| 1. |
- Bentzer, Peter, et al.
(author)
-
Supersensitivity in rat micro-arteries after short-term denervation
- 1997
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In: Acta Physiologica Scandinavica. - 0001-6772. ; 161:2, s. 125-133
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Journal article (peer-reviewed)abstract
- Contractile responses to phenylephrine and high-K+ were investigated in vitro in microvascular preparations from the rat medial plantar artery, a branch from the saphenous artery, obtained after short-term denervation in vivo. Two groups of animals were studied: (1) animals undergoing surgical resection of the saphenous nerve, and (2) animals undergoing surgical resection of both the sciatic and saphenous nerves. The animals were operated on one side only. Microvascular preparations (diameter about 325 microns) were obtained 10 days after surgery. Vessels from the non-operated side served as controls. Immunocytochemistry showed a decreased number of both neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres in vessels after resection of the saphenous nerve only. Resection of both the saphenous and the sciatic nerve caused a complete loss of immunoreactive nerve fibres. Mechanical measurements were performed using a wire myograph. In vessels subjected to resection of the saphenous nerve the sensitivity to phenylephrine was similar to controls. Vessels denervated by resection of both the saphenous and sciatic nerves showed significant increases in phenylephrine and potassium sensitivity. When depolarized in high-K+ solution the denervated vessels showed an increased sensitivity to extracellular Ca2+. The results show that complete short-term denervation of the rat medial plantar artery in vivo causes a pronounced supersensitivity in the vascular smooth muscle. The supersensitivity appears not to be restricted to the sympathetic alpha-receptors but also associated with changes in the cellular excitation-contraction coupling. Such altered reactivity of the vascular smooth muscle may contribute to vascular disturbances observed in vivo after nerve damage or surgical denervation.
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| 2. |
- Ekelund, Ulf, et al.
(author)
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Effects of the combined ETA and ETB receptor antagonist PD145065 on arteries, arterioles, and veins in the cat hindlimb
- 1995
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In: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 26:Suppl. 3, s. 211-213
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Journal article (peer-reviewed)abstract
- The aim of this study was to describe in quantitative terms the effects of ETA and ETB receptor blockade on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 microns), small arterioles (< 25 microns), and veins in the cat gastrocnemius muscle in vivo. In the muscle vascular bed, the combined ETA and ETB receptor antagonist PD145065 (1 mg/kg/min, intra-arterially) abolished the biphasic vascular responses (dilatation followed by constriction) to both ET-1 (0.4 microgram/kg/min, intra-arterially) and to the selective ETB receptor agonist IRL1620 (3.2 micrograms/kg/min, intra-arterially). In the cat femoral artery and vein in vitro, PD145065 competitively inhibited the contractile responses to both ET-1 and IRL1620. The contractile response to the latter agonist could be evoked only after long-term incubation of the vessels (37 degrees C for 5 days). These results indicate that PD145065 is a potent antagonist at both ETA and ETB receptors in vivo and in vitro. Therefore, this antagonist may prove useful for elucidating the possible physiologic and/or pathophysiologic roles of the endothelins. For example, it was shown that PD145065 had no effect on vascular tone in the resting state, indicating no role for the endothelins in the regulation of basal vascular tone in cat skeletal muscle.
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| 3. |
- Ekelund, A, et al.
(author)
-
Additional colloids have only a minor haemodilutive effect after surgery for aneurysmal subarachnoid haemorrhage
- 1999
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In: British Journal of Neurosurgery. - : Informa UK Limited. - 0268-8697 .- 1360-046X. ; 13:4, s. 399-404
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Journal article (peer-reviewed)abstract
- Haemodilution is commonly used as prophylaxis, as well as treatment for cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). Thirty-six patients operated for aneurysmal SAH were evaluated retrospectively; 24 received haemodilutive therapy and 12 patients, as a control group, received no additional therapy. There was a 'spontaneous' drop in haematocrit by 22% in both groups, and a corresponding drop in haemoglobin by 23% in the treatment group and 19% in the non-haemodiluted group, during the first 4 days after the SAH. After the initial decrease the haematocrit remained stable between 0.28 and 0.33 until day 14 in both groups. The haemodilutive group had only a minor lower haematocrit level during days 8-12 as the additional fluid resulted in increased renal excretion. This minor difference was, however, significant (p < 0.02).
