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Biomedical subjects

S M Muldoon

Publications and source records attributed to S M Muldoon.

At least 55 records · Page 3Linked to original sources
PubMed1985

In vitro responses of cat skeletal muscle to halothane and caffeine.

Strips of soleus (100% type I) and gracilis (90% type II) muscle were obtained from anesthetized cats and mounted in organ baths filled with aerated Krebs-Ringer solution (37 degrees C). The contractile patterns in response to electrical stimulation (0.1 Hz, 25 V, 5 ms), caffeine, halothane, and caffeine in the presence of halothane were examined in the two fiber types. The ability of 25 microM dantrolene to alter the contractile patterns was also evaluated. In vitro contractile properties in response to electrical stimulation were similar to properties observed in situ, except that twitch tension in soleus muscle was significantly less in vitro than in situ. In the presence of halothane, type I soleus muscle developed a rapid contracture. The contracture was blocked by pretreatment with dantrolene and was reversed by addition of dantrolene at the peak of the response. Halothane-induced contractures were not observed at any time in type II gracilis. Type I soleus was also significantly more sensitive both to caffeine alone and to caffeine in the presence of halothane than was type II gracilis. In both fiber types, halothane increased the sensitivity of the muscles to caffeine. Dantrolene attenuated caffeine-induced contractures in both fiber types, but the attenuating effect was less in the presence of halothane. The findings of a halothane-induced contracture in the cat soleus and differential sensitivities of the two muscle fiber types to caffeine indicate that further studies in these two muscles may be useful for delineating the mechanisms inducing contracture in muscle from individuals susceptible to malignant hyperthermia.

Animals↗
PubMed1985

The effect of etidocaine on spontaneous and evoked release of norepinephrine from rat brain synaptosomes.

Local anesthetics have been shown to have an effect on neurotransmission. In this study we examined the effect of a local anesthetic, etidocaine, on the uptake, efflux, and release of norepinephrine (NE) from central nerve terminals. The studies were performed on synaptosomes and vesicles prepared from rat brains. Etidocaine 10(-4) M inhibited synaptosomal accumulation of [3H]NE and did not significantly effect vesicular accumulation of this neurotransmitter. This concentration of etidocaine also augmented efflux of norepinephrine from synaptosomal preparations. This augmented efflux was primarily due to an increase in the deaminated metabolite 3,4-dihydroxyphenylglycol (DOPEG). The presence of etidocaine did not significantly alter the release of NE from synaptosomes superfused with high potassium (40 mM), a calcium-dependent exocytotic release process. These results indicate that in the central nervous system, as previously demonstrated in the peripheral nervous system, high concentrations of etidocaine alter vesicular storage of NE, resulting in more NE leaking into the cytoplasm where it is metabolized to an inactive metabolite.

Acetanilides↗
PubMed1985

Nalbuphine's reversal of hypovolemic shock in the anesthetized rat.

Nalbuphine is an agonist-antagonist analgesic chemically related to the opiate agonist oxymorphone and to the opiate antagonist naloxone. Because naloxone has been shown to be beneficial in hemorrhagic shock, this study was undertaken to investigate the hemodynamic effects of nalbuphine in anesthetized rats. The animals were bled 1% of body weight, which caused a significant decrease in mean arterial pressure (MAP) and heart rate (HR). Results indicate an immediate increase in MAP and HR above posthemorrhage values in the rats treated with 1 and 5 mg/kg nalbuphine compared with no improvement for the rats in the saline-treated group. The increases in MAP were sustained for periods up to 120 min postadministration of nalbuphine. Measurements of cardiac output and regional distribution of blood flow indicate that nalbuphine caused an increase in cardiac output, heart rate, stroke volume, and dP/dt with no change in total peripheral resistance.

Anesthesia↗
PubMed1984

Reversal of the antinociceptive effects of centrally-administered morphine by the benzodiazepine receptor antagonist Ro 15-1788.

