Mohammad Fahim

Brief femoral artery ischaemia provides protection against myocardial ischaemia–reperfusion injury in rats: the possible mechanisms

The present study was conducted to examine the role of nitric oxide (NO), mitochondrial ATP‐sensitive K+ channels (mito K+ATP channels) and reactive oxygen species (ROS) and their interdependence in brief femoral artery ischaemia‐induced myocardial preconditioning. To assess myocardial injury, myocardial infarction was induced by occlusion followed by reperfusion of the left anterior descending (LAD) coronary artery in anaesthetized rats and was assessed by triphenyl tetrazolium chloride (TTC) staining. Left ventricular function was assessed by left ventricular end‐diastolic pressure (LVEDP) and the maximal rate of rise of left ventricular pressure [LV(dP/dt)max]. Serum creatine kinase‐MB (CK‐MB) and lactate dehydrogenase (LDH) were determined by colorimetric kits. Remote preconditioning (RPC) was induced by 15 min occlusion of femoral arteries followed by 10 min of reperfusion just before LAD coronary artery occlusion. Brief femoral artery ischaemia led to a 61% reduction in myocardial infarct size, 57% reduction in elevated serum LDH and 72% reduction in elevated CK‐MB activities, and a significant improvement in LVEDP and LV(dP/dt)max compared with control animals. Pretreatment with 5‐hydroxydecanoate (5‐HD) or l‐NAME or N‐acetylcystein (NAC) blocked this protective effect of femoral artery ischaemia. Moreover, infusion of l‐arginine or diazoxide before coronary artery occlusion markedly reduced the myocardial infarction and improved the left ventricular function. This effect of l‐arginine was found to be abolished by the blockade of mito K+ATP channels with 5‐HD and, similarly, the effect of diazoxide was blocked in the presence of a ROS scavenger, NAC. The results suggest that brief femoral artery ischaemia‐induced RPC is mediated by a combination of increased NO synthesis, opening of mito K+ATP channels and increased ROS production. Moreover, it appears that NO is working upstream and acts via activation of mito K+ATP channels, which subsequently increases the production of ROS.

Terminalia arjuna Enhances Baroreflex Sensitivity and Myocardial Function in Isoproterenol-Induced Chronic Heart Failure Rats

Chronic heart failure (CHF) is characterized by left ventricular (LV) dysfunction along with impaired autonomic control functions. Herbal drugs are increasingly being used in the treatment of cardiovascular disorders. The present study was designed to examine the protective effect of Terminalia arjuna (T arjuna) bark extract on LV and baroreflex function in CHF and to elucidate the possible mechanistic clues in its cardioprotective action. The baroreflex was evaluated by measuring the changes in heart rate (HR) with changes in arterial blood pressure induced by bolus injections of phenylephrine (vasoconstrictor) and sodium nitroprusside (vasodilator). T arjuna bark extract and fluvastatin were tested/administered therapeutically and prophylactically in isoproterenol-induced rat model of CHF. Fifteen days after isoproterenol administration, rats exhibited cardiac dysfunction, hypertrophy, and LV remodeling along with reduced baroreflex sensitivity. Prophylactic and therapeutic treatment with T arjuna improved cardiac functions and baroreflex sensitivity. It also attenuated hypertrophy and fibrosis of the LV. Fluvastatin treatment exerted a similar protective effect against myocardial remodeling and heart failure. Further, T arjuna and fluvastatin significantly reduced oxidative stress and inflammatory cytokine level in CHF rats. In conclusion, T arjuna exerts beneficial effect on LV functions, myocardial remodeling, and autonomic control in CHF possibly through maintaining endogenous antioxidant enzyme activities, inhibiting lipid peroxidation and cytokine levels.

Antioxidative Action of Aspirin on Endothelial Function in Hypercholesterolaemic Rats

