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Notes: Ultrastructural Findings After RF Ablation. Introduction: We hypothesized that myocardial injury following radiofrequency (KF) catheter ablation may extend beyond the region of acute coagulation necrosis as defined by histochemical staining. Methods and Results: Five RF lesions were created in vivo in the left ventricle of two dogs using a 4-inm tipped ablation electrode in which RF power was adjusted to maintain an electrode-tissue interface temperature of 85°C for 60 seconds. The lesions were bisected; one half of the lesions were stained with nitroblue tetrazolium (NBT) and the other half processed for electron microscopy. Three zones of interest were identified extending 0–3 mm, 3–6 mm, and 〉 6 mm from the visible pathologic lesion border. The degree of Ultrastructural injury to the myocardium was scored for each zone. Electron microscopy demonstrated the presence of significant abnormalities of the plasma membrane, mitochondria, sarcomeres, sarcoplasmic reticuluni, and gap junctions of myocytes, as well as damage to the microvasculature extending up to 6 mm beyond the pathologic lesion edge. The plasma membrane and gap junctions of myocytes and the microvasculalure appeared particularly sensitive to thermal injury, whereas the intercalated discs were relatively thermally resistant. Conclusion: RF catheter ablation results in Ultrastructural damage to the myocardium extending up to 6 mm beyond the acute pathologic RF lesion border as denned by NBT histochemical staining.

Notes: Intracoronary Ethanol Ablation. Introduction: Physical or chemical ablation of arrhythmogenic tissue has been shown to be an effective modality of arrhythmia therapy. Chemical ablation by intracoronary infusion of ethanol into a specific coronary artery bed has been demonstrated, but the characteristics and distribution of necrosis relative to the coronary blood supply have not been delineated. Methods and Results: A total of 40 myocardial lesions were created in 21 pigs by infusion of 1.6 ± 0.6 ml of 50% ethanol and 50% iohexol contrast solution through a 2.7 French infusion catheter advanced into a branch of the left anterior descending or circumflex coronary artery. Prior to ethanol infusion, 5.3 ± 1.2 mCi technetium-99m (Tc-99m) methoxyisobutyl isonitrile (sestamibi) was infused into the coronary branch in order to delineate the perfusion bed. After completion of the lesions, each heart was removed, sliced transversely in 5-mm slices, and stained with nitro blue tetrazolium in order to define the ablation bed. The slices were then imaged with a gamma camera and the area of Tc-99m sestamibi uptake was defined as the perfusion bed. These respective areas were planimetered for each slice and compared. No difference was observed in hemodynamic parameters between preablation and postablation measures except mean arterial pressure, which fell from 122 ± 22 mmHg to 116 ± 24 mmHg (P = 0.02). Significant ventricular arrhythmias were observed after 60% of the ablations. The mean left ventricular ejection fraction fell from 55%± 9% to 45%± 15% after completion of all ablations. The areas of the ablation beds were related to the areas of the perfusion beds but the correlation was poor (r = 0.41, P = 0.0001). Generally, the ablation bed was smaller than the perfusion bed, but evidence of ethanol reflux was observed in 29% of the lesions resulting in injury beyond the targeted perfusion bed. Conclusions: Intracoronary ethanol ablation is a promising technique for the treatment of arrhythmias. Significant arrhythmias and a decrease in left ventricular ejection fraction are associated with this technique. Lesions are generally produced within the distribution of the targeted coronary bed, but are also frequently associated with reflux to a second vascular distribution.

Notes: Hyperthermic Myocardial Injury. Introduction: We hypothesized that intracellular calcium overload may play an important role in heat-induced myocardial injury. This postulate was investigated using a model of isolated guinea pig papillary muscle in which resting tension was measured as an indirect indicator of cytosolic free-calcium concentration and the fluorescence changes of Fluo-3 AM dye was measured as a direct indicator of cytosolic free-calcium concentration. Methods and Results: Excised guinea pig right ventricular papillary muscles were attached to a force transducer in a high-flow tissue bath and superfused with Tyrode's solution at 37°± 0.5°C. The temperature was rapidly changed to between 38.0° and 56.0°C for 60 seconds and then returned to 37.0°C. Hyperthermia caused a reversible increase in resting tension at temperatures between 45° and 50°C and irreversible contracture at ≥50°C. Rapid cooling contracture experiments and experiments measuring fluorescence of myocytes loaded with 5 μ M Fluo-3 AM dye demonstrated that the hyperthermia-induced rise in resting tension was likely due to an increase in intracellular calcium content. Inhibition of the sarcoplasmic reticulum calcium pump with 20 μ M thapsigargin resulted in irreversible contracture of the papillary muscles at temperatures between 45° and 50°C and significant increases in Fluo-3 fluorescence at 48°C. Blockade of sarcolemmal calcium channels with 0.5 mM cadmium or 40 μ M verapamil did not attenuate the heat-induced increase in resting tension and Fluo-3 fluorescence. Conclusion: Hyperthermia causes an increase in resting tension of cardiac muscle that most likely is mediated by a calcium channel-independent increase in calcium permeability of the sarcolemmal membrane and/or release of stored intracellular calcium.

Notes: Intracoronary Ethanol Ablation. Introduction: Intracoronary ethanol ablation has been successfully used as arrhythmia therapy, hut the dose response of ventricular function and arrhythmogenesis to varying ethanol concentrations is undefined. Methods and Results: Twenty-six anesthetized pigs weighing 50 ± 11 kg underwent left and right heart catheterization. Ablation solutions composed of normal saline with ethanol in concentrations of 0%, 10%, 25%, 50%, 75%, and 100% were mixed with metrizamide, a nonionic contrast agent (3.75 g per 20 mL), then infused into branch or distal coronary arteries in each of the left anterior descending and left circumflex coronary artery distributions. Hemodynamic measurements, and coronary and left ventricular angiography were performed before and after ablation. Programmed electrical stimulation was performed preablation and at a chronic-study at 4 to 6 days. Excised hearts were examined pathologically. Fifty-two lesions were created in 26 animals, and 24 animals survived to the follow-up study. Minimal hemodynamic alterations were observed in response to ablation. As the ethanol concentration of the ablation solution was increased, the prevalence of spontaneous nonsustained and sustained ventricular tachyarrhythmias increased (P = 0.0002), the ablation vessels were more persistently occluded (P = 0.028), and the postablation global left ventricular ejection fraction showed greater impairment (P = 0.002). Identifiable myocardial lesions were identified in all study groups, including those receiving the 0% ethanol infusion. Lesion size increased significantly with increasing ethanol concentration (P = 0.0004) but there was significant variance within groups. In response to programmed electrical stimulation, ventricular fibrillation was a nonspecific finding before and after ablation. In contrast, monomorphic ventricular tachycardia was induced only at postablation testing, and four of five of these animals underwent infusions with ethanol concentration of ≥ 50% ethanol. Conclusion: Concentrations of ≥ 50% ethanol are most effective in creating large ventricular lesions in intracoronary ethanol ablation, but are associated with more impairment of left ventricular function, and have a greater likelihood of acute and early chronic arrhythmia aggravation.

Notes: Thermometry and Radiofrequency Catheter Ablation. Introduction: Temperature monitoring has been proposed as a control for lesion occurrence and dimension during radiofrequency transcatheter ablation. Effective temperature measurement depends on thermistor positioning relative to the heated cardiac tissue and the convective cooling effects of the circulation. But the accuracy of a single tip thermistor as a measure of peak electrode-tissue interface temperature is unknown. Methods and Results: A standard 8-French, 4-mm electrode catheter with 5 thermistors (1 tip thermistor, 4 radial thermistors) was used to deliver radiofrequency energy in vitro to 3 porcine right ventricles and in vivo to 7 mongrel dogs. In vitro, the catheter orientation was varied. In vivo the catheter was positioned under fluoroscopy at a variety of atrial, tricuspid annular, and ventricular sites, with no attempt to adjust catheter orientation. In both cases varied discrete power levels were used so that a wide temperature range was attained. Lesions created in vivo with a standard, single thermistor tipped electrode were compared to those of a catheter with a thermistor extending 1 mm from the tip. Power was varied and tip thermistor temperatures recorded. All lesions were examined pathologically. Comparisons of radial thermistor temperature to tip thermistor temperature for 3 catheter orientations in vitro resulted in tip thermistor underestimation of peak electrode-tissue interface temperature by a median of 0.5°C in 35% of the perpendicular orientations, 1.9°C in 82% of the 45 orientations, and 5°C in 83% of the parallel orientations. During in vivo trials, the tip thermistor underestimated the peak electrode-tissue interface temperature during 2 of 51 lesions by 1.2°C and 7.6°C. There was a sudden rise in electrical impedance in 17 of 51 radiofrequency energy deliveries. Only one case was observed where the peak electrode-tissue interface temperature was below 95°C. The normal to extended tip thermistor configurations analysis showed similar relationships between lesion size and temperature. Conclusions: Accuracy of a single tip thermistor was found to be dependent upon catheterlissue orientation. With routine catheter positioning in vivo, the tip thermistor was a good indicator of peak electrode-tissue interface temperature. Thus with power regulation to avoid temperatures greater than 90°C, a single flush-mounted tip thermistor is probably adequate for temperature monitoring of lesion formation and avoidance of impedance rises.

Notes: RF Ablation and Creatine Kinase. Introduction: The primary mechanism of myocardial injury during radiofrequency (RF) catheter ablation in the heart is presumed to be thermal. Creatine Kinase has been measured in serum to assess the volume of myocardial injury after ablation. However, its thermal inactivation by RF ablation could lead to underestimation of the true volume of injury. Methods and Results: Serial RF lesions were created in 10 canine left ventricles in vivo, and serial serum Creatine Kinase activities were measured and compared to lesion volume. To assess the stability of myocardial Creatine Kinase during RF catheter ablation, 29 RF ablations were made on the epicardial surface of porcine left ventricle in vivo and a 2-mm core biopsy was rapidly removed. The cores were rapidly frozen, sectioned longitudinally in 1-mm slices, and homogenized in 0.3 M Tris buffer solution containing EDTA and dithiothreitol for subsequent analysis of Creatine Kinase activity. An additional 19 tissue cores from RF lesions were stained and used to determine mean lesion depth. Normal tissue biopsies were exposed to 60 seconds of hyperthermia (37° to 85°C, n = 190), or high-density RF current at 50X (0 to 100 mA/mm2, n = 50), and tissue Creatine Kinase activity was measured. There was no evidence of Creatine Kinase washout within the first 2 hours, and peak values were measured 5 to 7 hours postablation. Tissue Creatine Kinase activity in the first mm depth of RF lesions averaged 10% of control values and increased over the first 5 mm of lesion depth. The mean Creatine Kinase activity within the hemisphere of ablated myocardium was calculated to be 31% of control. Creatine Kinase activity declined significantly at temperatures above 65°C, but no difference in tissue Creatine Kinase activity was observed among differing levels of RF current exposure in the absence of significant heating. Conclusions: Creatine Kinase activity in myocardial tissue is significantly diminished within the RF lesion. Creatine Kinase activity is not stable at temperatures above 65°C, which are routinely achieved within the central zone of RF ablation, and is unaffected by RF current in the absence of hyperthermia. Measurements of serum Creatine Kinase activity after RF catheter ablation may significantly underestimate the volume of myocardial injury.