The effects of the benzodiazepine receptor antagonist, Ro 15-1788, were examined on analgesia induced by morphine after central (intracerebroventricular, i.c.v., or intrathecal, i.t.) and systemic administration. Analgesia was assessed in squirrel monkeys trained to respond under an electric shock titration procedure and in mice using the radiant heat tail-flick test. Central and systemic administration of morphine produced antinociceptive effects that were antagonized by 0.1 mg/kg of naloxone in both species. Ro 15-1788 antagonized the effects of morphine after central (i.c.v. or i.t.) administration but did not alter the effects of morphine given by the systemic route. This novel interaction suggests that Ro 15-1788 may be useful in pharmacologically separating neural substrates subserving opiate analgesia.

Animals↗
PubMed1984

Electrodiagnostic tests in the detection of malignant hyperthermia.

Malignant hyperthermia (MH) can be a catastrophic and sometimes fatal reaction in certain susceptible individuals who are exposed to skeletal muscle relaxants such as succinylcholine and/or certain inhalation anesthetics such as halothane. In an attempt to develop a safe, simple in vivo test to identify the at-risk patients, repetitive nerve stimulation (RNS) and electromyographic (EMG) studies were performed on 9 patients with MH, 15 patients suspected of having MH, and 9 control subjects. Serial recordings were made following injections of caffeine sodium benzoate, succinylcholine, and halothane at the test site. Measurements were done on the amplitude of the evoked compound motor action potentials (CMAP), on RNS, and on the number of negative peaks of motor unit potentials (MUP) on maximum EMG recruitment. The results showed the effects of the drugs on amplitudes of the CMAPs to be significant (P less than 0.001) in all three groups, but no significant differences were found among the groups (P = 0.93). The negative peaks of MUP on EMG recording showed a significant difference upon introducing succinylcholine (P less than 0.001), and significant interaction effects of the treatment by the patient group. Preliminary comparisons of in vivo tests with in vitro contracture tests in nine patients showed good correlation.

Adolescent↗
PubMed1984

Plasma histamine and hemodynamic responses following administration of nalbuphine and morphine.

A comparative study of plasma histamine levels following administration or morphine and nalbuphine in pentobarbital anesthetized dogs was performed. Two concentrations, 3 mg/kg and 0.3 mg/kg of these drugs were investigated. High dose morphine caused an immediate marked increase in plasma histamine from 5.0 +/- 0.4 to 340 +/- 72 ng/ml. Simultaneous with this increase in plasma histamine was a marked decrease in mean arterial blood pressure within the first minute. In contrast significant alterations in plasma histamine levels were not observed with high or low doses of nalbuphine. A low dose of morphine (0.3 mg/kg) did not increase plasma histamine levels. Heart rate was not changed by any drug treatment. The use of compound 48/80 a specific mast cell degranulating agent allowed for the identification of a specific pool of mast cells capable of responding to morphine. In vitro exposure of purified dog leukocytes to high doses of morphine did not result in histamine release. These results indicate that nalbuphine does not increase plasma histamine, while morphine does, and that the source of the increase in plasma histamine is from tissue mast cells.

Anesthesia↗
PubMed1983

Partial isolation of an endogenous norepinephrine uptake inhibitor in canine plasma.

We have previously reported that homologous plasma inhibits the accumulation of [3H]norepinephrine ( [3H]NE) by the canine saphenous vein. The purpose of this study was to extract the inhibitory substance(s) from plasma and to examine some of its properties. The net accumulation of tritium by saphenous vein strips following incubations in [3H]NE was inhibited 34.4 +/- 6.1% by a 60% plasma in Krebs solution. An acetone extract of this plasma reconstituted to 83% of its original unextracted volume also significantly inhibited net tritium accumulation by 24.5 +/- 4.7%. After lyophilization of this extract, the inhibitor was not readily solubilized in dilute acetic acid but was soluble in dilute sodium bicarbonate solutions. This extract solution, reconstituted to 66% of the original plasma volume, significantly inhibited the accumulation of [3H]NE by 35.0 +/- 9.8%. Kinetic analysis using this preparation suggests that the inhibition may be competitive in nature. The activity was not sensitive to heat but was abolished by the neuronal uptake blocker cocaine. Further purification with gel chromatography produced a small molecular weight fraction that inhibited tritium accumulation. When this sample was reconstituted in a volume equivalent to that of the unextracted plasma, the contractile response of the isolated canine saphenous vein to electrical stimulation was significantly enhanced. Thus the inhibitory activity of plasma on the uptake of [3H]NE by the canine saphenous vein is due in part to a heat-stable small molecule that inhibits the initial rate of [3H]NE uptake.

