Biomedical subjects

H Redl

Publications and source records attributed to H Redl.

At least 19 recordsLinked to original sources

PubMed2006

NON-activated protein C as post-treatment after spinal cord compression injury in rats.

BACKGROUND: Neuroprotective effects of recombinant human activated Protein C (rhAPC) in models of Spinal Cord Injury (SCI) and ischemic stroke have been reported in rodents. To rule out immunogenicity of rhAPC and to possibly maintain the physiological PC/thrombin balance the use of zymogen PC in SCI might be preferable. Although activation of Protein C (PC) has been demonstrated in rats, the efficacy and drug safety of NON activated PC has not been previously tested in experimental SCI. METHODS: Twelve rats were subjected to 40 g compression of the spinal cord at TH11 for 20 minutes and randomly allocated to either the NON activated PC (25 IU/kg) or the Placebo group (saline).Results. 25 IU treatment yielded improved recovery from SCI compared to placebo and the triple fold dose of PC (75 IU/kg) was subsequently tested to detect treatment associated complications (TAC). Treatment was administered as a single shot via the right vena jugularis forty minutes after onset of compression. The observation period was 5 weeks in 25 IU treated and 1 week in the 75 IU treated rats. Improvement of motor function recovery was measured with behaviour tests and electrophysiology. FINDINGS: Single shot treatment with 25 IU/kg of NON activated PC led to improved recovery in terms of behaviour and electrophysiology. TACs neither occurred in the 25 IU nor in the 75 IU group within one week. CONCLUSION: NON activated PC is a potent and safe drug in experimental SCI and should be considered for treatment in neurotrauma.

Animals↗

PubMed2006

Adverse effects of porcine small intestine submucosa implants in experimental ventral hernia repair.

BACKGROUND: Biomeshes made of porcine small intestine submucosa (SIS) have recently been suggested for repair of ventral hernia. A fully biodegradable combination of implant and fibrin sealant fixation was assessed in a new rat model with sutures serving as control. METHODS: In 10 Sprague-Dawley rats, two defects per animal were created in the abdominal wall left and right of the linea alba (1 cm in diameter), and the peritoneum was spared. The lesions were left untreated for 10 days to achieve a chronic condition and were then covered with SIS (2 x 2 cm), sealed or sutured (n = 10 per group). Randomization allowed sealant and sutures in one animal. Animals were killed on postoperative day 17, and implant sites were analyzed macroscopically, histologically, and microbiologically. RESULTS: Abscedation, encapsulation, and putrid seroma were observed in all samples, regardless of fixation technique. Histology revealed lytic necrosis and extensive inflammatory response of the surrounding tissue. Tissue samples obtained from three implant sites were positive for beta-hemolytic Streptococcus. SIS was not detectable after 17 days. CONCLUSIONS: Adverse effects were observed using SIS in an experimental model of ventral hernia and were not linked to fixation method or study design. Further experimental investigations on SIS are necessary before its clinical use in hernia repair.

Animals↗

PubMed2005

Fibrin sealing versus stapling of hernia meshes in an onlay model in the rat.

Incisional and inguinal hernia repair are among the most common procedures of general surgery. Mesh fixation by means of staples or sutures may lead to severe complications. The use of fibrin sealant (FS) has been suggested as alternative, but data on biocompatibility and adhesive strength of FS in combination with macroporous meshes is limited. Ventral hernia (n = 8 per group) was treated in rats in onlay technique with two types of meshes, fibrin sealed or stapled. TI-Mesh (TMxl) extralight and VYPROII (VPII) were tested 17 days post op. No failure in mechanical tests (tensile and burst strength) occurred in sealed or stapled meshes. Histology revealed equally good tissue integration and neovascularization in all groups. Fibrin sealant yields excellent fixation in experimental hernia repair. This rat model is suitable for testing meshes and fixation techniques.

Animals↗

PubMed2005

Chitosan particles agglomerated scaffolds for cartilage and osteochondral tissue engineering approaches with adipose tissue derived stem cells.

