Creatine kinase MM isoenzyme subforms in myocardium, cardiac lymph and blood after coronary artery occlusion in dogs

Abstract

A time-varying pattern of creatine kinase MM (CK-MM) isoenzyme subforms has been found in the blood of patients after acute myocardial infarction, but the site of enzyme modification has not been identified. Therefore, we studied the CK-MM subform patterns in myocardium, cardiac lymph and blood of dogs after coronary artery occlusion. In five conscious dogs, serial blood samples were taken for 72 h after occlusion of the left anterior descending coronary artery. Samples of non-infarcted and infarcted myocardium were taken after 72 h. In five other anaesthetised, open-chest dogs, cardiac lymph and blood samples were taken for 6 h after coronary artery occlusion. CK-MM subforms were quantitated by an isoelectric focusing method. Before coronary occlusion, 64% of the total CK activity in blood appeared as the anodal subform CK-MM 1 (pI 6.3); 20% and 9% as the cathodal subforms CK-MM 2 (pI 6.6) and CK-MM 3 (pI 6.9), respectively. However, after 2 h of coronary occlusion CK-MM 2 and CK-MM 3 were increased (38% and 17% of total activity respectively) compared with CK-MM 1. Between 4 h and 10 h, CK-MM 2 and CK-MM 3 decreased as CK-MM 1 increased restoring the control relative activities of subforms. In contrast to the subform changes in blood, CK-MM 3 was the predominant subform in both non-infarcted and infarcted myocardium after 72 h of coronary occlusion and in cardiac lymph during 6 h of coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of carboxypeptidase N as an enzyme responsible for C-terminal cleavage of stromal cell-derived factor-1α in the circulation

“…35 Another identified substrate for CPN is creatine kinase MM (CK-MM), an intracellular enzyme that catalyses the transfer of a phosphate group from adenosine triphosphate (ATP) to creatinine. 35,44 CPN cleaves the 2 carboxyterminal lysines from CK-MM to generate CK-MM1 and CK-MM2 detected in the circulation. 45 Increased levels of intact CK-MM compared with its cleaved forms CK-MM1 and CK-MM2 correlate with tissue damage following myocardial infarction.…”

Diagnostic changes in plasma creatine kinase isoforms early after the onset of acute myocardial infarction.

“…'-7 When heart muscle undergoes irreversible injury, it liberates MMA,8 9 the tissue MM CK isoform, into the circulation, along with other macromolecules such as MB CK, transaminase, and myoglobin. Judging from results in experimental animals, once MMA is exposed to plasma it undergoes sequential conversion to MMB and MM.2, 10 The rates of conversion are consistent when physiologic conditions do not change but may vary under conditions in which amounts or activities of converting factors in plasma vary." In dogs, the relative activities of isoforms in plasma after myocardial infarction change predictably with time.…”