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Biomedical subjects

J E Cottrell

Publications and source records attributed to J E Cottrell.

At least 19 recordsLinked to original sources
PubMed1992

The barbiturate thiopental reduces ATP levels during anoxia but improves electrophysiological recovery and ionic homeostasis in the rat hippocampal slice.

The barbiturate anesthetic thiopental enhances recovery of the evoked population spike recorded from rat hippocampal slices after short periods of anoxia. Thiopental reduces changes in sodium, potassium and calcium but enhances the fall in ATP levels during anoxia. The postsynaptic population spike recorded from the CA1 pyramidal cell region of the slices treated with thiopental (600 microM) recovered to 67% of the preanoxic amplitude after 3.5 min of anoxia. There was less recovery (24%) when a lower concentration of thiopental (250 microM) was used. Untreated slices recovered to only 10% of their preanoxic amplitude after 3.5 min of anoxia. Other studies have demonstrated that maintaining ATP levels during anoxia may be an important mechanism of protection. In contrast to those studies, thiopental was protective although it enhanced the fall of ATP levels after 3.5 min of anoxia in the CA1 region and after 3.5 and 5 min in the dentate region. Thus enhanced recovery of the population spike with thiopental is not due to its preservation of ATP levels. This result allows a clear separation of improved ATP levels during anoxia from other mechanisms of protection. We therefore looked for other mechanisms of protection. Sodium and potassium levels were measured after 10 min of anoxia. In untreated tissue, sodium levels in the slice rose and potassium levels fell significantly. In thiopental-treated tissue, changes in sodium and potassium caused by anoxia and by veratridine under normoxic conditions were significantly reduced. During anoxia calcium-45 uptake increases; thiopental significantly reduces this uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Midazolam improves electrophysiologic recovery after anoxia and reduces the changes in ATP levels and calcium influx during anoxia in the rat hippocampal slice.

Since blockers of excitatory transmission have been shown to reduce anoxic and ischemic neuronal damage, augmentation of inhibitory transmission by agents such as midazolam might have a similar protective effect. Rat hippocampal slices were maintained in vitro and used to determine whether and by what mechanism midazolam improves recovery of evoked responses after anoxia. The Schaffer collateral pathway in the slice was stimulated electrically, and an extracellular potential, the evoked population spike, was recorded from the CA1 pyramidal cells, which are postsynaptic. The slices were made anoxic by substituting artificial cerebrospinal fluid aerated with 95% nitrogen-5% carbon dioxide for fluid aerated with 95% oxygen-5% carbon dioxide. Percentage recovery was expressed as the amplitude of the evoked population spike 60 min after anoxia divided by its preanoxic amplitude. Protection in this model is defined as a significant (P less than 0.05) improvement in percentage recovery compared to the recovery of untreated slices. There was no recovery of the response recorded from CA1 pyramidal cells after 5 min of anoxia (4 +/- 2%) (mean +/- standard error of the mean [SEM]). Slices were treated with midazolam 10 min before, during, and 10 min after anoxia. Midazolam (1 microM) did not enhance recovery after anoxia when dissolved either in water (3 +/- 3%) or in dimethyl sulfoxide (DMSO) (1 +/- 1%). A higher concentration of midazolam (100 microM) did enhance recovery when dissolved in DMSO (27 +/- 7%) but not when dissolved in water (5 +/- 2%). To test whether prolonged pretreatment with midazolam dissolved in water would enhance recovery, slices were treated for 30 min prior to anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Paraben preservatives do not increase intracranial pressure in cats.

It has been hypothesized recently that succinylcholine-associated increases in intracranial pressure (ICP) are caused by the paraben preservatives contained in multidose vials. We tested that hypothesis in a standard feline model to determine the effects on ICP of equal-volume injections of preservative-free succinylcholine, succinylcholine with preservatives from multi-dose vials that contain both propylparaben and methylparaben, these preservatives alone at five times the dose contained in the succinylcholine, and normal saline. The preservatives alone increased ICP by 0.08 +/- 0.08 mmHg (+/- standard error; not significant). Normal saline had no effect on ICP. Preservative-free succinylcholine and succinylcholine with preservatives increased ICP by 4.2 +/- 0.10 and 3.8 +/- 0.07 mmHg respectively (P less than 0.01 compared to the preservatives alone and normal saline). The 99% upper confidence limit for the increase in ICP induced by the preservatives alone was 0.42 mmHg. This result suggests that parabens do not cause or substantially augment the ICP increase associated with succinylcholine administration.

