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Biomedical subjects

H Bundgaard

Publications and source records attributed to H Bundgaard.

At least 37 records · Page 2Linked to original sources
PubMed1999

Subdural pressure measurement during posterior fossa surgery. Correlation studies of brain swelling/herniation after dural incision with measurement of subdural pressure and tactile estimation of dural tension.

Thirty-two patients with posterior fossa tumours or arteriovenous malformations were subjected to elective craniotomy in the prone position. The intracranial pressure (ICP) was measured by a subdural approach in the open area of the exposed dura. Estimation of dural tension before dural incision and the degree of brain swelling/herniation after opening the dura were correlated with the subdural pressure measured with intact dura. The results indicate that at ICP < 10 mmHg, brain swelling/herniation rarely occurred, while at ICP > or = 10 mmHg some degree of brain swelling/herniation was always present. The neurosurgeon's tactile estimation of dural tension correlated poorly with any tendency to brain swelling/herniation. It is concluded that measurement of subdural pressure is a better predictor of the risk of brain swelling/herniation than the tactile estimation of dural tension during posterior fossa surgery.

Adolescent↗
PubMed1998

[Hypertrophic cardiomyopathy].

Hypertrophic cardiomyopathy is a heterogeneous, progressive disease with a variable age of debut. Hypertrophic cardiomyopathy is characterized by myocardial hypertrophy with a bizarre fibre disarray. Angina pectoris, dyspnoea and syncope are the most frequent symptoms. Hypertrophic cardiomyopathy is an important cause of sudden death, especially in children and young adults. The aetiology is genetic in more than 60% of the cases, with an autosomal dominant mode of inheritance. More than 50 different mutations involving six genes have so far been associated with the development of hypertrophic cardiomyopathy. These mutations are located to genes coding for several of the proteins in the cardiac sarcomere. The protein changes seem to compromise contractility as well as sarcomere assembly, thereby secondarily causing compensatory hypertrophy. The management of hypertrophic cardiomyopathy has been markedly improved within the last few years. This emphasizes the importance of determining prognostic markers in each patient. A specific genetic diagnosis may prove to be of major importance.

Adult↗
PubMed1998

[Treatment of hypertrophic cardiomyopathy].

The medical management of hypertrophic cardiomyopathy is reviewed. Four cases of hypertrophic cardiomyopathy are presented, and serve to describe the currently available invasive treatment modalities, i.e. septal myectomy, dual chamber pacing, cardioverter defibrillator implantation and heart transplantation. These different invasive treatments all seem to be symptomatically effective in carefully selected patients, but studies of prognostic effects are not available. Finally, new experimental procedures are presented.

Adolescent↗
PubMed1998

Chronic K-supplementation decreases myocardial [Na,K-ATPase] and net K-uptake capacity in rodents.

The effects of high K intake on plasma K, myocardial K content and Na,K-ATPase concentration and on myocardial K uptake during KCl infusion were evaluated in rodents. Myocardial Na,K-ATPase was quantified in crude homogenates by K-dependent pNPPase activity in rats, and in intact samples by3H-ouabain binding in guinea pigs. Na, K-ATPase alpha isoform distribution was assessed by immunoblotting. Plasma K was monitored in anesthetized rats during intravenous infusion of 0.75 mmol KCl/100 g body weight/h. A significant increase in plasma K was observed after 2 days of K supplementation, 4.9+/-0.2 (mean+/-s.e.m.)v 3.0+/-0.2 mmol/l in weight matched controls ( P<0.01,n=5) and this difference remained stable. After 1 day, a significant myocardial K content increase was obtained, 86. 2+/-3.0v 76.7+/-1.9 micromol/g wet weight (P<0.05, n=5); after 4 days myocardial K stabilized 4.9+/-1.2 micromol/g wet weight above control level (P<0.05,n=5). From the 4th day, a significant decrease in myocardial K-dependent pNPPase activity was observed, 1.18+/-0.04v 1. 31+/-0.01 micromol/min/g wet weight in weight matched controls (P<0. 05,n=5); after 2 weeks the decrease was 29% (P<0.05,n=5), with a reduction in alpha1-isoform abundance by 24% (P<0.05,n=5), and a tendency to a decrease in alpha2 of 10% (n.s.,n=5). The measurements were validated by 3H-ouabain binding to myocardial samples from guinea pigs K-supplemented for 2 weeks, showing a decrease of 21% (P<0.05,n=5). During KCl infusion, the myocardial K content increase rate was reduced by 52% (P<0.05) in the K-supplemented rats. The observed effects of K-supplementation on plasma K, myocardial K content and myocardial K-dependent pNPPase activity were abolished within 2 days after reallocation to chow with normal K content. In conclusion, high K-intake is associated with significantly and reversible increased plasma and myocardial K content, and decreased myocardial Na,K-ATPase concentration and net myocardial K uptake capacity. Thus, the heart is protected from major increases in intracellular K concentrations during chronically-high K-intake.

