Papers by Willehad Boemke
Jama the Journal of the American Medical Association, 2004
Der Anaesthesist, Oct 1, 2007
Despite substantial improvement in the management of patients with aneurysmal subarachnoid hemorr... more Despite substantial improvement in the management of patients with aneurysmal subarachnoid hemorrhage (SAH), including early aneurysm occlusion by endovascular techniques and surgical procedures, a significant percentage of patients with SAH still experience serious sequelae of neurological or cognitive deficits as a result of primary hemorrhage and/or secondary brain damage. Available neuromonitoring methods for early recognition of ischemia include, among others, measurement of brain tissue O(2) partial pressure, brain metabolism with microdialysis and monitoring of regional blood flow. The triple-H therapy (arterial hypertension, hypervolemia and hemodilution) is the treatment of choice of a symptomatic vasospasm and leads to an enduring recession of ischemic symptoms, if initiated early after the onset of a vasospasm-linked ischemic neurological deficit. Further promising therapy approaches are the administration of highly selective ET(A) receptor antagonists and intracisternal administration of vasodilators in depot form. This review summarizes the major neurological and non-neurological complications following aneurysm occlusion. Possible neuromonitoring techniques to improve diagnosis and therapy for treatment of symptomatic vasospasm as well as extracranial complications are discussed.
Experimental Biology and Medicine, Jun 1, 2006
Beneficial effects of inhaled nitric oxide (iNO) on arterial oxygenation in acute lung injury (AL... more Beneficial effects of inhaled nitric oxide (iNO) on arterial oxygenation in acute lung injury (ALI) suggest the presence of vasoconstriction in ventilated lung regions and this may be influenced by endothelin-1 (ET-1). We studied a possible interaction between ET-1 and iNO in experimental ALI. Sixteen piglets were anesthetized and mechanically ventilated (inspired O 2 fraction, 1.0). After induction of ALI by surfactant depletion, animals were randomly assigned to either inhale 30 ppm NO (iNO group, n ¼ 8), or to receive no further intervention (controls, n ¼ 8). Measurements were performed during the following 4 hrs. In all animals, induction of ALI significantly decreased arterial oxygen tension (PaO 2 ) from 569 6 15 (prelavage) to 58 6 3 mm Hg. Inhaled NO significantly increased PaO 2 when compared with controls (iNO group: 265 6 51 mm Hg; controls: 50 6 4 mm Hg, values at 4 hrs, P , 0.01). Prelavage ET-1 plasma levels were comparable between groups (iNO: 0.74 6 0.03, controls: 0.71 6 0.03 fmol/ml, NS). During the protocol, the ET-1 levels increased and were different at 3 hrs (iNO: 0.93 6 0.06, controls: 1.25 6 0.09 fmol/ml; P , 0.05). PaO 2 changes induced by iNO revealed a moderate and significant correlation with ET-1 plasma levels (R ¼ 0.548, P ¼ 0.001). Our data suggest that endogenous ET-1 production influences the efficacy of iNO in ALI. Furthermore, iNO reduced ET-1 plasma levels, possibly indicating antiinflammatory properties of iNO in the early phase of ALI. Exp Biol Med 231: [974][975][976][977][978] 2006
Experimental Biology and Medicine
The objective of this study was to investigate whether circulatory and hormonal changes during xe... more The objective of this study was to investigate whether circulatory and hormonal changes during xenon plus remifentanil or isoflurane plus remifentanil anesthesia are altered by endothelin-A (ET(A)) receptor blockade. Eight beagle dogs were studied in four protocols (n = 7 each). After a 30-min awake period, anesthesia was induced with 8 mg/kg propofol, administered intravenously (iv), and maintained with either 0.8% +/- 0.01% (vol/vol) isoflurane plus 0.5 microg/kg/min remifentanil (Protocol 1) or 63% +/- 1% (vol/vol) xenon plus 0.5 microg/kg/min remifentanil (Protocol 2) for 1 hr. Protocols 3 and 4 were preceded by ET(A) blockade with ABT-627 (Atrasentan; iv bolus of 1 mg/kg, then 100 microg/kg/h continuously). Irrespective of Atrasentan administration, the mean arterial blood pressure (MAP) ranged between 92 and 96 mm Hg in the awake state and fell to 67 +/- 3 mm Hg in controls (mean +/- SEM) and to 64 +/- 2 mm Hg in the Atrasentan group during isoflurane plus remifentanil anesthe...
