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Manfred Blobner

Publications and source records attributed to Manfred Blobner.

11 recordsLinked to original sources
PubMed2006

Neurologic outcome after cardiopulmonary bypass with deep hypothermic circulatory arrest in rats: description of a new model.

OBJECTIVE: Neurodevelopmental impairments after repair of congenital heart disease with cardiopulmonary bypass and deep hypothermic circulatory arrest continue to affect the lives of children. To date, the preclinical investigation of cerebral injury mechanisms related to deep hypothermic circulatory arrest has been restricted to expensive, personnel-demanding, and cumbersome large-animal models without validated neuropsychologic assessment. We aimed to establish a rodent recovery model of deep hypothermic circulatory arrest to overcome these disadvantages. METHODS: Male rats (n = 34) were cannulated for cardiopulmonary bypass, cooled to a rectal temperature of 16 degrees C to 18 degrees C within 30 minutes, and assigned to deep hypothermic circulatory arrest durations of 0, 45, 60, 75, 90 (n = 6, respectively), or 105 (n = 4) minutes. After rewarming within 40 minutes, animals were weaned from cardiopulmonary bypass at 35.5 degrees C. Neurologic and cognitive performance was assessed with the modified hole board test until postoperative day 14. Thereafter, brains were perfusion fixed and histologically analyzed. RESULTS: Logistic regression analyses identified dose-dependent associations between survival, neurologic or cognitive function, and duration of deep hypothermic circulatory arrest. Functional and histologic deficits were detectable after clinically relevant deep hypothermic circulatory arrest durations. The overall neurologic function did not correlate with histologic outcome (r = 0.51, P > .05). CONCLUSIONS: The current study presents a novel recovery model of cardiopulmonary bypass with deep hypothermic circulatory arrest in the rat. In contrast to studies in large animals, even clinically relevant deep hypothermic circulatory arrest durations up to 60 minutes resulted in detectable deficits. Consequently, this experimental model appears to be suitable to further elucidate the mechanisms associated with adverse cerebral outcome after cardiac surgery and deep hypothermic circulatory arrest and to investigate potential neuroprotective strategies.

Animals↗
PubMed2006

Xenon impairs neurocognitive and histologic outcome after cardiopulmonary bypass combined with cerebral air embolism in rats.

BACKGROUND: The neuroprotective properties of xenon may improve cerebral outcome after cardiac surgery using cardiopulmonary bypass (CPB). However, its disposition to expand gaseous bubbles that during CPB present as cerebral air emboli (CAE) could abolish any beneficial effect or even worsen cerebral outcome. Therefore, the authors studied the impact of xenon on neurologic, cognitive, and histologic outcome after CPB combined with CAE in rats. METHODS: With institutional review board approval, 40 rats were assigned to four groups (n = 10). In two CPB-CAE groups, rats were subjected to 90 min of normothermic CPB with 10 repetitively administered CAEs (0.3 microl/bolus). Rats in two sham groups were not exposed to CPB and CAE. Groups were further subdivided into xenon (56%; 20 min before, during, and 30 min after CPB) and nitrogen groups. Neurologic and cognitive function was tested until postoperative day 14, when cerebral infarct volumes were determined. RESULTS: Animals of the CPB-CAE groups showed transient deficits in gross neurologic function. Further, rats of the CPB-CAE-xenon group demonstrated impaired fine motor and cognitive performance persisting until postoperative day 14. Consistently, infarct volumes were larger in the CPB-CAE-xenon group compared with the CPB-CAE-nitrogen group (P = 0.03). CONCLUSIONS: This is the first demonstration in which the neurologic effects of CAE have been examined in a rat model of CPB. Xenon exposure aggravated the neurologic dysfunction that is produced by CAE during CPB; potential neuroprotective effects of xenon may have been masked by the effects of xenon on CAE.