4-Nitrophenylphosphatase↗
PubMed1998

Subdural monitoring of ICP during craniotomy: thresholds of cerebral swelling/herniation.

It is possible to define thresholds for cerebral swelling or herniation during craniotomy. In 178 patients subjected to craniotomy for space occupying processes subdural ICP was measured before opening of dura. The subdural ICP was correlated to the degree of cerebral swelling or herniation after opening of dura. At subdural ICP < 7 mm Hg cerebral swelling/herniation after opening of dura rarely occurs, while at ICP > or = 10 mm Hg cerebral swelling/herniation occurs with high probability. These ICP thresholds are independent of the pathophysiology (SAH, cerebral tumor), the anaesthetic agent (isoflurane, propofol) and the PaCO2 level (< or = 4.0 kPa, > 4.0 kPa). Generally, a good correlation between the tactile estimation of dural tension and the tendency to cerebral swelling or herniation after opening of dura was found. However, in 8.5% the surgeons were unable to predict swelling/herniation.

Anesthesia, General↗
PubMed1998

ICP during anaesthesia with sevoflurane: a dose-response study. Effect of hypocapnia.

In patients with a supratentorial cerebral tumor, an increase in sevoflurane concentration from 1.5% (0.7 MAC) to 2.5% (1.3 MAC) did not change the intracranial pressure (ICP) significantly (12 to 14 mm Hg (medians)). However, a significant increase in cerebral blood flow (CBF) from 29 to 39 ml/100 g/min (medians) was disclosed. During administration of sevoflurane 1.5% and 2.5%, a significant decrease in ICP (3.5 and 3.0 mm Hg (median) respectively) was found when PaCO2 was decreased by 0.8 kPa.

Anesthesia, Inhalation↗
PubMed1998

Effects of sevoflurane on intracranial pressure, cerebral blood flow and cerebral metabolism. A dose-response study in patients subjected to craniotomy for cerebral tumours.

BACKGROUND: Studies concerning the cerebrovascular effects of sevoflurane in patients with space-occupying lesions are few. This study was carried out as a dose-response study comparing the effects of increasing sevoflurane concentration (1.5% (0.7 MAC) to 2.5% (1.3 MAC)) on cerebral blood flow (CBF), intracranial pressure (ICP), cerebrovascular resistance (CVR), metabolic rate of oxygen (CMRO2) and CO2-reactivity in patients subjected to craniotomy for supratentorial brain tumours. METHODS: Anaesthesia was induced with propofol/fentanyl/atracurium and maintained with 1.5% sevoflurane in air/oxygen at normocapnia. Blood pressure was maintained constant by ephedrine. In group 1 (n = 10), the patients received continuously 1.5% sevoflurane. Subdural ICP, CBF and CMRO2 were measured twice at 30-min intervals. In group 2 (n = 10), sevoflurane concentration was increased from 1.5% to 2.5% after CBF1. CBF2 was measured after 20 min during 2.5% sevoflurane. Finally, CO2-reactivity was studied in both groups. RESULTS: In group 1, no time-dependent alterations in CBF, CVR, ICP and CMRO2 were found. In group 2, an increase in sevoflurane from 1.5% to 2.5% resulted in an increase in CBF from 29 +/- 10 to 34 +/- 12 ml 100 g-1 min-1 and a decrease in CVR from 2.7 +/- 0.9 to 2.3 +/- 1.2 mmHg ml-1 min 100 g (P < 0.05), while ICP and CMRO2 were unchanged. CO2-reactivity was maintained at 1.5% and 2.5% sevoflurane. CONCLUSION: Sevoflurane is a cerebral vasodilator in patients with cerebral tumours. Sevoflurane increases CBF and decreases CVR in a dose-dependent manner. CO2-reactivity is preserved during 1.5% and 2.5% sevoflurane.

