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K Messmer

Publications and source records attributed to K Messmer.

At least 127 records · Page 7Linked to original sources
PubMed1998

A novel model for the study of synovial microcirculation in the mouse knee joint in vivo.

A novel model for the investigation of the microcirculation in synovial tissue of the mouse knee joint is presented. The mouse knee joint was exposed on a specially designed plexiglass stage with a slight flexion. After partial resection of the skin, the patella tendon was cut transversally, which allowed for visualization of the "Hoffa's fatty body", an intraarticular fatty tissue containing synovial cells on the interior surface of the joint. An intravital fluorescence microscope was adjusted to observe the microcirculation of this intraarticular synovial tissue without opening of the joint capsula. For staining of the plasma, fluorescein isothiocyanate (FITC)-dextran was used, and for the staining of leukocytes rhodamine 6G was used. The tissue investigated presents with a high-density honeycomb-like capillary network, containing some postcapillary venules and a few arterioles. The following parameters were assessed off-line using a computer-assisted microcirculation analysis system: flow and diameter of arterioles and postcapillary venules, as well as functional capillary density. Moreover, leukocyte-endothelial cell interaction was quantified by counting the number of rolling cells and cells adhering to the endothelium in postcapillary venules. As an indication of endothelial leakage, macromolecular extravasation was also assessed. To validate the model, we investigated these parameters at three time points during an observation period of 60 min. There was no change in functional capillary density, nor in vessel diameter after 60 min of observation. Moreover, there was neither a change in the number of rolling cells, nor in the number of cells adhering to the endothelium nor in extravasation of FITC-dextran, thus indicating the stability of the preparation. The new model allows the quantitative analysis of the intraarticular microcirculation of the synovial fatty tissue in vivo. It provides insight into the dynamics of synovial microcirculation and leukocyte-endothelial cell interaction in acute or chronic joint inflammation.

Adipose Tissue↗
PubMed1998

Impact of ischemia-reperfusion injury on dimensional changes of hepatic microvessels.

Dimensional alteration of hepatic microvessels was demonstrated during reperfusion after normothermic hepatic ischemia. Using a specially designed cover glass, it was possible to relocate selected sites of observation and microvessels repeatedly throughout the whole reperfusion time. Twenty minutes of hepatic ischemia resulted in a decrease of sinusoidal diameter (mean +/- SEM; 10.0 +/- 0.3 microns at baseline, 8.2 +/- 0.2 microns after ischemia) and diameter of postsinusoidal venules (26.4 +/- 1.2 at baseline, 23.0 +/- 1.0 after ischemia). In the control group (no ischemia induced) no changes of these parameters were observed. Thus, the reduction of hepatic microvascular cross section was present during the early phase of reperfusion. Hepatic dysfunction was characterized by increased serum activity of liver enzymes and reduction of bile flow in the ischemia-exposed animals. It has been suggested that postischemic dimensional microvascular changes are involved in postischemic liver dysfunction.

Animals↗
PubMed1998

Differential effect of cyclooxygenase metabolites on proinflammatory cytokine release by Kupffer cells after liver ischemia and reperfusion.

BACKGROUND: Liver ischemia and reperfusion (I/R) induce Kupffer cell (KC) activation with increased release of proinflammatory cytokines. Prostaglandins are potent counterregulatory mediators to control the production of cytokines by macrophages. METHODS: To study the role of cyclooxygenase metabolites for the release of proinflammatory cytokines by KC in liver I/R, Sprague-Dawley rats were subjected to 20-minute global hepatic ischemia and 60 minutes of reperfusion. Sham-operated animals were used as controls. Kinetics of spontaneous and lipopolysaccharide (LPS)-induced release of proinflammatory cytokines and prostaglandin E2 (PGE2) by KC were assessed both in the presence and absence of the cyclooxygenase inhibitor ibuprofen. RESULTS: Early after liver I/R (4, 16 hours) the spontaneous secretion of TNF-alpha (+1,058%), IL-1alpha (+152%), and IL-6 (+161%) by KC was increased (P <0.05), while PGE2 release in the I/R group was reduced by 51% (P <0.05) in comparison with the sham-operated group. Increased release of PGE2 in the later period (32 hours) after I/R was associated with decreased TNF-alpha release by KC. Inhibition of PGE2 production by ibuprofen induced a prolonged and enhanced production of TNF-alpha, while the release of IL-1alpha and IL-6 was not affected. CONCLUSIONS: Liver I/R leads to a temporary suppression of PGE2 release by KC, while the release of TNF-alpha is increased. Thus, during early reperfusion, excessive secretion of TNF-alpha by KC may be the result of the absent negative feedback control of cyclooxygenase metabolites.

