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M H Zornow

Publications and source records attributed to M H Zornow.

At least 19 recordsLinked to original sources
PubMed1992

AMPA and NMDA receptor antagonists do not decrease hippocampal glutamate concentrations during transient global ischemia.

Increased extracellular concentrations of glutamate during episodes of cerebral ischemia may be due in part to a positive glutaminergic feedback loop. We evaluated the effect of selective AMPA or NMDA receptor antagonists on hippocampal extracellular concentrations of excitatory amino acids during ischemia and reperfusion. Thirteen New Zealand white rabbits were subjected to 10 min of global cerebral ischemia produced by neck tourniquet inflation (20 psi) combined with systemic hypotension during halothane (1-1.5%) anesthesia. Hippocampal extracellular concentrations of glutamate, aspartate, and glycine were monitored using in vivo microdialysis. NBQX (a selective AMPA receptor antagonist), MK801 (a noncompetitive NMDA receptor antagonist), or 5% dextrose was administered starting 1 h before ischemia. The NBQX group (n = 4) received 5 mg.kg-1 of NBQX intravenously (dissolved in 5% dextrose) over 5 min followed by an infusion of 5 mg.kg-1.h-1. The 5% dextrose group (n = 4) received an equivalent volume of 5% dextrose. The peak concentrations of glutamate, aspartate, and glycine in the early reperfusion period were 5-8-fold, 9-10-fold, and 4-5-fold higher than preischemic values, respectively. There were no significant differences, however, among the three groups in the concentrations of glutamate, aspartate, or glycine at any time during the study. These results do not support the existence of a positive feedback loop for glutamate mediated via AMPA or NMDA autoreceptors in the hippocampus during transient global ischemia or reperfusion.

Animals↗
PubMed1992

Effects of levemopamil on neurologic and histologic outcome after cardiac arrest in cats.

BACKGROUND AND METHODS: A study was performed to examine the effects of the calcium-channel blocker levemopamil on neurologic outcome and neuropathology in a clinically relevant model of complete global cerebral ischemia (ventricular fibrillation in cats). Levemopamil was administered to cats starting 5 mins after resuscitation from 14 mins of cardiac arrest. In a "blinded" manner, 46 animals received levemopamil 1 mg/kg over 15 mins followed by 10 micrograms/kg.min for 16 hrs or vehicle. In a nonblinded manner, eight additional animals were pretreated with levemopamil beginning 45 mins before cardiac arrest. After resuscitation, levemopamil was infused at 10 micrograms/kg.min for 16 hrs. Animals in all three groups remained sedated, paralyzed, and mechanically ventilated for 24 to 30 hrs after resuscitation. Neurologic examinations were performed at 2, 4, and 7 days after resuscitation. Thirty-five cats were entered into data analysis (16 levemopamil posttreated, 14 vehicle-treated, and 5 levemopamil pretreated). RESULTS: Neurologic deficit scores and over-all neuropathologic scores did not differ among groups at any interval after resuscitation. However, the occipital cortex and CA1 region of the pretreated animals showed less severe damage than was observed in the animals that received levemopamil or vehicle, starting after resuscitation (p less than .01). CONCLUSIONS: Postarrest administration of levemopamil was not associated with improved neurologic or neuropathologic outcome. However, the data suggest that prearrest administration may result in regionally selective improvement in neuropathology.

Animals↗
PubMed1992

The effect of cyclohexyladenosine on the periischemic increases of hippocampal glutamate and glycine in the rabbit.

