Fibronectin and the critically ill patient: current status.

In summary, deficiency of plasma fibronectin has now been documented in a variety of clinical entities. Persistently low fibronectin may have prognostic value, and in certain patients may provide a clue to occult sepsis and potential organ failure. The clinical benefit of infusion of fibronectin-rich cryoprecipitate or purified human plasma fibronectin has yet to be determined in well-controlled randomized clinical trials. However, if such results become available then infusion of plasma fibronectin may provide a valuable therapeutic modality in the care of the critically-ill patient.

Influence of radiotherapy on microvascular reconstruction in the head and neck region.

Over a 5-year period at the University of California San Francisco, 42 patients who required microvascular reconstruction for abnormalities in the head and neck area were identified. Twenty-four patients (Group I) underwent reconstruction for a variety of neoplastic and non-neoplastic conditions and did not receive radiotherapy. Eighteen patients (Group II) had undergone previous radiotherapy averaging 6,090 rads. The mean ages for Group I and II patients were 40.7 and 55.5 years, respectively. In Group I, 13 muscle, 7 fasciocutaneous, 4 osteocutaneous, and 2 jejunal transfers were performed. In Group II, 11 muscle, 5 fasciocutaneous, 3 osteocutaneous, and 2 jejunal transfers were performed. Flap survival at 3 months was 88% in Group I and 95% in Group II. Wound complication rates were similar in both groups (15% Group I, 19% Group II), as was donor site morbidity (15% Group I, 29% Group II). Operative times (10.9 hours Group I, 10.6 hours Group II) and median postoperative hospitalization (14 days Group I, 16 days Group II) were comparable as well. Four of the five patients in whom the flap procedures failed were subsequently treated by a second microvascular reconstruction. Previous irradiation of the recipient bed did not appear to affect the success of subsequent microvascular reconstruction or the difficulty of such reconstruction as judged by operative time.

Factor XIII as a modulator of plasma fibronectin alterations during experimental bacteremia.

Fibronectin is found in plasma as well as in association with connective tissue and cell surfaces. Depletion of plasma fibronectin is often observed in septic trauma and burned patients, while experimental rats often manifest hyperfibronectinemia with sepsis. Since Factor XIII may influence the rate of clearance and deposition of plasma fibronectin into tissues, we evaluated the temporal changes in plasma fibronectin and plasma Factor XIII following bacteremia and RE blockade in rats in an attempt to understand the mechanism leading to elevation of fibronectin levels in bacteremic rats, which is distinct from that observed with RE blockade. Clearance of exogenously administered fibronectin after bacteremia was also determined. Rats received either saline, Pseudomonas aeruginosa (1 X 10(9) organisms), gelatinized RE test lipid emulsion (50 mg/100 gm B.W.), or emulsion followed by Pseudomonas. Plasma fibronectin and Factor XIII were determined at 0, 2, 24, and 48 hours post-blockade or bacteremia. At 24 and 48 hr following bacteremia alone or bacteremia after RE blockade, there was a significant elevation (p less than 0.05) of plasma fibronectin and a concomitant decrease (p less than 0.05) of plasma factor XIII activity. Extractable tissue fibronectin from liver and spleen was also increased at 24 and 48 hours following R.E. blockade plus bacteremia. In addition, the plasma clearance of human fibronectin was significantly prolonged (p less than 0.05) following bacterial challenge. Infusion of activated Factor XIII (20 units/rat) during a period of hyperfibronectinemia (908.0 +/- 55.1 micrograms/ml) resulted in a significant (p less than 0.05) decrease in plasma fibronectin (548.5 +/- 49.9 micrograms/ml) within 30 min. Thus Factor XIII deficiency in rats with bacteremia may contribute to the elevation in plasma fibronectin by altering kinetics associated with the clearance of fibronectin from the blood.

Comparative effect of circulating bacterial or nonbacterial particulates on plasma fibronectin: relationship to lung deposition of blood-borne foreign particles.