Anesthetics, Inhalation↗
PubMed2006

Postoperative upper airway obstruction after recovery of the train of four ratio of the adductor pollicis muscle from neuromuscular blockade.

Anesthetics, and even minimal residual neuromuscular blockade, may lead to upper airway obstruction (UAO). In this study we assessed by spirometry in patients with a train-of-four (TOF) ratio >0.9 the incidence of UAO (i.e., the ratio of maximal expiratory flow and maximal inspiratory flow at 50% of vital capacity [MEF50/MIF50] >1) and determined if UAO is induced by neuromuscular blockade (defined by a forced vital capacity [FVC] fade, i.e., a decrease in values of FVC from the first to the second consecutive spirometric maneuver of > or =10%). Patients received propofol and opioids for anesthesia. Spirometry was performed by a series of 3 repetitive spirometric maneuvers: the first before induction (under midazolam premedication), the second after tracheal extubation (TOF ratio: 0.9 or more), and the third 30 min later. Immediately after tracheal extubation and 30 min later, 48 and 6 of 130 patients, respectively, were not able to perform spirometry appropriately because of sedation. The incidence of UAO increased significantly (P < 0.01) from 82 of 130 patients (63%) at preinduction baseline to 70 of 82 patients (85%) after extubation, and subsequently decreased within 30 min to values observed at baseline (80 of 124 patients, 65%). The mean maximal expiratory flow and maximal inspiratory flow at 50% of vital capacity ratio after tracheal extubation was significantly increased from baseline (by 20%; 1.39 +/- 1.01 versus 1.73 +/- 1.02; P < 0.01), and subsequently decreased significantly to values observed at baseline (1.49 +/- 0.93). A statistically significant FVC fade was not present, and a FVC fade of > or =10% was observed in only 2 patients after extubation. Thus, recovery of the TOF ratio to 0.9 predicts with high probability an absence of neuromuscular blocking drug-induced UAO, but outliers, i.e., persistent effects of neuromuscular blockade on upper airway integrity despite recovery of the TOF ratio, may still occur.

Adult↗
PubMed2005

GW280430A.

Explore the source record for details and available documents.

Anesthesia↗
PubMed2005

Nitric oxide is not a mediator of inflammation-induced resistance to atracurium.

Resistance to atracurium as a result of increased drug binding to alpha1-acid glycoprotein is associated with increased inducible nitric oxide synthase activity and increased nitric oxide levels in plasma. We investigated if the inhibition of inducible nitric oxide synthase and suppression of nitric oxide can reverse the resistance to atracurium. As a model of alpha1-acid glycoprotein and nitric oxide increase, 84 male Sprague-Dawley rats received an IV injection of either 60 mg/kg Corynebacterium parvum (CP) or saline (control). The 2 groups (CP/Control) were further divided into subgroups, receiving the selective inducible nitric oxide synthase inhibitor, N-Iminolysine, via drinking water at different concentrations. On day 4 post-CP injection, the pharmacodynamics of atracurium were determined. Plasma concentrations of nitric oxide, atracurium, and alpha1-acid glycoprotein were measured and acetylcholine receptor numbers were quantified. In the CP groups, N-Iminolysine suppressed nitric oxide levels in a dose-dependent manner. Resistance to atracurium persisted. alpha1-acid glycoprotein serum levels remained increased in all CP groups with no differences in acetylcholine receptor expression. Our results suggest that the mechanism leading to increased expression of alpha1-acid glycoprotein and consecutive increased protein binding of atracurium is not mediated by inducible nitric oxide synthase induction and nitric oxide expression.

Animals↗
PubMed2004

Up-regulation of acetylcholine receptors during subchronic infusion of pancuronium is caused by a posttranscriptional mechanism related to disuse.