Intensivmedizin up2date, 2007
Experimental biology and medicine (Maywood, N.J.), 2006
Inhalation of endothelin (ET)-A receptor antagonists has been shown to improve gas exchange in ex... more Inhalation of endothelin (ET)-A receptor antagonists has been shown to improve gas exchange in experimental acute lung injury (ALI) but may induce side effects by increasing circulating ET-1 levels. We investigated whether the inhaled ET(A) receptor antagonist, LU-135252, at low doses, improves gas exchange without affecting ET-1 plasma concentrations and lung injury in an animal model of ALI. Twenty-two piglets were examined in a prospective, randomized, controlled study. In anesthetized animals, ALI was induced by surfactant depletion. Animals received either LU-135252 at a dose of 0.3 mg/kg during 20 mins (LU group; n = 11), or nebulization of saline buffer (control group; n = 11). The Mann-Whitney U test was used to compare groups (P < 0.05). In the LU group, arterial partial pressure of oxygen (PaO2) and mean pulmonary artery pressure (MPAP) improved compared with the control group (PaO2, 319 +/- 44 mm Hg vs. 57 +/- 3 mm Hg; MPAP, 32 +/- 2 mm Hg vs. 41 +/- 2 mm Hg; values at...
Anesthesiology, 2004
The objective of this study was to determine whether endothelin-A receptor blockade (ETAB) impair... more The objective of this study was to determine whether endothelin-A receptor blockade (ETAB) impairs hemodynamic and hormonal regulation compared with controls and angiotensin II receptor blockade (AT1B) during hypotensive hemorrhage in dogs under isoflurane-nitrous oxide anesthesia. Six dogs were studied in four protocols: (1) control experiments (controls); (2) ETA blockade using ABT-627 (ETAB); (3) AT1 blockade using losartan (AT1B); and (4) combined AT1B and ETAB (AT1B + ETAB). After a 30-min awake period, isoflurane-nitrous oxide anesthesia was established (1.3 minimum anesthetic concentration). After 60 min of anesthesia, 20 ml blood/kg body weight was withdrawn within 5 min, and the dogs were observed for another hour. Thereafter, the blood was retransfused, and the dogs were observed for a final hour. Anesthesia: Cardiac output decreased in all protocols, whereas mean arterial pressure decreased more in AT1B and AT1B + ETAB than in controls and ETAB. Hemorrhage: After 60 min, ...
Clinical science (London, England : 1979), 2002
This study compares the haemodynamic and hormonal responses during haemorrhage of conscious dogs ... more This study compares the haemodynamic and hormonal responses during haemorrhage of conscious dogs pre-treated with an endothelin-A (ET-A) receptor inhibitor. The dogs were studied in two different randomized groups: the control group and a group that was given the ET-A receptor antagonist ABT-627 (as a bolus of 1 mg x kg of body weight(-1) followed by 0.01 mg x kg body weight(-1) x min(-1) intravenously). The time-course was the same for both groups: after a 1 h baseline period (pre-haemorrhage), blood (25 ml x kg of body weight(-1)) was withdrawn within 5 min. Haemodynamics were continuously recorded and hormone levels measured after 1 h (post-haemorrhage). Thereafter, the blood withdrawn was retransfused within 5 min and haemodynamics again observed for 1 h (post-retransfusion). In ABT-627-treated dogs, the decrease in mean arterial pressure from 87+/-3 to 64+/-3 mmHg (P<0.05 versus pre-haemorrhage), and cardiac output from 2.1+/-0.1 to 1.3+/-0.1 l x min(-1) (P<0.05 versus pr...
Clinical science (London, England : 1979), 2002
To investigate the hypothesis that the inhaled ET(A) receptor antagonist LU-135252 acts as select... more To investigate the hypothesis that the inhaled ET(A) receptor antagonist LU-135252 acts as selective pulmonary vasodilator, we compared inhaled LU-135252 and inhaled nitric oxide (iNO) in an experimental model of acute lung injury (ALI), in a prospective, randomized, controlled animal study. A total of 30 anaesthetized, tracheotomized and mechanically ventilated pigs underwent induction of ALI by repeated saline washout of surfactant. The animals were then randomly assigned to receive the nebulized ET(A) receptor antagonist LU-135252 (0.3 mg x kg(-1), inhaled over 20 min; ET(A)-A group; n=10), inhaled NO (30 p.p.m. continuously; iNO group; n=10) or nebulized saline buffer (5 ml inhaled over 20 min; control group; n=10). Measurements of pulmonary gas exchange and haemodynamics were performed hourly over a 4 h period after induction of ALI. In the ET(A)-A group, the arterial oxygen tension (Pa(2)) increased from 58+/-3 to 377+/-39 mmHg at 4 h after intervention, while the intrapulmona...
