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Biomedical subjects

R I Cohen

Publications and source records attributed to R I Cohen.

31 records · Page 2Linked to original sources
PubMed1996

A comparison between the acute effects of nitric oxide synthase inhibition and fluid resuscitation on myocardial function and metabolism in entotoxemic dogs.

PURPOSE: Nitric oxide (NO) synthase inhibitors increase mean arterial pressure (MAP) and systemic vascular resistance (SVR) in animal models of sepsis and in humans with septic shock. However, NO synthase inhibitors may cause coronary vessel constriction leading to myocardial ischemia and increased mortality in endotoxemic animals. This study was designed to test the acute effect of NG-nitro-L-arginine (L-NAME) on left ventricular (LV) function and coronary blood flow in a dog model of endotoxemia. METHODS: In open chest, anesthetized dogs endotoxemia was induced intravenously (IV) by Escherichia coli lipopolysaccharide at 2 mg/kg for 60 minutes. This resulted in hypotension, acidosis, and decreased SVR while cardiac index (CI) was maintained. When MAP was < or = 60 mm Hg, animals were resuscitated with either dextran (group I), or L-NAME 30 mg/kg IV bolus (group II). Group III received L-NAME only. A fourth group of dogs was given endotoxin and not resuscitated. Animals were followed up for 30 minutes after intervention. Animals in the fourth group were followed up until the MAP was approximately 30 mm Hg. Heart rate, CI, MAP, LV end systolic and diastolic pressures, dP/dt at a pressure of 40 mm Hg, left anterior descending artery coronary blood flow, regional LV contraction (sonomicrometer crystals), coronary pressures, gas tension, and lactates were continuously recorded. A catheter placed in the coronary sinus allowed measurement of coronary sinus pressure, as well as coronary sinus lactate and gas tensions. Stroke volume index, stroke work index, systemic vascular resistance index (SVRI), coronary vascular resistance, percent myocardial shortening, myocardial oxygen consumption (Mvo2) and net myocardial lactate production were calculated. RESULTS: In Group I, fluid administration increased MAP, stroke work index, coronary blood flow, percent myocardial shortening, and Mvo2. In Group II, L-NAME increased MAP to the same extent as fluid administration without evidence of coronary ischemia or myocardial dysfunction. L-NAME did not alter Mvo2 in either endotoxemic or nonendotoxemic animals. In group III, L-NAME alone resulted in a significant increase in MAP and SVRI, but its effects on coronary blood flow and LV function were not significant. We did not observe net lactate production in any of the groups. Coronary blood flow increased out of proportion to Mvo2 in group I animals. CONCLUSIONS: We conclude that although L-NAME at 30 mg/kg causes vasoconstriction, its effects on coronary blood flow and LV function were not significant.

Animals↗
PubMed1996

The effects of high dose NG-nitro-L-arginine-methyl ester on myocardial blood flow and left ventricular function in dogs.

PURPOSE: Nitric oxide (NO) synthase inhibition has been reported to cause elevation in mean arterial pressure (MAP) and a decrease in cardiac index (CI), the cause of which is not completely understood. It has been shown that increased concentrations of NO synthase inhibitors cause a further drop in cardiac output without a corresponding increase in arterial pressure, prompting the conclusion that NO inhibition results in direct myocardial depression. However, myocardial ischemia was not completely ruled out as a cause for myocardial dysfunction in these studies. The purpose of this study was to examine the effects of 30 mg/kg of the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) to those of 300 mg/kg and assess the effects on coronary ischemia and myocardial function. MATERIALS AND METHODS: Eight anesthetized dogs underwent median sternotomy and pericardiectomy. L-NAME 30 mg/kg was administered and the effects were recorded at 5, 15, and 30 minutes. Thereafter, 300 mg/kg was administered and the effects were observed for 5, 15, and 30 minutes. We measured MAP, heart rate (HR), CI, left ventricle (LV) and systolic and diastolic pressures, the first derivative of LV pressure (dP/dt), left anterior descending artery blood flow, regional LV contraction, gas tensions, and lactates. A coronary sinus catheter allowed for measurements of coronary sinus pressure, lactate, and gas tensions. Stroke volume, percent myocardial shortening (dL/dt) myocardial oxygen consumption, and net lactate myocardial production were calculated. RESULTS: Whereas 30 mg/kg had minimal effects on coronary blood flow and LV function, 300 mg/kg resulted in profound hypotension, drop in CI, and acidocsis. CONCLUSIONS: L-NAME at 30 mg/kg caused a rise in MAP and systemic vascular resistance; however, it had no effect on ventricular function. High dose NO synthase inhibition causes myocardial depression not related to increased afterload, coronary vasoconstriction, or myocardial ischemia.

