Summary Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury, but preclinical studies in large animal models are required to determine optimal cell preparation and delivery strategies to maximize functional benefits and to evaluate safety. Here, we utilized a porcine model of acute myocardial infarction (MI) to investigate the functional impact of intramyocardial transplantation of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells, in combination with a 3D fibrin patch loaded with insulin growth factor (IGF)-encapsulated microspheres. hiPSC-derived cardiomyocytes integrated into host myocardium and generated organized sarcomeric structures, and endothelial and smooth muscle cells contributed to host vasculature. Tri-lineage cell transplantation significantly improved left ventricular function, myocardial metabolism, and arteriole density, while reducing infarct size, ventricular wall stress and apoptosis without inducing ventricular arrhythmias. These findings in a large animal MI model highlight the potential of utilizing hiPSC-derived cells for cardiac repair.

Plasma concentration of high sensitive C-reactive protein (hsCRP) is used as a marker for inflammatory states and is directly correlated with the risk for coronary heart disease. Evidence concerning the role of inflammation in atheroma formation has been derived from several models of atherosclerosis. Inflammation should exert its adverse vascular effects by structural changes in the artery wall and consequently alterations in arterial elasticity, which could be detected already in asymptomatic early vascular disease. We hypothesized that CRP is related to large artery elasticity, but not to small artery elasticity in early vascular disease. Therefore, we examined the association between arterial stiffness of large and small arteries and inflammation in an asymptomatic population referred for primary prevention cardiovascular screening. Studies were performed in 391 subjects (age 21-82 years; 254 men, 137 women) who underwent screening at the Cardiovascular Disease Prevention Center. Large artery (C1) and small artery (C2) elasticity indices were obtained by the CVProfiler 2000 (HDI, Eagan, MN, USA). After overnight fasting, venous samples were taken for measurement of hsCRP, lipids, glucose. There was a significant inverse correlation between hsCRP (0.2970.40 mg/dl) and C1 (16.775.8 ml/mmHg), r ¼ À0.133, P ¼ 0.01; there was no significant correlation between hsCRP and C2 (6.673.2 ml/mmHg). C2, but not hsCRP, was inversely correlated with age, abnormal lipids and glucose, whereas C1, but not hsCRP, was inversely correlated with age and systolic blood pressure (SBP). In multiple regression analysis, the relationship between hsCRP and C1 was not affected by age, body mass index, SBP, serum glucose or lipids. In conclusion, these findings support the hypothesis that hsCRP, a marker for acute and low-grade inflammation, is associated with large artery but not with small artery elasticity in asymptomatic individuals undergoing primary prevention cardiovascular screening.

Mast cells and macrophages infiltrate healing myocardial infarcts and may play an important role in regulating fibrous tissue deposition and extracellular matrix remodelling. This study examined the time-course of macrophage and mast cell accumulation in healing infarcts and studied the histological characteristics and protease expression profile of mast cells in a canine model of experimental infarction. Although macrophages were more numerous than mast cells in infarct granulation tissue, macrophage density decreased during maturation of the scar, whereas mast cell numbers remained persistently elevated. During the inflammatory phase of infarction, newly recruited leucocytes infiltrated the injured myocardium and appeared to be clustered in close proximity to degranulating cardiac mast cells. During the proliferative phase of healing, mast cells had decreased granular content and were localized close to infarct neovessels. In contrast, macrophages showed no selective localization. Mast cells in healing canine infarcts were alcian blue/safranin-positive cells that expressed both tryptase and chymase. In order to explain the pro-inflammatory and angiogenic actions of tryptase--the major secretory protein of mast cells--its effects on endothelial chemokine expression were examined. Chemokines are chemotactic cytokines that play an important role in leucocyte trafficking and angiogenesis and are highly induced in infarcts. Tryptase, a proteinase-activated receptor (PAR)-2 agonist, induced endothelial expression of the angiogenic chemokines CCL2/MCP-1 and CXCL8/IL-8, but not the angiostatic chemokine CXCL10/IP-10. Endothelial PAR-2 stimulation with the agonist peptide SLIGKV induced a similar chemokine expression profile. Mast cell tryptase may exert its angiogenic effects in part through selective stimulation of angiogenic chemokines.

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In this retrospective cohort study of older male patients with Mobitz I AV block on ECG, CIED implantation was associated with longer survival.

Catheter ablation is an effective treatment for symptomatic atrial fibrillation. A thorough understanding of the left atrium anatomy and its adjacent structures is critical for the success of the procedure and for avoiding complications. Pre-procedural imaging aims at determining left atrial size, anatomy, and function and is also used to rule out an atrial thrombus. During the procedure, while fluoroscopy remains the gold standard imaging modality for guiding transseptal catheterization and catheter ablation, numerous other imaging modalities have been developed to improve 3D navigation and ablation. Finally, post-operative imaging intends to monitor heart function and to search for potential complications like pulmonary vein stenosis or the rare but dramatic atrio-oesophageal fistula. This review discusses the relative merits of all imaging modalities available in the context of catheter ablation of atrial fibrillation.

Congestive heart failure is prevalent in the elderly; recurrent hospital admissions for acute deterioration is a major health care problem. We examined tumor necrosis factor alpha levels in 31 congestive heart failure patients who were admitted to the hospital due to acute cardiogenic pulmonary edema. Blood samples were taken within 24 hours of admission and at the time of discharge after recovery. Tumor necrosis factor alpha levels were also measured in 10 stable congestive heart failure outpatients and 16 healthy controls. Tumor necrosis factor alpha level at admission was higher than at time of discharge (4.6Â+/-1.9 vs. 3.4Â+/-1.1 (rg/mL, p is less than 0.02). Mean tumor necrosis factor alpha level of stable congestive heart failure outpatient was 2.6Â+/-0.7 rg/mL healthy controls had significantly lower tumor necrosis factor alpha levels (1.7Â+/-0.7 rg/mL) than congestive heart failure patients (p is less than 0.01). tumor necrosis factor alpha levels were highest among acute congestive heart failure patients. Elevated tumor necrosis factor alpha appears to be related to the exacerbation of congestive heart failure and may be a marker for deterioration. (c) 2000 by CVRR, Inc.