Biomedical subjects

Kristin Engelhard

Publications and source records attributed to Kristin Engelhard.

11 recordsLinked to original sources

PubMed2006

Inhalational or intravenous anesthetics for craniotomies? Pro inhalational.

PURPOSE OF REVIEW: In neurosurgery, anesthesiologists and surgeons focus on the same target - the brain. The nature of anesthetics is to interact with brain physiology, leading to favorable and adverse effects. Research in neuroanesthesia over the last three decades has been dedicated to identifying the optimal anesthetic agent to maintain coupling between cerebral blood flow and metabolism, keep cerebrovascular autoregulation intact, and not increase cerebral blood volume and intracranial pressure. RECENT FINDINGS: Sevoflurane is less vasoactive than halothane, enflurane, isoflurane, or desflurane. The context sensitive half-life is short and similar to that of desflurane, which translates into fast on and offset. Compared with propofol, sevoflurane decreases cerebral blood flow to a lesser extent, while cerebral metabolism is suppressed to the same degree. Sevoflurane does not increase intracranial pressure, while propofol decreases intracranial pressure. SUMMARY: In neurosurgical patients with normal intracranial pressure, sevoflurane might be a good alternative to propofol. In patients with reduced intracranial elastance, caused by space occupying lesions, with elevated intracranial pressure or complex surgical approaches, propofol should remain first choice.

Anesthesia Recovery Period↗

PubMed2006

The long-term effect of sevoflurane on neuronal cell damage and expression of apoptotic factors after cerebral ischemia and reperfusion in rats.

We investigated the long-term effects of sevoflurane on histopathologic injury and key proteins of apoptosis in a rat hemispheric ischemia/reperfusion model. Sixty-four male Sprague-Dawley rats were randomly assigned to Group 1 (fentanyl and N2O/O2; control) and Group 2 (2.0 vol% sevoflurane and O2/air). Ischemia (45 min) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension (mean arterial blood pressure 40 mm Hg). Animals were killed after 1, 3, 7, and 28 days. In hematoxylin and eosin-stained brain sections eosinophilic hippocampal neurons were counted. Activated caspase-3 and the apoptosis-regulating proteins Bax, Bcl-2, Mdm-2, and p53 were analyzed by immunostaining. No eosinophilic neurons were detected in sevoflurane-anesthetized rats over time, whereas 9%-38% of the hippocampal neurons were eosinophilic (days 1-28) in control animals. On days 1 and 3, the concentration of Bax was 140%-200% larger in fentanyl/N2O-anesthetized animals compared with sevoflurane. Bcl-2 was 100% less in control animals during the first 3 days. Activated caspase-3 was detected in neurons of both groups (0.75%-2.2%). These data support a sustained neuroprotective potency of sevoflurane related to reduced eosinophilic injury after cerebral ischemia/reperfusion.

Anesthetics, Inhalation↗

PubMed2006

The effect of electroencephalogram-targeted high- and low-dose propofol infusion on histopathological damage after traumatic brain injury in the rat.

BACKGROUND: Propofol is commonly used to sedate patients after traumatic brain injury. However, the dose-dependent neuroprotective effects of propofol after head trauma are unknown. We compared histopathological damage after 6 h of electroencephalogram-targeted high- and low-dose propofol infusion in rats subjected to controlled cortical impact (CCI). METHODS: Animals were randomly assigned to CCI/propofol with electroencephalogram burst-suppression-ratio 1%-5% (CCI/lowprop), CCI/propofol with burst-suppression-ratio 30%-40% (CCI/highprop), control group CCI/1.0 vol % halothane (CCI/halo), or sham group with halothane anesthesia (SHAM/halo). Brain slices were stained with kresyl violet (KV) and hematoxylin/eosin (HE) to evaluate lesion volume, number of eosinophilic cells, and activation of caspase-3 in the hippocampus. RESULTS: Lesion volume (mm3) and number of eosinophilic cells in the hippocampus did not differ significantly [lesion volumes: CCI/lowprop 31.55 +/- 14.66 (KV) and 53.77 +/- 8.62 (HE); CCI/highprop 33.81 +/- 10.57 (KV) and 52.30 +/- 11.55 (HE); CCI/halo 36.42 +/- 17.06 (KV) and 57.95 +/- 8.49 (HE)]. Activation of caspase-3 occurred in the ipsilateral hippocampus in all CCI-groups. CONCLUSION: Despite different levels of cortical neuronal function, there were no relevant differences in the short-term histopathological damage. These results challenge the view that the neuroprotective effect of propofol relates to the suppression of cerebral metabolic demand.

Animals↗

PubMed2005

New cerebral protection strategies.

