To observe the myocardial apoptosis and the molecular mechanism of captopril inhibiting myocardial apoptosis on cardiac arrest (CA) after resuscitation in a porcine acute pulmonary embolism (APE) model.

In this study, 29 inbred Beijing Landrace were randomly (random number)divided into four groups (n=5, each group): control, APE-CA, restoration of spontaneous circulation (ROSC)-captopril, and ROSC-saline. The model of CA and ROSC was induced by APE through injection of thrombus followed by cardiopulmonary resuscitation and thrombolytic therapy (urokinase, 15 000 U/kg, iv). Ten of 19 pigs with CA recovered to spontaneous circulation were divided randomly into the ROSC-captopril and ROSC-saline groups. Pigs in the ROSC-captopril group were treated with captopril (22.22 mg/kg) via porcine femoral vein at 30 min after ROSC. Pigs in the ROSC-saline group were treated with equal normal saline at 30 min after ROSC. The myocardial tissues were evaluated at 6 h after ROSC. Western blot was used to evaluate the protein levels of Bax, Bcl-2, Caspase-3, phosphorylated (p)-Src and phosphorylated extracellular regulated protein kinase (p-ERK1/2). Immunohistochemistry was used to evaluate the protein expression of p-Src and p-ERK1/2. Enzyme-linked immunosorbent assay was used to detect myocardial Na+-K+-ATPase levels. Statistical analysis was performed using one-way analysis of variance and pearson correlation test.

Compared with the control group, the protein expression of Bax (0.25±0.01, 0.53±0.01, 0.37±0.05, F=14.16, P<0.05) and Caspase-3 (0.24±0.01, 0.33±0.01, 0.34±0.06, F=7.32, P<0.05) in the APE-CA and ROSC- saline group were increased significantly, and the Bcl-2 expression was significantly decreased (0.56±0.02, 0.19±0.01, 0.37±0.10, F=6.68, P<0.05). Captopril reduced the protein levels of Caspase-3 and Bax, while stimulated the Bcl-2 expression (all P<0.05). Compared with the control group, the protein expression of p-Src and p-ERK1/2 were higher and the Na⁺-K⁺-ATPase level was decreased on CA and ROSC induced by APE (all P<0.05). Compared with the APE-CA group, the p-Src expression in the ROSC-captopril group (0.46±0.01 vs. 0.35±0.06, P<0.05) was decreased significantly. Captopril inhibited the activation of p-ERK1/2 than saline group (0.41±0.10 vs. 0.26±0.07, P<0.05), but has no effect on the Na⁺-K⁺-ATPase level. The protein expression of p-Src and p-ERK1/2 were positively correlated with the Bax, and negatively correlated with the Bcl-2 respectively. The myocardial Na⁺-K⁺-ATPase level negatively correlated with Caspase-3 protein expression.

The molecular mechanism of cardiomyocyte apoptosis on CA and ROSC induced by APE might be related to decreased Na⁺-K⁺-ATPase level and activation of p-Src and p-ERK1/2. The cardiomyocyte apoptosis were inhibited by captopril through reducing the expression of p-Src and p-ERK1/2 in myocardium.

Acute pulmonary embolism; Cardiac arrest; Spontaneous circulation recovery; Myocardial apoptosis; Molecular mechanism