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Biomedical subjects

S L Gaffin

Publications and source records attributed to S L Gaffin.

At least 37 records · Page 2Linked to original sources
PubMed1988

Prophylactic corticosteroid increases survival in experimental heat stroke in primates.

It has been suggested that endotoxins or lipopolysaccharides (LPS), may contribute to heat stroke pathophysiology. In this study, 11 anesthetised monkeys were divided into 2 groups. The steroid group (n = 5) had received a dose of MPSS (30 mg.kg-1, i.v.) before being heat-stressed and the control animals (n = 6) received saline equivolumetrically. The animals were heat-stressed to a rectal temperature of 43.5 degrees C in an environmental temperature of 41 +/- 0.3 degrees C and 100% relative humidity and then allowed to recover at room temperature. Blood samples for LPS and anti-LPS IgG analyses were taken both before treatment and before and after heat-stress. The administration of prophylactic MPSS increased the survival rate significantly from 33% to 100% (p less than 0.05). The plasma LPS level in the steroid group showed very little change after heat-stress, whereas in the non-surviving controls there was a significant increase in plasma LPS level (from 0.089 +/- 0.007 to 0.257 +/- 0.031 ng.ml-1) (p less than 0.005). The control animals that survived showed very little increase in plasma LPS levels, but had about 300% greater plasma Anti-LPS IgG levels. We conclude that pretreatment with MPSS improves the survival rate during heat stroke, possibly by suppressing the rise in plasma LPS concentration.

Animals↗
PubMed1988

Endotoxaemia in racehorses following exertion.

Endotoxins (lipopolysaccharides-LPS) and anti-endotoxin IgG antibodies were measured in racehorses before and after races of 1,000, 2,000 and 2,800 m. Results show that the mean plasma concentration of endotoxin increased significantly (p less than 0.02) while the anti-LPS IgG concentration decreased significantly (p less than 0.005) in all horses following the races. Pre-race and post-race anti-LPS IgG levels in racing-fit racehorses were significantly higher than in untrained horses (p less than 0.05). The possibility therefore exists that training-induced stress leads to leakage of LPS into the systemic circulation which results in self-immunisation against LPS. The effects of plasma LPS and anti-LPS IgG concentrations on performance of racehorses require further studies.

Animals↗
PubMed1987

Radiation induced gram negative bacteremia and endotoxemia in rabbits: modification by anti-lipopolysaccharide hyperimmune equine plasma.

Lethal whole body irradiation damages the gut mucosa and leads to leakage of endotoxin or lipopolysaccharides (LPS) into the systemic circulation. Sixteen rabbits, irradiated with 900 rads 60Co, were randomly divided on day 4 into 2 groups, one of which received an intraperitoneal injection of normal saline (control) and the other (experimental) an equal volume of anti-LPS hyperimmune plasma. The time course of endotoxemia and bacteremia were determined for the duration of the experiment. While rabbits in both groups died within 13 days after irradiation, rabbits given saline died on average 2 days earlier, than rabbits given anti-LPS plasma. Plasma LPS concentrations rose to a small peak on day 2 prior to treatment. Thereafter plasma LPS in rabbits given saline increased forty fold by day 9. In contrast, in rabbits given anti-LPS plasma, LPS concentrations in the plasma remained within pretreatment limits (p 0.01). By day 12 after irradiation, plasma anti-LPS IgG had declined to 5.8% of pretreatment levels in rabbits given saline as compared to 46% in rabbits given anti-LPS plasma (p 0.005). Whilst both groups developed gram-positive bacteremia, rabbits given saline in addition also developed gram-negative bacteremia. No rabbits treated with Anti-LPS showed gram-negative bacteremia. Treatment with Anti-LPS plasma thus significantly protects radiated rabbits from the incidence of gram-negative bacteremia, development of high plasma LPS levels and hence endotoxemia, and prolongs survival to a certain extent.

Animals↗
PubMed1987

A morphological study of the action of equine anti-lipopolysaccharide plasma on gram-negative bacteria.

Three strains of gram-negative bacteria--one each of Escherichia coli, Klebsiella pneumoniae and Enterobacter sp.--were treated with anti-lipopolysaccharide hyperimmune equine plasma (anti-LPS) or non-immune control plasma and examined by scanning electronmicroscopy. Within a few minutes of treatment with anti-LPS, bacteria were agglutinated. Evidence of cell membrane destruction was observed shortly thereafter and total cell disintegration and disruption occurred within 1-2 h. In contrast, non-immune plasma had no effect on cell morphology. This confirms the findings in previous microbiological studies that specific antibodies in anti-LPS bind to lipopolysaccharide (LPS endotoxin), and thereby initiate the destruction of gram-negative bacteria.