The role of aspirin on vascular endothelial changes during hypercholesterolaemia prior to development of actual atherosclerotic lesions is not known. Therefore, in the present study, we tested the hypothesis that aspirin by its antioxidant action improves endothelial function in a rat model of hypercholesterolaemia. Hypercholesterolaemia was induced in Wistar rats by feeding a 1% cholesterol-rich diet for 10 weeks. Lipid profile, lipid peroxidation and reduced glutathione were estimated in serum. Endothelial function and beta(2)-adrenoceptor activity was tested by studying the dose-response relationship of acetylcholine and isoproterenol, respectively, on isolated aortic tissues in an organ bath setup. Hypercholesterolaemic rats showed a significant increase in total cholesterol, low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C), and a significant fall in high-density lipoprotein cholesterol (HDL-C) compared to the control rats. Isolated aortic tissues from hypercholesterolaemic rats showed endothelial dysfunction and decreased sensitivity to beta(2)-adrenoceptor. Treatment with aspirin was associated with a fall in total cholesterol, LDL-C and VLDL-C, and a significant rise in serum HDL-C. Aspirin treatment also restored endothelial function and beta(2)-adrenoceptor activity. Hypercholesterolaemic rats showed free radical generation, evident by increase in serum lipid peroxidation and reduction in serum reduced glutathione content compared to the control rats. Aspirin treatment was associated with reduction in free radical stress evident by decreased lipid peroxidation and significantly prevented reduction in glutathione content compared to hypercholesterolaemic controls. Aspirin improves endothelial function and beta(2)-adrenoceptor activity during experimentally induced hypercholesterolaemia in rats, possibly due to an antioxidant effect.

Improvement in myocardial function by Terminalia arjuna in streptozotocin-induced diabetic rats: possible mechanisms.

Vascular complications are a leading cause of mortality and morbidity in diabetic patients. Herbal drugs are increasingly being used in the treatment of cardiovascular disorders. The present study was designed to examine the therapeutic potential of Terminalia arjuna bark extract in improving myocardial function in streptozotocin (STZ)-induced diabetic rats. After 8 weeks of STZ administration, rats showed a decline in left ventricular pressure (LVP), maximal rate of rise and fall in LVP (LV [dP/dt] max and LV [dP/dt] min), cardiac contractility index (LV [dP/dt] max/LVP), and rise in LV end-diastolic pressure. Altered lipid profile, oxidative stress, and increased levels of endothelin 1 (ET-1), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) along with histological changes in heart and pancreas were observed in diabetic rats. T arjuna significantly attenuated cardiac dysfunction and myocardial injury in diabetic rats. It also reduced oxidative stress, ET-1, and inflammatory cytokine levels. The decreased body weight, heart rate blood pressure, and raised blood sugar in diabetic rats did not improve after T arjuna therapy. Results suggest that T arjuna bark extract improves the altered myocardial function in diabetic rats possibly through maintaining endogenous antioxidant enzyme activities, decreasing ET-1 and cytokine levels.

Effect of hypoxic breathing on cutaneous temperature recovery in man.

Effect of hypoxia (12% O2) on skin temperature recovery was studied on healthy young men. Forty male volunteers free of any respiratory disorder were randomly selected to participate in the study. Skin temperature, peripheral blood flow, heart rate and end expiratoryPO2 andPCO2 were measured. During hyoxic ventilation the peripheral blood flow was reduced and a corresponding drop in skin temperature occurred. This was partly due to hyperventilation associated with hypoxic ventilation. The recovery of skin temperature after cooling the hand for 2 min in cold water (10–12° C) took 5.5±0.1 min during normal air breathing; during hypoxic ventilation even after 9.1±0.3 min when the skin temperature recovery curve plateaued, the skin temperature remained about 2° C below control. The results of the present investigation indicate that hypoxia interferes with the normal functioning of the thermoregulatory mechanism in man. Hyperventilation associated with hypoxic ventilation is also partly responsible for incomplete recovery of skin temperature.

Altered alpha adrenergic vasoresponsiveness in a non‐cirrhotic portal hypertension model of E. coli injection

Background and Aim:  Portal hypertension is associated with decreased vascular responsiveness to vasoconstrictors, which may contribute to the hyperdynamic circulation in cirrhosis. Animal models of cirrhosis and portal vein ligation have helped in our understanding of portal hypertension. The etiopathogenesis of non‐cirrhotic portal fibrosis (NCPF), a common cause of portal hypertension, is still poorly understood. The aim of this study was to investigate the pathophysiology of NCPF in a rabbit model.

