Biomedical subjects

K Törnebrandt

Publications and source records attributed to K Törnebrandt.

At least 19 recordsLinked to original sources

PubMed2002

Bactericidal/permeability-increasing protein inhibits endotoxin-induced vascular nitric oxide synthesis.

BACKGROUND: Endotoxin (lipopolysaccharide, LPS) up-regulates inducible nitric oxide synthase (iNOS) in blood vessels during septic shock. This promotes the production of nitric oxide (NO), leading to dilation of the vessels. The aim of the study was to investigate the effects of the LPS-binding endogenous antibiotic bactericidal/permeability-increasing protein (BPI) on the action of LPS on the blood vessels wall and to identify possible influence on underlying NO-related mechanisms. METHODS: Isolated segments of rat thoracic aorta and cultured primary smooth muscle cells were incubated for 5-48 h in the presence of the following combinations of compounds: (a) LPS; (b) interleukin-1beta (IL-1beta); (c) BPI; (d) BPI + LPS; (e) BPI + IL-1beta or (f) neither BPI, LPS nor IL-1beta (control). After incubation of intact segments, we measured smooth muscle contraction in response to phenylephrine and accumulation of the NO end products nitrate and nitrite in surrounding medium. Western blot was used to assess the levels of inducible nitric oxide synthase (iNOS) in cultured cells. RESULTS: Both LPS and IL-1beta decreased contractility and increased NO production, as well as iNOS. Co-incubation with BPI attenuated all the effects of LPS but only the effects of prolonged exposure to IL-1beta in cultured cells. CONCLUSION: We conclude that BPI attenuates the LPS-induced changes in vascular reactivity by inhibiting the expression of iNOS resulting in decreased NO formation and restored responsiveness to vasoconstrictors. The data suggest that BPI can prevent circulatory disturbances during Gram-negative sepsis.

Animals↗

PubMed2001

Pain relief after esophagectomy: Thoracic epidural analgesia is better than parenteral opioids.

OBJECTIVE: To compare postoperative pain relief and pulmonary function in patients after thoracoabdominal esophagectomy treated by continuing perioperative thoracic epidural anesthesia or changing to parenteral opioids. DESIGN: Prospective, randomized study. SETTING: University teaching hospital. PARTICIPANTS: Thirty-three patients undergoing thoracoabdominal esophagectomy. INTERVENTIONS: General anesthesia was combined with thoracic epidural anesthesia during surgery. The patients either continued with thoracic epidural analgesia (n = 18) or were switched to patient-controlled analgesia with intravenous morphine (n = 15) for 5 postoperative days. Pain scores were estimated twice daily, at rest and after mobilization. Peak expiratory flow, forced expiratory volume, and vital capacity were measured the day before surgery, postoperative day 2, and postoperative day 6. Adverse events and complications were recorded. MEASUREMENTS AND MAIN RESULTS: At rest, there were no differences in pain relief between the groups. Pain scores at mobilization showed a significantly lower value in the epidural group (p < 0.027). No intergroup differences were found regarding pulmonary function, which decreased on postoperative day 2, but was improved on postoperative day 6. CONCLUSION: Continuation of intraoperative thoracic epidural anesthesia for 5 postoperative days provides better pain relief at mobilization compared with a switch to patient-controlled analgesia with intravenous morphine. There was no intergroup difference in the impact on measures of pulmonary function.

Adult↗

PubMed2000

A comparison of the effects on postoperative pain relief of epidural analgesia started before or after surgery.

In a randomized, prospective clinical study pain relief and pulmonary function were compared after upper abdominal surgery when thoracic epidural analgesia was instituted either before or after surgery. Twenty-six patients admitted for surgery to treat gastro-oesophageal reflux received thoracic epidural analgesia as an adjunct to general anaesthesia either before or after surgery. Twelve patients received epidural mepivacaine 20 mg mL(-1) and morphine perioperatively. Another 14 patients received an epidural bolus of bupivacaine 2.5 mg mL(-1) and morphine after skin closure. Bupivacaine 2.5 mg mL(-1) with morphine was adminstered to all patients for three postoperative days. No intergroup differences were found regarding pain at rest and mobilization. The requirement for additional analgesics was similar in both groups as well as peak expiratory flow. Thoracic epidural analgesia that had already been induced before surgery, and was continued into the postoperative period, does not seem to add any advantage regarding pain relief and lung function compared with thoracic epidural analgesia instituted in the immediate postoperative period.

