronary tone.