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Anil Gulati - One of the best experts on this subject based on the ideXlab platform.
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evidence for the involvement of et b receptors in et 1 induced changes in blood flow to the rat breast tumor
Cancer Chemotherapy and Pharmacology, 2003Co-Authors: Aarati Rai, Anil GulatiAbstract:Abstract Purpose. Structure, growth, and function of the blood vessels in breast tumors are markedly different from those in normal breast tissue due to changes in the production of growth factors such as vascular endothelial growth factor (VEGF), vasoactive substances such as endothelin-1 (ET-1) and cytokines. The role of ET-1 in breast tumor angiogenesis is not adequately understood. Studies have shown that the expression of proET-1, proET-3, and ETB receptors is increased in breast tumor. However, it is unclear whether there are any changes in ET-1-induced vascular responses in breast tumor. Hence, in the present study we investigated systemic hemodynamics and regional circulatory effects of ET-1 in rats with breast tumors. Methods. Female Sprague-Dawley rats weighing 180–200 g were divided into the following groups: (1) normal rats treated with saline (n=6), (2) tumor-bearing rats treated with methylnitrosourea (MNU) (n=6), (3) normal rats treated with saline plus the specific ETB receptor antagonist BQ 788 (n=5), and (4) tumor-bearing rats treated with MNU plus BQ 788 (n=5). Tumor development was monitored by regular palpation and measurement of tumor size. Once tumors had reached approximately 2–4 cm in diameter, the rats were anesthetized with urethane (1.5 g/kg i.p.) and their cardiovascular parameters were measured using a Radioactive Microsphere technique. Simultaneously, blood perfusion to the breast tissue was also measured using a laser Doppler technique. Results. ET-1 produced a significant increase in mean arterial pressure in normal and tumor-bearing rats. Blood flow to the tumor tissue increased significantly in response to ET-1 as compared to breast tissue in normal rats. This response was accompanied by a concomitant decrease in vascular resistance in the tumor tissue. These results were confirmed by laser Doppler flowmetry, which showed a significant increase in blood perfusion to breast tumor compared to normal breast tissue. This increase in blood perfusion was attenuated by pretreatment with BQ 788, suggesting an ETB receptor-mediated vasodilator action of ET-1 in rat breast tumor. Conclusions. The results indicate that ET-1 induced an increase in blood flow to breast tumor tissue mediated through ETB receptors.
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modulation of diaspirin crosslinked hemoglobin induced systemic and regional hemodynamic response by ethanol in normal rats
Life Sciences, 2001Co-Authors: Rameshraja Palaparthy, Bindu K Saini, Anil GulatiAbstract:Abstract DCLHb, a hemoglobin based oxygen carrier, has been extensively studied for the treatment of hemorrhagic shock in both animal models and humans. Numerous accidents resulting in trauma are due to ethanol intoxication, in particular cases of car accidents. Therefore, trauma patients might be intoxicated with drugs of abuse like ethanol. Ethanol has significant effects on the cardiovascular system including peripheral vasodilation and decreased myocardial contractility. Such effects are likely to alter the cardiovascular actions of DCLHb, a resuscitative agent. Hence, this study investigated the effect of ethanol on the cardiovascular actions of DCLHb. Urethane anesthetized male Sprague-Dawley rats were divided into following groups (i) Saline + DCLHb (400 mg/kg) (n = 9), (ii) Ethanol (1 g/kg) + DCLHb (400 mg/kg) (n = 9), and (iii) Ethanol (4 g/kg) + DCLHb (400 mg/kg) (n = 8). Cardiovascular parameters were determined using a Radioactive Microsphere technique. DCLHb when administered to saline treated rats produced an increase in MAP, TPR, decreased renal and hepatic blood flow and increased blood flow to the skin and mesentery & pancreas. A high dose of ethanol (4 g/kg) significantly attenuated the DCLHb induced pressor response (p
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dose response effect of diaspirin crosslinked hemoglobin dclhb on systemic hemodynamics and regional blood circulation in rats
