Biomedical subjects

T Saldeen

Publications and source records attributed to T Saldeen.

At least 37 records · Page 2Linked to original sources

PubMed1999

Inhibition of arterial thrombus formation by ApoA1 Milano.

The mutant form of human apoA1, known as apoA1 Milano, is formed as a result of arginine 173 to cysteine substitution and inhibits experimental atherosclerosis in cholesterol-fed animals. This study was designed to determine if apoA1 Milano would modify arterial thrombogenesis. Sprague Dawley rats were intravenously administered the carrier alone (n=8) or apoA1 Milano (20 mg. kg-1. d-1 for 4 to 10 days, n=17). The abdominal cavity was opened, and the abdominal aorta was isolated. Whatman paper impregnated with 35% FeCl3 was wrapped around the surface of the aorta, and aortic flow was recorded continuously. In carrier-treated rats, an occlusive platelet-fibrin-rich thrombus was formed in 21.2+/-4.1 (mean+/-SD) minutes. Treatment of rats with apoA1 Milano markedly delayed time to thrombus formation (38.8+/-11.9 versus 21.2+/-4.1 minutes, P<0. 01), inhibited platelet aggregation (25+/-7% versus 50+/-11%, P<0. 01), and reduced weight of the thrombus (18.5+/-1.8 versus 23.7+/-2. 3 mg/cm, P<0.01). Total cholesterol and HDL levels remained similar in both groups of rats, but plasma apoA1 Milano levels were elevated in apoA1 Milano-treated rats. In in vitro studies, incubation of platelets with apoA1 Milano reduced ADP-induced platelet aggregation by about 50%, but apoA1 Milano had no direct effect on vasoreactivity. This study provides further evidence for critical role of platelets in thrombosis. Use of apoA1 Milano offers a novel approach to inhibit arterial thrombosis.

Animals↗

PubMed1999

Relative Effects of alpha- and gamma-Tocopherol on Low-Density Lipoprotein Oxidation and Superoxide Dismutase and Nitric Oxide Synthase Activity and Protein Expression in Rats.

BACKGROUND: Increasing evidence suggests that vitamin E prevents the progression of atherosclerosis by inhibiting platelet aggregation, monocyte adhesion, and improving plaque stability and vasomotor function. Recently, controversy has arisen as to the relative effects of alpha- and gamma-tocopherol in modulating some mediators of atherosclerosis. METHODS AND RESULTS: We examined the effects of alpha- and gamma-tocopherol on constitutive nitric oxide synthase (cNOS) and superoxide dismutase (SOD) activity and protein expression in rats. Sprague-Dawley rats were fed regular chow or chow mixed with alpha- or gamma-tocopherol (100 mg/kg/day) for 7 to 10 days. Plasma alpha- and gamma-tocopherol levels, low-density lipoprotein (LDL) oxidation, and cNOS and SOD activity and protein expression were measured. Plasma alpha-tocopherol levels were significantly increased (eP <.01 vs control), but gamma-tocopherol levels fell (P <.01 vs control) in rats fed alpha-tocopherol. Plasma gamma-tocopherol levels were increased (P <.01 vs control), and alpha-tocopherol levels did not change in rats fed gamma-tocopherol. Both alpha- and gamma-tocopherol feeding decreased the rate of LDL oxidation induced by phorbol 12-myristate 13-acetate (PMA)-stimulated leukocytes (P <.01 vs control). Both alpha- and gamma-tocopherol increased SOD activity in plasma and arterial tissues as well as Mn SOD and Cu/Zn SOD protein expression in arterial tissues (all P <.01 vs control). gamma-Tocopherol was more potent than alpha-tocopherol in all these effects (P <.05). Both a- and gamma-tocopherol increased NO generation and cNOS activity (all P <.05 vs control). However, only gamma-tocopherol increased cNOS protein expression. CONCLUSIONS: These observations indicate that whereas both alpha- and gamma-tocopherol exert important effects on determinants of oxidationand vasomotor function, effects of dietary gamma-tocopherol supplementation in vivo are less pronounced than those of gamma-tocopherol supplementation.

