EFFECT OF DYSFUNCTIONAL VASCULAR ENDOTHELIUM ON MYOCARDIAL PERFORMANCE IN ISOLATED PAPILLARY-MUSCLES

Vascular endothelium has been shown to modify the contractile characteristics of vascular smooth muscle, and endocardial endothelium has been shown to modify the contractile characteristics of adjacent myocardium. In this study, whether vascular endothelium also modifies the contractile characteristics of adjacent myocardium and whether these effects are additive to those of endocardial endothelium were investigated. Rabbit hearts (n=54) were excised and mounted in a Langendorff preparation. Vascular reactivity was verified by acetylcholine infusion. One group of these hearts had Triton X-100 injected as a bolus into the coronaries to render the vascular endothelium dysfunctional. The other portion served as control hearts. Triton X-100 bolus injection resulted in little or no pathological changes on morphological examination; however, the vasodilatory response to acetylcholine in these hearts was abolished, suggesting vascular endothelial dysfunction. Vascular smooth muscle reactivity was verified in Triton X-100-injected hearts by nitroprusside infusion. In the control Langendorff-perfused hearts, there was little evidence of vascular endothelial dysfunction, with the coronary perfusion rate increasing from 8.9+/-0.4 to 11.0+/-0.3 ml/g per minute (p<0.01) in response to acetylcholine. All hearts were then removed, and right ventricular papillary muscles were excised for myocardial mechanical studies. Control Langendorff-perfused hearts had myocardial mechanical characteristics similar to those of muscles from 18 other control hearts without Langendorff perfusion, indicating that the Langendorff perfusion itself had little effect on myocardial mechanics. The muscles from the Triton X-100-injected Langendorff hearts had marked changes: a shortening of twitch duration (363+/-16 versus 449+/-9 msec, p<0.01) and decreases in total tension (2.2+/-0.2 versus 2.9+/-0.2 g/mm2, p<0.01), dT/dt (9+/-1 versus 12+/-1 g/mm2 per second, p<0.05), and maximum velocity of unloaded muscle shortening (V(max)) (0.89+/-0.06 versus 1.14+/-0.07 length at which maximum developed tension occurred [L(max)/sec, p<0.05). Endocardial endothelial removal of the papillary muscles in the two control groups (with and without Langendorff perfusion) by Triton X-100 caused the same changes in twitch characteristics as occurred in muscles from the Langendorff-perfused hearts injected with Triton X-100 but with intact endocardial endothelium, suggesting that vascular endothelial dysfunction had similar effects on contractile characteristics as endocardial endothelial removal. Endocardial endothelial removal of the papillary muscles from Langendorff-perfused hearts that had a bolus injection of Triton X-100 caused further shortening of twitch duration and a further decrease in total tension (1.7+/-0.2 versus 2.1+/-0.1 g/mm2, p<0.05), dT/dt, and V(max) (0.69+/-0.03 versus 0.89+/-0.01 L(max)/sec, p<0.01), suggesting that the myocardial contractile effects of endocardial and vascular endothelium are additive. Increasing extracellular calcium concentration to 15 mM normalized dT/dt and V(max) such that these parameters were similar in all groups of muscles before and after vascular and endocardial endothelial dysfunction. Total tension normalized completely only at higher extracellular calcium concentrations (20 and 25 mM). The addition of 10(-5) M phenylephrine to muscles with and without vascular endothelial dysfunction in a bath with 15 mM calcium normalized tension, also suggesting that the changes documented in this study were not due to myocardial damage but to endothelial dysfunction. These results suggest that both endocardial and vascular endothelium modulate the contractile characteristics of their adjacent myocardium and that their effects are additive.