Preventive effect of S-allyl cysteine sulfoxide (alliin) on lysosomal hydrolases and membrane-bound ATPases in isoproterenol-induced myocardial infarction in Wistar rats

In this study, S-allyl cysteine sulfoxide (SACS) was used to evaluate its preventive effect in isoproterenol (ISO)-induced myocardial ischemia in male Wistar rats. Rats were pretreated with SACS (40 and 80 mg kg(-1)) orally for 5 weeks. After the treatment period, ISO (150 mg kg(-1)) was administered subcutaneously to rats at an interval of 24 h for 2 days. The activities of beta-D-N-acetyl-glucosaminidase, beta-galactosidase, beta-glucosidase, and acid phosphatase increased in serum and heart in ISO-induced rats. In addition, these rats showed a significant (p < 0.05) increase in the activities of beta-glucuronidase and cathepsin-D in serum and heart and a significant (p < 0.05) decrease in their activities in lysosomal fraction of the heart. The activity of Na(+)K(+)-ATPase declined, while those of Ca(2+)- and Mg(2+)-ATPases significantly (p < 0.05) elevated in the heart of ISO-induced rats. Pretreatment with SACS (40 and 80 mg kg(-1)) showed a significant (p < 0.05) effect in all the biochemical parameters studied. The effect at a dose of 80 mg kg(-1) body weight was more effective than that at 40 mg kg(-1) body weight and brought back all the biochemical parameters to near normal levels. Hereby, our study shows the membrane-stabilizing as well as antioxidant effects of SACS in ISO-induced rats.     

Cardioprotective effect of alpha-mangostin, a xanthone derivative from mangosteen on tissue defense system against isoproterenol-induced myocardial infarction in rats

Increased oxidative stress and antioxidant deficit have been suggested to play a major role in isoproterenol-induced myocardial infarction. The present study was designed to evaluate the effect of alpha-mangostin on the antioxidant defense system and lipid peroxidation against isoproterenol-induced myocardial infarction in rats. Induction of rats with ISO (150 mg/kg body weight, ip) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT) and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GST, and GSH). Pre-treatment with alpha-mangostin (200 mg/kg of body weight per day) orally for 6 days prior to the ISO administration and 2 days along with ISO administration significantly attenuated these changes when compared to the individual treatment groups. These findings indicate the protective effect of alpha-mangostin on lipid peroxidation and antioxidant tissue defense system during ISO-induced myocardial infarction in rats.     

Protective effects of N-acetyl cysteine on membrane-bound adenosine triphosphatases and minerals in isoproterenol-induced myocardial-infarcted rats: an in vivo and in vitro study

The present study was aimed to evaluate the protective effects of N-acetyl cysteine (NAC) on changes in the activities/levels of adenosine triphosphatases and minerals in isoproterenol-induced myocardial-infarcted rats. Male albino Wistar rats were pretreated with NAC (10 mg/kg body weight) daily for a period of 14 days. After pretreatment period, rats were induced myocardial infarction (MI) by isoproterenol (100 mg/kg body weight). The activity of sodium/potassium-dependent adenosine triphosphatase was decreased, and the activities of calcium- and magnesium-dependent adenosine triphosphatases were increased in the heart of isoproterenol-induced myocardial-infarcted rats. Furthermore, the levels of potassium were lowered and the levels of sodium and calcium were increased in the heart of isoproterenol-induced rats. Increased plasma lipid peroxidation was observed in isoproterenol-induced rats. Pretreatment with NAC showed protective effects on adenosine triphosphatases, minerals, and lipid peroxidation. The in vitro study confirmed the reducing property of NAC. The observed effects are due to the membrane-stabilizing and antioxidant effects of NAC. The results of this study will be useful for the prevention of MI.     

Preventive effect of naringin on lipids, lipoproteins and lipid metabolic enzymes in isoproterenol-induced myocardial infarction in Wistar rats

This study was designed to evaluate the preventive effect of naringin in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Rats were pretreated with naringin (10, 20, and 40 mg/kg body weight) orally for a period of 56 days. After the treatment period, ISO (85 mg/kg body weight) was administered subcutaneously to rats at an interval of 24 h for 2 days. There was a significant increase in the levels of total, ester, and free cholesterol, triglycerides (TG), and free fatty acids (FFA) in serum and heart and decrease in heart phospholipids (PL) in ISO-induced rats. Altered levels of lipoproteins and activities of 3-hydroxy-3-methylglutaryl-Coenzyme reductase A in liver and heart, lecithin cholesterol acyl transferase and lipoprotein lipase in plasma were also observed in ISO-induced rats. Pretreatment with naringin (10, 20, and 40 mg/kg) for a period of 56 days significantly decreased the levels of total, ester, and free cholesterol, TG, FFA in serum and heart and increased PL in heart. It also minimized the alterations in serum lipoproteins and lipid metabolic enzymes in ISO-induced rats. Thus, naringin has a lipid-lowering effect in ISO-induced MI rats.     

