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J L Robotham

Publications and source records attributed to J L Robotham.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of aminophylline on high-energy phosphate metabolism and fatigue in the diaphragm.

BACKGROUND: Diaphragmatic fatigue causes respiratory failure, for which aminophylline has been used as therapy. Because the mechanism of action of aminophylline in reversing diaphragmatic fatigue is unclear, we used in vivo 31P magnetic resonance spectroscopy (MRS) to determine the relation between diaphragmatic activation, force output, and aerobic metabolism. METHODS: Bilateral phrenic stimulation was used to pace the diaphragm in pentobarbital-anesthetized piglets (6-10 weeks old; n = 44). Esophageal and abdominal pressures were measured to calculate transdiaphragmatic pressure (Pdi) (Pdi = abdominal pressure-esophageal pressure) as an index of force output. Activation was determined by the amplitude of the compound action potential of the diaphragmatic electromyogram. Aerobic metabolism was assessed with a 31P MRS surface coil on the right hemidiaphragm with the animal in a 4.7-T magnet. The animals were divided into four groups based on aminophylline loading dose: saline, aminophylline 10 mg/kg (A10), aminophylline 20 mg/kg (A20), and aminophylline 40 mg/kg (A40). After aminophylline loading the diaphragm was paced for 25 min followed by a 10-min recovery. RESULTS: Aminophylline concentrations were 12.2 +/- 0.7, 21.9 +/- 2.4, and 44.9 +/- 3.6 mg/l in the A10, A20, and A40 groups, respectively. Compound action potential amplitude decreased in all groups by 30% after 25 min of pacing. Conversely, Pdi remained at 100 +/- 3% of the initial value after 5 min of pacing in the A40 group but decreased to 75 +/- 3% in the saline group. Pdi recovered completely (103 +/- 17%) in the A40 group but remained depressed (72 +/- 6%) in the saline group. Pdi values were intermediate in the A10 and A20 groups. MRS data revealed inadequate energy supply/demand ratio in the saline group such that the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) increased to 1.01 +/- 0.09 after 5 min of pacing. Pi/PCr remained unchanged in the A40 group and was intermediate in the A10 and A20 groups. beta-Adenosine triphosphate and intracellular pH did not differ among groups or as a function of pacing. Diaphragmatic blood flow increased from a resting value of 35-60 to 300-410 ml.min-1 x 100 g-1 during pacing in all groups and was not affected by aminophylline dose. CONCLUSIONS: Aminophylline, in a dose-dependent fashion, delays the onset of fatigue and improves recovery from fatigue. Delayed fatigue is associated with improved aerobic metabolism as reflected in a low Pi/PCr ratio.

Action Potentials↗
PubMed1995

Hepatic heat shock and acute-phase gene expression are induced simultaneously after celiotomy in the anesthetized pig.

BACKGROUND: The liver plays a central role in the whole organism's response to injury. Expression of hepatic acute-phase and heat-shock genes likely contributes to the restoration of homeostasis after stressful events. However, after prolonged ischemia, hepatic transcription of heat-shock genes can exclude the simultaneous transcription of acute-phase genes. The issue of whether hepatic 72-kd heat-shock protein (hsp72) gene expression is induced under perioperative conditions that do not result in prolonged liver ischemia and whether this might further affect the expression of the acute-phase reactant inter-alpha-trypsin inhibitor (alpha-Ti) was examined. METHODS: Pigs were anesthetized with sodium pentobarbital and ketamine hydrochloride, tracheally intubated, and their lungs ventilated. After celiotomy, a hepatic biopsy sample was obtained. Arterial blood pressure, cardiac output, and total hepatic blood flow were measured. Subsequent biopsies were obtained at 1, 2, 3, 4, and 6 h after the initial biopsy. Arterial norepinephrine concentrations were measured using high-pressure liquid chromatography. Nuclear runoff (run on) analysis and Northern blotting were applied to estimate changes in hsp72 and alpha-Ti gene transcription rates and RNA levels. Western blotting was used to estimate changes in hsp72 levels. RESULTS: Hemodynamic parameters did not change significantly over time. Arterial norepinephrine concentrations were increased at all time points. Hepatic hsp72 RNA levels increased up to sixfold while nuclear runoff assays did not detect significant changes in hsp72 gene transcription rates. The increases in hsp72 RNA levels correlated with accumulation of hsp72 (up to sevenfold). Increases in alpha-Ti transcription rates up to 42-fold were associated with respective increases in alpha-Ti RNA levels (up to 17-fold). CONCLUSIONS: These data demonstrate that hepatic expression of hsp72 is not confined to conditions that lead to prolonged liver ischemia but is also part of the response of the liver to surgery under general anesthesia. Furthermore, these conditions are permissive for the simultaneous RNA expression of the acute-phase reactant alpha-Ti.

