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Biomedical subjects

J N Bates

Publications and source records attributed to J N Bates.

At least 19 recordsLinked to original sources
PubMed1992

Does epidural fentanyl decrease the efficacy of epidural morphine after cesarean delivery?

Earlier studies have suggested that epidural fentanyl improves intraoperative analgesia during cesarean section, but others have suggested that it worsens postoperative analgesia from epidural morphine. The purpose of this study was to determine whether epidural fentanyl given before epidural morphine improves the quality of intraoperative epidural anesthesia without worsening postoperative analgesia provided by epidural morphine. Sixty patients having epidural anesthesia for cesarean delivery were studied. Epidural anesthesia was established using 2% lidocaine with epinephrine 5 micrograms/mL. After delivery, either fentanyl 100 micrograms/10 mL or normal saline-control 10 mL was injected through the epidural catheter in a randomized, double-blind manner. All patients received 3.5 mg of morphine epidurally after uterine repair. After administration of the epidural study drug, there were no significant differences in the pain responses during surgery between the two groups. Patients in the fentanyl group experienced significantly less nausea and vomiting between delivery and the end of surgery than did patients in the normal saline-control group (P = 0.013). Postoperatively, visual analogue scale scores for pain, pruritus, nausea, and sedation were similar at 1, 2, 4, and 8 h in the two groups. We conclude that fentanyl 100 micrograms administered epidurally during cesarean delivery did not improve intraoperative analgesia, but significantly reduced intraoperative nausea and vomiting without diminishing the efficacy of postoperative analgesia provided by epidural morphine.

Adult↗
PubMed1991

Nitric oxide generation from nitroprusside by vascular tissue. Evidence that reduction of the nitroprusside anion and cyanide loss are required.

Nitric oxide (NO) was produced from sodium nitroprusside in the presence of vascular tissue but was not released spontaneously from the nitroprusside anion. In the absence of tissue in the dark nitroprusside did not release NO. When solutions of nitroprusside alone were irradiated with visible light, nitric oxide was released at rates linearly proportional to nitroprusside concentration and light intensity. Nitric oxide was produced from solutions of nitroprusside in the dark after the addition of vascular tissue, including lengths of rabbit aorta, subcellular fractions of aorta, and human plasma. NO was also released from nitroprusside after reaction with various reducing agents including cysteine and other thiols, ascorbic acid, sodium dithionite, ferrous chloride, hemoglobin, myoglobin, and partially purified cytochrome P450 with an NADPH-regenerating system. HCN was simultaneously produced in these solutions, and addition of KCN blocked NO release. Iodine oxidized intermediate cyanoferrates and blocked nitric oxide release. KCN or iodine also blocked NO production by tissue, but had no effect upon photochemical NO release. These results show that, apart from photolysis which makes no physiological contribution, release of nitric oxide from nitroprusside, in simple solutions and in biological tissue, occurs after nitroprusside has undergone reduction and lost cyanide.

Animals↗
PubMed1991

Effects of nitric oxide on platelet-activating factor- and alpha-adrenergic-stimulated vasoconstriction and glycogenolysis in the perfused rat liver.

Effects of nitric oxide (NO) on hemodynamic and glycogenolytic responses to platelet-activating factor (PAF) and phenylephrine were investigated in perfused livers derived from fed rats. Infusion of NO (34 microM) into perfused livers inhibited PAF (0.22 nM)-induced increases in hepatic glucose output and portal pressure approximately 90 and 85%, respectively, and abolished effects of PAF on hepatic oxygen consumption. NO attenuated PAF-stimulated increases in glucose output and portal pressure, the latter indicative of hepatic vasoconstriction, with a similar dose dependence with an IC50 of approximately 8 microM. In contrast to its effects on PAF-induced responses in the perfused liver, NO inhibited increases in hepatic portal pressure in response to phenylephrine (10 microM) approximately 75% without altering phenylephrine-stimulated glucose output and oxygen consumption. Similarly, infusion of NO into perfused livers significantly inhibited increases in hepatic portal pressure but not in glucose output in response to a submaximal concentration of phenylephrine (0.4 microM). Like NO, sodium nitroprusside (83 microM) significantly inhibited hemodynamic but not glycogenolytic responses to phenylephrine in perfused livers. However, PAF (0.22 nM)-stimulated alterations in hepatic portal pressure, glucose output, and oxygen consumption were unaffected by infusion of sodium nitroprusside (83 microM) into perfused livers. These results provide the first evidence for regulatory effects of NO in the perfused liver and support the contention that PAF, unlike phenylephrine, stimulates glycogenolysis by mechanisms secondary to hepatic vasoconstriction. These observations raise the intriguing possibility that NO may act in liver to regulate hemodynamic responses to vasoactive mediators.