Abdomen↗

PubMed2000

Effects of propofol on substance P-induced relaxation in isolated human omental arteries and veins.

To elucidate if an effect of propofol on endothelium-dependent relaxation could contribute to propofol-induced vasodilation, smooth muscle relaxation of isolated human omental artery and vein segments precontracted by endothelin-1 were measured. Substance P induced a concentration-dependent relaxation (mean +/- SEM) in both artery (63 +/-8.4% of precontraction, n = 9) and vein (60+/-11%, n = 7). The relaxation was enhanced by 10(-6) M propofol (artery, 72+/-9.5%, n = 9; vein, 81+/-12%, n = 7) but not affected by 10(-7), 10(-5) and 10(-4) M propofol. In the presence of Nomega-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 10(-6) M propofol still enhanced the substance P-induced relaxation in arteries but not veins, whereas 10(-4) M propofol inhibited the relaxation in both arteries (rightward shift of the concentration-response curve) and veins (28+/-7.5%, n = 8). In the presence of potassium chloride (to prevent hyperpolarization), the enhancement of substance P-induced relaxation by 10(-6) M propofol was abolished in both arteries and veins whereas 10(-5) and 10(-4) M propofol reduced the relaxation in arteries (38+/-13% at 10(-5) M, n = 6; 30+/-11% at 10(-4) M, n = 6) but not in veins. These results demonstrate that propofol, at lower, clinically relevant concentrations, promotes endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins.

Adult↗

PubMed1999

Substance P relaxes rat bronchial smooth muscle via epithelial prostanoid synthesis.

BACKGROUND: Substance P is present in bronchial nerve fibres. The physiological actions of substance P are mediated via tachykinin NK(1) receptors. Immunochemical studies have demonstrated tachykinin NK(1) receptors in the rat airway epithelium. OBJECTIVE: To elucidate how epithelial tachykinin NK(1) receptors affect smooth muscle response to substance P. METHODS: Contractile response of isolated rat bronchial trunk with or without epithelium was recorded. RESULTS: In intact segments precontracted by 5-hydroxytryptamine, relaxation was induced by substance P and the nitric oxide donor, sodium nitroprusside. Removal of the epithelium abolished relaxation induced by substance P but did not affect relaxation induced by sodium nitroprusside. The cyclo-oxygenase inhibitor, indomethacin, but not the nitric oxide synthase inhibitor, L-N(G)-monomethylarginine, reduced the relaxation in response to substance P. CONCLUSIONS: Epithelial tachykinin NK(1) receptors mediate substance-P-induced relaxation of rat bronchial smooth muscle via release of prostanoids but not nitric oxide.

Animals↗

PubMed1998

Relaxant effects of propofol on human omental arteries and veins.

We have investigated the relaxant effects of propofol on smooth muscle tension in human omental arteries and veins to determine if endothelium-related mechanisms are involved. Isolated vessel segments were precontracted with endothelin-1 and propofol was added cumulatively (10(-7)-10(-4) mol litre-1). In both artery and vein segments, propofol induced relaxation, which was not dependent on an intact endothelium. Relaxation was reduced when the extracellular K+ concentration was increased and in the presence of tetraethylammonium chloride (TEA). In intact segments, N-nitro-L-arginine methyl ester (L-NAME), indomethacin, glibenclamide, 4-aminopyridine, clotrimazole and atropine did not affect the concentration-response curve of propofol. This indicates that propofol relaxes human omental arteries and veins in an endothelium independent manner, and that hyperpolarization caused by activation of the K+ channel, BKCa, may be involved.

