Intravascular perfluorochemical (PFC) emulsions together with a high oxygen (O2) tension may increase the delivery of dissolved O2 to useful levels. A severely anemic model of cardiopulmonary bypass (CPB) was used to test the hypothesis that a novel PFC emulsion (PFCE; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA] 90% w/v perflubron) used at a high PO2 during bypass delivers sufficient O2 to ameliorate hypoxic myocardial contractile dysfunction. Acutely anemic dogs (N = 42; hematocrit = 15.8 ± 0.6% [mean ± SEM] before CPB and 10.9 ± 0.1% during CPB) were divided into four groups. Group 1 was a control (n = 12). As CPB was initiated, groups 2 (n = 10), 3 (n = 10), and 4 (n = 10) had 1.35 g PFC·kg-1, 2.7 g PFC·kg-1, or 5.4 g PFC·kg-1 added via the venous return cannula. Pre-CPB and post-CPB cardiac function was measured by the first derivative of left ventricular pressure (dP/dt(max)). The dP/dt(max) on separation from CPB was: group 1, 619 ± 96; group 2, 738 ± 56; group 3, 782 ± 101; and group 4, 828 ± 100 (p < 0.05 groups 3 and 4 versus group 1). Mortality during the first hour after separation from CPB was higher in group 1 than in PFCE treated dogs; however, this trend did not attain statistical significance (p < 0.065). The PFC dose was higher in survivors than in nonsurvivors (2.6 ± 0.4 g PFC·kg-1 versus 1.2 ± 0.5 g PFC·kg-1; p < 0.05). A PFCE used at a high PO2 provides sufficient physically dissolved O2 to relieve myocardial hypoxic injury in a severely anemic model of CPB. Current PFCEs are effective O2 carriers. This finding suggests that they can be used as a temporary erythrocyte substitute to diminish the need for allogeneic transfusions during cardiac operations.