Animals↗
PubMed1995

Single- and multiple-dose pharmacokinetics of dezocine in patients with acute or chronic pain.

The pharmacokinetic properties of dezocine were examined in 15 patients with acute or chronic pain. In 3 groups of 5 patients each, serum levels were determined at various intervals after single intravenous doses of 5, 10, and 20 mg. After these single doses, dezocine was very rapidly distributed (mean t1/2 alpha less than 2 minutes), and then rather rapidly eliminated (mean t1/2 beta about 4 hours); the apparent volume of distribution was large (mean Vz beta about 6 L/kg) as was the total clearance (mean CL about 1.5 L/h/kg). In 2 groups of 5 patients each, serum levels were determined after the first and third of 3 intravenous doses of 5 or 20 mg given at 3-hour intervals. The pharmacokinetic parameters after these multiple doses were consistent with those after the single doses. Although some observations were suggestive, there was no unequivocal evidence that the pharmacokinetics were dose-related. In 7 serum samples containing dezocine at concentrations ranging from 12.8 to 522 ng/mL, the mean (+/- SE) proportion of dezocine bound to protein was 91.6 +/- 0.8%.

Acute Disease↗
PubMed1994

Rat oligodendrocytes express muscarinic receptors coupled to phosphoinositide hydrolysis and adenylyl cyclase.

Muscarinic receptors expressed by rat oligodendrocyte primary cultures were examined by measuring changes in second messengers following exposure to carbachol, an acetylcholine analog, and by polymerase chain reaction. Inositol phosphate levels were measured in [3H]myo-inositol-labelled young oligodendrocyte cultures following stimulation with carbachol. Atropine, a specific muscarinic antagonist, prevented the carbachol-induced accumulation of inositol phosphates. The formation of inositol trisphosphate was concentration- and time-dependent, with the peak at 100 microM carbachol and 10 min. Carbachol increased intracellular calcium levels, which were dependent both on the mobilization of intracellular stores and influx of extracellular calcium. In initial experiments with more selective antagonists, the mobilization of intracellular calcium was preferentially inhibited by pirenzepine, a selective M1 antagonist, but not methoctramine, a selective M2 antagonist, suggesting M1 muscarinic receptor involvement. A role for protein kinase C in the regulation of carbachol-stimulated inositol phosphate formation and intracellular calcium mobilization was demonstrated, as acute pretreatment with phorbol-12,13-myristate acetate abolished the formation of both second messengers. Pretreatment with 100 microM carbachol abolished the 40% increase in the cyclic AMP accumulation stimulated by isoproterenol, a specific beta-adrenergic agonist. In turn, the inhibition was alleviated by pretreatment with atropine, suggesting muscarinic receptor involvement. Polymerase chain reaction carried out with specific m1 and m2 muscarinic receptor oligonucleotide primers, confirmed that these cells express, at least, the two muscarinic receptor subtypes. Without excluding the expression of other subtypes, these results suggest that developing oligodendrocytes express m1 (M1) and m2 (M2) muscarinic receptors capable of mediating phosphoinositide hydrolysis, mobilization of intracellular calcium and the attenuation of beta-adrenergic stimulation of cyclic AMP formation.

