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Cardiovascular Research 1998 37(2):515-523; doi:10.1016/S0008-6363(97)00279-4
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

Calcium uptake by the sarcoplasmic reticulum, high energy content and histological changes in ischemic cardiomyopathy

Kanigula Mubagwa*, Peter Kaplan1, Bharati Shivalkar2, Marc Miserez, Veerle Leunens, Marcel Borgers3 and Willem Flameng

Laboratory of Experimental Cardiac Surgery, Katholieke Universiteit Leuven, KUL Campus Gasthuisberg, B-3000 Leuven, Belgium

* Corresponding author. Tel.: +32 (16) 347132; fax: +32 (16) 347139; e-mail: kanigula.mubagwa@med.kuleuven.ac.be

Objectives: Sarcoplasmic reticulum (SR) Ca2+ uptake, myocardial high energy content and histology were examined in different zones of hearts from patients with ischemic cardiomyopathy. Methods and Results: Unfractionated homogenates were prepared from left ventricular samples obtained in three zones of each heart: an infarct-remote zone, an outer peri-infarct zone, and an inner peri-infarct zone. Oxalate-supported Formula uptake was measured at 37°C using a filtration method. Maximum rate (Vmax) of uptake in absence or in presence of ryanodine was lower in inner peri-infarct (7.4±0.7 and 9.5±0.8 nmol min–1 mg–1 of protein, respectively; mean±SEM) and outer peri-infarct tissues (8.8±0.8 and 12.0±0.8 nmol min–1 mg–1) than in infarct-remote myocardium (12.7±2.1 and 15.8±2.2 nmol min–1 mg–1). The apparent affinity constants for Ca2+ (KCa) as well as the Hill coefficients were not different. Homogenate DNA (1.6±0.1, 1.6±0.1 and 1.7±0.1 mg/g of remote, inner peri-infarct and outer peri-infarct myocardium, respectively) and adenine nucleotides contents (ATP: 15±1.3, 14±0.8 and 15±1.0 µmol/g dry weight, respectively) were similar in all tissues. Fibrosis was increased in inner peri-infarct tissue (37±6%; vs. 13±2% and 12±2% in both remote and outer peri-infarct tissues, respectively), but the number of abnormal cells was not significantly different. Conclusion: The decrease of Ca2+ uptake in ischemic cardiomyopathy is not homogeneous in the ventricular wall, and reflects a decreased number/activity of SR Ca2+-ATPase, without altered Ca2+-affinity or increased Ca2+ leakage through ryanodine receptors.

KEYWORDS Sarcoplasmic reticulum; Calcium uptake; Ischemia; Infarction; Cardiac; Human


1 Permanent address: Department of Biochemistry, Comenius University, Martin, Slovakia.

2 Department of Cardiology, University of Leuven, Campus Gasthuisberg, Leuven, Belgium.

3 Janssen Research Foundation, Beerse, Belgium.


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