The electrophysiologic and anatomic basis for fractionated electrograms were investigated in superfused epicardial preparations from infarcted canine hearts. Fractionated bipolar electrograms were frequently recorded in preparations from infarcts 2 weeks to 18 months old but only rarely in preparations from 5-day-old infarcts. The fractionated electrograms were not caused by movement artifacts. They were not associated with depressed transmembrane resting or action potentials (which were found in the 5-day-old infarcts), but rather transmembrane potentials recorded in the vicinity of the bipolar electrodes were normal. Despite the normal transmembrane potentials, activation time in regions where fractionated electrograms occurred was prolonged. However, prolonged activation time by itself did not cause fractionation, since fractionated electrograms were not recorded from normal preparations in which conduction was markedly slowed by a superfusate containing 16 mM potassium and epinephrine. Unipolar electrograms recorded with glass microelectrodes (tip size 1 to 5 ,m) showed that activation in regions where fractionated electrograms were recorded was inhomogeneous. Prepotentials were found preceding the upstrokes of some action potentials in regions where double potentials were recorded, suggesting the possibility of electrotonic transmission across high resistance or inexcitable gaps, but no electrotonic potentials were seen in regions with multicomponent fractionated electrograms. Fractionated electrograms were recorded in regions where infarct healing caused wide separation of individual myocardial fibers while distorting their orientation. The anatomic changes probably caused slow and inhomogeneous activation. Circulation 72, No. 3, 596 611, 1985. FRACTIONATED electrograms, 1-1l consisting of either two discrete deflections separated by an isoelectric interval (double potentials or split deflections4' 7, 8. 12) or comprised of many components'6 7 have been recorded during mapping studies on patients with ischemic heart disease and a history of chronic ventricular tachycardia. These kinds of electrograms have been found during sinus rhythm2'6 7'9-1 as well as during tachycardia. [1][2][3] It is important to determine why fractionated electrograms occur and what they mean. Their occurrence during sinus rhythm might sometimes assist in identifying patients who can develop ventricular tachycardia.6' 8 The site at which these electrograms are recordFrom the

SUMMARY. Structural and electrophysiological properties of the epicardial muscle which survives on the surface of transmural infarcts of the canine heart (epicardial border zone) were studied at different times after occlusion of the left anterior coronary artery (LAD). Isolated preparations were superfused in vitro, transmembrane potentials recorded, and impulse propagation mapped. In preparations from subacute infarcts (1 and 5 days), resting potential, action potential amplitude, upstroke velocity, and duration were all significantly reduced. Well-defined directional differences in propagation occurred. Propagation was more rapid in the direction perpendicular to the left anterior coronary artery than in the direction perpendicular to the base of the heart, because of the uniform anisotropic structure of the surviving muscle fibers which were arranged in tightly packed bundles oriented perpendicular to the left anterior coronary artery. The only ultrastructural abnormalities found in these muscle fibers was an accumulation of large amounts of lipid droplets. As the infarcts healed, resting potential, action potential amplitude, and upstroke velocity returned to normal by 2 weeks, although action potential duration decreased further. Lipid droplets had disappeared, and connective tissue had invaded the epicardial border zone, separating the muscle bundles. By 2 months, action potentials were normal, but the muscle fibers were widely separated and disoriented by the connective tissue (parallel bundles no longer were found). In these regions with a nonuniform anisotropic structure, the well-defined directional differences in impulse propagation were lost. However, activation was very slow, perhaps because of diminished connections between cells. The persistence of slow conduction in healed infarcts may contribute to the occurrence of chronic arrhythmias. {Circ Res 56: 436-451, 1985)

Samples of normal and atherosclerotic vessels obtained from vascular and cardiothoracic surgery were examined for the distribution of fibrinogen/fibrin I, fibrin II, and fibrin(ogen) degradation products (Fragment D/DD) by using recently characterized monoclonal antibodies that recognize and distinguish the three molecular forms (MAbs 18C6, T2G1, and GC4, respectively) with the ABC-immunoperoxidase technique. In normal aortas, little fibrinogen/fibrin I or fibrin II was present and no fibrin(ogen) degradation products could be detected. In early lesions and in fibrous plaques, fibrinogen/fibrin I and fibrin II were distributed in long threads and surrounding vessel wall cells and macrophages. Fibrin(ogen) degradation products were not seen in early lesions. In fibrous and advanced plaques, fibrinogen/fibrin I, fibrin II, and fibrin(ogen) degradation products were detected in areas of loose connective tissue, in thrombus, and around cholesterol crystals. The results of this study suggest that increased fibrin formation and degradation may be associated with progression of atherosclerotic disease. The observed distribution of the different molecular forms of fibrinogen also suggests the possibility that the cells present in the lesions actively participate in the fibrinogen-to-fibrin transition within the vessel wall.