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| 4. |
- Ekelund, A, et al.
(author)
-
Transcranial cerebral oximetry related to transcranial Doppler after aneurysmal subarachnoid haemorrhage
- 1998
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In: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 140:10, s. 1029-1036
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Journal article (peer-reviewed)abstract
- Noninvasive methods for detecting cerebral artery vasospasm, still a serious complication following aneurysmal subarachnoid haemorrhage, are of vital interest. Up-to-date transcranial Doppler ultrasound (TCD) has proved to be sensitive in detecting vasospasm in the middle cerebral artery, but has less accuracy for other cerebral arteries. Transcranial cerebral oximetry (TCCO) is a new non-invasive technique which may increase the reliability for detecting cerebral ischaemia. The purpose of the present study was to evaluate a putative correlation between TCCO and TCD. We examined the two hemispheres in 14 patients with the aim of evaluating a proposed correlation between TCD and TCCO. Analysis of all absolute values (maximum TCD mFV and minimum TCCO saturation, respectively) in all series indicate a correlation between TCCO and TCD, p < 0.01, r = -0.62. All patients with TCD mean flow velocity > 120 cm/s also presented TCCO saturation < 60%. Conversely, all patients with normal TCCO saturation (> or = 63%) presented normal or moderately increased TCD velocities. In clinical neurosurgical practice it is of great interest if a true correlation between TCD and TCCO exists. The present results support the assumption that TCCO may enhance the reliability for detecting cerebral ischaemia after aneurysmal subarachnoid haemorrhage.
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| 5. |
- Roijer, Anders, et al.
(author)
-
Cardiac changes in stroke patients and controls evaluated with transoesophageal echocardiography
- 1997
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In: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 31:6, s. 329-337
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Journal article (peer-reviewed)abstract
- In stroke patients several cardiac changes associated with embolism can be detected with transoesophageal echocardiography. Potential major cardiac embolic sources (e.g. atrial fibrillation, thrombi of left ventricle/atrium, vegetation, myxoma, dilated cardiomyopathy) have a causal relationship to embolism. Other changes with no certain causal relationship are regarded as potential minor cardiac embolic sources (e.g. atrial septal aneurysm, patent foramen ovale, mitral annular calcification, mitral valve prolapse, protruding atheroma of the aorta). We compared the prevalences of major and minor potential cardiac embolic sources in a stroke population with that in controls. One hundred and twenty-one patients with first-ever stroke were compared with 68 randomly selected controls. All subjects underwent magnetic resonance imaging of the brain, carotid ultrasound and transthoracic/transoesophageal echocardiography. The patients were slightly older (mean age 70.7 +/- 10.3 years) than the controls (65.5 +/- 15.5 years) (p < 0.05). Potential major cardiac embolic sources were found in 27% of the patients and in 4% of the controls (p < 0.001). The most common major potential embolic source was atrial fibrillation, detected in 22/121 patients. Fifteen of these also had spontaneous echocontrast in the left atrium. Eleven left atrial thrombi were found (four of these patients had atrial fibrillation and seven had sinus rhythm). A history of heart disease was more common in patients with a potential major cardiac embolic source or a carotid artery stenosis (77%) than in those patients without (44%) (p < 0.01). After excluding subjects with a major potential cardiac embolic source and/or carotid artery stenosis, no differences in the prevalence of minor potential cardiac embolic sources were found between patients (55%) and control subjects (47%) (p = NS). Even when subjects without a major potential cardiac embolic source or a carotid artery stenosis were categorized into three age groups (35-54, 55-74 and > 74 years) the prevalence of potential minor cardiac embolic sources did not differ between patients and controls. To conclude, major potential cardiac embolic sources are more common in an older population with first-ever stroke than in a comparable control group. However, potential minor cardiac embolic sources did not differ in prevalence in the patients compared with controls. Certain changes (e.g. atrial septal aneurysm) might have a potential embolic role in younger stroke patients but in our study no difference was found between older stroke patients and controls.