Journal Article↗

PubMed1999

Suicides may be overreported and accidents underreported among fatalities due to dextropropoxyphene.

Among prescribed drugs in Sweden dextropropoxyphene (DXP) is the medical compound most frequently responsible for self-inflicted fatal poisonings. To analyze the process leading to the classification of the manner of death in cases of fatalities where DXP caused or contributed to death, a set of explicit and implicit operational criteria was applied retrospectively to fatal DXP poisonings among autopsy cases performed at one department of forensic medicine in Sweden during the six-year period from 1992 to 1997. DXP fatality was found in 113 (2.6%) of the total 4306 autopsy cases. Suicide was recorded in 84 (74%) of these cases, and an undetermined manner of death in 24 (21%). Explicit unambiguous expressions of the intent of the decedent were found in 29 (26%) of the 109 analyzed cases. (In four cases no analysis could be performed). In 46 cases only implicit and no explicit criteria were found. The total number of implicit criteria in individual cases without explicit criteria never exceeded three and in 34 cases no criteria of any type were documented. It is concluded that the classification of the manner of death at DXP fatalities was often based on very limited grounds when the operational criteria were used as a standard for comparison. Information from relatives, friends and others concerning the decedent was rarely accessible. The shortage of information probably led to deficiencies in the death statistics concerning DXP fatalities. Considerable underreporting of accidents and probable overreporting of suicides were found. Failure to report DXP deaths as accidents may delay discovery of the high toxicity of this drug. This might be one of the reasons why the DXP fatality rate is still constantly high in Sweden, while both Denmark and Norway have managed to decrease their DXP death rates by vast restrictions, based on alarming reports of accidental DXP fatalities. In order to guarantee valid death statistics concerning self-inflicted poisoning, the information base leading to classification of the manner of death has to be enlarged. This requires implementation of new routines, including interviews of relatives, acquaintances and significant others to get the information needed to assess the decedent's intention to die. Operational criteria may facilitate the difficult classification process by providing a structured standard, and the set of explicit and implicit criteria applied in this study is recommended.

Accidents↗

PubMed1998

The prevalence of dextropropoxyphene in autopsy blood samples.

The prevalence of dextroproxyphene (DXP) in the total medico-legal autopsy material in Sweden during 1992 to 1996 was examined. Simultaneous findings of paracetamol and alcohol in the blood were considered in the analyses. DXP in peripheral blood was found in 1782 (7.5%) of the 23,691 cases analysed during 1992-1996. The autopsy prevalence of DXP increased by 25% from 1992 to 1996. The mean blood DXP concentration was 1.62 micrograms/g (the blood level of DXP after a therapeutic dose is 0.05-0.75 microgram/g). The blood DXP level was < 0.75 microgram/g in 947 cases and > or = 0.75 microgram/g in 835 cases. The cases < 50 years of age had a significantly higher mean concentration (2.36 micrograms/g) than those > or = 50 years (1.04 micrograms/g). Paracetamol in the blood was found in 53% of the DXP cases (mean 75.0 micrograms/g; therapeutic level 2.5-25 micrograms/g) and alcohol in 43% (mean level 0.14%). According to the death certificates 54% (956) died from fatal poisoning. Among these, 74% (707) showed a blood DXP concentration > or = 0.75 microgram/g. Other Scandinavian countries, Denmark and Norway have reduced the rate of fatal DXP poisonings through government regulations for prescription. As the defined daily dose/1000 inhabitants during a 12-month period (DDD) of DXP preparations in Sweden (14.4 in 1996) is six times as high as in Denmark and nine times as high as in Norway, introduction of similar regulations in Sweden should be considered.

