Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) (iPSC-CMs) are a promising cell source for myocardial regeneration, disease modeling and drug assessment. However, iPSC-CMs exhibit immature fetal CM-like characteristics that are different from adult CMs in several aspects, including cellular structure and metabolism. As an example, glycolysis is a major energy source for immature CMs. As CMs mature, the mitochondrial oxidative capacity increases, with fatty acid β-oxidation becoming a key energy source to meet the heart’s high energy demand. The immaturity of iPSC-CMs thereby limits their applications. The aim of this study was to investigate whether the energy substrate fatty acid-treated iPSC-CMs exhibit adult CM-like metabolic properties. After 20 days of differentiation from human iPSCs, iPSC-CMs were sequentially cultured with CM purification medium (lactate+/glucose-) for 7 days and maturation medium (fatty acids+/glucose-) for 3–7 days by mimicking the adult CM’s preference of utilizing fatty acids as a major metabolic substrate. The purity and maturity of iPSC-CMs were characterized via the analysis of: (1) Expression of CM-specific markers (e.g., troponin T, and sodium and potassium channels) using RT-qPCR, Western blot or immunofluorescence staining and electron microscopy imaging; and (2) cell energy metabolic profiles using the XF96 Extracellular Flux Analyzer. iPSCs-CMs (98% purity) cultured in maturation medium exhibited enhanced elongation, increased mitochondrial numbers with more aligned Z-lines, and increased expression of matured CM-related genes, suggesting that fatty acid-contained medium promotes iPSC-CMs to undergo maturation. In addition, the oxygen consumption rate (OCR) linked to basal respiration, ATP production, and maximal respiration and spare respiratory capacity (representing mitochondrial function) was increased in matured iPSC-CMs. Mature iPSC-CMs also displayed a larger change in basal and maximum respirations due to the utilization of exogenous fatty acids (palmitate) compared with non-matured control iPSC-CMs. Etomoxir (a carnitine palmitoyltransferase 1 inhibitor) but not 2-deoxyglucose (an inhibitor of glycolysis) abolished the palmitate pretreatment-mediated OCR increases in mature iPSC-CMs. Collectively, our data demonstrate for the first time that fatty acid treatment promotes metabolic maturation of iPSC-CMs (as evidenced by enhanced mitochondrial oxidative function and strong capacity of utilizing fatty acids as energy source). These matured iPSC-CMs might be a promising human CM source for broad biomedical application.
A 52-year-old woman presenting with shortness of breath and having no related past medical history was diagnosed with takotsubo cardiomyopathy. However, she revealed respiratory failure atypical with takotsubo cardiomyopathy. We diagnosed myasthenia gravis with myasthenic crisis by acetylcholine receptor-binding antibody titer with mediastinal tumor. Physical or emotional stress is well known to trigger the onset of takotsubo cardiomyopathy. Similarly, myasthenia crisis is also triggered by stress. Here, we report a case of simultaneous occurrence of takotsubo cardiomyopathy and myasthenia crisis.
The familial variant of cardiac myxomas is an autosomally dominant disease. Here, we report a case of recurrent multiple cardiac myxomas wherein the patient, a 36-year-old woman who was referred for palpitations and nocturnal dyspnea, had a relevant familial history. Her mother had undergone extirpation of cardiac myxoma when she was about 50 years old. Echocardiography showed the presence of multiple cardiac myxomas. One of the cardiac myxomas nearly obstructed the left ventricular inflow; therefore, we extirpated the myxomas under cardiopulmonary bypass and cardioplegic arrest. The operation was uneventful and the postoperative clinical course was good. Pathological examination confirmed that the extirpated mass was a myxoma. Approximately 3 years after the first cardiac operation, we found a recurrent cardiac myxoma in the same patient. She then underwent a second operation and was discharged without any complications. Pathological examination also confirmed that the cardiac mass was a myxoma and that there was no malignancy.
Background Although pump‐controlled retrograde trial off (PCRTO) is a practical method for weaning from venoarterial extracorporeal membrane oxygenation (VA‐ECMO), its advantages and safety for patients with pulmonary embolism are not yet reported. Case Presentation A 62‐year‐old man with coronavirus disease 2019 experienced sudden cardiac arrest, and VA‐ECMO was introduced. After confirming a massive acute pulmonary embolism, unfractionated heparin treatment was initiated. On day 6, the patient was confirmed stable with a flow rate of 1.0 L/min. However, decannulation led to cardiac arrest and reintroduction of VA‐ECMO. After further treatment, a residual thrombus was observed, and pulmonary arterial pressure remained high. On day 23, ECMO was decannulated successfully after a weaning test with PCRTO, which simulated ECMO withdrawal by generating a partial arteriovenous shunt. Conclusion PCRTO is a feasible weaning strategy and can be considered for patients with uncertain cardiorespiratory recovery.
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