| Malignant arrhythmia is main cause of sudden cardiac death and sympathetic storm, as well as a direct cause of death from heart disease. Therefore, the prevention and treatment of malignant arrhythmia is directly related to people's quality of life, thus the prevention and treatment of malignant arrhythmia has become an important issue, gaining increasing attention by the scholars.This study is divided into two parts, clinical studies and basic experimental study, where the clinical part of the study makes a comparison of the predicted indicators of malignant arrhythmia. Indicators commonly used in the past are, QT dispersion, heart rate variability, T wave alternans, sinus heart rate turbulence and ventricular late potentials. QT dispersion, heart rate variability, T wave alternans, sinus heart rate turbulence, due to the limitations of their measurement methods, have little clinical value: QT dispersion requires relatively more complicated calculation, results in relatively large human errors. Heart rate variability is available by a 24-hour Holter, but it doesn't only require a longer period, but is also less susceptible to interference when wearing the 24-hour Holter, so the results are not highly accurate. T-wave alternans results are aquired from a exercise load tests, since patients with severe heart disease have a higher risk in this test, it is difficult for severe heart disease patients to take such inspection in clinical. Therefore, these indicators have limited value as predictors of malignant arrhythmia. In recent years, along with the development of cardiac electrophysiology, People gradually increase their degree of attention on ventricular late potentials. Under quiet state, when taking normal ECG at the same time, it uses a special software to analyze results, and the results are more objective, more convenience and faster. In recent years, C-reactive protein, high-sensitivity C-reactive protein and brain natriuretic peptide (BNP) have also been found to be new risk factors in the malignant arrhythmia. This study aims to make a comparison between some of these indicators that are relatively easy to judge and simple to do, to find out their risk to the malignant arrhythmia,in order to filter out the most effective predictors. The results show that ventricular late potentials has the greatest risk to malignant arrhythmia, so it is the most effective predictor.The basic part of the experiment mainly uses of patch clamp technique to observe the electrophysiological effects in Ventricular myocytes when malignant arrhythmia occurs, and how it is affected by esmolol. Esmolol is a very short effectiveβ-receptor-blocker, with a short half-life and a fast onset of action. In recent years, as scholars have become more aware of the sympathetic storm, Increasing attention has been paid to the use ofβ-receptor-blocker deepened in malignant arrhythmia treatment, among them as to the most prominent is esmolol. When the sympathetic storm occurs, a high-dose injection of esmolol can effectively inhibit the sympathetic storm, the effect is superior to repeated defibrillation and the extensive use of anti-arrhythmia drugs. The objective of this study is to explore the prediction of malignant arrhythmias and the effect of esmolol on the Cardiac Ventricular Myocytes electrophysiology during Malignant arrhythmia。Methods: Clinical part: Patients were from January 2008 to December 2009 The Second Clinical Hospital of Jilin University, Department of Cardiology, 120 cases of hospitalized patients, male 68 cases, females 52 cases, aged 44 to 73 years old, mean age 57.9±4.3 years . Malignant arrhythmia group: 72 patients, 42 males and 30 females. Control group: 48 cases, male 26, female 22. C-reactive protein, high-sensitivity C-reactive protein, BNP measurement methods: the morning peripheral venous blood were collected, using enzyme-linked immunosorbent assay (ELASA) were measured (USA ADL), with the steps carried out according to instructions of the kit. Ventricular late potential measurement methods: The United States, GE ventricular late potentials detector.Animal parts: using rats as the experimental animals (by the Experimental Animal Center of Jilin University).Make ischemic malignant arrhythmia in rats and malignant reperfusion arrhythmias in rats to observe their heart rate changes and blood pressure. Isolate myocardial cells using the conventional method for isolation of adult cardiac myocytes methods,. With the patch-clamp technique and whole-cell channel current observed record method to observe the changes in action potential of ventricular muscle