Evaluation of myocardial perfusion and coronary vascular resistance following withdrawal of chronic nitroglycerin treatment in rabbits.
This investigation was performed to determine whether the abrupt withdrawal of chronically administered nitroglycerin (NTG) alters coronary vascular resistance and myocardial perfusion in an experimental rabbit model. New Zealand white rabbits received 2 inches of topical NTG (2%) applied 3 times daily over a 6 week period. Forty hours after abrupt withdrawal of NTG left ventricular blood flow was assessed by the radioactive microsphere technique. Coronary resistance was significantly increased in NTG-withdrawal rabbits at the baseline (21.5 +/- 3.1) compared to controls (13.5 +/- 1.2) and remained elevated after ergonovine administration at both the early (NTG-withdrawal: 20.9 +/- 3.5 vs controls 12.6 +/- 1.5) and late (NTG-withdrawal: 17.1 +/- 3.1 vs controls: 11.6 +/- 0.9) sampling periods. Neither ergonovine nor indomethacin significantly altered blood flow compared to earlier values. However, the NTG-withdrawal rabbits exhibited significantly lower blood flow to the left ventricle compared to controls after ergonovine administration at both early (NTG-withdrawal: 4.80 +/- 0.72 ml/min/gram vs controls: 6.98 +/- 0.79 ml/min/gram) and late (NTG-withdrawal: 5.30 +/- 0.80 ml/min/gram vs controls: 7/52 +/- 0.66 ml/min/gram) sampling periods and also following indomethacin administration (NTG-withdrawal: 4.24 +/- 0.46 ml/min/gram vs controls: 7.52 +/- 1.26 ml/min/gram). Electrocardiographic evidence of myocardial ischemia was noted in the NTG-withdrawal rabbits following intracardiac injection of microspheres. These studies show that increased sensitivity of NTG-withdrawal rabbits to ergonovine or microsphere injection is associated with increased coronary vascular resistance. However, severe myocardial ischemia was not observed.
D000818:Animals; D003326:Coronary Circulation; D004562:Electrocardiography; D004874:Ergonovine / Q000494:pharmacology; D006329:Heart Conduction System; D007213:Indomethacin / Q000494:pharmacology; D009200:Myocardial Contraction; D005996:Nitroglycerin / Q000009:adverse effects*; D010477:Perfusion; D011817:Rabbits; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014655:Vascular Resistance
D005996:Nitroglycerin; D004874:Ergonovine; D007213:Indomethacin