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Biomedical subjects

S I Myers

Publications and source records attributed to S I Myers.

At least 19 recordsLinked to original sources
PubMed2005

Bile duct ligation induced acute inflammation up-regulates cyclooxygenase-2 content and PGE2 release in guinea pig gallbladder smooth muscle cell cultures.

INTRODUCTION: This study examines hypotheses that BDL induces increased guinea pig gallbladder smooth muscle PGE2 release by up-regulation of COX-2. METHODS: BDL, Sham and Control Hartley guinea pig gallbladders were placed in cell culture, grown to confluence and underwent Western Blot analysis for smooth muscle cell content of COX-1, COX-2, Prostacylin Synthase, actin, caldesmon, vinculin, meta-vinculin and tropomyosin and were assayed for basal release of 6-keto-PGF(1alpha), PGE2 and TxB2 by EIA. RESULTS: BDL did not alter content of smooth muscle cytoskeletal proteins. BDL for 48 h increased smooth muscle cell release of PGE2 and 6-keto-PGF(1alpha) by 3-fold or more when compared to the Control and Sham groups. Western Blot analysis showed increased content of COX-2 in the BDL group. CONCLUSIONS: BDL for 48 h markedly increased endogenous guinea pig smooth muscle cell PG release, which was due to increased COX-2 synthesis.

Animals↗
PubMed2001

Effect of indomethacin on gallbladder inflammation and contractility during acute cholecystitis.

OBJECTIVE: The aim of this study was to determine whether the prostaglandin synthase inhibitor indomethacin reverses the inflammation and abnormal gallbladder contractility that occur after common bile duct ligation (CBDL), a model of acute cholecystitis. METHODS: Gallbladder muscle contractility was studied in vitro in normal, CBDL, and sham-operated guinea pigs. Animals were treated with saline or indomethacin in vivo. Acetylcholine (ACh) was used to directly contract the muscle and electric field stimulation (EFS) to activate intrinsic nerves. Hematoxylin and eosin-stained slides of muscle strips were scored for inflammation. RESULTS: CBDL in saline-treated animals increased the inflammation score and decreased gallbladder muscle contractility to ACh and EFS. Indomethacin decreased the inflammation score and partly reversed the smooth muscle contractile response to ACh 6 and 24 h after CBDL, but not at 48 h. Indomethacin did not reverse the CBDL-induced decrease in nerve-evoked contractions. CONCLUSION: Gallbladder inflammation and contractile dysfunction after CBDL are partly reversed with indomethacin at 6 and 24 h, but not at 48 h. This suggests that, early in the course of CBDL, the inflammation and contractile dysfunction are, in part, prostaglandin-mediated.

Acute Disease↗
PubMed2000

Effect of acalculous cholecystitis on gallbladder neuromuscular transmission and contractility.

BACKGROUND: Impaired smooth muscle contractility is important in the pathophysiology of acalculous cholecystitis. Common bile duct ligation (CBDL) is a model of acalculous cholecystitis, producing acute inflammatory changes and decrease in gallbladder smooth muscle contractility. The aim of this study was to determine whether there is coexistent dysfunction of neural efferent motor pathways of the gallbladder after CBDL. MATERIALS AND METHODS: Gallbladder muscle contractility was studied in vitro in normal, CBDL, and sham-operated guinea pigs. Electric field stimulation (EFS; 2-16 Hz) was used to activate intrinsic nerves and exogenous acetylcholine (ACh) was used to directly stimulate the muscle. H&E-stained slides of muscle strips were scored for inflammatory changes. RESULTS: After CBDL, there was a progressive increase in the inflammation score and decrease in gallbladder muscle contractility to ACh. There was also a progressive decline in EFS-induced contractility when expressed as absolute force or normalized to the maximal muscle contractile response to ACh. The nitric oxide synthase inhibitor l-NNA (10 microM) increased EFS-induced contractions by 50 +/- 25% (P = 0.05) in CBDL animals but had no effect in sham surgical controls. CONCLUSIONS: CBDL with its acute gallbladder inflammation affects gallbladder contractility by two mechanisms: (1) decreased smooth muscle contractility, and (2) decreased neurally mediated contractions. The neurally mediated alterations result from dysfunction of cholinergic excitatory nerves and upregulation of nitric-oxide-mediated inhibition of smooth muscle contractility.

