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Biomedical subjects

G W Smith

Publications and source records attributed to G W Smith.

At least 19 recordsLinked to original sources
PubMed2001

Species and organ specificity of fumonisin-induced endothelial alterations: potential role in porcine pulmonary edema.

Fumonisins, mycotoxins that commonly contaminate corn, induce cardiovascular toxicity and pulmonary edema in pigs, leukoencephalomalacia in horses, and nephropathy in rats, rabbits, and lambs. The mechanisms of these species-specific target organ toxicoses are poorly understood. We have previously reported perinuclear accumulation of membranous material in pulmonary capillary endothelial cells of pigs fed fumonisin-containing culture material. We hypothesized that these endothelial accumulations may be important in the pathogenesis of fumonisin-induced pulmonary edema and target organ toxicity in other species. Both target and non-target tissues from fumonisin-exposed pigs, sheep, rabbits, and rats were examined ultrastructurally. Specifically, lung, liver, heart and kidney were examined. In agreement with our previous work (Gumprecht, L.A., Beasley, V.R., Weigel, R.M., Parker, H.M., Tumbleson, M.E., Bacon, C.W., Meredith, F.I., Haschek, W.M., 1998. Development of fumonisin-induced hepatotoxicity and pulmonary edema in orally dosed swine: morphological and biochemical parameters. Tox. Pathol. 26, 777-788), endothelial alterations were present in the pulmonary capillary endothelial cells of pigs fed fumonisin-containing culture material, but at doses that did not induce pulmonary edema, as well as in pigs injected intravenously with purified fumonisin B(1). These alterations were present only in the pulmonary capillary endothelium of pigs and not in other species. In addition, these endothelial alterations were not present in any other organ of pigs or other species examined. Thus, these endothelial alterations are induced by fumonisin B(1), but only in pulmonary capillary endothelium and only in pigs. Although evidence that these alterations play a role in fumonisin-induced pulmonary edema is limited, other endothelial functions may be affected by fumonisin treatment.

Animals↗
PubMed2001

Pre-translational regulation of neutrophil L-selectin in glucocorticoid-challenged cattle.

L-selectin (CD62L) gene expression in neutrophils is commonly referred to as "constitutive" because circulating neutrophils require a constant supply of this adhesion molecule for continuous trafficking into peripheral tissues. Under normal circumstances, marginating blood neutrophils and neutrophils that become activated for migration into infected tissues rapidly shed surface CD62L that is ligated to the vascular endothelium. However, this does not shut down CD62L gene expression because these cells continue to express surface CD62L. In contrast, glucocorticoid challenges resulting from stress and hormone injections result in gradual and chronic down-regulation of CD62L on the surface of blood neutrophils. Rather than being associated with migration, this type of CD62L down-regulation associates with pronounced neutrophilia and increased susceptibility to infections. Nothing is currently known about glucocorticoid regulation of CD62L expression in neutrophils. In other cell systems, however, this steroid hormone binds to cytoplasmic glucocorticoid receptors (GR) that influence expression of glucocorticoid-responsive genes at multiple pre-translational levels. Thus, the hypothesis of the present study was that glucocorticoid challenge suppresses CD62L mRNA expression in blood neutrophils. Suppressed CD62L gene expression might help explain the chronic down-regulation of surface CD62L in neutrophils and accompanying neutrophilia. The main objectives of the study were to monitor neutrophil CD62L mRNA abundance before and during subtle and severe glucocorticoid challenges and to determine if CD62L mRNA expression correlates with degree of glucocorticoid challenge. Parturient dairy cows and dexamethasone-treated steers were used as models of subtle and severe (respectively) glucocorticoid challenges. Data presented from both models support the hypothesis and show for the first time that glucocorticoids regulate neutrophil CD62L at a pre-translational level. Results also showed that inhibited CD62L mRNA expression correlated precisely with down-regulated surface expression of CD62L on neutrophils and peak neutrophilia during severe glucocorticoid challenge. Therefore, results of this study indicate that bovine neutrophils are highly sensitive to the blood environment, displaying full capacity to alter CD62L gene expression and trafficking patterns in response to changing glucocorticoid levels. This may serve animals well when heightened inflammatory responses begin to lead to tissue damage, but may be detrimental to overall health if animals are exposed to opportunistic pathogens while stressed or undergoing glucocorticoid therapy. Although this study did not elucidate how glucocorticoids inhibit neutrophil CD62L mRNA expression, presented data implicate GR as possibly being involved because neutrophils from cattle in both models expressed GR mRNA. Further in vitro studies using purified populations of neutrophils will be required to determine if GR is directly involved in glucocorticoid regulation of CD62L gene expression and, if so, at what level.