Animals↗
PubMed1998

Efficacy of myocardial initial reperfusion with 2,3 butanedione monoxime after cardioplegic arrest is time-dependent.

OBJECTIVE: In a previous study, initial reperfusion of isolated hearts after cardioplegic arrest with 2,3 butanedione monoxime (BDM) for 5 min was markedly superior to warm hyperkalemic reperfusion in improving the initial oxygen balance and reducing reperfusion arrhythmias. However, left ventricular contractility was only marginally enhanced. The goal of the present study was to test, wether the efficacy of BDM reperfusion can be enhanced by prolonging the application period. METHODS: 32 Langendorff perfused guinea pig hearts were subjected to 50 min of cardioplegic arrest in St. Thomas Hospital II solution at 37 degrees C for 50 min. Control hearts (n = 8) were immediately reperfused with normal Krebs solution for 30 min. In BDM-5, BDM-20, and BDM-40 hearts (n = 8, each), a 5, 20, or 40 min period of initial BDM reperfusion preceded perfusion with normal Krebs. RESULTS: BDM markedly improved the O2 balance during initial reperfusion by reducing O2 demand by over 50% (p < 0.01) in all treatment groups while coronary flow was maintained. Reperfusion contracture, estimated by the end-diastolic balloon pressure was inhibited by more than 50% in BDM-20 and BDM-40 hearts. Recovery of left ventricular developed pressure, dP/dtmax, and -dP/dtmax was significantly enhanced throughout the reperfusion period only in the BDM-20 group (p < 0.05). Myocardial ultrastructure was best preserved in BDM-20 hearts. CONCLUSIONS: 20 min of initial BDM reperfusion were clearly superior to immediate Krebs reperfusion or a shorter (5 min) or longer (40 min) BDM treatment period in attenuating reperfusion damage. Thus, contraction uncoupling during initial reperfusion by BDM or similarly acting drugs may prove a viable technique to reduce myocardial reperfusion damage in patients undergoing open heart surgery.

Animals↗
PubMed1998

Endothelin 1 induces leukocyte adhesion in submucosal venules of the rat small intestine.

BACKGROUND & AIMS: The release of endothelin 1 (ET-1) and the activation of leukocytes are involved in the pathophysiology of gastrointestinal ischemia/reperfusion injuries. The aim of this study was to define the in vivo relation between ET-1 and endothelial cell-leukocyte interactions. METHODS: Anesthetized rats were studied to characterize the microvascular effects of increasing doses of local and systemic infusions of ET-1 in all layers of an ileal segment. Leukocyte-endothelial interactions were monitored with intravital fluorescence videomicroscopy. The ETA receptor-selective antagonist BQ 610, the novel ETA-receptor antagonist ETR-PI/fl peptide, and the ETB-receptor antagonist IRL 1038 were used to investigate the roles of receptor subtypes. RESULTS: The functional capillary density of the mucosa was significantly decreased by 3 nmol/kg intravenous ET-1. After 30 minutes the rolling fraction of leukocytes reached 90% in the postcapillary venules, and the number of adherent leukocytes was significantly increased after 90 minutes. ETR-PI/fl peptide inhibited leukocyte rolling by 88%, BQ 610 by 73%, and IRL 1038 by 30%. Both ETA-receptor antagonists prevented ET-1-induced firm adhesion. The ETA-receptor antagonists but not IRL 1038 inhibited the ET-1-induced lymphatic muscle and mucosal capillary perfusion failure. CONCLUSIONS: ET-1 induces leukocyte rolling and adherence through a predominantly ETA receptor-mediated mechanism in the submucosal venules of the intestinal microcirculation.

Animals↗
PubMed1998

Microhemodynamics and leukocyte sequestration after pulmonary ischemia and reperfusion in rabbits.

