930-102 Coronary Denervation Attenuates Vasospasm Induced by Pericoronary Application of Methacholine in Pigs

Abstract

Autonomic innervation of the coronary arteries is thought to intervene in the genesis of coronary vasospasm, We assessed the potential effect of selective coronary denervation in the inhibition of vasospasm. Chronic sympathetic and parasympathetic denervation was provoked by topical application of phenol to the proximal LAD in 20 pigs through a lateral thoracotomy. Two weeks later, we performed an midsternal thoracotomy. Heart rate, aortic and ventricular (LV) pressure, LV dP/dt, coronary blood flow (CBF) at the LAD, and 32–channel epicardial ST segment mapping were monitored during every MCH application. Phenol-induced coronary adrenergic and cholinergic denervation was confirmed by histofluorescence and cholinesterase staining, Isolated LAD rings of 5 phenol-denervated pigs were studied to confirm smooth muscle integrity, Application of MCH to control pigs (n = 10) induced an statistically significant fall in CBF (75 ± 19%) accompanied by electrical and mechanical signs of ischemia: mean ST segment elevation on the epicardial electrograms of 9,7 ± 4.7 mV, a drop in systolic LV pressure (-20 ± 8.4 mmHg) and a decrease in LV dP/dt (-404 ± 203 mmHg/s). There were no changes in heart rate. The parameters returned to normal values after 5 to 8 min. As compared to controls, phenol treated pigs showed a significant attenuation ofthe fall in CBF (25 ± 17%), lesser ST segment elevation (2.4 ± 2.1 mV), a lower drop in LV pressure (-8 ± 2.3 mmHg), and a smaller decrease in LV dP/dt (-167 ± 104 mmHg/s). Coronary angiography performed in 6 additional pigs evidenced that the coronary spasm occurred at the site of MCH exposure. Isolated LAD rings of phenol treated pigs constrict after incubation with endothelin-1 indicating preserved vascular smooth muscle function. In 5 control pigs, a second application of MCH after muscarinic receptor blockade with atropine (0.4 mg/kg iv.) resulted in complete abolition of the vasospasm confirming that vasospasm was mediated by the muscarinic receptor stimulation. In conclusion, pericoronary autonomic denervation protects against coronary constriction induced by direct muscarinic receptor stimulation with methacholine in situ the pig heart.