We investigated the ability of N6-cyclohexyladenosine (CHA), a potent and selective agonist of the adenosine A1 receptor, to attenuate elevations of levels of extracellular hippocampal glutamate and glycine that result from episodes of transient global cerebral ischemia (TGCI). A total of 30 New Zealand white rabbits were randomly assigned to receive 0 (n = 5), 0.1 (n = 8), 1.0 (n = 6), 10 (n = 6), or 100 (n = 5) microM CHA. The drug was dissolved in artificial CSF (vehicle) and administered via a microdialysis probe placed stereotactically into the dorsal hippocampus. A second microdialysis probe placed into the contralateral hippocampus of each animal was perfused with vehicle alone. Ten minutes of TGCI was induced by neck tourniquet inflation and deliberate hypotension from 0 to 10 min. Microdialysis samples were collected as follows: every 20 min preischemia (at -80, -60, -40, -20, and 0 min); every 5 min during ischemia and in the immediate reperfusion period (at 5, 10, 15, and 20 min); and every 20 min for the remainder of the reperfusion period (at 40, 60, and 80 min). Samples were then analyzed for their concentration of glutamate and glycine by HPLC. Following 10 min of ischemia, glutamate levels increased to a peak of 3.28 +/- 0.55 times baseline and returned to preischemic levels by 40 min, i.e., during reperfusion. Glycine concentrations increased to 5.41 +/- 0.91 times over baseline and remained elevated for the duration of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1992

Effects of ischemia duration on neurological outcome, CA1 histopathology, and nonmatching to sample learning in monkeys.

BACKGROUND AND PURPOSE: Male cynomolgus monkeys (n = 10) were subjected to varying durations of global cerebral ischemia to determine the relation between dose (ischemic duration) and response (outcome). METHODS: Each monkey was anesthetized with halothane, and global cerebral ischemia was produced by a neck tourniquet and trimethaphan-induced hypotension. The animal was subjected to 3 (n = 3), 9 (n = 3), or 12 (n = 4) minutes of ischemia. Neurological examinations were performed daily for 30 days or until the monkey was neurologically normal. Approximately 1 month after ischemia, the animal was evaluated for evidence of neurobehavioral abnormalities with the nonmatching to sample test. When testing was complete, the monkey was killed with an overdose of pentobarbital and the brain perfused with formalin and removed for histopathologic analysis, with particular attention devoted to the hippocampal CA1 region. RESULTS: Monkeys subjected to 3 or 9 minutes of ischemia were neurologically normal (except for a very mild injury in one 9-minute animal) immediately after ischemia and had normal CA1 histology. Monkeys subjected to 12 minutes of ischemia were grossly abnormal neurologically after ischemia, but two of the four animals made a complete recovery (neurological deficit score of 0) by 30 days. Monkeys subjected to 12 minutes of ischemia had mild damage in the CA1 region, with all other brain regions appearing normal. None of the animals had demonstrable decrements in neurobehavioral function as measured by the nonmatching to sample test. CONCLUSIONS: We conclude that neurobehavioral testing after global cerebral ischemia in primates is feasible, but the ischemic time necessary to produce CA1 damage that could potentially be quantified antemortem with the nonmatching to sample test is greater than 12 minutes in cynomolgus monkeys and may produce temporary severe gross neurological abnormalities as well.

Animals↗
PubMed1992

Intracranial pressure effects of dexmedetomidine in rabbits.

The alpha 2-adrenergic receptor agonist dexmedetomidine produces an anesthetic state in a variety of species. Although its effects on cerebral blood flow and the electroencephalogram have been investigated, the effect of this drug on intracranial pressure (ICP) has not been reported previously. Dexmedetomidine therefore was intravenously administered to 24 New Zealand white rabbits that had been anesthetized with halothane and mechanically ventilated to maintain a constant arterial CO2 tension (PaCO2) between 34 and 39 mm Hg. After placement of an arterial catheter and ventricular cannula, baseline measurements of monitored variables, including heart rate, mean arterial blood pressure, ICP, end-tidal CO2, body temperature, and arterial blood gases, were recorded. Dexmedetomidine (20, 80, or 320 micrograms/kg IV) or saline solution was then infused over a 10-min period. The ICP transiently decreased by 31% in the 20-micrograms/kg group (from a mean value of 9.4 +/- 1.3 [SEM] to 6.5 +/- 1.0 mm Hg, P less than 0.05). In the 320-micrograms/kg group, ICP remained unchanged over the course of the study despite a significant increase in arterial blood pressure (32 mm Hg). The effects of dexmedetomidine on ICP were next investigated in the presence of intracranial hypertension produced by a cryogenic lesion (mean baseline ICP 16.8 mm Hg). In addition to the previously monitored variables, sagittal sinus blood flow was measured by the hydrogen clearance technique before and after the administration of dexmedetomidine (320 micrograms/kg IV). In these experiments, dexmedetomidine was associated with a 14% decrease in sagittal sinus blood flow that was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1992

Tracheal intubation without the use of muscle relaxants: a technique using propofol and varying doses of alfentanil.

