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Biomedical subjects

H Redl

Publications and source records attributed to H Redl.

At least 127 records · Page 7Linked to original sources
PubMed1991

Hyperdynamic sepsis in baboons: I. Aspects of hemodynamics.

The baboon has a number of advantages as a shock model, as its physiological as well as its biochemical behaviour is similar to man. Therefore we have tried to set up a model to mimic the early hyperdynamic phase of clinical sepsis. Seven baboons, 21-25 kg body weight were kept under EEG servocontrolled anesthesia for 8 hr. During this time live E. coli (ATC #33985) 2 x 10(10) BW/8 hr were continuously infused intravenously. Adequate fluid supply with Ringer's solution (up to 40 ml/kg/hr) was given to keep the pulmonary artery wedge pressure at baseline levels; this procedure resulted in a hyperdynamic response with a cardiac output (CO) 20-35% above baseline and a decrease (20-39%) in mean arterial pressure (MAP), leading to a 50% decrease in peripheral resistance. The pulmonary vascular changes were reflected in an increase of the mean pulmonary pressure (PA) to 42% above baseline and a marked rise in pulmonary vascular resistance (PVR) to 50% above baseline with no additional changes in pulmonary gas exchange. After 8 hr both CO and MAP were inversely correlated (r = 0.9-1) with dramatically increased catecholamine plasma levels (15 times above baseline). With continuous infusion of live E. coli (blood levels 10(5)-10(6) CFU/ml) and massive fluid supply we have successfully mimicked hyperdynamic sepsis with severe organ failure after an 8-hr observation period.

Animals↗
PubMed1990

Effect of the PAF antagonist BN 52021 in ovine endotoxin shock.

It has been reported that a platelet-activating factor (PAF) antagonist ONO-6240 had little effect on pulmonary hypertension and lung lymph in sheep injected with endotoxin lipopolysaccharide (LPS); consequently we evaluated a new PAF antagonist, BN 52021. Twelve adult sheep were surgically prepared for chronic study including lung lymph drainage. LPS (S. abortus equii, 36 ng/kg/h over 7 h) was then administered with (BN group) or without (control group) infusion (1 h before LPS) of the PAF antagonist BN 52021 (4 mg/kg/30 min). Comparison of the hemodynamic data between the control group and the BN group reveals an almost identical pattern. In contrast, we find differences in the pulmonary response of the two experimental groups. The early elevation of pulmonary artery pressure after LPS administration is less in the treatment group, as is the duration of pulmonary hypertension. Similarly, thromboxane levels are lower in the treated animals. The increases in lymph flow (LQ) and transvascular protein clearance (L/P X LQ) as well as the protein flux were less prominent in the treatment group. The mean lymph flow per hour was significantly higher in the control group. The mean lymph flow per hour was significantly higher in the control group, as were the corresponding parameters for clearance and protein flux. Thus the pulmonary vasculature and lung fluid balance disruption produced by LPS was markedly reduced by treatment with the PAF blocker.

Animals↗
PubMed1990

[Bone replacement using demineralized allogeneic bone in animal experiments].

The implantation of bone matrix in muscle bag or trepanation defects of rats with greatest reproducibility will induce osteogenesis and defect healing. The phenomenon of osteo-induction was possible to obtain only in first steps in higher developed mammals. Investigations in nude rats have shown a clear difference in biologic reaction on the matrix of various species. The osteo-regeneration in replacement weak defect of ulnar bone in dogs showed a massive greater reactivity of autogenous spongiosa, whereas bank spongiosa and bone matrix produced not more new bone as the control. An increase of osteoinductive matrix potency is a supposition for practical use in case of severe bone defects.

Animals↗
PubMed1990

Net inotropic plasma activity in canine hypovolemic traumatic shock: low molecular weight plasma fraction after prolonged hypotension depresses cardiac muscle performance in vitro.

Numerous studies report controversial results about the occurrence and role of cardiodepressant substances in various forms of circulatory shock. We investigated the net inotropic effect of the low molecular weight fraction (mol wt less than or equal to 1,000) of plasma in prolonged canine hypovolemic traumatic shock using an in vitro guinea pig papillary muscle assay (isotonic mode). The shock plasma fractions (ultrafiltrates) after 4 hr of hypotension (mean arterial blood pressure 40-50 mm Hg) and immediately post-reinfusion significantly depressed papillary muscle function (P less than .02). The extent of papillary muscle shortening was decreased by 49.5 +/- 9.9% in pre- and 50.6 +/- 10.0% in post-reinfusion plasma ultrafiltrates (mean values +/- standard error of the mean; n = 6 shock experiments). In contrast, both the plasma ultrafiltrates from ten non-anesthetized healthy dogs and the control ultrafiltrates obtained prior to onset of shock in the experiments (-6.4 +/- 2.6; n = 6) induced no significant change of the in vitro performance of papillary muscle contraction. These results were achieved with plasma fractions in which ionized calcium and pH were adjusted to concentrations equivalent to the bioassay solution. Lactate acidosis and severe hypoglycemia (1.97 +/- 0.43 mM post-reinfusion) occurred in the shock experiments. Lack of energy substrate (glucose) was not responsible for the in vitro depression. Four depressive shock ultrafiltrates with glucose concentrations adjusted to control ultrafiltrate levels induced a 66.6 +/- 8.8% decrease in the extent of papillary muscle shortening. These results suggest that the possible occurrence of high net negative inotropic activity in plasma, especially just post-reinfusion, may play a role in the pathogenesis of irreversible circulatory shock.

