Premium
Myocardial Calcium Handling is Up‐Regulated During the Spontaneous Resolution of Endotoxemic Cardiomyopathy in Mice
Author(s) -
Hobai Ion,
Morse Justin,
Siwik Deborah,
Colucci Wilson
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.641.3
Subject(s) - phospholamban , cardiomyopathy , medicine , calcium , lipopolysaccharide , endocrinology , endoplasmic reticulum , serca , sepsis , cardiac function curve , homeostasis , calcium metabolism , chemistry , heart failure , biochemistry , enzyme , atpase
Sepsis and systemic inflammation induce a specific cardiomyopathy that resolves spontaneously in surviving patients, through mechanisms that are currently unknown. Here we studied cardiomyocyte calcium (Ca 2+ ) handling during endotoxemic cardiomyopathy (EC) resolution in mice. Male C57Bl6 mice were administered lipopolysaccharide (LPS, 7 μg/g, ip). LPS induced an inflammatory shock syndrome, cardiomyopathy and 59% mortality. We measured sarcomere shortening (SS) and Ca 2+ transients (ΔCa i ) in externally paced cardiomyocytes, at 37 o C. 12h after LPS administration, SS and ΔCa i were decreased to 53 ± 10% and 78 ± 5% of baseline, respectively (n >30 cells from 3 mice, 30/3, for each group; p<0.05 for this and the following) in association with a decrease in sarcoplasmic reticulum Ca 2+ pump (SERCA) reuptake (to 88 ± 5% of control, n > 19/3). In surviving mice, ΔCa i was fully recovered 3 days after LPS administration (Day 3, D3) and reached levels exceeding normal at D6 (124 ± 7 % of baseline, n > 18/3). ΔCa i recovery was associated with SERCA supra‐normal activation (138 ± 4% of control, n > 28/3) at D3, due to phospholamban (PLB) down‐regulation (to 35 ± 9% of control, n = 6 hearts each group). At D6, membrane Na + /Ca 2+ exchange (NCX) function was 51 ± 4 % of baseline (n > 12/3), contributing to the supra‐normal ΔCa i levels. In conclusion, myocardial recovery during the spontaneous resolution of EC is the result of active cellular mechanisms that include down‐regulation of PLB and NCX and lead to supra‐normal ΔCa i .