Biomedical subjects

Xiaoyin Wang

Publications and source records attributed to Xiaoyin Wang.

9 recordsLinked to original sources

PubMed2006

Hypercholesterolemia enhances tolerance to lethal systemic hypoxia in middle-aged mice: possible role of VEGF downregulation in brain.

Hypercholesterolemia (HCL) is commonly associated with impaired vascular relaxation response and augmented vasoconstriction. Interestingly, it was shown that animals with HCL were less vulnerable to seizures and several clinical studies also revealed a better outcome after stroke in the patients with HCL. To this context, the present study was designed to test the hypothesis that HCL would enhance the animals' resistance to severe systemic hypoxia and in turn prolong their survival time under such noxious condition. Four groups of middle-aged (mean age: 51.1 +/- 2.8 weeks) male C57BL/6J wild-type mice (C57BL-WT) and low-density lipoprotein receptor knockout mice (LDLR-KO) were included in the study: two groups were exposed to severe normobaric hypoxia (5% F(I)O(2)) and other two groups were used for brain tissue sample collection and Western blot analysis. The survival time under the hypoxic condition was recorded for each animal. Individual blood samples were collected immedtately after the cessation of spontaneous breathing for measuring plasma total cholesterol (TCL) and triglycerides. The results show that the hypoxia survival time was longer in LDLR-KO than C57BL-WT (i.e. 3.7 +/- 0.5 versus 2.3 +/- 0.2 min; P < 0.05). A positive correlation was found between TCL and the survival time (r (2) = 0.43; P < 0.05). Furthermore, a significant downregulation of vascular endothelial growth factor (VEGF) was observed in the brain tissue of LDLR-KO, as compared with C57BL-WT (n, = 3/group; P < 0.05), whereas expression of heme oxygenase 1 was similar in these two groups. We conclude that HCL enhances resistance to lethal systemic hypoxia (i.e. 61% increase in survival time) in middle-aged mice. This paradoxical protective effect of HCL was associated with a concomitant downregulation of cerebral VEGF expression, which could potentially blunt the hypoxia-triggered and VEGF-mediated pathophysiological events leading to death.

Animals↗

PubMed2006

A cost comparison of off-pump CABG versus on-pump CABG at one-year: The Canadian off-pump CABG registry.

BACKGROUND: Evidence suggests that off-pump coronary artery bypass graft surgery (CABG) is as safe and effective as on-pump CABG, and the cost of initial hospitalization for off-pump CABG is less expensive than on-pump CABG. However, it is uncertain whether the cost savings are sustained over a longer period of time. OBJECTIVE: To assess in-hospital and one-year direct medical costs of off-pump CABG versus on-pump CABG in the context of the Canadian health care system. METHODS AND RESULTS: From March 2001 to December 2002, 1657 consecutive patients enrolled in the Canadian Off-Pump CABG Registry were compared with 1693 consecutive on-pump patients from Hamilton Health Sciences CABG database. At one year, patients of both groups were followed by telephone interview. An economic analysis was conducted from the perspective of the Ontario Ministry of Health and Long-Term Care, and the data analysis was based on propensity score-matched registry patients (1233 pairs) to ensure the comparability of the two study groups. Clinical event and resource use information was collected from all patients. Unit costs from the Hamilton Health Sciences case-costing system were used to estimate hospital costs; all costs were reported in 2003 Canadian dollars. Sensitivity analyses were performed to account for uncertainties. The cost of initial hospitalization for off-pump CABG was significantly less than on-pump CABG (11,744 dollars versus 13,720 dollars, P < 0.001). Although follow-up costs were similar between the groups, the one-year total cost per patient for off-pump CABG remained significantly less than on-pump CABG (12,063 dollars versus 14,141 dollars, P < 0.001). CONCLUSION: Off-pump CABG offers significant savings during initial hospitalization that are also sustained after one year.

Coronary Artery Bypass, Off-Pump↗

PubMed2005

Pharmacological preconditioning with sildenafil: Basic mechanisms and clinical implications.

The phosphodiesterase type-5 (PDE5) inhibitor, sildenafil, is the first drug developed for treatment of erectile dysfunction in patients. Experimental data in animals show that sildenafil has a preconditioning-like cardioprotective effect against ischemia/reperfusion injury in the intact heart. Mechanistic studies suggest that sildenafil exerts cardioprotection through NO generated from eNOS/iNOS, activation of protein kinase C/ERK signaling and opening of mitochondrial ATP-sensitive potassium channels. Additional studies show that the drug attenuates cell death resulting from necrosis and apoptosis, and increases the Bcl2/Bax ratio through NO signaling in adult cardiomyocytes. Emerging new data also suggest that sildenafil may be used clinically for treatment of pulmonary arterial hypertension and endothelial dysfunction. Future demonstration of the cardioprotective effect in patients with the relatively safe and effective FDA-approved PDE5 inhibitors such as sildenafil could have an enormous impact on bringing the long-studied phenomenon of ischemic and pharmacologic preconditioning to the clinical forefront.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2005

Bayesian inference on the patient population size given list mismatches.