Actins↗
PubMed2001

The epic project: developing national evidence-based guidelines for preventing healthcare associated infections. Phase I: Guidelines for preventing hospital-acquired infections. Department of Health (England).

In 1998, the Department of Health (England) commissioned the first phase of national evidence-based guidelines for preventing healthcare associated infections. These focused on developing a set of standard principles for preventing infections in hospitals together with guidelines for preventing hospital-acquired infections (HAI) associated with the use of short-term indwelling ureteral catheters in acute care and with central venous catheters in acute care. These guidelines are systematically developed broad statements (principles) of good practice that all practitioners can use and which can be incorporated into local protocols. A nurse-led, multi-professional team composed of infection prevention practitioners, clinical microbiologists/retrovirologist, epidemiologists, and researchers developed the guidelines. A rigorous guideline development process was used to inform the systematic reviews, the clinical and critical appraisal of relevant evidence, and linking that evidence to evolving guidelines. Both general and specialist clinical practitioners were involved in all stages of developing these guidelines, as were representatives from relevant Royal Colleges, learned societies, other professional organisations and key stakeholders. The introduction to these guidelines describes a robust and validated guideline development model that can be used by others to develop future guidelines. This model is described in more detail in the associated technical reports that can be found on the project web site http://www.epic.tvu.ac.uk. Locating and appropriately using good quality evidence to inform guideline development in this field is challenging. Evidence from rigorously conducted experimental studies was frequently limited and consequently a range of other types of evidence were systematically retrieved and carefully appraised. The concluding discussion on implementation highlights potential issues for clinical governance and areas for future research and suggests issues that need to be addressed to allow practitioners to successfully incorporate these guidelines into routine clinical practice.

Acute Disease↗
PubMed2001

Fumonisin B(1) increases serum sphinganine concentration but does not alter serum sphingosine concentration or induce cardiovascular changes in milk-fed calves.

Fumonisin B(1) is the most toxic and commonly occurring form of a group of mycotoxins that alter sphingolipid biosynthesis and induce leukoencephalomalacia in horses and pulmonary edema in pigs. Purified fumonisin B(1) (1 mg/kg, iv, daily) increased serum sphinganine and sphingosine concentrations and decreased cardiovascular function in pigs within 5 days. We therefore examined whether the same dosage schedule of fumonisin B(1) produced a similar effect in calves. Ten milk-fed male Holstein calves were instrumented to obtain blood and cardiovascular measurements. Treated calves (n = 5) were administered purified fumonisin B(1) at 1 mg/kg, iv, daily for 7 days and controls (n = 5) were administered 10 ml 0.9% NaCl, iv, daily. Each calf was euthanized on day 7. In treated calves, serum sphinganine concentration increased from day 3 onward (day 7, 0.237 +/- 0.388 micromol/l; baseline, 0.010 +/- 0.007 micromol/l; mean +/- SD), whereas, serum sphingosine concentration was unchanged (day 7, 0.044 +/- 0.065 micromol/l; baseline, 0.021 +/- 0.025 micromol/l). Heart rate, cardiac output, stroke volume, mean arterial pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, central venous pressure, plasma volume, base-apex electrocardiogram, arterial Po(2), and systemic oxygen delivery were unchanged in treated and control calves. Fumonisin-treated calves developed metabolic acidosis (arterial blood pH, 7.27 +/- 0.11; base excess, -9.1 +/- 7.6 mEq/l), but all survived for 7 days. We conclude that calves are more resistant to fumonisin B(1) cardiovascular toxicity than pigs.

Acidosis, Respiratory↗
PubMed2001

An intensive outpatient program for patients with borderline personality disorder.

Intensive outpatient programs are designed to promote patients' functioning in the community by offering a more intensive level of structure and support than was previously available for outpatients. This paper describes the intensive outpatient program at McLean Hospital in Belmont, Massachusetts, which is tailored for patients with borderline personality disorder. These patients are susceptible to control struggles and regressive behaviors in more restrictive treatment settings. Through frequent contact with clinicians and other patients in this group-oriented program, patients with borderline personality disorders appear to feel sufficiently "held" and understood to develop their functional capacities as outpatients.