Animals↗
PubMed1990

TNF- and LPS-induced changes of lung vascular permeability: studies in unanesthetised sheep.

There have been reports that the administration of TNF produces many of the cardiopulmonary changes seen with endotoxin (LPS). We asked whether all of LPS effects can be mimicked by TNF infusion. The effects of infusion of (human recombinant) TNF (50 micrograms/kg/30 min) and LPS (3 micrograms/kg/30 min) on permeability characteristics of sheep lungs were compared. Thirteen sheep were chronically instrumented for cardiopulmonary studies including lung lymph data. Infusion of LPS and TNF result in an increase of body temperature and lung lymph protein clearance (measured as the product of Lymph Flow and Lymph/Plasma Protein Ratio). The two responses had entirely different time courses. This might be related to the significantly longer period of pulmonary hypertension (MPAP) with LPS, which was only transient with TNF. Similar differences in plasma levels of thromboxane B2 (TxB2) were also noted. There were also differences in leukocyte kinetics, arterial blood gases, and plasma lactate levels. This indicates that although TNF infusion results in an increased pulmonary microvascular permeability, this event occurs without concomitant changes in thromboxane metabolism and exhibits time characteristics somewhat different from endotoxin.

Animals↗
PubMed1989

Inhibition by halothane, but not by isoflurane, of oxidative response to opsonized zymosan in whole blood.

In an attempt to clarify some apparent discrepancies in reports of the effects of anesthetic agents upon granulocyte function, we studied the effects of halothane and isoflurane, using techniques that allowed us to perform the assays in and in sealed vials to prevent volatile gas evolution: assay gas concentrations were measured, rather than inferred. Chemiluminescence, superoxide production, and hydrogen peroxide production were assessed after presentation of opsonized zymosan as a phagocytic stimulus. Incubation with halothane led to a highly statistically significant dose-related inhibition of chemiluminescence (maximum 66%), H2O2 production (67%) and .O2- production (61%), within the concentration range observed in blood from patients undergoing general anesthesia. In contrast, the presence of isoflurane led to no statistically significant changes in any of the functions measured. Cells harvested from patients undergoing elective halothane anesthesia showed the same functional inhibition, but for quantitative differences likely due to the inability to control for dilution effects in clinical samples. It has been suggested that halothane anesthesia may be associated with excess mortality in septic patients; although the results we report are readily reversible, their presence during a prolonged anesthesia could be harmful in a patient who is not immunologically normal and/or who is already infected. Careful clinical trials will be necessary to determine if isoflurane is a superior agent in this context.

Blood↗
PubMed1989

Neutrophil function and lipid peroxidation in a rat model of multiple organ failure.

Multiple organ failure (MOF) was induced by sterile intraperitoneal inoculation of zymosan in the rat. This results in a typical triphasic illness with maximal clinical signs at Days 2 and 14. In this study, granulocyte superoxide production (unstimulated and phorbol myristic acid stimulated) was studied as well as lipid peroxidation (TBAR) in plasma, liver, and lung tissue. Mainly TBAR levels in liver and lung tissue closely correlated with the triphasic clinical illness, while bacteriological data did not. It is concluded that the severe inflammatory response in this experimental model probably is the result of excessive toxic oxygen radical production. The first phase of illness may mainly be due to oxygen radical formation by activated PMN, the third phase of illness to the production of lysosomal enzymes (proteinases) from PMN, and activated macrophages as indicated by elevated N-acetylglucosaminidase levels.

Alanine Transaminase↗
PubMed1989

Permeability studies in a hypovolemic traumatic shock model: comparison of Ringer's lactate and albumin as volume replacement fluids.

In order to shed light on the controversy surrounding the choice of resuscitative fluids in shock, we used a canine model which we feel to be a superior mimic of human traumatic shock, combining hemorrhage (to a mean arterial pressure of 50 mmHg), fracture of both femora, and soft tissue crush. After 90 min, animals were resuscitated by reinfusion of shed blood, supplemented by 5% albumin (n = 8) or lactated Ringer's solution (n = 8). Plasma colloid osmotic pressure (COP), transcapillary escape rate for albumin (TER), total lung water and extravascular lung water (EVLW) were measured. COP fell in both groups, but remained above 9 mmHg in the albumin recipients, while falling below 7 in those receiving crystalloid (P less than 0.05). Overall, the increase in EVLW averaged 20%; albumin recipients fared better (9.7%) than Ringer's recipients (31.1%), but wide inter-animal variation precluded statistical significance (P = 0.095). TER rose 30% per hour, without difference between groups. Quality of resuscitation (achieved blood pressure and cardiac output) was somewhat better in the albumin group. We conclude that this model allows study of the early microvascular leakage seen in shock; within the time-frame studied (maximum 4.5 h following shock), colloid and crystalloid resuscitation were approximately equivalent.