In applying capture-recapture methods for closed populations to epidemiology, one needs to estimate the total number of people with a certain disease in a certain research area by using several lists with information of patients. Problems of lists error often arise due to mistyping or misinformation. Adopting the concept of tag-loss methodology in animal populations, Seber et al. (Biometrics 2000; 56:1227-1232) proposed solutions to a two-list problem. This article reports an interesting simulation study, where Bayesian point estimates based on improper constant and Jeffreys prior for unknown population size N could have smaller frequentist standard errors and MSEs compared to the estimates proposed in Seber et al. (2000). The Bayesian credible intervals based on the same priors also have super frequentist coverage probabilities while some of the frequentist confidence intervals procedures have drastically poor coverage. Seber's real data set on gestational diabetics is analysed with the proposed new methods.

Bayes Theorem↗

PubMed2005

Silencing heat shock factor 1 by small interfering RNA abrogates heat shock-induced cardioprotection against ischemia-reperfusion injury in mice.

Induction of heat shock factor 1 (HSF1) is known to associate with cellular response to divergent pathophysiological stresses including whole body hyperthermia (WBH) and ischemia-reperfusion. However, a direct cause-effect relationship between HSF1 activation and cytoprotection induced by myocardial preconditioning has not been conclusively established, mainly due to the limitations of available experiment tools. In the present studies, we used a novel approach to block HSF1 with small interfering RNA (siRNA) technique in vivo. Male adult ICR mice were treated intraperitoneally with amine (vehicle) or siRNA specific to HSF1 (siRNA-HSF1). Three days later, WBH preconditioning protocol (rectal temperature 42 degrees C for 15 min) was applied to these mice under light anesthesia. WBH preconditioning resulted in 2.7-fold and 3.4-fold increase in cardiac HSF1 mRNA and protein expression respectively 2 hours after WBH, which was inhibited in the siRNA-treated mice. The silencing effect of siRNA on HSF1 was associated with complete loss of the infarct- limiting protection by WBH preconditioning after 48 hours. Pretreatment with siRNA-HSF1 had no effect on infarct size in the sham control animals as compared with the amine-treated group. DNA micro-array analysis revealed that siRNA-HSF1 caused a general inhibition on multiple members of HSP family, except Hsp32, Hsp47 and Hsp60. In addition, the silencing effect of siRNA on HSF1 and HSPs gene expression was transient and its inhibitory effect disappeared by 10 days after treatment. siRNA-HSF1 also impaired the thermotolerance of the heat shocked mice as indicated by higher mortality following WBH. For the first time, we have applied siRNA technique in the field of myocardial preconditioning to demonstrate HSF1 activation as an essential step in WBH preconditioning against cardiac ischemia-reperfusion injury.

Animals↗

PubMed2005

The Canadian off-pump coronary artery bypass graft registry: a one-year prospective comparison with on-pump coronary artery bypass grafting.

BACKGROUND: The authors sought to examine in-hospital and one-year outcomes of off-pump coronary artery bypass grafting (CABG) and to determine the subgroups of patients most likely to benefit from the off-pump procedure in a regular surgical practice. METHODS: From March 2001 to December 2002, 1657 consecutive patients were treated with off-pump CABG and 1693 consecutive patients were treated with on-pump CABG. Propensity score modelling was performed to control for treatment and selection bias. A propensity-matched analysis was performed to identify factors associated with survival benefit from the off-pump procedure. RESULTS: The mortality was similar postoperatively and at one year after surgery. The rate of stroke was decreased in the off-pump group postoperatively (OR=0.49, 95% CI 0.23 to 1.06) and significantly at one year after surgery (OR=0.49, 95% CI 0.27 to 0.90). A significant reduction in acute renal dialysis and a significant increase in myocardial infarction rates were seen in off-pump patients during the initial hospitalization but these differences disappeared during the follow-up period. The number of grafts completed was significantly lower in off-pump CABG than in on-pump CABG (2.62+/-1.00 versus 3.36+/-0.92, respectively; P<0.001). Hospital length of stay and the percentage of patients who required mechanical ventilation were significantly lower in the off-pump group than in the on-pump group. At one year after surgery, the adjusted rate of coronary angiogram and revascularization was similar between the two groups, and the adjusted rate of self-reported angina and memory status was significantly better in the off-pump CABG group. Almost all subgroups of patients had a neutral effect or a survival benefit with the off-pump technique. CONCLUSIONS: The results from a Canada-wide multicentre registry showed the safety and effectiveness of off-pump CABG in most subgroups of patients in a regular surgical practice.

Canada↗

PubMed2004

Opening of Ca2+-activated K+ channels triggers early and delayed preconditioning against I/R injury independent of NOS in mice.

