EFFECTS OF CGS-21680, A SELECTIVE A(2A) ADENOSINE RECEPTOR AGONIST, ON CARDIAC-OUTPUT AND VASCULAR-RESISTANCE IN ACUTE HEART-FAILURE IN THEANESTHETIZED RAT

1 The effects of CGS 21680, a selective A(2A) adenosine receptor agoni st, on cardiac output, blood pressure, mean circulatory filling pressu re (P-mcf), arterial and venous resistances, heart rate and left ventr icular end-diastolic pressure were assessed in rats with acute heart f ailure by means of coronary artery occlusion. 2 Animals (n=6 in each g roup) were divided into five groups: group I, sham-operated vehicle-tr eated (0.9% saline; 0.018 mL min(-1)); groups II-V, subject to coronar y artery occlusion and treated with vehicle (0.9% saline; 0.018 mL min (-1)) and CGS 21680 (0.1, 0.3 and 1.0 mu g kg(-1) min(-1)), respective ly. Haemodynamic measurements were taken one hour after completion of surgery, ninety minutes after coronary artery occlusion (except in gro up I), and fifteen minutes after infusion of saline or CGS 21680. 3 Ba seline haemodynamic measurements before occlusion were found not to di ffer significantly between the different groups of animals. However, a fter occlusion, cardiac output, rate of rise in left ventricular press ure (+dP/dt) and blood pressure were significantly reduced when compar ed to corresponding values in sham-operated animals. In addition, occl usion of the coronary artery resulted in a significant elevation in ve nous resistance, P-mcf and left ventricular end-diastolic pressure as compared to corresponding values in sham-operated animals. 4 Infusion with CGS 21680 at the highest dose significantly reduced blood pressur e, arterial resistance and left ventricular end-diastolic pressure whe n compared to occluded vehicle-treated animals (group II). Administrat ion of CGS 21680 at the highest dose also significantly increased card iac output (28%) and heart rate (10%) in comparison to occluded vehicl e-treated animals. In addition, the highest dose of CGS 21680 signific antly reduced P-mcf (9%) and venous resistance (62%) in comparison to occluded vehicle-treated animals. Administration of CGS 21680 did not significantly affect +dP/dt when compared to occluded vehicle-treated animals. 5 The results from the present investigation indicate that oc clusion of the coronary artery in rats results in a state of heart fai lure characterized by reduced arterial pressure and cardiac output, an d increased venous resistance, P-mcf and left ventricular end-diastoli c pressure. Administration of CGS 21680 to animals with acute heart fa ilure resulted in increased cardiac output which was due to reduced ve nous resistance, as well as increased heart rate.