Adult↗
PubMed1998

Mutation Detection by Cleavase in Combination With Capillary Electrophoresis Analysis: Application to Mutations Causing Hypertrophic Cardiomyopathy and Long-QT Syndrome.

Background: Genetic screening requires methods for mutation detection that are sensitive, precise, and robust. In population screening for complex genetic diseases in which large genes and/or several genes may be affected, automation of the mutation detection analysis is desirable. Methods and Results: The combined use of Cleavase nuclease and analysis of the DNA cleavage pattern by capillary electrophoresis was evaluated with respect to sensitivity, reproducibility, and dependency of experimental conditions in detecting mutations in the human genes MYH7 and KVLQT1 (KCNA9). The cleavage patterns obtained by capillary electrophoresis were very reproducible and robust. Conclusions: The combination of a sensitive enzymatic mutation detection method capillary electrophoresis may prove to be a useful system for automated, large-scale genetic screening.

Journal Article↗
PubMed1997

[Effect of indomethacin on the intracranial pressure].

Twenty patients subjected to craniotomy for supratentorial cerebral tumours were anaesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. A PaCO2 level averaging 4.8 kPa was achieved. The patients were randomized to intravenous indomethacin 50 mg or placebo administrated after exposure of the dura. A significant decrease in intracranial pressure from 6.5 to 1.5 mmHg (medians) was found after indomethacin administration. This decrease was caused by a significant decrease in cerebral blood flow associated with a significant increase in the arterio-venous oxygen difference. Indomethacin did not affect cerebral oxygen uptake, arteriovenous difference in lactate or the lactate/oxygen index, suggesting that indomethacin did not provoke global cerebral ischaemia. In the indomethacin group, dura was sufficiently relaxed in eight of nine patients, and dura was opened without the occurrence of cerebral swelling. In the placebo group, mannitol supplemented with hypocapnia was applied in five patients. These findings suggest that perioperative treatment with indomethacin is an excellent treatment of intracranial hypertension during normocapnic isoflurane anaesthesia for craniotomy.

Adult↗
PubMed1997

Reduced concentration of myocardial Na+,K(+)-ATPase in human aortic valve disease as well as of Na+,K(+)- and Ca(2+)-ATPase in rodents with hypertrophy.

Myocardial Na+,K(+)-ATPase was studied in patients with aortic valve disease, and myocardial Na+,K(+)- and Ca(2+)-ATPase were assessed in spontaneously hypertensive rats (SHR) and hereditary cardiomyopathic hamsters using methods ensuring high enzyme recovery. Na+,K(+)-ATPase was quantified by [3H]ouabain binding to intact myocardial biopsies from patients with aortic valve disease. Aortic stenosis, regurgitation and a combination hereof were compared with normal human heart and were associated with reductions of left ventricular [3H]ouabain binding site concentration (pmol/g wet weight) of 56, 46 and 60%, respectively (p < 0.01). Na+,K(+)- and Ca(2+)-ATPases were quantified by K(+)- and Ca(2+)-dependent p-nitrophenyl phosphatase (pNPPase) activity determinations in crude myocardial homogenates from SHR and hereditary cardiomyopathic hamsters. When SHR were compared to age-matched Wistar Kyoto (WKY) rats an increase in heart-body weight ratio of 75% (p < 0.001) was associated with reductions of K(+)- and Ca(2+)-dependent pNPPase activities (mumol/min/g wet weight) of 42 (p < 0.01) and 27% (p < 0.05), respectively. When hereditary cardiomyopathic hamsters were compared to age-matched Syrian hamsters an increase in heart-body weight ratio of 69% (p < 0.001) was found to be associated with reductions in K(+)- and Ca(2+)-dependent pNPPase activities of 50 (p < 0.001) and 26% (p = 0.05), respectively. The reductions in Na+,K(+)- and Ca(2+)-ATPases were selective in relation to overall protein content and were not merely the outcome of increased myocardial mass relative to Na+,K(+)- and Ca(2+)-pumps. In conclusion, myocardial hypertrophy is in patients associated with reduced Na+,K(+)-ATPase concentration and in rodents with reduced Na+,K(+)- and Ca(2+)-ATPase concentrations. This may be of importance for development of heart failure and arrhythmia in hypertrophic heart disease.

4-Nitrophenylphosphatase↗
PubMed1997

K+ supplementation increases muscle [Na+-K+-ATPase] and improves extrarenal K+ homeostasis in rats.

