Acute myocardial injury has been demonstrated as a remote sequela of severe lower torso ischemia-reperfusion (I/R) due to proinflammatory events. In a model of I/R injury, administration of C1 esterase inhibitor (C1-Inh) reduces myocardial necrosis. We investigated the susceptibility of the left (LV) versus right ventricle (RV) and the protective effect of transgenic C1-Inh-overexpressing mice. Two groups of mice (n = 6) underwent a 2-h lower torso ischemia followed by 3 h of reperfusion: transgenic and wild type with sham-operated controls. Animals were then injected with (125)I bovine albumin. Heart was removed and samples from right and left ventricular free wall were harvested, weighted, and radioactivity was determined. Permeability index for wild-type animals in the RV was 0.22 +/- 0.04, compared to 0.17 +/- 0.07 in controls (NS), and in the LV 0.36 +/- 0.08, compared to 0.21 +/- 0.05 in controls (p <.01). The LV showed a significantly higher value compared to the right (0.22 +/- 0.04 vs. 0.36 +/- 0.08, p <.01). No difference was seen in the RV between transgenic and wild-type mice; however, in the LV the values decreased significantly in transgenic animals (p <.015). Thus, remote myocardial injury after lower torso I/R is present in both ventricles; however, the LV seems to be more susceptible as assessed by albumin permeability. Inhibition of the classic complement cascade may be a promising therapeutic approach for myocardial protection in reperfusion injury.