Adult↗

PubMed1997

Effect of cooling on vascular smooth muscle response to endothelin-1 in human and rat veins.

BACKGROUND: The plasma level of endothelin-1 is locally increased during cooling but the net vasoconstrictor effect will be dependent on temperature effects on the vascular smooth muscle reactivity in response to the polypeptide. The aim of this study was to investigate the effect of cooling on the vascular smooth muscle response to endothelin-1 in human and rat veins. METHODS: Registration of vascular smooth muscle activity in vitro in vessel preparations from normal subjects. SETTING: Laboratory. PATIENTS AND ANIMALS: Superficial hand veins from 14 patients undergoing hand surgery and external jugular veins from 14 rats. INTERVENTIONS: Effects of endothelin-1, after denudation of the endothelium and during cooling, were compared with controls without these interventions. RESULTS: At 37 degrees C, endothelin-1 induced a concentration-dependent contraction in the human hand and rat jugular veins. The sensitivity to endothelin-1 was enhanced in segments without endothelium. At 37 degrees C, no relaxation in response to endothelin-1 was observed. Cooling to 10 degrees C did not alter precontraction achieved by endothelin-1 at 37 degrees C in the human hand veins, while it depressed the precontraction in the rat jugular vein. The effect of cold was reversible. Removal of the endothelium did not alter the response to cooling. CONCLUSIONS: The maintained reactivity in response to endothelin-1 during cooling of the human vessels suggests that the reported increase in endothelin-1 levels due to local cooling could contribute in the pathophysiology of peripheral vasospasm in humans.

Adolescent↗

PubMed1996

Binding of [3H]-5-hydroxytryptamine to human coronary artery and bypass graft vessels.

OBJECTIVES: 5-Hydroxytryptamine (5-HT) has a wide range of vascular effects mediated via specific receptors and it has been suggested to be a mediator in ischemic heart disease. The aim of the present study was to localise the 5-HT receptors within the vessel wall. METHODS: Epicardial coronary arteries obtained from patients undergoing cardiac transplantation, internal mammary arteries from heart donors and saphenous veins from patients undergoing coronary bypass surgery, were sectioned and incubated with [3H]-5-HT for in vitro receptor autoradiography. RESULTS: Microscopic analysis of high resolution autoradiographic images revealed a similar pattern of [3H]-5-HT binding in epicardial coronary and internal mammary artery, where it predominated in the lamina muscularis. In the saphenous vein, binding increased towards the adventitia which showed dense, displaceable binding to the vasa vasorum as well as to nerve-like structures, from which binding was only partially displaced. Computer-assisted densitometric analysis of low resolution autoradiographs revealed a high degree of specific binding to all vessels examined. CONCLUSIONS: The distribution of the [3H]-5-HT binding is different in the saphenous vein compared to epicardial coronary and internal mammary artery. The dense binding to vasa vasorum in the saphenous vein suggests a role for 5-HT in closure of these nutrient vessels, which could contribute to the formation of atherosclerotic changes in saphenous vein grafts.

Adult↗

PubMed1996

Characteristics of contractile 5-HT receptors in isolated human omental arteries: presence of 5-HT1 and 5-HT2 receptors.

5-Hydroxytryptamine (5-HT) has a variety of biological effects, e.g. it induces and modulates vascular smooth muscle activity. The effects are mainly mediated via a hetergenous group of 5-HT receptor subtypes. In order to elucidate the 5-HT receptor mechanisms in the human splanchnic circulation, in vitro studies were carried out on omental arteries obtained from patients undergoing abdominal surgery. Four 5-HT receptor agonists with different selectivity all induced concentration-dependent contraction (potency and order of potency indicated): 5-HT (non-selective; 6.12 +/- 0.14)=sumatriptan (5-HT1; 6.32 +/- 0.07) > alpha-methyl-5-HT (5-HT2; 5.41 +/- 0.05) > 2-methyl-5-HT (5-HT3; < or =4.46+/-0.05). The 5-HT1/5-HT2 receptor antagonist methiothepin antagonised the contraction induced by 5-HT, sumatriptan, alpha-methyl-5-HT and 2-methyl-5-HT. The 5-HT2 receptor antagonist ketanserin antagonised the contraction induced by 5-HT, alpha-methyl-5-HT and 2-methyl-5-HT. The 5-HT3 receptor antagonist tropisetron did not antagonise the contraction elicited by 2-methyl-5-HT. The results suggest that 5-HT-induced conataction in human omental arteries involves both 5-HT1 and 5-HT2, but maybe not 5-HT3-receptors.

