| PART ONEIsoproterenol and ventricular arrhythmias in miceObjectives In left ventricular hypertrophy, the sympathetic tone is increased, which leads to the increasing of the incidence of ventricular arrhthymia. In this part, the ?-receptor agonist isoproterenol (ISO) would be used in normal or left ventricular hypertrophic mice separately to evaluate the effect in inducing ventricular arrhythmias.Methods Pressure-overload left ventricular hypertrophy was induced in C57B/L6 male mice by thoracic aortic banding (TAB group). The sham operation was done in the control group (sham group). Echo ultrasonography were used to confirm whether the model was established successfully. Conscious mice ECG was recorded by ECG recorder both before and after ISO injection. The arrhythmias were scored according to the difficulty of the arrhythmias. Then the mice were executed and weighed the heart one by one. SPSS 17.0 software was used for data analysis.Results The echo ultrasonography measurements showed that LVAW;d, LVAW;s, LVPW;d, LVPW;s, and LV mass were significantly different between sham group and TAB group (P<0.05), while the EF and FS were similar in two groups (P>0.05). The H/BW was statistically different in two groups (P<0.05). The arrhythmia scores were comparable before ISO injection in two groups (P>0.05). However, after ISO injection, the scores in TAB group was increased significantly (P<0.05).Conclusions Compared with normal mice, the hypertrophic mice were prone to induce ventricular arrhthymias by ISO injection.PART TWOEffect of acute inhibition of CaMKII in left ventricular hypertrophic mice on ISO induced arrhythmiasObjectives In hypertrophic mice, the expression and activity of CaMKII increase significantly. CaMKII could increase the incidence of arrhythmias through regulating cellular Ca2+ and prolonging action potential duration. In this part, KN93 will be injected to inhibit CaMKII acutely in left hypertrophic mice to test whether the ISO induced ventricular arrhythmias will be reduced.Methods Pressure-overload left ventricular hypertrophy was induced in C57BL6 male mice by thoracic aortic banding (TAB). Echo ultrasonography were used to confirm whether the model was established successfully. The mice were divided into two groups, TAB group and TAB+KN93 group. Conscious mice ECG was recorded by ECG recorder. The mice in TAB group were injected with ISO only. The mice in TAB+KN93 group were injected KN93 first, and a subsequent ISO injection was administrated after 10 min. The arrhythmias were scored according to the difficulty of the arrhythmias. Then the mice were executed and weighed the heart one by one. SPSS 17.0 software was used for data analysis.Results The echo ultrasonography measurements showed that LVAW;d, LVAW;s, LVPW;d, LVPW;s, LV mass, EF and FS were similar in two groups (P>0.05). The H/BW was comparable in two groups (P>0.05).The arrhythmia scores were comparable before ISO injection in two groups (P<0.05). After injection, the scores in the TAB+KN93 group were decreased significantly (P<0.05).Conclusions The acute inhibition of CaMKII could reduce the ISO induced ventricular arrhythmias in left ventricular hypertrophic mice.PART THREEThe mechanism of acute inhibition of CaMK? in left ventricular hypertrophic mice on ISO induced arrhythmiasObjectives ISO could induce arrhthymia through several pathways including accelerating HR, inducing myocardial ischemia and enhancing intracellular Ca2+ concentreation and so on. CaMKII plays an important role in regulating cellular Ca2+ transporting and ischemia/ reperfusion injury. In this part, we will focus on whether acute inhibition of CaMKII could reduce the ISO induced arrhythmias through alleviating myocardial ischemia in left ventricular hypertrophic mice.Methods Pressure-overload left ventricular hypertrophy was induced in C57BL6 male mice by thoracic aortic banding. Three groups were involved:sham group, TAB group and TAB+KN93 group. The sham group and TAB group were stimulated by ISO only, but TAB+KN93 group was pretreated by KN93 before ISO injection. Data information such as HR, T wave amplitude and QTc interval were calculated by Ecg-auto. Then the mice were executed and weighed the heart one by one. SPSS 17.0 software was used for data analysis.Results After ISO injection, the increasing of HR in each group was statistically significant (P<0.05), but there was no significant difference between 3 groups (P>0.05). In TAB group and TAB+Kn93 group, the QTc interval was prolonged were prolonged and the T wave amplitude were elevated compared with sham group both before and after ISO or KN93+ISO stimulation (P<0.05). After ISO or KN93+ISO stimulation, the difference between TAB group and TAB+KN93 group was statistically significant (P<0.05). The H/BW was statistically different between sham group and other two groups (P<0.05), while the difference between TAB group and TAB+KN93 group was not statistically significant (P>0.05).Conclusions The acute inhibition of CaMKII could reduce the ISO induced arrhythmia through alleviating the myocardial ischemia in left ventricular hypertrophic mice. |
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