Abdomen↗
PubMed1995

Dysregulation of the veno-arterial response in the superior mesenteric artery during endotoxic shock.

OBJECTIVE: To investigate whether the vascular dysfunction in endotoxic shock is associated with inhibition of the veno-arterial response of the superior mesenteric artery. DESIGN: Prospective, concurrent trial. SETTING: Animal laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: Two groups of pigs were anesthetized with ketamine and pentobarbital, mechanically ventilated, and hemodynamically monitored. One group (n = 8) was challenged with Escherichia coli endotoxin (30 micrograms/kg iv), while the other group (n = 4) served as time controls. Portal vein pressure was transiently increased in a series of steps from baseline to 25 mm Hg by partially obstructing portal venous flow. MEASUREMENTS AND MAIN RESULTS: The effects of increases in portal pressure on superior mesenteric artery resistance, superior mesenteric artery fractional flow, and cardiac output were assessed. Under pre-endotoxin conditions, raising portal pressure induced an increase in superior mesenteric artery resistance, a decrease in superior mesenteric artery fractional flow, and no significant change in cardiac output (i.e., a normally regulating veno-arterial response). After endotoxin administration, raising portal pressure induced a decrease in superior mesenteric artery resistance, no change in superior mesenteric artery fractional flow, and a decrease in cardiac output (i.e., a dysregulated veno-arterial response). CONCLUSIONS: Under baseline conditions, a normally regulating veno-arterial response in the mesenteric vascular bed should minimize intestinal blood pooling with acute portal hypertension. Under conditions of endotoxemic shock, the dysregulation of the veno-arterial response could substantially contribute to blood pooling and edema formation in the intestinal vascular bed during septic shock. This phenomenon may account for many of the macro- and microcirculatory manifestations of septic shock.

Animals↗
PubMed1995

Alternations in liver hemodynamics in an intact porcine model of endotoxin shock.

Septic shock decreases preload, increases splanchnic blood pooling and edema formation, and induces hepatic dysfunction. We hypothesized that the hemodynamic effects of endotoxemic shock on the portal venous (PV) and hepatic arterial (HA) vascular beds contribute to this picture. Multipoint pressure-flow relationships were generated to evaluate the slope (resistance or conductance) and effective back pressure (Pback) in each bed in an intact porcine model of endotoxemia. Slope and Pback were determined during endotoxemia over 300 min (n = 8) and compared with sham-treated control studies (n = 5). At time (t) = 60 min, HA slope significantly decreased (P < 0.05) without a change in Pback. The HA buffer response (HABR), defined as a decrease in HA resistance produced by reduction in PV flow (Qpv), was abolished at t = 90 min. The PV Pback significantly increased without a change in PV slope. At t = 300 min, HA slope returned to baseline, and the HABR was present while PV slope and Pback increased (P < 0.05). Fractional flow (flow relative to cardiac output) was constant except for a transient increase in HA fractional flow at t = 60 min. Histological studies showed focal necrosis and hemorrhage without evidence of vasoconstriction or thrombosis. In conclusion, endotoxic shock leads to time-dependent impairment of Qpv with increased PV resistance, causing an increase in splanchnic blood pooling and subsequent decrease in venous return. The HA bed is dilated early with an absent HABR. Later an HABR is present but defined by increased HA resistance for a given Qpv.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of endotoxin on isolated porcine liver: pressure-flow analysis.