Adult↗

PubMed1995

Neurological complications after anaesthesia. A follow-up of 18,000 spinal and epidural anaesthetics performed over three years.

17 733 consecutive central blocks (8501 spinal and 9232 epidural anaesthetics) performed during a three-year period were analyzed for alleged complications. Neurological complications related to anaesthesia were reported in 17 cases of which 13 patients had persisting lesions after three spinal and ten epidural blocks. In two patients given spinal anaesthesia, the technique was inadequate. In seven epidural blocks, the connection between neurological lesion and the anaesthetic technique could be argued. In five of these cases, polyneuropathy or nonspecific neurological symptoms were present. Three complications after epidural blocks were paraplegias caused by spinal haematomas in patients with deranged haemostatic capacity.

Adult↗

PubMed1994

Nitrous oxide for colonoscopy discomfort: a randomized double-blind study.

The possibility of reducing recovery time after colonoscopy was studied using patient-administered nitrous oxide and comparing it with our standard treatment of ketobemidone plus midazolam. Fifty consecutive colonoscopy patients were randomized to receive either (i) intravenous ketobemidone hydrochloride 2.5 mg, midazolam 2.5 mg, and breathing air from a face mask with a demand valve (KHM) or (ii) intravenous saline and a breathing mixture of even parts of oxygen and nitrous oxide (Entonox) from the same valve setup. Patient discomfort during colonoscopy was assessed using visual analogue scales. All patients were allowed to stay for recovery as long as they wanted, and the time was measured. Modified recollection tests were performed prior to colonoscopy and when the patients left the Endoscopy Unit, in order to study the degree of mental impairment induced by the procedure and the medication. All patients had complete colonoscopies of the same duration in both groups. Discomfort during colonoscopy was rated the same in both groups (2p = 0.6413). Both groups of patients scored identically in the precolonoscopy recollection test. Most patients had a lower score after colonoscopy, but Entonox-treated patients scored significantly better than those with KHM (2p = 0.0250). Patients treated with Entonox opted to leave the Unit directly after the procedure (median 0 minutes; interquartile range 0-5 minutes) compared to 38 minutes for those with KHM (interquartile range 10-75 min), 2p < 0.001. It seems from our data that nitrous oxide gives pain relief equal to that in our standard treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Endothelial relaxing 5-hydroxytryptamine receptors in the rat jugular vein: similarity with the 5-hydroxytryptamine1C receptor.

Serotonin (5-HT) at low concentrations induces an endothelium-dependent relaxation in the rat jugular vein mediated via a 5-HT1-like receptor. The receptor mediating this relaxation was characterized in vitro using agonists and antagonists in segments precontracted with prostaglandin F2 alpha in the presence of the 5-HT2 receptor antagonist ketanserin. The following substances acted as agonists, with the order of potency: 5-HT > dl-alpha-methyl-5-hydroxytryptamine = 5-carboxamidotryptamine > quipazine > 8-hydroxy-2-(dl-n-propylamino) tetralin. dl-Propranolol, mesulergine and mianserin acted as competitive, methysergide, 6-methyl-1-(1-methylethyl)-ergoline-8 beta-carboxylic acid 2-hydroxy-1-methylpropyl ester and sumatriptan as non-competitive, and ritanserin acted as both a competitive and non-competitive antagonist of the 5-HT-induced relaxation. Neither the 5-HT2 antagonists ketanserin and spiperone nor the 5-HT3 antagonist 1 alpha-H,3 alpha,5 alpha-H-tropan-3-yl,3,5-dichlorbenzoate affected the 5-HT-induced relaxation. The pEC50 values of the agonists and the pA2 and pAh values of the antagonists correlated strongly with pKD values at the 5-HT1C binding site. These results are consistent with a peripheral vascular 5-HT1C receptor in the rat jugular vein.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

Heterogeneity of contractile 5-HT receptors in human hand veins.