OBJECTIVE: Investigation of leukocyte sequestration in alveolar capillaries and of microhemodynamic changes after pulmonary ischemia/reperfusion injury. METHODS: The kinetics of leukocyte passage and the hemodynamics in pulmonary microcirculation were investigated in 16 rabbits by intravital microscopy. Mean red blood cell velocity and the number of sticking leukocytes were measured in pulmonary arterioles, venules, and capillaries after 1 hour of tourniquet ischemia and 10 minutes and 1 hour after reperfusion. RESULTS: The decrease of red blood cell velocity after reperfusion was associated with a largely increased heterogeneity of blood flow. Immediately after the onset of blood flow, sequestered leukocytes were found in all microvascular segments. An increased number of leukocytes was present in arterioles, venules, and alveolar capillaries 10 minutes and 1 hour after reperfusion. Concomitantly, width of alveolar septa was increased while arterial oxygen tension was reduced, indicating the development of interstitial pulmonary edema. CONCLUSION: Leukocytes are sequestered after pulmonary ischemia and reperfusion not only in alveolar capillaries but also in arterioles and venules, and they may contribute to the development of reperfusion edema.

Animals↗
PubMed1998

Effects of the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl ester and aminoethyl-isothiourea on the liver microcirculation in rat endotoxemia.

BACKGROUND/METHODS: The question whether nitric oxide protects or impairs organ perfusion during early endotoxemia has not been completely answered. To evaluate the regulative function of nitric oxide on organ microvascular perfusion and leukocyte accumulation during endotoxemia, we studied the influence of a non-selective nitric oxide inhibitor and a preferential inducible nitric oxide synthase inhibitor (respectively, N(G)-nitro-L-arginine methyl ester and aminoethyl-isothiourea) on liver microcirculation (intravital fluorescence microscopy) in a rat model. RESULTS: Two hours after intraportal injection of lipopolysaccharide (5 mg/kg in 10 min) the rats were randomly treated and received a bolus dose of N(G)-nitro-L-arginine methyl ester (10 mg/kg, n = 7), aminoethyl-isothiourea (10 mg/kg, n = 6) or normal saline, (n = 7). After 1 h, N(G)-nitro-L-arginine methyl ester blockade yielded a higher rate of non-perfused sinusoids than normal saline (27 +/- 2% vs 19 +/- 5%, p < 0.05). LPS-induced leukocyte stagnation in sinusoids was further increased (p < 0.05) in all groups after 1 h treatment, but N(G)-nitro-L-arginine methyl ester clearly accentuated leukocyte accumulation in sinusoids as compared to normal saline (69 +/- 19% vs 16 +/- 4%, p < 0.05). Both modalities of nitric oxide blockade elicited a significant enhancement in the number of leukocytes adherent to the postsinusoidal venules in contrast to normal saline (N(G)-nitro-L-arginine methyl ester 48 +/- 17%, aminoethyl-isothiourea 33 +/- 9% vs normal saline 1 +/- 5%, p < 0.05). CONCLUSIONS: We conclude that complete nitric oxide blockade aggravates lipopolysaccharide-induced hepatic microvascular perfusion failure and enhances leukocyte accumulation, in both sinusoids and post-sinusoidal venules. The preferential inducible nitric oxide synthase inhibitor aminoethyl-isothiourea has a moderate negative effect, favoring leukocyte adhesion in postsinusoidal venules, and its usefulness demands further research, especially concerning its late effects.

Animals↗
PubMed1998

Programs for assessment of spatial heterogeneity of regional organ blood flow.

Regional organ blood flow (RBF) is spatially heterogeneous. Relative dispersion (standard deviation S.D./mean) is often used to assess heterogeneity of RBF. Relative dispersion is a global measure of heterogeneity and is strongly influenced by the tissue sample size making comparisons between research groups inappropriate. Spatial correlation (s.c.) of blood flow is, on the other hand, averaged local self similarity. Both parameters change oppositely secondary to interventions. Fractal dimension (D) is a scale-independent measure of spatial heterogeneity and thus facilitates comparison of data. Programs for calculation of s.c. and D have not been published. We present two portable computer programs written in C+2 for calculating s.c. and D. The programs were validated with six computer generated data sets of known heterogeneity. The results were in agreement with data from the literature: we conclude that the programs accurately calculate spatial correlation and fractal dimension of 1-, 2-, or 3-dimensional perfusion matrices.

Humans↗
PubMed1998

Formation of nitric oxide by rat and hamster alveolar macrophages: an interstrain and interspecies comparison.