Animals↗
PubMed1989

Treatment of intraoperative hypertensive emergencies in patients with intracranial disease.

In patients with neuropathologic processes leading to disturbed cerebrovascular autoregulation, sudden increases in arterial blood pressure may lead to a sudden elevation in cerebral blood flow and intracranial pressure. Therefore, sudden increases in arterial pressure should be assiduously avoided in the perioperative period. Hypertensive episodes may occur at any time during anesthesia, but are more likely to occur (1) during laryngoscopy and intubation, (2) at the time of skin incision, (3) at extubation, and (4) during awakening. In patients with cardiovascular disease, such hypertensive episodes may also cause deterioration of the cardiovascular situation. Catecholamines are the principal mediators of such intraoperative hypertensive reactions. There are 2 options available to the anesthesiologist: (1) attempt to suppress this response after it has occurred, or (2) prevent its occurrence at the outset. Treatment of hypertension often relies on agents that relax vascular smooth muscle. In patients with compromised intracranial compliance, however, cerebral vasodilation must be avoided because it leads to an increase in cerebral blood volume. This, in turn, may raise intracranial pressure and result either in herniation of brain contents or a decrease in cerebral perfusion pressure leading to brain ischemia. Different pharmacologic means of preventing or suppressing such intraoperative hypertensive reactions are reviewed. Many of the drugs reviewed resulted in adverse effects that could preclude their use in patients with reduced intracranial compliance. Alpha- and beta-adrenergic receptor blockers can safely be administered to such patients.

Antihypertensive Agents↗
PubMed1989

The N-methyl-D-aspartate antagonists aminophosphonovaleric acid and MK-801 reduce anoxic damage to dentate granule and CA1 pyramidal cells in the rat hippocampal slice.

The effect of the N-methyl-D-aspartate antagonists, aminophosphonovaleric acid and MK-801, on irreversible transmission loss subsequent to anoxia was examined using the hippocampal slice preparation. A population spike was recorded from either the dentate granule cells or the CA1 pyramidal cells and the amplitude of this spike was compared before and 60 min following anoxia. After 10 min of anoxia the dentate granule cells recovered to 16 +/- 7% (mean +/- SE) of their preanoxic level when untreated and to 54 +/- 15% when treated with aminophosphonovaleric acid (APV). In slices treated with MK-801 the population spikes recorded from dentate granule cells recovered to 85 +/- 4% of their preanoxic level after 10 min of anoxia. Untreated CA1 pyramidal cells recovered to 8 +/- 3% of their preanoxic amplitude after 5 min of anoxia; they recovered to 59 +/- 6% when treated with MK-801 and 31 +/- 13% when treated with APV. The recovery of slices treated with the drugs was significantly different from that of untreated slices. ATP levels were measured in both the dentate and the CA1 region of slices. ATP in both regions fell less during anoxia when the slices were pretreated with either APV or MK-801. These differences between drug-treated and untreated tissue were significant with APV and MK-801. These differences between drug-treated and untreated tissue were significant with APV and MK-801 in dentate tissue after 10 min of anoxia and with MK-801 in CA1 tissue after 5 min of anoxia. This reduced fall in ATP during anoxia was accompanied by better physiological recovery after anoxia. We conclude that these NMDA antagonists provide protection against anoxic damage to dentate granule and CA1 pyramidal cells in this in vitro hippocampal preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1989

Methods for studying the effect of anesthetics on anoxic damage in the rat hippocampal slice.

The rat hippocampal slice was used as a model system to study the effects of anesthetics on anoxic damage. Thiopental, but not isoflurane, allowed recovery of the postsynaptic population spike evoked from the dentate granule cells. Creatine preincubation protected both dentate granule and CA1 pyramidal cells against anoxic damage. Calcium-free, 10 mM magnesium artificial cerebrospinal fluid (ACSF) was shown to protect CA1 pyramidal cells against anoxic damage. The presynaptic population spike recovered to its preanoxic amplitude after anoxia even under conditions where the postsynaptic population spike demonstrated no recovery. Thus the hippocampal slice is a useful system for studying the effects of anesthetics and other pharmacological agents on anoxic damage.