Artificial Cells Blood Substitutes and Biotechnology, 1997Co-Authors: Abhijit Barve, Anil GulatiAbstract:Diaspirin crosslinked hemoglobin (DCLHbTM, Baxter Healthcare Corporation) a hemoglobin-based blood substitute has been found to increase mean arterial pressure (MAP) in a dose limiting manner. The present study was undertaken to determine dose-dependent effects of DCLHb on systemic hemodynamics and regional blood circulation. DCLHb (10% solution) in doses of 133, 400 and 1200 mg/kg i.v. was given to urethane anaesthetized rats. Normal saline (12 ml/kg) served as a control. Cardiovascular parameters were determined using a Radioactive Microsphere technique. DCLHb in the doses of 133, 400 and 1200 mg/kg i.v. produced a 46%, 67% and 65% increase in MAP, respectively. Total peripheral resistance (TPR) increased significantly with 133 and 400 mg/kg dose, while cardiac output increased significantly with 400 and 1200 mg/kg dose. There was no change in heart rate. A dose of 133 mg/kg of DCLHb produced a significant decrease in blood flow to the musculoskeletal system, kidney and liver. DCLHb in the dose of 400 a...
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yohimbine modulates diaspirin crosslinked hemoglobin induced systemic hemodynamics and regional circulatory effects
Critical Care Medicine, 1995Co-Authors: Avadhesh C. Sharma, Anil GulatiAbstract:OBJECTIVE: Diaspirin crosslinked hemoglobin, a hemoglobin-based blood substitute, is proposed to be an effective resuscitative solution. It produces an immediate, but limited increase in blood pressure when administered to conscious or anesthetized rats. This vasoactivity is associated with an increase in blood flow to several major organs. It has been shown that alpha-adrenergic receptors in the peripheral vascular system are sensitized by diaspirin crosslinked hemoglobin in rats. The present study was conducted to determine the effect of yohimbine, an alpha 2-adrenergic receptor antagonist on systemic hemodynamics and regional circulatory effects of diaspirin crosslinked hemoglobin. DESIGN: Prospective, randomized comparison of cardiovascular effects of diaspirin crosslinked hemoglobin in control and yohimbine-pretreated rats. SETTING: Laboratory of experimental medicine. SUBJECTS: Male Sprague-Dawley rats weighing 300 to 350 g. INTERVENTIONS: Modified, highly purified, and heat-pasteurized hemoglobin (diaspirin crosslinked hemoglobin) in control and yohimbine-treated (2 mg/kg i.v.) rats. MEASUREMENTS AND MAIN RESULTS: The systemic hemodynamics and regional circulation were measured using a Radioactive Microsphere technique. Diaspirin crosslinked hemoglobin (400 mg/kg i.v.) produced an increase in blood pressure and total peripheral resistance, while heart rate, cardiac output, and stroke volume were not significantly altered in control rats. In yohimbine-pretreated (2 mg/kg i.v.) animals, diaspirin crosslinked hemoglobin did not produce any change in heart rate, stroke volume, cardiac output, and total peripheral resistance, but a slight increase in blood pressure was observed compared with baseline values obtained after the administration of yohimbine. The increase in blood pressure induced by diaspirin crosslinked hemoglobin was significantly blocked by pretreatment with yohimbine. Yohimbine (2 mg/kg i.v.) per se decreased blood pressure, while other systemic hemodynamic parameters were not affected. Diaspirin crosslinked hemoglobin increased blood flow to the heart, gastrointestinal tract (stomach, small intestine, cecum, and large intestine), portal (spleen, mesentery, and pancreas) and skin, while blood flow to the brain (cerebral hemispheres, diencephalon, cerebellum, and brain stem), liver, kidneys, and musculoskeletal system was not affected in control rats. In yohimbine-pretreated animals, diaspirin crosslinked hemoglobin produced an increase in blood flow to the heart, brain (cerebellum and brain stem), liver, small intestine, cecum, spleen, mesentery and pancreas, kidneys, skin and musculoskeletal system, while blood flow to the stomach and large intestine was not affected. Yohimbine pretreatment significantly attenuated the diaspirin crosslinked hemoglobin-induced increase in blood flow to the large intestine, mesentery, and pancreas. CONCLUSIONS: The cardiovascular actions of diaspirin crosslinked hemoglobin are partially mediated through alpha 2-adrenergic receptors. Adrenergic receptor antagonists may be useful in attenuating the pressor effect of diaspirin crosslinked hemoglobin while maintaining the regional perfusion.
