Caroline M. Czarnecki

Effects of Furazolidone on the Development of Cardiomyopathies in Turkey Poults

SUMMARY Graded doses of furazolidone were added to feed mixtures given turkey poults the first five weeks post-hatching. Toxicity from as little as 300 ppm was confirmed. Mortality from 500 ppm for five weeks was high (41%). Furazolidone at 100 ppm apparently stimulated growth, since the poults in this group were significantly heavier at 3 to 5 weeks of age than other poults. At toxic levels, the growth rate of unaffected (normal) birds paralleled that of control birds. Incidence of cardiomyopathies increased with furazolidone dose. The cardiomyopathy observed most commonly was a combined right and left ventricular dilatation. To study spontaneous recovery, all birds were monitored for 7 weeks after removal of the drug. Both development of the round heart syndrome and spontaneous recovery were quite variable in rate.

Cardiomyopathy in turkeys

Round heart disease (RHD) is a spontaneous occurring cardiomyopathy in fowl affecting primarily inbred, small broad-breasted white strains of turkeys. Etiology of RHD is unknown but factors implicated include genetic, management, enzyme deficiencies, viral, immunologic, and metabolic. Investigations of proposed etiologic factors are reviewed. Furazolidone (FZ)-induced cardiomyopathy is indistinguishable from spontaneous RHD, but it remains to be shown that both are mediated by the same mechanism(s). Studies to date suggest that FZ-induced cardiomyopathy is an exaggeration of the spontaneous condition.

Animal models of drug-induced cardiomyopathy

Animal models of drug-induced cardiomyopathy relevant to clinical medicine have been difficult to produce. Animal species commonly used to study cardiomyopathies include the rabbit, rat, and mouse of which none are completely satisfactory. Recently, the turkey poult has been proposed as an attractive animal model for investigation of drug-induced cardiomyopathy.

Blood Glucose and Tissue Glycogen Levels in Turkey Poults With Spontaneous Round Heart Disease and Furazolidone-induced Cardiomyopathy'

Furazolidone (FZ) at 700 ppm was added to feed mixtures fed turkey poults two weeks posthatching to induce acute experimental cardiomyopathy. Poults in the control pen received the same ration but without FZ. Four of the control poults developed spontaneous round heart disease. From EKG data and blood samples obtained at weekly intervals, poults were selected for sacrifice at 5 weeks of age. Tissue samples from the left myocardial wall, liver, and pectoralis major and tibialis anterior muscles were analyzed for glycogen by biochemical assay. Blood glucose was determined with the Technicon autoanalyzer. Deposition of glycogen increased significantly (p less than 0.05) in the myocardium of all affected poults and in the liver of all FZ-treated poults. Glycogen levels of the pectoralis major and tibialis anterior muscles were not affected by FZ, but a significant increase (p less than 0.05) was apparent in the pectoralis major muscle of spontaneous round heart poults. It was concluded that FZ influences glycogen metabolism, probably by enzyme inhibition, and that it tends to magnify effects seen in the spontaneous round heart syndrome. Glycogen infiltration of tissues such as the heart and white skeletal muscle suggests that the round heart syndrome may be a manifestation of the glycogen storage disease, idiopathic generalized glycogenosis. Lack of significant differences in the blood serum glucose levels of all poults indicates that these levels are not a reliable clinical parameter for monitoring development of the round heart syndrome.

Ultrastructural features of ethanol-induced cardiomyopathy in turkey poults

Alcoholic cardiomyopathy, characterized by cardiac hypertrophy, was induced in young turkey poults with 5% ethanol. Ultrastructural features included accumulation of glycogen, swollen mitochondria, myofibrillar lysis, increased number of lysosomes, dilated sarcoplasmic reticulum and dense myofibers. Similarity of these alterations to those described in human alcoholic cardiomyopathy confirms the usefulness of the turkey poult as an animal model for this disease syndrome.

Effect of Furazolidone on Heart Weights and Myocardial Moisture Content in Turkey Poults

Furazolidone (FZ) at 700 ppm in feed mixtures fed turkey poults from 2 to 5 weeks posthatching significantly increased the ratio of heart weight to body weight (p less than 0.001) and myocardial moisture content (p less than 0.05). The increase in myocardial moisture content is believed to be related to increased glycogen deposition under the influence of FZ since FZ removal from the diet decreased myocardial glycogen levels and moisture content to normal levels.