Action Potentials↗
PubMed1989

The effect of blocking sodium influx on anoxic damage in the rat hippocampal slice.

The in vitro rat hippocampal slice was used to study the effect of tetrodotoxin, a sodium channel blocker, on anoxic damage. Tetrodotoxin improved recovery of the evoked population spike after anoxia and reduced the fall in adenosine 5'-triphosphate during anoxia. Electrophysiological responses to perforant pathway stimulation were recorded in the dentate granule cell layer before, during and after 10 min of anoxia, with and without tetrodotoxin. Preincubation with tetrodotoxin permitted recovery of the evoked population spike to 43 +/- 10% (mean +/- standard error) in the post-anoxic period; this compared to 3 +/-3% recovery in untreated tissue (P less than 0.005). Similar studies of the CA1 pyramidal cells, which are more sensitive to anoxia, showed that tetrodotoxin improved recovery of the postsynaptic response after 5 min of anoxia. The recovery was 69 +/- 15% of its pre-anoxic level when treated with tetrodotoxin. This compares to no recovery in untreated tissue (P less than 0.005). Biochemical studies demonstrated a significantly reduced fall in adenosine 5'-triphosphate levels during levels in the dentate granule cell layer fell to 1.4 nM/mg dry wt, whereas following treatment with tetrodotoxin they only fell to 2.2 nM/mg. Since it required only 5 min of anoxia to damage the CA1 pyramidal cells, adenosine 5'-triphosphate levels were measured in this region after 5 min of anoxia. Adenosine 5'-triphosphate levels in the CA1 region fell to 2.2 nM/mg in untreated tissue after 5 min of anoxia, compared to 2.9 nM/mg in the tetrodotoxin-treated tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

Rate of induction of hypotension with trimetaphan modifies the intracranial pressure response in cats.

An infusion of 0.1% trimetaphan was administered to eight cats with artificially increased intracranial pressure (ICP) in order to decrease their mean arterial pressure (MAP) from 121 +/- 9.5 (SEM) to 58 +/- 4.6 mm Hg in less than 1 min. All cats developed an increase in intracranial pressure (ICP) (from 16 +/- 1.4 to 23 +/- 3.2 mm Hg) accompanied by a partial rebound in MAP. Eight additional cats received 0.1% trimetaphan to decrease their MAP from 128 +/- 13.4 to 52 +/- 8.1 mm Hg over more than 2 min. Four of these cats followed the same pattern, with ICP increases from 19 +/- 1.1 to 31 +/- 3.9 mm Hg, while in the other four ICP did not change. In nine of the 12 cats with an ICP increase, that increase was initiated before the partial MAP rebound. We conclude that trimetaphan causes clinically significant ICP increases in cats with increased ICP, that partial rebound in MAP frequently exacerbates these increases in ICP, and that rapid induction of hypotension tends to increase the frequency with which trimetaphan increases ICP.

Animals↗
PubMed1988

Magnesium and cobalt, not nimodipine, protect neurons against anoxic damage in the rat hippocampal slice.

Brain tissue, maintained in vitro, was used to determine whether agents that block calcium entry into neurons can improve the recovery of evoked responses after anoxia. The hippocampus was dissected from a rat brain and sliced perpendicular to its long axis such that its main neuronal circuits remain functional. A pathway in the slice was stimulated electrically, and an extracellular potential, the evoked population spike, recorded from the neurons postsynaptic to that pathway. A bipolar stimulating electrode was placed in either the perforant path or the Schaeffer collaterals and a monopolar metal microelectrode placed, respectively, in either the dentate granule cell layer or the CA1 pyramidal cell layer. The slices were maintained in vitro by superfusing them with oxygenated (95% O2, 5% CO2) artificial cerebrospinal fluid (aCSF). In order to generate anoxia, the tissue was superfused with aCSF bubbled with 95% N2, 5% CO2 for either 5 or 10 min. All drugs examined were present in the aCSF before, during, and immediately after the anoxic period. Percentage recovery was expressed as the amplitude of the evoked population spike 60 min after anoxia divided by its preanoxic amplitude. Protection in this model is defined as a significant (P less than 0.05) improvement in percentage recovery compared with the recovery of untreated slices. There was no recovery of the response recorded from untreated dentate granule cells after 10 min of anoxia (0 +/- 0%, n = 5; mean +/- SE), whereas 5 min of anoxia was sufficient to cause damage to the untreated CA1 pyramidal cells (4 +/- 3%, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Anesthetic protection against anoxic damage in the rat hippocampal slice.