Adrenergic alpha-Antagonists↗
PubMed1991

EDRF: nitrosylated compound or authentic nitric oxide.

Endothelium-derived factor (EDRF) from bovine aortic endothelial cells was compared to solutions of authentic nitric oxide (NO) and to solutions of the nitrosothiol S-nitroso-L-cysteine. EDRF was produced from endothelial cells by basal release or by stimulation with the calcium ionophore A23187. Biological activity was measured as relaxation of porcine coronary arteries preconstricted with prostaglandin F2 alpha, and chemical analysis was made of the nitrosyl content by measurement of NO released after chemical reduction with 1% sodium iodide in glacial acetic acid. EDRF, NO, and nitrosocysteine had identical half-lives, were all inactivated by hemoglobin and methylene blue, and were all augmented in their biological activity by superoxide dismutase. When solutions were analyzed for their biological activity as a function of the NO content (after NaI/acetic acid reduction), nitrosocysteine showed more vasodilation per amount of contained NO than did authentic NO. Solutions containing EDRF (basal release or by stimulation with A23187) subjected to the same analysis appeared similar to nitrosocysteine, and were distinct from solutions of NO. These experiments show that nitrosyl compounds other than NO can have properties very similar or identical to EDRF, and that in this system EDRF appears more similar to nitrosocysteine than to NO.

Animals↗
PubMed1991

Nitric oxide: mediator of nonadrenergic noncholinergic responses of opossum esophageal muscle.

Nonadrenergic noncholinergic (NANC) nerves of the opossum esophagus mediate relaxation of circular muscle from the lower esophageal sphincter (LES) and the off contraction of circular esophageal muscle. The latencies between the end of the stimulus and the off contraction describe a gradient so that the latency is longest in muscle from the caudad esophagus. NG-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide (NO) synthase, and NO were used to test the hypothesis whether NO is a mediator of these nerve-induced responses. Both electrical field stimulation (EFS) of intrinsic esophageal nerves and exogenous NO relaxed LES muscle. Only EFS-induced relaxation was inhibited by L-NNA [half-maximal response (EC50) = 60.0 +/- 20.0 microM]. L-Arginine, the substrate for NO synthase, reversed the inhibitory effect of L-NNA. Exogenous NO did not contact circular esophageal muscle. Both the amplitude (EC50 = 14.7 +/- 4.0 microM) and the latency of the off contraction (EC50 = 41.1 +/- 5.6 microM) were diminished by L-NNA. L-Arginine prevented the action of L-NNA. NG-nitro-L-arginine also attenuated the gradient in the latency of the off response by shortening latencies in muscle from the caudad esophagus. It had no effect on cholinergic nerve-induced contraction of longitudinal esophageal muscle. These data support the hypothesis that NO or an NO-containing compound may be a mediator of NANC nerve-induced responses of the esophagus and LES.

Animals↗
PubMed1991

Nitric oxide: mediator of NANC hyperpolarization of opossum esophageal smooth muscle.