It is well accepted that natural tissue regeneration is unlikely to occur if the cells are not supplied with an extracellular matrix (ECM) substitute. With this goal, several different methodologies have been used to produce a variety of 3D scaffolds as artificial ECM substitutes suitable for bone and cartilage tissue engineering. Furthermore, osteochondral tissue engineering presents new challenges since the combination of scaffolding and co-culture requirements from both bone and cartilage applications is required in order to achieve a successful osteochondral construct. In this paper, an innovative processing route based on a chitosan particles aggregation methodology for the production of cartilage and osteochondral tissue engineering scaffolds is reported. An extensive characterization is presented including a morphological evaluation using Micro-Computed Tomography (microCT) and 3D virtual models built with an image processing software. Mechanical and water uptake characterizations were also carried out, evidencing the potential of the developed scaffolds for the proposed applications. Cytotoxicity tests show that the developed chitosan particles agglomerated scaffolds do not exert toxic effects on cells. Furthermore, osteochondral bilayered scaffolds could also be developed. Preliminary seeding of mesenchymal stem cells isolated from human adipose tissue was performed aiming at developing solutions for chondrogenic and osteogenic differentiation for osteochondral tissue engineering applications.

Adipose Tissue↗

PubMed2003

The effect of ketamine/xylazine anesthesia on sensory and motor evoked potentials in the rat.

STUDY DESIGN: Experimental laboratory investigation of the effect of anesthesia on evoked potentials in rats. OBJECTIVES: To define the optimal ketamine/xylazine anesthesia levels for the recording of different evoked potentials. SETTING: BioSurgery Preclinical Department, Baxter BioScience, Vienna, Austria. METHODS: Rats were implanted with cranial screws that allow stimulation and recording of evoked potentials. Somatosensory evoked potentials (SEPs), brainstem-derived motor evoked potentials (BMEPs) and corticomotor evoked potential (CMEPs) were recorded under different levels of anesthesia. The recorded signals were evaluated by measuring their latencies and amplitudes. The level of anesthesia was assessed by scoring the hind limb withdrawal reflex. RESULTS: All three signals showed a strong dependency on the level of anesthesia. The observed effects, however, differed between the three signals. SEP amplitudes and latencies declined as animals slowly transgressed from deep to light anesthesia. In contrast, BMEP amplitudes were larger and latencies shorter in light anesthesia than in deep anesthesia. CMEPs finally were hard to record under deep anesthesia, but were easily recorded in light anesthesia. BMEPs that were recorded during light anesthesia also showed a significant change in configuration that was coupled with a notable increase in the variability of its amplitudes. CONCLUSIONS: The level of ketamine/xylazine anesthesia affects evoked potentials and thus should be controlled during electrophysiological recording. Our results suggest that SEPs should be best recorded during deep anesthesia, while BMEPs and CMEPs are best recorded during intermediate and light anesthesia.

Adrenergic alpha-Agonists↗

PubMed2003

Circulating S100B is increased after bilateral femur fracture without brain injury in the rat.

BACKGROUND: S100B is an acknowledged marker of brain damage. However, trauma without brain damage also causes an increase in S100B. S100B concentrations are highest in multiple trauma patients with long bone fractures. Clinically, extensive long bone fractures are associated with haemorrhagic shock and haemorrhagic shock per se is associated with increased S100B. The aim of our experimental study was to verify the S100B increase in long bone fracture without haemorrhagic shock. METHODS: and results. Bilateral femur fracture was carried out in 10 anaesthetized rats. Blood samples were drawn for immuno-luminometrical S100B measurement 5, 15, 30, 120, and 240 min after fracture. Mean arterial pressure (MAP), heart rate, and body temperature were monitored continuously. S100B increased after bilateral femur fracture and reached a peak 30-120 min after fracture (P<0.001). MAP remained at a level which is not associated with shock in rats. Heart rate and body temperature remained unchanged. Autopsy verified open bilateral femur fracture surrounded only by small zones of clotted blood. CONCLUSIONS: S100B is increased in bilateral femur fracture without haemorrhagic shock in rats. This finding suggests that bone marrow is a potential extracerebral source of S100B.

Animals↗

PubMed2003

Delivery of high dose VEGF plasmid using fibrin carrier does not influence its angiogenic potency.

