AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits

BACKGROUND AND OBJECTIVES: Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. MATERIALS AND METHODS: HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. RESULTS: Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N⁵-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). CONCLUSION: Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.

[Factors associated with use of emergency medical service for acute myocardial infarction in Beijing].

OBJECTIVE: To examine the current ambulance transport rates and ascertain factors associated with use of emergency medical service (EMS) in patients with acute myocardial infarction (AMI) in Beijing. METHODS: Between January 1 and December 31, 2006, a cross-sectional and multicenter survey was conducted in 19 hospitals in Beijing and included patients with ST-elevation myocardial infarction (STEMI) admitted within 24 hours of onset of symptoms. Data were collected by structured interviews and medical records review within 1 week after admission. Patients were categorized into the EMS group and the self-transport group according to their modes of transport to the initial hospital. Data were analyzed by descriptive statistics, univariate and multivariate logistic analysis. RESULTS: Of the 789 patients with STEMI, only 260 (33.0%) arrived at the initial hospital by EMS, while the remaining 529 (77.0%) relied on self-transport. Multivariate logistic analysis showed that age >/= 65 years (OR: 1.530, 95%CI: 1.050 - 2.230, P = 0.027), higher education level (OR: 2.032, 95%CI: 1.257 - 3.284, P = 0.004), history of coronary artery disease (OR: 0.474, 95%CI: 1.049 - 2.458, P = 0.029), unbearable symptoms (OR: 0.592, 95%CI: 1.090 - 2.520, P = 0.008), anxiety (OR: 0.760, 95%CI: 1.238 - 3.695, P = 0.006) and attribution of symptoms to cardiac origin (OR: 0.402, 95%CI: 1.020 - 2.171, P = 0.041) were independent predictors of EMS use. However, presence of pre-infarction angina significantly decreased the likelihood of using EMS (OR: 0.626, 95%CI: 0.431 - 0.907, P = 0.013). CONCLUSIONS: Only one-third of patients with STEMI arrived at the hospital by EMS in Beijing. Demographics, history of coronary artery disease, symptoms characteristics and cognitive factors of patients were associated with the EMS use.

[Donor peripheral blood mononuclear cell infusion (DMNCI) for treatment of patients with relapsed leukemia after haploidentical bone marrow transplantation].

This study was aimed to investigate the therapeutic effect of growth factor-primed donor peripheral mononuclear stem cell infusion (DMNCI) for patients with relapsed leukemia after haploidentical bone marrow transplantation (BMT). The donor was the same individual for both BMT and DMNCI. All the three patients described here were Philadelphia chromosome positive leukemia before haploidentical BMT; one case was newly diagnosed as acute lymhoblastic leukemia (ALL) and the others were chronic myeloid leukemia (CML). Two cases (one with ALL and one with CML) manifested with clinical relapse and the third case was in the stage of molecular relapse. The former 2 patients received a single bulk dose of DMNCI, the inoculums of which contained mononuclear cells of 8.25 x 10(8)/kg or 5.24 x 10(8)/kg and CD3-positive cells of 1.87 x 10(8)/kg or 1.14 x 10(8)/kg respectively. The third case received initial dose of DMNCI which was 2.0 x 10(7)/kg, and received CD3 positive cells of 1.1 x 10(7)/kg. The results indicated that the different therapeutic responses were found in all three patients. Two patients with clinical relapse received temporal remission, and died of severe graft versus host disease (GVHD), relapse and failure at day 41 and 49 after DMNCI. The third patient with molecular relapse received molecular remission after 2 infusions of DMNCI. All three patients developed acute GVHD, but two patients among them developed GVHD of grad IV, other one developed GVHD of grad I and has survived in disease-free state during half a year follow-up. It is concluded that the DMNCI may be effective for the treatment of relapsed leukemia after haploidentical BMT and this treatment can be safe if the initial dose of DMNCI is 10(7)/kg and subsequent single dose of DMNCI gradually increases.