Acetaminophen↗

PubMed1998

The manner of death among fatalities where dextropropoxyphene caused or contributed to death.

Dextropropoxyphene (DXP) is one of the most prescribed analgesic compounds in Sweden. To investigate the manner of death among fatalities where DXP caused or contributed to death all medico-legal autopsies performed in Sweden in 1992-1996 were analysed on the bases of toxicological analyses and death certificates. DXP in peripheral blood was found in 1782 (7.5%) of the total 23,691 blood samples. According to the death certificates 956 (54%) of the 1782 cases were classified as fatal DXP poisoning. Among these, the manner of death was classified as accidental in 49 cases (5%), suicidal in 542 cases (57%) and undetermined in 365 cases (38%). The reported manner of death differed between the six forensic medicine districts in Sweden. The accident rate differed significantly between the district with the highest rate (9%) and the districts with the lowest rate (1%). One district had a significantly higher incidence of suicide (73%) than four of the other districts, while another district had a significantly lower incidence of suicide (33%) than all the other districts. The accident classification rate among the physicians performing ten or more autopsies varied from 0% to 17%, the suicide classification rate from 25% to 83% and the rate of undetermined manner of death from 8% to 71%. A major conclusion drawn from this study is that accidental DXP fatalities may be underestimated. This may have serious consequences, as under-reporting of accidental DXP fatalities will increase the risk that knowledge of the high toxicity of DXP will not reach the population consuming this drug. Since valid death statistics concerning the manner of death at DXP fatalities are needed to provide the base for preventive actions, special attention should be paid to the classification process, in order to increase the uniformity of the assessments among the different physicians, and to avoid under-reporting of accidents.

Adolescent↗

PubMed1998

Age-dependent modulation of heparan sulfate structure and function.

Heparan sulfate interacts with growth factors, matrix components, effectors and modulators of enzymatic catalysis as well as with microbial proteins via sulfated oligosaccharide domains. Although a number of such domains have been characterized, little is known about the regulation of their formation in vivo. Here we show that the structure of human aorta heparan sulfate is gradually modulated during aging in a manner that gives rise to markedly enhanced binding to isoforms of platelet-derived growth factor A and B chains containing polybasic cell retention sequences. By contrast, the binding to fibroblast growth factor 2 is affected to a much lesser extent. The enhanced binding of aorta heparan sulfate to platelet-derived growth factor is suggested to be due to an age-dependent increase of GlcN 6-O-sulfation, resulting in increased abundance of the trisulfated L-iduronic acid (2-OSO3)-GlcNSO3(6-OSO3) disaccharide unit. Such units have been shown to hallmark the platelet-derived growth factor A chain-binding site in heparan sulfate.

Adult↗

PubMed1998

A leukocyte elastase inhibitor reduces thrombin-induced pulmonary oedema in the rat: mechanisms of action.

The effect of a selective leukocyte elastase inhibitor, ICI 200,355, on thrombin-induced pulmonary oedema was studied in rats. Thrombin administration produced an increase in lung weight (P < 0.05), wet weight/ dry weight ratio (P < 0.05), and relative lung water content (P < 0.05). The lung weight increase was reduced by the elastase inhibitor in doses of 2000, 200 and 20 micrograms/kg per h (P < 0.05), but not by 2 micrograms/kg per h. A dose of 20 micrograms/ kg per h seems to be optimal, since 10-fold and 100-fold increases in dose did not further improve the effect. Free elastase activity in lung tissue was higher after thrombin infusion than in controls, but was not depleted by the elastase inhibitor in vivo (P < 0.05). This elastase activity in the lung was, however, inhibited by the elastase inhibitor in vitro, indicating that the inhibitor can block extracellular, but not intracellular elastase activity. Thrombin infusion resulted in a significant decrease in plasma elastase inhibitory capacity (P < 0.05), which was depleted by the elastase inhibitor (20 micrograms/kg per h) (P < 0.05). Myeloperoxidase activity was significantly increased in lung tissue after thrombin infusion (P < 0.05). Lung myeloperoxidase activity 5 min after thrombin infusion was not affected by the elastase inhibitor, but the inhibitor induced a further increase in myeloperoxidase as seen 90 min after thrombin infusion, indicating that the effect of this inhibitor on pulmonary oedema is not due to reduction of leukocyte infiltration in the lungs, but may partly be exerted by prevention of neutrophil destruction.