Ambulatory Care↗
PubMed2001

Mice that lack corticotropin-releasing factor (CRF) receptors type 1 show a blunted ACTH response to acute alcohol despite up-regulated constitutive hypothalamic CRF gene expression.

BACKGROUND: The purpose of this work was to determine the influence of acute alcohol treatment, injected intraperitoneally, on the hypothalamic-pituitary-adrenal axis of mice that lack type 1 receptor for corticotropin-releasing factor (CRFR1). METHODS: CRFR1-deficient (CRFR1-/-), heterozygous (CRFR1+/-), and wild-type (CRFR1+/+) mice were generated and maintained under standard conditions. Homozygous, heterozygous, and wild-type offspring were identified by polymerase chain reaction analysis of tail DNA. Experiments were performed on 9- to 16-week-old male and female mice. All blood samples were obtained by rapid decapitation of conscious mice conducted between 10 AM-12 PM. Blood sample collection was completed within 20 to 30 sec of disturbing the animals, and all samples were terminal. Preliminary experiments were conducted to determine the time-course of the ACTH and hypothalamic responses to alcohol in all three groups of mice, and a single time point (30 min and 2 hr, respectively), corresponding to peak responses, was chosen to measure the corresponding parameters in all subsequent studies. RESULTS: In vehicle-injected animals, basal ACTH and corticosterone levels were statistically comparable in heterozygotes and mice with a null allele for the CRFR1 gene, although values of this latter hormone were slightly lower in the mutants. Alcohol (4.0 g/kg) elicited the expected significant (p < 0.01) increase in plasma ACTH and corticosterone levels in heterozygous mice. These responses were virtually abolished or markedly decreased, respectively, in CRFR1-deficient animals. As previously reported, constitutive CRF mRNA levels were elevated in the paraventricular nucleus (PVN) of the hypothalamus in mice that lacked CRFR1, compared to wild-type control mice. Interestingly, this was not the case for transcripts of the immediate early gene NGFI-B. When measured 2 hr after alcohol, PVN NGFI-B gene expression was significantly (p < 0.01) increased in both control and mutant mice, as were CRF mRNA levels in mutant mice, but the hypothalamic responses of the mutants were larger (p < 0.01) than those of the control mice. This difference may be due, at least in part, to the lack of steroid feedback in the mutants. CONCLUSION: These results indicate that although the intraperitoneal injection of alcohol remains capable of eliciting PVN CRF neuronal activation in mice that lack CRFR1, the ACTH and corticosterone responses are significantly blunted, a phenomenon believed to be due to the lack of CRFR1 in the pituitary of these animals.

Adrenocorticotropic Hormone↗
PubMed2000

Exclusion limits on the WIMP-nucleon cross section from the cryogenic dark matter search.

The Cryogenic Dark Matter Search (CDMS) employs Ge and Si detectors to search for weakly interacting massive particles (WIMPs) via their elastic-scattering interactions with nuclei while discriminating against interactions of background particles. CDMS data, accounting for the neutron background, give limits on the spin-independent WIMP-nucleon elastic-scattering cross section that exclude unexplored parameter space above 10 GeV/c2 WIMP mass and, at >75% C.L., the entire 3sigma allowed region for the WIMP signal reported by the DAMA experiment.

Journal Article↗
PubMed2000

Ingestion of fumonisin B1-containing culture material decreases cardiac contractility and mechanical efficiency in swine.

Fumonisins are mycotoxins produced primarily by Fusarium verticillioides, a fungus that commonly contaminates corn. Fumonisin ingestion increases plasma and tissue sphingosine and sphinganine concentrations and causes porcine pulmonary edema, which has been attributed to acute left-sided heart failure or increased vascular permeability. We investigated the effect of short-term ingestion of fumonisin B1-containing culture material on cardiac function in pigs. Treated male pigs (n = 7) received fumonisin-containing culture material which was mixed into the grower diet at 20 mg fumonisin B1/kg body weight each day, while control pigs (n = 7) were fed only the grower diet on the same schedule as the treated pigs. Pigs were anesthetized after 3 days of receiving either diet and instrumented to accurately characterize the cardiovascular effects of fumonisin ingestion. Fumonisin-treated pigs had lower cardiac outputs and heart rates than control pigs. Fumonisin-treated pigs also had a marked reduction in cardiac contractility, as indicated by decreased values for end-systolic elastance (the gold standard in vivo measure of cardiac contractility), V(0) (the intercept value for the end-systolic pressure-volume relationship), and mechanical efficiency. These data indicate that in pigs, short-term ingestion of fumonisin B1-containing culture material produces negative inotropic and chronotropic effects and decreases mechanical efficiency of the left ventricle. Theses cardiovascular effects are consistent with fumonisin-induced, sphingosine-mediated l-type Ca(2+) channel blockade and suggest that pulmonary edema in pigs fed fumonisin is primarily due to acute left-sided heart failure instead of increased vascular permeability.

