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Julieta D Kolarova

Publications and source records attributed to Julieta D Kolarova.

4 recordsLinked to original sources
PubMed2006

Circulating levels of cytochrome c after resuscitation from cardiac arrest: a marker of mitochondrial injury and predictor of survival.

Ca(2+) overload and reactive oxygen species can injure mitochondria during ischemia and reperfusion. We hypothesized that mitochondrial injury occurs during cardiac resuscitation, causing release of cytochrome c to the cytosol and bloodstream while activating apoptotic pathways. Plasma cytochrome c was measured using reverse-phase HPLC and Western immunoblotting in rats subjected to 4 or 8 min of untreated ventricular fibrillation and 8 min of closed-chest resuscitation followed by 240 min of postresuscitation hemodynamic observation. A sham group served as control. Plasma cytochrome c rose progressively to levels 10-fold higher than in sham rats 240 min after resuscitation (P < 0.01), despite reversal of whole body ischemia (decreases in arterial lactate). Cytochrome c levels were inversely correlated with left ventricular stroke work (r = -0.40, P = 0.02). Western immunoblotting of left ventricular tissue demonstrated increased levels of 17-kDa cleaved caspase-3 fragments in the cytosol. Plasma cytochrome c was then serially measured in 12 resuscitated rats until the rat died or cytochrome c returned to baseline. In three survivors, cytochrome c rose slightly to <or=2 microg/ml and returned to baseline within 96 h. In nine nonsurvivors, cytochrome c rose progressively to significantly higher maximal levels [4.6 (SD 2.0) vs. 1.6 (SD 0.3) microg/ml, P = 0.029] and at faster rates [0.7 (SD 0.5) vs. 0.1 (SD 0.1) microg.ml(-1).h(-1), P = 0.046] than in survivors. Plasma cytochrome c may represent a novel in vivo marker of mitochondrial injury after resuscitation from cardiac arrest that relates inversely with survival outcome.

Animals↗
PubMed2005

Cariporide enables hemodynamically more effective chest compression by leftward shift of its flow-depth relationship.

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.

Animals↗
PubMed2002

Myocardial protection during ventricular fibrillation by inhibition of the sodium-hydrogen exchanger isoform-1.

Activation of the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) in response to the intense intracellular acidosis that develops during ischemia has been identified as an important mechanism of myocardial cell injury. NHE-1 inhibition in the quiescent (nonfibrillating) heart ameliorates functional manifestation of ischemia and reperfusion injury. We investigated in isolated heart and intact rat models of ventricular fibrillation whether NHE-1 inhibition, by using the selective inhibitor cariporide, could ameliorate myocardial abnormalities that develop during ventricular fibrillation and limit resuscitability and survival. In the isolated rat heart, cariporide significantly reduced the magnitude of ischemic contracture during ventricular fibrillation and the accompanying increases in coronary vascular resistance. Hearts that had received cariporide during ventricular fibrillation had no diastolic dysfunction after resuscitation and recovered their systolic function earlier. In intact rats, cariporide given immediately before starting chest compression allowed generation of a coronary perfusion pressure and end-tidal Pco2 comparable with control rats but with significantly less depth of compression. Cariporide had an unprecedented effect in this rat model, prompting spontaneous defibrillation after approximately 8 mins of chest compression. After resuscitation, rats treated with cariporide had significantly less ventricular ectopic activity, better hemodynamic function, and higher survival rates (22 of 24 [94%] vs. 15 of 24 [63%] in control rats, p <.05). We conclude that NHE-1 inhibition may represent a novel and highly effective form of treatment for resuscitation from ventricular fibrillation.

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