Regenerative Medicine Strategies for Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS), the most severe and common form of single ventricle congenital heart lesions, is characterized by hypoplasia of the mitral valve, left ventricle (LV), and all LV outflow structures. While advances in surgical technique and medical management have allowed survival into adulthood, HLHS patients have severe morbidities, decreased quality of life, and a shortened lifespan. The single right ventricle (RV) is especially prone to early failure because of its vulnerability to chronic pressure overload, a mode of failure distinct from ischemic cardiomyopathy encountered in acquired heart disease. As these patients enter early adulthood, an emerging epidemic of RV failure has become evident. Regenerative medicine strategies may help preserve or boost RV function in children and adults with HLHS by promoting angiogenesis and mitigating oxidative stress. Rescuing a RV in decompensated failure may also require the creation of new, functional myocardium. Although considerable hurdles remain before their clinical translation, stem cell therapy and cardiac tissue engineering possess revolutionary potential in the treatment of pediatric and adult patients with HLHS who currently have very limited long-term treatment options.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140239/1/ten.teb.2016.0136.pd

Malignant hyperthermia during laparoscopic adjustable gastric banding.

BACKGROUND: We report a rare case of malignant hyperthermia during laparoscopic adjustable gastric banding. CASE DESCRIPTION: A 32-y-old female with no previous history of adverse reaction to general anesthesia underwent laparoscopic adjustable gastric banding. Intraoperative monitoring revealed a sharp increase in end-tidal carbon dioxide, autonomic instability, and metabolic and respiratory acidosis, along with other metabolic and biochemical derangements. She was diagnosed with malignant hyperthermia. Desflurane, the anesthetic agent was discontinued, and the patient was started on intravenous dantrolene. RESULTS: The surgery was completed, and the patient was brought to the surgical intensive care unit for continued postoperative care. She developed muscle weakness and phlebitis that resolved prior to discharge. CONCLUSION: Prompt diagnosis and treatment of malignant hyperthermia leads to favorable clinical outcome. This clinical entity can occur in the bariatric population with the widely used desflurane. Bariatric surgeons and anesthesiologists alike must be aware of the early clinical signs of this rare, yet potentially fatal, complication

Malignant Hyperthermia During Laparoscopic Adjustable Gastric Banding

BACKGROUND: We report a rare case of malignant hyperthermia during laparoscopic adjustable gastric banding. CASE DESCRIPTION: A 32-y-old female with no previous history of adverse reaction to general anesthesia underwent laparoscopic adjustable gastric banding. Intraoperative monitoring revealed a sharp increase in end-tidal carbon dioxide, autonomic instability, and metabolic and respiratory acidosis, along with other metabolic and biochemical derangements. She was diagnosed with malignant hyperthermia. Desflurane, the anesthetic agent was discontinued, and the patient was started on intravenous dantrolene. RESULTS: The surgery was completed, and the patient was brought to the surgical intensive care unit for continued postoperative care. She developed muscle weakness and phlebitis that resolved prior to discharge. CONCLUSION: Prompt diagnosis and treatment of malignant hyperthermia leads to favorable clinical outcome. This clinical entity can occur in the bariatric population with the widely used desflurane. Bariatric surgeons and anesthesiologists alike must be aware of the early clinical signs of this rare, yet potentially fatal, complication

Human Neonatal Thymus Mesenchymal Stem/Stromal Cells and Chronic Right Ventricle Pressure Overload

Right ventricle (RV) failure secondary to pressure overload is associated with a loss of myocardial capillary density and an increase in oxidative stress. We have previously found that human neonatal thymus mesenchymal stem cells (ntMSCs) promote neovascularization, but the ability of ntMSCs to express the antioxidant extracellular superoxide dismutase (SOD3) is unknown. We hypothesized that ntMSCs express and secrete SOD3 as well as improve survival in the setting of chronic pressure overload. To evaluate this hypothesis, we compared SOD3 expression in ntMSCs to donor-matched bone-derived MSCs and evaluated the effect of ntMSCs in a rat RV pressure overload model induced by pulmonary artery banding (PAB). The primary outcome was survival, and secondary measures were an echocardiographic assessment of RV size and function as well as histological studies of the RV. We found that ntMSCs expressed SOD3 to a greater degree as compared to bone-derived MSCs. In the PAB model, all ntMSC-treated animals survived to the study endpoint whereas control animals had significantly decreased survival. Treatment animals had significantly less RV fibrosis and increased RV capillary density as compared to controls. We conclude that human ntMSCs demonstrate a therapeutic effect in a model of chronic RV pressure overload, which may in part be due to their antioxidative, antifibrotic, and proangiogenic effects. Given their readily available source, human ntMSCs may be a candidate cell therapy for individuals with congenital heart disease and a pressure-overloaded RV