Adrenergic beta-Antagonists↗
PubMed2000

Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress.

Corticotropin-releasing hormone (Crh) is a critical coordinator of the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, Crh released from the paraventricular nucleus (PVN) of the hypothalamus activates Crh receptors on anterior pituitary corticotropes, resulting in release of adrenocorticotropic hormone (Acth) into the bloodstream. Acth in turn activates Acth receptors in the adrenal cortex to increase synthesis and release of glucocorticoids. The receptors for Crh, Crhr1 and Crhr2, are found throughout the central nervous system and periphery. Crh has a higher affinity for Crhr1 than for Crhr2, and urocortin (Ucn), a Crh-related peptide, is thought to be the endogenous ligand for Crhr2 because it binds with almost 40-fold higher affinity than does Crh. Crhr1 and Crhr2 share approximately 71% amino acid sequence similarity and are distinct in their localization within the brain and peripheral tissues. We generated mice deficient for Crhr2 to determine the physiological role of this receptor. Crhr2-mutant mice are hypersensitive to stress and display increased anxiety-like behaviour. Mutant mice have normal basal feeding and weight gain, but decreased food intake following food deprivation. Intravenous Ucn produces no effect on mean arterial pressure in the mutant mice.

Animals↗
PubMed2000

The reproducibility of sputum gram film interpretation.

OBJECTIVES: To evaluate the reproducibility with which microbiologists interpret Gram-stained sputa and examine the effect of the smear preparation method. METHODS: Two hundred and ten coded slides prepared directly from a purulent portion of sputum (DS) and 140 slides prepared after homogenization of the same sputum (HS) were examined by three experienced microbiologists. A proportion of the slides prepared by each method were recorded and represented to the raters. Intraobserver and interobserver variation was assessed using the kappa statistic (kappa). RESULTS: Evaluation of the smear as being infected and predicting Streptococcus pneumoniae as the infecting organism showed the greatest intraobserver agreement (kappa=0.74-0.82) and interobserver agreement (kappa=0.50-0.82). The agreement concerning the number of cells and infection with Haemophilus influenzae was only fair to moderate. Differences in the interpretation of smears prepared by the two methods could be explained by the intrinsic disagreement that occurs when the same smear is examined twice. The positive predictive value of a positive S. pneumoniae smear for a positive culture ([10(6)/ml) was 81% with the DS and 97% with the HS. CONCLUSION: In this laboratory, a sputum Gram film interpretation suggesting infection with S. pneumoniae was reproducible and predictive of a significant positive culture.

Adolescent↗
PubMed2000

Purified fumonisin B(1) decreases cardiovascular function but does not alter pulmonary capillary permeability in swine.

Fumonisins are mycotoxins produced by Fusarium verticillioides, which induce acute pulmonary edema in swine. We previously reported that ingestion of fumonisin-containing culture material decreases cardiovascular function in swine (1996,a,b; Fundam. Appl. Toxicol. 31, 169-172; 33, 140-148; 1999, Am. J Vet. Res. 60, 1291-1300). The main purpose of this study was to confirm that fumonisin B(1) was responsible for the observed cardiovascular changes. Treated pigs (n = 6) were given daily intravenous injections of purified fumonisin B(1) at 1 mg/kg for 4 days, while controls (n = 6) were injected with equal volumes of saline. On day 5, pigs were anesthetized with butorphanol-chloralose and instrumented for hemodynamic studies. Terminally, bronchoalveolar lavage was performed on each pig to determine the relative permeability index of the pulmonary endothelium. Fumonisin B(1)-treated pigs had marked decreases in the maximal rate of change of left ventricular pressure (dP/dt(max)), mean aortic pressure, cardiac output, and arterial pO(2), accompanied by increases in mean pulmonary artery pressure, oxygen extraction ratio, and blood hemoglobin concentration. Plasma and left ventricular sphingosine and sphinganine concentrations were markedly increased in treated pigs at day 5; however, there was no difference in the relative permeability index between groups. Serum cholesterol concentrations and activities of hepatic-derived enzymes were increased, and hepatocyte apoptosis and mitoses were present in the livers of fumonisin-treated pigs. In the lungs of treated pigs, there was proteinaceous edema and membranous accumulations in capillary endothelial cells. These results indicate that cardiovascular function is altered by fumonisin B(1), and that fumonisin-induced pulmonary edema is caused by left-sided heart failure and not by altered endothelial permeability. Because of the potential for contamination of human foodstuffs by fumonisins, the cardiovascular toxicity of these compounds must be taken into consideration.

