Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function.

With extended stays aboard the International Space Station (ISS) becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function. We utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity on cell-level cardiac function and gene expression. The hiPSC-CMs were cultured aboard the ISS for 5.5 weeks and their gene expression, structure, and functions were compared with ground control hiPSC-CMs. Exposure to microgravity on the ISS caused alterations in hiPSC-CM calcium handling. RNA-sequencing analysis demonstrated that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples, including genes involved in mitochondrial metabolism. This study represents the first use of hiPSC technology to model the effects of spaceflight on human cardiomyocyte structure and function

Ross-Konno and Endocardial Fibroelastosis Resection After Hybrid Stage I Palliation in Infancy: Successful Staged Left-Ventricular Rehabilitation and Conversion to Biventricular Circulation After Fetal Diagnosis of Aortic Stenosis

We report a patient who presented during fetal life with severe aortic stenosis, left-ventricular dysfunction, and endocardial fibroelastosis (evolving hypoplastic left heart syndrome). Management involved in utero and postnatal balloon aortic valvuloplasty for partial relief of obstruction and early postnatal hybrid stage I palliation until recovery of left-ventricular systolic function had occurred. The infant subsequently had successful conversion to a biventricular circulation by combining resection of endocardial fibroelastosis with single-stage Ross-Konno, aortic arch reconstruction, hybrid takedown, and pulmonary artery reconstruction

Autologous deep vein reconstruction of infected thoracoabdominal aortic patch graft

AbstractGraft infection remains a serious complication of prosthetic aortic repair. Infection of thoracoabdominal aortic prosthetic grafts, in particular, is a significant clinical challenge and is associated with high mortality. We report successful in situ reconstruction of an infected thoracoabdominal aortic prosthetic patch graft with autogenous superficial femoral vein. To our knowledge, this is the first such case described in the North American and English language surgical literature. At 24-month follow-up the patient remains well, with no evidence of sepsis or graft complication at clinical and radiologic assessment

Myocardial transcription factors are modulated during pathologic cardiac hypertrophy in vivo

ObjectivesIn the current study we describe and characterize a novel ovine model of biventricular hypertrophy and heart failure and evaluate the role of selected cardiac transcription factors in the regulation of cardiac gene expression during pathologic hypertrophy in vivo. The cardiac troponin T promoter is used as a model gene.Methods and ResultsTransient transfections of ovine cardiomyocytes in culture show that Sp1, transcriptional enhancer factor-1, and myocyte enhancer factor-2 activate cardiac troponin T promoter constructs. Cotransfection of Sp3 inhibits cardiac troponin T promoter activity and represses Sp1-mediated activation of the cardiac troponin T promoter. By chromatin immunoprecipitation, transcriptional enhancer factor-1, myocyte enhancer factor-2, NKX2.5, GATA-4, and Sp factors bind the cardiac troponin T promoter in vivo. To assess the role of cardiac transcription during pathologic hypertrophy, in vivo, we created surgical aorta-pulmonary shunts in utero in fetal lambs. Two weeks after spontaneous delivery, shunted lambs showed failure to thrive, significant biventricular hypertrophy, and heart failure. Shunted hearts had significant increases in myosin and cardiac troponin T protein expression. There was a shift in expression to the high-molecular-weight fetal isoforms. Transcriptional enhancer factor-1, myocyte enhancer factor-2, GATA-4, NKX2.5, and Sp1 transcription factor levels were increased in all heart chambers of shunted animals. Sp3 expression was decreased in shunted ventricles. Immunoprecipitated Sp3 was associated with significant increases in histone acetyl transferase activity and decreases in histone-deacetylase activity.ConclusionThe shunted neonatal lamb is a valid, novel model of pathologic biventricular hypertrophy. During pathologic hypertrophy myocardial transactivators are upregulated while repressors are downregulated