Early alterations in the function of sarcoplasmic reticulum in a naturally occurring model of congestive cardiomyopathy.

In a naturally occurring model of congestive cardiomyopathy-round heart disease of turkeys, Ca2+ transport of isolated cardiac sarcoplasmic reticulum was evaluated at 1, 10, 28, and 56 days of age. Ca2+ binding in round heart disease birds was reduced to between 55% and 75% of values measured in age-matched commercial control turkeys (P less than 0.05 to less than 0.01). Similarly, Ca2+ uptake in round heart disease birds was reduced to between 52% and 87% of values measured in age-matched commercial control turkeys (P less than 0.05 and less than 0.01). Ca2+-stimulated ATPase values were similar in 1-, 10-, and 28-day-old round heart disease and commercial control turkeys. However at 56 days of age, when all round heart disease birds showed moderate to marked left ventricular dilatation. Ca2+-stimulated ATPase was reduced to 75% of control values (P less than 0.05). Depression of Ca2+ binding and Ca2+ uptake preceded the appearance of cardiac dilatation and may contribute to the pathogenesis of round heart disease. Depression of Ca2+-stimulated ATPase, present only after cardiac dilatation developed, appears to be secondary to cardiac failure. Sarcoplasmic reticulum function in round heart disease birds immunosuppressed by cyclophosphamide treatment (40 mg . kg-1 . d-1 for the first 4 days of age) was evaluated at 10 days of age. This treatment increased Ca2+ binding by 73% (P less than 0.05), and Ca2+-uptake by 58% (P less than 0.01) over values measured in untreated round heart disease birds. Reversal of the altered Ca2+ transport in sarcoplasmic reticulum by early immunosuppression supports the hypothesis that the immune system plays an integral part in the development of the congestive cardiomyopathy of round heart disease.