Acetylcholine↗
PubMed1999

Enhanced bradykinin-stimulated prostaglandin release in the acutely inflamed guinea pig gallbladder is due to new synthesis of cyclooxygenase 1 and prostacyclin synthase.

BACKGROUND: Our previous studies have shown that acute gallbladder (GB) inflammation increases endogenous bradykinin (BK)-stimulated prostaglandin (PG) release and inhibits guinea pig (GP) GB contractility. This study examines the hypothesis that exaggerated PG release following BK stimulation in the inflamed guinea pig GB is due to new protein synthesis of cyclooxygenase 1 (COX-1) and prostacyclin synthase (PS). MATERIALS AND METHODS: Male Hartley GPs (450-550 g) were anesthetized and underwent common bile duct ligation (BDL, a model of acute inflammation). GBs were harvested after 3 days from BDL and control groups. Tissue slices were prepared and placed in oxygenated tissue culture medium at 37 degrees C for 1 h (basal) and for a second hour in medium alone (carrier, Car), medium plus 10(-6) M BK, or medium plus 10(-6) M BK plus cycloheximide 100 microgram/ml (BK + CX). The medium was assayed for net release of 6-keto-PGF1alpha (PGI2 metabolite), thromboxane B2 (TxB2), PGE2, leukotriene B4 (LTB4), and C4 (LTC4) by enzyme immunoassay and data are reported as nanograms per milligram of protein. GB tissue from control and BDL groups was examined for COX-1, COX-2, PS, and inducible nitric oxide synthase (iNOS) content by Western blot analysis, analyzed by densitometry, and reported as densitometry units. RESULTS: All data were analyzed by ANOVA and t test and reported as means +/- SEM, N >/= 5.BK increased the release of PGI2 and PGE2 from the control group and markedly exaggerated release of PGI2 and PGE2 from the BDL GP gallbladder. This exaggerated PGI2 and PGE2 release was greatly diminished by inhibition of new protein synthesis with cycloheximide. TxB2, LTB4, and LTC4 showed no significant differences between any groups. COX-1 and PS contents were significantly elevated in the BDL group compared with control. COX-2 and iNOS were not present in control or BDL GBs. CONCLUSIONS: These data suggest that the enhanced BK-stimulated PG release seen in the acutely inflamed GP gallbladder is due to the synthesis of new COX-1 and PS enzymes.

Acute Disease↗
PubMed1999

Effect of experimental acalculous cholecystitis on gallbladder smooth muscle contractility.

Gallbladder motility is impaired in chronic cholelithiasis but has not been studied in acute acalculous cholecystitis. The aim of this study was to determine the effects of acute acalculous inflammation on gallbladder contractility using the common bile duct ligation (CBDL) model in guinea pigs. Three groups of guinea pigs were studied: CBDL, normal, and sham surgical controls. Gallbladder dimensions were measured, and muscle strips were used for histology and in vitro contractility studies. CBDL resulted in progressive gallbladder distension, increased serum bilirubin, and gallbladder inflammation. There was a progressive decline in muscle contractility in the CBDL group as evidenced by a decrease in the contractile response to potassium and bethanechol with the duration of CBDL. In conclusion, CBDL in the guinea pig produces acute gallbladder inflammation and decreased gallbladder muscle contractility. Direct inhibition of muscle function is indicated by impaired contractile responses to potassium depolarization and bethanechol stimulation. Although the mechanism of the decrease in contractility with CBDL is unknown, we speculate that impaired muscle contractility is secondary to inflammation and may play a role in the clinicopathology of acute acalculous cholecystitis.