Evoked population spikes were recorded from the dentate granule cell layer of hippocampal slices obtained from adult rats. These slices were subjected to short periods of anoxia in the presence of different anesthetics. The recovery of the population spike after anoxia was compared across treatments. Little or no recovery was found after 10 min of anoxia when no anesthetic (4 +/- 4%), 1.5% isoflurane (5 +/- 5%), or 15% isoflurane (0 +/- 0%) was present during the anoxic periods. However, the population spike did recover to 81 +/- 7% of its preanoxic amplitude within 1 h after the anoxia if thiopental 160 mg/liter was present in the perfusate during the anoxia. Fifteen percent isoflurane and 160 mg/liter thiopental were equipotent in reducing the amplitude of the evoked population spike before anoxia but only thiopental protected against the damage after 10 min of anoxia. Our results suggest that the blocking of the evoked population spike by thiopental is not the sole mechanism of its protection against anoxic damage. Isoflurane (1.5%) was able to provide a small degree of protection against shorter periods (7 min) of anoxia.

Animals↗
PubMed1987

Effect of alpha-tocopherol and free radicals on anoxic damage in the rat hippocampal slice.

The effect of alpha-tocopherol on irreversible transmission loss subsequent to anoxia was examined using the hippocampal slice preparation. A population spike was recorded from the dentate granule cell layer after stimulation of the perforant path. The amplitude of the population spike was compared before and after anoxia. Control slices recovered to 22 +/- 7% of their preanoxic amplitude after 7 min of anoxia. Slices treated with alpha-tocopherol showed significantly greater recovery after anoxia (P less than 0.001). The population spike recovered to 64 +/- 15% of its preanoxic amplitude. As alpha-tocopherol is a free radical scavenger, our results provide evidence that free radicals are partly responsible for irreversible anoxic damage. alpha-Tocopherol is not toxic and may prove efficacious in protecting the brain against anoxic damage.

Animals↗
PubMed1987

Nitrous oxide reduces thiopental-induced prolongation of survival in hypoxic and anoxic mice.

Arnfred's mouse model was used to test the effect of thiopental during hypoxia (5% O2) and anoxia, with and without simultaneous administration of nitrous oxide. As found by Arnfred and others, thiopental without N2O more than doubled survival time during hypoxia (from 5.2 +/- 0.6 to 13.9 +/- 2.6 min). This effect was completely offset by simultaneous use of N2O (from 13.9 +/- 2.6 to 4.8 +/- 0.7 min). Thiopental without N2O also increased survival time during complete anoxia (from 26 +/- 1 to 59 +/- 1 sec). This effect was diminished by 58% when N2O was added (from 59 +/- 1 to 40 +/- 1 sec). We conclude that nitrous oxide diminishes the effect of barbiturates upon survival time in hypoxic and anoxic mice.

Animals↗
PubMed1986

In vitro induction of somatic cell hybridization by the local anesthetic chloroprocaine.

