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

We examined 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. Twenty-three mongrel dogs were prepared with catheters in the aorta and left atrium and snares on the left anterior descending coronary artery. Seven days later, myocardial infarction was produced by complete coronary occlusion. Serial serum samples were obtained for CK analysis over 72 hours 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 minutes, 2, 6 and 24 hours after occlusion using 7-10-ju 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 of ± 23 g, indicating a poor linear relationship. The relationship between EE and HI was described best by the power function equation EE = 18.6 HI' 46 (r = 0.91), 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 K, was calculated from HI and the Shell equation, the relationship between Kr and HI over the entire range of HI was described by the equation Kr = 5.53 HI0.54 (r = -0.93), 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/g during the interval of CK release (r = 0.81, ± 20 SEE). This procedure reduced the HI size in the larger infarcts preferentially. This study indicates that 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.