Animals↗
PubMed1998

The effect of sequential injuries on splanchnic perfusion and eicosanoid release.

BACKGROUND: This study examines the hypothesis that sequential burn injury followed by intraabdominal sepsis induces significantly greater splanchnic hypoperfusion and reduced intestinal PGI2 release than either injury independently. MATERIALS AND METHODS: Anesthetized Sprague-Dawley rats were randomized to one of four groups: BURN (45% body surface area scald burn) + cecal ligation and puncture (CLP); BURN alone; CLP alone; or uninjured controls (SHAM). Twenty-four hours following injury, superior mesenteric artery (SMA) blood flow was measured with a doppler flow probe. Splanchnic eicosanoid release (6-keto-PGF1alpha, metabolite of PGE2; TxB2, metabolite of TxA2; and PGE2) was measured in mesenteric venous effluent utilizing an isolated, perfused bowel preparation. RESULTS: SMA blood flow was no different than that of controls 72 h following BURN injury alone; whereas CLP alone resulted in a 80% reduction in splanchnic blood flow when compared with controls (P < 0.001). SMA blood flow in animals sustaining BURN + CLP was only modestly reduced from controls (P = 0.04) and 3.6 times greater than that of animals sustaining CLP alone (P < 0.001). PGI2 was the dominant eicosanoid released by the intestine with levels 10 times greater than TxB2 and nearly 50 times greater than PGE2. CLP either alone or when combined with BURN was associated with a 60% decrease in splanchnic PGI2 release when compared to controls (P < 0.05). CONCLUSIONS: These data suggest that moderate BURN injury in rats attenuates the severe reduction in splanchnic perfusion associated with intraabdominal sepsis and that this occurs despite profound reductions in the release of the endogenous splanchnic vasodilator PGI2.

Animals↗
PubMed1998

Mediators of restenosis.

The multitude of actions and interacting components involved in inciting and sustaining myointimal hyperplasia and restenosis effectively precludes the use of a single type of intervention. No pharmacologic approach has been conclusively shown to prevent coronary restenosis after balloon angioplasty or graft restenosis after peripheral arterial bypass. Although no human studies have been performed to prevent restenosis with gene therapy, the animal data are compelling, and the local delivery of various inhibitory agents may represent a novel way of preventing restenosis in vascular beds subjected to endovascular or traditional open procedures. Until these modalities are proved effective, the treatment of vascular stenosis due to internal hyperplasia remains within the domain of the surgeon.

Angioplasty, Balloon↗
PubMed1998

Alveolar macrophage response to remote organ injury.

Intestinal reperfusion (IR)-induced pulmonary edema has been related to endogenous pulmonary thromboxane A2 (TxA2) release. This study examines the hypothesis that alveolar macrophages (aMphis) activated during IR are an important cellular source of TxA2 in this model. Anesthetized Sprague Dawley rats underwent 120 min of intestinal ischemia and 60 min of reperfusion (IR) or sham operation (Sham). aMphis were isolated by bronchoalveolar lavage and incubated in Krebs buffer for 30 min, after which the supernatant was analyzed for TxB2 (metabolite of TxA2) and prostaglandin E2. Other parameters of aMphi activation measured included lysosomal enzyme release (beta-glucuronidase), superoxide (O2-) release, and procoagulant activity. aMphis from animals sustaining IR generated more than twice as much TxA2 and prostaglandin E2 as did those isolated from controls (p < .05). Other evidence of aMphi activation included a nearly 100-fold increase in procoagulant activity, a 7-fold increase in beta-glucuronidase release, and a 2.5-fold increase in O2- release over that of controls (p < .05). These data suggest that TxA2 is a major eicosanoid product of aMphis during IR and that aMphis may be an important cellular participant in IR-induced pulmonary microvascular injury, either directly by releasing O2-, lysosomal enzymes, and pro-coagulant factors, or indirectly by generating TxA2.

