PubMed Health⌕ Search

Biomedical subjects

J D Michenfelder

Publications and source records attributed to J D Michenfelder.

At least 19 recordsLinked to original sources
PubMed1992

The effect of profound levels of hypothermia (below 14 degrees C) on canine cerebral metabolism.

The goal of this study was to determine the temperature coefficient (Q10) for canine CMRO2 at temperatures below 14 degrees C. Eight dogs were anesthetized with halothane for surgical preparation. The animals were placed on total cardiopulmonary bypass and CBF was measured by direct sagittal sinus outflow. Duplicate measurements were taken at 37, 13, and 7 degrees C. The EEG became isoelectric at a temperature of 12.0 +/- 0.8 degrees C. The Q10 between 13 and 7 degrees C was 2.19 +/- 0.59. With rewarming to 37 degrees C, cerebral metabolic variables returned to control levels. Brain biopsies taken at the end of the study yielded normal values for brain energy stores. We conclude that the Q10 for CMRO2 at temperatures between 7 and 37 degrees C can be profoundly affected by the state of cerebral function as reflected by the EEG. In the absence of EEG activity, an expected Q10 value of 2.2 reflects only the direct effect of temperature on the rates of biologic reactions.

Animals↗
PubMed1992

Detection and hemodynamic consequences of venous air embolism. Does nitrous oxide make a difference?

Volume expansion of intravascular air by nitrous oxide (N2O) may improve the sensitivity of monitors used to detect venous air embolism (VAE) and/or exacerbate hemodynamic changes following VAE. The purpose of this study was to determine if the administration of N2O alters the sensitivity (i.e., threshold of detection) of monitors used to detect VAE or the hemodynamic consequences of VAE. Twenty-one dogs were monitored for VAE with precordial Doppler ultrasound, transesophageal echocardiography (TEE), changes in end-tidal carbon dioxide tension (ETCO2), and changes in pulmonary artery pressure (PAP). Venous air was infused at rates between 0.005 and 0.4 ml.kg-1.min-1 during 1 MAC (total anesthetic level) of isoflurane with and without 50% N2O (group 1, n = 7) or isoflurane with and without 75% N2O (group 2, n = 7). The mean quantity of infused air necessary to elicit a positive response in both the presence and absence of N2O was calculated for each monitor. Positive responses were defined as follows: unmistakable audible change in frequency on Doppler ultrasound, visualization of densities consistent with air bubbles in the right cardiac chambers or outflow tract on TEE, a decrease in ETCO2 greater than or equal to 2 mmHg, and an increase in mean PAP greater than or equal to 3 mmHg. In group 3 (n = 7), venous air was infused at rates between 0.1 and 0.8 ml.kg-1.min-1 during 1 MAC (total anesthetic level) of isoflurane with and without 50% N2O. In group 3, N2O administration was discontinued immediately upon Doppler detection of VAE and air infusion continued until mean arterial pressure (MAP) decreased by 10 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Postischemic canine cerebral blood flow is coupled to cerebral metabolic rate.

Following complete global cerebral ischemia and reperfusion, a brief period of reactive hyperemia is followed by a prolonged period of low flow commonly referred to as the delayed postischemic hypoperfusion state. It is generally assumed that this low-flow state may be injurious because of inadequate substrate delivery, thus implying that flow is no longer coupled to metabolic needs. This relationship of CBF to CMRO2 was examined in six anesthetized dogs that were subjected to 12 min of complete ischemia induced either by CSF compression or aortic occlusion. Following reperfusion and onset of the low-flow state, which stabilized at 45 min postischemia, control normothermic (37 degrees C) measurements of CBF and CMRO2 were determined. Thereafter, femoral arterial blood was circulated through a heat exchanger (42.5 degrees C), and brain temperature was increased to 40 degrees C and measurements were repeated. The brain was then cooled back to 37 degrees C for a final set of normothermic measurements. Thereafter, brain biopsies were taken to determine the energy state of the brain. CMRO2 changed approximately 6%/degrees C. CBF paralleled the change in CMRO2. Accordingly, the ratio of CBF to CMRO2 remained constant throughout at a value of 8 to 9, demonstrating maintained coupling. The brain energy state was normal at the end of the study. The authors conclude that postischemic CBF is modulated by the brain's metabolic needs.

Adenine Nucleotides↗
PubMed1991

Ischemia-reperfusion does not affect reactivity of isolated canine basilar artery.