Activation of intrinsic nonadrenergic noncholinergic (NANC) esophageal nerves during peristalsis or by electrical field stimulation (EFS) in vitro produces a hyperpolarization followed by a depolarization of the circular smooth muscle of the opossum esophagus. N omega-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase, and nitric oxide (NO) were used to test the hypothesis that NO or a NO-containing compound is a mediator of this NANC nerve-induced hyperpolarization of circular esophageal smooth muscle. The transmembrane potential difference of esophageal circular smooth muscle cells was recorded with glass microelectrodes. Nerve-mediated membrane responses were evoked by single electrical pulses of 0.5 ms duration and 50 V amplitude. L-NNA abolished the initial hyperpolarization and reduced the amplitude of and the time to maximal depolarization. L-Arginine (1 mM), the substrate for NO synthase, antagonized the effect of L-NNA. Exogenous NO produced hyperpolarization of the smooth muscle membrane potential and attenuated the amplitudes of EFS-induced hyperpolarization and depolarization. The effect of NO was blocked neither by L-NNA nor by tetrodotoxin (1 microM). The data support the hypothesis that NO or a NO-containing compound mediates NANC nerve-induced responses of the esophageal smooth muscle membrane.

Amino Acid Oxidoreductases↗
PubMed1991

Mechanisms responsible for the heterogeneous coronary microvascular response to nitroglycerin.

Nitroglycerin dilates large (greater than or equal to 100 microns) but not small coronary arterial microvessels, and a putative metabolite of nitroglycerin, S-nitroso-L-cysteine, has been shown in vitro to dilate both large and small coronary microvessels. Based on this evidence, we tested the hypothesis that the lack of response of small coronary microvessels was due to an inability of small coronary microvessels to convert nitroglycerin into its vasoactive metabolite and examined possible explanations for this phenomenon. We studied left ventricular epicardial microvessels in vivo using video microscopy and stroboscopic epi-illumination in anesthetized, open-chest dogs. Diameters were determined while the epicardium was suffused with nitroglycerin, S-nitroso-L-cysteine, or S-nitroso-D-cysteine (all 10 microM) and nitroglycerin in the presence of L- or D-cysteine (100 microM). None of the agents affected systemic hemodynamics. Nitroglycerin dilated large arterioles (20 +/- 2%) but not small arterioles (1 +/- 1%). Both S-nitroso-L-cysteine and S-nitroso-D-cysteine were potent dilators of all size classes of microvessels. Concomitant application of L-cysteine and nitroglycerin evoked dilation in small microvessels (22 +/- 4%, p less than 0.5 versus nitroglycerin alone) and larger microvessels (27 +/- 6%, p = NS versus nitroglycerin alone). D-Cysteine did not alter the microvascular response to nitroglycerin in either small (7 +/- 4%, p = NS versus nitroglycerin alone) or large (18 +/- 3%, p = NS versus nitroglycerin alone) microvessels. Neither L-cysteine nor D-cysteine had a direct effect on microvascular diameter. These findings suggest that 1) sulfhydryl groups are required for the conversion of nitroglycerin to its vasoactive metabolite; 2) the interaction between nitroglycerin and sulfhydryl residues is a stereospecific process, indicating either an intracellular mechanism or a membrane-associated enzymatic reaction; and 3) a lack of available sulfhydryl groups may be responsible for the lack of response of small coronary arterioles to nitroglycerin.

Analysis of Variance↗
PubMed1990

Is there a role for an endothelium-derived relaxing factor in nociception?

Many of the circulating algesic agents released in response to ischemia produce a profound vasodilatation possibly through the release of an endothelium-derived relaxing factor (EDRF) as well as pain. We report here that intravenously administered S-nitrosocysteine, a putative EDRF, and not the nitric oxide liberating compound sodium nitroprusside produces significant alterations in nociceptive behavior that are abolished by bilateral vagotomy. These results are consistent with a role for EDRF in peripheral nociceptive mechanisms.

Analysis of Variance↗
PubMed1990

Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide.