Animals↗
PubMed1997

Thromboxane A2 mediates increased pulmonary microvascular permeability after intestinal reperfusion.

This study examines the hypothesis that intestinal reperfusion (IR)-induced pulmonary thromboxane A2 (TxA2) release increases local microvascular permeability and induces pulmonary vasoconstriction. Sprague-Dawley rats underwent 120 min of intestinal ischemia and 60 min of IR. Sham-operated animals (Sham) served as controls. After IR or Sham, the pulmonary vessels were cannulated, and the lungs were perfused in vitro with Krebs buffer. Microvascular permeability was quantitated by determining the filtration coefficient (Kf), and pulmonary arterial (Ppa), venous (Ppv), and capillary (Ppc) pressures were measured to calculate vascular resistance (Rt). After baseline measurements, imidazole (TxA2 synthase inhibitor) or SQ-29,548 (TxA2-receptor antagonist) was added to the perfusate; then Kf, Ppa, Ppv, and Ppc were again measured. The Kf of lungs from IR animals was four times greater than that of Sham (P = 0.001), and Rt was 63% greater in the injured group (P = 0.01). Pc of IR lungs was twice that of controls (5.4 +/- 1.0 vs. 2.83 +/- 0.3 mmHg. IR vs. Sham, respectively; P < 0.05). Imidazole or SQ-29,548 returned Kf to baseline measurements (P < 0.05) and reduced Rt by 23 and 17%, respectively (P < 0.05). IR-induced increases in Pc were only slightly reduced by 500 micrograms/ml imidazole (14%; P = 0.05) but unaffected by lower doses of imidazole (5 or 50 micrograms/ml) or SQ-29,548. These data suggest that IR-induced pulmonary edema is caused by both increased microvascular permeability and increased hydrostatic pressure and that these changes are due, at least in part, to the ongoing release of TxA2.

Animals↗
PubMed1997

Downstream effects of splanchnic ischemia-reperfusion injury on renal function and eicosanoid release.

This study examines the hypothesis that intestinal ischemia-reperfusion (I/R) injury contributes to renal dysfunction by altered renal eicosanoid release. Anesthetized Sprague-Dawley rats underwent 60 min of sham or superior mesenteric artery (SMA) occlusion with 60 min of reperfusion. The I/R groups received either allopurinol, pentoxifylline, 1-benzylimidazole, or carrier before SMA occlusion. In vivo renal artery blood flow was measured by Transonic flow probes, the kidneys were then perfused in vitro for 30 min, and the effluent was analyzed for eicosanoid release and renal function. Intestinal I/R caused a twofold increase in the ratio of renal release of thromboxane B2 to prostaglandin E2 and to 6-ketoprostaglandin F1alpha compared with the sham level, with a corresponding 25% decrease in renal sodium and inulin clearance and renal blood flow. Pentoxifylline or allopurinol pretreatment restored renal eicosanoid release and renal sodium and inulin clearance to the sham level but did not alter renal blood flow. Pretreatment with 1-benzylimidazole restored renal function, eicosanoid release, and renal blood flow to sham levels. These data suggest that severe intestinal I/R contributes to the downregulation of renal function. The decrease in renal function is due in part to toxic oxygen metabolites, which occur in the milieu of altered renal eicosanoid release, reflecting a decrease in vasodilator and an increase in vasoconstrictor eicosanoids.

Allopurinol↗
PubMed1996

The effect of intestinal reperfusion on renal function and perfusion.