Animals↗
PubMed2000

Dissociation of locomotor activation and suppression of food intake induced by CRF in CRFR1-deficient mice.

Corticotropin-releasing factor (CRF) systems are involved in locomotor and feeding behaviors. Two distinct CRF receptor subtypes, CRFR1 and CRFR2, are thought to mediate CRF actions in the central nervous system. However, the role for each receptor in locomotor activity and feeding remains to be determined. Using CRFR1 null mutant mice, the present study examined the functional significance of this receptor in ambulation and feeding. CRF treatment of wild-type mice resulted in increased levels of locomotion whereas no change was observed in CRFR1-deficient mice as compared to vehicle-treated mutant mice. In contrast, CRF decreased food-water intake in both wild type and CRFR1-deficient mice equally. These results support an important role for CRFR1 in mediating CRF-induced locomotor activation, whereas other receptor subtypes, likely CRFR2, may mediate the appetite-suppressing effects of CRF-like peptides.

Animals↗
PubMed1999

Emerging marine diseases--climate links and anthropogenic factors.

Mass mortalities due to disease outbreaks have recently affected major taxa in the oceans. For closely monitored groups like corals and marine mammals, reports of the frequency of epidemics and the number of new diseases have increased recently. A dramatic global increase in the severity of coral bleaching in 1997-98 is coincident with high El Niño temperatures. Such climate-mediated, physiological stresses may compromise host resistance and increase frequency of opportunistic diseases. Where documented, new diseases typically have emerged through host or range shifts of known pathogens. Both climate and human activities may have also accelerated global transport of species, bringing together pathogens and previously unexposed host populations.

Animals↗
PubMed1999

Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 1.

Corticotropin-releasing factor (CRF) has been hypothesized to be involved in the pathophysiology of anxiety, depression, cognitive and feeding disorders. Two distinct CRF receptor subtypes, CRFR1 and CRFR2, are thought to mediate CRF actions in the CNS. However, the role for each receptor subtype in animal models of neuropsychiatric disorders remains to be determined. Using CRFR1 deficient mice, the present study investigated the functional significance of this CRF receptor subtype in anxiety-like and memory processes. CRFR1 knockout mice displayed an increased exploratory behavior in both the Elevated Plus-maze (EPM) and the Black and White (B-W) test box models of anxiety, indicating an anxiolytic-like effect of the CRFR1 gene deletion. In contrast, during the retrieval trial of a two-trial spatial memory task wild type mice made more visits to and spent more time in the novel arm as opposed to the two familiar ones of a Y-maze apparatus. No increase in the level of exploration of the novel arm by the CRFR1 deficient mice was observed. This indicates that CRFR1 knockout mice are impaired in spatial recognition memory. These results demonstrate that genetic deletion of the CRFR1 receptor can lead to impairments in anxiety-like and cognitive behaviors, supporting a critical role for this receptor in anxiety and cognitive biological processes.

Animals↗
PubMed1999

CRF type I receptor-deficient mice exhibit a pronounced pituitary-adrenal response to local inflammation.

