Matrix metalloproteinases are not involved in early brain edema formation after cardiac arrest in rats.
BACKGROUND
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 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 degrees C) 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 microM. Animals were resuscitated with CPR, ventilation and epinephrine. Brain edema was determined by brain wet-to-dry weight ratio at one hour after resuscitation.


RESULTS
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 + GM6001 (p = 0.17 vs. CA and 0.42 vs. CA + ETOH).


CONCLUSIONS
MMPs are not involved in brain edema formation one hour following CA.
Xiao
F
F
Department of Emergency Medicine, Louisiana State University Health Science Center, Shreveport 71130, USA. fxiao@lsuhsc.edu
Arnold
T
T
Zhang
S
S
Imtiaz
N
N
Khan
A
A
Alexander
J S
JS
Conrad
S
S
Carden
D
D
D000818:Animals; D001929:Brain Edema / Q000209:etiology*; D004151:Dipeptides / Q000494:pharmacology; D006324:Heart Arrest, Induced; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases