Abstract: Objective To compare the effects of high frequency oscillatory ventilation (HFOV) combined with incremental positive end-expiratory pressure (IP) and those of pure HFOV on myocardial ischemia and hypoxia and apoptosis of cardiomyocytes in dogs with smoke inhalation injury. Methods Twelve healthy male dogs were divided into group HFOV and group HFOV+ IP according to the random number table, with 6 dogs in each group. After being treated with conventional mechanical ventilation, dogs in both groups were inflicted with severe smoke inhalation injury, and then they received corresponding ventilation for 8 hours respectively. After treatment, the blood samples were collected from heart to determine the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase 1 (LDH1) in plasma. The dogs were sacrificed later. Myocardium was obtained for determination of content of TNF-α per gram myocardium by ELISA, apoptotic rate of cardiomyocytes by flow cytometer, degree of hypoxia with HE staining, and qualitative and quantitative expression of actin (denoted as integral absorbance value) with streptavidin-biotin-peroxidase staining. Data were processed with t test. The relationship between the content of TNF-α per gram myocardium and the apoptotic rate of cardiomyocytes was assessed by Spearman linear correlation analysis. Results (1) After treatment for 8 h, the values of activity of CK-MB and LDH1 in plasma of dogs in group HFOV+ IP were respectively (734±70) and (182±15) U/L, which were both lower than those in group HFOV [(831±79) and (203±16) U/L, with t values respectively 2.25 and 2.35, P values below 0.05]. (2) Compared with that in group HFOV [(0.060±0.018) μg], the content of TNF-α per gram myocardium of dogs in group HFOV+ IP after treatment for 8 h was decreased significantly [(0.040±0.011) μg, t=2.32, P<0.05]. (3) Compared with that in group HFOV [(33.4±2.2)%], the apoptotic rate of cardiomyocytes of dogs in group HFOV+ IP after treatment for 8 h was significantly decreased [(28.2±3.4)%, t=3.15, P<0.05]. There was a positive correlation between the content of TNF-α per gram myocardium and the apoptotic rate of cardiomyocytes (r=0.677, P<0.05). (4) HE staining showed that myocardial fibers of dogs in both groups were arranged in wave shape in different degrees, indicating there was myocardial hypoxia in different degrees. Compared with that of group HFOV, the degree of hypoxia in group HFOV+ IP was slighter. (5) The results of immunohistochemical staining showed that there was less loss of actin in myocardial fibers of dogs in group HFOV+ IP than in group HFOV. The expression level of actin in myocardium of dogs in group HFOV+ IP after treatment for 8 h (194.7±3.1) was obviously higher than that in group HFOV (172.9±2.6, t=13.20, P<0.01). Conclusions Compared with pure HFOV, HFOV combined with IP can alleviate the inflammatory reaction in myocardium of dogs, reduce the apoptosis of cardiomyocytes, and ameliorate the myocardial damage due to ischemia and hypoxia.