Up-regulation of Intracellular Calcium Handling Underlies the Recovery of Endotoxemic Cardiomyopathy in Mice
| Autor: | Ion A. Hobai, Natasha Khona, Wilson S. Colucci, Deborah A. Siwik, Joanne Huang, Justin C. Morse, Edward J. Miller |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cardiac function curve Male Sarcomeres medicine.medical_specialty chemistry.chemical_element 030204 cardiovascular system & hematology Calcium Ryanodine receptor 2 Calcium in biology Contractility 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Animals Myocytes Cardiac Calcium metabolism Ejection fraction business.industry Endotoxemia Phospholamban Up-Regulation Mice Inbred C57BL Disease Models Animal 030104 developmental biology Anesthesiology and Pain Medicine Endocrinology chemistry Cardiology business Cardiomyopathies |
| Zdroj: | Anesthesiology. 126(6) |
| ISSN: | 1528-1175 |
| Popis: | Background In surviving patients, sepsis-induced cardiomyopathy is spontaneously reversible. In the absence of any experimental data, it is generally thought that cardiac recovery in sepsis simply follows the remission of systemic inflammation. Here the authors aimed to identify the myocardial mechanisms underlying cardiac recovery in endotoxemic mice. Methods Male C57BL/6 mice were challenged with lipopolysaccharide (7 μg/g, intraperitoneally) and followed for 12 days. The authors assessed survival, cardiac function by echocardiography, sarcomere shortening, and calcium transients (with fura-2-acetoxymethyl ester) in electrically paced cardiomyocytes (5 Hz, 37°C) and myocardial protein expression by immunoblotting. Results Left ventricular ejection fraction, cardiomyocyte sarcomere shortening, and calcium transients were depressed 12 h after lipopolysaccharide challenge, started to recover by 24 h (day 1), and were back to baseline at day 3. The recovery of calcium transients at day 3 was associated with the up-regulation of the sarcoplasmic reticulum calcium pump to 139 ± 19% (mean ± SD) of baseline and phospholamban down-regulation to 35 ± 20% of baseline. At day 6, calcium transients were increased to 123 ± 31% of baseline, associated with increased sarcoplasmic reticulum calcium load (to 126 ± 32% of baseline, as measured with caffeine) and inhibition of sodium/calcium exchange (to 48 ± 12% of baseline). Conclusions In mice surviving lipopolysaccharide challenge, the natural recovery of cardiac contractility was associated with the up-regulation of cardiomyocyte calcium handling above baseline levels, indicating the presence of an active myocardial recovery process, which included sarcoplasmic reticulum calcium pump activation, the down-regulation of phospholamban, and sodium/calcium exchange inhibition. |
| Databáze: | OpenAIRE |
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