Matrix metalloproteinases are not involved in early brain edema formation after cardiac arrest in rats
Resuscitation from cardiac arrest (CA) often results in a poor neurological outcome possibly due to an incomplete understanding of the pathophysiology of brain injury following CA-induced global cerebral ischemia. Brain edema is an important manifestation
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© Springer-Verlag 2003
Matrix metalloproteinases are not involved in early brain edema formation after cardiac arrest in rats F. Xiao l , T. Arnold', s. Zhang', N. Imtiaz ', A. Khan 1, J.
s. Alexander", s. Conrad', and D. Carden'
1 Department 2
of Emergency Medicine, Louisiana State University Health Science Center, Shreveport, USA Department of Physiology, Louisiana State University Health Science Center, Shreveport, USA
Summary Introduction. Resuscitation from cardiac arrest (CA) often results in a poor neurological outcome possibly due to an incomplete understanding of the pathophysiology of brain injury following CAinduced global cerebral ischemia . Brain edema is an important manifestation after CA and is associated with significant morbidity and mortality. The matrix metalloproteinases (MMPs) contribute to brain edema formation following focal cerebral ischemia. The objective of this study was to investigate the role of an MMP inhibitor, GM6001 , in CA-elicited brain edema . Methods. Eighteen rats were subjected to normothermic (37.5 ± 0.5 QC) CA induced by eight minutes of asphyxiation and assigned to a CA-control group (CA), an alcohol-placebo group (CA + ETOH), or a GM6001-treated group (CA + GM6001) . GM6001 in 100% alcohol or a vehicle was given i.v. before CA to achieve a whole blood concentration of 10 J.1M. Animals were resuscitated with CPR , ventilation and epinephrine. Brain edema was determined by brain wetto-dry weight ratio at one hour after resuscitation. Findings. Brain wet-to-dry weight ratio was 4.86 ± 0.09 in CA, 4.76 ± 0.12 in CA + ETOH (p = 0.30 vs. CA), and 4.72 ± 0.03 in CA + GM600l (p = 0.17 vs. CA and 0.42 vs. CA + ETOH). Interpretation. MMPs are not involved in brain edema formation one hour following CA . Keywords: Cardiac arrest; brain-blood barrier; matrix metalloproteinase; brain edema; cerebral ischemia and reperfusion .
Introduction Cardiopulmonary resuscitation (CPR) attempts outside of special care units have achieved suboptimal results. Improved neurological recovery in humans after normothermic sudden cardiac arrest (CA) of up to eight minutes would represent an important breakthrough since urban-suburban ambulance response times of eight minutes are feasible. Even when restoration of spontaneous circulation (ROSC) is achieved by current treatments, about 30% of survivors suffer permanent brain damage, including motor and cognitive deficits [19]. The search for brain-damage miti-
gating treatments has been disappointing, primarily due to an incomplete understanding of the pathophysiological alterations following CA. The pathophysiological mechanisms of brain damage caused by CA and resuscitation are complicated and multifactorial [28], including the primary insult of CA (complete temporary global brain ischemia) and secondary inflammatory responses during and after resuscitation, also known as the post-resuscitation syndrome. A characteristic feature of this syndrome is an increased microvascular permeability that ultimately leads to interstitial edema [33]. We have
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