The role of fibrinogen degradation products in the pathogenesis of the respiratory distress syndrome

Pulmonary dysfunction in awake rabbits was induced by intravenous infusion of a highly purified human fibrin split product (fragment D). The dose of infused fragment D was chosen to achieve observed plasma concentrations of fibrin split products in hospitalized patients with severe burns or trauma (about 100mug of FSP/ml of blood). Four hours after infusion, the animals displayed a clinical and pathological pattern which closely resembled post-traumatic acute respiratory distress syndrome, including hypoxia, hypocarbia, thrombocytopenia, increased pulmonary capillary permeability to albumin, interstitial edema, hypertrophy of alveolar lining cells, and intra-alveolar hemorrhage. In vivo production of fibrin split products by infusion of thrombin with induction of secondary fibrinolysis produced similar pulmonary changes, although intravascular clots and platelet aggregates also were prominent. Infusion of human fibrinogen and human albumin at identical doses failed to induce pulmonary dysfuction. The results suggest that fibrin split products (fragment D) alone are toxic to the respiratory system and may contribute to the development of acute respiratory distress syndrome in severely traumatized or burned patients.     

Effect of irradiation on the degradation of rat thymocyte chromatin

Genome instability of adaptive nature is formed under the experimental influence on a cell. Under critical conditions, strategy of organism is to damage the cells that cannot be restored and controlled by including the program of apoptosis. The ordered internucleosomal DNA degradation is considered to be one of the proof attributes of immunocompetent cell apoptosis. We investigated the effects of various doses of irradiation on the thymocytes chromatine fragmentation in 1,2,3 hours after a single X-ray exposure or after chronic influence in conditions of Chernobyl research base. By the means of electrophoresis in agarose and judging by polydeoxyribonucleotides accumulation we observed the "ladder pattern" of degradation in 3 hr after single 1 Gr irradiation (the smallest dose displaying the effect). We suppose that the influence of both chronic low-intensity irradiation taking place in Chernobyl and single X-ray exposure result in intensifying of DNA fragmentation in the cells of immunocompetent organs.     

The effects of treatment with lipopolysaccharide on responsiveness of rat blood vessels

Effects of treatment with lipopolysaccharide (LPS) both in vivo (intraperitoneal administration of 20 mg.kg-1 LPS for 6 hours) and in vitro (incubation with 1 microgram.kg-1 LPS for 6 hours) on the responsiveness of the rat thoracic aorta, carotid, renal, femoral, mesenteric, pulmonary arteries, and the femoral and mesenteric veins were examined. Intraperitoneal administration of LPS did not change the blood pressure of rats, but increased the heart rate significantly. The same amplitude of relaxation was produced by L-arginine in the aortic strips treated by LPS in vivo and in vitro, and the responses were inhibited by NG-nitro-L-arginine (L-NOARG). The contractile responses to phenylephrine in the aortic strips were reduced by LPS-treatment in vivo or in vitro, but the extent of inhibition was greater in vivo than in vitro. Further, the attenuation of contractile responses to phenylephrine was completely reversed by L-NOARG in the strips treated with LPS in vitro, whereas the reversal by L-NOARG was incomplete in the strips treated with LPS in vivo. Different amplitudes of relaxations were also produced by L-arginine or SNP in the blood vessels treated by LPS in vivo or in vitro. However, the tail artery treated with LPS in vivo or in vitro did not relax in response to L-arginine but did produce a relaxation to SNP. These results suggest that the hyporesponsiveness of rat blood vessels after treatment with LPS in vivo or in vitro may be related to an enhanced NO production in the smooth muscle cells and that there is a possible heterogeneity of regional induction or activation of L-arginine/NO pathway by LPS in rat blood vessels.     

Effect of amifostine (Ethyol) on the development of extraembryonic blood vessels in chick embryos

An unrecognised right aortic arch (RAA) found at thoracotomy may complicate the repair of oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF). This paper analyses the patient characteristics, peri-operative management, and outcome of 16 infants with a RAA, and proposes management guidelines. Between 1948 and 1996, 709 patients with OA/TOF were admitted to the Royal Children's Hospital, of whom 13 had a RAA. Three additional cases from two other paediatric surgical units were included. All 16 case records were reviewed retrospectively. The overall incidence of RAA in OA was 1.8%. Neither a chest radiograph in 16, nor antenatal ultrasonography in 7 detected a RAA. Post-natal echocardiography (ECHG) detected a RAA in only 1 of 7 infants examined; that patient underwent repair of the OA through a left (L) thoracotomy. The other 15 infants underwent initial right (R) thoracotomy. Six of these had a complete repair from the R side and 5 had division of the fistula only; 2 of these 5 had initial division of the fistula, and the OA was repaired through a repeat R thoracotomy 4 and 7 weeks later. In the remaining 4 infants where the fistula could not be located at the initial R thoracotomy, complete repair proved possible through the L chest. Three of these infants underwent an immediate L thoracotomy; the 4th had a delayed L thoracotomy 1 week later. There were 6 deaths: these occurred early in the study and were related to severe prematurity, congenital heart disease (CHD), and post-operative respiratory complications. CHD was identified in 11 of 16 infants (71%). Routine pre-operative ECHG is unreliable in determining the laterality of the aortic arch. Should a RAA be encountered during a R thoracotomy for OA, it is often possible to divide the fistula and repair the OA from that side, but where repair looks potentially difficult it is wise to proceed to an immediate L thoracotomy.     

Effect of starvation on organ blood flow in the senescent rat

Since the first true hernioplasty performed by Edoardo Bassini more than 100 years ago (1884) all surgical reconstruction techniques have shared a common defect i.e. tension on suture line. This is the first etiologic factor of recurrent hernia. On the contrary by the use of modern prosthetic materials (mesh and plug) it is now possible to marriage all hernia repairs without distorting normal body anatomy and avoid undesirable tensions. The technique proposed is simple, efficient, characterized by a rapid performing procedure, giving way to an excellent clinical outcome: postoperative pain relief permitting the patient to resume in a short time his normal physical activities. In this paper the authors present their experience in wall defects reconstruction by means of outpatient surgery and in general anesthesia in the period spanning from 1994 to 1996. Five different types of hernia mesh in hernioplasty procedures were evaluated and used.     

Delayed and prolonged vascular leakage in inflammation: the effects of dehydromonocrotaline on blood vessels in the rat cremaster

Local application of dehydromonocrotaline to the rat cremaster produces a delayed prolonged increase in vascular permeability with a time course similar to that of the pulmonary oedema seen after intravenous injection of the same substance. Study of the injured area by the carbon labelling technique and by electron microscopy shows that the increased permeability involves both capillaries and venules of all sizes within the region exposed to dehydromonocrotaline. The vascular leakage appears to be due to a direct effect on the endothelium of small blood vessels. Carbon deposition in labelled capillaries and venules is predominantly intramural and indicative of increased vascular permeability. Accumulation of carbon within the lumen of capillaries is uncommon, and accounts for only a small fraction of total capillary labelling. The findings indicate that capillaries are a major source of inflammatory exudate in this type of injury and suggest that the importance of leakage from capillaries has been underestimated in other types of delayed prolonged increase in vascular permeability.     

Effect of nitroprusside on smooth muscle and adrenergic nerve terminals in isolated blood vessels

Experiments were designed to assess the mode of action of nitroprusside on isolated blood vessels and its relative potency on venous and arterial smooth muscle. Strips from dog blood vessels were mounted in an organ bath for isometric tension recording. Sodium nitroprusside (10(-5) M) depressed the contraction of saphenous vein strips caused by electric stimulation, tyramine, K+, Ba++, norepinephrine and acetylcholine. The depression of the norepinephrine-induced contractions also occurred in a Ca++- free medium and when Ca++ influx was inhibited by verapamil. Nitroprusside reduced the frequency of the spontaneous contractions of strips of portal-mesenteric veins. It depressed the contraction caused by norepinephrine in tibial artery strips more than in saphenous vein strips. Saphenous vein strips were incubated with (3H)norepinephrine and mounted for superfusion and isometric tension recording. Sodium nitroprusside (10(-5) M) had no effect on the basal efflux of 3H compounds. During electric stimulation, it did not change the output of (3H)norepinephrine but increased the outflow of deaminated and O-methylated metabolites. Thus sodium nitroprusside 1) has a direct effect on the smooth muscle cells which is independent of Ca++ influx, 2) depresses contractions of different types of vascular smooth muscle and 3) does not inhibit the release of norepinephrine from the nerve endings.     