OBJECTIVE: Contrasting with the classic theory that competitive block of the acetylcholine receptor induces up-regulation of the receptor, recent studies show that irreversible block of acetylcholine receptors with alpha-bungarotoxin decreases acetylcholine receptor number within hours. This study investigated the early effects of competitive acetylcholine receptor block with the reversible, competitive muscle relaxant, pancuronium. DESIGN: Prospective, randomized, placebo-controlled experimental study. SUBJECTS: Healthy adult Sprague-Dawley rats. SETTING: Animal laboratory in a university hospital. INTERVENTIONS: After internal review board approval, Sprague-Dawley rats were anesthetized and received pancuronium at a rate to completely suppress neuromuscular twitch. The control group received saline. Infusion times were 0, 3, 6, or 12 hrs (n = 8 per group). One sciatic nerve was stimulated to induce muscle twitch, and the other nerve remained unstimulated. Total acetylcholine receptor expression, as well as expression of messenger RNA of the five subunits, was assayed. MEASUREMENTS AND MAIN RESULTS: There were no differences in acetylcholine receptor number between groups at time points 0, 3, and 6 hrs. At 12 hrs, acetylcholine receptor numbers in both the stimulated (35.2 +/- 4.8 fmol acetylcholine receptor/mg protein) and nonstimulated (38.3 +/- 4.8) pancuronium group, as well as the nonstimulated control saline group (37.5 +/- 4.6), were significantly increased compared with stimulated controls (27.6 +/- 4.0). Pancuronium did not potentiate the acetylcholine receptor up-regulation of the nonstimulated control group at 12 hrs. There were no changes in messenger RNA expression between groups. CONCLUSIONS: Infusion of the reversible competitive inhibitor pancuronium up to 12 hrs does not reduce acetylcholine receptor number and therefore contrasts with the irreversible acetylcholine receptor blocker alpha-bungarotoxin. This study documents that 12 hrs of disuse per se leads to an increased expression of the acetylcholine receptor number by a posttranscriptional mechanism that can be prevented by nerve-evoked muscle contraction.

Animals↗
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

Systemic inflammation leads to resistance to atracurium without increasing membrane expression of acetylcholine receptors.

BACKGROUND: Systemic inflammation may be associated with resistance to nondepolarizing neuromuscular blocking drugs, the mechanisms of which are, however, uncharacterized. The authors therefore investigated the pharmacodynamics of atracurium and its relation to the expression of nicotinic acetylcholine receptors and alpha1 -acid glycoprotein in a rat model of systemic inflammation. METHODS: To induce a systemic inflammation, male CD rats received 56 mg/kg corynebacterium parvum intravenously. On days 2, 4, 6, 8, 10, 12, 14, or 16 after infection, neuromuscular transmission was measured. The individual effective dose of atracurium was determined, followed by an atracurium infusion at a rate to establish a steady state neuromuscular block of 50%. Total and unbound plasma concentrations of atracurium for 50% paralysis were measured using high-performance liquid chromatography. Acetylcholine receptors were quantitated using 125I-alpha-bungarotoxin. alpha1 -Acid glycoprotein concentrations in the serum were measured using a competitive chemiluminescence immunoassay. RESULTS: The effective dose of atracurium was increased on days 4, 6, and 8. Total atracurium plasma concentrations at 50% neuromuscular paralysis were increased on days 4, 6, 8, and 10, with a peak at day 8 (8.0 +/- 1.3 micro g/ml) compared with control rats (4.23 +/- 0.82 micro g/ml). The alpha1 -acid glycoprotein concentrations were increased between days 2 and 10, with a peak on day 4 (6.52 +/- 1.45 mg/ml), and recovered to control values (0.61 +/- 0.33 mg/ml) on day 12. Unbound plasma concentrations of atracurium to achieve 50% depression, as well as the expression of acetylcholine receptors, did not differ between groups. CONCLUSION: Resistance to atracurium during corynebacterium parvum-induced systemic inflammation is due to increased drug binding to alpha1 -acid glycoprotein and is unrelated to changes in acetylcholine receptor expression.

Anesthesia↗
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↗