• Justin C Morse, Joanne Huang, Natasha Khona, Edward J Miller, Deborah A Siwik, Wilson S Colucci, and Ion A Hobai.
• From the Department of Medicine, Section of Cardiovascular Medicine, Boston University Medical Center, Boston, Massachusetts (J.C.M., J.H., N.K., E.J.M., D.A.S., W.S.C., I.A.H.); Department of Radiology, Boston University Medical Center, Boston, Massachusetts (E.J.M.); Department of Anesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts (I.A.H.); and Harvard University Medical School, Boston, Massachusetts (I.A.H.).
• Anesthesiology. 2017 Jun 1; 126 (6): 1125-1138.

BackgroundIn 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.MethodsMale 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.ResultsLeft 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).ConclusionsIn 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.

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