We have noted that tracheal intubation can be accomplished in many patients after induction of anesthesia with propofol and alfentanil without the simultaneous use of muscle relaxants. This study was designed to evaluate airway and intubating conditions after administration of propofol and alfentanil in 75 ASA physical status I or II outpatients with Mallampati class I airways undergoing various surgical procedures. The patients were randomly assigned to one of five groups for induction of anesthesia. All patients received midazolam 1 mg IV before induction of anesthesia. Group I patients (n = 15) received d-tubocurarine 3 mg, thiamylal 4 mg/kg, and succinylcholine 1 mg/kg IV. Groups II-V patients (n = 15 each) received alfentanil 30, 40, 50, or 60 micrograms/kg followed by propofol 2 mg/kg IV. No muscle relaxants were given to patients in groups II-V. Airway management was performed by one of the authors who was blinded as to the dose of alfentanil administered. After loss of consciousness, patients' lungs were ventilated via face mask, and the ease of ventilation was recorded. Jaw mobility was also assessed. Ninety seconds after administration of the propofol or thiamylal, laryngoscopy was performed and exposure of the glottis and position of the vocal cords were noted. Intubation of the trachea was performed and patient response was noted. Heart rate and arterial blood pressure were also recorded before induction of anesthesia, after induction, and then again after intubation of the trachea. The lungs of all patients were easily ventilated via mask, and the jaw was judged to be relaxed in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Antinociceptive properties of intrathecal dexmedetomidine in rats.

Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist. In this study, the intrathecal administration of dexmedetomidine into the rat lumbar subarachnoid space produced dose-dependent, prolonged antinociception as measured by hot plate and tail flick testing. Intrathecal administration of 3 or 10 micrograms of dexmedetomidine increased hot plate and tail flick latencies to cutoff values within 15 min of injection. Animals receiving 1 microgram of intrathecal dexmedetomidine did not show any significant antinociception when compared to saline controls. The intrathecal administration of the alpha 2-adrenoceptor antagonist, idazoxan, ablated all measurable antinociception produced by the prior injection of 10 micrograms of dexmedetomidine.

Adrenergic alpha-Agonists↗
PubMed1991

Ventilatory, hemodynamic and sedative effects of the alpha 2 adrenergic agonist, dexmedetomidine.

Dexmedetomedine is a potent alpha 2 adrenergic agonist which can reduce anesthetic requirements by over 90% in rats and dogs. This study examined the effects of various doses of dexmedetomidine on the following monitored variables in New Zealand white rabbits: arterial blood gases, mean arterial pressure, respiratory rate, heart rate, and level of sedation. Following the percutaneous insertion of arterial and venous catheters, 21 rabbits received an infusion of saline or dexmedetomidine (20, 80 or 320 micrograms/kg). Monitored variables were recorded at 5, 15, 30 and 60 min following the infusion. Dexmedetomidine produced significant dose-dependent increases in PaCO2 and level of sedation. There were significant decreases in heart rate, PaO2 and respiratory rate. There was no significant change in mean arterial pressure even at the highest (320 micrograms/kg) dose. To examine the ability of an alpha 2 adrenergic antagonist to reverse the effects of dexmedetomidine, 5 rabbits initially received 320 micrograms/kg of dexmedetomidine as described above. Seven minutes after completion of the infusion, 900 micrograms/kg of the alpha 2 adrenergic antagonist, idazoxan, was administered. This resulted in a prompt and sustained reversal of the hypercarbia and sedation produced by the dexmedetomidine.

