Pharmacological intervention for renal protection during cardiopulmonary bypass.
The possibility of minimizing organ damage following cardiopulmonary bypass (CPB) was examined. In the control group, n = 21, upon completion of CPB, elevation of the lysosomal enzyme beta-glucuronidase, which is a sensitive indicator of cellular damage, was affected by the concentration of granulocyte elastase (r = 0.59) or the endothelial-derived constricting factor, endothelin, (r = 0.8). Renal damage, which was detected by an increase in renal tubular enzymes (N-acetyl-beta-D-glucosaminidase and gamma-glutamyltranspeptidase) in urine, was also affected by endothelin (r = 0.79, r = 0.56), elastase (r = 0.6, r = 0.71), and by free hemoglobin levels (r = 0.76, r = 0.82). Next, the efficacy of pharmacological intervention for the prevention of renal damage was evaluated. During CPB, the administration of an elastase inhibitor (ulinastatin, 3 x 10(5) IU), n = 8, or a calcium antagonist (nicaldipine HCl, elastase release inhibitor; 5 gamma/kg per min), n = 8, significantly reduced the elevation of beta-glucuronidase and renal tubular enzymes (p < 0.05). Although the ulinastatin and nicardipine groups demonstrated low values of elastase in the Intensive Care Unit (ICU), only the values of the nicardipine group reached statistical significance (p < 0.05). A reduction in endothelin levels compared to the control group was observed in the nicardipine group. However, preventive and counteractive effects of nicardipine against vasoconstriction caused by endothelin were also considered to play an important role in the prevention of renal damage. The addition of haptoglobin (4,000 IU) to the priming solution of the CPB also reduced levels of renal tubular enzymes (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Hashimoto
K
K
Department of Cardiovascular Surgery, Jikei University School of Medicine, Tokyo, Japan.
Nomura
K
K
Nakano
M
M
Sasaki
T
T
Kurosawa
H
H
D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016232:Endothelins / Q000097:blood; D005966:Glucuronidase / Q000032:analysis; D006023:Glycoproteins / Q000494:pharmacology*; D006242:Haptoglobins / Q000494:pharmacology*; D006454:Hemoglobins / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008875:Middle Aged; D009529:Nicardipine / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000097:blood; D011480:Protease Inhibitors / Q000097:blood
D016232:Endothelins; D006023:Glycoproteins; D006242:Haptoglobins; D006454:Hemoglobins; D011480:Protease Inhibitors; D009529:Nicardipine; D005966:Glucuronidase; D010196:Pancreatic Elastase; C028665:urinastatin