The effect of ischemia-reperfusion on endothelium-dependent relaxations and reactivity of vascular smooth-muscle cells was studied in rings of basilar arteries obtained from six dogs exposed to 12 min of complete global cerebral ischemia followed by 100 min of reperfusion. Three sham-operated control dogs served as controls. Ischemia was induced either by an increase in intracranial pressure or by aortic occlusion. The rings were suspended for isometric tension recording in physiological salt solution. Ischemia-reperfusion did not affect endothelium-dependent relaxations to vasopressin and bradykinin. In rings without endothelium relaxations to sodium nitroprusside, molsidomine (SIN-1), and papaverine as well as contractions to 5-hydroxytryptamine and KCl were preserved. These results demonstrate that in large canine cerebral arteries, ischemia-reperfusion of these durations does not affect relaxations mediated by activation of endothelium or direct relaxations and contractions of vascular smooth-muscle cells.

Animals↗
PubMed1991

The relationship among canine brain temperature, metabolism, and function during hypothermia.

Cerebral protection by hypothermia is commonly attributed to cerebral metabolic suppression. However, at temperatures below 28 degrees C, the relationship of temperature to cerebral metabolic rate of oxygen consumption (CMRO2) has not been well characterized. Accordingly, the relationship between brain temperature and CMRO2 was determined in eight dogs during cooling from 37 to 14 degrees C while the EEG was continuously monitored. Cardiopulmonary bypass was initiated and control measurements were made at 37 degrees C during anesthesia with nitrous oxide 50-60% inspired and morphine sulfate 2 mg.kg-1 intravenously (iv). Upon cooling to 27 degrees C, the nitrous oxide was discontinued and the morphine was antagonized with naloxone 2 mg iv. Measurements were repeated at 27, 22, 18, and 14 degrees C and in four dogs again at 37 degrees C after nitrous oxide 50-60% had been reestablished at 27 degrees C along with administration of morphine sulfate 2 mg.kg-1. For each temperature interval, the temperature coefficient (Q10) for CMRO2 was calculated (Q10 = CMRO2 at x degrees C divided by CMRO2 at [x - 10] degrees C). Between 37 and 27 degrees C the Q10 was 2.23, but between 27 and 14 degrees C the mean Q10 was doubled to 4.53. With rewarming to 37 degrees C, CBF and CMRO2 returned to control levels, and brain biopsies revealed a normal brain energy state. During cooling, the EEG developed burst suppression at or below 22 degrees C. With further cooling, the periods of suppression increased; however, burst activity continued in seven of eight dogs even at 14 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Pretreatment with U74006F improves neurologic outcome following complete cerebral ischemia in dogs.

We examined the 21-aminosteroid U74006F, a potent inhibitor of lipid peroxidation, for potential neuroprotective effects in a canine model of complete cerebral ischemia. Two 1.5-mg/kg boluses were administered to six dogs, the first bolus 15 minutes prior to a 12-minute episode of complete cerebral ischemia and the second bolus after 11 minutes of ischemia, 1 minute prior to reperfusion. Using this dosage regimen, plasma U74006F levels of greater than 0.3 microgram/ml were maintained for up to an hour postischemia. An additional six animals received equal volumes of the citrate vehicle solution. At 24 and 48 hours postischemia, the dogs were neurologically evaluated by an observer blinded as to treatment selection. All six U74006F-treated animals had a normal neurologic outcome at 48 hours postischemia, while the citrate vehicle-treated animals all suffered moderate to severe neurologic deficits. The difference in outcome was significant at both 24 and 48 hours (p less than 0.005). Although U74006F is a 21-aminosteroid, it is not reported to possess glucocorticoid activity. This is supported by the present finding that no changes in plasma glucose concentration were observed following administration of the drug. The systemic vitamin E levels of citrate vehicle-treated animals decreased significantly (from 4.10 +/- 0.46 micrograms/ml to 2.95 +/- 0.38 micrograms/ml, p less than 0.05), whereas the vitamin E levels in U74006F-treated animals did not decrease significantly. These results suggest that U74006F may be of benefit in improving neurologic outcome when administered prior to an episode of complete cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effects of dizocilpine maleate (MK-801), an antagonist of the N-methyl-D-aspartate receptor, on neurologic recovery and histopathology following complete cerebral ischemia in primates.

