Effects of Heme Oxygenase-1 on c-Kit-Positive Cardiac Cells.

Heme oxygenase-1 (HO-1) is one of the most powerful cytoprotective proteins known. The goal of this study was to explore the effects of HO-1 in c-kit-positive cardiac cells (CPCs). LinNEG/c-kitPOS CPCs were isolated and expanded from wild-type (WT), HO-1 transgenic (TG), or HO-1 knockout (KO) mouse hearts. Compared with WT CPCs, cell proliferation was significantly increased in HO-1TG CPCs and decreased in HO-1KO CPCs. HO-1TG CPCs also exhibited a marked increase in new DNA synthesis during the S-phase of cell division, not only under normoxia (21% O2) but after severe hypoxia (1% O2 for 16 h). These properties of HO-1TG CPCs were associated with nuclear translocation (and thus activation) of Nrf2, a key transcription factor that regulates antioxidant genes, and increased protein expression of Ec-SOD, the only extracellular antioxidant enzyme. These data demonstrate that HO-1 upregulates Ec-SOD in CPCs and suggest that this occurs via activation of Nrf2, which thus is potentially involved in the crosstalk between two antioxidants, HO-1 in cytoplasm and Ec-SOD in extracellular matrix. Overexpression of HO-1 in CPCs may improve the survival and reparative ability of CPCs after transplantation and thus may have potential clinical application to increase efficacy of cell therapy.

Approach to Left Bundle Branch Pacing.

Cardiac pacing refers to the implantation tool serving as a treatment modality for various indications, the most common of which is symptomatic bradyarrhythmia. Left bundle branch pacing has been noted in the literature to be safer than biventricular pacing or His-bundle pacing in patients with left bundle branch block (LBBB) and heart failure, thereby becoming the focus of further research on cardiac pacing. A review of the literature was conducted using a combination of keywords, including "Left Bundle Branch Block," "Procedural techniques," "Left Bundle Capture," and "Complications." The following factors have been investigated as key criteria for direct capture: paced QRS morphology, peak left ventricular activation time, left bundle potential, nonselective and selective left bundle capture, and programmed deep septal stimulation protocol. In addition, complications of LBBP, inclusive of septal perforation, thromboembolism, right bundle branch injury, septal artery injury, lead dislodgement, lead fracture, and lead extraction, have also been elaborated on. Despite clinical implications based on clinical research comparing the use of LBBP with other forms such as right ventricular apex pacing, His-bundle pacing, biventricular pacing, and left ventricular septal pacing, a paucity in the literature on long-term effects and efficacy has been noted. LBBP can thus be considered to have a promising future in patients requiring cardiac pacing, assuming that additional research on clinical outcomes and the limitation of significant complications such as thromboembolism can be established.

Approach to Lymphoma-Associated Cardiomyopathy.

Cardiomyopathy is a disease of the myocardium that affects the heart structure and function, eventually resulting in heart failure, valvular regurgitation, arrhythmia, or even sudden cardiac death. Occurring following treatment of lymphoma, both Hodgkin's and Non-Hodgkin's, cardiomyopathy is a feared complication in these cancer survivors due to its significant association with morbidity and mortality. A review of the literature was conducted using a combination of keywords including "Cardiomyopathy," "Anthracycline," "Radiation," "Pathogenesis," and "Management." Anthracyclines and radiation are prominent entities explored in the discussion of lymphoma-associated cardiomyopathy, whereby the formation of reactive oxygen species following treatment with both has been seen in the pathogenesis. The current standard of care thus far for anthracycline-induced cardiomyopathy includes heart failure medications such as beta-blockers, angiotensin-converting enzyme inhibitors, aldosterone receptor antagonists, and loop-diuretics. On the other hand, radiation-induced cardiomyopathy management has not been well-established yet in literature, with agents such as antioxidants and anti-inflammatory drugs still being studied in rat models. The treatment approach to cardiotoxicity in a lymphoma patient should consist of a collaboration between the oncologist and cardiologist prior to lymphoma treatment initiation, to stratify the risk of development of cardiomyopathy in the patient, and decide the best chemotherapy or radiotherapy agent, dosing, and surveillance technique.