Chloroprocaine, an aminoester local anesthetic commonly used for epidural block, has been found to induce interspecies somatic cell hybrids in vitro. Mixed cultures of human amniocytes and mouse hepatoma cells, deficient in hypoxanthine phosphoribosyl transferase, were exposed to 1.6, 0.8, or 0.4 X 10(-3)M chloroprocaine for 3 hr at 37 degrees C, then maintained for 3 weeks in a double-selective medium of hypoxanthine, aminopterin, and thymidine (HAT) and ouabain to eliminate the unfused parental cells. Clones of actively multiplying cells appeared in cultures exposed to 1.6 and 0.8 X 10(-3)M chloroprocaine. Chromosome analysis confirmed they were hybrids. Cultures treated with 0.8 X 10(-3)M chloroprocaine exhibited the highest frequency of cell hybridization (8.8 X 10(-5). The hybrid clones bore the morphologic characteristics of both parents although their growth pattern closely resembled the mouse parent. Procaine, sodium bisulfite (the antioxidant present in the commercial solutions of chloroprocaine), and the two chloroprocaine metabolites, chloroaminobenzoic acid and diethylaminoethanol, were nonfusogenic. The hybridogenic effect of chloroprocaine has not been previously described with other local anesthetics.

Animals↗
PubMed1986

Effect of vecuronium on intracranial pressure, mean arterial pressure and heart rate in cats.

The effect of vecuronium on intracranial pressure (ICP) was investigated in six cats with normal and increased ICP. Cats were anaesthetized with pentobarbitone 33 mg kg-1 i.p. and acepromazine 0.6 mg kg-1 i.p., the trachea was intubated, and the lungs ventilated with nitrous oxide in oxygen. Mean arterial pressure (MAP), heart rate (HR), twitch response and ICP were recorded continuously. After the effect of vecuronium had been ascertained under the condition of normal ICP, and after full recovery of twitch response, pH-adjusted Ringer's lactate solution was infused to the cisterna magna until an ICP baseline of 26 +/- 2 mm Hg was established, and had stabilized. Vecuronium was administered again to determine its effect under the condition of increased ICP. Complete ablation of twitch response was obtained in 68 +/- 15 s with vecuronium 80 micrograms kg-1, and there was no significant change in ICP, MAP, HR or cerebral perfusion pressure (CPP) under either ICP condition.

Animals↗
PubMed1985

Comparison of metaproterenol, isoetharine and salbutamol in the relief of methacholine-induced bronchospasm in dogs.

We evaluated cardiovascular effects and effectiveness of isoetharine, metaproterenol and salbutamol, when administered intratracheally to relieve methacholine-induced bronchospasm in dogs anaesthetized with 50 per cent nitrous oxide, oxygen, halothane and mechanically ventilated. Methacholine 2 micrograms X kg-1 X hour-1 was administrated first followed by halothane (1 MAC) for 30 minutes (control), then metaproterenol, isoetharine or salbutamol. Metaproterenol (15 mg) significantly decreased transpulmonary pressure to 20.1 +/- 0.5 (SE) from 22.5 +/- 1.15 cmH2O (p less than 0.025) after three min and to 15 +/- 0.5 cmH2O (p less than 0.005) after 90 min. Isoetharine (2.5 mg) decreased transpulmonary pressure after five min to 22.1 +/- 1 from 24.5 +/- 1.5 cmH2O (p less than 0.05), and to 21.75 +/- 0.55 mmH2O after 90 min. Salbutamol 25 micrograms X kg-1 decreased transpulmonary pressure to 20.7 +/- 0.75 from 24.25 +/- 1.28 after three min and to 16 +/- .5 after 90 min. The peak effects on airway pressure occurred at 15 min for metaproterenol, 25 min for salbutamol and 20 min for isoetharine. Pulmonary vascular resistance was not significantly changed during halothane anaesthesia alone but decreased significantly after metaproterenol and isoetharine infusion. Heart rate increased ten per cent after metaproterenol, three per cent after isoetharine, and five per cent after salbutamol. No arrhythmias occurred in any group. Cardiac output increased significantly to 3.25 +/- 0.2 from 1.5 +/- 0.17 L X min-1 (p less than 0.025) after metaproterenol to 3.2 +/- .025 from 1.45 +/- .009 after salbutamol and was unchanged after isoetharine. Metaproterenol and salbutamol in the presence of 1 MAC halothane anaesthesia relieved methacholine-induced bronchospasm more rapidly than did isoetharine. The onset of effect was 3 +/- 0.05 min for metaproterenol and salbutamol and 5 +/- 0.01 min for isoetharine. The effect lasted 210 +/- 10.5 min for metaproterenol, 170 +/- 12.5 min for salbutamol and 90 +/- 4.75 min for isoetharine.

Airway Resistance↗