Effect of autotransfusion on fibrinolysis in open heart patients.

Autotransfused blood is often used as an alternative to banked blood. The fibrinolytic consequences of autotransfused blood are undefined. This prospective study was designed to determine the effect of intraoperative autotransfused blood on fibrinolysis and other coagulation parameters. Ten consecutive patients undergoing cardiopulmonary bypass (CPB) for open-heart procedures were studied. All patients received autotransfused blood intraoperatively and tolerated the procedure. Blood samples were taken preoperatively, intraoperatively, and at 6, 12, and 24 hours postoperatively. Coagulation parameters including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin degradation products, and D-dimer levels were measured at each time point. In addition, the quantity of autotransfused blood and additional standard blood products were recorded. Nonparametric repeated measures analyses with post hoc tests adjusted using the Bonferroni correction were used to analyze the data. Mean PT increased from 13.9 +/- 3.0 seconds preoperatively to 15.7 +/- 1.6 seconds intraoperatively, but then gradually declined to 14.5 +/- 1.1 seconds 24 hours postoperatively. A similar temporal pattern was observed for PTT, which reached a peak of 55.7 +/- 33.0 seconds intraoperatively from a preoperative baseline of 44.0 +/- 15.3 seconds. Adjusted post hoc comparisons of fibrinogen levels indicated a statistically significant difference between preoperative and 6 hour postoperative medians, (p < .0083). Fibrin degradation products had a modest and nonsignificant decrease over the 24-hour study period, (from 12.6 +/- 6.7 mcg/mL preoperatively to 9.0 +/- 1.6 mcg/ml 24 hours postoperatively), while D-dimer levels rose from a baseline of 0.54 +/- 0.09 mcg/mL to 0.98 +/- 0.48 mcg/mL 6 hours postoperatively, but declined nearly to baseline by 24 hours postoperatively, (0.62 +/- 0.11 mcg/mL). We conclude that although autotransfused blood may activate the fibrinolytic pathway, its use remains safe and does not require the use of additional banked blood products.

Cyclosporin A augments human platelet sensitivity to aggregating agents by increasing fibrinogen receptor availability.

Clinical use of cyclosporin A (CsA) has been associated with platelet hypersensitivity and an increased incidence of thrombotic and vasoactive events. The purpose of this study was (1) to confirm that CsA enhances platelet sensitivity to the soluble agonists, adenosine diphosphate (ADP) and epinephrine (EPI), and (2) to determine if this enhancement is mediated by alteration in the availability of platelet surface fibrinogen receptors, a final mediator of platelet activation. Mean log dose of ADP required to achieve complete second-wave platelet aggregation in vitro decreased from 1.90 to 1.49 microM (n = 19, paired t test, P less than 0.05) and 2.86 to 2.11 microM (n = 16, P less than 0.05) following a 15-min and 3-hr incubation in the absence (saline) and presence of CsA (1000 ng/ml), respectively. At the threshold dose of ADP, concurrent thromboxane B2 levels at 15 min were 245 +/- 44 ng/ml (n = 12, saline) and 265 +/- 54 ng/ml (n = 9, CsA; P greater than 0.05). At 3 hr respective levels were 333 +/- 57 and 442 +/- 81 ng/ml (P greater than 0.05). Similar results were obtained with EPI. The number of fibrinogen binding sites in response to 50 microM ADP was determined in washed platelets in the absence and presence of CsA by radioligand binding. In 6 of 7 volunteers, CsA increased fibrinogen receptors from 26,635 +/- 4841 to 35,925 +/- 7290 sites/platelet (means +/- SEM; P less than 0.05). No change in receptor affinity was noted. In conclusion, cyclosporine does augment platelet reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of simulated extracorporeal circulation on human leukocyte elastase release, superoxide generation, and procoagulant activity.

Activated leukocytes are thought to contribute to respiratory dysfunction, alterations in microvascular permeability, disseminated intravascular coagulation, and thrombosis, all of which can complicate extracorporeal circulation. The purpose of this work was to determine the effects of extracorporeal circulation on leukocyte functions likely to mediate organ damage. White blood cell counts in the bubble circuits (n = 5) fell to 51% +/- 7% (mean +/- standard error of the mean; p less than 0.05) of initial levels within 2 hours of recirculation. In contrast, counts from both the spiral coil (n = 5) and hollow-fiber (n = 5) groups remained at 91% +/- 12% and 100%, respectively. Plasma levels of human neutrophil elastase rose from 0.28 +/- 0.06 micrograms/ml to 3.14 +/- 0.36 micrograms/ml (p less than 0.05) and 0.20 +/- 0.02 micrograms/ml to 1.61 +/- 0.35 micrograms/ml (p less than 0.05) in bubble and spiral coil circuits, respectively, but from only 0.20 +/- 0.03 micrograms/ml to 0.96 +/- 0.42 micrograms/ml in the hollow-fiber circuit despite 2 hours of recirculation. Consistently, in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine, a chemotactic peptide, cells from spiral coil and bubble circuits released and generated significantly less elastase and superoxide anion, respectively. In contrast, neutrophils from the hollow-fiber circuits demonstrated enhancement of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced elastase release and superoxide generation. Finally, mixed leukocytes from all circuits expressed procoagulant activity reaching statistical significance in bubble circuits. In conclusion, extracorporeal circulation has pronounced effects on neutrophil elastase release, superoxide anion generation, and leukocyte procoagulant activity. Spiral coil and bubble oxygenators cause granule release and, subsequently, reduced sensitivity to soluble agonists. In contrast, hollow-fiber oxygenators "prime" cells, actually enhancing reactivity. Recirculation through all circuits induces leukocyte procoagulant activity that is likely to contribute to surface-induced thromboses and excessive bleeding.

Cardiac ischemia and endothelial function in the isolated rabbit heart.

Truly effective prevention of reperfusion myocardial damage is precluded in part by a lack of understanding of the earliest events which accompany ischemia. The purpose of this study was to assess the coronary endothelial response to two forms of ischemic injury in an isolated crystalloid perfused rabbit heart. Global cardiac ischemia, confirmed by NADH fluorescence photography, was induced either by mechanically reducing coronary flow by 90% (MRCF, N = 11) or by an infusion of N-formyl-methionyl-leucyl-phenylalanine (fMLP, N = 11), a known stimulus for leukotriene synthesis and coronary vasospasm. Compared with control, MRCF resulted in an increase in effluent concentrations of both prostacyclin (152 +/- 22 pg/ml vs 951 +/- 214 pg/ml, P less than 0.05) and plasminogen activator (0.8 +/- .3 IU/ml vs 1.4 +/- 0.5, P less than 0.05) but no detectable increase in effluent thromboxane B2 or leukotriene C4 concentrations. fMLP infusion resulted in an immediate reduction in coronary flow coincident with diffuse myocardial ischemia. In contrast to MRCF, however, fMLP-induced ischemia resulted in a significant but smaller increase in effluent prostacyclin concentration (210 +/- 47 pg/ml vs 606 +/- .55 pg/ml, P = 0.05) and a marked increase in both thromboxane B2 (less than or equal to 33 +/- 4 pg/ml vs 1141 +/- 375 pg/ml, P less than 0.05) and leukotriene C4 (less than 0.25 ng/ml vs 3.3 +/- 1.2 ng/ml, P less than 0.05) concentrations. Additionally, fMLP caused a reduction in effluent plasminogen activator activity (0.5 +/- 0.1 IU/ml vs 0.39 +/- 0.1 IU/ml, N = 4).(ABSTRACT TRUNCATED AT 250 WORDS)