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Biomedical subjects

G Redl

Publications and source records attributed to G Redl.

17 recordsLinked to original sources

Mechanism of immunoreactive atrial natriuretic factor release in an ovine model of endotoxemia.

We have previously reported an increase in plasma levels of atrial natriuretic factor (ANF) in an ovine model of endotoxemia. The purpose of this study was to determine if this IR-ANF release was mediated by the increase of right atrial pressure (RAP) and right heart volumes concomitantly observed following endotoxin (LPS) administration. We studied right ventricular function, renal blood flow (RBF), urinary output (UO), urinary clearance of free water (CH20), urinary osmolality (UOSM), sodium excretion (UENA), and the plasma IR-ANF concentration (radioimmunoassay), following the administration of an E. coli LPS bolus (1 microgram/kg) with (group O, n = 8) and without (group E, n = 10) pretreatment with OKY-046, a selective thromboxane synthetase inhibitor. LPS induced early increases in RAP, right ventricular end-systolic (RVESV) and end-diastolic (RVEDV) volumes, heart rate (HR), and IR-ANF, and delayed increases in RBF, UO, and CH20. OKY-046 prevented the elevation of RAP, RVEDV, and RVESV; however, both groups showed virtually identical increases in IR-ANF (E: 20.03 +/- 3.8 to 192.33 +/- 35.47 pg/ml, O: 17.9 +/- 4.1 to 159.5 +/- 23 pg/ml) as well as an increase of HR, RBF, UO, and CH20. The increase in IR-ANF release noted following the administration of LPS in an ovine model does not appear to be related to the early elevations in right heart volumes or atrial distension.

Animals

Inhibition of thromboxane synthesis reduces endotoxin-induced right ventricular failure in sheep.

BACKGROUND AND METHODS: There is a marked decrease of the right ventricular ejection fraction after the administration of a bolus of endotoxin to sheep. This hemodynamic response may be the result of thromboxane-mediated pulmonary hypertension. Right ventricular function was studied in an ovine model after the administration of endotoxin (1 microgram/kg Escherichia coli) with and without pretreatment with OKY-046, a selective thromboxane synthetase inhibitor. RESULTS: OKY-046 attenuated the endotoxin-induced increase in pulmonary arterial pressure and prevented the early decreases in right ventricular ejection fraction and cardiac output. However, thromboxane synthetase inhibition failed to prevent endotoxin-induced hypoxemia. The marked increase in plasma thromboxane concentrations, which is usually seen after the administration of endotoxin, was prevented by pretreating the animals with OKY-046. On the other hand, increased plasma prostacyclin concentrations were observed in sheep treated with the thromboxane synthetase inhibitor. CONCLUSION: This series of experiments shows that the early endotoxin-induced decrease in right ventricular ejection fraction can be alleviated by the application of OKY-046.

Animals

Cardiac function in an ovine model of endotoxemia.

Eight awake sheep were monitored with ultrasonic crystals, positioned at the anterior and posterior left ventricular wall. A left-sided intraventricular pressure transducer and a right ventricular ejection fraction catheter were positioned in the right and left hearts, respectively. After administration of endotoxin (Escherichia coli, LPS 1.5 micrograms/kg in 30 min), the hemodynamic variables showed a triphasic course. Phase I, (0-1 hr post LPS) was characterized by an increased pulmonary artery pressure and a decreased right ventricular ejection fraction. The inability of the right ventricle to compensate for the increased preload resulted in a fall of the left ventricular preload, stroke volume, and cardiac output. Three hours after LPS administration a second drop of the cardiac output was noted (phase II). This occurred as a result of a fall in preload. Eight hours post LPS a hyperdynamic phase (phase III) was distinguished, with a high cardiac output and a low systemic vascular resistance. During this time there was evidence of probable reduced myocardial contractility.

Animals

[Right heart function and endotoxemia in animals].