Animals↗

PubMed1998

Sudden infant death syndrome and nitrogen metabolism: further development of a hypothesis.

BACKGROUND: A hypothesis suggesting an inducible inability of the enteric bacteria to metabolize urea in infants, resulting in metabolic alkalosis and subsequent respiratory insufficiency, has been proposed as the cause of sudden infant death syndrome (SIDS). METHODS: Microbiological cultivation and determination of faecal urease activity and faecal urea content were carried out in 30 cases of unexpected infant deaths out of which 22 were considered to be due to SIDS and eight from other causes. The concentration of nitric oxide (NO) in sealed test tubes was determined after incubation of faeces in normal saline. RESULTS: The SIDS subjects differed significantly from the control cases in two respects: they had low or no sigmoid faecal urease activity and an unmetabolized sigmoid faecal urea content, whereas the control subjects had normal faecal urease activity and none, or very little, remaining faecal urea. The NO concentration in faeces was correlated with the faecal content of urea in the SIDS cases. CONCLUSION: The present findings lend support to the hypothesis of an insufficient metabolism of enteric urea in infants with SIDS.

Case-Control Studies↗

PubMed1998

Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double-blind placebo-controlled study.

OBJECTIVE: To study whether intravenous nitroglycerin (NTG) reduces the incidence of ischaemic events and leucocyte activation, as well as inhibiting platelet aggregation in patients with unstable angina pectoris. DESIGN: Randomized double-blind placebo-controlled study. SUBJECTS: One hundred and sixty-two patients with a history and electrocardiographic changes suggesting unstable angina pectoris. INTERVENTIONS: A 48-hour titrated intravenous infusion of NTG or placebo. RESULTS: Of the 162 randomized patients, 19 were excluded because of an acute myocardial infarction on randomization (11 patients) or proven presence of a non-ischaemic cause of the pain (6 patients). Other causes (2 patients). No differences in the clinical findings were detected between the groups on randomization. In the comparison of NTG and placebo, fewer patients in the former group had more than two new attacks of chest pain lasting for < 20 min or one new attack of chest pain lasting > 20 min, despite sublingual NTG (13/25, P < 0.03). In addition, the attacks of pain lasting > 20 min in the NTG group were delayed compared to those in the placebo group (P < 0.05), suggesting a beneficial effect on these more severe episodes. Fewer patients in the NTG group required more than two sublingual NTG tablets (P < 0.005). NTG also reduced the rate-pressure product (P < 0.05), compared to placebo after 2 h but not after 24 h. Compared to baseline, platelet aggregation was inhibited in the patients who had received an NTG infusion for 2 h (P < 0.05). In both groups, leucocytes were activated at baseline, but remained unchanged thereafter. CONCLUSIONS: Intravenous NTG seems to reduce myocardial ischaemia in patients with unstable angina pectoris more than the placebo.

Adult↗

PubMed1998

Effect of in vitro stability of dietary fish oil on lipid peroxidation and prostanoids in vivo.

