title: Myocardial ischemia during vasodilator therapy in a canine model of pulmonary hypertension and coronary insufficiency.
abstract: Pulmonary vasodilator therapy during increased right ventricular (RV) afterload and insufficient RV myocardial perfusion might further impair RV performance by lowering systemic and, thus, coronary perfusion pressure. This hypothesis was tested by initially inducing pulmonary hypertension (80% increase in resting pulmonary artery pressure by injection of autologous muscle) and subsequent right coronary artery stenosis (40% decrease in flow by external cuff occlusion) in eight open-chest dogs. Then the effects of nitroglycerin (5 micrograms.kg-1.min-1), prostaglandin E1 (0.2 microgram.kg-1.min-1), and hydralazine (mean 0.14 mg/kg) on global and regional (ultrasonic dimension technique) RV performance and coronary hemodynamics (electromagnetic flow probes) were determined. Following all three drugs, right coronary artery flow decreased by 40-65% (mean values) accompanied by severe regional myocardial dysfunction suggestive of ischemia (akinesis, systolic lengthening, and postsystolic shortening). Heart rates increased by 20-40%; aortic pressure decreased by 15-25%; and RV end-diastolic pressure remained unchanged. Despite similarly adverse effects on regional RV performance and comparable effects on heart rate, perfusion and filling pressures with all three drugs, RV systolic pressure, RV dP/dt, and pulmonary artery pressure during nitroglycerin and prostaglandin E1 remained unchanged, and stroke volume and pulmonary artery flow decreased, but they all increased or were maintained (stroke volume) during hydralazine. Gas exchange was not affected by any of the vasodilators. Thus, in this model of combined acute pulmonary hypertension and right coronary artery insufficiency, nitroglycerin, prostaglandin E1, and hydralazine elicited severe regional dysfunction suggestive of ischemia, probably related to concomitant increases in heart rate and decreases in coronary perfusion pressure. Despite such evidence of severe regional RV ischemia, hydralazine maintained global RV pump function. These results indicate 1) that in the presence of increased RV afterload and coronary insufficiency, reduction in coronary perfusion pressure during pulmonary vasodilator therapy may be deleterious, and 2) that even severe regional myocardial ischemia may not necessarily be accompanied by respective changes in global hemodynamics and thus may go undetected.
authors.affiliation: Department of Anesthesia, University Hospital, Freiburg, Federal Republic of Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Priebe
mesh_terms: D000527:Alprostadil / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D003327:Coronary Disease / Q000139:chemically induced*; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D006830:Hydralazine / Q000009:adverse effects / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008955:Models, Cardiovascular; D005996:Nitroglycerin / Q000009:adverse effects / Q000627:therapeutic use*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012119:Respiration / Q000187:drug effects
chemical_list: D006830:Hydralazine; D000527:Alprostadil; D005996:Nitroglycerin