Animals↗
PubMed1987

Properties of equine anti-lipopolysaccharide hyperimmune plasma: binding to lipopolysaccharide and bactericidal activity against gram-negative bacteria.

Anti-lipopolysaccharide equine hyperimmune plasma (anti-LPS), which has been used successfully to treat LPS (endotoxin)-mediated disorders, has been further characterised. IgG present in anti-LPS had the highest affinity for LPS prepared from Salmonella typhimurium, S. typhi, S. abortus equi and Shigella flexneri and intermediate affinity for Escherichia coli O55:B5, E. coli O127:B8 and S. enteritidis. Anti-LPS destroyed by means of complement activation a wide range of gram-negative bacteria, including various species and strains of Klebsiella, Enterobacter, E. coli, Sh. flexneri, Providencia, Salmonella and Pseudomonas. Control plasmas or saline had little or no effect. Maximum killing occurred within seconds to minutes. Electronmicroscopy showed that anti-LPS treatment of K. pneumoniae caused extensive cell wall and cytoplastic membrane disruption, followed by the appearance of spheroplasts and cell ghosts. Antibodies were required in 100,000-fold excess to inhibit the limulus amoebocyte lysate reaction with LPS from E. coli. Anti-LPS thus contains IgG that binds to a wide range of LPS, and can destroy a wide range of gram-negative bacteria by means of complement activation.

Animals↗
PubMed1987

Prevention of endotoxaemia by non-absorbable antibiotics in heat stress.

Four anaesthetised monkeys were given oral kanamycin (15 mg 1 kg 12 hourly) over five consecutive days before being heat stressed. Four other anaesthetised monkeys served as controls. The plasma lipopolysaccharide concentration in control primates increased initially from 0.044 (SEM 0.004) ng/ml to 0.062 (0.006) ng/ml as the rectal temperature increased from 37.5 to 39.5 degrees C. A second increase in lipopolysaccharides started at 42 degrees C and reached 0.308 (0.038) ng/ml (p less than 0.01) at 44.5 degrees C. Before heat stress the plasma lipopolysaccharide concentration in the primates who had been pretreated with kanamycin was 0.007 (0.006) ng/ml, and despite heating these animals to 44.5 degrees C no increase in plasma lipopolysaccharide concentrations were seen in this group. The cardiovascular variable during heat stress were more unstable in the control group and began to deteriorate at a lower temperature than in the group receiving antibiotic. These data suggest that the increased plasma lipopolysaccharide concentration during heat stress originates mainly from the gut.

Animals↗
PubMed1987

Anti-pseudomonas activity of anti-lipopolysaccharide hyperimmune equine plasma.

Passive immunotherapy with anti-lipopolysaccharide hyperimmune equine plasma (Anti-LPS) is effective in treating experimental Gram-negative bacterial infections. The bactericidal activity of anti-LPS towards five different Pseudomonas species, including two multiresistant Pseudomonas aeruginosa isolates was tested here, as well as the ability of anti-LPS to inhibit the quantitative chromogenic limulus amoebocyte lysate (LAL) assay. Anti-LPS caused a mean reduction of 84.4 +/- 3.2% (P less than 0.001) in the number of colony forming units (cfu) of all isolates, whereas saline and complement inactivated anti-LPS induced no reduction. Nonimmune control plasma caused a small reduction in % cfu but much less than anti-LPS hyperimmune plasma (13.5% vs 84.4%, P less than 0.001). In order to cause 99% inhibition of the LAL test of 5 ng/ml Pseudomonas aeruginosa LPS, IgG antibodies were required in 10(5)-fold excess. These results suggest that anti-LPS has potential in the therapy and prophylaxis of Gram-negative bacterial infections, especially where LPS is involved in the disease process.

Animals↗
PubMed1987

Antilipopolysaccharide improves survival in primates subjected to heat stroke.