The peripheral vascular response to sepsis is characterized by a vasodilatation of the systemic arterial vessels. Pulmonary hypertension with an increase in resistance and back pressure to flow defined by pressure-flow (P-Q) relationships has been reported in experimental sepsis. We hypothesized that endotoxin can induce differential alterations in resistance and back pressure to flow in the liver venous and arterial beds. Ninety minutes after endotoxin administration in intact anesthetized pigs (n = 8), the liver was vascularly isolated and perfused. Steady-state P-Q relationships in both the portal vein (PV) and hepatic artery (HA) were generated at multiple outflow pressures (Pout; 0, 5, 10, and 15 mmHg) and compared with those obtained in control livers (n = 6). Extrapolated zero-flow pressure intercepts (Pback) and slopes of the P-Q relationships were obtained by least squares linear regression analysis. Endotoxemia increased PV Pback (P < 0.05), and Pback always exceeded Pout (P < 0.05) when the latter was raised. In contrast, in controls, no difference was observed between Pback and Pout when the latter was raised. Endotoxemia also increased the PV slope compared with control. Raising Pout from 0 to 15 mmHg decreased PV slope in the endotoxin group to a greater degree than in controls (P < 0.05). In the HA, endotoxin caused a decrease in slope but did not alter Pback. The simultaneous increase in the PV Pback and slope that occurs with endotoxemia decreases splanchnic venous return, pooling blood in the splanchnic compartment for a given total blood volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Role of nitric oxide in porcine liver circulation under normal and endotoxemic conditions.

The role of nitric oxide (NO) in the liver vasculature during baseline and endotoxic shock states was evaluated in 17 anesthetized pigs. Mean systemic arterial pressure, pulmonary arterial pressure, and portal venous pressure and flow, hepatic arterial pressure and flow, and cardiac output were measured. Pressure-flow (P-Q) relationships defined resistances as a back pressure and a slope. Inhibition of nitric oxide synthase (NOS) with NG-nitro-L-arginine methyl ester (L-NAME) at baseline increased mean arterial pressure, pulmonary arterial pressure, hepatic arterial pressure, and the slopes of their P-Q relationships (P < 0.05) but had no effect on portal venous pressure or its P-Q relationship. After endotoxin (10 micrograms/kg iv), NO induced arterial dilation and attenuated increases in portal venous and pulmonary arterial resistances (P < 0.05) that were reversed by L-NAME. NOS inhibition was stereospecifically reversed by L-arginine. Local control of liver blood flow at baseline via the hepatic arterial buffer response and hepatic arterial autoregulation were increased in gain after L-NAME. Endotoxic shock ablated the hepatic arterial buffer response and autoregulation independent of either NO or an alpha-adrenergic-receptor agonist (P < 0.05). Under baseline conditions, NO modulates pulmonary, systemic, and hepatic arterial but not portal venous resistances. NO production during endotoxic shock induces arterial hypotension and hepatic arterial vasodilation and attenuates increases in both portal and pulmonary resistances. NOS inhibition in endotoxic shock could increase morbidity due to a loss of local control of liver blood flow and marked increases in resistance to venous return across both the liver and lungs.

Animals↗
PubMed1995

Effects of PEEP on liver arterial and venous blood flows.

Total venous return decreases with positive end-expiratory pressure (PEEP). It is likely that the liver plays an important role in this response, either through the development of an increase in venous resistance or through an increase in the venous backpressure at the outflow end of the liver. In addition, hepatic arterial flow is reported to be selectively decreased by the application of PEEP. Therefore, to clarify the effects of PEEP on liver hemodynamics, we generated pressure-flow (P-Q) relationships in both liver vascular beds of anesthetized, mechanically ventilated pigs at PEEP of 0, 5, 10, and 15 cm H2O to obtain values of backpressure (Pback, mm Hg) from linear extrapolation of the P-Q relationships and resistance (mm Hg/ml/min/kg) from its slope. PEEP decreased portal vein flow (Qpv) and caused an increase in the liver venous resistance (from 0.08 +/- 0.01 to 0.16 +/- 0.02 mm Hg/ml/min/kg; p < 0.05). Ppvback and right atrial pressure (Pra) increased equally (from 5.1 +/- 0.3 to 9.9 +/- 0.4 mm Hg, p < 0.05, and from 4.0 +/- 0.2 to 8.6 +/- 0.5 mm Hg, p < 0.05, respectively, at PEEP 15). The reduction in portal venous flow was related to an increase in the backpressure to flow (as a result of an increase in Pra) and to an increase in liver venous resistances that may cause blood pooling in the splanchnic compartment and decrease venous return through the liver. PEEP increased Phaback (from 11.2 +/- 0.9 to 14.5 +/- 0.7 mm Hg at PEEP 15, p < 0.05) but did not change hepatic arterial resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Regional control of venous return: liver blood flow.