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| 6. |
- Ekelund, Ulf
(author)
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Effects of angiotensin-converting enzyme inhibition on arterial, venous and capillary functions in cat skeletal muscle in vivo
- 1996
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In: Acta Physiologica Scandinavica. - 0001-6772. ; 158:1, s. 29-37
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Journal article (peer-reviewed)abstract
- The aim of the present study was to analyse quantitatively, on a cat gastrocnemius muscle preparation in vivo, the effects of local angiotensin-converting enzyme (ACE) inhibition by enalaprilat on total regional vascular resistance (tone) and its distribution to the large-bore arterial resistance vessels (> 25 microns), the small arterioles (< 25 microns) and the veins. Associated effects on capillary pressure and fluid exchange were also studied. Close-arterial infusion of enalaprilat (0.05-0.20 mg kg muscle tissue min-1) elicited a moderate dilator response in all three consecutive sections of the muscle vascular bed, an increase in capillary pressure and transcapillary fluid filtration. This dilation could be abolished by the selective bradykinin B2-receptor antagonist Hoe 140 (2 mg kg-1 min-1, i.a.), indicating that the dilator mechanism of ACE inhibition was an increased local concentration of bradykinin, and hardly at all a decreased concentration of angiotensin (AT) II. The generalized dilator response to ACE inhibition along the vascular bed suggested a relatively uniform distribution of ACE from artery to vein and this was further supported by the finding that a close-arterial infusion of AT I (0.04-0.32 microgram kg-1 min-1), which was vasoactive only after conversion to AT II by local ACE, elicited a generalized constrictor response in all three vascular sections. In contrast, infused AT II (0.01-0.16 microgram kg-1 min-1) constricted almost selectively the large-bore arterial vessels. The specific angiotensin AT1-receptor antagonist losartan (2 mg kg-1 min-1, i.a.) abolished the constrictor response to AT II but did not affect vascular tone under control conditions, indicating that AT II is not involved in the initiation of basal vascular tone in muscle. These results, taken together, indicate that under basal conditions vascular ACE contributes to the local control of vascular tone in skeletal muscle by degrading the endogenous dilator bradykinin, and not by converting AT I into vasoconstrictor AT II.
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| 7. |
- Ekelund, Ulf, et al.
(author)
-
Endogenous nitric oxide as a physiological regulator of vascular tone in cat skeletal muscle during haemorrhage
- 1996
-
In: Acta Physiologica Scandinavica. - 0001-6772. ; 157:4, s. 471-479
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Journal article (peer-reviewed)abstract
- The problem whether endogenous nitric oxide (NO) may serve as a true physiological regulator of vascular tone in vivo was approached by testing its role during graded acute haemorrhage with the aid of the nitric oxide synthase (NOS) inhibitor L-NAME. The study was performed on the vascular bed of cat skeletal muscle with a technique permitting quantitative recordings of vascular resistance in the whole vascular bed (RT) and in its consecutive sections, the proximal arterial resistance ('feeder') vessels (> 25 microns; Ra,prox), the small arterioles (< 25 microns) and the veins. NO blockade by close-arterial L-NAME infusion in the control situation increased RT from 16.3 to 33.0 PRU (+102%), because of a selective increase in Ra,prox by 16.7 PRU. A 35% blood loss per se raised RT from 13.6 to 21.7 PRU. Superimposed NO blockade in this state caused a much stronger vasoconstriction than in the control situation, increasing RT to 60.9 PRU (+181%) and Ra,prox by 40.5 PRU, which indicated an approximately 2.4-fold increase (P < 0.001) in the NO dilator influence in the Ra,prox section above control. The effect was independent of autonomic nerves. The increased NO dilator influence during haemorrhage most likely was caused by an increased production of endothelium-derived nitric oxide (EDNO), The constrictor response to L-NAME was graded in relation to the blood loss (17.5 vs. 35%). The results indicate that EDNO functions as a physiological regulator of vascular tone in the arterial 'feeder' vessels during haemorrhage, serving to counterbalance to a significant extent the concomitant adrenergic constriction, and thereby preventing critical reduction of blood flow and untoward heterogeneous flow distribution within the tissue.
