Objective-A diabetic mouse model of accelerated neointimal formation would be a useful tool to understand the increased incidence of restenosis in patients with diabetes. Methods and Results-Femoral artery endoluminal wire injury was performed in diabetic insulin 2 Akita (ins2 Akita ) and leptin receptor db/db (lepr db/db ) mutant mice. Neointima size in ins2 Akita mouse arteries was unchanged compared with nondiabetic wild-type littermates. Although Ki67 labeling demonstrated similar rates of replication in the neointima of lepr db/db mouse arteries, neointimal formation in lepr db/db mice was surprisingly reduced by Ϸ90% compared with nondiabetic lepr ϩ/ϩ mice. Four hours after arterial injury, medial smooth muscle cell death was diminished in lepr db/db arteries, suggesting that the initial response to arterial injury was altered in lepr db/db mice. Conclusions-These studies highlight a differential response to arterial injury in lepr db/db mice and suggest a potential role for leptin in the regulation of neointimal formation in response to arterial injury. Key Words: leptin Ⅲ diabetes Ⅲ arterial injury Ⅲ smooth muscle cell proliferation Ⅲ restenosis N umerous clinical trial and observational data have indicated that diabetic patients have a higher incidence of restenosis after percutaneous coronary transluminal angioplasty and stent implantation compared with patients without diabetes. [1][2][3][4][5] Serial intravascular ultrasound studies suggest that excessive neointimal hyperplasia is responsible for accelerated restenosis after angioplasty and coronary stent placement in patients with diabetes and impaired glucose tolerance. 6,7 However, the relationships between the metabolic abnormalities present in diabetes and the cellular and molecular processes involved in restenosis are poorly understood.A diabetic mouse model of accelerated neointimal formation would be a useful tool to understand the increased incidence of restenosis in patients with diabetes. Balloon angioplasty is technically challenging in the mouse because of the small vessel size, and a variety of wire injury models exist. 8 -14 Recent work has demonstrated that reproducible arterial injury can be performed in the mouse femoral artery using an angioplasty guidewire. 8,15 We chose to study neointimal formation after bilateral femoral arterial injury in the diabetic, nonobese insulin 2 Akita (ins2 Akita ) and diabetic, obese leptin receptor db/db (lepr db/db ) mouse strains. Ins2Akita mice have a spontaneous dominant mutation in the insulin 2 gene, resulting in defective proinsulin chain folding, reduced ␤ cell mass, hypoinsulinemia, and hyperglycemia. 16 The ins2 Akita mouse serves as a type I model of diabetes that does not require administration of a chemical diabetogen such as streptozotocin. lepr db/db mice have a mutation in the leptin receptor gene, resulting in a mutant protein lacking the cytoplasmic domain required for intracellular signaling. 17 The lepr db/db model has many of the metabolic abnormalities (albeit more severe) not...

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Background-A left bundle-branch block (LBBB)-like pattern with a dominant S-wave in V 1 is common in idiopathic ventricular arrhythmias (VA). Discrimination between idiopathic and scar-related LBBB pattern VA has important clinical implications. We hypothesized that the VA QRS morphology is influenced by the presence of ventricular scar, allowing ECG discrimination of VA arising from structurally normal versus scarred myocardium. Methods and Results-Twelve-lead ECGs of 297 LBBB pattern monomorphic VA were recorded during catheter ablation procedures. QRS morphology characteristics associated with scar-related VA were identified in retrospective analysis of 118 LBBB pattern VA (95 scar-related, 23 idiopathic) to develop a stepwise algorithm that was prospectively tested in 179 LBBB pattern VA (120 scar-related, 59 idiopathic). The diagnosis of scar was based on sinus rhythm surface ECG, cardiovascular imaging, and electroanatomic catheter mapping. A precordial transition beyond V 4 , notching of the S-wave downstroke in lead V 1 or V 2 , and a duration from the onset of QRS to the S-nadir in V 1 Ͼ90 ms were independent predictors for scar-related VA. The proposed algorithm classified a VA as scar-related if any of these criteria was met. If none of the criteria was present, a VA was classified as idiopathic. In prospective validation, the algorithm was highly sensitive (96%) and specific (83%) for the identification of scar-related LBBB pattern VA. Conclusions-The QRS morphology of VA is different between scar-related and idiopathic VA. A simple ECG algorithm is sensitive for identifying scar-related LBBB VA, which could be helpful in guiding further evaluation of these patients. (Circ Arrhythm Electrophysiol. 2011;4:486-493.)

ABSTRACT. Despite the achievement of acute conduction block during catheter ablation, the recovery of conduction at previously ablated sites remains a primary factor implicated in arrhythmia recurrence after initial ablation. Real-time markers of adequate ablation lesion creation are needed to ensure durable ablation success. However, the assessment of acute lesion formation is challenging, and requires interpretation of surrogate markers of lesion creation that are frequently unreliable. Careful monitoring of impedance changes during radiofrequency catheter ablation has emerged as a highly specific marker of local tissue destruction. Ablation strategies guided by close impedance monitoring during ablation applications have been demonstrated to achieve high levels of success for ablation of atrial fibrillation. Impedance decrease during ablation may therefore be used as an additional endpoint beyond acute conduction block, in order to improve the durability of ablation lesions. In this manuscript, available methods of real-time lesion assessment are reviewed, and the rationale and technique for impedance-guided ablation are described.