Quantitative morphological alterations during the development of furazolidone-induced cardiomyopathy in turkeys

Cardiac structures were measured to determine the sequence of alterations during the development of spontaneous and furazolidone-induced cardiomyopathy in turkey poults 20 to 31 days after hatching. Samples of tissue from the free walls of the ventricles were removed and processed for electron microscopy. Volumetric density of cardiac structures was determined by the point-counting technique. The results indicate that the sequence of myocardial alterations is similar in both spontaneous and furazolidone-induced cardiomyopathy, but that these changes are more pronounced in the latter condition. Major changes include an early diminution in myofibrillar density, accompanied by a small reduction in mitochondrial density. This is followed by dilatation of the ventricular lumina and a decrease in the volume fraction of Z-bands. The increase in mass of the free walls of the ventricles in affected poults is due primarily to an increase in extracellular components and sarcoplasm devoid of organelles. The results suggest that the development of this myopathy is initiated by damage to the myofibrils of the cardiocytes.

Quantitation of Cardiac Gross Morphology During the Development of FZ-Induced Cardiomyopathy in Turkey Poults

Furazolidone (FZ) at a dose of 700 ppm was fed to turkey poults 2-5 weeks posthatch. At 3, 4, and 5 weeks of age, seven poults each were sacrificed from control and FZ-fed groups. A section of ventricular tissue 1 mm thick was excised from the heart distal to the base at a level one-fourth of the distance between the base and apex. Parameters estimated from tracings of each section were area and circumference of both right and left ventricular lumen profile, area and circumference of entire heart profile, area of right ventricular free wall profile, area of left ventricular and septal wall profile, and area of entire heart muscle profile. A major finding was a sequential increase in the area of the ventricular lumina in the FZ-fed poults. Differences between the control and FZ-fed poults were statistically significant for the right lumen profile at 3 and 5 weeks of age and for the left lumen profile at 4 and 5 weeks of age. The area of the heart muscle profile was decreased in FZ-fed poults, but this difference was statistically significant only at 4 weeks of age. Data suggest that the pathogenesis of FZ-induced cardiomyopathy involves a dilation of ventricular lumina resulting in increased intraventricular blood volume and altered ECG patterns. Relationships between gross morphology and ECGs may be seen only in terminal cases of several weeks duration. This explains the inability to correlate ECGs with gross morphologic changes in all poults observed at necropsy.

Characterization of glycogen in selected tissues of turkey poults with spontaneous round heart disease and furazolidone-induced cardiomyopathy

Furazolidone (FZ) at 700 ppm was added to feed mixtures fed turkey poults 2--5 weeks after hatching to induce acute experimental cardiomyopathy. Poults in the control pen received the same ration but without FZ. From EKG data obtained at weekly intervals, poults were selected for sacrifice at 5 and 10 weeks of age. Poults were sacrificed by cervical dislocation and appropriate samples of tissue from the left ventricle, liver, pectoralis and tibialis cranialis muscles were removed for glycogen assays. Character of glycogen, as determined by percent of branching and number of glucose units per segment, was not significantly altered in poults with spontaneous round heart disease or FZ-induced cardiomyopathy. This suggests that the glycogen accumulation noted in these conditions most closely resembles type II glycogenosis.

Cardiac taurine levels and sarcolemmal calcium binding activity in furazolidone-induced cardiomyopathy.

Abstract 1. Cardiac taurine levels and sarcolemmal calcium binding activity were investigated in control turkey poults and in poults with furazolidone (FZ)-induced cardiomyopathy. 2. FZ at a dose of 700 ppm added to the feed of poults from 2 to 5 weeks post-hatching significantly reduced cardiac taurine levels and elevated the sarcolemmal calcium bindingactivity at high calcium levels. 3. The effect of FZ on cardiac taurine levels was reversed by removing the drug from the diet for a period of 2 weeks. 4. Data suggests that the cardiotoxicity of FZ is associated with severe damage to the sarcolemma.