Journal of applied physiology (Bethesda, Md. : 1985), 2002
Acute hypoxia causes hyperventilation and respiratory alkalosis, often combined with increased di... more Acute hypoxia causes hyperventilation and respiratory alkalosis, often combined with increased diuresis and sodium, potassium, and bicarbonate excretion. With a low sodium intake, the excretion of the anion bicarbonate may be limited by the lower excretion rate of the cation sodium through activated sodium-retaining mechanisms. This study investigates whether the short-term renal compensation of hypoxia-induced respiratory alkalosis is impaired by a low sodium intake. Nine conscious, tracheotomized dogs were studied twice either on a low-sodium (LS = 0.5 mmol sodium x kg body wt-1 x day-1) or high-sodium (HS = 7.5 mmol sodium x kg body wt-1 x day-1) diet. The dogs breathed spontaneously via a ventilator circuit during the experiments: first hour, normoxia (inspiratory oxygen fraction = 0.21); second to fourth hour, hypoxia (inspiratory oxygen fraction = 0.1). During hypoxia (arterial PO2 34.4 +/- 2.1 Torr), plasma pH increased from 7.37 +/- 0.01 to 7.48 +/- 0.01 (P < 0.05) becaus...
Journal of the autonomic nervous system, Jan 7, 1996
Studies were performed in partly free moving Beagle dogs, kept under standardized environmental a... more Studies were performed in partly free moving Beagle dogs, kept under standardized environmental and dietetic conditions (food intake: once daily at 8:30 a.m., 5.5 mmol Na/kg body weight per 24 h). The dogs were chronically instrumented with an inflatable cuff around the aorta above the renal arteries, two aortic catheters above and below the cuff, and a bladder catheter. Three protocols were performed in 7 dogs each: (i) urine collection in 20-min intervals and measurement of Na excretion, continuous registration of mean arterial blood pressure (MABP) and heart rate for 4 consecutive days. (ii) As (i), but additional servocontrolled reduction of the renal perfusion pressure (rRPP) to stimulate renin secretion and the formation of angiotensin II and aldosterone. (iii) As (ii), but additional constant infusion of the angiotensin converting enzyme inhibitor Captopril. Despite rRPP Na is only transiently retained (pressure escape). MABP level is elevated, as long as total-body Na is aug...
Clinical science (London, England : 1979), 1995
1. We studied post-prandial changes in renal function in dogs adapted to either low or high sodiu... more 1. We studied post-prandial changes in renal function in dogs adapted to either low or high sodium intake with and without concomitant post-prandial infusion of angiotensin II. Six trained dogs were exposed to diets containing either 0.5 or 14.5 mmol Na+ day-1 kg-1 body weight (low or high sodium respectively). They were studied from 20 min before to 4 h after food intake. In half of the experiments a physiological dose of angiotensin II (4 ng min-1 kg-1 body weight) was administered after food intake for four post-prandial hours. The water intake was high and equal on both diets (91 ml day-1 kg-1 body weight). 2. On a high-salt diet post-prandial sodium excretion and urine volume increased considerably above fasting values. This post-prandial increase was attenuated when angiotensin II was infused (post-prandial sodium excretion was 31% +/- 3% of intake without versus 10% +/- 1% with angiotensin II, post-prandial urine volume was 22% +/- 2% without versus 8% +/- 1% with angiotensin...
Die Anästhesiologie, 2012
Veterinary Anaesthesia and Analgesia, 2010
Objective To test the compensatory role of endothelin-1 when acute blood loss is superimposed on ... more Objective To test the compensatory role of endothelin-1 when acute blood loss is superimposed on anaesthesia, by characterizing the effect of systemic endothelin receptor subtype A (ET A ) blockade on the haemodynamic and hormonal responses to haemorrhage in dogs anaesthetized with xenon/ remifentanil (X/R) or isoflurane/remifentanil (I/R).
The Veterinary Journal, 2010
This study investigated the applicability of two human radio-immunoassays (RIA) to detect epineph... more This study investigated the applicability of two human radio-immunoassays (RIA) to detect epinephrine (EPI), norepinephrine (NE), and their O-methylated metabolites metanephrine (MN) and normetanephrine (NMN) in canine plasma. The analysis yielded a positive correlation between metabolites and their respective parent compounds: EPI and MN (r = 0.63), NE and NMN (r = 0.47), as well as between parent compounds, EPI and NE (r = 0.48), and between metabolites MN and NMN (r = 0.71). Moreover, EPI (r = 0.99) and NE (r = 0.77) concentrations determined by RIA did correlate positively with high pressure liquid chromatography (HPLC). However, there was limited agreement between both methods. It was concluded that complete validation tests for accuracy, precision and agreement are needed before this RIA can be applied to quantify catecholamines, metanephrine, and normetanephrine in canine plasma. The assay may prove to be a potential alternative to HPLC or tandem mass spectrometry in the workup of pheochromocytoma and the detection of overall sympathetic activity in dogs.
