Vasodilator signals from the ischemic myocardium are transduced to the coronary vascular wall by pertussis toxin-sensitive g proteins: A new experimental method for the analysis of the interaction between the myocardium and coronary vessels

Abstract Objectives We sought to detect cross-talk between the beating heart and coronary vascular bed during myocardial ischemia and to test the hypothesis that the cross-talk is mediated by pertussis toxin (PTX)-sensitive G proteins (G PTX ) in vessels. Background Coronary flow is closely related to the myocardial metabolic state, indicating the existence of a close interaction between cardiac muscle and coronary vascular beds. Experimental methods for the analysis of the interaction, however, have not been established. Methods Coronary detector vessels (DVs) were isolated from rabbit hearts. One end of the vessel was cannulated to a micropipette, and the other end was ligated. After the DV was pressurized (60 cm H 2 O), it was gently placed on the myocardium, which was perfused by the left anterior descending coronary artery (LAD) of anesthetized, open-chest dogs (n = 23). The LAD was occluded, and the DV diameter was observed using an intravital microscope with a floating objective system. To evaluate the involvement of G PTX , the DV was pre-incubated with PTX (100 ng/ml). Results The LAD occlusion of the beating heart produced significant dilation of DVs (241 ± 25 μm) by 10%. The DVs pretreated with PTX (250 ± 27 μm) did not dilate in response to myocardial ischemia. N ω-nitro-l-arginine (100 μmol/l), but not glibenclamide (5 μmol/l), abolished the ischemia-induced DV dilation. Conclusions We have established experimental methods for direct analysis of the interaction between the myocardium and coronary microvessels. We conclude that the ischemic myocardium releases transferable vasodilator signals that are transduced by means of the G PTX located in the vascular walls. The nitric oxide pathway is involved in the signal transduction.