Study objective: Plasma volume expansion is frequently recommended to correct the low output state resulting from right ventricular (RV) infarction. However, any subsequent increase in pericardial and RV filling pressures from volume expansion could impair RV collateral blood flow. We examined whether volume expansion in dogs before right coronary Ligation reduced collateral perfusion and worsened the extent of RV necrosis. Design: Randomized experimental study. Setting: Animal research laboratory in university medical center. Participants: Forty anesthetized, closed-chest dogs were randomly assigned to normovolemic, pericardium opened (n=10) or intact (n=10) groups, and hypervolemic, pericardium opened (n=10) or intact (n=10) groups. Interventions: Hypervolemic animals received 24 mL/kg of 6% hetastarch. All animals underwent 90 min right coronary ligation, followed by 120 min reperfusion. Collateral coronary blood flow (radioactive microspheres) and area of necrosis (An) were determined in the area at risk (Ar). Measurements and results: Stroke volume decreased in all groups with ischemia but remained 25 to 40% greater in both hypervolemic groups than in normovolemic animals (p<0.05). In hypervolemic animals with intact pericardium, RV end-diastolic pressure increased to 10.4+/-2.1 mm Hg (mean+/-SD), a value that significantly exceeded those of the other three groups. During RV ischemia, collateral perfusion in the Ar was similar in both normovolemic groups and in hypervolemic animals with opened pericardium (mean range, 12.9+/-8.8 to 13.8+/-7.6 mL/min/100 g; p=NS), and the An/Ar varied from 11.8+/-6.3 to 18.6+/-17.4% (p=NS). In contrast, in hypervolemic animals with intact pericardium, collateral perfusion decreased to 7.2+/-3.5 mL/min/100 g and the An/Ar was increased to 38.2+/-18.6% (p<0.05 compared with other groups, respectively). Overall, An/Ar was inversely related to collateral blood flow in the Ar (r=-0.46; p<0.05) and correlated positively with RV end-diastolic pressure (r=0.61; p<0.05). Conclusions: Volume expansion preserved stroke volume during RV ischemia, independent of pericardial integrity. However, volume expansion in animals with an intact pericardium increased RV infarct size by twofold to threefold secondary to reduced periischemic collateral perfusion. This detrimental effect of volume expansion on infarct size was prevented by opening the pericardium.