Changes in blood coagulation during and following cardiopulmonary bypass: lack of correlation with clinical bleeding.

Although previous studies have documented a wide variety of derangements in laboratory measurements of blood coagulation and platelets during cardiopulmonary bypass, limited data are available concerning the magnitude of these changes and any association with excessive bleeding. To determine whether abnormalities in commonly available laboratory tests for the evaluation of coagulation, fibrinolysis and hemostasis correlate with postoperative blood loss and transfusion requirements as measures of clinical outcome, 47 consecutive patients undergoing coronary artery bypass grafting with hypothermic cardiopulmonary bypass (CPB) were studied prospectively at 12 time points before, during, and following CPB. Routine blood coagulation tests, coagulation factor levels (fibrinogen, V, VII, VIII, and IX) and fibrinolysis (FDP) became abnormal within 15 minutes after patients were placed on CPB, remained abnormal for the duration of CPB, and recovered at varying rates after discontinuation of CPB. Mean factor V levels declined by the greatest percentage, to 15% of normal, followed by factor VIII which decreased to 30%. Platelet counts declined to below 100 x 10(9)/L after the initiation of CPB and remained low in the postoperative period. Twenty-eight percent of patients had mediastinal output > or = 100 mL per hour during the immediate postoperative period, and were considered to be "bleeders." There were no clinically relevant differences in any of the laboratory measurements between patients with normal postoperative blood loss and those defined as bleeders. Thus, the absence of significant correlations between various laboratory measurements of hemostasis and actual postoperative bleeding indicates that these laboratory derangements are transient, are not predictive of clinically important hemostatic abnormalities, and should not be used in isolation to guide the use of blood components in these patients. Furthermore, although bleeders received more blood components, there was surprisingly little effect on the coagulation factor levels measured.

Correction of congenital hydronephrosis in utero IV: in utero decompression prevents renal dysplasia.

Renal dysplasia (RD) is commonly seen in babies with urinary tract obstruction (UTO). Recent experimental evidence suggests that early fetal UTO leads to the development of RD. The RD seen in children with congenital UTO is usually not reversible, even when the obstruction is relieved soon after birth. Is the RD associated with congenital UTO preventable or reversible by decompression of the urinary tract early in gestation? If so, at what stage of development must this decompression be performed? We produced complete unilateral ureteral obstruction in 25 early second trimester (62 to 65 days) lamb fetuses, a procedure that results in ipsilateral RD at term (140 days). At a second operation, 20, 40, or 60 days after the initial procedure, we decompressed the obstructed kidney by a cutaneous end-ureterostomy. The contralateral unobstructed kidneys served as controls. Renal function (urine output and iothalamate clearance) and histopathology were evaluated after delivery at term. Recovery of renal function was directly proportional to the duration of in utero decompression and inversely proportional to duration of obstruction. In addition, in utero decompression prevented or greatly ameliorated the development of RD. However, some postobstructive changes persisted; these were proportional to the length of in utero obstruction. These results substantiate the clinical impression that some human fetuses with congenital UTO may benefit from early in utero decompression.

Correction of congenital hydronephrosis in utero III. Early mid-trimester ureteral obstruction produces renal dysplasia.

Is the renal dysplasia (RD) commonly seen in babies with urinary tract obstruction a developmental consequence of the obstruction or is it an associated embryologic malformation? We produced complete unilateral ureteral obstruction in six 58- to 66-day old lamb fetuses by clipping a silastic ring on the ureter. Three fetuses survived to term. All obstructed kidneys were not only grossly hydronephrotic but dysplastic by histologic criteria; ie, parenchymal disorganization, primitive epithelial structures, and marked fibrosis. The contralateral unobstructed control kidneys were normal. The changes were similar to those seen in the human neonate with obstruction and RD, suggesting that in this model RD was caused by obstruction to the flow of urine early in fetal development.

Modification of tyrosine residues of the lactose repressor protein.

Reaction of the lactose repressor protein from Escherichia coli with high molar excesses (up to 800 fold) of tetranitromethane resulted in modification of tyrosine residues in the amino-terminal and core regions of the molecule. Tyrosines 7 and 17 exhibit significant reactivity at low levels (5-10 fold molar excess) of tetranitromethane. The loss of operator binding activity upon nitration at these low concentrations of reagent indicates involvement of these two tyrosines in the binding process. Inducer binding activity was maintained at approx. 90% of unreacted repressor for all excesses of reagent studied. Addition of inducer to the repressor prior to reaction resulted in decreased modification of tyrosines in the core region, but anti-inducers did not affect the reaction significantly. The effect of inducers on the pattern of reaction apparently reflects the conformational change which occurs upon binding of these ligands. Acetylation of the repressor protein with N-acetylimidazole modified lysines and tyrosines with complete loss of operator binding activity and retention of 75-80% of inducer binding activity.