Adenylyl Cyclases↗
PubMed1993

Serial intravenous doses of dezocine, morphine, and nalbuphine in the management of postoperative pain for outpatients.

Adult patients who had arthroscopic surgery under general anesthesia and requested postoperative pain relief were randomized to receive treatment in a double-blind protocol with 5 mg of intravenous dezocine (20 patients), morphine (22 patients), nalbuphine (18 patients), or saline (24 patients). At 10-min intervals, starting with the first dose of analgesic, patients could choose up to three additional doses of the primary treatment, or choose an alternative analgesic if the primary drug was unsatisfactory. One to four doses of morphine were given as the alternate treatment if the initial treatment was dezocine or nalbuphine, and one to four doses of dezocine were given if the initial treatment was saline or morphine. The proportion of patients treated successfully by the initial treatments (i.e., not requesting alternate treatment), with P value for difference from placebo treatment, were saline 25%, nalbuphine 33% (P = 0.048), morphine 54% (P = 0.04), and dezocine 75% (P = 0.003). Dezocine and morphine are more efficacious than nalbuphine in the management of early postoperative pain. As an alternate analgesic in this study, dezocine required fewer doses to achieve patient satisfaction and was thus more efficacious than morphine. The incidence of treatment-related, adverse effects was different from that of saline or other treatments only for nalbuphine-related pain or burning on injection and dezocine-related facial itching. With respect to analgesic actions and side effects, dezocine seems more like morphine than nalbuphine.

Adult↗
PubMed1993

Norepinephrine-stimulated PI hydrolysis in oligodendrocytes is mediated by alpha 1A-adrenoceptors.

Oligodendrocyte progenitors were labelled with [3H]-myo-inositol in order to determine the effect of adrenergic agents on the accumulation of [3H]-inositol phosphates (InsP). Both norepinephrine and phenylephrine, a selective alpha 1-adrenoceptor agonist, increased the formation of [3H]-InsP, while isoproterenol, a beta-adrenoceptor agonist, did not. Propranolol (beta) and yohimbine (alpha 2), two adrenoceptor antagonists, had no significant effect on the NE-stimulated [3H]-InsP formation. By contrast, the response to NE was significantly blocked by phenoxybenzamine and the alpha 1-receptor antagonist, prazosin. Pretreatment with chloroethylclonidine, which selectively inactivates alpha 1B receptors, had no effect on NE-induced [3H]-InsP formation, while WB4101 had high potency in inhibiting this response. Pertussis toxin, which inactivates certain G-proteins, caused a approximately 60% reduction. NE-stimulated formation of [3H]-InsP depended on extracellular calcium influx, because it was decreased by 55% and 75% by chelation with EGTA or the addition of 1 mM CdCl2, respectively. These results suggest that oligodendrocyte progenitors express alpha 1-adrenoceptors characteristic of the alpha 1A subtype.

Adrenergic alpha-Agonists↗
PubMed1985

Controlled trial of Iodosorb in chronic venous ulcers.

Cadexomer iodine (Iodosorb) is a hydrophilic starch powder containing iodine, which is a suitable dressing for granulating wounds such as venous ulcers. A total of 61 outpatients with chronic venous ulcers participated in a randomised optional crossover trial using cadexomer iodine or a standard dressing for their ulcers. The trial lasted for 24 weeks or until the ulcer had healed. Two patients withdrew during the course of the trial. Both treatments were highly effective, but the epithelium of ulcers dressed with cadexomer iodine grew again significantly faster (p less than 0.001). At the midpoint of the trial (12th week) 13 of 30 patients receiving standard treatment were changed to cadexomer iodine, while only three of 29 receiving cadexomer iodine changed to the standard dressing (p less than 0.02). In most cases ulcers were dressed and rebandaged daily by the patients themselves after instruction and supervision. This may be better than having dressings and bandages applied by professionals less regularly.

Adult↗