The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the ...The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the combination therapy with these two synergistic drugs at low doses through a suitable form of administration could provide optimal therapeutic benefit, we further evaluated the effects of a 42 d period of anti-hypertensive treatment in spontaneously hypertensive rats. Rats were divided into the following five groups： control （blank patch）, bisoprolol fumarate tablets （BP-FT, 20.0 mg/kg, i.g.）, bisoprolol transdermal patch （BP-TP, 20.0 mg/kg）, isosorbide dinitrate transdermal patch （ISDN-TP, 20.0 mg/kg）, and the combination of BP and ISDN in a transdermal patch at low doses （8 and 12 mg/kg, respectively）. The effects of treatment were evaluated via biochemical indicators related to cardiovascular protection, structure and function. The combination therapy had synergistic anti-hypertensive effects and significantly reduced blood pressure with the benefit of controlling blood pressure variability compared to BP-FT and BP-TP. The combined treatment also reduced heart rate as well as BP-FT and BP-TP, while ISDN-TP had no evident effects on blood pressure, heart rate, and cardiovascular protection. Combination therapy was superior to BP-TP and BP-FT at increasing blood atrial natriuretic peptide and nitric oxide, while also reducing cardiac hydroxyproline and endothelin-1 with no difference in blood endothelin-1 and cardiac malondialdehyde levels. Cardiovascular remodeling differed among the groups, with the combination therapy reducing cardiac hypertrophy and the aortic media/lumen ratio. The consequential improvements in relaxation in response to cumulative concentrations of acetylcholine may explain the associated improvement in endothelial function. Combi- nation treatment with a transdermal patch exhibited a synergistic therapeutic effect. Such favorable cardiovascular effects with nitric oxide donors and β-blockade combination through a transdermal patch may provide long-term cardiovascular protection during anti-hypertensive treatment.展开更多
AIM: To systematically assess the efficacy and safety of β-adrenergic blocker plus 5-isosorbide mononitrate (BB + ISMN) and endoscopic band ligation (EBL) on prophylaxis of esophageal variceal rebleeding. METHODS: Ra...AIM: To systematically assess the efficacy and safety of β-adrenergic blocker plus 5-isosorbide mononitrate (BB + ISMN) and endoscopic band ligation (EBL) on prophylaxis of esophageal variceal rebleeding. METHODS: Randomized controlled trials (RCTs) comparing the efficacy and safety of BB + ISMN and EBL on prophylaxis of esophageal variceal rebleeding were gathered from Medline, Embase, Cochrane Controlled Trial Registry and China Biological Medicine database between January 1980 and August 2007. Data from five trials were extracted and pooled. The analyses of the available data using the Revman 4.2 software were based on the intention-to-treat principle. RESULTS: Four RCTs met the inclusion criteria. In comparison with BB + ISMN with EBL in prophylaxis of esophageal variceal rebleeding, there was no significant difference in the rate of rebleeding [relative risk (RR), 0.79; 95% CI: 0.62-1.00; P = 0.05], bleeding-related mortality (RR, 0.76; 95% CI: 0.31-1.42; P = 0.40), overall mortality (RR, 0.81; 95% CI: 0.61-1.08; P = 0.15) and complications (RR, 1.26; 95% CI: 0.93-1.70; P = 0.13). CONCLUSION:In the prevention of esophageal variceal rebleeding, BB + ISMN are as effective as EBL. There are few complications with the two treatment modalities. Both BB + ISMN and EBL would be considered as the first-line therapy in the prevention of esophageal variceal rebleeding.展开更多
基金‘863'High Technology R&D Project of Ministry of Science and Technology of China(Grant No.2004AA2Z3073).
文摘The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the combination therapy with these two synergistic drugs at low doses through a suitable form of administration could provide optimal therapeutic benefit, we further evaluated the effects of a 42 d period of anti-hypertensive treatment in spontaneously hypertensive rats. Rats were divided into the following five groups： control （blank patch）, bisoprolol fumarate tablets （BP-FT, 20.0 mg/kg, i.g.）, bisoprolol transdermal patch （BP-TP, 20.0 mg/kg）, isosorbide dinitrate transdermal patch （ISDN-TP, 20.0 mg/kg）, and the combination of BP and ISDN in a transdermal patch at low doses （8 and 12 mg/kg, respectively）. The effects of treatment were evaluated via biochemical indicators related to cardiovascular protection, structure and function. The combination therapy had synergistic anti-hypertensive effects and significantly reduced blood pressure with the benefit of controlling blood pressure variability compared to BP-FT and BP-TP. The combined treatment also reduced heart rate as well as BP-FT and BP-TP, while ISDN-TP had no evident effects on blood pressure, heart rate, and cardiovascular protection. Combination therapy was superior to BP-TP and BP-FT at increasing blood atrial natriuretic peptide and nitric oxide, while also reducing cardiac hydroxyproline and endothelin-1 with no difference in blood endothelin-1 and cardiac malondialdehyde levels. Cardiovascular remodeling differed among the groups, with the combination therapy reducing cardiac hypertrophy and the aortic media/lumen ratio. The consequential improvements in relaxation in response to cumulative concentrations of acetylcholine may explain the associated improvement in endothelial function. Combi- nation treatment with a transdermal patch exhibited a synergistic therapeutic effect. Such favorable cardiovascular effects with nitric oxide donors and β-blockade combination through a transdermal patch may provide long-term cardiovascular protection during anti-hypertensive treatment.
文摘AIM: To systematically assess the efficacy and safety of β-adrenergic blocker plus 5-isosorbide mononitrate (BB + ISMN) and endoscopic band ligation (EBL) on prophylaxis of esophageal variceal rebleeding. METHODS: Randomized controlled trials (RCTs) comparing the efficacy and safety of BB + ISMN and EBL on prophylaxis of esophageal variceal rebleeding were gathered from Medline, Embase, Cochrane Controlled Trial Registry and China Biological Medicine database between January 1980 and August 2007. Data from five trials were extracted and pooled. The analyses of the available data using the Revman 4.2 software were based on the intention-to-treat principle. RESULTS: Four RCTs met the inclusion criteria. In comparison with BB + ISMN with EBL in prophylaxis of esophageal variceal rebleeding, there was no significant difference in the rate of rebleeding [relative risk (RR), 0.79; 95% CI: 0.62-1.00; P = 0.05], bleeding-related mortality (RR, 0.76; 95% CI: 0.31-1.42; P = 0.40), overall mortality (RR, 0.81; 95% CI: 0.61-1.08; P = 0.15) and complications (RR, 1.26; 95% CI: 0.93-1.70; P = 0.13). CONCLUSION:In the prevention of esophageal variceal rebleeding, BB + ISMN are as effective as EBL. There are few complications with the two treatment modalities. Both BB + ISMN and EBL would be considered as the first-line therapy in the prevention of esophageal variceal rebleeding.
