AVE4454B--a novel sodium-hydrogen exchanger isoform-1 inhibitor--compared less effective than cariporide for resuscitation from cardiac arrest.
AVE4454B--a novel sodium-hydrogen exchanger isoform-1 inhibitor--compared less effective than cariporide for resuscitation from cardiac arrest.
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DOI：
10.1016/j.trsl.2010.11.004
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Gazmuri RJ
中科院分区：
文献类型：
--
作者：
Radhakrishnan J;Kolarova JD;Ayoub IM;Gazmuri RJ
We compared the efficacy of the novel sodium-hydrogen exchanger (NHE-1) inhibitor AVE4454B with cariporide for resuscitation from ventricular fibrillation (VF) assessing effects on left ventricular myocardial distensibility during chest compression, myocardial function after return of spontaneous circulation, and survival. Three groups of ten rats each were subjected to 10 minutes of untreated VF and resuscitation attempted by providing chest compression for up to 8 minutes with the depth of compression adjusted to attain an aortic diastolic pressure between 26 and 28 mmHg (to secure a coronary perfusion pressure above 20 mmHg), followed by electrical shocks. Rats received AVE4454B (1 mg/kg), cariporide (1 mg/kg), or vehicle control immediately before chest compression. We observed that NHE-1 inhibition preserved left ventricular myocardial distensibility during chest compression evidenced by less depth of compression required to attain the target aortic diastolic pressure corresponding to (mean ± SD) 14.1 ± 1.1 mm in the AVE4454B group (p < 0.001 vs control), 15.0 ± 1.4 mm in the cariporide group (p < 0.01 vs control), and 17.0 ± 1.2 mm in controls. When the depth of compression was related to the coronary perfusion pressure generated (CPP/Depth ratio) – an index of left ventricular distensibility – only cariporide group attained statistical significance. Post-resuscitation, both compounds ameliorated myocardial dysfunction evidenced by lesser reductions in mean aortic pressure and +dP/dtmax and earlier normalization of left ventricular end-diastolic pressure increases. This effect was associated with improved survival corresponding to 55% in the AVE4454B group (NS) and 70% in the cariporide group (p < 0.01 vs control by Gehan-Breslow analysis). There was an inverse correlation between plasma cytochrome c and indices of left ventricular function at post-resuscitation 240 minutes suggesting that NHE-1 inhibition exerts beneficial effects in part by attenuating mitochondrial injury. We conclude that cariporide is more effective than AVE4454B for resuscitation from cardiac arrest given its more prominent effect on preserving left ventricular myocardial distensibility and promoting survival.
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影响因子：
4.6
作者：
Mentzer, Robert M.;Bartels, Claus;Weisel, Richard D.
通讯作者：
Weisel, Richard D.
影响因子：
37.8
作者：
Ayoub, IM;Kolarova, J;Gazmuri, RJ
通讯作者：
Gazmuri, RJ
DOI：
10.1067/mlc.2001.111693
发表时间：
2001-01-01
期刊：
JOURNAL OF LABORATORY AND CLINICAL MEDICINE
影响因子：
--
作者：
Gazmuri, RJ;Hoffner, E;Han, Y
通讯作者：
Han, Y
影响因子：
8.8
作者：
Ayoub IM;Radhakrishnan J;Gazmuri RJ
通讯作者：
Gazmuri RJ
影响因子：
6.5
作者：
Ayoub, Iyad M.;Kolarova, Julieta;Gazmuri, Raul J.
通讯作者：
Gazmuri, Raul J.