Shock, 2010
The authors aimed to test the hypothesis that xenon anesthesia limits adverse hypotensive effects... more The authors aimed to test the hypothesis that xenon anesthesia limits adverse hypotensive effects of losartan during acute hemorrhage. In six conscious unsedated Beagle dogs, the systemic and pulmonary circulation were monitored invasively, and two subsequent 60-min hypotensive challenges were performed by (a) induction (propofol) and maintenance of anesthesia with isoflurane/remifentanil or xenon/remifentanil and by (b) subsequent hemorrhage (20 mL kg⁻¹ within 5 min) from a central vein. The same amount of blood was retransfused 1 h after hemorrhage. Experiments were performed with or without acute angiotensin II receptor subtype 1 blockade by i.v. losartan (100 μg·kg⁻¹·min⁻¹) starting 45 min before induction of anesthesia. Four experiments were performed in each individual dog. Xenon/remifentanil anesthesia provided higher baseline mean arterial blood pressure (85 ± 6 mmHg) than isoflurane/remifentanil anesthesia (67 ± 3 mmHg). In losartan-treated animals, isoflurane/remifentanil caused significant hypotension (42 ± 4 mmHg for isoflurane/remifentanil vs. 71 ± 6 mmHg for xenon/remifentanil). Independent of losartan, hemorrhage did not induce any further reduction of mean arterial blood pressure or cardiac output in either group. Spontaneous hemodynamic recovery was observed in all groups before retransfusion was started. Losartan did not alter the adrenaline, noradrenaline, and vasopressin response to acute hemorrhage. Losartan potentiates hypotension induced by isoflurane/remifentanil anesthesia but does not affect the hemodynamic stability during xenon/remifentanil anesthesia. Losartan does not deteriorate the hemodynamic adaptation to hemorrhage of 20 mL kg⁻¹ during xenon/remifentanil and isoflurane/remifentanil anesthesia. Therefore, xenon/remifentanil anesthesia protects against circulatory side effects of losartan pretreatment and thus may afford safer therapeutic use of losartan during acute hemorrhage.
Laboratory Animals, 1991
Catheter-related infections pose a hazard to both humans and laboratory animals. The aim of this ... more Catheter-related infections pose a hazard to both humans and laboratory animals. The aim of this study was to develop a technique preventing bacterial colonization of intravascular catheters.
Kidney and Blood Pressure Research, 1996
ABSTRACT
Kidney and Blood Pressure Research, 1995
The diurnal time course of urinary flow rate (UV), urinary sodium (UNaV), and potassium (UKV) exc... more The diurnal time course of urinary flow rate (UV), urinary sodium (UNaV), and potassium (UKV) excretion, and of hormones such as atrial natriuretic peptide (ANP) and aldosterone, was investigated during 5 days of continuous captopril infusion (15 micrograms.kg body weight-1.min-1) in 4 conscious dogs on a high sodium diet (14.5 mmol Na.kg body weight-1.24 h-1). All food and water was given once daily at 8.30 a.m. On the control day and on days 1, 3, and 5 of captopril infusion, urine was collected by an automated system at 20-min intervals over 24 h, blood was taken every 4 h. Mean arterial blood pressure (MABP) and heart rate were evaluated as 5-min averages. Time courses of UNaV, UV, and UKV were compared with the individual control day without captopril. With captopril, 24-hour balances for Na and H2O were slightly negative, while the K balance was slightly positive for 2-3 days. Thereafter, all 24-hour balances were restored. MABP continued to decrease even after Na and water intake and output had come into balance again. Captopril treatment changed the diurnal excretion pattern for UNaV and UV characteristically. In the postprandial period until 5 p.m., less Na and urine were excreted than on the control day, whereas during the evening and night more Na and urine were excreted. The changes in the excretion pattern persisted for the entire observation period. The results indicate that disturbances in the regulating systems, induced by converting-enzyme blockade, bring about complex reactions of, e.g., MABP, ANP and aldosterone that finally restore Na and water 24-hour input/output balances.
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Papers by Willehad Boemke