Dietary supplementation of rats with fish oil for 18 days resulted in signs of lipid peroxidation, with increased malondialdehyde production in plasma and myocardium. This increase in malondialdehyde could be completely prevented by supplementing the fish oil with a new natural antioxidant mixture (Pufanox) which is known to markedly increase the in vitro stability of fish oils. Addition of Pufanox to fish oil also tended to increase the ratio between the vasodilator prostacyclin and the vasoconstrictor thromboxane A2. The concentration of vitamin E decreased, both in plasma and in the heart after the period of fish oil ingestion, indicating that the fish oil used contained too little vitamin E. Plasma cholesterol and triglyceride levels decreased markedly after fish oil supplementation but with no apparent difference between fish oil with or without Pufanox, probably due to the insufficient content of vitamin E. The results obtained emphasize the importance both of the in vitro stability of the fish oil given and of the amount of vitamin E added.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

Analgesic use disorders among orthopedic and chronic pain patients at a rehabilitation clinic.

Interviews were conducted with 265 orthopedic and chronic pain patients, using a structured diagnostic instrument (ADDIS/SUDDS) concerning their use of analgesics. Twenty-two percent of the patients met criteria for analgesic use disorders in accordance with DSM-III-R; 18.5% fulfilled DSM-IV criteria. Dextropropoxyphene was the most common analgesic prescribed and was used by 47% of the patients who met criteria for analgesic use disorders. It is concluded that patients with chronic pain using narcotic analgesics are at considerable risk of developing analgesic use disorders. Assessment of the use of analgesics should be offered to pain patients taking narcotic drugs.

Adult↗

PubMed1998

Mitochondrial DNA sequencing of shed hairs and saliva on robbery caps: sensitivity and matching probabilities.

Sequencing of mitochondrial DNA (mtDNA) has been used for human identification based on teeth and skeletal remains. Here, we describe an amplification system for the mtDNA control region (D-loop) suited for the analysis of shed hair, which constitutes the most common biological evidence material in forensic investigations. The success rate was over 90% when applied to evidence materials such as shed hair, saliva stains and saliva on stamps. The analysis of evidence materials collected from three similar robberies revealed the presence of mtDNA sequences identical to those of the suspects in the three crimes. The use of mtDNA control region sequences for individual identification was evaluated. The probability of identity by chance for the mtDNA types of the suspects in the robberies was found to vary between Pr = 0.017 - < 0.0017, depending on the reference population used, emphasizing the need for large population databases to obtain the appropriate estimate.

Base Sequence↗

PubMed1998

Melagatran, a low molecular weight thrombin inhibitor, counteracts endotoxin-induced haemodynamic and renal dysfunctions in the pig.

Coagulation and fibrinolysis are crucial in septic shock and inhibition of thrombin may be beneficial in this circumstance. Since porcine endotoxaemia has been found to replicate severe septic shock, a low molecular weight thrombin inhibitor, melagatran, was infused during the first 3 out of 6 h of endotoxaemia in pigs. Plasma creatinine (p <0.01) and urinary output (p <0.05) were less affected in the melagtran + endotoxin group (n=6) as compared to endotoxaemic controls (n=9). The left ventricular stroke work index, systemic vascular resistance index and oxygen extraction were all less affected (p <0.05) by endotoxin during the infusion of melagatran. The plasma concentration of melagatran declined with an apparent plasma half-life of 5 h as soon as the infusion was stopped. APTT, however, continued to increase after the infusion of melagatran had stopped and reached a maximum of 113 s at 5 h (baseline 17 s). APTT in endotoxaemic control pigs reached a maximum of 22 s. Thus, melagatran may counteract some consequences of endotoxaemia.

Animals↗

PubMed1997

Biocompatibility reflected by haemostasis variables during cardiopulmonary bypass using heparin-coated circuits.