Nitric oxide (NO) plays an important role in non-specific host defense, which can be recognized by its antimicrobial and cytotoxic activity against pathogens. However, there appear to exist interspecies differences in the ability of macrophages to generate NO. The object of this study was to determine whether there exist intraspecies differences in the production of NO. We compared NO formation by alveolar macrophages (AM) from five different rat strains (Sprague Dawley, Wistar, Lewis, Fisher, and Brown Norway), two different stocks of Syrian Golden hamsters, and one stock of Chinese hamsters. The AM were harvested by bronchoalveolar lavage and stimulated in vitro with various concentrations of LPS and/or IFN-gamma. The oxidation product of NO, nitrite, was measured in the AM supernatant by the Griess reaction. Upon stimulation with LPS and/or IFN-gamma, AM from all five rat strains were able to release NO, but the amount of NO produced differed significantly among the rat strains. However, none of the stimuli was able to induce AM from the two stocks of Syrian Golden hamsters as well as AM from the stock of Chinese hamsters to release measurable amounts of NO. These findings point to distinct regulatory mechanisms of the NO pathway in AM from different species and to variations of this mechanism in the AM from the investigated rat strains.

Animals↗
PubMed1998

Non-invasive temperature mapping using MRI: comparison of two methods based on chemical shift and T1-relaxation.

PURPOSE: To implement and evaluate the accuracy of non-invasive temperature mapping using MRI methods based on the chemical shift (CS) and T1 relaxation in media of various heterogeneity during focal (laser) and external thermal energy deposition. MATERIALS AND METHODS: All measurements were performed on a 1.5 T superconducting clinical scanner using the temperature dependence of the water proton chemical shift and the T1 relaxation time. Homogeneous gel and heterogeneous muscle phantoms were heated focally with a fiberoptic laser probe and externally of varying degree ex vivo by water circulating in a temperature range of 20-50 degrees C. Magnetic resonance imaging data were compared to simultaneously recorded fiberoptic temperature readings. RESULTS: Both methods provided accurate results in homogeneous media (turkey) with better accuracy for the chemical shift method (CS:+/-1.5 degrees C, T1:+/-2.0 degrees C). In gel, the accuracy with the CS method was +/-0.6 degrees C. The accuracy decreased in heterogeneous media containing fat (T1:+/-3.5 degrees C, CS: +5 degrees C). In focal heating of turkey muscle, the accuracy was within 1.5 degrees C with the T1 method. CONCLUSION: Temperature monitoring with the chemical shift provides better results in homogeneous media containing no fat. In fat tissue, the temperature calculation proved to be difficult.

Animals↗
PubMed1998

Normovolaemic haemodilution and hyperoxia have no effect on fractal dimension of regional myocardial perfusion in dogs.

Hypervolaemic haemodilution makes myocardial perfusion more homogenous as reflected by reduced fractal dimension of regional myocardial perfusion. The clinically more commonly performed acute normovolaemic haemodilution, however, has not yet been studied in this respect. Hyperoxic ventilation with 100% oxygen is used in conjunction with haemodilution to compensate for low oxygen content by increasing physically dissolved oxygen in plasma. Since hyperoxia is known to cause disturbance in microcirculatory regulation we studied the effects of acute normovolaemic haemodilution to haematocrit (hct) 20 +/- 1% and hyperoxia on regional myocardial perfusion heterogeneity in 22 anaesthetized dogs using fractal and correlation analysis. Regional myocardial perfusion was assessed with radioactive microspheres. The results of the study were that heart rate, blood volume and arterial pressure were unchanged during haemodilution. Cardiac index was 3.6 +/- 0.7 L min-1 m-2 before and 4.6 +/- 0.7 L min-1 m-2 after haemodilution (P < 0.05). Fractal dimension (D) of regional myocardial perfusion was 1.17 +/- 0.10 at baseline. Neither haemodilution (D = 1.19 +/- 0.10) nor hyperoxia (D = 1.17 +/- 0.10) altered fractal properties of regional myocardial perfusion. Spatial correlation of blood flow to adjacent tissue samples before haemodilution was 0.58 +/- 0.15. Haemodilution and hyperoxia did not significantly influence spatial correlation (0.57 +/- 0.12 vs. 0.60 +/- 0.09; ns). We conclude that neither acute normovolaemic haemodilution nor haemodilution in combination with hyperoxic ventilation alter physiological myocardial perfusion heterogeneity.

