Cardiac Reactive Oxygen Species After Traumatic Brain Injury
ABSTRACT Cardiovascular complications after traumatic brain injury (TBI) contribute to morbidity and mortality and may provide a target for therapy. We examined blood pressure and left ventricle contractility after TBI, and tested the hypothesis that β-adrenergic blockade would decrease oxidative stress after TBI.
Rodents received fluid-percussion injury or sham surgery, confirmed with magnetic resonance imaging (MRI) and histopathology. We followed recovery with sensorimotor coordination testing and blood pressure measurements. We assessed left ventricular ejection fraction using ECG-gated cardiac MRI and measured myocardial reactive oxygen species (ROS) with dihydroethidium. We randomized additional TBI and sham animals to postoperative treatment with propranolol or control, for measurement of ROS.
Blood pressure and cardiac contractility were elevated 48 h after TBI. Myocardial tissue sections showed increased ROS. Treatment with propranolol diminished ROS levels following TBI.
TBI is associated with increased cardiac contractility and myocardial ROS; decreased myocardial ROS after β-blockade suggests that sympathetic stimulation is a mechanism of oxidative stress.
SourceAvailable from: Beydolah Shahouzehi[Show abstract] [Hide abstract]
ABSTRACT: Accidents are the second reason for mortality and morbidity in Iran. Among them, brain injuries are the most important damage. Clarification of the effects of brain injuries on different body systems will help physicians to prioritize their treatment strategies. In this study, the effect of pure brain trauma on the cardiovascular system and lungs 24 hours post trauma was assessed.Iranian biomedical journal 10/2014; 18(4):225-31.
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ABSTRACT: Traumatic brain injury (TBI) has been reported to increase the concentration of nitric oxide (NO) in the brain and can lead to loss of cerebrovascular tone; however, the sources, amounts, and consequences of excess NO on the cerebral vasculature are unknown. Our objective was to elucidate the mechanism of decreased cerebral artery tone after TBI. Cerebral arteries were isolated from rats 24 hours after moderate fluid-percussion TBI. Pressure-induced increases in vasoconstriction (myogenic tone) and smooth muscle Ca(2+) were severely blunted in cerebral arteries after TBI. However, myogenic tone and smooth muscle Ca(2+) were restored by inhibition of NO synthesis or endothelium removal, suggesting that TBI increased endothelial NO levels. Live native cell NO, indexed by 4,5-diaminofluorescein (DAF-2 DA) fluorescence, was increased in endothelium and smooth muscle of cerebral arteries after TBI. Clamped concentrations of 20 to 30 nmol/L NO were required to simulate the loss of myogenic tone and increased (DAF-2T) fluorescence observed following TBI. In comparison, basal NO in control arteries was estimated as 0.4 nmol/L. Consistent with TBI causing enhanced NO-mediated vasodilation, inhibitors of guanylyl cyclase, protein kinase G, and large-conductance Ca(2+)-activated potassium (BK) channel restored function of arteries from animals with TBI. Expression of the inducible isoform of NO synthase was upregulated in cerebral arteries isolated from animals with TBI, and the inducible isoform of NO synthase inhibitor 1400W restored myogenic responses following TBI. The mechanism of profound cerebral artery vasodilation after TBI is a gain of function in vascular NO production by 60-fold over controls, resulting from upregulation of the inducible isoform of NO synthase in the endothelium. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.Journal of the American Heart Association 10/2014; 3(6). DOI:10.1161/JAHA.114.001474 · 2.88 Impact Factor
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ABSTRACT: Traumatic brain injury (TBI) is associated with a systemic hyperadrenergic state. Through activation of beta adrenoreceptors, catecholamines may induce hypermetabolism and increase both cardiac and cerebral oxygen demands. We conducted a systematic review to appraise the available evidence examining the safety and efficacy of beta blockers in patients with acute TBI. We systematically searched CENTRAL, MEDLINE, EMBASE and the reference lists of relevant articles from database inception until March 19, 2013. The outcomes assessed were in-hospital mortality, functional outcome and quality of life. Common adverse effects of beta blockers were examined including clinically significant hypotension, bradycardia, bronchospasm and congestive heart failure. Data on study outcomes and quality were abstracted in duplicate. The results were summarized descriptively and quantitatively. One randomized controlled trial was found with a high risk of bias. Eight retrospective cohort studies were found with a moderate risk of bias; however, only four of these studies were identified as unique after excluding overlapping cases. The cohort studies reported mortality outcomes; however, none of these included studies assessed functional outcomes or quality of life. Meta-analysis on the cohort studies (n = 4,782 patients) demonstrated that exposure to beta blockers after TBI was associated with a reduction in the adjusted odds of in-hospital mortality by 65 % (pooled adjusted odds ratio 0.35; 95 % CI 0.27-0.45). The current body of evidence is suggestive of a benefit of beta blockers following TBI. However, methodologically sound randomized controlled trials are indicated to confirm the efficacy of beta blockers in patients with TBI.Neurocritical Care 09/2013; DOI:10.1007/s12028-013-9903-5 · 2.60 Impact Factor