Opening of Ca2+-activated K+ (KCa) channels has been shown to confer early cardioprotection. It is unknown whether the opening of these channels also induces delayed cardioprotection. In addition, we determined the involvement of nitric oxide synthases (NOSs), which have been implicated in cardioprotection induced by opening of mitochondrial ATP-sensitive K+ (KATP) channels. Adult male ICR mice were pretreated with the KCa-channel opener NS-1619 either 10 min or 24 h before 30 min of global ischemia and 60 min of reperfusion (I/R) in Langendorff mode. Infusion of NS-1619 (10 microM) for 10 min before I/R led to smaller infarct sizes as compared with the vehicle (DMSO)-treated group (P <0.05). This infarct-limiting effect of NS-1619 was associated with improvement in ventricular functional recovery after I/R. The NS-1619-induced protection was abolished by coadministration with the KCa-channel blocker paxilline (1 microM). Similarly, pretreatment with NS-1619 (1 mg/kg ip) induced delayed protection 24 h later (P <0.05). Interestingly, the NS-1619-induced late protection was not blocked by the NOS inhibitor Nomega-nitro-L-arginine methyl ester (15 mg/kg ip). Unlike diazoxide (the opener of mitochondrial KATP channels), NS-1619 did not increase the expression of inducible or endothelial NOS. Western blot analysis demonstrated the existence of alpha- and beta-subunits of KCa channels in mouse heart tissue. We conclude that opening of KCa channels leads to both early and delayed preconditioning effects through a mechanism that is independent of nitric oxide.

Animals↗

PubMed2003

The effect of oxygenator membranes on blood: a comparison of two oxygenators in open-heart surgery.

Open-heart surgery (OHS) requires cardiopulmonary bypass (CPB) in most patients. Membrane oxygenators are a critical component of the CPB system. Despite advancements in CPB technology, injury to blood components during CPB still occurs and may result in complications after surgery. The purpose of the present study was to evaluate the performance of the Medtronic Affinity NT with Trillium coating and the Cobe Optima XP oxygenators and compare their influence on blood components. Two hundred and fifty-six male and female patients scheduled for urgent or elective cardiac surgery with CPB were randomly assigned to either the Affinity NT or the Optima XP oxygenators. Outcomes included platelets, hemoglobin, leukocyte counts, and O2 transfer, measured preoperatively and at 15, 45 and 75 min of CPB time. Blood loss was measured at six and 12 hours postoperatively. A modified intention-to-treat analysis was conducted. The two groups were similar for age, sex, height, weight, body surface area, and blood components at baseline. There were no differences between the Affinity NT and Optima XP for any outcome measure, although a significant change with time was seen in platelets, hemoglobin, hematocrit and leukocytes, as well as O2 transfer for both groups (p < 0.001). The Affinity NT oxygenator had a significantly lower difference in pressure across the membrane (p < 0.001) compared with the Optima XP. In conclusion, the two oxygenators performed similarly with respect to their impact on blood components, O2 transfer, and blood loss postoperatively during OHS with CPB. The Affinity NT had the smaller transmembrane pressure drop of the two.

Aged↗

PubMedDate not supplied

Economic evaluation of the MEDENOX trial: a Canadian perspective. Medical Patients with Enoxaparin.

OBJECTIVE: To perform an economic evaluation of the Prophylaxis in Medical Patients with Enoxaparin (MEDENOX) trial from a Canadian perspective. METHOD: Using a decision tree model, cost effectiveness analysis was carried out to compare the costs and consequences of thromboprophylaxis using enoxaparin 40 mg with placebo in tertiary and community settings. From a third party payer's perspective, the model calculated the expected rate of symptomatic venous thromboembolism (VTE), and the total expected cost of prophylaxis and VTE management, including inpatient and outpatient treatment, professional fees and long term therapy. Data were derived directly from the MEDENOX trial. Costs are direct medical costs in year 2000 Canadian dollars. RESULTS: In a tertiary setting in which the estimated inpatient to outpatient deep vein thrombosis treatment ratio was 10%:90%, the total expected cost per patient was 64 dollars in the enoxaparin group and 62 dollars in the placebo group. The expected symptomatic VTE rates were 0.8% and 3.1% in the enoxaparin and placebo groups, respectively. The incremental cost effectiveness of enoxaparin 40 mg versus placebo was 87 dollars/VTE avoided. In a community hospital setting (with a 50%:50% inpatient to outpatient deep vein thrombosis treatment ratio), the total expected cost per patient was 68 dollars in the enoxaparin group compared with 72 dollars in the placebo group, indicating that prophylaxis with enoxaparin 40 mg was cost saving. The model was sensitive to the inpatient to outpatient ratio. However, within each setting, the results were not sensitive to changes in key variables. CONCLUSION: For patients hospitalized for acute respiratory failure, congestive heart failure or acute infectious disease and who are at moderate risk of developing VTE, thromboprophylaxis with enoxaparin 40 mg daily is a cost effective strategy in both tertiary and community settings.

Adult↗