P J O'Brien1. 1. Human Safety Department 500 Miami Valley Laboratories, Procter & Gamble, Cincinnati, OH 45253-8707, USA.
Abstract
OBJECTIVE: To test the hypothesis that the derangement of myocardial energy homeostasis characteristic of idiopathic dilated cardiomyopathy (IDCM) of Doberman Pinschers was attributable to deficiency of creatine kinase (CK) isoenzyme MB relative to CK isoenzyme MM and troponin-T (Tn-T). ANIMALS: 9 Doberman Pinschers with advanced congestive heart failure attributable to IDCM and 9 mixed-breed dogs without cardiac disease (controls). PROCEDURE: Myocardial myofibrillar CK-MM, mitochondrial CK, and cytosolic CK-MB activities were determined in comparison with the concentration of cardiac-specific, myofibrillar protein Tn-T. Myocardial biopsy specimens were obtained after euthanasia and were ultrafrozen. Isoenzymes of CK were separated electrophoretically, and their activity was determined, using a coupled-enzyme, kinetic, fluorescent assay and densitometry. Troponin-T content was determined by immunoassay. RESULTS: Myofibrillar CK-MM and mitochondrial CK activities and Tn-T content were 25% lower in the dogs with IDCM than in controls, whereas cytosolic CK-MB activity was 50% lower. CONCLUSION: Deficiency of CK-MB activity is a component of and may have a central role in the energy deficiency characteristic of failing myocardium in IDCM of Doberman Pinschers. A side-product of this study was the observation that, in dogs, CK-MB activity and Tn-T content of myocardium are sufficiently high to be candidate serum markers for active cardiac injury.
OBJECTIVE: To test the hypothesis that the derangement of myocardial energy homeostasis characteristic of idiopathic dilated cardiomyopathy (IDCM) of Doberman Pinschers was attributable to deficiency of creatine kinase (CK) isoenzyme MB relative to CK isoenzyme MM and troponin-T (Tn-T). ANIMALS: 9 Doberman Pinschers with advanced congestive heart failure attributable to IDCM and 9 mixed-breed dogs without cardiac disease (controls). PROCEDURE: Myocardial myofibrillar CK-MM, mitochondrial CK, and cytosolic CK-MB activities were determined in comparison with the concentration of cardiac-specific, myofibrillar protein Tn-T. Myocardial biopsy specimens were obtained after euthanasia and were ultrafrozen. Isoenzymes of CK were separated electrophoretically, and their activity was determined, using a coupled-enzyme, kinetic, fluorescent assay and densitometry. Troponin-T content was determined by immunoassay. RESULTS: Myofibrillar CK-MM and mitochondrial CK activities and Tn-T content were 25% lower in the dogs with IDCM than in controls, whereas cytosolic CK-MB activity was 50% lower. CONCLUSION:Deficiency of CK-MB activity is a component of and may have a central role in the energy deficiency characteristic of failing myocardium in IDCM of Doberman Pinschers. A side-product of this study was the observation that, in dogs, CK-MB activity and Tn-T content of myocardium are sufficiently high to be candidate serum markers for active cardiac injury.