Effects of a broad-spectrum caspase inhibitor and volume-regulatory Cl− channel inhibitors on global ischemia followed by 24 hr of reperfusion. (A) Percentages of TUNEL-positive myocytes in transplanted hearts administered the inhibitors. Treatment with a broad-spectrum caspase inhibitor (+ Z-Asp-DCB [24 hr] group, n=6) or a volume-regulatory Cl− channel inhibitor (+ DIDS [24 hr] or + NPPB [24 hr] group, n=6 each) resulted in a decrease in the TUNEL-positive cardiomyocytes compared with in the vehicle-treated warm I/R (24 hr) group (*P <0.001, n=7). (B) Administration of the inhibitors prevented DNA ladders. (C) Global warm I/R increased caspase-3-like activity in the transplanted hearts at 4 hr after reperfusion (warm I/R [4 hr]) approximately 2.5-fold compared with in control hearts without I/R (*P <0.001, n=3). The inhibitors significantly decreased the caspase-3-like activity in the 4-hr reperfused hearts (†P <0.005, n=3 each).