This study examines the effect of intestinal reperfusion injury (IIR) on renal blood flow and relates this temporally to changes in renal ATP levels and renal tubular function. Sprague-Dawley rats underwent 120 min of intestinal ischemia and 60 min of reperfusion (IIR). Renal blood flow was measured with radiolabeled microspheres and a Doppler flow probe. Renal dysfunction was quantitated by measuring inulin clearance and fractional excretion of sodium (FENa) in the isolated perfused organ. Renal tissue ATP levels were measured using a luciferase-luciferin assay. Sham-operated animals served as controls (SHAM). Renal blood flow was reduced by > 80% in the animals sustaining IIR when compared to baseline measurements (P < 0.05) or SHAM (P < 0.05). Temporally this reduction in renal blood flow was associated with a 25% reduction in tissue ATP levels (P < 0.05). The kidneys of animals sustaining IIR had a significantly greater FENa than did those of controls. These data support the notion that IIR is associated with a profound reduction in renal blood flow which is temporally related to reduced renal tissue ATP levels and renal tubular dysfunction.

Adenosine Triphosphate↗
PubMed1996

Hepatic hypoperfusion after intestinal reperfusion.

BACKGROUND: Intestinal ischemia-reperfusion injury (IIR) induces hepatic and pulmonary dysfunction and thus has been used as a model of multiple organ failure syndrome. This study examines the hypothesis that hepatic blood flow is markedly reduced in this injury model. METHODS: Sprague-Dawley rats underwent 120 minutes of intestinal ischemia and 60 minutes of reperfusion (IIR). Hepatic blood flow was measured with radiolabeled microspheres and Doppler flow probes. Hepatic dysfunction was quantitated by measuring bile flow and serum alanine aminotransferase and hepatic tissue adenosine triphosphate levels. Sham-operated animals served as controls. RESULTS: Intestinal ischemia reduced portal flow by 66% when compared with sham-operated animals (p = 0.0001) but had no effect on hepatic arterial flow. In contrast, reperfusion reduced hepatic artery flow by 80% when compared with controls (p = 0.002) with most of this change occurring within 5 minutes of reperfusion. IIR induced a 63% reduction in bile flow (p < 0.05), a fivefold rise in serum alanine aminotransferase level (p < 0.0002), and a 33% reduction in hepatic adenosine triphosphate level (p < 0.05). CONCLUSIONS: These data suggest that IIR induces profound hepatic hypoperfusion, which is temporally related to acute hepatic dysfunction. This observation suggests that hepatic ischemia may contribute to IIR-induced liver injury.

Alanine Transaminase↗
PubMed1996

Late outcome of amputees with premature atherosclerosis.

BACKGROUND: Peripheral atherosclerosis in young adults has been associated with a high amputation rate. Our purpose was to examine the natural history of amputees with premature atherosclerosis. METHODS: We compared 50 consecutive young patients undergoing dysvascular amputation who were 49 years of age or younger (mean age +/- SEM, 43 +/- .7 years) with 75 consecutive men and women ranging in age from 60 to 75 years (mean age, 67 +/- .6 years) who were undergoing major amputations for atherosclerosis during the same period. RESULTS: Before undergoing amputation 46 (92%) patients in the study group underwent a mean of 3 +/- 0.3 vascular operations, and 49 (65%) older patients in the control group underwent a mean of 2 +/- 0.2 vascular operations (p = 0.003). The mean time from onset of symptoms to first amputation was not different in the study group versus the control group. Of those patients surviving until discharge, 20 (45%) patients in the study group and 21 (31%) patients in the control group became community or household ambulators, whereas 24 (55%) patients in the study group and 47 (69%) patients in the control group were confined to wheelchairs or were bedridden (p = 0.17). Seventeen (74%) patients in the study group who did not require contralateral amputations became community ambulators, as did 18 (38%) members of the control group (p = 0.01). Twenty (40%) patients in the study group and 39 (52%) patients in the control group died during the study period. The mean age at death was 48 +/- 1 years for the study group and 69 +/- .8 years for the control group (p < 0.001). Cumulative 5-year survival (62% patients in study group, 47% patients in control group) was not different between the two groups (p = 0.41, Kaplan-Meier). CONCLUSIONS: Compared with older counterparts, amputees with premature atherosclerosis have a higher number of failed bypasses before undergoing amputation and die at a younger age. However, both groups have a similar cumulative survival after amputation. Fewer than one half of young patients undergoing dysvascular amputation ultimately achieve ambulation, suggesting that major amputations are a harbinger of long-term disability and dependency in these patients. Because young patients had a higher potential for rehabilitation after unilateral amputation, these patients should be monitored closely for development of ischemia in the contralateral limb.