The aim of the study was to determine whether closing pressures or vascular distensibility can be used to describe liver venous hemodynamics when right atrial pressure is raised. The study was performed using a vascularly isolated pig liver preparation that allowed the independent control of portal vein and hepatic artery inflows and of outflow pressure (Pout). Pressure-flow (P-Q) relationships of both liver vessels were generated at multiple levels of Pout. At Pout of 0 mm Hg, the portal vein P-Q relationship was linear, with a convexity toward the pressure axis at low flows (5 to 10 ml/min/kg). The zero flow pressure was 1.5 +/- 0.2 mm Hg, greater than Pout (p < 0.05). On raising Pout from 0 to 15 mm Hg, the shape of the portal vein P-Q relationships became progressively more linear, with a decrease in slope; no difference between zero flow pressure and Pout was observed. At Pout of 0 mm Hg, the hepatic artery presented a zero flow pressure > Pout. Raising Pout from 0 to 15 and 30 mm Hg resulted in a zero flow pressure always > Pout (p < 0.05). The behavior of the liver vein system is characterized by a zero flow pressure mimicking a classic vascular waterfall and by distensibility, once the waterfall is exceeded. Both factors act to minimize the reduction in venous return with an increased central venous pressure. Flow through the hepatic artery is affected by an increase in backpressure occurring upstream from the sinusoids, reducing arterial inflow for a constant perfusion pressure.

Animals↗
PubMed1995

The acute-phase response.

Inflammation and tissue injury elicit profound changes in the concentrations of several plasma proteins. These proteins are predominantly synthesized in the liver and named acute-phase proteins. The regulatory mechanisms that control this response are highly complex and include the release of various mediators affecting specific subsets of acute-phase genes. Individual mediators can either synergistically enhance or inhibit the effects of other mediators. Binding of mediators to their respective receptors on hepatocytes and transduction of this signal induce changes in acute-phase protein gene expression that are primarily regulated on a transcriptional level. However, under certain conditions post-transcriptional mechanisms may also be involved in this process. Although some acute-phase proteins have been shown to minimize tissue damage, as well as to participate in hemostasis, tissue repair, and regeneration in response to injury, the actual in vivo functions of several acute-phase reactants remain speculative. Measurements of acute-phase protein plasma concentrations can be of diagnostic or prognostic value under certain clinical conditions. Further characterization of the regulatory mechanisms that govern the acute-phase response in vivo could lead to the development of new therapeutic strategies aimed at improving the organism's integrated response to injury.

Acute-Phase Proteins↗
PubMed1995

Endotoxin induces organ-specific endothelial cell injury.

Endothelial cell (EC) injury is observed in clinically important pathological processes, including bacterial endotoxemia. We hypothesized that such pathological processes may exhibit target organ heterogeneity due to organ-specific heterogeneity of endothelial cells. To test this hypothesis, endothelial cells of aorta (AO), pulmonary artery (PA), left ventricle (LV), and right ventricle (RV) were cultured from individual sheep and exposed to bacterial endotoxin. Marked heterogeneity in endotoxin-induced cytotoxicity was observed. AOEC were the most sensitive, followed by PAEC, LVEC, and RVEC. This cytotoxicity was manifested as programmed cell death (apoptosis). All cells were able to express both interleukin-6 and endothelin-1 (ET-1) transcripts. Following exposure to bacterial endotoxin, interleukin-6 transcripts accumulated in all cells, whereas ET-1 expression was constant or slightly decreased. These data suggest that organ-specific heterogeneity of EC responsiveness to endotoxin is a potential determinant of organ-specific resistance to endotoxin and other mediators of injury.

Animals↗
PubMed1994

Pressure-flow analysis of portal vein and hepatic artery interactions in porcine liver.

