Pertussis toxin (PTX) blunts intrinsic ischemia–reperfusion tolerance with cardiac specific Cav-3 overexpression (Cav-3 OE). Hearts from Cav-3 OE mice treated with PTX (3OE PTX) show higher left ventricular (LV) end-diastolic pressure (A) during 45 min reperfusion and lower LV developed pressure (B) compared with hearts from untreated Cav-3 OE (3OE) mice. Data were analyzed with repeated-measure two-way ANOVA and Bonferroni post hoc comparison. Significance was accepted when *P < 0.05; #P < 0.05. Data presented as mean ± SD, n = 11–13 per group. C57 = C57Bl/6 mice; Pre-Isch = preischemia.