Cardiopulmonary bypass (CPB) is associated with haemostatic disturbances and signs of acute inflammatory response, most likely related to poor biocompatibility of the artificial surfaces. Some haemostatic variables are known as markers of acute-phase reaction, blood cell trauma, and endothelial damage. The aim of the study was to evaluate the effect of heparin-coating of artificial surfaces on those variables of hemostasis. 14 patients operated on with elective coronary artery revascularization were randomized into two groups. In group H (n = 7), heparin-coated CPB circuits and in control group C (n = 7), noncoated CPB sets were used. Patients in group C received normal heparinization, e.g. bolus 300 IU/kg and additional doses to maintain activated coagulation time (ACT) over 400 sec during CPB. In group H, a bolus heparin dose was reduced by 25% (to 225 IU/kg) in order to compensate for the amount of heparin immobilized on circuit surfaces and the corresponding ACT limit was 300 sec. There were significant increases of the von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI) and tissue-plasminogen activator (tPA) starting at CPB end and rising to about twice the baseline levels postoperatively. This reaction was less evident in group H, as indicated by significantly lower levels of tPA compared to group C at CPB end (135% +/- 9 in group H versus 241% +/- 15 in group C, p < 0.0005) and at two hours postoperatively. The rates of tPA and vWF increase were lower in group H, also indicating reduced endothelial damage in this group. Marginally significant, a higher value of PAI was found in the C group early after CPB onset. Group H showed significantly lower concentrations of circulating complex between elastase and alpha 1-antitrypsin at CPB end and postoperatively, implicating a reduced granulocyte activation (60 min after protaminization 41 micrograms/L +/- 5 in group H versus 256 micrograms/L +/- 55 in group C, p < 0.05). It was concluded that the heparin-coated CPB circuits demonstrated improved biocompatibility which may be related to less disturbed haemostasis.

Anticoagulants↗

PubMed1997

Vitamin A exerts potential therapeutic effects in the endotoxaemic pig.

BACKGROUND: Pretreatment with an injection of vitamin A has beneficial effects on cardiac and pulmonary functions in normally bred endotoxaemic pigs. The present study was performed in order to elucidate whether the response of an ongoing infusion of E. coli can be modulated by a single injection of vitamin A. METHODS: Sixteen healthy (not vitamin A-depleted) pigs were anaesthetized, monitored, mechanically ventilated and subjected to an infusion of E. coli endotoxin (10 micrograms.kg-1.h-1). This infusion resulted within 30 min in a progressive haemodynamic derangement. When the mean pressure in the pulmonary artery was twice the baseline value, vitamin A (460 IU.kg-1) or a corresponding volume of vehicle was injected intravenously. After sacrificing the animals, the right lung was excised and weighed, and biopsy specimens were taken from the left lung for microscopical examination. RESULTS: Mean arterial blood pressure was significantly less affected (P < 0.01) between the 1st and 6th hour in endotoxaemic pigs treated with vitamin A than in those given vehicle. The mean lung weight in the vitamin A-treated pigs was significantly lower than that in the vehicle group (164 +/- 5.3 vs 199 +/- 19.8 g; P < 0.01). Microscopical examination showed significantly less oedema (0.93 +/- 0.17 vs 2.00 +/- 0.26; P < 0.01) and microatelectasis (0.56 +/- 0.17 vs 1.75 +/- 0.31; P < 0.01) in the vitamin A group. Endotoxaemia was also accompanied by an initial, steep decline in neutrophil counts in all animals; this decrease was significantly less pronounced (P < 0.05) in vitamin A-injected pigs than in the vehicle-injected group. The major difference was a more rapid restitution in the vitamin A group. CONCLUSION: Several manifestations of endotoxaemia were expressed less in the vitamin A group. Thus, vitamin A may turn out to be a tool in the management of endotoxaemia.

Animals↗

PubMed1996

Whole blood production of thromboxane, prostacyclin and leukotriene B4 after dietary fish oil supplementation in man: effect of vitamin E.