Recent investigations have suggested that endotoxins or lipopolysaccharides (LPS) may play a role in heat stroke pathophysiology. In this study we wish to investigate whether prophylactic administration of anti-LPS hyperimmune plasma improves survival of experimental heat stroke in primates. Eleven monkeys were anesthetised and heat-stressed to a rectal temperature of 43.5 degrees C (group A) and then allowed to recover at room temperature. Five had received a prophylactic i.v. dose of equine anti-LPS (experimental group), while the other six (control group) received an equivalent i.v. dose of nonimmune equine plasma. All the experimental monkeys survived, while only one out of the six controls survived (chi 2 = 4.65, p less than 0.025). All the control animals that succumbed had significantly elevated plasma LPS levels (p less than 0.05) as compared to the experimental group and the single surviving control. The latter showed very little or no change in plasma LPS levels. A further eight monkeys (group B) were heat-stressed to a rectal temperature of 43.8 degrees C. Of these eight, four had received a prophylactic i.v. dose of equine anti-LPS plasma. Although all eight animals died, the four which were pretreated with anti-LPS plasma had a significantly longer survival time (427.5 +/- 61.39 min) than the untreated group (81.25 +/- 33.94 min) (p less than 0.05). Furthermore, the plasma LPS levels in the treated monkeys remained unchanged whereas in the untreated group, a significantly elevated plasma LPS level was noticed (p less than 0.005). We conclude that LPS may have a role in heat stroke pathophysiology and that prophylactic treatment with anti-LPS antibodies would seem to offer protection against the effects of heat stress.

Animals↗
PubMed1987

Endotoxemia associated with cardiopulmonary bypass.

Endotoxin (lipopolysaccharide) concentrations were determined in the systemic venous blood in nine patients undergoing cardiopulmonary bypass. Lipopolysaccharide concentrations were low and stable until institution of cardiopulmonary bypass (preanesthetic concentration 0.128 +/- 0.032 ng/ml [mean +/- standard error of the mean]; prebypass level 0.136 +/- 0.03 ng/ml). After the start of bypass, the plasma concentration of lipopolysaccharide rose progressively with time to a mean value of 0.347 +/- 0.044 ng/ml (p less than 0.01), which was 0.227 ng/ml above baseline. Upon release of the aortic clamp, an additional rise in lipopolysaccharide concentration occurred after to 5 to 15 minutes to a mean value of 0.428 +/- 0.06 ng/ml (p less than 0.001) above baseline. The concentration then decayed to the baseline level 45 to 75 minutes after termination of bypass. The peak lipopolysaccharide concentration above the baseline positively correlated with both the length of bypass (r = 0.839, p less than 0.005) and the duration of aortic cross-clamping (y = 0.0030X + 0.173 r = 0.85, p less than 0.001) when flow was nonpulsatile. The peak occurred during the period of myocardial and pulmonary reperfusion. This rise in endotoxin concentration may be one of the factors responsible for the prolonged postoperative recovery seen in some patients.

Adult↗
PubMed1987

Time course of endotoxemia and cardiovascular changes in heat-stressed primates.

Heat stress causes a marked reduction in splanchnic blood flow in order to compensate for the increased flow to the skin. Splanchnic ischemia causes a leakage of endotoxins from the gut lumen into the portal circulation and, especially in the presence of a compromised reticuloendothelial system, may cause severe systemic endotoxemia. Since many of the pathological features of heat stroke are similar to the shock state produced by LPS, we examined whether heat-stress causes endotoxemia. Five anesthetized monkeys were subjected to an environmental temperature of 41 degrees +/- 0.3 degrees C and relative humidity of 100%, until death. Rectal temperatures were recorded continuously, blood pressure and ECG were recorded at 5-min intervals, and arterial blood samples were taken at 15-30 min intervals. A decline in mean arterial pressure and rapid rise in heart rate occurred at about 42 degrees C. Plasma LPS remained at 0.071 +/- 0.006 ng.ml-1 until a rectal temperature of +/- 42 degrees C. Thereafter, it increased slowly until beyond 43 degrees C when it rose rapidly to 0.347 +/- 0.024 prior to death. Endotoxemia may have been a contributing factor in the pathogenesis of heat stroke. If so, then the use of anti-LPS antibodies may be expected to be beneficial.

Animals↗
PubMed1986

Effect of corticosteroid prophylaxis on lipopolysaccharide levels associated with intestinal ischemia in cats.

