Coma Research Today is a free monthly online journal that collates and summarizes the latest research about Coma, including details on causes, diabetes, gcs, recovery.

Acute beta-blockade prevents myocardial beta-adrenergic receptor desensitization and preserves early ventricular function after brain death.

Pandalai PK, McLean KM, Bulcao CF, Duffy JY, D'Souza KM, Merrill WH, Pearl JM, Akhter SA

Department of Surgery, Section of Cardiothoracic Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

OBJECTIVE: Beta-adrenergic receptor desensitization through activation of the G protein-coupled receptor kinase 2 is an important mechanism of early cardiac dysfunction after brain death. We hypothesized that acute beta-blockade can prevent myocardial beta-adrenergic receptor desensitization after brain death through attenuation of G protein-coupled receptor kinase 2 activity, resulting in improved cardiac function. METHODS: Adult pigs underwent either sham operation, induction of brain death, or treatment with esmolol (beta-blockade) for 30 minutes before and 45 minutes after brain death (n = 8 per group). Cardiac function was assessed at baseline and for 6 hours after the operation. Myocardial beta-adrenergic receptor signaling was assessed 6 hours after operation by measuring sarcolemmal membrane adenylate cyclase activity, beta-adrenergic receptor density, and G protein-coupled receptor kinase 2 expression and activity. RESULTS: Baseline left ventricular preload recruitable stroke work was similar among sham, brain death, and beta-blockade groups. Preload recruitable stroke work was significantly decreased 6 hours after brain death versus sham, and beta-blockade resulted in maintenance of baseline preload recruitable stroke work relative to brain death and not different from sham. Basal and isoproterenol-stimulated adenylate cyclase activities were preserved in the beta-blockade group relative to the brain death group and were not different from the sham group. Left ventricular G protein-coupled receptor kinase 2 expression and activity in the beta-blockade group were markedly decreased relative to the brain death group and similar to the sham group. Beta-adrenergic receptor density was not different among groups. CONCLUSION: Acute beta-blockade before brain death attenuates beta-adrenergic receptor desensitization mediated by G protein-coupled receptor kinase 2 and preserves early cardiac function after brain death. These data support the hypothesis that acute beta-adrenergic receptor desensitization is an important mechanism in early ventricular dysfunction after brain death. Future studies with beta-blocker therapy immediately after brain death appear warranted.

Published 31 March 2008 in J Thorac Cardiovasc Surg, 135(4): 792-8.
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Articles on Coma published 17 March 2008:

Comparison of the novel hydroxyethylstarch 130/0.4 and hydroxyethylstarch 200/0.6 in brain-dead donor resuscitation on renal function after transplantation.   Br J Anaesth, 100(4): 504-8.

BACKGROUND: The renal effect of hydroxyethylstarch (HES) solutions remains controversial. We hypothesized that the use of HES with a mean molecular weight of 130 kDa would reduce renal dysfunctions in the recipients. Our study was aimed at comparing the effects of two fluid regimens (HES 130/0.4 or HES 200/0.6) used for the resuscitation of brain-dead donors on the rate of delayed graft function (DGF) and the serum creatinine levels post-transplantation. METHODS: This retrospective ... [Abstract] [Full-text]

Articles on Coma published 22 January 2008:

Variability of brain death determination guidelines in leading US neurologic institutions.   Neurology, 70(4): 284-9.

BACKGROUND: In accordance with the Uniform Determination of Death Act, guidelines for brain death determination are developed at an institutional level, potentially leading to variability of practice. We evaluated the differences in brain death guidelines in major US hospitals with a strong presence of neurology and neurosurgery to determine whether there was evidence of variation from the guidelines as put forth by the American Academy of Neurology (AAN). METHODS: We requested the guidelines ... [Abstract] [Full-text]

Articles on Coma published 18 December 2007:

Therapeutic hypothermia in comatose patients after out-of-hospital cardiac arrest.   Anaesthesia, 63(1): 15-9.

Our intensive care unit has been treating comatose patients, following an out-of-hospital cardiac arrest, with therapeutic hypothermia since 2002. In all, 139 out-of-hospital cardiac arrest patients were admitted in the 4-year period 2002-5. Of these, 27% had a favourable outcome (discharged home or to rehabilitation). Forty-one per cent of patients presenting with ventricular fibrillation (VF) and 7% of non-VF patients had a favourable outcome. No patient with an estimated time from collapse ... [Abstract] [Full-text]

Articles on Coma published 12 December 2007:

Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial.   JAMA, 298(22): 2644-53.

CONTEXT: Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction. OBJECTIVE: To determine ... [Abstract] [Full-text]

Articles on Coma published 6 December 2007:

Coma with diffuse white matter hemorrhages in juvenile diabetic ketoacidosis.   Pediatrics, 120(6): e1540-6.

Cerebral edema is the most common neurologic complication of diabetic ketoacidosis in children. A minority of young patients with intracerebral crises in diabetic ketoacidosis present with cerebrovascular accidents. We report 2 adolescent patients with diabetic ketoacidosis who presented with coma and diffuse white matter hemorrhages in the absence of either cerebral edema or cerebrovascular accidents. These 2 cases illustrate a novel clinical and neuropathologic description of diffuse white ... [Abstract] [Full-text]

Articles on Coma published 8 October 2007:

The endothelin axis and gelatinase activity in alveolar macrophages after brain-stem death injury: a pilot study.   J Heart Lung Transplant, 26(10): 1040-7.

BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstricting mitogen that has been implicated in the development of primary graft dysfunction. Increased activity of matrix metalloproteinases (MMPs), specifically MMP-2 and -9, has been associated with tissue damage in acute lung injury and after lung transplantation. Using a validated model of brain-stem death (BSD), we aimed to determine whether alveolar macrophage up-regulation in the pulmonary system is an early feature of BSD injury and if ... [Abstract] [Full-text]

Articles on Coma published 27 September 2007:

Hypersensitivity of the anesthesia-induced comatose brain.   J Neurosci, 27(39): 10597-607.

Increasing levels of anesthesia are thought to produce a progressive loss of brain responsiveness to external stimuli. Here, we present the first report of a state window within anesthesia-induced coma, usually associated with an EEG pattern of burst suppression, during which brain excitability is dramatically increased so that even subliminal stimuli elicit bursts of whole-brain activity. We investigated this phenomenon in vivo using intracellular recordings of both neurons and glia, as well ... [Abstract] [Full-text]

Articles on Coma published 8 August 2007:

Dopamine treatment in brain-dead rats mediates anti-inflammatory effects: the role of hemodynamic stabilization and D-receptor stimulation.   Transpl Int, 20(9): 790-9.

Brain death (BD) is associated with profound inflammation in end-organs. Dopamine (DA) treatment reduces this inflammatory response, but the underlying mechanisms remain thus far largely unknown. In this study, we investigated if the anti-inflammatory effect of DA was related to hemodynamic stabilization and by which receptors it was mediated. BD was induced in F344 donor rats. DA was given either before BD for 24 h or after BD induction during a definite time. Adrenergic or D-receptor blockers ... [Abstract] [Full-text]

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