12 subjects were given 30 ml/day of a fish oil already stabilized with vitamin E (1.5 IU/g) and other natural antioxidants (fish oil, FO), and the same fish oil supplemented with extra vitamin E (to total 4.5 IU/g) (FO+E), in a randomized double-blind cross-over study. The whole blood production of thromboxane B2, measured in serum, was reduced after 4 weeks of ingestion of both FO+E (by 47%, P < 0.01) and of FO (by 40%, P < 0.05) whereas 6-keto-PGF1 alpha increased slightly in both cases, by 4% and 5% respectively, both NS. Leukotriene B4 production decreased on both FO+E (by 20%, NS) and FO (by 17%, P < 0.05). This study thus showed that a stabilized fish oil had marked effects on eicosanoid production, which may be important for its cardiovascular effect. Further supplementation with vitamin E had no additional effect, indicating that the vitamin E content (1.5 IU/g) in this stabilized fish oil might have been optimal.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

Dietary fish oil decreases superoxide generation by human neutrophils: relation to cyclooxygenase pathway and lysosomal enzyme release.

12 volunteers with slightly elevated serum triglyceride levels were given 30 ml fish oil (5.4 g eicosapentaenoic acid and 3.2 g docosahexaenoic acid) daily for 4 weeks. The percentage of eicosapentaenoic acid increased (P < 0.01) and the percentage of linoleic (P < 0.05) and arachidonic acid (P < 0.01) decreased in neutrophil phospholipids. Superoxide generation by neutrophils initiated by phorbol myristate acetate decreased significantly from 48.6 +/- 8.8 to 34.7 +/- 11.1 nmol/10 min/400,000 cells (means +/- SD, P < 0.01, n = 11). Treatment of the cells with the cyclooxygenase inhibitor indomethacin had no significant influence on the decrease in superoxide generation, indicating that cyclooxygenase products were not involved in this effect of fish oil. Neutrophil elastase release did not change significantly, suggesting that neutrophil lysosomal enzyme release and superoxide generation may be under separate control. In conclusion, dietary fish oil decreased superoxide generation by human neutrophils without involvement of the cyclooxygenase pathway and without altering neutrophil lysosomal enzyme release. Dietary fish oil could have beneficial effects in pathological conditions with activated neutrophils, such as ischaemic heart disease.

Adult↗

PubMed1996

Beneficial effects of pre-treatment with vitamin A on cardiac and pulmonary functions in endotoxaemic pigs.

BACKGROUND: Septic shock is associated with high mortality despite the development of new antibiotics. Since Vitamin A has an immunomodulating ability and is able to lower the concentrations of endotoxin and some cytokines, we decided to study whether supplementation with vitamin A may have a beneficial effect in experimental endotoxaemia. METHODS: A porcine model was used, in which normally bred (i.e., not vitamin A depleted) animals were anaesthetised, monitored and injected intramuscularly with a non-toxic dose of vitamin A (230 IU.kg-1) (n = 9) or the corresponding volume of vehicle (n = 9) 1 hour before an infusion of purified E. coli endotoxin was given in a dose of 10 micrograms.kg-1.h-1 over 6 hours. Another 3 pigs also injected with vitamin A, but not endotoxin, served as controls. RESULTS: Vitamin A- and endotoxin-injected pigs were significantly less affected in several circulatory and respiratory variables as compared to vehicle-and endotoxin-injected animals (e.g., blood pressure; heart rate; cardiac index; pulmonary capillary wedge pressure; left and right ventricular stroke work indices; pH; base excess; oxygen delivery; and oxygen extraction). Vitamin A did not per se significantly affect these variables. Hb increased significantly in the vehicle group, indicating a more pronounced capillary permeability. Urinary output or fluid supply did not differ between the groups. Myocardial production of metabolites of prostacyclin or thromboxane A2 did not differ between the groups. CONCLUSION: Pre-treatment with vitamin A had a beneficial effect on several variables, such as oxygen delivery and metabolic acidosis in the endotoxaemic pig. Improvement of these variables is associated with increased survival in septic shock and may indicate reduced tissue hypoxia. Thus, vitamin A may turn out to be useful as a prophylactic agent in conditions where septic shock is apt to occur.

6-Ketoprostaglandin F1 alpha↗