Studies of cultured bovine aortic endothelial cells using quantitative chemiluminescence techniques have shown that the amount of nitric oxide released under basal conditions, or in response to either bradykinin or the calcium ionophore A23187 is insufficient to account for the vasorelaxant activities of the endothelium-derived relaxing factor (EDRF) derived from the same source. This observation contradicts previous suggestions that nitric oxide and EDRF are the same compound, but may be explained if EDRF is a compound that contains nitric oxide within its structure but is a much more potent vasodilator than nitric oxide. Such a molecule could be one of several nitrosothiols which may yield nitric oxide after a one-electron reduction. The present experiments were carried out to test the possibility that the biological activities of the endothelium-derived relaxing factor might more closely resemble those of one of these compounds, S-nitrosocysteine, than nitric oxide. Nitric oxide release from cultured bovine aortic endothelial cells was detected by chemiluminescence and bioassay experiments compared the vasodilator potencies of nitric oxide, S-nitrosocysteine, and EDRF. The results suggest that EDRF is much more likely to be a nitrosylated compound such as a nitrosothiol than authentic nitric oxide.

Animals↗
PubMed1990

Continuous epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor.

A randomized, double-blind, placebo-controlled study was performed to evaluate the analgesic efficacy and influence of continuing an epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor in nulliparous women. When the cervix was fully dilated, coded study solution was substituted for the known bupivacaine-fentanyl solution. The study solution for 29 patients was 0.0625% bupivacaine-0.0002% fentanyl; 34 patients received saline placebo. The two groups had similar pain scores during the first stage of labor. During the second stage, pain scores were significantly higher in the saline-placebo group at each 30-min interval between 60 and 150 min after the diagnosis of full cervical dilation. Similarly, there was a significant difference between the two groups in global assessment of analgesia quality during the second stage, but the difference occurred in those patients with a second-stage duration of greater than or equal to 60 min. Among the women who delivered vaginally, eleven of 28 (39%) women in the bupivacaine-fentanyl group, versus five of 34 (15%) in the saline-placebo group, had surgical perineal anesthesia for vaginal delivery (P less than .05). Six of 28 (21%) women in the bupivacaine-fentanyl group, and five of 34 (15%) in the saline-placebo group, underwent instrumental vaginal delivery (P = NS). The median duration of the second stage of labor was 53 min (range = 5-283) in the bupivacaine-fentanyl group, and 63 min (range = 16-181) in the saline-placebo group (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1990

Influence of vessel size on the sensitivity of porcine coronary microvessels to nitroglycerin.

The responses of small (60-100 microns), medium (101-190 microns), and large (191-300 microns) porcine coronary microvessels to nitroglycerin were examined in vitro using a video-imaging apparatus. Large coronary microvessels, preconstricted with acetylcholine, relaxed by 90% in response to nitroglycerin, whereas small microvessels relaxed only 20% to nitroglycerin. Responses to putative metabolites of nitroglycerin, S-nitrosocysteine, and nitric oxide, were also examined. S-Nitrosocysteine produced equal relaxations in all sizes of coronary microvessels. Nitric oxide was 10 times more potent in large coronary arteries than in small but produced greater than 90% relaxation of all sizes of coronary microvessels at the highest concentrations. Bradykinin and the calcium ionophore A23187, which release endothelium-derived relaxing factor (EDRF), produced similar relaxation in small, medium, and large microvessels. The compound LY 83583 (which depletes vascular guanylate cyclase) reduced responses to nitroglycerin, nitric oxide, S-nitrosocysteine, bradykinin, and the calcium ionophore A23187 in microvessels of all sizes. Our data are compatible with the concept that nitroglycerin must undergo reductive processing to exert its vasodilator effect, likely through the formation of nitrosothiols. In small coronary microvessels, this biotransformation of nitroglycerin is diminished compared with larger coronary arteries. This may be caused by a relative deficiency of available sulfhydryl groups or a lack of enzymes necessary for conversion of nitroglycerin to its active metabolites in small coronary resistance vessels.

Animals↗
PubMed1990

Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta.