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| 8. |
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| 9. |
- Dahm, Peter
(author)
-
Nitric oxide in experimental sepsis
- 1998
-
Doctoral thesis (other academic/artistic)abstract
- Nitric oxide (NO) is important in the control of blood pressure and organ perfusion. In septic shock, NO produced by inducible NO-synthase (NOS) has been claimed to mediate pathological vasodilation and cell injury, while NO produced by constitutive NOS may be protective in counteracting hypoperfusion and organ injury. This thesis comprises studies on the effects of inhaled NO on pulmonary function in a porcine model of unresuscitated Gram-negative septic shock and acute lung injury (ALI). In this model and in normal pigs, we also investigated the effects of non-selective NOS inhibition on global and regional haemodynamics and oxygen extraction. NO inhalation: Inhaled NO (57 and 60 ppm) selectively attenuated pulmonary vasoconstriction without direct effects on the systemic circulation. Early NO inhalation preserved gas exchange by reducing venous admixture and alveolar dead space, but had no effects on respiratory mechanics. The effects on pulmonary haemodynamics and gas exchange were repeatable. Inhaled NO may mitigate endotoxic lung injury by reducing leukocyte sequestration in the pulmonary microvasculature. NOS inhibition: In both normal and endotoxic pigs, the pulmonary vasculature was more sensitive to the vasoconstricting effects of NOS inhibition than the systemic. In normal pigs, this pulmonary vasoconstriction was enhanced by prior stimulation with acetylcholine. The enhancement may be related to an associated release of a vasoconstricting prostanoid. In endotoxic shock, NOS inhibition caused several animals, with extreme pulmonary hypertension, to die before the end of the observation time. In spite of the fatal overall effects, hepatic perfusion was unharmed by NOS inhibition. The capacity to increase oxygen extraction, in response to the decrease in oxygen delivery, was preserved. In hypodynamic shock, compensatory mechanisms other than NO may be more important in the regulation of hepatic blood flow.
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| 10. |
- Ekbäck, Gustav, et al.
(author)
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Perioperative autotransfusion and functional coagulation analysis in total hip replacement
- 1995
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 39:3, s. 390-395
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Journal article (peer-reviewed)abstract
- Functional coagulation analyses like Sonoclot and thromboelastography have not been evaluated during perioperative autotransfusion. We have prospectively studied three different transfusion regimes in 45 patients undergoing total hip arthroplasty. Blood losses were replaced either with heterologous erythrocyte concentrate (group I), intra- and postoperative autotransfusion of blood salvaged with cellsaver technique (group II) or predonated autologous erythrocyte concentrates together with salvaged blood (group III). Routine and functional coagulation analyses with a Sonoclot were performed preoperatively, 6 hours postoperatively (6 h), day 1–5 and 10. An early postoperative hypo- and late postoperadve hypercoagulative phase could be detected with Sonoclot signs of platelet function and fibrin deposition in all groups. Sonoclot coagulation analyses better correlated to both blood loss and dextran dosage than APTT and platelet count in the routine coagulation analyses. Functional coagulation analysis has a potential use in individualizing plasmasubstitution and thromboprophylaxis regimes during autotransfusion in THR.
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| 11. |
- Islander, Gunilla
(author)
-
In vitro contracture testing for the diagnosis of malignant hyperthermia susceptibility
- 1999
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Doctoral thesis (other academic/artistic)abstract
- Malignant hyperthermia (MH) susceptibility is a rare inherited muscular disorder, which may cause a lethal increase in metabolism during anaesthesia with certain commonly used anaesthetic. Susceptible individuals are without any signs or symptoms. It is important to identify individuals at risk, since the MH reaction is preventable. Susceptibility to MH is diagnosed with an in vitro contracture test (IVCT) performed on viable skeletal muscle. The muscle is exposed to halothane/caffeine in an organ bath. An increase in baseline tension >=0.2g is abnormal. There have been few thorough validations of the IVCT and false diagnoses do occur, which make genetic research difficult. We have investigated 1) the reliability of a negative diagnosis, 2) the inheritance pattern suggested by IVCT and 3) the validation the IVCT results in 706 patients in 175 families. Fourteen patients diagnosed MH negative revealed no signs of MH when exposed to anaesthetics known to cause MH. Judged from outcome of IVCT in 101 families, there is more than one mode of inheritance. The IVCT was validated with comparisons within and between laboratories, between different types of tests and within and between monozygotic twins. We found that increase in baseline tension exceeding 0.5g were almost always reproducible within and between laboratories, between different types of tests and within and between monozygotic twins. Our conclusions are that 1. There are no indications of false negative diagnoses. 2. There could be more than one mode of inheritance. 3. For scientific purposes when a high specificity is needed the threshold could be increased to 0.5g. However the clinical diagnostic cut off limits should be unchanged.