Delivery of DNA mixed with a degradable matrix carrier was supposed to improve transgene expression. Using a rabbit hind-limb ischemia model, we tested the angiogenic potency of plasmid encoding human vascular endothelial growth factor (pSG5-VEGF165) entrapped in fibrin sealant. Animals were injected intramuscularly with 500 microg of pSG5-VEGF165 or control plasmid, dissolved in saline (PBS) or fibrin glue. After 14 days, presence of delivered constructs and expression of transgene was confirmed in injected muscles of all animals. There were no significant differences in the levels of human VEGF mRNA and protein between VEGF-PBS and VEGF-fibrin groups (Mann-Whitney test). Accordingly, pSG5-VEGF165 regardless of the way of delivery, induced similar increases in capillary density within treated muscles (ANOVA). Control plasmid did not show any effects. In conclusion, injection of pSG5-VEGF165 into ischemic adductor muscle leads to synthesis of human VEGF and increases the number of capillaries. Fibrin carrier does not influence its angiogenic potential.

Animals↗

PubMed2002

Applying circular posterior-hinged craniotomy to malignant cerebral edemas.

Malignant brain edemas are often fatal, regardless of whether they are treated conservatively with sedation, blood pressure management, mannitol-therapy, hyperventilation and hypothermia, or non-conservatively with routine trepanation. Unfortunately, temporal trepanation may result in significant brain damage through herniation of the cerebrum at the edges of the trepanation openings. In one case of a 26-year-old male with severe head injury, a circular posterior-hinged craniotomy (CPHC) was performed after an ineffective unitemporal trepanation for evacuation of an acute subdural hematoma. This ultimately successful operation prompted experimental and morphologic investigations on a new surgical procedure for lowering intracranial pressure (ICP). In 12 of 15 human cadavers, an experimentally ICP was lowered by a CPHC with between 9-21 mm of frontal elevation of the calvaria. Using computer simulation, the frontal elevations of the calvaria were "virtually" performed on 3D reconstructions from CT scans of skulls, and the intracranial volume gained was measured with a computer software program. The volume increase of the cranial cavity showed a relatively constant relation to the cranial capacity and was increased by 6.0% (+/-0.4%) or 78 cm(3) with a 10 mm elevation and by 12.4% (+/-0.7%) or 160 cm(3) with a 20 mm elevation. There were no significant differences with skulls of different ages or ethnic origin; however, a significant effect of gender (F = 7.074; P < or = 0.013) on the gained volume in percent of the cranial capacity for the 20 mm elevation was observed. This difference can be explained by the inverse relationship between volume increase and cranial capacity (r = -0.507; P < or = 0.004).

Adult↗

PubMed2002

Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats.

BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.

Animals↗

PubMed2001

Experimental evidence suggesting that nitric oxide diffuses from tissue into blood but not from blood into tissue.

The aim of this study was to evaluate in vivo whether nitric oxide (NO) is able to diffuse from blood into tissues and vice versa from tissues into blood. We used an in vivo model of intestinal ischemia (superior mesenteric artery occlusion) selectively increasing NO levels in intestinal tissue and an infusion of L-arginine selectively increasing NO levels in blood. In this model we followed formation of nitrosyl complexes of hemoglobin (Hb-NO) in blood and nitrosyl-diethyldithiocarbamate-iron complexes (DETC--Fe--NO) in ischemic intestine and normoxic tissues by means of electron paramagnetic resonance spectroscopy. NO trapping by DETC--Fe in the tissues resulted in a reduction of Hb--NO levels in blood accompanied by the formation of water-insoluble DETC--Fe-NO complexes in ischemic intestine and normoxic tissues both during ischemia and during reperfusion. Administration of L-arginine increased NO levels in blood but neither in ischemic intestine nor in normoxic tissue. Our data suggest that NO released in blood from endothelial cells does not diffuse into tissue. In contrast, NO formed in tissue diffuses into blood. The latter indicates that NO formed in tissues may exert its biological activities systematically.

Animals↗

PubMed2001

[Callus development after bored and unbored femoral interlocking nailing. An experimental study].

