To determine whether nitrous oxide (N2O) worsens myocardial ischemia by diminishing coronary pressure, we performed two sets of experiments using an acutely instrumented swine model of regional coronary ischemia. In constant pressure experiments (n = 11), coronary pressure and heart rate were kept constant as N2O (77%-79%) was substituted for N2 in the inspired gas. Nitrous oxide decreased systolic shortening, measured by sonomicrometry, from 68.0% to 63.6% (P less than 0.05) of preischemic control values in the ischemic zone and from 116.2% to 103.2% (P less than 0.05) of control values in the adjacent normal myocardium. There was no disproportionate effect of N2O on ischemic myocardium, and the N2O-induced depression of contractile function was fully reversible. In a series of constant external stenosis experiments (n = 13), the effects of N2O on heart rate, mean arterial pressure, and the coronary stenosis itself were not controlled. In these experiments, substitution of N2O for N2 induced deterioration in both the ischemic zone (systolic shortening decreased from 68.7% to 58.4% of preischemic control values, P less than 0.05) and in the adjacent normal myocardium (systolic shortening decreased from 113% to 102.9% of preischemic control, P less than 0.05). Nitrous-oxide-induced ischemic zone contractile dysfunction was often not reversible. The pressure gradient across the coronary stenosis did not increase and peripheral coronary pressure did not decrease because of N2O. Diffusion hypoxia was also excluded. This study confirms that N2O has a significant but mild depressant effect on the performance of both normal and ischemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)