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| 12. |
- Kongstad, Lis
(author)
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Transvascular fluid exchange with application to the brain. An experimental study in cat skeletal muscle and brain.
- 1999
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Doctoral thesis (other academic/artistic)abstract
- This study evaluated transcapillary fluid exchange in the cat brain and in a cat skeletal muscle enclosed in a plethysmograph. A method for determination of capillary permeability (capillary filtration coefficient and reflection coefficient) and effects of transcapillary hydrostatic pressure changes were studied We found that capillary fluid permeability in a tissue can be determined by the capillary filtration coefficient, even when arterial pressure and vascular tone are changed. By evaluating relative variations in the reflection coefficient for albumin rather than absolute values, common error factors were reduced. The reflection coefficient for albumin decreased following surgical trauma, with a resultant decrease in plasma albumin, whereas the influence on fluid permeability was insignificant. Dural puncture reduces intracranial pressure due to a hydrostatic pressure gradient generated by the distal opening of the spinal fluid column, especially in the upright position. This may cause an increased transvascular pressure, dilation of the cerebral outflow veins and - when the blood-brain barrier is disrupted - increased fluid filtration to the interstitial tissue, causing oedema and even brain stem herniation. We found that in our muscle model and in the cat brain with depressed autoregulation and disrupted blood-brain barrier (induced by intrathecal endotoxin), the arterial pressure and the tissue pressure changed in parallel. Variations in venous pressure and in the surrounding fluid volume did not influence the tissue pressure. We conclude that following a traumatic head injury, or during a cerebral infection, elevation of the arterial pressure will increase transcapillary filtration and aggravate the interstitial brain oedema, whereas a decreased arterial pressure will decrease the oedema.
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| 13. |
- Lindberg, Lars
(author)
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Endothelial function during ischemia-reperfusion and effects of inhalation of nitric oxide
- 1996
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Doctoral thesis (other academic/artistic)abstract
- The vascular endothelium is an important regulatory organ in circulatory physiology and plays a central role in the response to acute inflammation and ischemia/reperfusion. Activation and dysfunction of the pulmonary vascular endothelium are closely related to clinical findings of pulmonary dysfunction. The endothelial-derived relaxing factor, nitric oxide (NO), is a gas, which can be administered by inhalation and may have beneficial effects in clinical conditions of pulmonary dysfunction. In this thesis a ventilatory system for inhalation of NO was tested and used to evaluate the effects of inhalation of NO in humans after ischemia and reperfusion caused by cardiopulmonary bypass, and in a pig model of single lung transplantation combined with contralateral pneumonectomy. The endothelial function of isolated pulmonary artery segments from the pigs was simultaneously studied in organ baths. Finally, we tried to attenuate the endothelial dysfunction seen during organ preservation by adding NO donors to the preservation solution. The ventilatory system delivered accurate concentrations of NO in the inspiratory gas during both short and long term delivery. After cardiopulmonary bypass surgery, there was a dose-independent decrease in pulmonary vascular resistance (PVR) down to the lowest dose tested, 2 parts per million (ppm), indicating that inhalation of NO influences PVR in this condition and that the level at which the response is dose dependent is even lower. Pig lungs which had been preserved for 24 hours and then transplanted showed clinical signs of endothelial dysfunction, which were confirmed by organ bath studies. Inhalation of NO reduced PVR in the transplanted lung in a dose-dependent manner in the intervall 5-80 ppm NO. This response to inhalation of NO increased in direct correlation with the degree of endothelial dysfunction. In sham-operated pigs inhalation of NO reduced PVR less and the reduction was independent of dose. With the termination of NO inhalation there was an oxygen-dependent rebound effect, with pulmonary vasoconstriction in the sham-operated pigs, but not in the lung-transplanted pigs. Pharmacological manipulation of the NO pathways in the preservation solution did not improve endothelium-dependent relaxation after storage. Inhalation of NO in ppm doses is possible with adequate equipment and may be beneficial after cardiopulmonary bypass and lung transplantation. The response will depend on dose, duration of inhalation, endothelial function and oxygen tension.