Determination of tranexamic acid (AMCA) and fibrin/fibrinogen degradation products in cerebrospinal fluid after aneurysmal subarachnoid haemorrhage

Six patients with recently ruptured intracranial aneurysms were treated preoperatively with tranexamic acid (AMCA). Two patients received 6 g daily in i.v. infusion, two had 6 g daily by i.v. injection, and two patients were given AMCA 9 g daily by mouth during the first week after bleeding. Serial assays of AMCA and fibrin/fibrinogen degradation products (FDP) in cerebrospinal fluid (CSF) were performed during 6--13 days after the initial subarachnoid haemorrhage (SAH). Judged from the decline in CSF-FDP, an assumed therapeutic level of greater than or equal to 1 mg/l of AMCA in CSF was reached within 24--36 hours after the first dose when the drug was administered intravenously and within 48 hours when the drug was given orally.     

The dimensional characteristics of smooth muscle in rat blood vessels. A computer-assisted analysis

This investigation was undertaken to provide precise information about the dimensional characteristics of vascular smooth muscle cells as related to their paracellular matrix. The representative types of vessels were fixed at the mean blood pressures of adult male Wistar rats. The shapes, positions of the nucleus, linear dimensions, volumes, and orientation within the vessel wall were determined by a computer-assisted reconstruction of the cells from serial sections. Wall-to-lumen and cellular-to-paracellular ratios also were assessed. The smooth muscle cells were elongate, but whereas some are spindle shaped, most are not, and may be shaped like flattened triangles, paddles, boomerangs, or hourglasses, and in addition, any one of these shapes may be forked. The nucleus tended to be in the largest part of the cell, wherever that region occurred. Thus, the majority of the nuclei (61%) were not centrally located, but overlapped the middle and end thirds of the elongate cells. Of the three arteries investigated, the muscular type tail artery had cells with volumes two to three times larger (P less than 0.01) than cells in a musculoelastic (femoral) or elastic (mesenteric) artery, and six times larger (P less than 0.01) than those of the portal vein. Therefore, the smooth muscle cells of the vein were significantly smaller than those in any artery (P less than 0.01). The smooth muscle cells were aligned at a steeper angle in the vessel wall (15 degrees +/- 2 degrees) of the muscular artery than in those with more elastic tissue (9 degrees +/- 2 degrees), with a higher percentage of circumferential cells in the latter. The wall-to-lumen ratios decreased as the relative amount of paracellular matrix, particularly elastic tissue, increased in the three arteries. Therefore, irregularly shaped cells, with the nucleus in the thickest region, and having characteristic cell volumes depending on the type of vessel, form the vascular smooth muscle tissue. These factors are relevant if stereology, or measuring from two dimensions, is used to estimate size characteristics in cardiovascular disease such as hypertension. In addition, the optimum angle at which vascular strips are cut would vary, for example, when used in testing pharmacological agents.     

Effect of coronary thrombus age on fibrinogen uptake

A study was carried out to define the time limits during which an experimental coronary thrombus remains capable of incorporating fibrinogen. 131I-fibrinogen was given to intact anesthetized dogs at different time intervals, up to 67 hours, following the formation of a coronary thrombus by catheter-electrode. Radioactivity of the recovered thrombi as a whole and segmentally divided, was determined following variable time intervals of exposure to circulating fibrinogen and was expressed as thrombus/blood ratio. The results indicate that coronary thrombi formed in a normal coronary vessel remain capable of incorporating fibrinogen for at least eighteen hours, with no significant differences in the segmental distribution of radioactivity. These findings do not support the view that the recovery of isotopic fibrinogen, which was given after the onset of coronary symptoms, in thrombi from patients with myocardial infarction establishes that the thrombus was initiated after the ischemic process.