Adult↗
PubMed1996

Lipoprotein (a), homocysteine, and hypercoagulable states in young men with premature peripheral atherosclerosis: a prospective, controlled analysis.

PURPOSE: Elevated lipoprotein (a) (Lp[a]) lipoprotein, total homocysteine, and hypercoagulable states (HCS) have all been implicated as risk factors for premature-onset atherosclerosis. This study was performed to determine the prevalence of these abnormalities in young men with chronic lower extremity ischemia (peripheral vascular disease [PVD]) and to determine their relative strengths as risk factors for premature peripheral atherosclerosis. METHODS: We analyzed 50 young white men (aged 45 years or younger at onset of symptoms) and compared them with 45 age-matched white male control subjects. RESULTS: Atherosclerotic risk factors were similar in both groups. The mean (+/- SEM) Lp(a) lipoprotein level was 36 +/- 6 mg/dl among the study patients, compared with 14 +/- 2 mg/dl among control subjects (p = 0.02, Mann-Whitney). Twenty (40%) study patients and seven (16%) control subjects had Lp(a) lipoprotein levels of 30 mg/dl or greater (atherosclerotic risk threshold) (p = 0.01, odds ratio = 3.62, confidence interval (CI) 1.4 to 9.5). Positive HCS panels (antiphospholipid antibodies or deficiencies in antithrombin III, protein C, or protein S) were nearly twice as prevalent in study patients (n = 15, 30%) as in controls (n = 8, 18%), but this difference did not achieve statistical significance. The mean total plasma homocysteine level among the study patients was 15.9 +/- 0.9 mumol/L, which was not significantly different from the mean control value of 14.7 +/- 0.7 mumol/L. Lp(a) lipoprotein was related to risk of premature PVD through a linear logistic relationship (p = 0.003, odds ratio per each 1 mg/dl Lp(a) change was 1.03, CI 1.0 to 1.1). Multivariate analysis with stepwise logistic regression selected two variables: Lp(a) lipoprotein > or = 30 mg/dl (p = 0.01, odds ratio = 3.6, CI 1.3 to 9.9) and family history (p = 0.07, odds ratio = 2.2, CI 0.9 to 5.3). Tests of interaction demonstrated no effect between Lp(a) lipoprotein, HCS, and homocysteine. CONCLUSIONS: Lp(a) lipoprotein of 30 mg/dl or greater is an independent risk factor for premature peripheral atherosclerosis in men. None of the other examined variables exhibited a significant association with premature PVD.

Adult↗
PubMed1996

Estrogen increases male rat aortic endothelial cell (RAEC) PGI2 release.