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| 14. |
- Nergelius, Görel
(author)
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Renal dysfunction in orthopaedic surgery - with special reference to drug effects in the elderly
- 1997
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Doctoral thesis (other academic/artistic)abstract
- Total hip replacement (THR) is a common procedure, generally performed in elderly persons. Previous studies indicated that the use of isoxazolyl penicillins could induce a transient post-operative renal dysfunction in these patients. By measuring urinary levels of markers for glomerular (albumin, IgG) and tubular (protein HC) function we studied the influence of systemic cloxacillin, the gentamicin in bone cement and the bone cement itself on renal function following THR or total knee replacement (TKR). We studied peroperative pharmacokinetics of cloxacillin in THR and TKR patients. In healthy elderly we studied the influence of diclofenac on cloxacillin pharmacokinetics, and also investigated exercise-induced proteinuria, and the possible effect of prostacyclin on it. Patients undergoing THR or TKR developed a transient increase in glomerular and tubular markers. This was not primarily caused by cloxacillin, gentamicin or bone cement. THR patients had lower creatinine clearance and lower clearance for cloxacillin than TKR patients, and lower than healthy elderly. Diclofenac did not alter the pharmacokinetics for cloxacillin in healthy, unstressed, elderly. Exercise induced a transient glomerular and proximal, but not distal, tubular impairment in the volunteers. The exercise-induced proteinuria was not altered by prostacyclin. Present surgical and anesthetic techniques have partly overcome the risk for developing postoperative renal failure, but THR patients probably still are at an increased risk. Proteinuria following surgery or exercise is suggested to share, in part, common pathways.
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| 15. |
- Roth, Bengt
(author)
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Fat metabolism during total parenteral nutrition: A biochemical and ultra-structural study
- 1997
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Doctoral thesis (other academic/artistic)abstract
- This thesis evaluates alterations in lipid metabolism and Kupffer cell morphology seen during total parenteral nutrition in healthy rats. During infusion of lipid emulsions, cholesterol and phospholipids accumulated in non-high density lipoproteins, while high density lipoproteins were enriched in triglycerides. Triglycerides also accumulated in hepatic tissue, and the activity of hepatic lipase decreased. Although lipoprotein lipase activity in the heart was up-regulated and serum levels of triglycerides were normal, suggesting that the total elimination rate of triglycerides was not impaired, ultra-structural investigations indicated that Kupffer cells were involved in clearing exogenous lipids from the blood during the infusion of long-chain triglycerides. Furthermore, the Kupffer cells were activated, according to morphological criteria. When high doses of fat were given intravenously, the Kupffer cells were grossly distended by fat vacuoles, and serum levels of lactate dehydrogenase increased. During treatment with fat emulsions containing medium-chain triglycerides and long-chain triglycerides in equal amounts, the alterations in lipid transport were less pronounced, and signs of Kupffer cell activation were weaker than during infusion with long-chain triglycerides only. To some extent, the experimental findings may be related to clinical observations of a head injured patient who developed signs of acute, severe macrophage activation with haemophagocytosis during and after accumulation of exogenous fat in the blood after treatment with intravenous fat emulsions. The condition was considered to be a consequence of impaired lipid elimination and altered macrophage function during clearance of fat from the blood.
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| 16. |
- Schou, Henning
(author)
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Extreme hemodilution: Effects of inhalation anesthetics, hypoxia, and blood loss. An Experimental study in pigs.