cells, sodium channels, calcium channels, and potassium channels. Add esmolol 50μmol ? L-1 and esmolol 100μmol ? L-1 both in the ventricular myocytes of the Ischemic malignant arrhythmia group and the malignant arrhythmia after reperfusion group, then observe the action potential of ventricular muscle cells, sodium ions channels, calcium channels, potassium channels.Results: The late potential-positive rate of the malignant arrhythmia group was higher, where the difference was significant (P <0.01). The C-reactive protein level in the malignant arrhythmia group (5.78±3.68) is different from that of the control group (3.05±1.21), where the difference was significant (P <0.01). The High-sensitivity C-reactive protein level in the malignant arrhythmia group(3.34±2.27) is different from that of the control group(2.13±1.01), where the difference was significant (P <0.01). The BNP level in the malignant arrhythmia group (143.10±38.53) is significantly higher compared to the one in the control group (32.56±12.99), where the difference was statistically significant (P <0.01). Use Logistic regression to analyze the OR value of each of the risk factors, where the results are, ventricular late potentials (OR = 3.145), C-reactive protein (OR = 1.121), high-sensitivity C-reactive protein( OR = 1.182), BNP( OR = 1.453). The OR value of all these factors are greater than 1, proving all the ventricular late potentials, the C-reactive protein, the high-sensitivity C-reactive protein and the BNP are risk factors of malignant arrhythmia. Among these factors, the ventricular late potentials has the highest risk, followed by the BNP, the high-sensitivity C-reactive protein and the C-reactive protein, thus make the ventricular late potentials a greater predicted indicators of malignant arrhythmia.Sodium channels: the sodium channel currents of both the ischemic group and the after reperfusion group of malignant arrhythmia were significantly increased compared to the control group. 2 minutes after adding esmolol 50μmol ? L-1 and esmolol 100μmol ? L-1 to both groups, the sodium channel currents were significantly decreased compared to where Esmolol is not added, and the difference was statistically significant.Calcium channel: the calcium channel currents of both the ischemic group and the after reperfusion group of malignant arrhythmia were significantly increased, where the difference is significant. After adding esmolol 50μmol ? L-1 and esmolol 100μmol ? L-1 to the myocytes in both groups, the calcium channel currents were significantly decreased compared to where Esmolol is not added, and the difference was statistically significant.Potassium channels: the potassium channel currents of both the ischemic group and the after reperfusion group of malignant arrhythmia were significantly increased. It is observed that, 2minutes after adding esmolol 50μmol ? L-1 and esmolol 100μmol ? L-1 to both groups, the potassium channel currents where esmolol 50μmol ? L-1 were added did decrease compared to where esmolol is not added, but the difference was not statistically significant, however, the currents where esmolol 100μmol ? L-1 were added were significantly decreased compared to where esmolol is not added, and the difference was statistically significant.Action Potential: Compared to the control group , both the ischemic group and the after reperfusion group have higher Vmax, APA, APD20, APD50 and APD90 (P<0.05). The results showed that after esmolol 50μmol ? L-1 and esmolol 100μmol ? L-1 were added to both group, Vmax, APA and APD20 were significantly reduced (P<0.05). Even though adding esmolol 50μmol ? L-1 didn't affect APD50 and APD90 (P>0.05), adding esmolol 50μmol ? L-1 did significantly reduce the APD50 and APD90, where the difference was statistically significant (P <0.05)The impact of esmolol on malignant arrhythmias: maintaining intravenous of Esmolol 50μg.kg-1.min-1, and intravenous of Esmolol 10μg.kg-1.min-1, compared to non-application of esmolol, within a certain period of time, the frequency of occurrence of malignant arrhythmias significantly decreased (P <0.01).Effect of esmolol on blood pressure in malignant arrhythmias: blood pressure in the ischemia-reperfusion group decreased significantly (P <0.01) compared to the control group. The blood pressure of the esmolol 50μg group, compared to the ischemia-reperfusion group, has been restored, there was no statistical significance after 15 minutes of ischemia, while after 30 minutes of ischemia, reperfusion for 15 minutes and 30 minutes, there were statistically significant restorations (P < 0.05). When compare