Protective effects of N-acetyl cysteine on lipid peroxide metabolism on isoproterenol-induced myocardial infarcted rats

The present study was designed to evaluate the preventive effects of N-acetyl cysteine on lipid peroxide metabolism in isoproterenol (ISO) induced myocardial infarcted rats. Male albino Wistar rats were pretreated with N-acetyl cysteine (5 and 10 mg/kg) daily for a period of 14 days. After the pretreatment period, ISO (100 mg/kg) was subcutaneously injected to rats twice at an interval of 24 h. Increased activities of serum creatine kinase, creatine kinase-MB, lactate dehydrogenase, and increased intensities of serum lactate dehydrogenase-isoenzyme bands (LDH-1, LDH-2) were observed in ISO-induced rats. The heart lipid peroxidation products were significantly increased, and the antioxidant system was significantly reduced in ISO-induced rats. Pretreatment with N-acetyl cysteine (5 and 10 mg/kg) to ISO-induced rats showed significant effects on all the biochemical parameters studied. Histopathological findings of the myocardium also showed the protective role of N-acetyl cysteine in ISO-induced rats. Furthermore, in vitro study confirmed the potent-free radical scavenging activity of N-acetyl cysteine. The effect at a dose of 10 mg/kg of N-acetyl cysteine was more pronounced than the dose, 5 mg/kg. The results of our study show that N-acetyl cysteine protects the heart against ISO-induced myocardial infarction by its free radical scavenging effect.     

Protective effect of morin on cardiac mitochondrial function during isoproterenol-induced myocardial infarction in male Wistar rats

Abstract

Altered mitochondrial function and free radical-mediated tissue damage have been suggested as an important pathological event in isoproterenol (ISO)-induced cardiotoxicity. This study was undertaken to know the preventive effect of morin on mitochondrial damage in ISO-induced cardiotoxicity in male Wistar rats. Myocardial infarction (MI) in rats was induced by ISO (85 mg/kg) at an interval of 24 hours for 2 days. Morin was given to rats as pre-treatment for 30 days orally using an intragastric tube. ISO-treated rats showed a significant elevation of mitochondrial thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (HP) level and pre-treatment with morin significantly prevented the increase of TBARS and HP level to near normality. The level of enzymic and non-enzymic antioxidants was decreased significantly in ISO-treated rats and pre-treatment with morin significantly increased the levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and reduced glutathione to normality. The activities of mitochondrial enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase were decreased significantly in ISO-treated myocardial ischemic rats and upon pre-treatment with morin restored these enzymes activity to normality. In addition, the decreased activities of cytochrome-C oxidase and NADH-dehydrogenases were observed in ISO-treated rats and pre-treatment with morin prevented the activities of cytochrome-C oxidase and NADH-dehydrogenase to normality. Pre-treatment with morin favorably restored the biochemical and functional parameters to near normal indicating morin to be a significant protective effect on cardiac mitochondrial function against ISO-induced MI in rats.     

Protective effects of caffeic acid on lactate dehydrogenase isoenzymes, electrocardiogram, adenosine triphosphatases, and hematology on isoproterenol-induced myocardial infarcted rats

The present study aims to evaluate the protective effects of caffeic acid on isoproterenol-treated myocardial infarction. Male albino Wistar rats were pretreated with caffeic acid (15 mg/kg) daily for 10 days. After the pretreatment, rats were injected with isoproterenol (100 mg/kg) at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol-treated rats showed increased intensity of lactate dehydrogenase-1 and 2 isoenzyme bands and elevated ST segments. The activity of the heart sodium potassium adenosine triphosphatase was decreased, and the activities of the heart magnesium adenosine triphosphatase and calcium adenosine triphosphatase were increased in isoproterenol-treated rats. Isoproterenol-treated rats also showed a significant increase in the concentration of heart calcium. Furthermore, it significantly increased the counts of red blood cells, hemoglobin, white blood cells, and neutrophils and decreased significantly the concentration of erythrocyte sedimentation rate and the counts of lymphocytes and eosinophils. Pretreatment with caffeic acid showed protective effects on all the biochemical parameters, hematology and minimized alterations in lactate dehydrogenase isoenzymes and electrocardiogram. In vitro study confirmed the free radical scavenging potential of caffeic acid. The observed effects might be due to the free radical scavenging and membrane-stabilizing property of caffeic acid.     

