Specificity of synergistic coronary flow enhancement by adenosine and pulsatile perfusion in the dog

Coronary flow elevation from enhanced perfusion pulsatility is synergistica lly amplified by adenosine. This study determined the specificity of this i nteraction and its potential mechanisms. 2. Mean and phasic coronary flour responses to increasing pulsatile perfusi on were assessed in anaesthetized dogs, with the anterior descending corona ry artery servoperfused to regulate real-time physiological flow pulsatilit y at constant mean pressure. Pulsatility was varied between 40 and 100 mmHg . Hearts ejected into the native aorta whilst maintaining stable loading. 3. Increasing pulsatility elevated mean coronary flow +11.5 +/- 1.7% under basal conditions. Go-infusion of adenosine sufficient to raise baseline flo w 66% markedly amplified this pulsatile perfusion response (+82.6 +/- 14.3% increase in mean flow above adenosine baseline), due to a leftward shift o f the adenosine-coronary flow response curve at higher pulsatility. Flow au gmentation with pulsatility was not linked to higher regional oxygen consum ption, supporting direct rather than metabolically driven mechanisms. 4. Neither bradykinin, acetylcholine nor verapamil reproduced the synergist ic amplification of mean flow by adenosine and higher pulsatility, despite being administered at doses matching basal flow change with adenosine. 5. ATP-sensitive potassium channel (II-ATP) activation (pinacidil) amplifie d the pulse-flow response 3-fold, although this remained significantly less than with adenosine. Go-administration of the phospholipase A, inhibitor q uinacrine virtually eliminated adenosine induced vasodilatation, yet synerg istic interaction between adenosine and pulse perfusion persisted, albeit a t a reduced level. 6. Thus, adenosine and perfusion pulsatility specifically interact to enhan ce coronary flow. This synergy is partially explained by K-ATP agonist acti on and additional non-flow-dependent mechanisms, and may be important for m odulating flow reserve during exercise or other high output states where in creased flow demand and higher perfusion pulsatility typically co-exist.