Adrenergic alpha-Agonists↗
PubMed1991

Failure of nimodipine to improve neurologic outcome after eighteen minutes of cardiac arrest in the cat.

The calcium entry blocker nimodipine was administered to cats following resuscitation from 18 min of cardiac arrest to evaluate its effect on neurologic and neuropathologic outcome in a clinically relevant model of complete cerebral ischemia. Cardiac arrest (ventricular fibrillation) was maintained for 18 min and resuscitation was performed by a standardized protocol in 40 cats. Beginning at 5 min post-resuscitation, nimodipine, 10 micrograms/kg over 2 min followed by 1 microgram/kg per min for 10 h, or the same volume of placebo was administered in a randomized, blinded fashion. Neurologic deficits were scored at 2, 4, and 7 days post-resuscitation by observers blinded to the treatment group. Thirty cats were evaluated neurologically at 7 days post-resuscitation and were entered into data analysis (n = 15 per group). Neither neurologic deficit scores nor neuropathologic scores were significantly different between groups. The authors conclude that nimodipine administration in the manner and doses stated does not improve neurologic outcome in cats following resuscitation from cardiac arrest.

Animals↗
PubMed1991

Drug contamination from opening glass ampules.

Recently there have been several reports of postoperative sepsis due to the intravenous injection of contaminated solutions of propofol (Diprivan). The mechanism by which this contamination occurred has not been identified. This study sought to determine whether bacterial contamination of the contents of glass ampules can be decreased by swabbing the neck of the vial with alcohol prior to opening. Glass ampules of 1% propofol and 1% lidocaine were swabbed with a solution of Staphylococcus epidermidis. Half of these ampules were subsequently wiped with alcohol pads prior to being opened. An aliquot from each ampule was pipetted into a nutrient broth and allowed to incubate overnight at 37 degrees C. These solutions were plated on agar, incubated for 24 h, and then examined for bacterial growth. Three of the eight lidocaine ampules and six of the eight propofol ampules not cleaned with alcohol demonstrated evidence of bacterial contamination. The contents of all ampules that had been wiped with alcohol prior to being opened remained sterile (P less than 0.001 vs. non-alcohol-treated group for propofol ampules and P = 0.20 vs. non-alcohol-treated group for lidocaine ampules). These data suggest that bacterial contamination of propofol and lidocaine may occur as a result of opening glass ampules. Wiping the outside of the ampule with alcohol immediately prior to opening may decrease this risk.

Alcohols↗
PubMed1991

Changes in extracellular concentrations of glutamate, aspartate, glycine, dopamine, serotonin, and dopamine metabolites after transient global ischemia in the rabbit brain.

Although considerable evidence supports a role for excitatory amino acids in the pathogenesis of ischemic neuronal injury, few in vivo studies have examined the effect of increasing durations of ischemia on the extracellular concentrations of these agents. Recently, other neurotransmitters (e.g., glycine and dopamine) have been implicated in the mechanism of ischemic neuronal injury. Accordingly, this study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, glycine concentrations in the hippocampus, and dopamine, serotonin, and dopamine metabolites in the caudate nucleus with varying durations (5, 10, or 15 minutes) of transient global cerebral ischemia as evidence to support their pathogenetic roles. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. Glutamate and aspartate concentrations in the dialysate increased from baseline by 1-, 5-, and 13-fold and by 4-, 9-, and 31-fold, respectively, for the three ischemic durations. The concentrations returned to baseline rapidly after reperfusion. The peak concentrations of glutamate and aspartate were significantly higher with increasing ischemic duration. Dopamine concentrations increased by approximately 700-fold in response to all three ischemic durations and returned to baseline within 10 min of reperfusion. Glycine, in contrast, increased during ischemia by a mean of 4-fold, but remained elevated throughout the 80-min period of reperfusion. The final concentrations of glycine were significantly higher than baseline levels (p = 0.0002, Mann-Whitney test). That glutamate and aspartate concentrations in the hippocampus co-vary with the duration of global ischemia is taken as supportive evidence of their pathogenetic role in ischemic neuronal injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1991

Hypothermia prevents ischemia-induced increases in hippocampal glycine concentrations in rabbits.

