Search PubMed⌕ Search

Biomedical subjects

C R Baxter

Publications and source records attributed to C R Baxter.

124 records · Page 7Linked to original sources

Elastase and alpha 1-protease inhibitor in burn wound exudates.

By degrading antithrombin III, polymorphonuclear neutrophil (PMN) elastase can become a procoagulant. Because intravascular coagulation may accompany severe burn injury, this study examined burn wound exudates for PMN elastase and its physiologic inhibitor, plasma alpha 1-protease inhibitor (alpha 1-PI), as a step in evaluating their contributions to coagulopathy in patients with burns. Each of the nine exudates examined were inhibitory for PMN elastase. Chromatographic characterization of the inhibitor indicated that it was alpha 1-PI; its elution volume for four exudates was identical to that of pure alpha 1-PI. Confirmation of the inhibitor's identity was achieved by reaction of anti-alpha 1-PI antibody with each exudate and with inhibitory chromatographic fractions of exudates with the most inhibitory activity. Inhibitor potency, determined from dose-response curves against a standard PMN elastase activity, varied twentyfold among exudates. Only one exudate had catalytic activity with the PMN elastase substrate. Although this enzyme had elastase-like properties, it appeared to differ from PMN elastase. The presence of alpha 1-PI in the wound exudate suggests that this inhibitor may act to diminish fibrin formation from the level that might otherwise have been seen if excess elastase were free to degrade antithrombin III.

Burns↗

Tumor necrosis factor mediates hypertriglyceridemia during thermal injury in mice genetically susceptible to lipopolysaccharides.

A rise in plasma triglycerides has been noted after thermal injury in a number of animal species including humans. In this study we identified a factor, tumor necrosis factor, which was responsible for increased plasma triglycerides during thermal injury that was induced by scalding. Two strains of mice that differed genetically in susceptibility to lipopolysaccharides were used. These were CH3HEB/HeJ (LPS-) and CH3HEB/FeJ (LPS+). A 15% total body surface area was burned; this resulted in an increase of plasma triglycerides of 126% of preburn levels in the LPS+ strain 24 hours after burn injury. No change in triglycerides was noted in the LPS- mice at any time after burn injury. Sera from LPS+ mice at 1 to 2 hours after burn injury was injected into nonburned animals of the same strain; this caused a 62% +/- 5% increase in plasma triglycerides 24 hours after injection. When thermally injured LPS+ mice were injected with anti-tumor necrosis factor-alpha at 1 hour after injury, they did not show a rise in plasma triglycerides at any time between 24 to 72 hours after injury. Hepatic secretion of triglycerides was also measured 1 day after burn; the average secretion of triglycerides was significantly reduced (2.69 +/- 0.36 mg/kg/hr, compared with 3.83 +/- 0.15 mg/kg/hr for the control). We conclude that tumor necrosis factor, a cytokine that inhibits lipoprotein lipase, causes hypertriglyceridemia during thermal injury in spite of a decreased secretion of triglycerides. This is the first report that demonstrates that hypertriglyceridemia that is secondary to thermal injury is induced by tumor necrosis factor.

Animals↗

Equations for the estimation of energy expenditures in patients with burns with special reference to ventilatory status.

There are advantages to the use of easily assessed variables for the prediction of energy expenditures of patients with burns. The purpose of this study was to determine whether height, age, sex, weight, ventilatory status, and diagnosis could be correlated with measured energy expenditures of hospitalized patients. With the use of data from 200 patients, stepwise, multivariate regression analysis derived the following equations: EEE(v) = 1925 - 10(A) + 5(W) + 281(S) + 292(T) + 851(B) (R2 = 0.43); EEE(s) = 629 - 11(A) + 25(W) - 609(O) (R2 = 0.50); where EEE = estimated energy expenditure (kcal/day), v = ventilatory dependency, s = spontaneously breathing, A = age (yr), W = body weight (kg), S = sex (male = 1, female = 0), diagnosis of T = trauma, B = burn, O = obesity present = 1, absent = 0). The equations were tested on 100 patients. Measured energy expenditures were not significantly different from calculated EEE(s) or EEE(v) (paired t test, p greater than 0.25). Energy expenditures can be accurately estimated in a variety of patients, including those with major burns with the use of easily attained information.

Adult↗

The effects of epinephrine, ibuprofen, and tetrachlorodecaoxide on cutaneous microcirculation in thermally injured hamsters.

