Close relationship of PAI-1 (plasminogen activator inhibitor-1) with multiple organ dysfunction syndrome and abnormal glucose metabolism investigated by means of artificial pancreas

Background

There are many reports in recent years that the PAI-I is related to cardiovascular diseases and glucose intolerance especially in diabetic patients. But the role of role of PAI-1 to organ dysfunction and glucose in acutely ill patients is not clearly analysed. We invesigated the contribution of coagulopathy including abnormal PAI-1 level to organ dysfunction and to abnormal glucose metabolism in serious patients by means of the bedside type artificial pancreas (AP).

Materials and methods

Thirty-five serious patients with glucose intolerance, consisting of 25 males and 10 females aged from 23 years to 75 years, were investigated. Primary diseases were as follows: 12 patients with pneumonia, seven with abdominal diseases treated by surgery, six with acute pancreatitis, three with hepatobiliary disorders, two with diabetic foot, and five with other diseases. Analysed items were, 1) regarding multiple organ failure (MOF), MOFscore (calculated from the MOF criteria of Japanese Association for Critical Care Medicine), 2) regarding glucose metabolism, (a) M value (mg/kg per min: measured by the euglycemic hyperinsulinemic glucose clamp method with AP. The clamped blood glucose level was 80 mg/dl with the insulin infusion rate of 1.12 mU/kg per min) as an indicator of peripheral glucose tolerance, (b) MCRI (ml/kg per min: metabolic clearance rate of insulin: measured by the glucose clamp method) as an indicator of insulin metabolic rate, 3) regarding coagulation and fibrinolysis, (a) DIC (disseminated intravascular coagulation) score calculated from the DIC criteria of the Ministry of Health and Wealth of Japan, (b) PAI-I, (c) tPA-PAI (tissue plasminogen activator-PAI-1 complex), (d) FDP, (e) anti-thrombin III, (f) D-dimer, (g) PIC, (h) TAT, (i) plasminogen, (j) protein-C, 4) TM (thrombomodulin) as a parameter of endothelial cell injury, and 5) serum fat (free fatty acid (FFA), triglyceride, cholsterol). AP used was STG-22, made by NIKKISOH Corp. in Japan.

Results

There were correlations between the following parameters. 1) Between MOF and other parameters; positive correlation between DICscore and MOFscore (y = 0.533x + 2.70, n = 26, r² = 0.705), MOFscore and PAI-I (y = 0.00996x + 0.588, n = 14, r² = 0.282), MOFscore and tPA-PAI (n = 15, r² = 0.239), 2) between PAI-I or tPA-PAI and other parameters; (a) negative correlation between tPA-PAI and M value (y = -17.4x + 98.9, n = 13, r² = 0.665), b) positive correlation between PAI-I and MCRI (y = 16.4x-108, n = 8, r² = 0.532), tPA-PAI and MCRI (n = 8, r² = 0354), TM and PAI-1 (y = 0.0155x + 2.55, n = 13, r² = 0.635), TM and tPA-PAI (n = 14, r² = 0.660), FFA and PAI-1 (y = 0.000490x + 0.144, n = 10, r² = 0.477), FFA and tPA-PAI (n = 11, r² = 0.429). Other parameters but PAI-I and tPA-PAl related to coagulopathy showed no definite relationships with MOFscore, M value, MCRI, TM and FFA

Conclusion

Multiple organ dysfunction syndrome, glucose intolerance, and increased insulin metabolism were revealed to be closely related to increased PAI-I or tPA-PAI, which reflect decreased fibrinolysis. Injury of endothelium and increased serum FFA level were thought to be related to increased PAI-I and tPA-PAI, which may explain the progression of MOF partly. In addition, PAI-1 and tPA-PAI seemed to be sensitive marker of, and might be one of the risk factors of multiple organ dysfunction syndrome and nutritional metabolic disorder.