Nonlinear relationship between creatine kinase estimates and histologic extent of infarction in conscious dogs: effects of regional myocardial blood flow.

Abstract

The relationships between creatine kinase (CK) enzyme estimates of infarction (EE), histologic extent of infarction (HI) and regional myocardial blood flow (RMBF) over a wide range of infarct sizes in chronically prepared awake dogs were examined. Mongrel dogs (23) dogs were prepared with catheters in the aorta and left atrium and snares on the left anterior descending coronary artery. Myocardial infarction was produced by complete coronary occlusion 7 days later. Serial serum samples were obtained for CK analysis over 72 h and EE was calculated using the Shell formula, which assumes constant serum CK appearance ratio (Kr) from infarcted myocardium. Regional myocardial blood flow was measured before occlusion and at 15 min, 2, 6 and 24 h after occlusion using 7-10 .mu. microspheres. Six days after occlusion, HI and RMBF were determined from 1-2 g samples of the entire left ventricle. The histologic extent of infarction ranged from 1-54 g. Linear regression analysis between EE and HI demonstrated an r value of 0.75 and SEE [standard error of estimation] of .+-. 23 g, indicating a poor linear relationship. The relationship between EE and HI is described by 2 power function equation indicating relatively less CK appeared in the blood as HI increased. When the analysis was limited to infarcts of less than 20 g, a good linear relationship was observed (r = 0.94). When Kr was calculated from HI and the Shell equation, the relationship between Kr and HI over the entire range of HI was described by an equation, suggesting CK release from infarcted myocardium was not constant, but decreased as a power function as HI increased. In the total group of dogs, the best linear relationship between EE and HI resulted from modifying the HI by subtracting regions that remained severely ischemic, RMBF < 0.1 ml/min per g during the interval of CK release (r = 0.81, .+-. 20 SEE). This procedure reduced the HI size in the larger infarcts preferentially. Over a large range of infarction, the relationship between EE and HI is best described by a power function rather than a linear function. This relationship may be caused by progressive reduction in CK release from regions of severely reduced blood flow. Estimation of infarct size from serum CK measurements using a constant Kr introduced an error that increased as infarct size increased.