To investigate the effects of diltiazem on myocardial ischemia-reperfusion injury (MIRI) and the underlying mechanisms.

Wistar rats were randomly divided into three groups: normal group (N group), ischemia-reperfusion group (I-R group), diltiazem+ ischemia-reperfusion group (D/I-R group). The isolated rat hearts in different groups were given different perfusion treatments: The N group was given continuous perfusion of K-H liquid for 150 min; the I-R group was given stable perfusion of K-H liquid for 30 min followed by ligating the left anterior descending coronary artery for 30 min, and K-H liquid reperfusion for 90 min; the D/I-R group underwent reperfusion with diltiazem (5 μmo/L) for 15 min and reperfusion with K-H liquid for 75 min. Left ventricular cardiac function (LVDP), maximal rise/fall rate of left ventricular pressure (±dp/dtmax), reperfusion arrhythmia (RA) score, calculated myocardial infarct (MI) size, and ALDH2, Bcl-2, and BAX expression in the left ventricular apex were recorded in each group.

The LVDP at 30 min and 45 min in the D/I-R group was significantly higher than that of the I-R group, respectively [(92.68±5.09) mmHg vs (75.77±5.33) mmHg, F=72.81, P=0.001; (90.39±4.29) mmHg vs (72.34±7.49) mmHg, F=51.92, P=0.001]. The ±dp/dtmax at 30 min and 45 min in the D/I-R group were significantly higher than that of the I-R group, respectively [+ dp/dtmax: (2885.45±286.47) mmHg vs (2063.64±105.57) mmHg, F=64.22, P=0.001 and (2712.73±236.52) mmHg vs (2053.64±92.33) mmHg, F=70.55, P=0.001; -dp/dtmax: (2214.55±104.63) mmHg vs (1710.91±217.97) mmHg, F=69.77, P=0.001 and (2119.09±84.43) mmHg vs (1544.55±207.72) mmHg, F=54.64, P=0.001, respectively]. The number of ventricular pre-contractions in the I-R group was significantly higher than that of the D/I-R group (P=0.001). The incidence of ventricular tachycardia, the time history of ventricular fibrillation, and the duration of ventricular tachycardia in the I-R group were also significantly higher than those of the D/I-R group (P=0.013, 0.049, and 0.001, respectively). The reperfusion arrhythmia score in the I-R group [5(3, 6), 57.36] was significantly higher than that of the D/I-R group [3(1, 4), 34.77] (P=0.001). Compared with the I-R group, the D/IR group had significantly smaller MI size [(55.51±1.43)% vs (17.01±1.13)%, P<0.01]. In the I-R group, the expression of mitochondrial ALDH2 was significantly reduced and that of Bcl-2 and Bax increased. Compared with the I-R group, the expression of mitochondrial ALDH2 was not significantly decreased in the D/IR group (P=0.11), while the expression of Bcl-2 and Bax was significantly increased. Compared with the I-R group, the D/I-R group had significantly increased Bcl-2/Bax ratio (0.44 vs 0.22, P=0.001).

Diltiazem reduces MIRI possibly by up-regulating the expression of mitochondrial Bcl-2 and down-regulating the expression of Bax. However, the therapeutic effect of diltiazem is not related with the gene and protein expression of mitochondrial ALDH2.

Myocardial, reperfusion injury; Diltiazem; Mitochondrial; Aldehyde dehydrogenase 2