We used a chronic instrumented ovine model to investigate right heart function following an endotoxin bolus. Primary aim of the experiments was to elucidate the influence of the right heart on the cardiopulmonary system. Furthermore, we tried a thromboxane synthetase inhibitor as a therapeutical approach. At least we investigated the IR-ANF release, as the endocrinal function of the right heart, in this model. Following the endotoxin administration we observed a massive increase of the pulmonary arterial pressure. As a result of the increased right ventricular afterload right ventricular ejection fraction decreased and end-systolic volume increased. Impaired right heart function could not be compensated sufficiently using Frank Starling mechanism. Consequently, decreased left ventricular preload, stroke volume and cardiac output followed. Pretreatment with OKY-046, a selective thromboxane synthase inhibitor, attenuated the increase in pulmonary arterial pressure and prevented the early right heart failure including the drop of cardiac output. Furthermore, OKY-046 changed the thromboxane-prostacyclin relationship. Therefore we consider the cardiopulmonary reactions following pretreatment with OKY-046 as a result of the attenuated right ventricular afterload as well as of the increased prostacyclin concentration. Endotoxin induced hypoxaemia could not be prevented by pretreatment with OKY-046 and might be caused by interstitial edema following endothelial leakage. IR-ANF release in our model, accompanied by polyuria and natriuresis, seemed to be independent of right heart dysfunction and increase of right atrial pressure. We suggest endotoxin or a endotoxin induced mediator as a trigger of IR-ANF release.

Animals

Serum vasopressin (AVP) levels in polyuric brain-dead organ donors.

Hydromineral metabolism and serum arginine-vasopressin (AVP) levels were investigated in 11 patients who sustained brain death. They showed various degrees of polyuria with low osmolality and low fractional sodium excretion. Urine osmolality was always below that of serum, and AVP levels were between 1.3 and 50.0 pg/ml vs 0.7-8.0 pg/ml in ten normal subjects. Thus central diabetes insipidus was excluded. A renal mechanism inducing water diuresis has to be assumed. The type of renal lesion, however, remains unclear.

Adolescent

Bronchial blood flow reduction with positive end-expiratory pressure after acute lung injury in sheep.

Smoke inhalation increases bronchial blood flow (Qbr) and produces edema of the airway system. This study investigates whether the increased Qbr seen 24 h after inhalation injury can be affected by mechanical ventilation with PEEP (5, 10, 15 cm H2O). Sheep (n = 8) previously prepared with cardiopulmonary catheters and ultrasonic transit time flow probes mounted around their bronchial arteries were insufflated with four sets of 12 breaths each of cotton smoke. Different levels of PEEP were added to the mechanical ventilation 24 h after injury; each PEEP level was applied for 45 min. There were significant increases in Qbr and lung lymph flow (QL) associated with a marked decrease in bronchial vascular resistance (BVR) 24 h after injury. However, no change was observed in mean arterial pressure (MAP) or cardiac index (CI). There was a substantial reduction in PaO2/FIO2 (P/F), which indicated a deterioration in arterial oxygenation. The application of varying levels of PEEP decreased Qbr (p less than .05) while BVR increased (p less than .05), but QL and P/F did not. CI and MAP were recorded. After removal of PEEP, none of the cardiopulmonary variables were significantly different from their postsmoke control values. These findings suggest that mechanical ventilation with PEEP markedly decreases the smoke-induced hyperemia edema frequently seen after inhalation injury without any significant alterations in MAP or CI.

Animals

Control of the total artificial heart: new aspects in human versus animal experience.

Control strategies for total artificial heart application have generally been based on experience with healthy animals. Human patients in a bad state of health who have impaired organ functions and who are subjected to intensive care procedures can develop atypical hemodynamic behavior. In these patients, both unstable and hyperstable behavior of the vascular resistance were observed. Therefore, regulation of cardiac output (CO) by pressure parameters only was avoided and CO was adjusted to obtain an appropriate O2-utilization (O2U). Intending to keep the O2U within ranges of 20-25%, we obtained cardiac indexes between 3.3 and 4.4 L/m2/min (CO 6-8 L/min), which is higher than other cardiac indexes reported. A CO of 10.5 L/min was even necessary to obtain an O2U of 30% in a septic patient. This strategy caused a stable driving management and led to a rapid hemodynamic stabilization and general improvement of the patients' condition. Results indicate that it is also very important to monitor metabolic parameters for appropriate driver adjustment as well, especially in the early postoperative phase, and that O2-U is a sensitive and useful parameter for this purpose.

Animals

[Differences in the neuromuscular blockade of the larynx and thenar muscles following relaxation with vecuronium].