Effects of K+ supplementation (approximately 200 mmol KCl/100 g chow) on plasma K+, K+ content, and Na+-K+-adeonsinetriphosphatase (ATPase) concentration ([Na+-K+-ATPase]) in skeletal muscles as well as on extrarenal K+ clearance were evaluated in rats. After 2 days of K+ supplementation, hyperkalemia prevailed (K+-supplemented vs. weight-matched control animals) [5.1 +/- 0.2 (SE) vs. 3.2 +/- 0.1 mmol/l, P < 0.05, n = 5-6], and after 4 days a significant increase in K+ content was observed in gastrocnemius muscle (104 +/- 2 vs. 97 +/- 1 micromol/g wet wt, P < 0.05, n = 5-6). After 7 days of K+ supplementation, a significant increase in [3H] ouabain binding site concentration (344 +/- 5 vs. 239 +/- 8 pmol/g wet wt, P < 0.05, n = 4) was observed in gastrocnemius muscle. After 2 wk, increases in plasma K+, K+ content, and [3H]ouabain binding site concentration in gastrocnemius muscle amounted to 40, 8, and 68% (P < 0.05) above values observed in weight-matched control animals, respectively. The latter change was confirmed by K+-dependent p-nitrophenyl phosphatase activity measurements. Fasting for 1 day reduced plasma K+ and K+ content in gastrocnemius muscle in rats that had been K+ supplemented for 2 wk by 3.1 +/- 0.3 mmol/l (P < 0.05, n = 5) and 15 +/- 2 micromol/g wet wt (P < 0.05, n = 5), respectively. After induction of anesthesia, arterial plasma K+ was measured during intravenous KCl infusion (0.75 mmol KCl x 100 g body wt(-1) x h(-1)). The K+-supplemented fasted group demonstrated a 42% (P < 0.05) lower plasma K+ rise, associated with a significantly higher increase in K+ content in gastrocnemius muscle of 7 micromol/g wet wt (P < 0.05, n = 5) compared with their control animals. In conclusion, K+ supplementation increases plasma K+, K+ content, and [Na+-K+-ATPase] in skeletal muscles and improves extrarenal K+ clearance capacity.

Animals↗
PubMed1997

Effect of nitroglycerin in patients with increased pulmonary vascular resistance undergoing cardiac transplantation.

Acute right ventricular failure due to persistent pulmonary hypertension is a risk factor for premature death after cardiac transplantation. The purpose of this study was to follow changes in pulmonary haemodynamics in patients with pulmonary hypertension undergoing heart transplantation, and to examine whether postoperative changes can be predicted from a preoperative nitroglycerin (NTG) challenge. Seventeen consecutive patients with NYHA class IV heart failure and pulmonary hypertension (pulmonal vascular resistance (PVR) > 2.5 Wood units) underwent an NTG infusion before cardiac transplantation and were followed up using measurements of pulmonary haemodynamics before, early (24 h) and late (6 months) after cardiac transplantation. The effect of NTG was measured preoperatively and compared with posttransplantation values. Postoperative (24 h) PVR was reduced in all patients when compared with preoperative findings (PVR from 4.1 +/- 0.2 to 1.9 +/- 0.2 Wood units, Mean +/- SEM, p < 0.05). Mean pulmonary artery pressure (mPAP) was lowered in 16 of out 17 patients (41 +/- 2 to 26 +/- 1 mmHg, p < 0.05). None of the parameters were significantly changed during the subsequent 6 months. Postoperative PVR and mPAP were accurately estimated by preoperative NTG infusion (NTG vs 24 h posttranspl: PVR 2.2 +/- 0.2 vs 1.9 +/- 0.2 Wood units, p > 0.05; mPAP 30 +/- 2 vs 26 +/- 1 mmHg, p > 0.05). Heart transplantation candidates with pulmonary hypertension responsive to NTG can be expected to obtain a postoperative immediate fall in pulmonary pressures and PVR. The magnitude of this circulatory improvement can be predicted from a preoperative NTG infusion and is not different from values measured 6 months after transplantation.

Acute Disease↗
PubMed1996

Reduction of cerebral cortical [3H]ouabain binding site (Na+,K(+)-ATPase) density in dementia as evaluated in fresh human cerebral cortical biopsies.

