Isoflurane pre-treatment before cardiopulmonary bypass alleviates neutrophil accumulation in dog lungs.

OBJECTIVE: This study investigated the effect of isoflurane pretreatment on cardiopulmonary bypass (CPB)-related lung injury. METHODS: Twelve dogs were randomly divided into two groups of six each. In one group, 1.0 minimum alveolar concentration (MAC) of isoflurane was dministered for 30 min before CPB, while the control group received no anaesthetic. Both groups then underwent 100 min of mild hypothermic CPB with 60-min aortic cross clamping. Haemodynamic parameters, respiratory mechanics and alveolar arterial oxygen difference (AaDO2) were measured during the experiment. One hundred and fifty minutes after CPB, lung tissue samples from the non-dependent and dependent portions of the left and right lungs were harvested for polymorphonulear leukocyte (PMNs) counts. RESULTS: Following CPB, within the control group, pulmonary vascular resistance (PVR) was significantly increased at 60, 120 and 180 min after declamping, AaDO2 deteriorated at 180 min post-declamping, and dynamic lung compliance (DLC) was reduced dramatically after declamping. Isoflurane pretreatment before CPB significantly reduced PVR compared to the controls. AaDO2 was impaired at 180 min after declamping and DLC was decreased after declamping within the isoflurane group. No differences in AaDO2 and DLC were found between the isoflurane and control groups. At 180 min after declamping, the PMN count in both the non-dependent and dependent regions of the isoflurane pre-treated lungs was significantly lower than that of the controls. CONCLUSIONS: Our results suggest that 30-min pre-treatment with 1.0 MAC isoflurane before CPB caused a reduction in PMN accumulation in the dog lungs, inhibition of increases in PVR, and it did not affect AaDO2 in the early post-CPB stage.

Genetic factors contribute to patient-specific warfarin dose for Han Chinese.

BACKGROUND: Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboses. To address the association of genetic factors and warfarin dosage for ethnic Han Chinese, we genotyped six candidate genes involved in the warfarin interactive pathway with focus on SNPs with reported association with warfarin dose. METHODS: We recruited a study population consisted of 318 patients receiving warfarin treatment and 995 healthy controls. PCR and direct sequencing were used to identify the sequence polymorphisms. RESULTS: In our study population, SNP rs1799853 of CYP2C9, rs1687390 of ORM1-2, and rs2069919 of PROC showed no variation. SNPs rs12714145 of GGCX and rs1799809 of PROC showed no significant correlation with warfarin dose. The associations of SNPs rs9934438 and rs9923231 of VKORC1, the 3 (rs1057910) and C(-65) (rs9332127) alleles of CYP2C9, and SNP rs4653436 of EPHXI with the dose of warfarin were significant. CONCLUSION: A multiple regression model based on the genetic polymorphisms of VKORC1, CYP2C9, EPHX1 and the non-genetic factors of age and body weight can explain 40.2% of the variance in warfarin dose in Han Chinese patients. Translation of this knowledge into clinical guidelines for warfarin prescription may improve the safety and efficacy of warfarin treatment among Han Chinese.