ACADESINE INCREASES BLOOD-FLOW IN THE COLLATERALIZED HEART DURING EXERCISE

Acadesine, an adenosine-regulating agent, has been shown to increase c oronary flow and exert cardioprotective effects in acutely ischemic my ocardium, but a beneficial effect on coronary collateral flow during e xercise has not been demonstrated. We examined the effect of acadesine , 100 mu mol/min, i.v., on myocardial blood flow during treadmill exer cise in six normal dogs and seven dogs with moderately well-developed coronary collateral vessels. Collateral vessel growth was produced wit h 2-min intermittent occlusions of the left circumflex coronary artery followed by permanent occlusion. During resting conditions, myocardia l blood flow in the collateral zone was not significantly less than in the normal zone, but during exercise, blood flow increased by only 79 +/- 21% (from 0.98 +/- 0.29 ml/min/g to 1.64 +/- 0.19 ml/min/g; p < 0 .05) in the collateral zone as compared with 118 +/-:32% (from 1.09 +/ - 0.28 ml/min/g to 2.14 +/- 0.2 ml/min/g; p < 0.01) in the normal zone . During exercise, acadesine further increased mean blood flow in the collateral-dependent region by 24 +/-: 5% (to 2.04 +/-: 0.26 ml/min/g; p < 0.05) with no change in the transmural distribution of perfusion. The increase in collateral zone blood flow in response to acadesine r esulted from a decrease in both transcollateral resistance from 25.1 /- 2.7 mm Hg/min/g/ml to 18.8 +/- 8 mm Hg/min/g/ml (p < 0.05) and smal l-vessel resistance in the collateral-dependent myocardium from 45.3 /- 6.6 mm Hg/min/g/ml to 36.4 +/- 5.8 mm Hg/min/g/ml (p < 0.05). Acade sine also significantly increased normal-zone flow in the collateraliz ed dogs (to 2.62 +/- 0.33 ml/min/g; p < 0.05). In contrast, acadesine had no effect on coronary blood flow in normal dogs. In dogs with mode rately well-developed collateral vessels, acadesine increased blood fl ow in both the collateral-dependent and normal myocardial zones during exercise. Ln contrast, acadesine did not increase blood flow in norma l dogs. These findings suggest that adenosine metabolism is altered no t only in the collateral-dependent region but also in the normal regio n of hearts with a coronary artery occlusion.