Animals↗
PubMed1982

Determination of morphine in cerebrospinal fluid and plasma by high-performance liquid chromatography with electrochemical detection.

Two methods for the extraction of morphine from cerebrospinal fluid or plasma with quantitation by high-performance liquid chromatography with electrochemical detection were compared for accuracy, precision and ease of preparation. One procedure was a standard extraction procedure and the other utilized a commercially available liquid-liquid extraction column. Both methods produced linear calibration curves over the concentration range of 1-200 ng/ml with coefficients of correlation of 0.999. Since the electrochemical detector is capable of detecting 20 pg of morphine, biological samples as small as 0.1 to 0.4 ml can be quantified with an average relative precision of 4.1 +/- 3.9% over the concentration range 1-200 ng/ml. The potential clinical importance of the assay is demonstrated using a time course distribution study of morphine in the cerbrospinal fluid and plasma of a Rhesus monkey.

Animals↗
PubMed1982

Accumulation of [3H]norepinephrine in canine saphenous vein: influence of plasma.

This study was designed to systematically characterize the neuronal and extraneuronal uptake systems for norepinephrine (NE) in isolated nerve-rich vascular tissue and then to explore the possibility that circulating factors may alter these uptake systems. Strips from canine saphenous vein were incubated in Krebs-Ringer solution containing L-[3H]NE, and both tissue and medium were analyzed for total tritium, [3H]NE, and [3H]metabolite content. Under these conditions neuronal uptake (uptake1) played the dominant role in NE disposition. The addition of cocaine, ouabain, or potassium or the reduction of sodium decreased the activity of uptake1, and extraneuronal uptake (uptake 2) then played a major role in NE metabolism. The addition of 30, 60, and 90% plasma reduced NE accumulation and 3,4-dihydroxyphenylglycol (DOPEG) formation to 71 and 62% of control values, respectively; the formation of normetanephrine (NMN) and O-methylated deaminated compounds (OMDA) was not significantly different. In the presence of cocaine and uptake 1 inhibitor, 30% plasma did not cause a further significant decrease in neuronal accumulation of NE. The inhibitory activity of plasma on NE accumulation was not significantly affected by boiling or standing at room temperature for 45 min. These studies show that in the isolated canine saphenous vein the addition of plasma, like low sodium, cocaine, or ouabain, decreases neuronal uptake. The identity of the component in plasma responsible for inhibition of NE uptake appears to be a nonprotein, heat-stable molecule.

Animals↗
PubMed1981

Epidural morphine following epidural local anesthesia: effect on ventilatory and airway occlusion pressure responses to CO2.

The authors measured the minute inspired ventilation (VI) and airway occlusion pressure (P 100) responses to CO2 during rebreathing in ten patients who were given epidural morphine for analgesia following lower extremity or lower abdominal surgery. All patients were studied and blood samples for morphine analysis were obtained at four different times: preoperatively, postoperatively premorphine, and one and six hours after a single 10-mg epidural dose of preservative-free morphine in 10 ml of saline. All patients reported effective analgesia with a duration ranging from 8-25.5 h. There were no differences between the pre- and postoperative VI vs. PCO2 and P100 vs. PCO2 response slopes, indicating that the epidural local anesthetic alone had no effect on respiratory drive. Administration of 10 mg morphine epidurally caused a significant 22 per cent decrease in the average VI vs. PCO2 slope and a 33 per cent decrease in the average P100 vs. PCO2 slope one hour postmorphine when compared to the postoperative slopes. The average decrease in VI vs. PCO2 at 6 h postmorphine was not significant. The average P100 vs. PCO2 response slope was decreased significantly at 6 h postmorphine by 27 per cent. There was no significant correlation between serum morphine concentration and the ventilatory responses. The authors conclude that morphine administered by the epidural route produces decreased respiratory drive and that there is a high degree of individual variability in the magnitude and time course of this effect.

Adult↗
PubMed1981

Effects of fentanyl on adrenergic function in canine coronary arteries.