Fluctuations in the diameter of selected arterioles in the cutaneous microcirculation of Syrian golden hamster dorsal skin flap chambers, which ranged in size from 10 to 70 microns at different branching order sites, were measured before burn, at the same sites after burn and after injection of the drug. Three different drugs epinephrine (administered intravenously), ibuprofen (administered intravenously), and tetrachlorodecaoxide (administered intravenously and topically) were evaluated. Results show that the response to thermal injury in the control group involved extensive vasodilation in the arterioles, prolonged flow irregularities including flow obstructions and stasis, and a decrease in the level of vasoactivity of the microvessels. In two treatment groups, the ibuprofen and tetrachlorodecaoxide groups, significant improvement as indicated by reduced vasodilation and edema and improved microcirculatory blood flow after injury were observed. Further testing of tetrachlorodecaoxide as a topically applied wound dressing is indicated.

Animals↗

Burn-induced alterations in vasoactive function of the peripheral cutaneous microcirculation.

Alterations in the cutaneous vasomotion function caused by scald burns to a large area on the flank were observed and quantified in a dorsal skin flap window with a hamster model. Subsequent to chronic implantation of the window chamber to provide direct microscopic observation of blood flow for an entire thickness of skin, control measurements of vasoactivity in a defined network of arterioles were taken by means of a digital video image splitter over a period of several days. A 100 degrees C, 5-second water scald was then effected over 17% to 55% of the total body surface area, and the vasoactivity was remeasured in the targeted set of sites at serial time intervals for 2 to 4 days. Data were acquired directly into a computer and analyzed for both the magnitude and time pattern of diameter fluctuations during 3-minute observation periods. Average and standard deviations of diameters were computed, and the Prony power spectral analysis method was applied to identify the presence and strength of fluctuation frequencies. In general, vasomotion was suppressed for several hours subsequent to the burn, and the activity was dominated by much slower contractions than control. No direction of vessel diameter changes prevailed uniformly throughout the peripheral microcirculation. Large alternate constrictions and dilations were also observed for some arteriolar and venular components, but others exhibited no significant change at all. The incidence and magnitude of peripheral microvascular response was proportional to the size of the injured area.

Anesthesia, Inhalation↗

Local macromolecular extravasation in thermal burns quantified by fluorescent video microscopy and computer vision.

A dorsal skin flap chamber model was developed for analysis of the microvascular response to moderate intensity local thermal burns. Fluorescein isothiocyanate tagged 70,000 d dextran was introduced to visualize the extravasation and interstitial transport of macromolecules at the burn site. Contact burns 0.5 cm in diameter were affected by touching a thermostated metal rod onto the exposed epidermal side of the chamber preparation. All burns were of 5-second duration at temperatures between 55 degrees C and 70 degrees C. Postburn leakage of the fluorescein-labeled probed was monitored at numerous sites in the preparation on a fluorescent microscope equipped with a low-light-level intensified silicon intensified target video camera and recorded on tape for subsequent quantitative analysis. Selected scenes were digitized and subjected to a sequence of computer-image processing operations to extract quantitative information about the concentration distribution and net accumulation of dextran in the interstitial space as a function of postburn time. A diffusion model based on cylindrical geometry was fit to the concentration profile data at each site analyzed, and an apparent diffusion coefficient describing the interstitial transport process was determined. The interstitial transport increased with burn temperature up to a threshold of 70 degrees C, where other factors resulted in significant reduction in the loss of fluorescent macromolecule from the vasculature.

Animals↗

Proteolytic activity in burn wound exudates and comparison of fibrin degradation products and protease inhibitors in exudates and sera.

Proteolytic (caseinolytic) activity in burn wound exudates was screened over the range pH 5.3 to 8.4. Although activity was greatest at pH 8.4 in four of seven exudates, individual differences indicated that different proteases predominate in the local environment of the wound. Paired exudate and serum samples were compared with regard to fibrin degradation products and three protease inhibitors: antithrombin III, a1-protease inhibitor, and a2-antiplasmin. Fibrin degradation products concentration was higher in exudates than in paired sera, indicating the wound as the source of circulating fibrin degradation products rather than intravascular coagulation followed by fibrinolysis. In contrast, all three protease inhibitors exhibited higher concentrations in serum than in the paired exudate. The serum/exudate ratio for AT III differed significantly from that for a1-protease inhibitor and a2-antiplasmin, and the ratio of two inhibitors in serum differed from the ratio of the same two inhibitors in the exudate in two of three comparisons. These findings emphasize the importance of exudate examinations as a reflection of events in the wound itself. The importance of microenvironments is invoked to account for the significant exudate fibrin degradation products titers, which are seen despite the presence of antithrombin III, which could inhibit coagulation, and the presence of a2-antiplasmin, which could inhibit fibrin degradation.