To objectivate the clinical impression of different neuromuscular depression in the larynx- and limb-musculature, an attempt was made in 5 patients to quantify laryngeal muscle relaxation by electromyographic recordings of evoked responses from the vocalis muscle during endolaryngeal microsurgery. Mechanographic and evoked electromyographic recordings of the thenar muscles were obtained simultaneously. Nearly total suppression of evoked responses at the peripheral muscle site was observed after a bolus dose of either 60 micrograms/kg or 100 micrograms/kg of the nondepolarising muscle relaxant Vecuronium. However, the vocalis muscle was not blocked completely. The neuromuscular depression ranged from 61 to 92% depending on the dose. In no case was the recommended intubating dose (ED 95) of 60 micrograms/kg sufficient for complete relaxation of the vocalis muscle. The present results do not support that the extent and/or time course of intrinsic laryngeal muscle relaxation correlates with peripheral neuromuscular depression in a quantitative manner. The different degree of relaxation achieved by Vecuronium in the hand and larynx is probably due to their different content of acetylcholine receptors.

Adult

[The pharmacodynamics of vecuronium on the musculature of the vocal cords and the ball of the thumb. Preliminary report].

During endolaryngeal microsurgery, an attempt was made to quantify laryngeal muscle relaxation by electromyographic recording of evoked responses from the vocal cord musculature in 5 patients. Both mechanographic and electromyographic recordings from the adductor pollicis were obtained simultaneously. Following a bolus dose of vecuronium (60 micrograms/kg, n = 3, and 100 micrograms/kg, n = 2), nearly total (97%-100%) suppression of evoked responses at the peripheral muscle site was observed; the vocal cords, however, did not show complete neuromuscular (nm) blockade, but rather varying degrees of nm depression ranging from 61%-92%. The present results clearly show that quantitative information as to duration and degree of neuromuscular depression in the vocal musculature may be obtained by electromyographic recordings of evoked potentials in the clinical setting; it is impossible however, to quantitatively estimate the extent of intrinsic laryngeal muscle relaxation from peripheral nm depression. The pharmacodynamic differences observed might be due to the varying acetylcholine receptor density of the muscle groups studied.

Adult

[Monitoring kidney function in abdominal infection].

In ICU patients suffering from abdominal sepsis acute renal failure (ARF) is a common (50% incidence) and often lethal (more than 80% mortality) complication. Continuous monitoring of renal function is necessary for both adequate fluid replacement and early detection of ARF. Using a programmable handheld computer the following parameters are calculated at least daily: creatinine, osmolal and free water clearance, fractional excretion of sodium and potassium and non-saline loss. The clearance values are corrected to 1.73 m2 body surface area. Free water clearance proved to be a particularly valuable guide for fluid therapy as well as for early diagnosis of ARF. In all septic patients renal function is impaired to some degree, since despite increased cardiac output creatinine clearance is only normal or even decreased. More than 50% of our patients with abdominal sepsis develop ARF, resulting in a dramatic increase in mortality. Goal of renal monitoring in sepsis is to detect ARF as early as possible and to differentiate between extrarenal and septic origin to enable immediate surgical treatment.

Acute Kidney Injury

[Continuous hemofiltration in peritonitis].

During a period of 3 years 27 patients in acute renal failure (ARF) due to peritonitis underwent pump driven continuous hemofiltration (PDHF). PDHF caused neither hemodynamic nor metabolic disturbances, which in contrary are frequently seen during intermittent hemodialysis treatment in septic patients. BUN and creatinine levels fell significantly (p less than 0.001) and remained at 60 mg% and 2.0 mg%, respectively (mean values). Severe coagulation disorders occurred in 5 patients; in 2 patients PDHF was continued under protamine administration into the venous line, in 3 patients PDHF was stopped for 24 hours and than started again. Bleeding stopped in all cases, therefore surgery was not necessary. Other major complications of PDHF were not observed. Kidney function recovered in 44.4% of patients, and mortality was 70.4%. This is clearly lower than in abdominal septic patients under intermittent hemodialysis. Despite much higher costs (2.5 times the costs of hemodialysis treatment per day) PDHF seems to be a promising alternative in the treatment of ARF complicating septic multiple organ failure.

Acute Kidney Injury