Interactions between the hepatic arterial and portal venous circulations were investigated in nine intact and eight isolated perfused porcine livers. Pressure-flow (P-Q) relationships were obtained in either the portal vein or hepatic artery with constant baseline or low flow in the other bed and a stable hepatic venous pressure (Phv). The slope was obtained by linear regression analysis of the P-Q relationship, and effective back pressure (Pback) was obtained from the pressure intercept for the portal vein and the measured zero-flow pressure for the hepatic artery. The Pback in the hepatic artery (13.4 +/- 1.5 mmHg) and the portal vein (4.6 +/- 0.3 mmHg) were higher than Phv (P < 0.05). Reducing portal vein flow (Qpv) produced an increase in hepatic artery flow (Qha) (P < 0.05) due only to a decrease in slope (P < 0.05). Decreasing Qha caused an identical change in Pback of the portal vein (P < 0.05) in the intact and isolated liver preparations. A change in Qpv alters the hepatic arterial resistance upstream from the site of a constant arterial Pback. Changes in total flow through the common sinusoidal compartment appear to alter the Pback of the portal vein via hydraulic mechanisms.

Animals↗
PubMed1994

Effect of sleep deprivation on responses to airway obstruction in the sleeping dog.

The effect of sleep deprivation on sleep architecture and respiratory responses to repetitive airway obstruction during sleep was investigated in four chronically instrumented tracheostomized dogs during 12-h nocturnal experiments. A 24-h period of prior sleep deprivation increased (P < 0.05) the rate at which airway obstruction could be induced from 20 +/- 3 (SE) to 37 +/- 10 times/h compared with non-sleep-deprived dogs. During non-rapid-eye-movement sleep the duration of obstruction, minimum arterial hemoglobin saturation, and peak negative inspiratory effort at arousal were 20.5 +/- 1.0 s, 91.7 +/- 0.5%, and 28.4 +/- 1.8 mmHg, respectively, in non-sleep-deprived dogs. Sleep deprivation increased (P < 0.01) the duration of obstruction to 28.0 +/- 0.9 s, worsened (P < 0.05) the minimal arterial hemoglobin desaturation to 85.4 + 3.1%, and increased (P < 0.025) the peak negative inspiratory effort at arousal to 36.1 +/- 1.6 mmHg. Sleep deprivation also caused increases (P < 0.025) in total sleep time, rapid-eye-movement (REM) sleep time, and percentage of time in REM sleep in a 2-h recovery period without airway obstruction at the end of the study. We conclude that airway obstruction in the sleeping dog can reproduce the disturbances in sleep architecture and respiration that occur in obstructive sleep apnea and that prior sleep deprivation will increase apnea severity, degree of somnolence, and REM sleep rebound independent of change in upper airway collapsibility.

Airway Obstruction↗
PubMed1994

Relationship between blood pressure and airway obstruction during sleep in the dog.

The relationship between airway obstruction during sleep and changes in mean arterial pressure (MAP) was investigated in four chronically instrumented tracheostomized dogs during 12-h nocturnal experiments. The MAP response was determined 1) during experimental airway obstruction whenever sleep occurred, 2) over each 12-h experiment, and 3) during a 2-h recovery period at the end of each experiment. The effects of 24 h of sleep deprivation and changes in plasma levels of renin and atrial natriuretic peptide were assessed. In non-rapid-eye-movement sleep, a period of airway obstruction caused MAP to increase (P < 0.002) from 95 +/- 3 (SE) mmHg to 112 +/- 3 mmHg, and this difference was enhanced (P < 0.04) by sleep deprivation. There was an increase of 12 +/- 2 mmHg in the overall MAP over time (P < 0.001) in non-rapid-eye-movement sleep that was sustained in the 2-h recovery period. Plasma levels of renin and atrial natriuretic peptide were constant and unrelated to changes in MAP. We conclude that in the sleeping dog airway obstruction causes an increase in MAP that can be accentuated by prior sleep deprivation and that repetitive airway obstruction will cause an increase in MAP over time that is sustained for > or = 2 h when normal airway patency is restored.

Airway Obstruction↗
PubMed1993

Right and left ventricular cultured endocardial endothelium produces prostacyclin and PGE2.

The endothelium profoundly affects subjacent vascular smooth muscle function. An analogous relationship between endothelial endocardial cells (EEC) and the myocardium is suggested by Brutsaert et al.'s observation that EEC modulate the contractility of subjacent myocardium. Prostanoids are a major product by which vascular endothelium affects smooth muscle, but similar prostanoid production by EEC has not been described. To determine whether both right and left ventricular EEC produce prostacyclin (PGI2) and prostaglandin E2 (PGE2), ovine EEC were cultured. EEC prostanoid production was measured under basal conditions and after stimulation with arachidonic acid or calcium ionophore A23187. EEC from both ventricles demonstrated sustained prostacyclin and PGE2 production. Prostacyclin production was 10 times greater than PGE2. These results suggest that endocardial prostanoid production could act both locally, to modulate platelet and myocardial function, and distally, on downstream vascular tone.