We examined the hypothesis that impaired endothelium-dependent vasodilation in atherosclerosis is associated with decreased synthesis of nitrogen oxides by the vascular endothelium. The descending thoracic aortae of rabbits fed either normal diet, a high cholesterol diet for 2-5 wk (hypercholesterolemic, HC), or a high cholesterol diet for 6 mo (atherosclerotic, AS) were perfused in a bioassay organ chamber with physiologic buffer containing indomethacin. Despite a dramatic impairment in the vasodilator activity of endothelium-dependent relaxing factor (EDRF) released from both HC and AS aortae (assessed by bioassay), the release of nitrogen oxides (measured by chemiluminescence) from these vessels was not reduced, but markedly increased compared to NL. Thus, impaired endothelium-dependent relaxation in atherosclerosis is neither due to decreased activity of the enzyme responsible for the production of nitrogen oxides from arginine nor to arginine deficiency. Because the production of nitrogen oxides increased in response to acetylcholine in both hypercholesterolemic and atherosclerotic vessels, impairments in signal transduction are not responsible for abnormal endothelium-dependent relaxations. Impaired vasodilator activity of EDRF by cholesterol feeding may result from loss of incorporation of nitric oxide into a more potent parent compound, or accelerated degradation of EDRF.

Animals↗
PubMed1989

The influence of pH-adjusted 2-chloroprocaine on the quality and duration of subsequent epidural bupivacaine analgesia during labor: a randomized, double-blind study.

A randomized, double-blind study was performed to determine whether pH-adjustment of 2-chloroprocaine hastens the onset of epidural analgesia, and improves the quality and duration of subsequent epidural bupivacaine analgesia during labor. One milliliter of either 8.4% sodium bicarbonate or normal saline was added to a 30-ml vial of 2% 2-chloroprocaine. At 0, 5, and 7 min, each patient received 2, 5, and 3 ml of 2-chloroprocaine, respectively. At 22 min, any patient who did not yet have satisfactory analgesia received an additional 5 ml of 2-chloroprocaine. At 35, and, again, at 36 min, each patient received 5 ml of 0.25% bupivacaine. The median onset of 2-chloroprocaine analgesia was slightly more rapid in the bicarbonate group than in the saline-control group (12 versus 14 min, P less than .05). Two of 31 women in the bicarbonate group, versus 10 of 31 women in the saline-control group, required an additional 5 ml of 2-chloroprocaine at 22 min to achieve satisfactory analgesia (P = .01). There was no significant difference between groups in median duration of subsequent bupivacaine analgesia (60 min in each group) or mean (+/- SD) dosage of bupivacaine during the first stage of labor (64 +/- 43 versus 72 +/- 57 mg). Also, there was no significant difference between groups in pain scores over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia, Epidural↗
PubMed1989

Metoclopramide versus droperidol for prevention of nausea and vomiting during epidural anesthesia for cesarean section.

In a randomized, double-blind study, we compared the efficacy of metoclopramide hydrochloride with that of low-dose droperidol for prevention of nausea and vomiting during and after elective cesarean section with epidural anesthesia. Immediately after the umbilical cord was clamped, each patient received fentanyl (50 micrograms) and the study drug intravenously over 30 to 60 seconds. In one study group, 40 women received metoclopramide (15 mg); in the other group, 41 women received droperidol (0.5 mg). Twelve women (30%) in the metoclopramide group, versus eight (20%) in the droperidol group, had intraoperative, postdelivery nausea (P = NS). One woman (3%) in the metoclopramide group, versus two women (5%) in the droperidol group, had intraoperative, postdelivery vomiting (P = NS). During the first four postoperative hours, five women (12%) in each group complained of nausea. Three women (7%) in each group had postoperative vomiting. We conclude that metoclopramide (15 mg) and droperidol (0.5 mg) were similarly effective.