Albumins↗
PubMed1989

Relationship between neopterin and granulocyte elastase plasma levels and the severity of multiple organ failure.

In a series of 56 patients (24 uncomplicated postoperative and 32 septic patients), neopterin and elastase alpha 1 protease inhibitor complex (E-alpha 1 PI) plasma levels were measured daily. The clinical course of each patient was evaluated with the Multiple Organ Failure (MOF) score according to Goris. Neopterin could differentiate between septic and nonseptic patients (p less than .001), and E-alpha 1 PI between septic nonsurvivors and nonseptic patients only (p less than .01). In septic patients, acute pulmonary insufficiency was indicated by elevated E-alpha 1 PI values (greater than or equal to 400 micrograms/L) 1 day before mechanical ventilation was performed with a sensitivity of 81% and a specificity of 82%. Defining a patient with MOF whose score was greater than or equal to 5 as a high-risk septic patient, a comparison neopterin greater than or equal to 40 nmol/L and E-alpha 1 PI greater than or equal to 400 micrograms/L, measured 1 day before the evaluation of an MOF score of greater than or equal to 5 yielded a sensitivity of 91% and a specificity of 99% when patients fulfilled both criteria. We conclude that neopterin and E-alpha 1 PI might be useful parameters for the diagnosis of septicemia and monitoring of the clinical course in septic patients. Moreover, they might indicate the possible central role of macrophage and PMN activation in the development of MOF.

Adult↗
PubMed1989

Dog bone less osteogenetic than rat bone. Bone-matrix transplants in nude rats.

Demineralized bone matrix and bone-matrix gelatin prepared from cortical rat bone, and from cortical and cancellous canine bone were implanted into muscle pouches of nude rats for 6 weeks. Evaluation was done by histology, histomorphometry, and determination of alkaline phosphatase. Rat matrix consistently induced new bone and high phosphatase levels. Canine matrix induced but small amounts of bone and lower phosphatase levels, with cortical matrix somewhat more inductive than cancellous matrix; demineralized cancellous bone matrix from the dog was the only material tested not showing any inductivity. Irrespective of bone type or species, gelatin had clearly higher induction capacity than demineralized bone matrix.

Alkaline Phosphatase↗
PubMed1989

The influence of fibrin sealant on demineralized bone matrix-dependent osteoinduction. A quantitative and qualitative study in rats.

Allogeneic demineralized bone matrix (DBM) and bone matrix gelatin (BMG) were implanted with or without fibrin sealant (FS) ectopically (abdominal wall) and orthotopically (7-mm trepanation defect) in 38 male Sprague-Dawley rats. Evaluation was done by descriptive histology, histomorphometry of orthotopic implants, and determination of alkaline phosphatase in ectopic implants. The observation period was 21 days with ectopic implantation and 26 days with orthotopic implantation. In all ectopic specimens, new bone developed without any qualitative difference between specimens with and without FS. The alkaline phosphatase activity did not change significantly upon addition of FS. Morphometry revealed slight differences between the groups with and without FS. The peripheral bone deposits in the BMG + FS group, was significantly larger than in the BMG group. These investigations demonstrated neither a clearly positive nor negative effect of FS on ectopic osteoinduction or BMG-dependent osteoregeneration.

Alkaline Phosphatase↗
PubMed1989

Comparison of the cardiopulmonary responses to single bolus and continuous infusion of endotoxin in an ovine model.

We compared the cardiopulmonary responses to a single bolus (1.5 microgram/kg) vs. continuous infusion of endotoxin (LPS) (24 ng/kg/hr) in unanesthetized sheep. A single bolus produced an initial marked increase in pulmonary arterial pressure and plasma thromboxane levels and an elevated flow rate of lung lymph low in protein. Concomitantly, the cardiac output dropped and systemic vascular resistance rose. In the animals that received a continuous infusion of LPS, only very small changes in these variables were noted during this early period. Later, lung lymph flow rate and protein flux were elevated in both groups with a greater response in the bolus group. At 6 hr after LPS, the systemic vascular resistance fell in both groups, but to a greater extent in the bolus group, whereas the cardiac output rose to the same extent. Plasma levels of neutrophils, lymphocytes, and plasma prekallikrein levels decreased in both groups; neutropenia was more pronounced in the bolus group. The most important difference between both endotoxemia models during this phase was the reduction of the stroke work index in the bolus model, which was not observed with the continuous infusion. The apparent myocardial depression, the early reduction in cardiac output, and eicosanoid mediated pulmonary hypertension are the major differences between the two responses.

Animals↗