Alterations in cardiac electrophysiology that accompany myocardial infarction were studied in dogs subjected to a two-stage ligation of the anterior descending coronary artery. A multipolar transmural needle electrode was used to record electrical activity from the in situ infarcted heart 24 hours after coronary occlusion. Bipolar electrograms recorded from subendocardial regions of infarcted myocardium demonstrated the persistence of early, rapid deflections suggesting Purkinje fiber activity; evidence of ventricular muscle activity in the infarct was absent in both subendocardial and intramural electrograms. The infarcted myocardium and the adjacent non-infarcted tissue were then excised and studied with intracellular microelectrodes in vitro. Transmembrane action potentials could be recorded from one or two cell layers of subendocardial Purkinje fibers at all sites within the infarcted region, but no ventricular muscle action potentials were found. Subendocardial Purkinje fibers which survived in the infarct had reduced maximum diastolic potentials, action potential amplitudes, and maximum depolarization velocities compared with normal subendocardial Purkinje fibers; also, action potential durations in these surviving fibers were extraordinarily prolonged. Spontaneous diastolic depolarization was evident in some surviving fibers. Since subendocardial Purkinje fibers that generate abnormal action potentials survive in an infarct, these fibers may participate in the genesis of ventricular arrhythmias that accompany infarction. KEY WORDS coronary occlusion cardiac arrhythmias microelectrode bipolar electrogams transmembrane action potentials From the 597 by guest on June 9, 2015 http://circres.ahajournals.org/ Downloaded from 598 FRIEDMAN, STEWART, FENOGLIO, WIT MethodsElectrophysiological studies were performed on both in situ infarcted myocardium and excised, superfused infarcted myocardium. In addition, isolated preparations from dogs without infarction were also studied.Surgical Production of Myocardial Infarction.-Nine mongrel dogs, (10-14 kg) were anesthetized with sodium pentobarbital (30 mg/kg, iv), intubated with a cuffed endotracheal tube, and ventilated by a positivepressure mechanical pump. A lead II electrocardiogram was continuously monitored and recorded on a switched-beam oscillographic recorder (Electronics for Medicine). Using sterile technique, the chest was opened through the fourth left intercostal space and the pericardium was reflected widely. The anterior descending branch of the left coronary artery was isolated from the accompanying vein 10-15 mm distal to its point of origin, and a two-stage ligation was performed according to the technique previously described by Harris (5). The chest was then closed in layers and an airtight seal was maintained.All dogs subjected to this surgical procedure developed extensive infarction of the anterior left ventricular wall, left anterior papillary muscle, and anterior interventricular septum, as verified by subsequent histological study. Two of the d...

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The electrophysiological properties of subendocardial Purkinje fibers surviving in myocardial infarcts were studied with intracellular microelectrodes in isolated superfused preparations and correlated with subsequent light and electron microscopic studies. Transmembrane action potentials could always be recorded from one or two cell layers of subendocardial Purkinje fibers in infarcted regions 3 days to 7 weeks after coronary artery occlusion; ventricular muscle action potentials were rarely found. Microscopic studies also demonstrated several layers of intact subendocardial Purkinje fibers; the subjacent ventricular muscle cells were irreversibly injured and replaced by scar. At all time intervals, surviving Purkinje fibers had significantly reduced maximum diastolic potentials, action potential amplitudes, and depolarization velocities as well as prolonged action potential durations. These parameters normalized between 24 hours and 7 weeks after coronary artery occlusion. Surviving Purkinje fibers with electrophysiological abnormalities at 24 hours and 3 days contained vast lipid deposits. Lipid was less prevalent at 10 days when action potential characteristics had improved. By 7 weeks, action potentials were nearly normal and lipid was absent. Subendocardial Purkinje fibers surviving in infarcts are subject to conditions which cause electrophysiological and ultrastructural abnormalities. Persistent abnormalities in the electrophysiological properties of these surviving Purkinje fibers may cause persistent altered electrophysiological properties of the infarcted heart.

SUMMARY. Although previous studies have described the electrophysiological and ultrastructural characteristics of human cardiac fibers, no attempt has been made as yet to describe quantitatively the relationship between the ultrastructural and cellular electrophysiological derangements occurring with cardiac disease, and their clinical manifestations. In this study, we used standard microelectrode techniques to record the action potential characteristics of human atrial fibers obtained during cardiac surgery and correlated the electrophysiological parameters with clinical and ultrastructural data. Ultrastructure was studied by optical and electron microscopy. We found a multiple linear regression among maximum diastolic potential, atrial size and pressure, P wave duration and ultrastructure changes. Proliferations of Z band material, widening of intercalated discs, and degenerative changes were quantified and correlated with electrophysiological and clinical data. These studies emphasize the relationship between hemodynamic anomalies and resultant changes in both human atrial fiber structure and electrical function. Finally, the likelihood of occurrence of arrhythmias can be predicted using the analytic method described. (Ore Res 52: 188-199, 1983)

Pericardial cysts are generally described as round radiodensities typically found at the right cardiophrenic angle in asymptomatic individuals. A review of all cases of pericardial cysts from the files of this Institute reveals that approximately one third of the cysts are found in other locations and that approximately one third of patients have symptoms of chest pain, dyspnea, or persistent cough. The radiographs of 41 patients show that in all but 6 of the cases the cyst is visualized as a round radiodensity touching both the hemidiaphragm and the anterior chest wall. Surprisingly, 15 of the 41 occurred on the left border of the heart. The six cysts significantly above the diaphragm were difficult to diagnosis radiologically and were usually mistaken for thymomas or pulmonary masses; two such cysts caused bronchial obstruction. In general, the possibility that a mass in either anterior cardiophrenic angle is a pericardial cyst should be strongly considered, even if the mass is on the left side and even if the patient is symptomatic.