The present study was designed to determine if the noncompetitive excitatory amino acid antagonist, dizocilpine maleate, when administered after a 17 min period of complete cerebral ischemia in primates, would improve postischemic neurologic function and hippocampal histopathologic outcome when compared to placebo-treated animals. Ten pigtail monkeys were anesthetized and subjected to complete cerebral ischemia using an established neck tourniquet model. Five minutes postischemia, five monkeys received dizocilpine 300 micrograms/kg i.v. over 5 min, followed by an infusion of 150 micrograms/kg/h for 10 h. This produced plasma levels of the drug in excess of 30 ng/ml for the duration of the infusion. An additional five monkeys were treated with an identical volume of saline placebo. All monkeys received intensive care for the initial 24 to 48 h postischemia. At 96 h postischemia, there was no significant difference in neurologic function between the two groups (p = 0.53, with the placebo group having the numerically better outcome). There also was no significant difference between hippocampal histopathology scores between dizocilpine and placebo-treated monkeys. The authors conclude that dizocilpine is not an efficacious therapy in the treatment of neurologic injury that occurs following complete cerebral ischemia in this primate model.

Animals↗
PubMed1990

Postischemic canine cerebral blood flow appears to be determined by cerebral metabolic needs.

Following a period of complete global cerebral ischemia and reperfusion there ensues a low flow state referred to as the delayed postischemic hypoperfusion state. It is unknown whether this low flow state contributes to neuronal injury or whether the magnitude of hypoperfusion correlates with the duration of ischemia. The latter question was addressed in 20 dogs in which complete global ischemia was induced by cerebrospinal fluid (CSF) compression for periods of 3, 9, 12, or 18 min. Following reperfusion, CBF (by sagittal sinus outflow) and CMRO2 were determined for 90 min, and results were correlated with the duration of ischemia. At 90 min postischemia the magnitude of decrease in CBF correlated crudely with the duration of ischemia (r = -0.67, p less than 0.01). For CMRO2 correlation of the magnitude of decrease with the duration of ischemia was more evident (r = -0.74, p less than 0.001). Furthermore, the postischemic ratio of CBF to CMRO2 was virtually identical for all dog groups regardless of the ischemic time. The adequacy of the ratio of CBF to CMRO2 was reflected by adequate oxygen levels in the sagittal sinus blood of all dogs. The authors conclude that the delayed postischemic hypoperfusion state is probably not an important determinant of neuronal injury since its magnitude appears to be primarily determined by the metabolic needs of the brain.

Animals↗
PubMed1990

Influence of intraoperative antibiotic choice on the incidence of early postcraniotomy seizures.

Because of a suspicion that intraoperative penicillin antibiotics might be causing early postoperative seizures in craniotomy patients, a deliberate effort was initiated in 1987 to avoid these agents in favor of nonpenicillin antibiotics. This permitted a retrospective comparison of the incidence of early postoperative seizures in craniotomy patients who did and who did not receive intraoperative penicillins. Records of patients treated between July 1, 1984, and July 1, 1985, and between July 1, 1987, and July 1, 1988, were reviewed, for a total of 1316 procedures. There were no seizures in the 323 patients who underwent suboccipital craniectomy. However, among the 993 patients receiving supratentorial procedures there were 30 with seizures within the first 6 hours postoperatively, 19 of which were generalized seizures. The incidence of early seizures was 4.7% (20 cases) of the 427 patients given penicillins and only 1.8% (10 cases) of the 566 not given penicillins (p less than 0.01). Since patients undergoing surgery for intractable seizures have a high incidence of early postoperative seizures (11 of 92 in this series, or 12%), creation of a subgroup eliminated these from consideration but did not alter the relationship of penicillins to early seizures (p less than 0.02). The authors conclude that intraoperative (and early postoperative) penicillin antibiotic administration should be avoided, if possible, in patients undergoing craniotomy for supratentorial pathology.

Anti-Bacterial Agents↗
PubMed1989

The effect of the excitatory amino acid receptor antagonist dizocilipine maleate (MK-801) on hemispheric cerebral blood flow and metabolism in dogs: modification by prior complete cerebral ischemia.