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effect of stroma free hemoglobin and diaspirin cross linked hemoglogbin on the regional circulation and systematic hemodynamics
Life Sciences, 1994Co-Authors: Anil Gulati, Avadhesh C. Sharma, Kenneth E BurhopAbstract:Abstract The effects of unmodified stroma-free hemoglobin (SFHb) and diaspirin cross-linked hemoglobin (DCLHb) on the regional blood circulation and systematic hemodynamics were studied in rats using a Radioactive Microsphere technique. SFHb and DCLHb increased mean arterial blood pressure without affecting heart rate. SFHb produced a 24.9 % decrease in the cardiac output while DCLHb produced an 44.8 % increase in the cardiac output. Stroke volume was decreased (−27.3 %) by SFHb and increased (+36.4 %) by DCLHb. Total peripheral resistance increased with both SFHb and DCLHb. DCLHb increased blood flow to the heart, spleen, stomach, small intestine and skin, and had no effect on blood flow to the brain, kidneys, liver, mesentery, pancreas, caecum, large intestine and musculo-skeletal system. In contrast, in animals infused with SFHb, blood flow decreased to the kidneys, liver and spleen, increased to the heart, small intestine and skin, and had no effect to the brain, caecum, large intestine and musculo-skeletal system. DCLHb had no effect on vascular resistance in any organ except for an increase in the musculo-skeletal system. In contrast, SFHb increased vascular resistance in the kidneys, liver, spleen, skin, mesentery and pancreas, and had no effect on vascular resistance in the musculo-skeletal system, brain, heart, stomach, small intestine, caecum and large intestine. SFHb had no effect on distribution of cardiac output to the brain, gastrointestinal tract (GIT), kidneys, skin, musculo-skeletal and portal system, while DCLHb significantly decreased the percent cardiac output to the musculo-skeletal system. DCLHb did not affect the distribution of cardiac output to the brain, GIT, kidneys, skin and portal system. SFHb and DCLHb increased the percent cardiac output to the heart. It is concluded that similar concentrations and doses of DCLHb and SFHb produce different effects on the regional blood circulation and systematic hemodynamics.
Avadhesh C. Sharma - One of the best experts on this subject based on the ideXlab platform.