We subjected 10 New Zealand White rabbits to 10 minutes of global cerebral ischemia under either normothermic (37 degrees C) or moderately hypothermic (29 degrees C) conditions. Hippocampal concentrations of glutamate, aspartate, and glycine were monitored using in vivo microdialysis. Outcome was assessed by both neurological and neuropathologic criteria. Hypothermia afforded nearly complete protection from ischemic injury. Ischemia-induced increases in the concentrations of glutamate, aspartate, and glycine in the normothermic group (3, 12, and 3 times baseline) were strikingly attenuated in the hypothermic group. In addition, the prolonged postischemic elevation of glycine levels seen in the normothermic group was absent in the hypothermic group. These results suggest that the neuroprotective properties of hypothermia may reside, in part, in their ability to prevent increases in the extracellular concentrations of amino acids that enhance the activity of the N-methyl-D-aspartate receptor complex.

Animals↗
PubMed1990

A comparison of the cerebral and haemodynamic effects of mannitol and hypertonic saline in an animal model of brain injury.

There has recently been an increased interest in the use of hypertonic saline solutions in the fluid resuscitation of trauma victims and to control intracranial hypertension. In this study, the cerebral and haemodynamic effects of a 3.2% hypertonic saline solution were compared with those of either a 0.9% saline or 20% solution were compared with those of either a 0.9% saline or 20% mannitol solution in a rabbit model of brain injury. Forty-five minutes following the creation of a left hemispheric cryogenic brain lesion, equal volumes of hypertonic saline, 0.9% saline, or mannitol were infused over a 5 minute period. Monitored variables over the ensuing 120 minutes included mean arterial pressure, central venous pressure, intracranial pressure, hematocrit, serum osmolality and oncotic pressure. Upon conclusion of the two hour study period, hemispheric water contents were determined by the wet/dry weight method. There were no significant differences in mean arterial pressure between the three groups at any point during the experiment. Plasma osmolality was significantly increased by 10-11 mOsm/kg in both the mannitol and hypertonic groups. The infusion of either mannitol or hypertonic saline produced a transient decrease in intracranial pressure lasting approximately 60 minutes whereas animals in the saline group demonstrated a continual increase in intracranial pressure. The lesioned hemisphere demonstrated a significantly greater water content than the non-lesioned hemisphere.

Animals↗
PubMed1990

Cardiac output and stroke volume in swimming harbor seals.

Cardiac output was measured by the thermodilution method in three young harbor seals, at rest and while swimming up to the maximum effort for which they could be trained. Stroke volume was determined by counting heart rate simultaneously with determination of cardiac output. Cardiac outputs varied widely between surface breathing (7.8 ml.kg-1.s-1) and breath-holding while swimming under water (1.8 ml.kg-1.s-1). Stroke volume while at the surface was almost twice the volume while submerged. Surface cardiac output was always near maximal despite work effort, whereas submerged cardiac output gradually increased at higher work efforts. The cardiovascular performance of seals at the maximum MO2 we could induce from them is equivalent to that of the domestic goat.

Animals↗
PubMed1990

Influence of hypotension and hypotensive technique on the area of profound reduction in cerebral blood flow during focal cerebral ischaemia in the rat.

We have studied the effect of induced hypotension on reduction in regional cerebral blood flow (CBF) during middle cerebral artery occlusion (MCAO). Rats were anaesthetized with 2% isoflurane. MCAO was performed during four conditions: normotension (mean arterial pressure (MAP) 107 (SD 15) mm Hg); hypovolaemic hypotension (blood withdrawn to reduce MAP to 43 (2) mm Hg); nitroprusside (SNP) hypotension (MAP reduced to 45 (3) mm Hg); isoflurane hypotension (MAP reduced to 44 (3) mm Hg with 3.5 (0.48)% isoflurane). Hypotension was established before MCAO and was maintained for 10 min, at which time the dimension of the brain areas with zero CBF was determined autoradiographically. All hypotensive regimens were associated with significantly larger areas of extreme CBF reduction. In a coronal section at the centre of the MCA distribution, the area with zero CBF (expressed as a percentage of the area of the entire coronal section) was: normotension 4.7 (4.5)%; hypovolaemic hypotension 10.1 (2.8)%; nitroprusside hypotension 13.5 (2.0)%; and isoflurane hypotension 11.8 (3.9)%. There were no differences between the three hypotensive regimens. The data indicate that, when focal cerebral ischaemia occurs during hypotension (MAP 45 mm Hg) induced by any of the three regimens evaluated, extreme CBF reduction occurs over larger areas than are observed during normotension. These data confirm the importance of arterial pressure as a determinant of collateral flow during focal cerebral ischaemia.