Na+,K(+)-ATPase density in human cerebral cortex was for the first time studied by vanadate facilitated [3H]ouabain binding to intact samples. Fresh human cerebral cortical biopsies were obtained as a result of diagnostic frontal lobe biopsy from patients with normal pressure hydrocephalus (NPH) syndrome and associated dementia. For control measurements post-mortem samples were obtained from patients without clinically observed dementia. [3H]ouabain binding kinetics were evaluated: when incubating samples in 1 microM [3H]ouabain binding equilibrium was obtained after 6 h of incubation, non-specific uptake and retention amounted to only 2.3% of total uptake and retention of [3H]ouabain and release of specifically bound [3H]ouabain during washout in the cold occurred only slowly (T1/2 = 37 h). Evaluation of receptor affinity for ouabain was in agreement with a heterogeneous population of [3H]ouabain binding sites. [3H]Ouabain binding was significantly reduced after frozen storage of samples before measurements. Post-mortem degradation of cerebral [3H]ouabain binding sites occurred only slowly (T1/2 = 75 h). No significant variation in [3H]ouabain binding site density was observed between the cerebral lobes with occipital, parietal and temporal values (means +/- S.E.M., n = 5) amounting to 10281 +/- 649, 11267 +/- 1011 and 9263 +/- 615 pmol/g wet wt., respectively. [3H]Ouabain binding measured in frontal cortical samples gave values of (means +/- S.E.M., n = 5) 4274 +/- 1020 and 11397 +/- 976 pmol/g wet wt. delta % = 62; P < 0.05) in patients with dementia and controls, respectively. Human cerebral cortical capacity for active K+ uptake was around 37- and 16-fold greater than in skeletal muscular and myocardial tissue, respectively.

Aged↗
PubMed1996

Effects of perioperative indomethacin on intracranial pressure, cerebral blood flow, and cerebral metabolism in patients subjected to craniotomy for cerebral tumors.

This study was carried out to evaluate the effects of perioperative indomethacin on intracranial pressure (ICP), cerebral blood flow (CBF), and cerebral metabolism. Twenty patients subjected to craniotomy for supratentorial cerebral tumors were anesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. A PaCO2 level averaging 4.8 kPa (median) was achieved. The patients were randomized to intravenous indomethacin 50 mg or placebo administrated after exposure of the dura. ICP was measured continuously subdurally with a 22-gauge canula connected to a transducer. CBF and the arteriovenous difference of oxygen (AVDO2) were measured twice, before and after indomethacin/placebo administration. A significant decrease in ICP from 6.5 to 1.5 mm Hg (median) was found after indomethacin administration. This decrease was caused by a significant decrease in CBF associated with a significant increase in AVDO2. Indomethacin did not affect the cerebral metabolic rate of oxygen, the arteriovenous difference of lactate, or the lactate/oxygen index, suggesting that indomethacin did not provoke global cerebral ischemia. In the indomethacin group, dura was sufficiently relaxed in eight of nine patients and dura was opened without the occurrence of cerebral swelling. In one patient, mannitol treatment was necessary to prevent dural tightness. In the placebo group, mannitol supplemented with hypocapnia was applied in five patients. These findings suggest that perioperative treatment with indomethacin is an excellent treatment of intracranial hypertension during normocapnic isoflurane anesthesia for craniotomy.

Adult↗
PubMed1995

Drug delivery studies in Caco-2 monolayers. Synthesis, hydrolysis, and transport of O-cyclopropane carboxylic acid ester prodrugs of various beta-blocking agents.

A series of O-cyclopropane carboxylic acid ester prodrugs of various beta-blocking agents was synthesized. All prodrugs were hydrolyzed to give their parent compounds in aqueous phosphate buffer of pH 7.4 and in 80% human plasma. The half-lives in buffer solutions varied from 4 hours for the timolol prodrug to about 1 day for the prodrug of alprenolol. In human plasma the half-lives were shorter, ranging from 1 to 7 hours. The formation of the O-cyclopropane carboxylic acid ester derivatives significantly increased the lipophilicities of the beta-blockers as measured by the distribution coefficient between n-octanol and aqueous phosphate buffer of pH 7.4. To characterize the biomembrane permeability characteristics of the beta-blockers, transport properties across Caco-2 cell monolayers were investigated. An increase in lipophilicity resulted in a higher permeability of the prodrugs as compared to the parent compounds. Hence, acebutolol experienced an increment of a factor 17 on the apparent permeability coefficient, Papp, whereas Papp for the more lipophilic drug propranolol was increased by a factor of only 1.26. Some conversion of the prodrugs to their parent compounds was observed during the transport and appeared to be due to enzymatic intracellular metabolism.

Acebutolol↗