Animals↗
PubMed1998

In vivo assessment of the influence of cold preservation time on microvascular reperfusion injury after experimental small bowel transplantation.

BACKGROUND: This study describes the impact of prolonged cold storage on microvascular reperfusion injury of transplanted rat small bowel isografts. METHODS: In vivo fluorescence microscopy was used to assess intestinal microcirculation after 6, 12, 18 and 24 h of cold (4 degrees C) ischaemia in University of Wisconsin solution and 20-90 min of reperfusion. Sham-operated animals served as controls. RESULTS: Whereas 6 and 12 h of ischaemia did not affect functional capillary density of the intestinal graft mucosa, villous perfusion was significantly impaired after 18 and 24 h of cold preservation. Similarly, microvascular perfusion of circular and longitudinal muscle was not affected after 6 h, but deteriorated following prolonged cold ischaemia. Leucocyte-endothelial cell interaction in submucosal venules was significantly enhanced after 6 h of ischaemia with peak values after 12 and 18 h. A progressive reduction of lymphatic capillary drainage indicated an ischaemia time-related deterioration in graft function. CONCLUSION: The results provide evidence that leucocyte-endothelial cell interaction in submucosal venules of the transplanted intestine is a primary step in the manifestation of reperfusion injury following short periods of cold ischaemia.

Animals↗
PubMed1998

Effects of adenosine on cardiopulmonary functions and oxygen-derived variables during endotoxemia.

OBJECTIVES: To determine the effects of a prophylactic intravenous infusion of adenosine on cardiopulmonary functions and oxygen-derived variables in a porcine model of endotoxemia. DESIGN: Prospective, randomized, placebo-controlled, unblinded study. SETTING: University research laboratory. SUBJECTS: Thirty country bred pigs, aged 6 to 7 wks, weighing 24.9 +/- 0.65 (SEM) kg body weight. INTERVENTIONS: Pigs were anesthetized by i.v. pentobarbital and fentanyl, intratracheally intubated, and mechanically normoventilated with a gas mixture of nitrous oxide/oxygen = 1:1. Intravascular catheters were inserted to allow for determination of arterial, central venous blood pressure, pulmonary artery occlusion pressure, cardiac output, and sampling of blood for gas analyses. Group 1 (n = 10) received a 330-min intravenous infusion of Salmonella abortus equi endotoxin (5 microg/kg body weight x hr). Group 2 (n = 10) received an additional intravenous infusion of adenosine (150 microg/kg body weight x min), started 30 mins before the infusion of endotoxin. Control groups 3 and 4 (n = 5 for both groups) received adenosine or physiologic saline, respectively. MEASUREMENTS AND MAIN RESULTS: Parameters of cardiopulmonary function and oxygen-derived variables were calculated from pulmonary artery catheter measurements and blood gas analyses using standard formula. Plasma concentrations of purine compounds (adenosine, inosine, hypoxanthine) were determined by high-performance liquid chromatography. Since tumor necrosis factor-alpha plays a central role in the development of endotoxic shock, concentrations of this cytokine were determined in serum by enzyme-linked immunosorbent assay. Infusion of adenosine before the beginning of the infusion of endotoxin increased plasma concentrations of the nucleoside from 193 +/- 72 to 553 +/- 65 nmol/L and decreased the systemic vascular resistance by 50%. Although acting as a potent vasodilator under control conditions, adenosine did not aggravate the arterial hypotension elicited by endotoxemia but significantly increased cardiac output by a comparably small decrease in systemic vascular resistance, prevention of pulmonary vasoconstriction, and improvement of left ventricular performance. Despite significant pulmonary vasodilation, gas exchange was not worsened but slightly improved by adenosine. With the increase in cardiac output and arterial oxygenation, systemic oxygen delivery almost doubled. This adenosine-induced oxygen flux was not a surplus but was most likely utilized by tissues, as suggested by the much earlier beginning of the increase in the systemic oxygen consumption and the attenuation of the decrease in the gastric mucosal pHi. No effects of adenosine were observed on the endotoxin-induced increase in serum concentrations of tumor necrosis factor-alpha. CONCLUSIONS: Infusion of adenosine might be useful to improve flow-dependent oxygen delivery and tissue oxygenation during endotoxic shock without the induction of adverse cardiopulmonary side effects. The beneficial hemodynamic effects of adenosine appear not to be mediated by the inhibition of the release of tumor necrosis factor-alpha.