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yohimbine modulates diaspirin crosslinked hemoglobin induced systemic hemodynamics and regional circulatory effects
Critical Care Medicine, 1995Co-Authors: Avadhesh C. Sharma, Anil GulatiAbstract:OBJECTIVE: Diaspirin crosslinked hemoglobin, a hemoglobin-based blood substitute, is proposed to be an effective resuscitative solution. It produces an immediate, but limited increase in blood pressure when administered to conscious or anesthetized rats. This vasoactivity is associated with an increase in blood flow to several major organs. It has been shown that alpha-adrenergic receptors in the peripheral vascular system are sensitized by diaspirin crosslinked hemoglobin in rats. The present study was conducted to determine the effect of yohimbine, an alpha 2-adrenergic receptor antagonist on systemic hemodynamics and regional circulatory effects of diaspirin crosslinked hemoglobin. DESIGN: Prospective, randomized comparison of cardiovascular effects of diaspirin crosslinked hemoglobin in control and yohimbine-pretreated rats. SETTING: Laboratory of experimental medicine. SUBJECTS: Male Sprague-Dawley rats weighing 300 to 350 g. INTERVENTIONS: Modified, highly purified, and heat-pasteurized hemoglobin (diaspirin crosslinked hemoglobin) in control and yohimbine-treated (2 mg/kg i.v.) rats. MEASUREMENTS AND MAIN RESULTS: The systemic hemodynamics and regional circulation were measured using a Radioactive Microsphere technique. Diaspirin crosslinked hemoglobin (400 mg/kg i.v.) produced an increase in blood pressure and total peripheral resistance, while heart rate, cardiac output, and stroke volume were not significantly altered in control rats. In yohimbine-pretreated (2 mg/kg i.v.) animals, diaspirin crosslinked hemoglobin did not produce any change in heart rate, stroke volume, cardiac output, and total peripheral resistance, but a slight increase in blood pressure was observed compared with baseline values obtained after the administration of yohimbine. The increase in blood pressure induced by diaspirin crosslinked hemoglobin was significantly blocked by pretreatment with yohimbine. Yohimbine (2 mg/kg i.v.) per se decreased blood pressure, while other systemic hemodynamic parameters were not affected. Diaspirin crosslinked hemoglobin increased blood flow to the heart, gastrointestinal tract (stomach, small intestine, cecum, and large intestine), portal (spleen, mesentery, and pancreas) and skin, while blood flow to the brain (cerebral hemispheres, diencephalon, cerebellum, and brain stem), liver, kidneys, and musculoskeletal system was not affected in control rats. In yohimbine-pretreated animals, diaspirin crosslinked hemoglobin produced an increase in blood flow to the heart, brain (cerebellum and brain stem), liver, small intestine, cecum, spleen, mesentery and pancreas, kidneys, skin and musculoskeletal system, while blood flow to the stomach and large intestine was not affected. Yohimbine pretreatment significantly attenuated the diaspirin crosslinked hemoglobin-induced increase in blood flow to the large intestine, mesentery, and pancreas. CONCLUSIONS: The cardiovascular actions of diaspirin crosslinked hemoglobin are partially mediated through alpha 2-adrenergic receptors. Adrenergic receptor antagonists may be useful in attenuating the pressor effect of diaspirin crosslinked hemoglobin while maintaining the regional perfusion.
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effect of stroma free hemoglobin and diaspirin cross linked hemoglogbin on the regional circulation and systematic hemodynamics
Life Sciences, 1994Co-Authors: Anil Gulati, Avadhesh C. Sharma, Kenneth E BurhopAbstract:Abstract The effects of unmodified stroma-free hemoglobin (SFHb) and diaspirin cross-linked hemoglobin (DCLHb) on the regional blood circulation and systematic hemodynamics were studied in rats using a Radioactive Microsphere technique. SFHb and DCLHb increased mean arterial blood pressure without affecting heart rate. SFHb produced a 24.9 % decrease in the cardiac output while DCLHb produced an 44.8 % increase in the cardiac output. Stroke volume was decreased (−27.3 %) by SFHb and increased (+36.4 %) by DCLHb. Total peripheral resistance increased with both SFHb and DCLHb. DCLHb increased blood flow to the heart, spleen, stomach, small intestine and skin, and had no effect on blood flow to the brain, kidneys, liver, mesentery, pancreas, caecum, large intestine and musculo-skeletal system. In contrast, in animals infused with SFHb, blood flow decreased to the kidneys, liver and spleen, increased to the heart, small intestine and skin, and had no effect to the brain, caecum, large intestine and musculo-skeletal system. DCLHb had no effect on vascular resistance in any organ except for an increase in the musculo-skeletal system. In contrast, SFHb increased vascular resistance in the kidneys, liver, spleen, skin, mesentery and pancreas, and had no effect on vascular resistance in the musculo-skeletal system, brain, heart, stomach, small intestine, caecum and large intestine. SFHb had no effect on distribution of cardiac output to the brain, gastrointestinal tract (GIT), kidneys, skin, musculo-skeletal and portal system, while DCLHb significantly decreased the percent cardiac output to the musculo-skeletal system. DCLHb did not affect the distribution of cardiac output to the brain, GIT, kidneys, skin and portal system. SFHb and DCLHb increased the percent cardiac output to the heart. It is concluded that similar concentrations and doses of DCLHb and SFHb produce different effects on the regional blood circulation and systematic hemodynamics.