Adult↗
PubMed1987

Stimulatory effects of halothane and isoflurane on fluoride release and cytochrome P-450 loss caused by metabolism of 2-chloro-1,1-difluoroethene, a halothane metabolite.

The structural similarity of the halothane metabolite, 2-chloro-1,1-difluoroethene (CDE), to haloethenes that are metabolized by and inactivate cytochrome P-450, suggests that CDE may undergo secondary metabolism and degrade these isozymes. This possibility was examined in hepatic microsomes by determining fluoride release and cytochrome P-450 loss due to CDE metabolism in the presence of several anesthetics. CDE alone decreased cytochrome P-450 from phenobarbital-treated rats by as much as 37%, but the addition of isoflurane or halothane to incubations containing CDE increased the loss of cytochrome P-450 nearly twofold. Fluoride release was enhanced approximately 2.5 to 3 times by halothane or isoflurane; however, fluroxene inhibited fluoride release and did not enhance the loss of cytochrome P-450. Extrapolation of these results to the clinical situation suggests that the metabolism of CDE produced during halothane anesthesia and the accompanying cytochrome P-450 loss may contribute to the inhibition of drug metabolism produced by halothane.

Animals↗
PubMedDate not supplied

Metabolism of 2-chloro-1,1-difluoroethene to glyoxylic and glycolic acid in rat hepatic microsomes.

The complete metabolic fate of the volatile anesthetic halothane is unclear since 2-chloro-1,1-diflurorethene (CDE), a reductive halothane metabolite, is known to readily release inorganic fluoride upon oxidation by cytochrome P-450. This study sought to clarify the metabolism of CDE by determining its metabolites and the roles of induce cytochrome P-450 forms in its metabolism. Upon incubation of [14C]CDE with rat hepatic microsomes, two major radioactive products were found which accounted for greater than 94% of the total metabolites. These compounds were determined to be the nonhalogenated compounds, glyoxylic and glycolic acids, which were formed in a ratio of approximately 1 to 2 of glyoxylic to glycolic acid. No other radioactive metabolites could be detected. Following incubation of CDE with hepatic microsomes isolated from rats treated with cytochrome P-450 inducers, measurement of fluoride release showed that phenobarbital induced CDE metabolism to the greatest degree at high CDE levels, isoniazid was the most effective inducer at low CDE concentrations, and beta-naphthoflavone was ineffective as an inducer. These results suggest that CDE biotransformation primarily involves the generation of an epoxide intermediate, which undergoes mechanisms of decay leading to total dehalogenation of the molecule, and that this metabolism is preferentially carried out by the phenobarbital- and ethanol-inducible forms of cytochrome P-450.

Animals↗
PubMedDate not supplied

Comparative defluorination and cytochrome P-450 loss by the microsomal metabolism of fluoro- and fluorochloroethenes.

Halogenated ethenes are oxidatively metabolized by cytochrome P-450 to intermediates which inactivate cytochrome P-450 by destroying heme and to epoxides which may react with cellular macromolecules or decompose to other products. To determine the relative capabilities of fluoroethenes to inactivate cytochrome P-450 and undergo metabolism, fluoride release, cytochrome P-450 loss, and heme loss due to the metabolism of trifluorochloroethene (TFCE), chlorodifluoroethene (CDE), difluoroethene (DFE), and trifluoroethene (TFE) were compared in rat hepatic microsomes. Fluoride release, in order of decreasing amounts of fluoride released, followed the order: CDE greater than TFCE much greater than TFE greater than DFE. In contrast, in order of each compound's decreasing effectiveness to destroy both cytochrome P-450 and heme, the following sequence was obtained: TFE greater than CDE greater than TFCE greater than DFE. In phenobarbital-induced hepatic microsomes, TFE inactivated up to 67% of the cytochrome P-450, whereas DFE inactivated only up to 17%. The results of this study indicate that chloro substituents enhance defluorination of the ethenes, and that cytochrome P-450 inactivation by the fluoroethenes is highly dependent on the degree and nature of the halogen substituents.

Animals↗