Reticuloendothelial (RE) phagocytic function and plasma fibronectin are altered early after trauma and during septic shock. Since fibronectin-coated particles will tend to aggregate if not efficiently phagocytized, we hypothesized that elevated fibronectin levels during hepatic and/or splenic RE depression could potentiate the lung deposition of blood-borne foreign microparticles. To evaluate this concept, we measured plasma fibronectin, hepatic RE function, and tissue deposition of blood-borne colloids in rats after they were injected with nonbacterial and bacterial particulates. Rats were injected intravenously with gelatin-coated colloids (50 mg/100 gm) to simulate blood-borne collagenous tissue debris after trauma, or with live Pseudomonas aeruginosa (1 X 10(9)/rat) to simulate bacterial entrance into the blood with sepsis, or with both to simulate sepsis after trauma. Phagocytic function was evaluated by liver and spleen uptake of gelatinized 125I RE test emulsion. Fibronectin was quantified by electroimmunoassay. There was an acute 60-80% decrease in plasma fibronectin 2 hr following either colloid or colloid coupled with bacterial infusion. Bacterial infusion alone elicited only a mild 20% decrease in fibronectin by 2 hr. By 24 hr, restoration of fibronectin levels was observed in all groups with hyperfibronectinemia observed in animals challenged with Pseudomonas. Following colloid alone, liver uptake of the RE test particle was acutely depressed at 2 hr in association with an acute depletion of fibronectin, but at 24 hr the RE depression persisted even with normalization of fibronectin. In contrast, with only bacteremia, the rebound elevation of fibronectin was associated with increased hepatic RE function. In rats given both colloid and Pseudomonas, the hyperfibronectinemia (60-100% above controls) at 24 hr coexisted with inadequate liver phagocytic uptake ability. This resulted in a significant 20-fold (P less than 0.05) increment in lung localization of the blood-borne test microparticles. Thus, hyperfibronectinemia without a parallel increase in liver phagocytic ingestive ability may actually enhance lung localization of blood-borne microparticles, which have a high affinity for fibronectin.

Clearance and tissue distribution of fibronectin in septic rats: relationship to synthetic rate.

Fibronectin is a glycoprotein found in a soluble form in plasma and in an insoluble form in many tissues. We evaluated the influence of postoperative intraperitoneal sepsis on the clearance, tissue distribution, and synthesis of plasma fibronectin in rats (300-400 g). Experimental sepsis was induced by cecal ligation following laparotomy, whereas control animals underwent laparotomy (5 cm) alone. At 24 and 48 h after laparotomy, plasma fibronectin levels were normal. After laparotomy plus cecal ligation, plasma fibronectin increased by 47% at 24 h and remained elevated (52% above 0 time) at 48 h. At 24 h postsurgery the disappearance and tissue distribution of 75Se-plasma fibronectin and 75Se-plasma albumin was evaluated. Tissue distribution was quantified at 2 and 24 h after intravenous injection of both tracer proteins in separate groups. Both fibronectin and albumin demonstrated an initial distribution between vascular and extravascular sites and then a progressive decrease in plasma. In control (laparotomy) rats the half-life (t1/2) for plasma clearance of 75Se-plasma fibronectin was 25.33 +/- 2.53 h compared with 13.21 +/- 0.78 h in the septic rats. Septic rats manifested decreased sequestration of 75Se-fibronectin at the area of surgical incision (laparotomy), increased sequestration at the focus of intraperitoneal infection, and increased uptake in the nonviable portion of the cecum. The synthetic rate for plasma fibronectin in laparotomized control rats was 3.03 +/- 0.29 mg X 100 g-1 X 24 h-1, whereas after laparotomy plus cecal ligation the synthetic rate increased to 4.58 +/- 0.35 mg X 100 g-1 X 24 h-1. In contrast the synthetic rate for albumin decreased from 84.70 +/- 1.66 mg X 100 g-1 X 24 h-1 in controls to 52.38 +/- 1.77 mg X 100 g-1 X 24 h-1 in the septic animals. Thus intraperitoneal sepsis in the rat will enhance the vascular clearance, alter the distribution, and increase the synthetic rate for plasma fibronectin.