Immunologic assessment of patients treated with bovine fibrin as a hemostatic agent.

Twenty-one cardiothoracic surgical patients have been treated with fibrin as a topical hemostatic/sealing agent, prepared from bovine fibrinogen clotted with bovine thrombin. Serum samples have been collected before treatment with fibrin and postoperatively between 1 and 9 days, 3 and 12 weeks, and 6 and 8 months. The titers of anti-bovine fibrinogen antibodies, measured by ELISA specific for immunoglobulins IgG or IgM, increased to maximal values after about 8 or 6 weeks, respectively. After 8 months, IgG titers were on average 20-fold lower than the mean maximal value, while IgM titers returned to the normal range. IgG was the predominant anti-bovine fibrinogen immunoglobulin as documented by ELISA, affinity chromatography and electrophoresis. Anti-bovine fibrinogen antibodies present in patients reacted readily with bovine fibrinogen, but did not cross-react with human fibrinogen as measured by ELISA or by immunoelectrophoresis. A significant amount of antibodies against bovine thrombin and factor V has been found, many cross-reacting with the human counterparts. No hemorrhagic or thrombotic complications, or clinically significant allergic reactions, occurred in any patient, in spite of antibody presence against some bovine and human coagulation factors. The treatment of patients with bovine fibrin, without induction of immunologic response against human fibrinogen, appeared to be an effective topical hemostatic/sealing measure.

Exposure of the intramyocardial left anterior descending artery.

A systematic approach incorporating several discrete technical maneuvers is described that facilitates localization of the intramyocardial left anterior descending coronary artery. These simple maneuvers reliably afford localization of the initially hidden intramyocardial vessel and are easily incorporated into one's technical armamentarium.

Activated pulmonary vascular neutrophils as early mediators of endotoxin-induced lung inflammation.

Pulmonary vascular sequestration of leukocytes has been reported to increase in some models of lung injury, including that induced by gram-negative bacterial lipopolysaccharide (LPS). Neutrophils recruited to the lung likely participate in LPS-induced lung inflammation and associated injury, but the functional activities of these pulmonary vascular neutrophils have not been directly assessed. In the current study, cells were recovered by pulmonary vascular lavage (PVL) of isolated rat lungs, harvested 2 h after intravenous infusion of LPS (3 mg/kg) or saline in intact rats, at which time LPS-induced neutrophil recruitment to the lung could be appreciated histologically but not by airway lavage. Relative concentrations of leukocytes recovered from the pulmonary vasculature by PVL were compared with those present in circulating blood, normalizing for lavage dilution on the basis of erythrocyte counts. Excess neutrophils, lymphocytes, monocytes, and eosinophils were recovered from the pulmonary vasculature of controls, and LPS infusion increased recovery of neutrophils (most prominently), lymphocytes, and monocytes. Compared with cells recovered from controls, PVL neutrophils from LPS-infused animals were primed for increased zymosan-stimulated superoxide generation, determined by ferricytochrome C reduction, and were more adherent to nylon wool columns. Northern blots of extracted RNA demonstrated that LPS infusion also upregulated interleukin-1 beta (IL-1 beta) mRNA expression in PVL leukocyte samples, but not BAL or circulating blood samples. Ficoll-hypaque separation demonstrated that the LPS-induced IL-1 beta signal in PVL leukocytes was derived primarily from polymorphonuclear rather than mononuclear leukocytes. In conclusion, all circulating leukocyte populations are sequestered in rat lungs, and LPS increases pulmonary vascular sequestration of leukocytes, recruiting most prominently an activated pool of neutrophils that are more adherent, primed for increased oxygen radical production, and expressing increased IL-1 beta message. These findings suggest a more prominent role than previously appreciated for sequestered neutrophils in sepsis-induced lung inflammation.

Reversal of cardiac transplant rejection without massive immunosuppression.

Although cyclosporine has decreased the severity of acute cardiac transplant rejection, most centers have continued to use high-dose intravenous steroids to treat acute rejection. To minimize the morbidity of antirejection therapy, acute rejection episodes in 37 cardiac transplant recipients were treated prospectively with only a boost of oral prednisone. Cyclosporine was continued at the same maintenance dose while oral prednisone was increased to 100 mg/day for 3 days, then rapidly tapered over 1 week to the maintenance dose. Seventy-six of 85 acute rejection episodes (90%) showed histologic resolution of mycocyte necrosis on repeat biopsy. Three acute rejection episodes (3.5%) resolved only after "rescue therapy" with intravenous steroid, and an additional three episodes (3.5%) required the combination of intravenous steroid and rabbit antithymocyte globulin to effect resolution. In addition, three acute rejection episodes (3.5%) resulted in graft loss. This was fatal in two patients and one patient underwent successful retransplantation. Oral steroid therapy alone is adequate therapy for most acute rejection episodes in cyclosporine-treated heart transplant recipients, and low infectious morbidity and mortality has been associated with this antirejection protocol.