Background: In the present study, the effects of extracorporeal cardiac shock waves combined with different concentrations of sulfur hexafluoride ultrasound microbubbles on myocardial ultrastructure in rats were observed.

Methods: Thirty-six rats were randomly divided into 6 groups: control group (N), extra-corporeal cardiac shock wave group, and combined group, i.e., extracorporeal cardiac shock wave combined with different concentrations of sulfur hexafluoride microbubble (0.225 mL/kg/min, 0.45 mL/kg/min, 0.9 mL/kg/min, 1.8 mL/kg/min). The combination of extracorporeal cardiac shock wave combined with sulfur hexafluoride microbubbles of different concentrations had no significant effect on hemodynamic indexes and left ventricular function in rats.

Results: There were significant differences in cardiac troponin I (cTnI) and nitric oxide among different groups. Histopathology showed that inflammatory cells infiltrated in the shock wave + microbubble 0.9 and shock wave + microbubble 1.8 groups. The myocardial ultrastructural injury score of shock wave + microbubble1.8 group was significantly higher than that of the N group, shock wave group, shock wave + microbubble 0.225 group, and shock wave + microbubble 0.45 group. The score of shock wave + microbubble 0.9 group was higher than that of the control group (P =.009). Western blot results showed that the expression of vascular endothelial growth factor and endothelial nitric oxide synthase (eNOS) protein in the rats treated with extracorporeal cardiac shock wave combined with sulfur hexafluoride microbubbles of different concentrations was higher than that in the N group and shock wave group, with shock wave + microbubble 0.45 group having the strongest expression.

Conclusion: Myocardial ultrastructure damage occurs when high concentrations of sulfur hexafluoride microbubbles are present, but a proper concentration of sulfur hexafluoride microbubbles could promote the cavitation effect of extracorporeal cardiac shock waves. Thus combination therapy may become a new paradigm in coronary heart disease, especially contributing to the treatment of refractory angina. Combination therapy may change coronary heart disease treatment, especially for refractory angina.