D M Van Winkle - One of the best experts on this subject based on the ideXlab platform.
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fluorescent vs Radioactive Microsphere measurement of regional myocardial blood flow
Cardiovascular Research, 1995Co-Authors: G L Chien, C G Anselone, R F Davis, D M Van WinkleAbstract:Objectives: This study compared simultaneous regional myocardial blood flow (RMBF) measurements using fluorescent Microspheres (FM) and radiolabeled Microspheres (RM). The utility of an internal standard during processing was also examined. Methods: Paired FM and RM were injected into the left atrium of 9 anaesthetised rabbits. RMBF was altered by use of either regional ischaemia or (−)- N 6-(2-phenylisopropyl)-adenosine. Radioactivity of blood reference and tissue samples was quantitated using standard methods. Samples were then digested with potassium hydroxide and Microspheres recovered by vacuum filtration, with an additional label of FM as the internal standard. FM labels were extracted using Carbitol® acetate and quantitated using fluorescence spectroscopy. Agreement between the fluorescent and Radioactive methods was assessed using both orthogonal regression and difference-against-mean analyses. Results: Using recovery- un corrected data, the slope of the orthogonal regression of RM and FM-determined RMBF was not statistically different from 1, but the intercept was statistically different from 0 [−0.03(0.01), P = 0.005] and the mean RMBF by each method differed from one another [1.24(0.08) vs. 1.17(0.08) ml · min−1 · g−1, P = 0.0002]. The mean ±2 s.d. of the differences of RMBF (RM minus FM) was +0.07 ± 0.30 ml · min−1 · g−1. Although recovery of FM from tissue averaged 97.6(1.2)%, use of the internal standard to correct for losses substantially improved the agreement between RM and FM-determined RMBF: the orthogonal regression slope was not statistically different from 1, the intercept was not statistically different from 0, and the means of the flows were not different. The mean ±2 s.d. of the differences of RMBF was −0.01 ± 0.22 ml · min−1 · g−1. The internal standard also improved RMBF estimates from samples with simulated large spillage during processing. Conclusion: Fluorescent Microspheres are an equivalent alternative to radiolabeled Microspheres for the estimation of RMBF. Although the overall recovery of Microspheres using this technique was high, use of an internal standard is recommended for correction of random losses.
Andres T Blei - One of the best experts on this subject based on the ideXlab platform.