PURPOSE OF REVIEW: This article presents an overview of the most recent and important strategies to reduce secondary brain damage. RECENT FINDING: There is currently no magic bullet available to protect the brain after neuronal injury. This is related to the complex pathophysiology of cerebral ischemia, which makes it unlikely that a single pharmacological intervention results in sustained neuroprotection. Analyses of clinical studies reveal that acute physiologic derangements (e.g. fever, hypertension and hypotension, hypoxemia, hypercapnia, hyperglycemia) are the most important predictors of unfavorable outcome after brain injury and have to be treated. The effectiveness of anesthetic agents to extend the ischemic tolerance of neurons has been demonstrated in experimental settings, but such benefits have not been demonstrated in humans. The effectiveness of osmodiuretics to decrease elevated intracranial pressure, a factor with relevance to outcome, has been demonstrated. Infusion of magnesium in patients with subarachnoidal hemorrhage can reduce the occurrence of delayed ischemia caused by cerebrovascular spasm. The prophylactic administration of glucocorticoids should be avoided. While the positive effects of chronic administration of statins to reduce the incidence of stroke has been demonstrated in several clinical studies, the protective effect of acute administration of statins after a cerebral insult has do be defined. SUMMARY: Control of physiological variables, avoidance of hyperthermia, intensive control of plasma glucose concentrations, use of anesthetic agents and osmodiuretics to control intracranial hypertension and the possible prophylactic administration of magnesium in patients at risk of vasospasm and of statins in patients with cerebrovascular risk factors are currently the most important strategies to reduce neuronal injury.

Journal Article↗

PubMed2005

Sevoflurane impairs cerebral blood flow autoregulation in rats: reversal by nonselective nitric oxide synthase inhibition.

UNLABELLED: In this study, we investigated the effects of 1.0 and 2.0 minimum alveolar anesthetic concentration (MAC) sevoflurane on cerebral blood flow (CBF) autoregulation before and after nonselective inhibition of nitric oxide (NO) synthase in rats. Rats were randomly assigned as follows: Group 1 (n = 8): 1.0 MAC sevoflurane; Groups 2 and 3 (n = 8 per group): 2.0 MAC sevoflurane. Assessment of autoregulation within a mean arterial blood pressure range of 140-60 mm Hg was performed by graded hemorrhage before and after administration of l-arginine methyl ester (l-NAME, 30 mg/kg IV, Groups 1 and 2) or during hypocapnia (Group 3). In 10 additional animals, brain tissue NO(2)(-) concentrations were measured at 1.0 and 2.0 MAC sevoflurane. CBF autoregulation was maintained with 1.0 MAC sevoflurane (Group 1) regardless of NO synthase status indicating that CBF autoregulation might not be related to NO availability. Sevoflurane dose-dependently increased brain tissue NO(2)(-) and impaired CBF autoregulation. Administration of l-NAME (Group 2) but not hypocapnia (Group 3) restored CBF autoregulation. This suggests that sevoflurane impairs the autoregulatory capacity secondary to an increase of the perivascular NO availability and questions the importance of basal cerebrovascular tone in terms of vasodilatory capacity during hypotensive challenges. IMPLICATIONS: The present study suggests that the volatile anesthetic sevoflurane dose-dependently impairs cerebrovascular autoregulation by mechanisms secondary to increase of perivascular nitric oxide availability.

Anesthetics, Inhalation↗

PubMed2004

Influence of propofol on neuronal damage and apoptotic factors after incomplete cerebral ischemia and reperfusion in rats: a long-term observation.

BACKGROUND: Propofol reduces neuronal damage from cerebral ischemia when investigated for less than 8 postischemic days. This study investigates the long-term effects of propofol on neuronal damage and apoptosis-related proteins after cerebral ischemia and reperfusion. METHODS: Male Sprague-Dawley rats were randomly assigned as follows: group 1 (n = 32, control): fentanyl and nitrous oxide-oxygen; group 2 (n = 32, propofol): propofol and oxygen-air. Ischemia (45 min) was induced by carotid artery occlusion and hemorrhagic hypotension. Pericranial temperature and arterial blood gases were maintained constant. After 1, 3, 7, and 28 postischemic days, brains were removed, frozen, and sliced. Hippocampal eosinophilic cells were counted. The amount of apoptosis-related proteins Bax, p53, Bcl-2, and Mdm-2 and neurons positive for activated caspase-3 were analyzed. RESULTS: In propofol-anesthetized rats, no eosinophilic neurons were detected, whereas in control animals, 16-54% of hippocampal neurons were eosinophilic (days 1-28). In control animals, the concentration of Bax was 70-200% higher after cerebral ischemia compared with that in animals receiving propofol over time. Bcl-2 was 50% lower in control animals compared with propofol-anesthetized rats during the first 3 days. In both groups, a maximal 3% of the hippocampal neurons were positive for activated caspase-3. CONCLUSIONS: These data show sustained neuroprotection with propofol. This relates to reduced eosinophilic and apoptotic injury. Activated caspase-3-dependent apoptotic pathways were not affected by propofol. This suggests the presence of activated caspase-3-independent apoptotic pathways.