Seismic Performance of Stone Masonry Buildings Used in the Himalayan Belt

Rubble-stone masonry structures are found abundantly in the Asian countries along the Himalayan range. Such structures are usually constructed in dry-stone masonry or are constructed in mud mortar, which makes them susceptible to damage and collapse in earthquakes. In order to study the seismic behavior of these structures, dynamic shake table tests on three reduced-scale rubble-stone masonry models were conducted. The models comprised a representative school building, a residential building, and a model incorporating simple cost-effective features in the form of horizontal and vertical reinforced concrete elements. This paper presents the results of shake table tests carried out on rubble-stone masonry buildings including: damage pattern, capacity curves, damage limit states, and response modification factors of these structures. Test data indicates that seismic performance of rubble-stone masonry structures can be significantly improved by incorporating cost-effective features such as vertical members and relatively thin horizontal bands.

Endothelium modulated vasorelaxant response of a polypharmaceutical herbal drug (lipotab) and its individual constituents.

The present study was undertaken to examine the endothelium modulated effects of polypharmaceutical drug lipotab and its individual ingredients in isolated aortic rings of rat. Endothelium intact and denuded aortic rings were precontracted with phenylephrine 10(-6) M and drugs were added in cumulative manner in concentration ranging from 1 to 50 microg/ml. The results demonstrated an endothelium-dependent vasorelaxant effect of lipotab and its individual ingredients, with the exception of nicotinic acid. The dose dependent relaxant response of nicotinic acid was not altered significantly in the endothelium-denuded rings, suggesting a direct effect of the drug on the vascular smooth muscle. Vasorelaxant effect of lipotab and its individual constituents suggests the therapeutic potential of these compounds in certain cardiovascular diseases.

Effects of a novel ACE inhibitor, 3-(3-thienyl)-l-alanyl-ornithyl-proline, on endothelial vasodilation and hepatotoxicity in l-NAME-induced hypertensive rats

Nitric oxide (NO) is a widespread biological mediator involved in many physiological and pathological processes, eg, in the regulation of vascular tone and hypertension. Chronic inhibition of NO synthase by NG-nitro-l-arginine methyl ester (l-NAME) hydrochloride results in the development of hypertension accompanied by an increase in vascular responsiveness to adrenergic stimuli. Recently, we developed a novel sulfur-containing angiotensin-converting enzyme inhibitor: 3-(3-thienyl)-l-alanyl-ornithyl-proline (TOP). Our previous studies indicated a superior nature of the molecule as an antihypertensive agent in spontaneously hypertensive rats (showing the involvement of renin–angiotensin–aldosterone system) in comparison to captopril. The aim of the present study was to investigate the effect of TOP on NO pathway in l-NAME-induced hypertensive rats, and captopril was included as the standard treatment group. Treatment with both TOP (20 mg/kg) and captopril (40 mg/kg) prevented the development of hypertension in l-NAME model, but TOP showed better restoration of NO and normal levels of angiotensin-converting enzyme. In addition, in vitro vasorelaxation assay showed an improvement in endothelium-dependent vasodilation in both the cases. Further, the biochemical (malondialdehyde, alanine aminotransferase, and aspartate aminotransferase) and the histopathological effects of TOP on rat liver tissues revealed a protective nature of TOP in comparison to captopril in the l-NAME model. In conclusion, TOP at 50% lesser dose than captopril was found to be better in the l-NAME model.

Effects of Coriandrum Sativum Extract and Simvastatin in Isopreterenol Induced Heart Failure in Rats

Abstract Heart failure is a syndrome, caused due to structural and functional cardiac abnormalities, characterized by changes in the hemodynamic and neurohumoral mechanisms. It is becoming a major health burden worldwide. More effective therapies are desperately needed. Coriandrum sativum (C. sativum), a traditional spice crop has been known to possess many biological and medicinal properties. The present study was designed to investigate the cardioprotective efficacy of C. sativum in rat model of isoproterenol induced heart failure. Heart failure was produced by injecting isoproterenol subcutaneously (85 mg/kg twice at an interval of 24 h). Oral efficacy of seed extract was assessed on hemodynamic profile, antioxidant enzyme activities, lipid peroxidation, lipid profile, atherogenic indices, mRNA and protein expression of endothelin receptors (ETA and ETB) and histopathology. Treatment of heart failure rats with C. sativum orally (1g/kg b.wt) improved the altered hemodynamics, restored the cardiac antioxidant enzymes armory, attenuated oxidative stress, improved lipid profile, lowered atherogenic indices, decreased the levels of ETA and ETB receptor mRNA and protein, and restored the cardiac morphology. In conclusion, our results suggest C. sativum to be a cardioprotective agent in heart failure, possibly by the virtue of its ability to alleviate oxidative stress, improve lipid profile and endothelial dysfunction.