This was a prospective randomized baboon animal study, the study protocol was approved by the ethical committee according to the international guidelines for animal research projects. In 8 animals a midschaft femoral osteotomy was stabilized with reamed femoral interlocking nailing and in 8 animals by unreamed locked femoral nailing. Polychrome sequence bone labeling was done 5 weeks postop. with calcein-green, 8 weeks postop. with xylenol-orange and 10 weeks postop. with oxytetracycline. 10 weeks postop. the animals were sacrificed, the femurs explanted and planimetric and epifluorescence histomorphometric evaluation of serial transverse sections were done. In planimetric histomorphometric evaluation in unreamed femoral nailing a mean endostal callus formation was recorded with 28.0 +/- 9.9 mm2 per section and in reamed femoral nailing with 11.5 +/- 5.0 mm2 (p < 0.001). Periostal callus formation was recorded in the unreamed group with 238.7 +/- 87.1 mm2 per section and in the reamed group with 142.1 +/- 71.9 mm2 (p < 0.001). In epifluorescence histological evaluation endostal as well as periostal callus formation was more extensive and earlier after unreamed than reamed femoral nailing. Endostal callus formation was found in all animals after unreamed femoral nailing, and was present in 2 out of 8 specimen in the reamed group. Also 1 out of 8 animals in the reamed group developed a non-union. Unreamed femoral nailing with low diameter interlocking nails proved to be safe regarding bone healing in this experimental model with obvious advantages both in amount and time course of callus formation compared to reamed femoral nailing. Based on this results unreamed femoral nailing techniques can be recommended for femoral fractures.

Animals↗

PubMed2001

Evaluation of total vs. regional blood perfusion with a laser Doppler imaging system in the rat epigastric flap.

Monitoring systems to measure flap survival are either invasive, touch the surface of the tissue, or have problems in reproducibility. The authors sought to determine the efficacy of a laser Doppler imaging (LDI) system to measure perfusion in a myocutaneous flap, by producing a two-dimensional picture of the flap without touching the surface. They compared total flap perfusion with perfusion in selected areas of interest after flap surgery. The perfusion in the left groin of Sprague-Dawley rats was measured before and after surface rubbing, skin injury, and during different lighting conditions. The perfusion of the epigastric flap before and over a period of 60 min after elevation was measured, and values were compared to pre-surgical values and to sham-operated animals. They determined the differences between single and running-suture techniques after flap surgery, as well as between venous and/or arterial occlusion. Surface rubbing, skin injury, and light influenced the LDI image. After flap elevation, total flap perfusion remained stable, while the distal area (area 8, n = 7) of the flap showed a statistically significant decrease in perfusion (71 +/- 5.9 vs. 92 +/- 9.5 percent perfusion units--PU; p < .05). The proximal areas (1 to 3, n = 7) of the flap had a higher perfusion at 60 min after flap surgery, compared with sham-operated (n = 8) animals (118 +/- 12.5 vs. 97 +/- 10.4 percent PU; p < .05). The running-suture technique was followed by decreased perfusion on the peripheral side of the flap, compared with the single-suture technique (73.7 +/- 9.2 vs. 99.2 +/- 4.9 percent PU; n = 2). The LDI was able to visualize venous and/or arterial occlusion after flap surgery. Under standardized circumstances (light, temperature), the LDI was efficient in measuring regional flap circulation experimentally. While total flap perfusion after flap surgery remained stable, perfusion in the distal flap decreased significantly.

Animals↗

PubMed2001

Circulatory changes after prolonged ischemia in the epigastric flap.

The circulation system seems to have early encounters with pathophysiologic processes during ischemia and reperfusion, such as overproduction of oxygen radicals, nitric oxide depletion, and leukocyte plugging. The aim of this study was to determine the superficial perfusion and vessel distribution of the epigastric flap with a laser Doppler Imaging (LDI) system during ischemia/reperfusion, and to observe the clinical outcomes 7 days after reperfusion in a separate set of animals. An epigastric flap from male Sprague-Dawley rats (320 to 380 g) was used to assess perfusion in sham animals (n=6) or in 12 hr-ischemia animals (12 hr of ischemia and 3 hr of reperfusion, n = 10) with the LDI system. In a separate experiment, flap size, flap failure index, and histologic sections of the flap from sham animals (n=6) and 12-hr ischemia animals (n=6) were evaluated 7 days after reperfusion. Evaluation of the vessel distribution demonstrated a diffuse picture of flap perfusion after clamp release. Moreover, in the distal portion of the flap, circulation stopped immediately, resulting in a significantly decreased perfusion in the 12-hr ischemia animals during reperfusion, when compared with pre-surgical values (100 percent) or sham animals (77 +/- 26.5 vs. 108 +/- 9.6 percent PU). On day 7, the flaps of animals after ischemia and reperfusion showed significant shrinkage, an increase in flap failure index, as well as necrosis, edema, and leukocyte infiltration. Based on the findings, the authors propose that, after prolonged ischemia, the circulation becomes diffuse, and "no-reflow" occurs in the distal portions of the myocutaneous flap during reperfusion. Perfused areas, assessed with the LDI early during reperfusion, might still become necrotic after several days. In the authors' flap model, edema formation and leukocyte infiltration seem to be related more to ischemia reperfusion damage than to thrombus formation.

