Significance of CD25 positive cells and macrophages in noncrescentic IgA nephropathy.

The aim of this study was to determine whether infiltration by CD25 positive cells, macrophages, and activated macrophages in the kidney is predictive of chronic histological injury and renal prognosis in adults with noncrescentic IgA nephropathy. Renal biopsies of 36 patients with noncrescentic IgA nephropathy were examined by immunohistochemistry for glomerular and interstitial CD4, CD8, and CD25 positive cells, monocytes/macrophage (Mac387), and activated macrophages (27E10). Renal injury (glomerulosclerosis, mesangial cell hypercellularity, tubular atrophy, and interstitial fibrosis) at the time of biopsy and renal prognosis (follow-up creatinine and creatinine clearance) were assessed. The mean follow-up period was 22.5 +/- 16.5 months. The number of interstitial CD8 positive cells was the best predictor of renal injury at the time of biopsy, and was positively correlated with glomerulosclerosis (p = 0.04), tubular atrophy (p = 0.04), and interstitial fibrosis (p = 0.01) but not with mesangial cell hypercellularity. The number of interstitial Mac387 and 27E10 positive cells were the best predictors of renal prognosis (r2 = 0.33 and 0.34 respectively, both p < 0.01). These data suggest the presence of CD8 cells and macrophages in the kidney at the time of biopsy could potentially serve as pathological markers to identify patients with IgA nephropathy, which may warrant more aggressive medical therapy.

Comparison of radiofrequency ablation in normal versus scarred myocardium.

INTRODUCTION: Reentrant circuits causing ventricular tachycardia are closely associated with previously scarred myocardium. The presence of scar has been blamed for the poor success rate of radiofrequency ablation (RFA) in that context. This article investigates the in vivo effects of radiofrequency ablation in myocardium scarred from acute myocardial infarction. METHODS AND RESULTS: Anterior myocardial infarction was induced in five dogs by ligating the left anterior descending artery. The mean left ventricular ejection fraction after infarction was 38%. At a mean of 15 weeks following myocardial infarction, 50 RFA lesions were created in random order, 25 in scarred and 25 in normal myocardium using a needle electrode (21 gauge, 5 mm in length) introduced from the epicardium of the left ventricle at thoracotomy. During unipolar temperature-controlled RFA (90 degrees C for 60 seconds), intramural temperatures were measured by thermistors at distances of 1, 2, 3, 4, and 5 mm from the ablating electrode. The margins of the lesions were clearly discernible in scar at histological examination in 64% of ablations where the scarring was patchy. There were no significant differences between lesion sizes, intramural temperatures at different distances, total energy required for ablation, or mean impedance during ablation of normal versus scarred myocardium. CONCLUSIONS: Scar does not affect lesion size or intramural temperature profile during RFA if electrode size, tissue contact, and tip temperature are controlled. More radiofrequency energy is not required to maintain tip temperature at 90 degrees C in scar compared to normal myocardium.

Cooled needle catheter ablation creates deeper and wider lesions than irrigated tip catheter ablation.

OBJECTIVES: To design and test a catheter that could create deeper ablation lesions. BACKGROUND: Endocardial radiofrequency (RF) ablation is unable to reliably create transmural ventricular lesions. We designed an intramural needle ablation catheter with an internally cooled 1.1-mm diameter straight needle that could be advanced up to 14 mm into the myocardium. The prototype catheter was compared with an irrigated tip ablation catheter. METHODS: Ablation lesions were created under general anesthesia in 14 male sheep (weight 44 +/- 7.3 kg) with fluoroscopic guidance. Each of the catheters was used to create two ablation lesions at randomly allocated positions within the left ventricle. The irrigation rate, target temperature, and maximum power were: 20 mL/min, 85 degrees C, 50 W for the intramural needle catheter and 20 mL/min, 50 degrees C, 50 W for the irrigated tip catheter, respectively. All ablations were performed for 2 minutes. After the last ablation, blue tetrazolium (12.5 mg/kg) was infused intravenously. The heart was removed via a left thoracotomy after monitoring the sheep for one hour. RESULTS: There was no evidence of cardiac tamponade in any sheep. The intramural needle catheter lesions were significantly wider (10.9 +/- 2.8 mm vs 10.1 +/- 2.4 mm, P = 0.01), deeper (9.6 +/- 2.0 mm vs 7.0 +/- 1.3 mm, P = 0.01), and more likely to be transmural (38% vs 0%, P = 0.03). CONCLUSIONS: Cooled intramural needle ablation creates lesions that are significantly deeper and wider than endocardial RF ablation using an irrigated tip catheter in sheep hearts. This technology may be useful in treating ventricular tachycardia resistant to conventional ablation techniques.

Automated ventricular substrate mapping--evaluation in an ovine chronic myocardial infarction model.

INTRODUCTION: We hypothesized that automated electrogram analysis might enable rapid localization of ventricular scar. This would allow the delivery of interventions such as radiofrequency ablation or therapeutic agents to critical areas within the scar and scar periphery. METHODS: Substrate mapping was performed on seven sheep 36.5 +/- 32.9 weeks after a left anterior descending artery myocardial infarction had been induced. Contact electrograms and the mapping catheter three-dimensional (3D) location were recorded simultaneously. A computer program was written in-house to automatically identify sinus beats, analyze electrogram characteristics (e.g., electrogram amplitude and minimum slope), and integrate the analysis results into a 3D scar map. RESULTS: The total time required to produce the scar maps was a mean of 8.3 +/- 2.0 minutes. The automated substrate mapping (ASM) system beat detection algorithm had a high sensitivity (i.e., detected 87.4% of the recorded beats) and excellent specificity (only one false activation over 58.2 minutes of total recorded data). The system was able to classify the detected beats ('sinus' or 'ectopic') with high specificity (specificity = 97.3% confidence interval (CI): 96.9-97.7) and moderate sensitivity (sensitivity = 78.3% CI: 77.3%-79.5%). The scar area identified by the ASM system correlated well with the pathologically defined scar area (R2 = 0.87 p < 0.001). CONCLUSIONS: ASM enables accurate scar maps to be produced rapidly. This strategy may play an important role for both clinical and research applications, allowing therapeutic agents and radiofrequency ablation to be delivered to critical locations in and around ventricular scar.