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The aim of the present study was to analyze the effect of diltiazem on myocardial fibrosis and remodeling of connexin43 (Cx43) in myocardial ischemic rats and mechanisms underlying these processes. A total of 36 Sprague‑Dawley rats were randomly allocated into three groups (control, isoproterenol and isoproterenol with diltiazem). The myocardial ischemic model was established by 5 mg/kg/day isoproterenol administration for 7 days, and the diltiazem group received 25 mg/kg/day diltiazem for 4 weeks. Following the treatment, paraffin sections were prepared to observe microstructural changes and to evaluate the concentration of Ca2+ in myocardium. The expression of transforming growth factors‑β1 (TGF‑β1), mothers against decapentaplegic homologues (Smad)2 and 7 and Cx43, were analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting. The percentage Cx43 expression in intercalated disks was evaluated using immunohistochemistry. Fibrosis did not differ significantly between the control and the diltiazem‑treated group. The concentration of Ca2+ increased in the myocardium of model rats. The expression of Smad7 and Cx43 was decreased in the rat model, while the expression of TGF‑β1 and Smad2 was increased. There was a significant decrease in the relative abundance of intercalated disk Cx43 in the model group. The results of the present study suggest that diltiazem may serve a protective role during remodeling of myocardial ischemia, especially in fibrosis and Cx43 remodeling.
The aim of the present study was to analyze the effect of diltiazem on myocardial fibrosis and remodeling of connexin43 (Cx43) in myocardial ischemic rats and mechanisms underlying these processes. A total of 36 Sprague‑Dawley rats were randomly allocated into three groups (control, isoproterenol and isoproterenol with diltiazem). The myocardial ischemic model was established by 5 mg/kg/day isoproterenol administration for 7 days, and the diltiazem group received 25 mg/kg/day diltiazem for 4 weeks. Following the treatment, paraffin sections were prepared to observe microstructural changes and to evaluate the concentration of Ca2+ in myocardium. The expression of transforming growth factors‑β1 (TGF‑β1), mothers against decapentaplegic homologues (Smad)2 and 7 and Cx43, were analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting. The percentage Cx43 expression in intercalated disks was evaluated using immunohistochemistry. Fibrosis did not differ significantly between the control and the diltiazem‑treated group. The concentration of Ca2+ increased in the myocardium of model rats. The expression of Smad7 and Cx43 was decreased in the rat model, while the expression of TGF‑β1 and Smad2 was increased. There was a significant decrease in the relative abundance of intercalated disk Cx43 in the model group. The results of the present study suggest that diltiazem may serve a protective role during remodeling of myocardial ischemia, especially in fibrosis and Cx43 remodeling.
Background:Several studies have been conducted in search of appropriate drugs to attenuate hemodynamic responses in laparoscopic cholecystectomy, but till date, no such study has been conducted on patients undergoing laparoscopic nephrectomy.Aim:The study was designed to assess the effect of esmolol and diltiazem infusions on hemodynamic changes during routine laparoscopic transperitoneal simple nephrectomy.Settings and Design:A prospective double-blinded randomized control trial.Subjects and Methods:A total of 120 nonhypertensive patients of the American Society of Anesthesiologists physical Status I and II aged 20–60 years about to undergo laparoscopic nephrectomy were enrolled for the study after obtaining Institute Ethical committee approval. The patients were randomly allocated to one of the three groups. Group I (control group) received 10 ml normal saline intravenously (i.v.) before induction of anesthesia, followed by continuous infusion 10–20 ml/h. Group II (esmolol group) received i.v. esmolol 1 mg/kg diluted in 10 ml similarly, followed by continuous infusion of 10–20 ml/h (5–10 μg/kg/min). Group III (diltiazem group) received i.v. diltiazem 0.2 mg/kg diluted in 10 ml before induction of anesthesia, followed by continuous infusion at 10–20 ml/h (0.08–1.25) μg/kg/min. After completion of surgery, all the infusions were stopped. Data recording were done for changes in hemodynamics throughout the surgery.Statistical Analysis:was done using Chi-square test for categorical data and one-way ANOVA for continuous data. Tukey (“honestly significant difference”) post hoc test was applied for intra- and inter-group comparison in cases where ANOVA was significant. P < 0.05 is considered statistically significant.Results:All hemodynamic data: Heart rate (HR), systolic, diastolic, and mean arterial pressure were observed to be significantly higher (P < 0.001) from baseline in control group at the time of creation of pneumoperitoneum, till 20 min thereafter. The values were comparable to baseline in both esmolol and diltiazem group. On intergroup comparison, the patients in esmolol group had significantly lower HR and blood pressures than in diltiazem group at the creation of pneumoperitoneum and at extubation (P < 0.05). Mean dose of esmolol and diltiazem used were 7.25 ± 1.33 μg/kg/min and 1.14 ± 0.77 μg/kg/min, respectively.Conclusion:Both esmolol and diltiazem infusion provide stable intraoperative hemodynamics and protection against stress response triggered by pneumoperitoneum in patients undergoing laparoscopic transperitoneal nephrectomy.
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