Coronary artery spasm after abrupt withdrawal of nitroglycerin in rabbits

Abstract

The potential for abrupt withdrawal of nitroglycerin (NTG) to create coronary artery spasm was assessed in New Zealand white rabbits. In the control setting, electrocardiograms were taken from 7 anesthetized rabbits. The administration of intravenous ergonovine did not provoke ST-segment shifts or arrhythmias. Two inches of topical NTG (2%) was applied 3 times daily to a shaved area on the back of each rabbit over a 6-week period. Forty hours after abrupt withdrawal of NTG, intravenous ergonovine and indomethacin were given. Six of 7 rabbits had electrocardiographic changes: ventricular tachycardia in 2, ventricular fibrillation in 1, and significant (1 mm or more) ST-segment shifts in 5 rabbits. Three rabbits died. Sixty-four hours after NTG administration the remaining 4 rabbits were reexamined. One had baseline electrocardiographic evidence of severe myocardial ischemia. Repeat ergonovine and indomethacin testing in the others revealed ventricular tachycardia progressing to asystole in 1, premature ventricular complexes in 1, and ST-segment elevation in another. Two of the remaining 4 rabbits died. Eighty-two hours after NTG administration the remaining 2 rabbits were found dead in their cages. Nitroblue tetrazolium studies revealed extensive myocardial infarction in both animals. Additional studies were performed in 10 normal rabbits. Neither ergonovine nor indomethacin induced ST-segment shifts or arrhythmias in this control population. It is concluded that abrupt withdrawal of NTG and subsequent administration of ergonovine and indomethacin created myocardial ischemia, ventricular arrhythmias and myocardial infarctions in these rabbits. The cause of these abnormalities is probably coronary artery spasm.