Ischemia of the intestines damages the permeability of the intestinal wall, allowing lipopolysaccharide (LPS) (endotoxin) to leak from the gut lumen into the blood circulation, causing shock and death. We measured LPS levels associated with corticosteroid treatment vs. no treatment in cats whose superior mesenteric artery had been occluded for 60 min. In untreated cats, the preocclusion mean plasma LPS concentration remained stable at 0.069 +/- 0.015 ng/ml. Toward the end of the occlusion period, mean plasma LPS rose to 0.239 +/- 0.032 ng/ml (p less than .01). Release of the clamp and reperfusion with oxygenated blood was followed within 20 min by a large rise in plasma LPS concentration to 0.825 +/- 0.11 ng/ml (p less than .01), which had returned to preocclusion levels about 80 min later. Methylprednisolone (30 mg/kg) was infused into a second group of cats 1.5 h before SMA occlusion. In these cats there was a complete inhibition of the LPS rise both during and after occlusion. These data suggest that the reported beneficial effect of corticosteroids in the treatment of septic shock may be mediated, in part, by reducing LPS leakage from the gut.

Animals↗
PubMed1986

Superior mesenteric artery occlusion shock in cats: modification of the endotoxemia by antilipopolysaccharide antibodies (anti-LPS).

We measured the time course of elevated plasma LPS concentration caused by a temporary intestinal ischemia using the superior mesenteric artery (SMA) occlusion shock model in anesthetized cats. The systemic plasma LPS increased from 0.075 +/- 0.006 ng/cc to 0.219 +/- 0.026 ng/cc (P less than 0.001) during the occlusion period. On release of the clamp, the plasma LPS concentration rose rapidly to 0.716 +/- 0.122 ng/cc (P less than 0.001) within 20 min. Thereafter, it declined to reach baseline levels after 100-120 min reperfusion. A total of 21 animals received IV 1.0 cc/kg antilipopolysaccharide hyperimmune equine plasma (anti-LPS) either 1.5 hr before the occlusion or at 0, 10, or 20 min after release of the occlusion. Prophylactic anti-LPS prevented any rise in plasma LPS both during and after release of the occlusion. The administration of anti-LPS during the reperfusion period completely reversed the endotoxemia caused by intestinal ischemia within 5-10 min. This rapidity of response to anti-LPS may be important in the previously reported therapeutic benefit of anti-LPS.

Animals↗
PubMed1986

Hypoxia-induced endotoxemia in primates: role of reticuloendothelial system function and anti-lipopolysaccharide plasma.

Acute hypoxia is known to cause a marked reduction in intestinal and peripheral blood flow, in favor of blood flow to the brain and heart. Complete occlusion of the intestinal circulation is known to damage the gut wall, allowing potentially lethal endotoxins present within the intestines to escape into the circulation. We examined here whether the breathing of a hypoxic gas mixture could lead to sufficient damage of the intestinal wall to cause endotoxemia. Six anesthetized monkeys breathed air for 1 hr, then an hypoxic mixture (FIO2 = 0.13) containing N2O for 1 h and, finally, 100% O2. Plasma endotoxin concentrations were determined by two methods. After approximately 40 min of hypoxia, the plasma endotoxin level rose significantly from 0.39 to 1.60 ng X ml-1 (p less than 0.001) and then subsided to near control levels. Control monkeys breathing air only or 70% N2O in oxygen (FIO2 = 0.3) for 3 h showed no such elevation in plasma endotoxin concentration. We conclude that hypoxia leads to a temporary endotoxemia in primates. Reticuloendothelial system depression by whole body X-irradiation (200 rads) increased both the magnitude and duration of the hypoxia-induced endotoxemia. Prior administration of equine anti-lipopolysaccharide (anti-LPS) hyperimmune plasma greatly reduced the magnitude of the induced endotoxemia. Since endotoxemia may be lethal, the use of anti-LPS as possible prophylaxis should be considered in persons breathing artificial atmospheres or where acute hypoxia may be a danger.

Animals↗
PubMed1985

Prophylaxis of superior mesenteric artery occlusion shock in rabbits by antilipopolysaccharide (anti-LPS) antibodies.

Occlusion of the superior mesenteric artery (SMA) is known to produce lethal shock in experimental animals, probably due to the presence of endotoxins released from the gut. A 60-min SMA occlusion shock was produced in 20 rabbits. Eight were pretreated with equine antilipopolysaccharide (anti-LPS) hyperimmune plasma, and seven survived (87.5%) for 10 days. However, only 2 out of 12 (16.6% chi 2 = 9.73, P less than 0.001) control rabbits survived. These results support the concept that endotoxins are involved in the etiology of SMA occlusion shock and that anti-LPS therapy may therefore be useful in the prevention of endotoxic shock.

Animals↗