Animals↗

PubMed2001

Serial recording of sensory, corticomotor, and brainstem-derived motor evoked potentials in the rat.

A method is presented for serial recording of corticomotor evoked potentials (CMEPs), brainstem-derived motor evoked potentials (BMEPs), and somatosensory evoked potentials (SEPs) via permanently implanted cranial screws. One screw was positioned posterior to lambda (posterior screw), and two screws were positioned over the cortical hind limb areas (cortical screws). SEPs were elicited by stimulation of the hind paw and recorded from the contralateral cortex. BMEPs were stimulated via the posterior screw and recorded from both hind limbs, whereas CMEPs were elicited by repeated bipolar stimulation of the cortex and recorded from the contralateral hind limb. BMEPs and CMEPs differed in several points and can be considered as completely separate motor evoked potentials. While BMEPs consisted of a prominent negative peak with short latency (5-7.5 ms), CMEPs were represented by polyphasic signals with long latencies (17-22 ms). The cortical origin of the CMEPs was confirmed by transecting the corticospinal tracts, which abolished the CMEPs but spared the BMEPs. SEPs consisted of three consecutive peaks with mean latencies of the initial peak ranging between 15 and 17 ms. Dorsal column transection also abolished SEPs. In healthy rats, all three signals were recorded for six consecutive weeks. Signal parameters did not change significantly within this observation period. Rats tolerated the screws and the repeated measurements very well and no negative affect on animal behavior was noted. Thus, this method allows serial recording of SEPs, CMEPs, and BMEPs in chronic rat models.

Animals↗

PubMed2001

Continuous venovenous hemofiltration improves arterial oxygenation in endotoxin-induced lung injury in pigs.

BACKGROUND: Hypoxemia is common in septic acute lung failure. Therapy is mainly supportive, and most trials using specific inhibitors of key inflammatory mediators (ie., tumor necrosis factor alpha, interleukin 1) have failed to prove beneficial. The authors investigated if a nonspecific blood purification technique, using zero-balanced high-volume continuous venovenous hemofiltration (CWH), might improve arterial oxygenation in a fluid-resuscitated porcine model of endotoxin-induced acute lung injury. METHODS: Piglets of both sexes weighing 25-30 kg were anesthetized and mechanically ventilated. After baseline measurements, animals received an intravenous infusion of 0.5 mg/kg endotoxin (Escherichia coli lipopolysaccharide). One hour after endotoxin, animals were randomly assigned to either treatment with CWH (endotoxin + hemofiltration, n = 6) or spontaneous course (endotoxin, n = 6). At 4 h after randomization, animals were killed. Hemofiltration was performed from femoral vein to femoral vein using a standard circuit with an EF60 polysulphone hemofilter. RESULTS: Endotoxin challenge induced arterial hypoxemia, an increase in peak inspiratory pressure, pulmonary hypertension, and systemic hypotension. Treatment with CWH did not improve systemic or pulmonary hemodynamics. However, arterial oxygenation was increased in endotoxin-challenged animals at 5 h after completion of endotoxin infusion, as compared with animals not receiving CVVH (arterialoxygen tension, 268+/-33 vs. 176+/-67 mm/Hg, respectively, P < 0.01). In addition, treatment with CWH attenuated the endotoxin-induced increase in peak inspiratory pressure and increased lung compliance. CONCLUSION: These results suggest that nonspecific blood purification with high-volume CWH improves arterial oxygenation and lung function in endotoxin-induced acute lung injury in pigs, independent of improved hemodynamics, fluid removal, or body temperature.

Animals↗

PubMed2001

Organ specific formation of nitrosyl complexes under intestinal ischemia/reperfusion in rats involves NOS-independent mechanism(s).