Adenosine↗
PubMed1998

Noninvasive measurement of regional cerebral blood flow by near-infrared spectroscopy and indocyanine green.

Clinicians lack a practical method for measuring CBF rapidly, repeatedly, and noninvasively at the bedside. A new noninvasive technique for estimation of cerebral hemodynamics by use of near-infrared spectroscopy (NIRS) and an intravenously infused tracer dye is proposed. Kinetics of the infrared tracer indocyanine green were monitored on the intact skull in pigs. According to an algorithm derived from fluorescein flowmetry, a relative blood flow index (BFI) was calculated. Data obtained were compared with cerebral and galeal blood flow values assessed by radioactive microspheres under baseline conditions and during hemorrhagic shock and resuscitation. Blood flow index correlated significantly (rs = 0.814, P < 0.001) with cortical blood flow but not with galeal blood flow (rs = 0.258). However, limits of agreement between BFI and CBF are rather wide (+/- 38.2 +/- 6.4 mL 100 g-1 min-1) and require further studies. Data presented demonstrate that detection of tracer kinetics in the cerebrovasculature by NIRS may serve as valuable tool for the noninvasive estimation of regional CBF. Indocyanine green dilution curves monitored noninvasively on the intact skull by NIRS reflect dye passage through the cerebral, not extracerebral, circulation.

Algorithms↗
PubMed1998

Reduction of skin flap necrosis by transdermal application of buflomedil bound to liposomes.

The influence of the vasoactive drug buflomedil hydrochloride bound to liposomes (2 mg/ml) was investigated in an arterial pattern skin flap model using the ear of hairless mice. For flap creation, the ear is cut at four-fifths of its base, which leaves the anterior artery as the only feeding vessel of the flap. Liposomes were locally applied daily for 30 minutes up to 5 days after flap creation. Microvascular perfusion in the proximal, central, and distal parts of the flap was measured by laser Doppler flowmetry. The border between perfused and nonperfused tissue was visualized by intravital fluorescence microscopy using fluorescein isothiocyanate (FITC)-labeled dextran (Mr 150,000) for contrast enhancement of microvessels. The area of nonperfused tissue was assessed by digital planimetry. Five days after flap creation the nonperfused area amounted to 23.8 +/- 3.1 percent of total flap surface in treated ears compared with 46.1 +/- 5.6 percent in untreated ears (p < 0.05) of the contralateral side. Additional preoperative treatment for 5 days did not further reduce the area of nonperfused tissue (treated ears, 23.0 +/- 1.3 percent; control ears, 44.6 +/- 5.1 percent). Microvascular perfusion was higher in the postoperatively treated ears in all parts of the flap from day 1 after flap creation until termination of the experiment. Five days after flap creation, perfusion as measured by laser Doppler flowmetry was reduced to 46.0 +/- 10.8 percent in the distal part in control ears compared with 91.9 +/- 8.3 percent (p < 0.05) in treated animals. Additional preoperative treatment for 5 days did not result in further improvement. It is concluded that local application of the vasoactive drug buflomedil docked to liposomes could be of therapeutic use in the treatment of ischemic tissue, including skin flaps.

Animals↗
PubMed1998

Endothelin (ET)-1 induced mucosal damage in the rat small intestine: role of ET(A) receptors.

The role of endothelin (ET)-1 as a mediator of small intestinal mucosal perfusion failure and tissue damage was investigated in the rat using intravital fluorescence videomicroscopy. The effects of intravenous infusion of ET-1 (3 nmol/kg) on functional capillary density, mucosal thickness, and the degree of mucosal damage were evaluated. Administration of ET-1 caused pronounced mucosal injury with a significant reduction of mucosal thickness compared with vehicle-treated control animals. Concomitantly, villous functional capillary density was markedly reduced 30 and 90 min after the infusion of ET-1. ET(A) receptor blockade by pretreatment with BQ 610 or with the novel ET(A) receptor antagonist ETR-P1/FL peptide prevented ET-1 induced capillary perfusion failure and mucosal damage. In contrast, the ET(B) receptor antagonist IRL 1038 was not effective. These results indicate that, acting via the ET(A) receptor, elevated levels of circulating ET-1 under various pathophysiological conditions, such as septic or hemorrhagic shock, might impair nutritive perfusion of the intestinal mucosa and contribute to tissue injury.

Animals↗