Recent studies indicate that the regulation of adrenocorticotropin (ACTH) secretion by corticotropin-releasing factor (CRF) is mediated predominantly by the type I CRF receptor (CRF-R1). Indeed, CRF-R1-deficient (CRF-R1 -/-) mice show marked impairment of the pituitary-adrenal axis. However, the plasma ACTH concentrations of unstressed CRF-R1 -/- mice are similar to those in wild-type mice. We show here that arginine vasopressin (AVP) is a major ACTH secretagogue in CRF-R1 -/- mice in resting conditions, since administration of anti-AVP serum, but not anti-CRF serum, markedly reduced (by 60%) resting plasma ACTH concentrations in these mutants. We also investigated the pituitary-adrenal response to turpentine-induced local inflammation in CRF-R1 -/- mice. Administration of turpentine into the hind-limb of CRF-R1 -/- mice produced a slightly (15-25%) smaller swelling of the limb, but a 10 fold greater rise in plasma IL-6 levels, compared to CRF-R1 +/+ controls. Turpentine-induced local inflammation produced pronounced elevations in the plasma concentrations of both ACTH and corticosterone in both CRF-R1 -/- and wild-type mice, but ACTH secretion could be inhibited by anti-CRF and anti-AVP sera only in wild-type mice. These data indicate that resting ACTH secretion in CRF-R1 -/- mice is in part attributable to AVP-dependent mechanisms. Furthermore, while in normal mice the pituitary-adrenal response to local inflammation is mediated largely via CRF-dependent mechanisms, mice deficient in CRF-R1 are still able to mount a pituitary-adrenal response via mechanisms that do not depend critically on either CRF or AVP action.

Adrenocorticotropic Hormone↗
PubMed1999

Regulation of ovarian extracellular matrix remodelling by metalloproteinases and their tissue inhibitors: effects on follicular development, ovulation and luteal function.

In most organs, remodelling of tissues after morphogenesis is minimal; however, normal ovarian function depends upon cyclical remodelling of the extracellular matrix (ECM). The ECM has a profound effect on cellular functions and probably plays an important role in the processes of follicular development and atresia, ovulation, and development, maintenance and regression of corpora lutea. Matrix metalloproteinases (MMPs; collagenases, gelatinases, stromelysins and membrane-type MMPs) cleave specific components of the ECM and are inhibited by tissue inhibitors of metalloproteinases (TIMPs). MMPs have been detected at all stages of follicular development and probably modulate follicular expansion or atresia within the ovarian stroma. In addition, increased MMP activity appears to be required for ovulation since follicular rupture occurred in the absence of plasminogen activator activity and inhibitors of MMPs blocked follicular rupture. Development and luteolysis of the corpus luteum are accompanied by extensive remodelling of the ECM. Differentiation and regression of luteal cells are associated with construction and degradation of ECM, respectively. There is increasing evidence that ECM components enhance luteinization; whereas loss of ECM results in luteal cell death. Ovine large luteal cells may be the primary type of cell responsible for controlling the extent of remodelling of luteal ECM since they produce TIMP-1, TIMP-2 and plasminogen activator inhibitor 1. The ratio of active MMPs to TIMPs may be important in maintaining an ECM microenvironment conducive to the differentiation of follicular-derived cells into luteal cells, and maintenance of the phenotype of luteal cells.

Animals↗
PubMed1999

Sequence of cardiovascular changes leading to pulmonary edema in swine fed culture material containing fumonisin.

OBJECTIVES: To determine the sequence of cardiovascular and blood gas changes induced by ingestion of fumonisin-containing culture material in swine and to examine the temporal relationship of these changes to plasma sphinganine and sphingosine concentrations. ANIMALS: 12 healthy castrated pigs (38 to 50 kg). PROCEDURE: Pigs were instrumented to permit cardiovascular monitoring and collection of blood samples. Baseline values were obtained, and pigs were randomly assigned to 1 of 2 groups. Control pigs (n = 6) were fed a standard grower diet, whereas culture material that contained 20 mg of fumonisin B1/kg of body weight was added to the feed of treated pigs (n = 6) each day. Hemodynamic data, results of arterial and mixed venous blood gas analyses, and plasma sphinganine and sphingosine concentrations were recorded every 12 hours until treated pigs were euthanatized because of impending death from pulmonary edema. RESULTS: Sphinganine and sphingosine concentrations were increased in plasma of treated pigs within 24 hours of initial fumonisin exposure and continued to increase dramatically until euthanasia. Fumonisin-treated pigs had increased respiratory rate, mean pulmonary artery pressure, and pulmonary artery wedge pressure, along with decreased heart rate and cardiac output in the 12-hour period before euthanasia. Fumonisin-treated pigs also had systemic arterial hypotension, arterial and mixed venous hypoxemia, metabolic acidosis, decreased oxygen delivery, and increased oxygen consumption immediately before euthanasia. CONCLUSIONS AND CLINICAL RELEVANCE: Fumonisin-induced pulmonary edema in swine is probably caused by acute left-sided heart failure. Onset of hemodynamic changes was associated with plasma sphinganine concentration > or = 2.2 microM/L and plasma sphingosine concentration > or = 1 microM/L.

Animal Feed↗