The effects of fentanyl on sympathetic nerve endings in canine coronary arteries have been examined. Measurements were made of change in endogenous norepinephrine in isolated coronary artery in the presence of fentanyl, and of the effects of fentanyl on norepinephrine release and metabolism using superfused strips of coronary arteries in which transmitter stores had been prelabeled with [3H]norepinephrine. [3H]Norepinephrine and its 3H metabolites were separated from samples of superfusate (physiologic salt solution flowing continuously over the prelabeled coronary artery) by column chromatography and measured by scintillation spectrometry. The addition of fentanyl (2 x 10(-6) and 8 x 10(-6) M) caused the overflow of total radioactivity (radiolabeled norepinephrine and radiolabeled metabolites of norepinephrine entering the superfusate) to increase significantly above basal levels in both unstimulated and electrically stimulated arteries. The increased overflow could be accounted for by a small increase in norepinephrine and a sizeable increase in 3,4-dihydroxyphenylglycol, the metabolite arising from the intraneuronal metabolism of norepinephrine. Because this metabolite is without agonist activity and the increases in norepinephrine were small, fentanyl in the concentrations studied had minimal effects on adrenergic neurotransmission in this vascular bed.

Animals↗
PubMed1980

Disposition of norepinephrine during nerve stimulation in dog saphenous vein.

The relative importance of neuronal and extraneuronal uptake in the disposition of norepinephrine (NE) released by electrical stimulation (ES) from adrenergic nerves in isolated dog saphenous vein was determined. Helical strips of vein were incubated in L-[7-(3)H]NE (1 x 10(-6)M) and mounted for superfusion. Superfusate was collected continuously before, during, and after ES (10 V; 2 ms; 1, 2, and 5 Hz). Measurements were made of [3H]NE and its metabolites in vein and in superfusate. Previous studies have established that 3,4-dihydroxyphenylglycol (DOPEG) is of neuronal origin and O-methylated metabolites (OMM) are of extraneuronal origin. Thus, extraneuronal uptake was estimated directly by measuring the amounts of OMM in superfusate, and neuronal uptake followed by metabolism was estimated by measuring [3H]DOPEG. The magnitude of the neuronal uptake fraction that enters vesicles for reuse was estimated from the compensatory increases in [3H]NE and in OMM when neuronal uptake was blocked. Similar amounts of released NE were taken up by neuronal uptake, by extraneuronal uptake, and diffused out of the synaptic cleft. Between 5-20% of the released NE was sequestered in vesicles for reuse.

Adrenergic Fibers↗
PubMed1979

Measurement of endogenous norepinephrine overflow from canine saphenous veins.

A method for the measurement of norepinephrine (NE) overflow from isolated superfused canine saphenous veins is described. This method involves concentrating NE present in the superfusate, followed by measurement of its concentration by high-performance liquid chromatography with electrochemical detection. The limit of sensitivity of the method (defined as a signal-to-noise ratio of 5) was 25 pg. NE concentration measured by this method correlated well (r = 0.95) with that measured by standard fluorometric methods. Electrical stimulation caused an initial overflow of a mean of 115 X 10(-18) mol NE/mg of vein per pulse; this was associated with an increase in isometric tension. With continued stimulation, less NE overflowed into the superfusate, although tension was not reduced appreciably.

Animals↗
PubMed1979

Increased reactivity of isolated rabbit saphenous vein after treatment with estrogen and progesterone.

The effect of estrogen and progesterone on the reactivity of isolated rabbit saphenous veins to adrenergic stimulation by norepinephrine, methoxamine, phenylephrine, and electrical stimulation and the effect of progesterone on the reactivity to barium ions were studied. 8 days after ovariectomy, a saphenous vein was removed and studied in vitro. After 1 and 4 days of hormone therapy, the contralateral vein was removed and its reactivity was compared with that of the first vein and with that of veins from untreated, sham-operated control animals. The reactivity to adrenergic and noradrenergic stimulation was increased after 4 days of treatment with progesterone (5 mg/day); treatment for 4 days with estrogen (100 micrograms/day) increased the reactivity to norepinephrine, electrical stimulation, methoxamine, and phenylephrine. The results with progesterone suggest that the increased adrenergic responsiveness is not related to a mechanism controlling adrenergic transmission in veins.

Animals↗