the esmolol 100μg group to the ischemia-reperfusion group, the blood pressure has also been restored, there was no statistical significance after 15 minutes of ischemia, while after 30 minutes of ischemia, reperfusion for 15 minutes and 30 minutes, the blood pressure restoration was not only statistically significant (P < 0.01), but also more significant than the group maintaining intravenous with a smaller dose.Conclusion:Use Logistic regression to analyze each of the risk factors: ventricular late potentials (OR = 3.145), C-reactive protein (OR = 1.121), high-sensitivity C-reactive protein( OR = 1.182), BNP( OR = 1.453). The OR value of all these factors are greater than 1, proving all the ventricular late potentials, the C-reactive protein, the high-sensitivity C-reactive protein and the BNP are risk factors of malignant arrhythmia. Among these factors, the ventricular late potentials has the highest risk, followed by the BNP, the high-sensitivity C-reactive protein and the C-reactive protein.Role in Myocardial cell electrophysiology: role in the sodium channel: when malignant ventricular arrhythmia occurs in rat, the influx of sodium channels in ventricular myocytes increased. Observation after esmolol is added shows that, both the Ischemic malignant arrhythmia group and the malignant arrhythmia after reperfusion group have signficantly decreased sodium channel currents compared to where esmolol was not used, where the difference is significant. Results suggest that when malignant arrhythmia occurs esmolol inhibits sodium influx. The role in calcium channels: Malignant ventricular arrhythmias in rat ventricular myocytes increase calcium ion influx. when esmolol is added, both the Ischemic malignant arrhythmia group and the malignant arrhythmia after reperfusion group have signficantly decreased calcium channel currents compared to where esmolol was not used, where the difference is significant. Results suggest that when malignant arrhythmia occurs esmolol inhibits calcium influx. The role in potassium channels: Malignant ventricular arrhythmias in rat ventricular myocytes increase the outflow of potassium ion through channels. Though the group where esmolol 50μmol·L-1 was added has the current amplitude decreased compared to the unused group, the difference is not significant. The currents where esmolol 100μmol ? L-1 were added, however, were significantly decreased compared to where esmolol is not added, and the difference was statistically significant. This shows that small doses of esmolol had no significant effect on potassium channels, while large doses of it has more obvious effect. Role in the action potential: record parameters of action potentials in single cell. The results showed that malignant arrhythmia after ischemia and malignant ventricular arrhythmia after reperfusion, compared with the control group, their Vmax, APA, APD20, APD50 and APD90 were increased, where there is a significant difference. When esmolol is added in both groups the Vmax, the APA and the AOD20 all decreased significantly, while small dose esmolol had no effect on APD50 and APD90, large dose esmolol significantly shortened APD50 and APD90. Effect on the incidence of malignant arrhythmia: maintaining intravenous of Esmolol, compared to non-application of esmolol, within a certain period of time, the frequency of occurrence of malignant arrhythmias significantly decreased. As esmolol can reduce the incidence of malignant arrhythmias, it has a preventive effect to malignant arrhythmia.Esmolol malignant arrhythmia effect of blood pressure: blood pressure ischemia and reperfusion than the control group blood pressure decreased, blood pressure Esmolol gradually recovered, the greater the pressure to restore the more obvious dose. Esmolol to correct blood pressure when malignant arrhythmias, ischemia and reperfusion group compared with the control group blood pressure decreased, blood pressure Esmolol has resumed intravenous dose of the more obvious the greater the recovery.Effect of esmolol on blood pressure in malignant arrhythmias: blood pressure in the ischemia-reperfusion group decreased compared to the control group. After application of esmolol the blood pressure has been restored, larger dose results in more significant restoration. Esmolol can correct blood pressure decrease in malignant arrhythmias. Both the ischemic and reperfusion group compared have blood pressure decreased, and the blood pressure is restored after intravenous of esmolol, where the larger dose of the more obvious the restoration. |
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