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist dizociplipine maleate (MK-801) on cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), intracranial pressure and systemic variables was examined in 6 normal dogs (Group I). In 6 additional dogs (Group II), the effects of a prior 11 min episode of complete cerebral ischemia on the response to dizocilipine was studied. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arterial to sagittal sinus O2 content difference. Dizocilipine was administered as a 150 micrograms/kg i.v. bolus followed by a 75 micrograms.kg-1.h-1 infusion for 90 min. Plasma dizocilipine levels were greater than 25 ng/ml for the duration of the infusion. The CSF levels were approximately half the plasma levels. Five minutes after initiation of dizocilipine treatment, Group I dogs experienced a 63% increase in heart rate (P less than 0.01) and an 8% decrease in the mean arterial blood pressure (P less than 0.05). Over the same time interval. CBF increased by 85% (P less than 0.01) and intracranial pressure nearly doubled (P less than 0.05). In addition, dizocilipine treatment in all Group I animals resulted in EEG quasiperiodic bursts of delta-waves and polyspikes on a background of beta-activity. With the exception of the intracranial pressure, the above changes in systemic and cerebral variables persisted for the duration of the drug infusion. Intracranial pressure was no longer significantly elevated after 80 min of drug infusion. Hemispheric CMRO2 was unchanged by dizocilipine in Group I dogs. There was a decrease in the cortical glucose level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with 6 laboratory normals. An identical dose of dizocilipine administered after an 11 min episode of complete cerebral ischemia resulted in no significant changes in either cerebral or systemic variables. The absence of systemic effects in Group II dogs suggests that dizocilipine administration in normal dogs results in a centrally mediated activation of the peripheral sympathetic nervous system. The uncoupling of CBF and CMRO2 observed following dizocilipine treatment is similar to that reported for two other known NMDA antagonists, ketamine and phencyclidine. If administration of dizocilipine results in improved histopathological and neurological outcome following an episode of complete cerebral ischemia, this improvement is unrelated to changes in postischemic CBF or hemispheric CMRO2.

Animals↗
PubMed1989

Evaluation of the glutamate antagonist dizocilipine maleate (MK-801) on neurologic outcome in a canine model of complete cerebral ischemia: correlation with hippocampal histopathology.

This study was designed to determine if dizocilipine maleate (MK-801), administered following 11 min of complete ischemia in dogs, could favorably alter neurologic outcome and hippocampal damage. Eighteen dogs were anesthetized and subjected to complete cerebral ischemia by temporary occlusion of the ascending aorta and the venae cavae via a thoracotomy. Five min postischemia, 9 dogs were given dizocilipine 150 micrograms/kg, followed by an infusion of 1.25 microgram/kg/min for 8 h. Control dogs were given equal volumes of placebo. Dogs were evaluated neurologically at 24, 48, and 72 h; thereafter, the brains were perfused, fixed and harvested. There was no significant difference in outcome between dizocilipine- and placebo-treated dogs: 5 of 9 given dizocilipine were normal, 1 was mildly injured and 3 were severely injured or dead. In the control animals given placebo, 3 of 9 were normal, 2 were mildly injured and 4 were moderately to severely injured. Histopathologic examination was limited to the hippocampus. CA1 and CA2,3,4 pyramidal neurons were graded according to degree of injury on a 5-point scale. There were no differences in histopathologic grades between the two groups. However, in both groups combined there was a significant correlation between neurologic outcome grade and histopathologic grade. The only notable systemic effect of dizocilipine appeared to be prolonged sedation which extended beyond 24 h postischemia but was not evident at 48 h postischemia. The authors conclude that more outcome studies in more sensitive models are needed.

Animals↗
PubMed1989

Parameters affecting occurrence of paradoxical air embolism.

The effects of different patterns of ventilation and intravascular volume infusion on the occurrence of paradoxical air embolism (PAE) were evaluated in 15 pigs with a surgically created atrial septal defect (ASD). A balloon atrial septostomy was created transvenously in anesthetized pigs (mean diameter 8.6 mm +/- 1 mm). Monitoring included transesophageal echocardiography (TEE) of the right and left heart, ECG, EEG, direct arterial pressure, right and left atrial pressures (RAP and LAP), pulmonary artery pressure, and pulmonary capillary wedge pressure (PCWP). With the animal in a head up tilt, air was infused into the superior vena cava at a rate of 0.27 ml.kg-1.min-1 for 6 min or until PAE was identified on the TEE. Four situations were studied--intermittent positive pressure ventilation (IPPV), intermittent positive pressure ventilation with 10 cm H2O positive end-expiratory pressure (PEEP), spontaneous ventilation, and IPPV following infusion of 500 ml hetastarch. The incidence of PAE was not different in any of the four situations. Release of PEEP resulted in an increase in the amount of PAE or new PAE in nine of 14 animals. PAE occurred both with and without mean RAP exceeding mean LAP and the incidence of PAE was not significantly different based on the atrial pressure gradient. In situations during which the mean LAP remained greater than mean RAP throughout the venous air infusion and PAE occurred, transient reversal of the right to left atrial pressure gradient during a portion of each cardiac cycle was demonstrated.