To increase our knowledge of human peripheral vasospasm we characterized the contractile 5-hydroxytryptamine (5-HT) receptors in human superficial hand vein segments in vitro. The 5-HT1 receptor agonist, sumatriptan, the 5-HT2 receptor agonist, dl-alpha-methyl-5-HT, and the 5-HT3 receptor agonist, 2-methyl-5-HT, all induced concentration-dependent contractions. The contractile response to sumatriptan was antagonized by the non-selective 5-HT receptor antagonist, methiothepin, but was unaffected by the 5-HT2 receptor antagonist, ketanserin. The contractile response to dl-alpha-methyl-5-HT was antagonized by both methiothepin and ketanserin. The contraction elicited by 2-methyl-5-HT was not affected by the 5-HT3 receptor antagonist, MDL 72222, but was antagonized by ketanserin. The results suggest that serotonergic contraction in the human superficial hand vein involves both 5-HT1 and 5-HT2 but not 5-HT3 receptors. Such receptor heterogeneity in human blood vessels should be considered when using drugs and when designing future compounds for medical use.

Adult↗

PubMed1990

Cooling enhances alpha 2-adrenoceptor-mediated vasoconstriction in human hand veins.

The contribution of different receptor subtypes in the contractile response during cooling in human hand vessels is of considerable interest in the understanding of cold-induced peripheral vasospasm as it appears in Raynaud's phenomenon. Subcutaneous vein segments from 50 patients undergoing hand operations not related to vascular disorders were examined in vitro. The temperature in the organ bath was initially 37 degrees C and was either continuously lowered to 10 degrees C or kept constant at 37 degrees C, 29 degrees C or 20 degrees C. The characteristics of the alpha-adrenoceptor-mediated motor response were elucidated with the use of the alpha 1-antagonist, prazosin, and the alpha 2-antagonist, yohimbine. A great variability between individuals in the proportions of alpha 1- and alpha 2-adrenoceptors was found. In the majority of the vessels continuous cooling to 25 degrees C augmented a noradrenaline-induced contraction. This augmentation was unaltered in the presence of prazosin but abolished by yohimbine, suggesting that it was mediated via the alpha 2-adrenoceptor. In the remaining vessels with a predominating alpha 1-adrenoceptor-mediated response a cold-induced relaxation was registered. This could be the result of a reduced alpha 1-adrenoceptor-mediated contraction at this low temperature. These varying reactions to cooling were unaffected by the beta-antagonist, propranolol, and by endothelial denudation. The results obtained in corresponding experiments with the alpha 1-agonist methoxamine and alpha 2-agonist, oxymetazoline, were conflicting, probably due to the poor selectivity of these agonists in human tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

PubMed1990

Effect of cooling on smooth muscle response to 5-hydroxytryptamine in human hand veins.

5-Hydroxytryptamine has been suggested to be a mediator in peripheral cold-induced vasospasm. In order to investigate the contribution of different 5-hydroxytryptamine receptor subtypes in the contractile response during cooling, segments of subcutaneous hand veins obtained from 50 patients undergoing hand surgery were examined in vitro in organ baths. The temperature in the bath was initially 37 degrees C and was either continuously lowered to 10 degrees C or kept constant at 37 degrees C, 29 degrees C. Cooling to 25 degrees C augmented the contractile response to 5-hydroxytryptamine in intact as well as in endothelium-denuded segments. The 5-hydroxytryptamine2 receptor antagonist ketanserin antagonized the contractile response to 5-hydroxytryptamine at 37 degrees C, and in addition abolished the cold-induced enhancement of the response during cooling. This points to a major role of the 5-hydroxytryptamine2 receptor in the cold-induced augmentation of the response to 5-hydroxytryptamine, which was further supported by increased contractions to the 5-hydroxytryptamine2 receptor agonist alpha-methyl-5-hydroxytryptamine during cooling. Contractile responses were also obtained by the selective 5-hydroxytryptamine1-like receptor agonist GR43175 interpreted to indicate the presence of a smaller 5-hydroxytryptamine1-like receptor population. However, the response to GR43175 was unaffected by cooling. These results warrant further investigations of the role of 5-hydroxytryptamine in cold-induced peripheral vasospasm.