Animals↗

PubMed2004

Managing elevated intracranial pressure.

PURPOSE OF REVIEW: Elevated intracranial pressure is one of the major deteriorating factors in patients with intracerebral lesions. Therefore, every year many experimental and clinical studies are performed to identify the best method for managing elevated intracranial pressure in head-injured patients. The current review summarizes the most important recent findings for the treatment of increased intracranial pressure. RECENT FINDINGS: The currently most discussed treatments of elevated intracranial pressure are the use of hypertonic saline, which seems to be equal to mannitol, the use of hypothermia, and the performance of decompressive craniectomy. SUMMARY: The treatment strategy to manage increased intracranial pressure includes decisions about anaesthetics, ventilation, head and body position, hypothermia, the use of osmotic drugs and surgical procedures. Propofol seems to be suitable for the sedation of patients with elevated intracranial pressure. Sudden increases in intracranial pressure can be treated using hyperosmotic agents, high-dose thiopental, or short episodes of mild hyperventilation. Surgical decompression of the cranium seems to improve the outcome in patients below the age of 50 years, especially children.

Journal Article↗

PubMed2003

The effect of the alpha 2-agonist dexmedetomidine and the N-methyl-D-aspartate antagonist S(+)-ketamine on the expression of apoptosis-regulating proteins after incomplete cerebral ischemia and reperfusion in rats.

In this study, we investigated whether the neuroprotection previously seen with dexmedetomidine or S(+)-ketamine involves regulation of proapoptotic (Bax and p53) and antiapoptotic (Bcl-2 and Mdm-2) proteins. Rats were anesthetized with isoflurane. After surgical preparation of isoflurane was discontinued, animals were randomly assigned to receive fentanyl and nitrous oxide (N(2)O)/oxygen plus 100 microg/kg of dexmedetomidine intraperitoneally 30 min before ischemia (n = 8), 1 mg x kg(-1) x min(-1) of S(+)-ketamine and oxygen/air (n = 8), or fentanyl and N(2)O/oxygen (n = 8; control group). In all three treatment groups, incomplete cerebral ischemia (30 min) was induced by unilateral carotid artery occlusion and hemorrhagic hypotension to a mean arterial blood pressure of 30-35 mm Hg. Four hours after the start of reperfusion, the brains were removed, and the expression of apoptosis-regulating proteins was determined by using immunofluorescence and Western blot analysis. The results were compared with sham-operated animals (n = 8). After cerebral ischemia/reperfusion, the relative protein concentration of Bax was increased by 110% in control animals compared with the dexmedetomidine- and S(+)-ketamine-treated rats and by 140% compared with the sham-operated animals. In animals treated with dexmedetomidine, the expression of Bcl-2 and Mdm-2 was larger compared with control (68% and 210%, respectively) or sham-operated (110% and 180%, respectively) animals. Therefore, it is possible that the neuroprotective properties of dexmedetomidine and S(+)-ketamine seen in previous studies involve ultra-early modulation of the balance between pro- and antiapoptotic proteins.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2003

The effect of hypothermia on the expression of the apoptosis-regulating protein Bax after incomplete cerebral ischemia and reperfusion in rats.

This study investigated the effects of hypothermia on apoptosis-regulating proteins in a rat model of incomplete cerebral ischemia. Twenty-seven fasted male Sprague-Dawley rats (300-420 g) were anesthetized, intubated, and mechanically ventilated with 2.0% isoflurane and N(2)O/O(2) (FiO(2) = 0.33). Catheters were inserted and cerebral blood flow velocity was measured using bilateral laser Doppler flowmetry. At the end of preparation, the administration of isoflurane was replaced by fentanyl (25 microg. kg(-1). h(-1)). Animals were randomly assigned to one of the following groups: group 1 (n = 9, normothermia), normothermia (37.5 degrees C) during ischemia; group 2 (n = 9, hypothermia), 34 degrees C pericranial temperature during ischemia; and group 3 (n = 9, sham-operated animals), normothermia, no cerebral ischemia. Ischemia (30 minutes) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension (mean arterial blood pressure 30-35 mm Hg). Arterial blood gas tensions and pH were maintained constant. Four hours after 30 minutes of incomplete cerebral ischemia, the brains were removed for determination of the expression of the apoptosis-regulating proteins Bax, Bcl-2, p53, and Mdm-2 using immunofluorescence and Western blot analysis. Four hours after cerebral ischemia there was a significant increase in the expression of the pro-apoptotic protein Bax in normothermic animals compared with hypothermic (85-260%) and sham-operated animals (60-190%). The proteins Bcl-2, p53, and Mdm-2 showed no statistically significant differences between the groups or between the hemispheres. In conclusion, hypothermia during ischemia decreased Bax protein expression that is associated with programed cell death. This suggests that neuroprotection seen with hypothermia may be related to a reduction of pro-apoptotic events.