Animals↗
PubMed1988

Post-ischemic neurologic recovery and cerebral blood flow using a compression model of complete "bloodless" cerebral ischemia in dogs.

Complete "bloodless" cerebral ischemia was produced in 14 dogs by increasing intracranial pressure above systolic blood pressure (compression ischemia) for 10 min after the onset of an isoelectric EEG. Six dogs were observed for 48 h post-ischemia to assess neurologic recovery, and in 6 other dogs, acute post-ischemic cerebral blood flow was determined for 2 h. In 2 additional dogs, pre-ischemic and intra-ischemic cerebral blood volume (CBV) was measured using 111In-labeled red blood cells. Compression ischemia resulted in 2 of 6 dogs that were normal at 48 h post-ischemia, 3 dogs had moderate cerebral injury, and 1 dog died. These results were similar to results from previous studies in our laboratory in which complete "stagnant" cerebral ischemia of a comparable duration was produced in dogs using aortic and caval cross-clamping. Restoration of cerebral perfusion pressure following compression ischemia was accompanied by an initial phase of cerebral hyperemia followed by a delayed period of hypoperfusion similar to that observed following stagnant ischemia. The CBV studies in 2 dogs revealed that compression ischemia decreased CBV to 12% and 14% of pre-ischemic control values, respectively. The authors conclude, contrary to previous reports, that compression ischemia, although producing near bloodless ischemia, does not improve the brain's tolerance to ischemia.

Animals↗
PubMed1988

Effects of atracurium, vecuronium or pancuronium pretreatment on lignocaine seizure thresholds in cats.

Among the non-depolarizing neuromuscular blocking drugs, atracurium appears to be unique in its ability to produce cerebral stimulation in lightly anaesthetized animals. This effect is attributed to the atracurium metabolite, laudanosine. The following studies were performed to determine if pretreatments with the non-depolarizing neuromuscular blockers pancuronium, atracurium or vecuronium would differ in their effects on the seizure threshold of lignocaine. Adult mongrel cats were anaesthetized with 1.0 MAC halothane in oxygen and nitrogen. Ventilation, blood-gas tensions, acid-base balance and temperature were controlled. Cats received pancuronium 0.2 mg kg 1 i.v. (n = 7), atracurium 1.0 mg kg-1 i.v. (n = 7) or vecuronium 0.2 mg kg-1 i.v. (n = 7). Ten minutes after the administration of the myoneural blocker, all cats received lignocaine 4 mg kg-1 min-1 i.v. until the onset of EEG evidence of generalized seizure activity. At seizure onset, there were no statistically significant differences among the cumulative lignocaine doses or the serum lignocaine concentrations in cats pretreated with pancuronium, atracurium or vecuronium.

Anesthesia, Inhalation↗
PubMed1988

Cerebral effects of high-dose midazolam and subsequent reversal with Ro 15-1788 in dogs.

The effects of a continuous high-dose infusion of midazolam on cerebral function, metabolism, and hemodynamics were studied in nine dogs receiving a spinal anesthetic and breathing 65% nitrogen/35% oxygen. In five dogs, the effects of 65% nitrous oxide (N2O) inspired and the benzodiazepine antagonist Ro 15-1788 were also examined. Midazolam was infused at a rate of 0.66 mg.kg-1.min-1 for 60 min for a total dose of 40 mg.kg-1. Cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) (measured by venous outflow technique) both decreased until a plateau level was reached at approximately 75% of control values (4.0 +/- 0.2 ml.min-1.100 g-1 and 49 +/- 3 ml.min-1.100 g-1, respectively, mean +/- SEM). This occurred after 6-10 mg.kg-1 of midazolam, corresponding to serum midazolam levels between 18.4 +/- 3.8 and 31.2 +/- 3.3 micrograms.ml-1. Serum midazolam levels increased throughout the midazolam infusion, reaching a mean value of 53 +/- 5.5 micrograms.ml-1 by the end of the midazolam infusion. A similar plateau was seen for changes in the electroencephalogram (EEG), which never developed burst suppression. Five dogs inspired 65% nitrous oxide/35% oxygen during minutes 30-45 of the midazolam infusion, rather than 65% nitrogen/35% oxygen. Nitrous oxide had no effect upon CMRO2, but significantly increased CBF when compared to dogs receiving nitrogen. Ro 15-1788, 1.0 mg.kg-1 caused a return of CMRO2 and EEG activity to control levels. CBF and intracranial pressure (ICP) increased markedly, to greater than control levels immediately following Ro 15-1788.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