Animals↗
PubMed1993

Effect of anesthesia and surgery on plasma cytokine levels.

Cytokines released in response to stress may have a profound impact on circulatory stability. There is no information on the effect of general anesthesia alone on plasma cytokine levels and little information on cytokine release following surgery. Plasma cytokine levels and hemodynamic parameters were measured during anesthesia and abdominal surgery under sterile and nonpyrogenic conditions in seven pigs anesthetized with ketamine and pentobarbital. Tumor necrosis factor (TNF) was measured by bioassay. Bioassays of low and high sensitivity were used to measure interleukin 6 (IL-6). Measurements were made sequentially during: (1) 4 hours observation with anesthesia alone; (2) 2 hours following laparotomy and traumatic intestinal manipulation (IM) sufficient to produce shock; and (3) after an intravenous bolus of 1 microgram/kg endotoxin as a positive control. Arterial blood pressure decreased following IM from 91.5 +/- 5.8 to 48.6 +/- 3.2 mm Hg, (mean +/- SE, P < .05), with no further change following endotoxin. Heart rate was unchanged during the experiment, and central venous pressure decreased after endotoxin (P < .05). There were no increases in TNF or IL-6 (using a low sensitivity assay) with anesthesia alone or following IM with shock, but both increased after endotoxin administration (P < .05); using a high sensitivity assay, IL-6 did not change during anesthesia alone but did increase fivefold following IM with shock (P < .05) and 50-fold following endotoxin administration (P < .05). We conclude that in a porcine model under sterile and nonpyrogenic conditions, prolonged anesthesia does not increase plasma cytokine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1993

Regulation of acute phase gene expression following surgery and endotoxin administration in the anesthetized pig.

BACKGROUND: The hepatic acute phase response (APR) reflects an organism's integrated response to stress. This APR results in augmented synthesis and secretion of specific procoagulants and antiproteases and a complementary decrease in the synthesis and secretion of several constitutive proteins, such as albumin. The cytokines tumor necrosis factor (TNF) or interleukin-6 (IL-6) have been identified as proximal mediators of the APR in response to endotoxin stress. The authors hypothesized that TNF, IL-6, or both would be the proximal mediators of the APR in response to anesthesia and surgical stress. METHODS: The effects of a standardized surgical stress on the APR in pigs under general anesthesia with sodium pentobarbital and ketamine hydrochloride was investigated. Acute phase gene transcription was assayed in nuclei from serial liver biopsies obtained before and after 2.5 h of surgical stress, and after endotoxin administration. Tumor necrosis factor and IL-6 mRNA levels in this liver tissue were examined by Northern blot hybridization, and simultaneous plasma levels of these cytokines were measured using bioassays. RESULTS: The transcription rates of three positive acute phase genes--chymotrypsin inhibitor, inter-alpha-trypsin inhibitor and beta-fibrinogen--increased seven-, six-, and twofold, respectively (P < 0.05), and the transcription rate of albumin, a negative acute phase gene, decreased to 34% of baseline (P < 0.01) during the 2.5 h of anesthesia and surgical stress. During this initial 2.5 h, plasma concentrations of TNF and IL-6 did not change. Hepatic IL-6 mRNA expression was never observed, and TNF mRNA expression was undetectable in six of seven pigs. Subsequent 10-micrograms/kg endotoxin administration caused 20- and 100-fold increases in plasma concentrations of TNF and IL-6, respectively (P < 0.01), and were associated with substantial hepatic expression of the TNF and IL-6 mRNAs. These increments in cytokines were not associated with any further increase in the acute phase gene transcription rates. Thus, the APR was initially regulated at the transcriptional level during surgical stress independent of, and not augmentable by, an endotoxin-provoked increase in either plasma levels or hepatic mRNA expression of TNF or IL-6. CONCLUSIONS: Surgical stress induced hepatic acute phase gene transcription within 2.5 h in the absence of either systemic or local (hepatic) increases in TNF or IL-6. Subsequent endotoxin-induced increases in TNF or IL-6 did not alter this surgical stress-induced acute phase gene transcription.

Acute-Phase Proteins↗