Methyl isobutyl amiloride alters regional brain reperfusion after resuscitation from cardiac arrest in rats.
In a rat model of cardiac arrest and resuscitation, [(14)C]-iodoantipyrene (IAP) autoradiography was used to measure the regional variations in cerebral blood flow 15 and 60 min after reperfusion. The purpose of this study was to investigate the hypothesis that the inhibition of the Na+/H+ antiporter with methyl isobutyl amiloride (MIA) would decrease postischemic pericapillary cytotoxic edema and, therefore, improve vascular perfusion dynamics. Vehicle-treated rats responded to cardiac arrest and resuscitation as expected with initial hyperemia after 15 min of reperfusion, except for thalamic and midbrain structures which were hypoperfused. All brain structures were perfused at half the baseline blood flow at 60 min after resuscitation, and the residual blood flow in each region was proportional to the baseline flow of each region. MIA treatment was associated with decreased blood flow in every region examined at both 15 min and 60 min of reperfusion. No hyperemia was observed at 15 min in any region after MIA treatment. Sixty minutes after resuscitation in MIA-treated rats, all structures were hypoperfused (to 25+/-7% of baseline, 48+/-8% of vehicle-treated rats). These effects are unlikely to be due to prevention of cytotoxic edema, but may be due to MIA protection of capillary endothelium by prevention of neutrophil activation.
Department of Pulmonary and Critical Care Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
K L
KL
Lauro
H
H
Kabert
J C
JC
LaManna
D000584:Amiloride / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D016887:Cardiopulmonary Resuscitation; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006323:Heart Arrest / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; C056369:5-(N-methyl-N-isobutyl)amiloride