Preventive effect of naringin on cardiac mitochondrial enzymes during isoproterenol-induced myocardial infarction in rats: a transmission electron microscopic study

Dietary flavonoids intake has been reported inversely related to the incidence of cardiovascular diseases (CVD). The present study is undertaken to evaluate the preventive role of naringin on mitochondrial enzymes in isoproterenol (ISO)-induced myocardial infarction in male albino Wistar rats. Rats subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for 2 days, resulting in significant (p < 0.05) increase in the levels of mitochondrial lipid peroxides. ISO-induction also showed significant (p < 0.05) decrease in the activities of mitochondrial tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and alpha-ketoglutarate dehydrogenase) and respiratory chain enzymes (NADH dehydrogenase and cytochrome c oxidase). Oral pretreatment with naringin (10, 20, and 40 mg/kg) to ISO-induced rats daily for a period of 56 days significantly (p < 0.05) minimized the alterations in all the biochemical parameters and restored the normal mitochondrial function. Transmission electron microscopic (TEM) observations also correlated with these biochemical findings. Thus, our findings demonstrate that naringin prevents the mitochondrial dysfunction during ISO-induced myocardial infarction in rats.     

Protective effects of thymol on altered plasma lipid peroxidation and nonenzymic antioxidants in isoproterenol-induced myocardial infarcted rats

This study evaluates the protective effects of thymol on altered plasma lipid peroxidation products and nonenzymic antioxidants in isoproterenol (ISO)‐induced myocardial infarcted rats. Male albino Wistar rats were pre and cotreated with thymol (7.5 mg/kg body weight) daily for 7 days. ISO (100 mg/kg body weight) was subcutaneously injected into rats on 6th and 7th day to induce myocardial infarction (MI). Increased activity/levels of serum creatine kinase‐MB (CK‐MB), plasma thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes with decreased levels of plasma reduced glutathione (GSH), vitamin C, and vitamin E were observed in ISO‐induced myocardial infarcted rats. Pre and cotreatment with thymol (7.5 mg/kg body weight) showed normalized activity of serum CK‐MB and near normalized levels of plasma lipid peroxidation products, reduced GSH, vitamin C, and vitamin E in myocardial infarcted rats. Furthermore, the in vitro study on reducing power of thymol confirmed its potent antioxidant action. Thus, thymol protects ISO‐induced MI in rats by its antilipid peroxidation and antioxidant properties. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:368–373, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21431     

Preventive effect of rutin on lipids, lipoproteins, and ATPases in normal and isoproterenol-induced myocardial infarction in rats

The present study was designed to evaluate the preventive role of rutin on lipids, lipoproteins, and ATPases in normal and isoproterenol (ISO)-induced myocardial infarction in rats. Rutin (40 and 80 mg/kg) was orally administered to rats for a period of 42 days. After that period, isoproterenol (150 mg/kg) was injected subcutaneously to male wistar rats at an interval of 24 h for 2 days. The weight of heart and the concentrations of total cholesterol, triglycerides, and free fatty acids were increased significantly (p < 0.05), and the concentration of phospholipids was decreased significantly (p < 0.05) in the heart of ISO-treated rats. ISO-treated rats also showed a significant increase (p < 0.05) in the levels of total cholesterol, triglycerides, phospholipids, low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C) with a significant decrease (p < 0.05) in high-density lipoprotein cholesterol (HDL-C) level in serum. The activities of sodium potassium dependent adenosine triphosphatase (Na(+)/K(+) ATPase) and magnesium-dependent adenosine triphosphatase (Mg(2+) ATPase) were decreased significantly (p < 0.05), and the activity of calcium-dependent adenosine triphosphatase (Ca(2+)ATPase) was increased significantly (p < 0.05) in the heart in ISO-treated rats. Pretreatment with rutin at doses of 40 or 80 mg/kg to ISO-treated rats showed a significant (p < 0.05) effect in all the parameters studied. Oral administration of rutin to normal rats did not show any significant effect. Thus, the results of our study show that pretreatment with rutin maintained the levels of lipids, lipoproteins, and ATPases in ISO-induced myocardial infarcted rats. The observed effects might be due to the antioxidant potential of rutin.     

Spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine levels in cardiomyocytes after myocardial infarction in rats

Temporary or persistent heart failure is one of the major complications after myocardial infarction (MI). In order to elucidate the pathogenesis of MI, we studied the spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in cardiomyocytes in a rat model of ligation of the left anterior descending branch of the coronary artery. The lethality in this model was 18%. Hearts were dissected at 0, 3, 6, 12, 24, 48 h, and 1, 2, 4, 6 weeks after the operation. The cardiac level of 8-OHdG was evaluated biochemically as well as by immunohistochemistry with monoclonal antibody N45.1. Three to 6 h after ligation, the 8-OHdG levels were increased in the cardiomyocytes of MI (six-fold) and peri-MI (four-fold) areas. After 24 h, the myocardium in the MI area was necrotized, and thereafter the 8-OHdG level decreased. 8-OHdG levels in the myocardium of peri-MI areas returned once to a normal level, but were significantly increased at 2-4 weeks along with the appearance of apoptotic cardiomyocytes in this area. The heart after MI has been generally considered as clinically stable after four weeks. However, cardiomyocytes near the infarcted area were oxidatively stressed even after four weeks when the affected lesion was extensive. The present data support the use of supplementary antioxidant therapies to save functional myocardium after MI. (213 words)     

Preventive effect of (-)epigallocatechin-gallate (EGCG) on lysosomal enzymes in heart and subcellular fractions in isoproterenol-induced myocardial infarcted Wistar rats

This study was aimed to evaluate the preventive role of (-)epigallocatechin-gallate (EGCG) on lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarcted rats. Male albino Wistar rats were pretreated with EGCG (30 mg/kg) daily for a period of 21 days. After the treatment period, ISO (100 mg/kg) was subcutaneously injected to rats at intervals of 24h for 2 days. The activities of lysosomal enzymes (beta-glucuronidase, beta-N-acetylglucosaminidase, beta-galactosidase, cathepsin-B and cathepsin-D) were increased significantly (P<0.05) in serum and the heart of ISO-induced rats. ISO-induction also resulted in decreased stability of membranes, which was reflected by decreased activities of beta-glucuronidase and cathepsin-D in mitochondrial, nuclear, lysosomal and microsomal fractions. Pretreatment with EGCG daily for a period of 21 days to ISO-induced rats prevented the changes in the activities of these enzymes. Oral treatment with EGCG (30 mg/kg) to normal control rats did not show any significant effect in all the biochemical parameters studied. Thus, the results of our study shows that EGCG protects the lysosomal membrane against ISO-induced cardiac damage. The observed effects might be due to the free radical scavenging and membrane stabilizing properties of EGCG.     

Protective efficacy of ellagic acid on glycoproteins, hematological parameters, biochemical changes, and electrolytes in myocardial infarcted rats

The cardioprotective property of ellagic acid in rats has been reported previously. The present study reveals the protective role of ellagic acid in biochemical parameters including serum iron, plasma iron binding capacity, uric acid, glycoprotein, and electrolytes along with hematological parameters. Rats were subcutaneously injected with isoproterenol (ISO) (100 mg/kg) for 2 days to induce myocardial infarction. ISO-induced rats showed a significant increase in their levels of serum iron, serum uric acid, and blood glucose, and a significant decrease in their levels of plasma iron binding capacity, serum total protein, albumin/globulin ratio, and heart glycogen, when compared with normal control rats. The altered hematological parameters were also observed in ISO-induced rats when compared with normal control rats. Pretreatment with ellagic acid at doses of 7.5 and 15 mg/kg produced significant beneficial effect by returning all the above-mentioned biochemical and hematological parameters to near normal levels.     

Preventive effect of caffeic acid on lysosomal dysfunction in isoproterenol‐induced myocardial infarcted rats

We evaluated the preventive effect of caffeic acid (CA) on lysosomal enzymes in isoproterenol (ISO)‐treated myocardial infarcted rats. Male albino Wistar rats were pretreated with CA (15 mg/kg) daily for a period of 10 days. After the pretreatment period, ISO (100 mg/kg) was subcutaneously injected to rats twice at an interval of 24 h. The activity of serum creatine kinase‐MB and lactate dehydrogenase was increased significantly (P < 0.05) in ISO‐induced myocardial infarcted rats. The levels of plasma thiobarbituric acid reactive substances and lipid hydroperoxides were significantly (P < 0.05) increased, and the level of plasma‐reduced glutathione was significantly (P < 0.05) decreased in ISO‐induced myocardial infarcted rats. The activities of lysosomal enzymes (β‐glucuronidase, β‐N‐acetylglucosaminidase, β‐galactosidase, cathepsin‐B and cathepsin‐D) were increased significantly (P < 0.05) in the serum and heart of ISO‐induced myocardial infarcted rats. ISO induction also resulted in decreased stability of membranes, which was reflected by lowered activities of β‐glucuronidase and cathepsin‐D in different fractions except cytosol. Pretreatment with CA (15 mg/kg) to ISO‐treated rats significantly (P < 0.05) prevented the changes in the activities of cardiac marker enzymes, the levels of lipid peroxidation products, reduced glutathione and the activities of lysosomal enzymes in the serum, heart, and subcellular fractions. Oral treatment with CA (15 mg/kg) to normal control rats did not show any significant effect. Thus, the results of our study showed that CA prevented the lysosomal membrane damage against ISO‐induced myocardial infarction. The observed effects of CA are due to membrane‐stabilizing, antilipo peroxidative, and antioxidant effects. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:115–122, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20319     

Preventive effect of (−)epigallocatechin gallate on lipids,lipoproteins, and enzymes of lipid metabolism in isoproterenol‐induced myocardial infarction in rats

This article reports data on the preventive effect of (?)epigallocatechin gallate (EGCG) on lipid metabolism and lipoproteins in isoproterenol (ISO)‐induced myocardial infarction (MI) in Wistar rats. The rats were induced MI by ISO (100 mg/kg) at an interval of 24 h for 2 days. EGCG (30 mg/kg) was given to rats as pretreatment for 21 days orally using an intragastric tube. EGCG significantly reduced the increased serum levels of cholesterol, triglycerides, and free fatty acids in the heart and serum phospholipids (PLs) in ISO‐treated rats. It also significantly increased the reduced levels of heart PLs in ISO‐induced rats. EGCG reduced the levels of serum low‐density lipoprotein cholesterol and very low‐density lipoprotein cholesterol and increased serum high‐density lipoprotein (HDL)‐cholesterol in ISO‐treated rats. It also reduced the increased cholesterol/PL ratio and atherogenic index and significantly increased the reduced ratio of HDL‐cholesterol/total cholesterol. Also EGCG significantly increased the reduced activity of lecithin cholesterol acyl transferase in ISO‐treated rats. Thus, EGCG prevented the accumulation of lipids and altered the levels of lipoproteins in myocardial‐infarcted rats. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:387–393, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20302     

On the antioxidant,neuroprotective and anti-inflammatory properties of S-allyl cysteine: An update

Therapeutic approaches based on isolated compounds obtained from natural products to handle central and peripheral disorders involving oxidative stress and inflammation are more common nowadays. The validation of nutraceutics vs. pharmaceutics as tools to induce preventive and protective profiles in human health alterations is still far of complete acceptance, but the basis to start more solid experimental and clinical protocols with natural products has already begun. S-allyl cysteine (SAC) is a promising garlic-derived organosulfur compound exhibiting a considerable number of positive actions in cell models and living systems. An update, in the form of review, is needed from time to time to get access to the state-of-the-art on this topic. In this review we visited recent and refreshing evidence of new already proven and potential targets to explain the benefits of using SAC against toxic and pathological conditions. The broad spectrum of protective actions covered by this molecule comprises antioxidant, redox modulatory and anti-inflammatory activities, accompanied by anti-apoptotic, pro-energetic and signaling capacities. Herein, we detail the evidence on these aspects to provide the reader a more complete overview on the promising aspects of SAC in research.     

