Hemodynamic changes due to intracoronary injections of nonionic contrast medium Omnipaque-350 (OM), ionic dimer Hexabrix (HB), and ionic contrast medium Renografin-76 (R76) were compared at baseline and during reperfusion after a 30-minute left anterior descending coronary artery (LAD) occlusion. In 11 open chest, anesthetized, and atrially paced dogs, 4 ml of either OM, HB, R76, or 0.9% NaCl were injected into the carotid-LAD bypass system. Coronary blood flow (CBF) and coronary vascular resistance (CVR) were measured before, during and after the intracoronary injection. The maximal hyperemic change (in percentage) from the preinjection value of CBF and CVR were calculated. The results at baseline and during reperfusion for CBF were: 104 +/- 14% vs. 85 +/- 10% for OM (NS); 76 +/- 11% vs. 39 +/- 9% for R76 (p less than 0.05); 57 +/- 8% vs. 33 +/- 5% for HB (P less than 0.05); and 30 +/- 7% vs. 9 +/- 4% for 0.9% NaCl (p less than 0.05). Consequently, the hyperemic changes of CVR at baseline and during reperfusion were: -49 +/- 3 vs. -42 +/- 4% for OM (NS); -44 +/- 3% vs. -24 +/- 6% for R76 (p less than 0.01); -36 +/- 3% vs. -24 +/- 4% for HB (p less than 0.05); and -18 +/- 4% vs. -7 +/- 3% for 0.9% NaCl (p less than 0.05). Thus, ischemia and reperfusion significantly dampened the coronary hemodynamic and vascular response to R76, HB, and 0.9% NaCl but not to OM. The preserved coronary vascular reserve with high flow in this canine post-ischemic reperfusion model may explain the advantage of nonionic over ionic contrast media used in emergency coronary angiography following thrombolysis.