Anti-arrhythmic effects of taurine-magnesium coordination compound on torsades de pointes / 中国应用生理学杂志

OBJECTIVES@#To investigate the effect of taurine magnesium coordination compound (TMCC) on torsades de pointes (TdP) in isolated guinea pig hearts.@*METHODS@#Healthy male guinea pigs weighting 250~300 g were randomly divided into 4 groups:①TdP model group (=7):Isolated hearts were perfused by normal K-H solution 20 minutes, then perfused by slowly activated delayed rectifier potassium current(IKs) blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) to establish TdP model;②~④ TdP model + TMCC group (=6):Isolated hearts were perfused by normal K-H solution for 20 minutes, then perfused by IKs blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) for 60 minutes, at the same time TMCC which concentration was 1, 2, 4 mmol/L was administered respectively by Langendorff retrograde aortic perfusion method. Cardiac surface electrocardiogram of guinea pigs was collected and recorded by Biopac electrophysiological recorder. Incidence of TdP, transmural dispersion of repolarization (TDR), instability of QT interval were acquired from Lead Ⅱ electrocardiograph (ECG) wave forms to describe the effect of TMCC on TdP model. Datas were acquired at the time of 20 min and pre-TdP, in case there was no TdP observed, a value of 60 min was entered for calculation purpose.@*RESULTS@#Incidence of TdP in TdP model group was 6/7. TdP incidence could be decreased significantly by 1, 2, 4 mmol/L TMCC, and was 5/6, 1/6, 0/6 respectively. Compared with the pre-drug, Chromanol 293B under hypokalemic solution in TdP model group increased TDR(corrected) evidently(0.05). Compared with the TdP model group, 2, 4 mmol/L TMCC could evidently decrease the instability of QT interval induced by Chromanol 293B under hypokalemic solution(<0.05). During the establishment of TdP model, P waves in more than one cardiac cycle continuously were disappeared in ECG. However, P wave could always be seen independent in ECG acquired from TdP model + TMCC group.@*CONCLUSIONS@#TMCC can play the role against TdP through decreasing TDR and instability of QT interval, and inhibiting early after depolarization(EAD).

Presence of intrinsic myocardial systolic and diastolic dysfunctions at early stage of sepsis in mild CLP rats / 中国病理生理杂志

AIM:To observe the time pattern of intrinsic myocardial dysfunction and other organ dysfunction in a rat model of mild cecal ligation and puncture (CLP).METHODS:Male SD rats were randomly divided into sham group and CLP group.At 6 h, 9 h and 12 h after sham operation or CLP, intrinsic myocardial systolic and diastolic functions were determined by Langendorff system.The expression of cardiac tumor necrosis factor (TNF)-α, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was measured.In addition, serum activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as blood urea nitrogen (BUN) were analyzed.For evaluating pulmonary edema, the lung wet-dry weight (W/D) ratio was calculated.RESULTS:In mild CLP rats, the mortality rate was 26.7% on day 10 after CLP.At 9 h and 12 h after CLP, the maximum rate of positive and negative changes in left ventricular pressure (±dp/dt) were decreased in CLP group compared with sham group.At 6 h after CLP, cardiac mRNA expression of TNF-α, ICAM-1 and VCAM-1 was increased in septic rats compared with the controls.At 9 h after CLP, cardiac protein levels of TNF-α and VCAM-1 were higher in CLP group than that in sham group (P<0.05).The serum AST activity at 9 h and ALT activity at 12 h after CLP were increased in CLP group compared with sham group.However, no difference in BUN and lung W/D ratio at 6 h, 9 h and 12 h between CLP group and sham group was observed.CONCLUSION:Our findings highlight the presence of intrinsic myocardial dysfunction at 9 h after CLP in a rat model of mild CLP.Intrinsic myocardial dysfunction occurs earlier than the liver and kidney dysfunctions.

Effects and mechanism of TG6 on myocardial ischemia and reperfusion injury / 药学实践杂志

Objective To investigate the protective effects and mechanism of TG 6 on myocardial ischemia/reperfusion injury . Methods the protective effects of TG 6 on myocardial ischemia/reperfusion was investigated by setting up models of ischemia and reperfusion of rats induced by ligating the left coronary anterior descending artery in vivo,isolated rat hearts through an improved Lange-ndorff device, and hypoxia /reoxygenation injury of neonatal rat cardiomyocytes , and the serum CK,LDH,T-SOD, MDA were taken as research markers .Results TG6 significantly reduced the myocardial infarct size , decreased the activity of CK and the content of MDA in serum, reduced the activity of LDH, and increased the activity of T-SOD in vivo;TG6 obviously increased the coronary blood flow after low rate perfusion and reperfusion , decreased the content of MDA and the leakage of CK , LDH in myocardial tissue , elevated the activity of T-SOD in vitro of isolated rat hearts;TG6 had no effects on cells in normal growth condition , raised the viability of cardio-myocytes significantly, and reduced the rate of CK leakage and the content of [Ca2+]i obviously in Na2S2O4 treated cells in vitro of neonatal rat cardiomyocytes .Conclusion TG6 could effectively protect myocardial ischemia/reperfusion injury .

Myocardial protective effects of nicorandil and verapamil during ischemia-reperfusion in an isolated perfused rat heart

BACKGROUND: To reduce or prevent myocardial injury during an ischemia-reperfusion episode, some pharmacological interventions, including administering nicorandil or verapamil, have becomepopular in clinical situations. Nicorandil is a N-(2-hydroxyethyl)- nicotinamide nitrate ester, and it's effective mainly by opening the K+ ATP channels in the mitochondrial membrane, and verapamil is useful for reducing the endothelial injury of coronary vessels during ischemia. In this study, we aimed to determine the cardioprotective effect when both drugs are used simultaneously. METHODS: Isolated rat hearts (the Langendorff perfusion model) were perfused with Krebs-Henseleit bicarbonate buffer. After 30 minutes of controlled perfusion, we added nicorandil or verapamil separately and both drugs were administered together in another group (the mixed group) and we then induced ischemia for 30 minutes. We measured the heart rate, the developed ventricularpressure and the dP/dT during the control period during drug infusion and during reperfusion at 15, 30, 45 and 60 minutes. RESULTS: During reperfusion, the mixed group showed more favorable results for the developed left ventricular pressure (LVP), the dP/dT and the rate pressure product (RPP). The heart rate was significantly decreased as reperfusion processed in all the groups. CONCLUSIONS: For myocardial protection during ischemia-reperfusion, a mixed drug regimen is more beneficial than a single drug regimen, and this occurs without inducing a significant decrease of the heart rate.