Terminalia pallida fruit ethanolic extract ameliorates lipids,lipoproteins, lipid metabolism marker enzymes and paraoxonase in isoproterenol-induced myocardial infarcted rats

The present study aimed to evaluate the effect of Terminalia pallida fruit ethanolic extract (TpFE) on lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase (PON) in isoproterenol (ISO)-induced myocardial infarcted rats. PON is an excellent serum antioxidant enzyme which involves in the protection of low density lipoprotein cholesterol (LDL-C) from the process of oxidation for the prevention of cardiovascular diseases. ISO caused a significant increase in the concentration of total cholesterol, triglycerides, LDL-C, very low density lipoprotein cholesterol and lipid peroxidation whereas significant decrease in the concentration of high density lipoprotein cholesterol. ISO administration also significantly decreased the activities of lecithin cholesterol acyl transferase, PON and lipoprotein lipase whereas significantly increased the activity of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Oral pretreatment of TpFE at doses 100, 300 and 500?mg/kg body weight (bw) and gallic acid (15?mg/kg bw) for 30?days challenged with concurrent injection of ISO (85?mg/kg bw) on 29th and 30th day significantly attenuated these alterations and restored the levels of lipids, lipoproteins and the activities of lipid metabolizing enzymes. Also TpFE significantly elevated the serum antioxidant enzyme PON. This is the first report revealed that pretreatment with TPFE ameliorated lipid metabolic marker enzymes and increased the antioxidant PON in ISO treated male albino Wistar rats.     

Antioxidant and cardioprotective effects of Danshensu (3-(3, 4-dihydroxyphenyl)-2-hydroxy-propanoic acid from Salvia miltiorrhiza) on isoproterenol-induced myocardial hypertrophy in rats

Myocardial hypertrophy has been linked to the development of a variety of cardiovascular diseases, and is a risk factor for myocardial ischemia, arrhythmias, and sudden cardiac death. The objective of the present study was to evaluate the cardioprotective effects of Danshensu (DSS), a water-soluble active component of Danshen, on cardiac hypertrophy in rats. We are the first to report that DSS reversed Cx43 down-regulation in ventricular tissue. Cardiomyopathy in rats was produced using isoproterenol (Iso) treatment (2.5 mg/kg/d, s.c.) for seven days. DSS (3 and 10 mg/kg/d, i.p.) and Valsartan (Val) (10 mg/kg, i.g.) were administered on days 4-7 of Iso-treatment. Heart weight index, hemodynamic parameters, and ECG II parameters were monitored and recorded; protein expression of left ventricular connexin 43 (Cx43) and the activity of the redox system were assayed, and arrhythmias were produced using a coronary ligation/reperfusion procedure. The results demonstrated that DSS treatment significantly decreased heart weight/body weight (HW/BW) and left ventricular weight/body weight (LVW/BW) ratios. The protective role of DSS against Iso-induced myocardial hypertrophy was further confirmed using ECG. The incidences of ventricular tachycardia and ventricular fibrillation (VT, VF) and arrhythmic scores were higher in the model group and were suppressed by DSS. DSS decreased the serum and myocardium levels of creatine kinase, lactate dehydrogenase, and malondialdehyde (CK, LDH, and MDA) and increased serum activity of superoxide dismutase (SOD) in a dose-dependent manner. Cx43 expression in the left ventricle was down-regulated, and there was significant oxidative stress in this model of cardiomyopathy. DSS reversed the down-regulated Cx43 protein levels and showed potent anti-oxidative activities and cellular protection. These data demonstrate that DSS can prevent cardiac I/R injury and improve cardiac function in a rat model of hypertrophy, the effects partially resulting from antioxidants and the protection from Cx43 expression.     

早期足量应用美托洛尔对急性心肌梗死疗效及安全性的研究

目的:研究早期足量应用美托洛尔对急性心肌梗死的疗效及安全性.方法:将40例AMI患者随机分为治疗组和对照组.治疗组静脉缓慢注射美托洛尔15mg后予关托洛尔150-200mg/d口服;对照组按常规剂量给予美托洛尔25-50mg/d口服.其它治疗相同,两组治疗4周.比较两组治疗后QTcd、心律失常发生的种类、心肌耗氧指数、梗死后心绞痛、梗死延展的发生率和心功能的变化.结果:治疗组QTcd、室性心律失常发生率、心肌耗氧指数、梗死后心绞痛和梗死延展的发生率均低于对照组(P<0.05).心功能两组无显著性差异.结论,AMI患者早期足量使用美托洛尔可以从多方面获益,安全性高.