Key points During compensated hypertrophy in vivo fractional shortening (FS) remains constant until heart failure (HF) develops, when FS decreases from 70% to 39%. Compensated hypertrophy is accompanied by an increase in INa,late and a decrease in Na+,K+‐ATPase current. These changes persist as HF develops. SR Ca2+ content increases during compensated hypertrophy then decreases in HF. In healthy cells, increases in SR Ca2+ content and Ca2+ transients can be achieved by the same amount of inhibition of the Na+,K+‐ATPase as measured in the diseased cells. SERCA function remains constant during compensated hypertrophy then decreases in HF, when there is also an increase in spark frequency and spark‐mediated Ca2+ leak. We suggest an increase in INa,late and a decrease in Na+,K+‐ATPase current and function alters the balance of Ca2+ flux mediated by the Na+/Ca2+ exchange that limits early contractile impairment. Abstract We followed changes in cardiac myocyte Ca2+ and Na+ regulation from the formation of compensated hypertrophy (CH) until signs of heart failure (HF) are apparent using a trans‐aortic pressure overload (TAC) model. In this model, in vivo fractional shortening (FS) remained constant despite HW:BW ratio increasing by 39% (CH) until HF developed 150 days post‐TAC when FS decreased from 70% to 39%. Using live and fixed fluorescence imaging and electrophysiological techniques, we found an increase in INa,late from –0.34 to –0.59 A F−1 and a decrease in Na+,K+‐ATPase current from 1.09 A F−1 to 0.54 A F−1 during CH. These changes persisted as HF developed (INa,late increased to –0.82 A F−1 and Na+,K+‐ATPase current decreased to 0.51 A F−1). Sarcoplasmic reticulum (SR) Ca2+ content increased during CH then decreased in HF (from 32 to 15 μm l−1) potentially supporting the maintenance of FS in the whole heart and Ca2+ transients in single myocytes during the former stage. We showed using glycoside blockade in healthy myocytes that increases in SR Ca2+ content and Ca2+ transients can be driven by the same amount of inhibition of the Na+,K+‐ATPase as measured in the diseased cells. SERCA function remains constant in CH but decreases (τ for SERCA‐mediated Ca2+ removal changed from 6.3 to 3.0 s−1) in HF. In HF there was an increase in spark frequency and spark‐mediated Ca2+ leak. We suggest an increase in INa,late and a decrease in Na+,K+‐ATPase current and function alters the balance of Ca2+ flux mediated by the Na+/Ca2+ exchange that limits early contractile impairment.
Cardiovascular complications are leading causes of morbidity and mortality in patients with chronic kidney disease (CKD). CKD significantly affects cardiac calcium (Ca2+) regulation, but the underlying mechanisms are not clear. The present study investigated the modulation of Ca2+ homeostasis in CKD mice. Echocardiography revealed impaired fractional shortening (FS) and stroke volume (SV) in CKD mice. Electrocardiography showed that CKD mice exhibited longer QT interval, corrected QT (QTc) prolongation, faster spontaneous activities, shorter action potential duration (APD) and increased ventricle arrhythmogenesis, and ranolazine (10 µmol/L) blocked these effects. Conventional microelectrodes and the Fluo‐3 fluorometric ratio techniques indicated that CKD ventricular cardiomyocytes exhibited higher Ca2+ decay time, Ca2+ sparks, and Ca2+ leakage but lower [Ca2+]i transients and sarcoplasmic reticulum Ca2+ contents. The CaMKII inhibitor KN93 and ranolazine (RAN; late sodium current inhibitor) reversed the deterioration in Ca2+ handling. Western blots revealed that CKD ventricles exhibited higher phosphorylated RyR2 and CaMKII and reduced phosphorylated SERCA2 and SERCA2 and the ratio of PLB‐Thr17 to PLB. In conclusions, the modulation of CaMKII, PLB and late Na+ current in CKD significantly altered cardiac Ca2+ regulation and electrophysiological characteristics. These findings may apply on future clinical therapies.
Hepatoblastoma is the most common primary hepatic tumor of children. However, only a very few cases have been reported in adults. Most studies support treatment with chemotherapy followed by surgical resection. We present the first reported case of adult hepatoblastoma in Taiwan. A 52-year-old female suffered from sudden onset of abdominal pain and general weakness for days. Internal bleeding with hemorrhagic shock was suspected and two massive lesions in both lobes of the liver with hemoperitoneum were noted from imaging studies. Surgical resection of the larger left lobe tumor and radio-frequency ablation of the right smaller one were performed. The histopathology diagnosis was of a hepatoblastoma.
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