Pulmonary administration of activated recombinant factor VII.

Diffuse alveolar haemorrhage (DAH) is a serious pulmonary complication seen in patients with autoimmune disorders and patients treated with chemotherapy or after hematopoietic stem cell transplantation. The clinical management of DAH is complex and the condition has a high mortality rate. During inflammation, tissue factor is expressed in the lung alveoli and therefore pulmonary administration of human recombinant activated factor VIIa (rFVIIa) could be a rational treatment option (4.1). A case report of the patient with an acute, bronchoscopically confirmed DAH from intensive care unit university hospital is described. The patient was treated by the intrapulmonary administration of 50 microg/kg rFVIIa in 50 ml of 0.9% sodium chloride; 25 ml into each of the main bronchi. An excellent response, defined as complete and sustained haemostasis after a single dose of rFVIIa was achieved. The oxygenation capacity, as reflected by the paO2/FiO2 (arterial oxygen pressure/inspiratory fractional oxygen content) ratio, decreased immediately after the bronchoscopy and the local rFVIIa instillation, but the following course of the patient's illness was favourable. Symptomatic therapy--intrapulmonary administration of one dose of rFVIIa was found to have an excellent haemostatic effect in the patient with DAH. The intrapulmonary administration of rFVIIa seemed to have a high benefit-to-risk ratio. These findings warrant further exploration (Ref. 12).

Natriuretic peptides and endothelin-1 in patients undergoing coronary artery bypass grafting.

Off-pump coronary artery bypass grafting (CABG) is an alternative to conventional CABG using cardiopulmonary bypass. Off-pump technique reduces the complications of CABG performed with extracorporeal circulatory assistance (Lancey et al. 2000; Mack et al. 2004a,b). The object of this study was to compare peri- and postoperative time courses of vasoactive peptides - atrial natriuretic poptide (ANP), brain natriuretic poptide (BNP) and endothelin-1 (ET-1) in off-pump versus on-pump CABG. 22 patients, who underwent on-pump (group A, n = 11) or off-pump CABG (group B, n = 11) were studied. The peri- and postoperative time courses of plasma ANP and BNP were similar in both groups. A statistically significant difference between ET-1 plasma level 2 h after surgery in the group A and ET-1 plasma level 2 h after surgery in the group B (2.46 + or - 1.14 pg/ml/Ht versus 0.74 + or - 0.09 pg/ml/Ht, p < 0.0001) was found. Different CABG techniques were not associated with significant changes in peri- and postoperative plasma ANP and BNP. By contrast, plasma ET-1 significantly rose in the group A 2 h after surgery, indicating endothelial damage.

Antioxidant status of patients after on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: It has been convincingly established that cardiopulmonary bypass routinely used in cardiac surgery induces an oxidative stress. The extensive production of reactive oxygen species occurring during cardiopulmonary bypass has a deleterious effect on the endogenous antioxidant defense pool. The recovery of antioxidant enzyme activities as well as other antioxidatively substances is one of the important tasks for the effective defense of patients in the postoperative period. AIM OF THE STUDY: Oxidative stress markers and the antioxidant status and the activities of some antioxidant enzymes were studied in patients during one-week period after cardiac revascularization performed using cardiopulmonary bypass and the results were compared with patients operated by off-pump technique. PATIENTS AND METHODS: Thirty-nine patients undergoing elective surgical revascularization (coronary artery bypass grafting) were divided in two groups: twenty-two patients operated using cardiopulmonary bypass (group A) and a group B of seventeen patients undergoing pump-off surgery. Blood samples were drawn before operation and then in course of the first week after surgery. The following biochemical parameters were estimated: plasma levels of total antioxidant status (TAS) and of thiobarbituric acid reactive substances (TBARS) as well as erythrocyte activities of two antioxidant enzymes--superoxide dismutase (SOD) and glutathione peroxidase (GPx). RESULTS: There was a significantly decreased preoperative and also postoperative levels of TAS associated with a preoperatively increased level of TBARS in group A only. In both groups of patients (especially in group B), markedly decreased activity of SOD was observed. The increase of GPx activity--especially on the third postoperative day--was not significant. CONCLUSIONS: Regardless of the surgical technique, both groups of patients had a markedly decreased antioxidant capacity with a significantly increased production of lipid peroxides especially in patients operated with cardiopulmonary bypass. The decreased antioxidant status was connected with decreased erythrocyte activity of SOD. Therefore, we recommend the regular supply of antioxidant acting substances (antioxidant vitamins and coenzyme Q10) be included in their standard therapeutic strategy especially in the preoperative period. (Tab. 2, Fig. 4, Ref: 22.)

Cytokine levels in patients with a very low left ventricular ejection fraction after open heart surgery.

INTRODUCTION: Cardiopulmonary bypass and cardiac operations are obligatorily connected with systemic inflammatory reaction. Production of proinflammatory cytokines is responsible also for negative effects on the myocardial function. OBJECTIVE OF STUDY: Follow-up of the dynamic changes of proinflammatory and antiinflammatory cytokine levels in patients with left ventricular dysfunction during the first week after cardiac surgery. PATIENTS AND METHODS: A total of nine patients with a very low left ventricular ejection fraction (22.75 +/- 0.65%) who had undergone cardiac surgery (for coronary artery bypass grafting or aortic valve reconstruction) were investigated during the first after week operation. The preoperative and postoperative plasma levels of tumor necrosis factor (TNF), interleukin-8 (IL-8) and interleukin-10 (IL-10) were estimated by means of ELISA technique. RESULTS: With respect to the preoperative levels, on the first postoperative day the levels IL-8 (from 9.36 to 16.65 pg/ml) (p < 0.05) and of IL-10 (from 6.93 to 28.09 pg/ml) (p < 0.02) significantly rose with a stepwise decrease down to the seventh day after surgery. From the third to seventh day an insignificant increase in TNF level was also noted. CONCLUSIONS: The results have shown that open heart surgery in patients with a severe left ventricular dysfunction evoked a systemic inflammatory response demonstrated by early increase in proinflammatory cytokine IL-8 and was accompanied by increased level of antiinflammatory cytokine IL-10. Despite stepwise decrease in IL-8 levels, they did not reach the preoperative levels, not even on the seventh postoperative day. (Tab. 1, Fig. 3, Ref. 21.)