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cerebral hyperemia and nitric oxide synthase in rats with ammonia induced brain edema
Journal of Hepatology, 2001Co-Authors: Jeanne Gottstein, Fin Stolze Larsen, Andres T BleiAbstract:Abstract Background/Aim : Brain edema is a common fatal complication in acute liver failure. It is related to an acute change in brain osmolarity secondary to the glial accumulation of glutamine. Since high cerebral blood flow (CBF) precedes cerebral herniation in fulminant hepatic failure we first determined if an increase in brain water and glutamine are prerequisite to a rise in CBF in a model of ammonia-induced brain edema. Secondly, we determined if such a cerebral hyperperfusion is mediated by nitric oxide synthase (NOS). Methods : Male rats received an end-to-side portacaval anastomosis (PCA). At 24 h, they were anesthetized with ketamine and infused with ammonium acetate (55 μ M/kg per min). Studies were performed at 60, 90, 120, 150 and 180 min after starting the ammonia infusion and once the intracranial pressure had risen three-fold (mean 210′). Brain water (BW) was measured using the gravimetry method and CBF with the Radioactive Microsphere technique. Glutamine (GLN) in the CSF was sampled via a cisterna magna catheter. The neuronal NOS was specifically inhibited by 1-2-trifluoromethylphenyl imidazole (TRIM, 50 mg/kg intraperitoneally) and in separate studies nonspecifically by N -omega-nitro- l -arginine ( l -NNA, 2 μ g/kg per min intravenously) Results : At 90′, brain water was significantly increased ( P r =0.88, n =36, P l -NNA did not prevent the development of cerebral hyperperfusion and edema. Conclusion : We observed that cerebral hyperemia follows an initial rise in brain water content, rather than in the cerebrospinal fluid concentration of glutamine. The rise in CBF further correlated with brain water accumulation and was of critical importance for the development of intracranial hypertension. The unique mechanism for the rise in CBF in hyperammonemia was not prevented by NOS inhibition indicating that NO is not the mediator of high CBF and intracranial hypertension.
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cerebral blood flow and the hyperdynamic circulation of rats after portacaval anastomosis
Journal of Hepatology, 1993Co-Authors: Amit Srivastava, Jeanne Gottstein, Andres T BleiAbstract:Both increased and decreased values of cerebral blood flow have been reported in liver disease. Furthermore, the relation between the cerebral circulation and the generalized hemodynamic disturbance seen in chronic liver disease with portal-systemic shunting has not been fully characterized. We studied this problem in a well defined model of the hyperdynamic circulation, the rat after portacaval anastomosis (PCA). Using the Radioactive Microsphere technique, cardiac output and regional blood flows were measured; regional vascular resistances were then calculated. While the fraction of cardiac output perfusing the splanchnic bed was significantly increased, the corresponding brain fraction was reduced. Blood flow to the cerebral hemispheres and midbrain was significantly decreased. Arterial vasodilatation was demonstrated by the fall in arterial pressure, systemic vascular resistance as well as splanchnic and renal resistances; cerebrovascular resistance, however, was unchanged. No relation between values of arterial pressure and cerebral blood flow was seen, making a failure of cerebrovascular autoregulation unlikely. The decrease in hemispheric and midbrain perfusion without changes in vascular resistance suggests that a drop in blood flow is appropriately coupled to a reduction in brain metabolism. The cerebral circulation does not participate in the hyperdynamic state that is seen in this model.
Daniel L Traber - One of the best experts on this subject based on the ideXlab platform.
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increased organ blood flow in chronic endotoxemia is reversed by nitric oxide synthase inhibition
Journal of Applied Physiology, 1994Co-Authors: Jorg Meyer, Frank Hinder, Joseph C Stothert, L D Traber, David N Herndon, John T Flynn, Daniel L TraberAbstract:We evaluated regional blood flows in a hyperdynamic sepsis model and the reversal of increased flows by blockade of nitric oxide (NO) synthase. Seven awake sheep were continuously infused with Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1] for 48 h. The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg) was injected after 24 h. Blood flows to systemic organs were determined with the Radioactive Microsphere technique. LPS induced elevation of cardiac index by 36% (P < 0.05) and a fall in systemic vascular resistance index by 37% (P < 0.05) at 0 h [time of L-NAME administration, 24 h after infusion of LPS had begun] L-NAME administration normalized cardiac index [6.1 +/- 0.5 at 4 h posttreatment, 6.1 +/- 0.5 l.min-1.m-2 at -24 h (baseline)] and systemic vascular resistance index (1,333 +/- 105 at 4 h posttreatment, 1,280 +/- 163 dyn.s.cm-5.m2 at -24 h) and reduced all regional blood flows to near-baseline levels for the remainder of the study period (24 h). O2 consumption was unaffected by treatment.