Estrogen has been proposed as a negative risk factor for development of peripheral vascular disease yet mechanisms of this protection are not known. This study examines the hypothesis that estrogen stimulates rat aortic endothelial cell (RAEC) release of PGI2. Male Sprague-Dawley rat abdominal aortic 1-mm rings were placed on 35 mm matrigel plates, and incubated for 1 week. The cells were transferred to a Primaria 60-mm dish and maintained from passage 3 in RAEC complete media and experiments performed between passages 4-10. Cells were incubated with Krebs-Henseleit buffer (pH 7.4) containing carrier or increasing concentrations of beta-estradiol or testosterone for 60 min. The effluent was analyzed for eicosanoid release of 6-keto-PGF1 alpha (6-keto, PGI2 metabolite), PGE2 and thromboxane B2 (TXB2) by EIA (hormone stimulated-basal). Cells were analyzed for total protein by the Bradford method and for cyclooxygenase-1 (COX-1) and prostacyclin synthase (PS) content by Western blot analysis and densitometry. Testosterone did not alter RAEC 6-keto-PGF1 alpha release, whereas estrogen increased RAEC 6-keto-PGF1 alpha release in a dose-related manner. Estrogen preincubation (10 ng/ml) decreased COX-1 and PS content by 40% suggesting that the estrogen-induced increase in male RAEC PGI2 release was not due to increased synthesis of COX-1 or PS. These data support the hypothesis that estrogen stimulation can increase endogenous male RAEC release of PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Long-term resuscitation of hemorrhage/reperfusion injury (H/R) stimulates renal PGE2 release.

This study examines the hypothesis that long-term resuscitation with hyperalimentation (TPN) following acute hemorrhage/reperfusion (H/R) injury stimulates renal release of PGE2. Male Sprague-Dawley rats were anesthetized and subjected to sham or hemorrhage to 30 mmHg for 30 min followed by reperfusion. All rats were placed on TPN for 5 days, then underwent laparotomy for in vivo renal artery and aortic blood flow for 60 min. The kidney was perfused in vitro with Krebs-Henseleit buffer at 3 ml/min (pH 7.4, 37 degrees C) and venous effluent was collected for analysis of PGE2, 6-keto-PGF1 alpha and thromboxane B2 by EIA. Hemorrhage/reperfusion followed by TPN for 5 days increased renal PGE2 2-fold and decreased in vivo renal artery blood flow by 50% compared to the sham group. Hemorrhage/reperfusion followed by TPN did not alter release of the other eicosanoids measured. These data suggest that the kidney has a limited capacity to maintain renal blood flow by increasing release of PGE2 when the animal is subjected to long-term resuscitation with TPN following mild hemorrhage/reperfusion injury.

Animals↗
PubMed1996

Endotoxic shock after long-term resuscitation of hemorrhage/reperfusion injury decreased splanchnic blood flow and eicosanoid release.

OBJECTIVE: The authors examine the hypothesis that hemorrhage/reperfusion injury predisposes the splanchnic bed to decreased prostacyclin (PGl2) release and blood flow after subsequent endotoxin challenge. SUMMARY BACKGROUND DATA: Prostacyclin is a potent vasodilator that has been demonstrated to be an important regulator of splanchnic blood flow. Previous studies have demonstrated that during resuscitation from severe hemorrhage, there is a marked reduction in intestinal PGl2 levels, which is associated with reduced splanchnic perfusion. METHODS: Anesthetized Sprague-Dawley rats underwent hemorrhage to a mean arterial pressure of 30 mmHg for 30 minutes followed by the reinfusion of shed blood. Then the animals were maintained on total parenteral nutrition (TPN) for 10 days, after which time they received 20 mg/kg Escherichia coli endotoxin intraperitoneally. Aortic and superior mesenteric artery (SMA) blood flow was monitored with a Doppler flow probe. The splanchnic bed was excised and perfused in vitro for measurement of venous effluent eicosanoid concentrations. Controls consisted of animals that received TPN and endotoxin but did not undergo hemorrhage and resuscitation (sham). RESULTS: Total parenteral nutrition support of sham animals followed by endotoxin challenge did not alter splanchnic eicosanoid release or blood flow. Hemorrhage/reperfusion animals supported by long-term TPN and challenged with endotoxin demonstrated a threefold decrease in splanchnic prostacyclin metabolite (6-keto-PGF1 alpha) release and a 50% decrease in SMA blood flow. CONCLUSIONS: Hemorrhage/reperfusion injury predisposes the splanchnic bed from rats sustained with long-term TPN to decreased release of PGl2 and SMA blood flow when challenged with endotoxin as a second injury.

Animals↗