Animals↗
PubMed1990

Cerebral effects of sevoflurane in the dog: comparison with isoflurane and enflurane.

The cerebral effects of sevoflurane were compared in dogs with those of enflurane and isoflurane. Initially, the minimum alveolar concentrations (MAC) of sevoflurane and enflurane were determined and the electroencephalographic (EEG) responses to increasing doses of sevoflurane (1.5, 2.0 and 2.5 MAC) or enflurane (1.5 and 2.0 MAC) in unparalysed animals were examined. Administration of sevoflurane was not associated with seizure activity at any concentration either during normocapnia (PaCO2 5.3 kPa) or hypocapnia (PaCO2 2.7 kPa), even in the presence of intense auditory stimuli. All dogs anaesthetized with enflurane demonstrated sustained EEG and motor evidence of seizure activity induced by auditory stimuli at concentrations of enflurane greater than 1 MAC, particularly during hypocapnia. In a separate group of dogs, the effects of increasing concentrations of sevoflurane and isoflurane (0.5, 1.5 and 2.15 MAC) were compared directly on arterial pressure, cardiac output and heart rate, cerebral blood flow and the cerebral metabolic rate for oxygen (CMRO2) using the venous outflow technique. Sevoflurane, in common with isoflurane, had minimal effects on cerebral blood flow at the concentrations studied, but significantly reduced the CMRO2 at end-tidal concentrations sufficient to produce a burst suppression pattern on the EEG (approximately 2.15 MAC). Both sevoflurane and isoflurane significantly decreased arterial pressure in a dose-dependent manner, but neither drug significantly altered cardiac output.

Acoustic Stimulation↗
PubMed1990

Glucose administration before cardiac arrest worsens neurologic outcome in cats.

The effects of glucose on neurologic and neuropathologic outcome following global cerebral ischemia were examined in 20 cats subjected to 14 min of cardiac arrest, followed by closed chest resuscitation and intensive care monitoring. Beginning 30 min prior to cardiac arrest, 15 ml/kg of 5% dextrose in 0.45% saline or the same volume of 0.9% saline was administered in a blinded fashion over 15 min. Ventricular fibrillation was electrically induced and cardiac resuscitation was performed according to a standardized protocol, which included closed chest cardiac compressions, epinephrine, lidocaine, sodium bicarbonate administration, and electrical defibrillation. Animals not resuscitated within 4 min were excluded from further study. Resuscitated animals were managed in an intensive care setting for 24 h postresuscitation. Neurologic deficits were scored at 2, 4, and 7 days postresuscitation. Subsequently, the animals' brains underwent histologic examination. Nine cats were excluded from data analysis. Three did not meet protocol criteria and six could not be resuscitated within 4 min. As a result of a technical error, the brain of one glucose-treated cat was not analyzed. Six saline-treated and five glucose-treated animals met all protocol criteria and survived for 7 days postresuscitation. Plasma glucose concentration before cardiac arrest was 118 +/- 24 mg/dl (mean +/- SD) in the saline group and 269 +/- 21 mg/dl in the glucose group (P less than 0.01). Neurologic outcome rank at 2, 4, and 7 days postresuscitation was significantly worse in glucose-treated cats (P less than 0.01, P less than 0.01, and P less than 0.01, respectively). The neuropathologic score did not differ between glucose- and saline-treated groups (P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