Burns↗

Effects of supplemented omega-3 and omega-6 fatty acid rich oils on the cardiovascular system of thermally injured rabbits: changes in plasma and platelet fatty acids.

The effects of omega-3 fatty acid rich oil (MaxEPA oil), omega-6 fatty acid rich oil (soybean oil), and a combination of omega-3 and omega-6 oils (MaxEPA oil + soybean oil) on cardiovascular health-related parameters of thermally injured and control (sham) rabbits were determined. Plasma and platelet analyses of burned rabbits fed with MaxEPA oil revealed significantly higher concentrations of eicosapentaenoic acid and docosahexaenoic acid + myristic acid. Linolenic acid concentrations declined in animals supplemented with soybean oil + MaxEPA oil. At the end of this study the lowest concentrations of linoleic acid and arachidonic acid were found in the sham and burned groups supplemented with soybean oil + MaxEPA oil. Overall, favorable significant differences in plasma and platelet fatty acids concentrations were found in burned or sham groups supplemented with MaxEPA when compared with those of groups supplemented with soybean oil. These favorable changes in plasma and platelet lipids may have an impact on the risk of cardiovascular disease in thermally injured patients.

Animals↗

The effect of intravenous administration of GABA and brain extracts on blood pressure in the rat.

1. A rat bioassay was used to study pressor substances in brain extracts. 2. A compound with pressor activity in pentolinium-treated rats was extracted from brain, purified using Dowex, Sephadex electrophoresis and identified as gamma-aminobutyric acid (GABA) by HPLC and mass spectrometry. 3. Intravenous GABA (1-5 microgram) or brain extracts caused a dose dependent decrease in blood pressure in pentobarbitone-anaesthetized rats. 4. After ganglion blockade with pentolinium (2 mg/kg subcutaneously), GABA or brain extracts cause a dose dependent increase in rat blood pressure. 5. This pressor effect is reduced by alpha- and beta-blockers (intravenous phentolamine, 0.5 mg/kg and propranolol, 0.05 mg/kg). 6. It is concluded that GABA causes a fall in blood pressure by a central mechanism and ganglion blockade unmasks a pressor effect.

Animals↗

Effects of omega-3 and omega-6 fatty acid-rich oils on the cardiovascular system of thermally injured rabbits: changes in plasma triglycerides, plasma cholesterol, relative blood viscosity, platelet count, and bleeding time.

New Zealand white male rabbits were studied to determine how supplements of soybean oil, soybean + MaxEPA oil, or MaxEPA oil affected their cardiovascular status when they were burned. Plasma triglyceride concentrations increased at 2 hours after burn injury (28 days after supplement administration) and declined by the end of the study in all three experimental groups of rabbits. These same animals showed no noticeable differences in the plasma concentrations of total cholesterol or in the high-density lipoprotein cholesterol subfractions. Plasma low-density/very-low-density lipoprotein cholesterol levels remained unchanged at 2 hours after burn injury/sham treatment but increased by the end of the study in all three experimental groups of rabbits. The mean platelet number was significantly higher in burned/sham treated rabbits given soybean oil supplement as compared with numbers in those given either soybean oil + MaxEPA oil or MaxEPA oil supplement. Plasma relative viscosity was highest in the soybean oil-supplemented rabbits, decreased in animals fed soybean oil + MaxEPA, and lowest in MaxEPA oil-supplemented rabbits. Mean bleeding time was lowest in soybean oil-fed rabbits. The bleeding time was higher in rabbits fed soybean oil+MaxEPA oil and highest in MaxEPA oil-supplemented animals. Platelet number and plasma viscosity were highest in the soybean oil-supplemented rabbits and lowest in the MaxEPA oil-supplemented group. The reverse pattern occurred when bleeding time was established. Overall results obtained suggest that supplementation with oils rich in omega-3 and omega-6 fatty acids may have significant effects on the cardiovascular health of burned male New Zealand white rabbits.

Animals↗