Adolescent↗

PubMed1990

Comparison of ethanol absorption during continuous and intermittent flow irrigation in transurethral resection.

Transurethral resection of the prostate was performed using intermittent-flow bladder irrigation (n = 50), or by continuous-flow irrigation, using a suprapubic trocar (n = 50). The irrigant solution contained 1.5% glycine +1% ethanol and fluid absorption was measured from the ethanol content of the expired breath. Fluid absorption was significantly lower in patients receiving continuous-flow irrigation (p less than 0.007) although major absorption occurred in one of these patients. The immediate detection of absorption with the ethanol method allowed us to stop one of the operations performed with intermittent bladder irrigation, at which 2 l of fluid had been absorbed in 20 min. With correction for the amount of removed prostatic tissue, there were no differences in operation time or blood loss between the two types of irrigation.

Aged↗

PubMed1989

Cooling augments contractile response to 5-hydroxytryptamine via an endothelium-dependent mechanism.

The interaction between cooling and vasoactive substances, e.g. 5-hydroxytryptamine (5-HT), plays an important role in the pathophysiology of cold-induced vasospasm. Our objective was to study the effect of cooling on the 5-HT vascular response, classify the involved 5-HT receptors, and to analyze the role of the endothelium. Ring segments from the rat jugular vein, a preparation without alpha-adrenergic receptors, were suspended in organ baths to record the circular motor activity. The temperature was initially 37 degrees C and was thereafter either continuously lowered to 10 degrees C or kept constant at different temperatures within this range. 5-HT at low concentrations (10(-11) to 3 x 10(-8) M) induced relaxation at 37 degrees C in segments precontracted by prostaglandin F2 alpha. The relaxation was recognized to be mediated via an endothelium-dependent 5-HT1-like receptor mechanism presumably involving the release of endothelium-derived relaxing factor (EDRF). Cooling to 29 and 20 degrees C diminished the relaxation, probably due to an attenuated release of EDRF. 5-HT at concentrations of more than 10(-8) M induced a contraction in all vessels at 37 degrees C mediated via a 5-HT2 receptor. An increased 5-HT-induced contraction was seen at temperatures below 37 degrees C in vessels with an intact endothelium. Endothelial denudation diminished the cold-induced enhancement of the contraction to 5-HT. These studies suggest that endothelial mechanisms contribute to a cold-induced augmented response to 5-HT.

Animals↗

PubMed1986

Heart involvement in metastatic carcinoid disease.

Sixteen patients with metastatic carcinoid tumors of ileal or cecal origin were studied in order to evaluate the frequency and degree of cardiac involvement in a nonselected patient group. We have also studied the correlation between plasma hormone levels (e.g., 5-hydroxytryptamine (5-HT) and substance P) and the degree of cardiac involvement. The patients underwent physical examinations, electrocardiograms, chest x-rays, cardiac catheterization, and echocardiography. Plasma levels of 5-HT and substance P were analyzed. Carcinoid heart involvement was found in 3 of 16 patients (19%) but no patient had subjective symptoms associated with heart disease. Four patients (25%) had slight pulmonary hypertension. No left-sided heart lesions were seen. No correlation between blood levels of 5-HT or substance P and heart involvement was found. Eight patients died during the follow-up period, but in none of these was the cause of death cardiac failure. Carcinoid heart disease is not as common in our patients as in patients selected on a cardiological basis described in earlier studies. Echocardiography appears to be the most efficient technique for detection of even subclinical heart involvement and a useful tool for following its progress.

Adult↗