This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Weinmann, P. Articles by Maruyama, Y. Search for Related Content PubMed PubMed Citation Articles by Weinmann, P. Articles by Maruyama, Y. Related Collections Animal models of human disease Apoptosis Ischemic biology - basic studies

(Circulation. 2000;101:e75.)
© 2000 American Heart Association, Inc.

Circulation Electronic Pages

Attenuation of Ischemia/Reperfusion Injury by a Caspase Inhibitor

Pierre Weinmann, MD, PhD

Avicenne University Hospital Bobigny, France

Alain Meulemans, PhD; Doumit Daou, MD; Dominique Le Guludec, MD, PhD

Bichat University Hospital, Paris, France

	Introduction

 
To the Editor:

Yaoita et al¹ present an interesting study of the attenuation of ischemia/reperfusion injury in rats by Z-Val-Ala-Asp (OMe)-CH₂F (ZVAD-fmk), a caspase inhibitor. In a previous study, Gottlieb et al² reported that ZVAD-fmk was an apoptosis inhibitor in a preconditioning rabbit cardiomyocyte model.

Because ZVAD-fmk seemed to exhibit interesting properties in the inhibition of the caspase cascade, we undertook a study to inhibit apoptosis in an animal model.

ZVAD-fmk was directly purchased from the manufacturer (Enzyme Systems Products), and our first step was to check the purity of the compounds. High-performance liquid chromatography was performed on a µC18 column (Hypersil, England) with a mobile phase (ammonium acetate pH 4.4, 0.1 mol · L^-1/acetonitrile: 40/60) pumping at 0.5 mL/min. Detection was performed with a photodiode array detector (Waters, France) for a 2-hour run. ZVAD-fmk was dissolved in dimethylsulfoxide and diluted with water at 2 mmol/L as recommended by the manufacturer. Three different peaks could be identified during the first 5 minutes, and no other peak in the remaining time. Since the manufacturer claims a 91% purity, we repeated the same experiment with a different lot. Unfortunately, we obtained similar results with a purity <50%. According to the chromatograms sent by the manufacturer from their quality-control record, it seems that their thin-layer chromatography does not have sufficient resolution and therefore is not capable of checking the purity of the compounds.

ZVAD-fmk probably has the interesting biological properties that the 2 cited studies^{1 2} have reported, but the exact identification . . . [Full Text of this Article]

Hiroyuki Yaoita, MD; Kazuei Ogawa, MD; Kazuhira Maehara, MD; Yukio Maruyama, MD

First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan