title: Cariporide enables hemodynamically more effective chest compression by leftward shift of its flow-depth relationship.
abstract: When given during closed-chest resuscitation, cariporide (4-isopropyl-methylsulfonylbenzoyl-guanidine methanesulfonate; a selective inhibitor of the Na(+)/H(+) exchanger isoform-1) enables generation of viable perfusion pressures with less depth of compression. We hypothesized that this effect results from greater blood flows generated for a given depth of compression. Two series of 14 rats each underwent 10 min of untreated ventricular fibrillation followed by 8 min of chest compression before defibrillation was attempted. Compression depth was adjusted to maintain an aortic diastolic pressure (ADP) between 26 and 28 mmHg in the first series and between 36 and 38 mmHg in the second series. Within each series, rats were randomized to receive cariporide (3 mg/kg) or NaCl (0.9%; control) before chest compression was started. Blood flow was measured using 15-mum fluorescent microspheres. Less depth of compression was required to maintain the target ADP when cariporide was present in both series 1 (13.6 +/- 1.2 vs. 16.6 +/- 1.2 mm; P < 0.001) and series 2 (15.3 +/- 1.0 vs. 18.9 +/- 1.5 mm; P < 0.001). Despite less compression depth, the cardiac index in cariporide-treated rats was comparable to control rats in series 1 (11.1 +/- 0.7 vs. 11.3 +/- 1.4 ml.min(-1).kg(-1); P = not significant) but higher in series 2 (15.5 +/- 2.3 vs. 9.9 +/- 1.4 ml.min(-1).kg(-1); P < 0.05). Increases in compression depth (from series 1 to series 2) increased myocardial, cerebral, and adrenal blood flow in cariporide-treated rats. We conclude that cariporide enhances the efficacy of closed-chest resuscitation by leftward shift of the flow-depth relationship.
authors.affiliation: Medical Service (111F North Chicago VA Medical Center, 3001 Green Bay Rd., North Chicago, IL 60064, USA.
authors.forename: Julieta D
authors.initials: JD
authors.lastname: Kolarova
authors.forename: Iyad M
authors.initials: IM
authors.lastname: Ayoub
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Gazmuri
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D035641:Chest Wall Oscillation / Q000379:methods*; D004554:Electric Countershock; D006146:Guanidines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D013450:Sulfones / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D013450:Sulfones; C093373:cariporide