Rabbits were fed a low cholesterol atherogenic diet for up to 5 years. Arterial lesions during the first 12 months consisted of smooth muscle cell and lipid accumulation in the intima, with smaller amounts of elastin and collagen. By 24 months, considerable degeneration and necrosis of smooth muscle foam cells had occurred, lipid had decreased in relative proportion, and collagen was predominant. These trends continued during the final 3 years. By 48 months most plaques were calcified and a few had hemorrhage. Atherosclerosis was extensive in rabbits with serum cholesterol concentrations greater than 300 mg/100 ml and minimal in rabbits with concentrations consistently less than 150 mg/100 ml. Thicker lesions tended to have more atheromas while thinner ones were more fibrous and less fatty. Significant regression of fatty streaks occurred in a group of rabbits fed the atherogenic diet for 2 years and a stock diet during the third year but more advanced lesions did not regress. This study illustrates the importance of time as a variable in atherogenesis, and demonstrates that modest hypercholesterolemia can lead to atherosclerosis in rabbits that is qualitatively unlike atherosclerosis induced in rabbits by cholesterol rich diets and that resembles several stages of human atherosclerosis. A theromatous lesions have been produced in rabbits for more than 70 years by feeding cholesterol-supplemented (0.5% to 3.0%) stock diets, but feeding periods have seldom been longer than 16 weeks because of the toxicity of dietary cholesterol in this species. 1 " 4 Occasionally, feeding times were extended by intermittent feeding of a high cholesterol diet.4 ' 5 During the past two decades, a number of low cholesterol and cholesterol-free atherogenic diets have been used, but experiments, with few exceptions, have been less than 1 year. " 17On the other hand, atherosclerosis in humans probably begins early in life and progresses over several decades.18 ' 19 Time itself may be an important variable in atherogenesis, a factor largely ignored in previous studies. In the present study, arterial lesions were evaluated at various times in rabbits fed a low cholesterol diet for up to 5 years. Changes in arterial lesions were also studied in rabbits fed the atherogenic diet for 2 years and then a stock diet for 1 year. Methods AnimalsWe purchased 250 weanling male rabbits of the Dutch-Belted breed from a single supplier. The rabbits were housed individually in wire-bottomed cages in temperature-and humidity-controlled rooms, with 12 hours of light and 12 hours of darkness daily. The rabbits were observed daily and weighed once a month.
To reinvestigate the relationship between diabetes and atherosclerosis in rabbits, we fed alloxan-diabetic, alloxan-nondiabetic, and control rabbits a low cholesterol atherogenic diet for up to 40 weeks. Concentrations of plasma total cholesterol, phospholipids, and triglycerides were higher, the percentage of very low density lipoproteins was higher, and the percentage of high density lipoproteins was lower in diabetic than in nondiabetic rabbits. Smooth muscle cell proliferation was prominent, atherosclerosis was more extensive, and a high incidence (29%) of large, sharply demarcated, ischemic myocardial lesions occurred in the diabetic rabbits. These results are in contrast to those of earlier studies where the diabetic state resulted in a partial protection against atherogenesis in alloxan-diabetic rabbits fed larger amounts of cholesterol. (Arteriosclerosis 4:586-591, November/December 1984) P lasma cholesterol and triglyceride concentrations are higher in alloxan-diabetic rabbits fed cholesterol (0.5% to 2%) compared to cholesterolfed nondiabetic rabbits.1 -3 Serum phospholipid concentrations are also increased in cholesterol-fed diabetic rabbits but there is a reduction in the cholesterol/phospholipid ratio, 4 and the Sf 12-30 lipoproteins. 5Although cholesterol-fed diabetic rabbits develop atherosclerotic lesions, there is a paradoxical decrease in the extent of disease unless insulin therapy is instituted, and then the degree of atherosclerosis in the diabetic rabbits is increased to the level found in the nondiabetic rabbits. 6 A number of undesirable toxic effects are present in rabbits fed 0.5% cholesterol or more. Development of low cholesterol atherogenic diets for rabbits permitted reinvestigation of the relationship between diabetes and atherosclerosis in rabbits under more physiologic conditions.
We report three cases of corrected transposition (CT), all with Ebstein's disease, ventricular septal defect (VSD) and ventricular preexcitation. In cases 1 and 2, the ECG revealed sinus rhythm, with type A fusion preexcitation QRS complexes, suggesting left-sided Kent bundles and intact conduction system (CS). Complete serial section (SS) of the CS in both cases revealed an anterior CS and a Kent bundle in the posteroseptal wall of the morphologic right ventricle (MRV). Case 3 had intermittent preexcitation, with periods of complete atrioventricular (AV) block with narrow QRS escape rhythm. The preexcitation complexes suggested the presence of a left lateral Kent bundle. SS of the CS revealed a blind posterior and two anterior AV nodes, one on either side of the pulmonary trunk. The left anterior AV node was blind. The right anterior node formed the anterior bundle, which ended blindly. This bundle emerged again and joined a posterior bundle to form an interrupted sling around the closed VSD. In addition, there was a tenous Kent bundle at the posterolateral wall of the MRV. In summary: (1) preexcitation in CT with Ebstein's disease of the left AV valve is associated with Kent bundles; (2) fusion complexes reflected intact CS; and (3) intermittent preexcitation with AV block was associated with the presence of tenuous Kent bundl and discontinuity of the CS.
Contradirectional interference results when 2 stimuli arising in different foci in any part of the heart spread in opposite directions toward each other. Interference dissociation is defined as that type of dissociation which is due to repetitive contradirectional interference. The electrocardiograms of 12 cases have been selected for analysis to illustrate many of the important features of interference dissociation. The various centers between which dissociation may theoretically occur are listed for reference. This series includes examples of dissociation due to interference between the following pairs of rhythms: Normal sinus rhythm and A-V nodal rhythm, normal sinus rhythm and multifocal idioventricular rhythms, sinus tachycardia and paroxysmal ventricular tachycardia, paroxysmal atrial tachycardia with block and idioventricular rhythm, simultaneous dissociated paroxysmal A-V nodal and ventricular tachycardias, and normal sinus rhythm and A-V nodal rhythm in the presence of the Wolff-Parkinson-White syndrome. Interference may occur at any level between the points of origin of the 2 rhythms, and the most common sites of interference are illustrated diagrammatically. Interference at the upper end of the A-V junction is of particular importance, and a clear understanding of isolated interference in this region is of help in resolving some of the more difficult problems of dissociation. For this reason the concept of the zone of potential interference is introduced. This is the time interval in the cardiac cycle during which interference between an A-V nodal, or ventricular, and oncoming S-A beat may be anticipated. Certain important deductions are derived from theoretical considerations of the zone of potential interference. The various mechanisms leading to the onset and termination of interference dissociation are described, and the rates of the dissociated rhythms are compared. Aberrancy of the ventricular response to A-V nodal impulses is discussed. This phenomenon is ascribed to uneven spread of the excitation wave from an eccentrically located focus, due to the fact that in the A-V node longitudinal is faster than horizontal transmission. Ventricular and atrial captures are considered in detail. Of particular interest is the occasional occurrence of both types of capture in the same case. This paradox is explained on the basis of either intermittent retrograde block or simultaneous bidirectional conduction through the A-V node in the presence of functional longitudinal dissociation. The relationship of other forms of heart block to interference dissociation is pointed out. Heart block predisposes to, and frequently complicates, interference dissociation. A differential diagnosis between interference dissociation and other disturbances of rhythm is presented. Interference dissociation is one of the most complex arrhythmias and familiarity with all its possible variations is essential to the correct interpretation of any given tracing.
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