Since the introduction of the proteinase inhibitor aprotinin in cardiac surgery, a strong increase of the activated clotting time (ACT) during the extracorporeal circulation phase (ECC) was reported in many clinical studies, but with a lack of correlation between ACT and heparin concentration. In searching for a cause of this inconsistency we investigated different surface activators of the ACT in a clinical study. During ECC ACT was measured in parallel, using a Hemochron device and corresponding tubes (nominally 12 mg celite activator) for celite ACT, and a HemoTec device with corresponding double tubes (nominally 0.1 ml kaolin activator) for kaolin ACT. Under the conditions of ECC, the kaolin ACT values (482 +/- 145 sec) were significantly lower than the celite ACT values (985 +/- 267 sec). These results were confirmed in ex-vivo experiments using an activated partial thromboplastin time (aPTT) model. With heparin alone, aPTT activated with celite and kaolin were similar. Including aprotinin in this model, the celite aPTT showed no correlation to the heparin concentration, whereas the kaolin aPTT remained well correlated to the heparin concentration and similar to the values without aprotinin. With aprotinin alone there were no changes of the aPTT times, whereas the celite ACT times were without any correlation. Our results indicate that using kaolin instead of celite the ACT measurements under aprotinin therapy stay in the same ranges as without application of aprotinin: aprotinin has no detectable influence on kaolin-activated ACT. In our opinion, kaolin should be used as the surface activator for ACT measurements under the conditions of ECC, heparinization, and aprotinin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

In a prospective randomized double-blind study, the activated clotting time (ACT), heparin use, parameters of anticoagulation, and thrombin activation during extracorporeal circulation were studied in 20 patients who underwent aortocoronary bypass operations. The patients were divided into two groups: Group A was given a placebo, while Group B was given aprotinin according to the high-dosage Trasylol scheme. During ACT-controlled heparinization (ACT > 460 s) there was a significant heparin reduction in Group B (22,100 USP-E) in comparison to Group A (35,200 USP-E). Despite this lower quantity of total heparin, the ACT in Group B was significantly extended (Group B = 837 s, Group A = 492 s). The ACT did not correlate thereby with the heparin concentration or the total quantity of heparin in either group. In contrast to the control group, there was no increased thrombin generation in the aprotinin group. The thrombin-antithrombin III complexes (Group A = 143 micrograms/L, Group B = 102 micrograms/L) as well as the specific dimers (Group A = 2755 ng/ml, Group B = 448 ng/ml) were significantly lower under the use of aprotinin. The connection between the ACT, the heparin concentration, and the aprotinin concentration was further investigated in an ex-vivo model. The ACT samples were diluted with the aim of eliminating the influence of aprotinin. Under these conditions it was shown that for heparin concentrations between 2-4 U/ml there was a parallel shift of the ACT/heparinconcentration curve with the addition of aprotinin in a defined concentration range of 200-300 KIU.(ABSTRACT TRUNCATED AT 250 WORDS)

The plasma levels of protein C, AT III, the perioperative administration of fresh frozen plasma (FFP) and AT III concentrate were compared under the use of various drugs in a randomized, prospective double-blind study in 40 patients in whom an aortocoronary bypass operation was carried out. We formed four groups of ten patients: group A served as a control group, group B received a prostacyclin (PGI2) infusion of 10 or 20 ng/kg/min, group C high-dose aprotinin substitution, and group D was treated with a combination of prostacyclin and aprotinin. After an initial short-term rise in the inhibitors protein C and AT III, there was a fall in all groups in the further course of extracorporeal circulation. The initial preoperative values were reached again on the morning of the first postoperative day. This indicates a raised turnover and in association with this a raised rate of elimination of these factors caused by an increased thrombin activation during the extracorporeal circulation which cannot be prevented by the usual heparinization. Whereas prostacyclin had no effect on our results mediated by thrombocytic mechanisms, use of aprotinin led to a significant saving in the requirement for perioperative fresh frozen plasma and AT III substitution therapy. A clinical advantage of prostacyclin and aprotinin combination was not observed. In view of our results (individual analyses were mainly in the normal range), we consider that AT III and fresh frozen plasma should not be substituted routinely during or after extracorporeal circulation.

Mitral valve replacement (MVR) is still associated with a relatively high mortality. To prove the benefits of chordal preservation at mitral valve replacement, we investigated its effects in a series of 65 consecutive MVR patients. Of those patients, in 42 preservation of the mitral subvalvular structures was possible whereas in the other 23 they had to be excised. Both groups showed no differences in age, sex, preoperative NYHA class, and valve pathology. Intra- and postoperative management was similar in both groups. The surgical techniques employed are described and the early postoperative course of both groups are analysed. Clinical, electrocardiographic and echocardiographic investigations, measuring left-atrial and -ventricular diameters, right-ventricular diameters and left-ventricular length, demonstrated that whereas beneficial effects were evident in both groups, the amount of benefits was higher in patients with chordal preservation. Chordal preservation also provided less arrhythmias than chordal resection.