Intestinal ischemia/reperfusion may lead to local and distant organ damage involving nitric oxide (NO). NO rapidly reacts with heme/non-heme-iron-yielding nitrosyl complexes, which can be determined directly by electron paramagnetic resonance spectroscopy. The aim of the present study was to characterize nitrosylation reactions induced by transient intestinal ischemia in blood and tissues. We used electron paramagnetic resonance spectroscopy and reverse transcription polymerase chain reaction analyses to estimate nitrosyl complex levels and inducible NO synthase mRNA expression in rats subjected to superior mesenteric artery occlusion for 60 min followed by the reperfusion. Nitrosyl hemoglobin concentrations in circulating blood were significantly increased during ischemia and reperfusion. Nitrosyl hemoglobin complexes were detected in ischemic intestine, but not in normoxic lung and liver or reperfused intestine. Administration of N-G-monomethyl-L-arginine, a non-specific NO synthase inhibitor, did not affect the formation of circulating nitrosyl complexes. Moreover, inducible NO synthase mRNA was not found in intestinal tissues at 30 min of reperfusion. Our data suggest an organ-specific NO formation indicated by the increased nitrosylation reaction in ischemic intestinal tissue, but not in the distant normoxic organs, in spite of high circulating nitrosyl hemoglobin levels. NO involved in nitrosylation under intestinal ischemia/reperfusion is probably formed by NO synthase-independent mechanism(s).

Animals↗

PubMed2001

Possible role of TNF on procalcitonin release in a baboon model of sepsis.

Procalcitonin (PCT) has been described as an early and discriminating marker of bacteria-associated sepsis in patients. However, little is known of its source and actions, especially with regard to its relation to tumor necrosis factor (TNF). TNF is responsible for the release of several other mediators of sepsis e.g., chemokines. We tested the hypothesis that plasma PCT levels during sepsis differ with regard to the degree of TNF availability. Severe hyperdynamic sepsis was induced in baboons (n = 14) by i.v. infusion of live E. coli (approximately 2 x 10(9) colony-forming units/kg) over 2 h. Animals were pretreated 2 h before E. coli either with 1 mg/kg humanized anti-TNF antibody (CDP571) or placebo (Ringer solution). Plasma PCT levels at baseline was barely detectable, but increased to about 4000 pg/mL at 4 h after E. coli infusion. Levels were maximal between 8 and 24 h and had returned nearly to baseline at 72 h. Although no TNF could be measured in the treated group, PCT levels were not different between the placebo and the TNF antibody treatment group. We conclude that PCT levels are not dependent on the systemic presence of TNF in an E. coli sepsis model in baboons. Such sepsis induced PCT release is clearly different from the previously reported PCT release during infusion of rhTNF in volunteers or chimpanzees.

Animals↗

PubMed2001

Beat-to-beat evaluation of cardiac function in low-dose endotoxemia using a conscious sheep model.

The effects of very low doses of endotoxin (20 ng/kg/h for 8 h) were evaluated in a conscious sheep model in which introducers for catheters for monitoring pressure and ventricular dimensions had been previously inserted so that the studies could be performed without anesthesia and without a previous thoracotomy. Analog data was obtained at hourly intervals for 10 h and again at 24 h and was used to construct a beat-to-beat analysis of left ventricular performance. Only minimal effects were observed on heart rate, end diastolic pressure, arterial pressure, cardiac output, or cardiac work, although there was a significant rise in pulmonary artery pressure at 1 h of infusion. Despite the absence of changes in heart rate, preload, or afterload, maximal dp/dt decreased significantly by 4 h and remained decreased for the 10-h observation period; it returned to normal at 24 h. End systolic elastance decreased at 6 h and Pmax/EDV, a new indicator of performance, also decreased at 6 and 9 h. Thus, systolic performance decreased. Negative dp/dt did not change, but time for relaxation from 80% to 20% of peak ventricular pressure increased significantly at 5, 6, and 8 h. Plasma TNF-alpha was also measured and showed a significant rise at 2 h, but rapidly decreased thereafter. These results indicate an early depression of myocardial contractility and distensibility at doses of endotoxin insufficient to produce measurable effects on arterial pressure or cardiac output.

Animals↗