Animals↗

PubMed2003

The effect of sevoflurane and propofol on cerebral neurotransmitter concentrations during cerebral ischemia in rats.

UNLABELLED: Sevoflurane and propofol are neuroprotective possibly by attenuating central or peripheral catecholamines. We evaluated the effect of these anesthetics on circulating catecholamines and brain neurotransmitters during ischemia in rats. Forty male Sprague-Dawley rats were randomly assigned to one of the following treatment groups: fentanyl and N(2)O/O(2) (control), 2.0% sevoflurane, 0.8-1.2 mg x kg(-1) x min(-1) of propofol, and sham-operated rats with fentanyl and N(2)O/O(2). Ischemia (30 min) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 32 +/- 2 mm Hg. Pericranial temperature, arterial blood gases, and pH value were maintained constant. Cerebral catecholamine and glutamate concentrations, sampled by microdialysis, and plasma catecholamine concentrations were analyzed using high-pressure liquid chromatography. During ischemia, circulating catecholamines were almost completely suppressed by propofol but only modestly decreased with sevoflurane. Sevoflurane and propofol suppressed brain norepinephrine concentration increases by 75% and 58%, respectively, compared with controls. Intra-ischemia cerebral glutamate concentration was decreased by 60% with both sevoflurane and propofol. These results question a role of circulating catecholamines as a common mechanism for cerebral protection during sevoflurane and propofol. A role of brain tissue catecholamines in mediating ischemic injury is consistent with our results. IMPLICATIONS: During incomplete cerebral ischemia, the neuroprotective anesthetics sevoflurane and propofol suppressed cerebral increases in norepinephrine and glutamate concentrations. In contrast, propofol, but not sevoflurane, suppressed the ischemia-induced increase in circulating catecholamines to baseline levels. The results question a role for plasma catecholamines in cerebral ischemic injury.

Anesthetics, Inhalation↗

PubMed2002

Effect of the alpha2-agonist dexmedetomidine on cerebral neurotransmitter concentrations during cerebral ischemia in rats.

BACKGROUND: This study investigates whether neuroprotection seen with dexmedetomidine is associated with suppression of peripheral or central sympathetic tone. METHODS: Thirty fasted male Sprague-Dawley rats were intubated and ventilated with isoflurane and N2O/O2 (fraction of inspired oxygen = 0.33). Catheters were inserted into the right femoral artery and vein and into the right jugular vein. Cerebral blood flow was measured using laser Doppler flowmetry. Bilateral microdialysis probes were placed into the cortex and the dorsal hippocampus. At the end of preparation, the administration of isoflurane was replaced by fentanyl (bolus: 10 microg/kg; infusion: 25 microg x kg(-1) x h(-1)). Animals were randomly assigned to one of the following groups: group 1 (n = 10): control animals; group 2 (n = 10): 100 microg/kg dexmedetomidine administered intraperitoneally 30 min before ischemia; group 3 (n = 10): sham-operated rats. Ischemia (30 min) was produced by unilateral carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 30-35 mmHg to reduce ipsilateral cerebral blood flow by 70%. Pericranial temperature, arterial blood gases, and pH were maintained constant. Cerebral catecholamine and glutamate concentrations and plasma catecholamine concentrations were analyzed using high-performance liquid chromatography. RESULTS: During ischemia, dexmedetomidine suppressed circulating norepinephrine concentrations by 95% compared with control animals. In contrast, brain norepinephrine and glutamate concentrations were increased irrespective of dexmedetomidine infusion before ischemia. CONCLUSIONS: The current data show that the increase of circulating catecholamine concentrations during cerebral ischemia was suppressed with dexmedetomidine. In contrast, dexmedetomidine does not suppress elevation in brain norepinephrine and glutamate concentration associated with cerebral ischemia. This suggests that the neuroprotective effects of dexmedetomidine are not related to inhibition of presynaptic norepinephrine or glutamate release in the brain.

Adrenergic alpha-2 Receptor Agonists↗