- 1997
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Doctoral thesis (other academic/artistic)abstract
- Hemodilution reduces the need for blood transfusion and hereby the risk for transmission of infectious agents. The present study investigated effects on systemic and myocardial circulation and oxygenation, and blood lactate concentrations; induced by nitrous oxide, isoflurane, hypoxia, and uncompensated blood loss, in pigs hemodiluted to a hematocrit of 11%. In addition, indicators of hypovolemia and insufficient oxygen delivery, as well as the correlation between mixed and central venous blood oxygen were studied. It was found that nitrous oxide had insignificant circulatory effects, but oxygen delivery decreased during isoflurane administration, hypoxia or uncompensated blood loss, and delivery dependent oxygen uptake and hyperlactemia was observed when systemic oxygen delivery decreased below 10 ml x kg-1 x min-1. The heart was more tolerant to the reduced oxygen delivery than were other organs, when judged by arterial lactate concentration and myocardial lactate uptake. The decrease in mixed venous oxygen saturation and systemic oxygen delivery correlated well with the increase in arterial lactate concentration. There was a close relation between central and mixed venous oxygen saturation. A decrease in arterial blood pressure was the first sign of hypovolemia during hemodilution, wheras central venous and pulmonary capillary wedge pressures were insensitive indicators of hypovolemia. It is concluded that the risk of compromising cardiovascular function and inducing severe tissue hypoxia is high during extreme acute normovolemic hemodilution. Nevertheless our findings suggest that in young individuals a hematocrit as low as 11% can be accepted temporarily providing adequate monitoring is available, and if caution is taken to avoid further decrease in systemic oxygen delivery.
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| 17. |
- Sonesson, Björn, et al.
(author)
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Influence of sympathetic stimulation on the mechanical properties of the aorta in humans
- 1997
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In: Acta Physiologica Scandinavica. - 0001-6772. ; 159:2, s. 139-145
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Journal article (peer-reviewed)abstract
- The mechanical properties of the aorta play a major role in the regulation of blood pressure and cardiac performance. The effect of sympathetic stimulation on the mechanical properties of the human abdominal aorta was studied in 19 healthy volunteers, divided into young (25 +/- 2 years) and elderly individuals (69 +/- 2 years) of both sexes. A non-invasive ultrasonic echo-tracking system for measurement of systolic/diastolic variation of aortic diameter in combination with intra-aortic pressure measurements was used to determine wall mechanics. The pressure-diameter (P-D) relationship and the distensibility indices, stiffness (beta) and pressure strain elastic modulus (Ep) of the abdominal aorta were obtained. Measurements were made at rest and during sympathetic stimulation induced by lower body negative pressure (LBNP). As a sign of sympathetic activation, the peripheral resistance increased by 74-96% (P < 0.001) during LBNP. However, the mechanical properties of the abdominal aorta remained unaltered, as estimated either from the P-D relationship or from the indices Ep and beta, both in the young (rest: Ep = 0.53 +/- 0.18, beta = 4.5 +/- 1.5; LBNP: Ep = 0.51 +/- 0.15, beta = 4.5 +/- 1.2, NS) and in the elderly (rest: Ep = 2.17 +/- 0.70, beta = 17.6 +/- 5.8; LBNP: Ep = 2.11 +/- 0.60, beta = 16.9 +/- 3.9, NS). In conclusion, this investigation shows that LBNP-induced sympathetic activation does not change aortic wall mechanics. Thus, sympathetic modulation of the aortic smooth muscle contractile activity seems to be unimportant in the blood pressure regulation.
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| 18. |
- Wallerstedt, Susanna
(author)
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Reactivity of human omental blood vessels. Effects of 5-hydroxytryptamine, substance P and the intravenous anaesthetic propofol
- 1998
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Doctoral thesis (other academic/artistic)abstract
- Regulation of blood flow involves several endogenous substances and mechanisms, and exogenous substances may also affect the blood flow. In the present thesis, human omental blood vessels were investigated in vitro concerning (i) characteristics of 5-hydroxytryptamine (5-HT) receptors; (ii) mediators of substance P (SP)-induced relaxation; (iii) direct and indirect (via effects on sympathetic neurotransmission) effects of the intravenous anaesthetic propofol. In human omental arteries, contractile 5-HT1 and 5-HT2 receptors were demonstrated. No evidence for contractile 5-HT3 or 5-HT4 and relaxing 5-HT1, 5-HT2, 5-HT3 or 5-HT4 receptors was found. In human omental arteries and veins, SP-induced relaxation seems to be mediated via nitric oxide (NO) and endothelium-dependent hyperpolarization, possibly due to activation of high conductance Ca2+-sensitive K+-channel (BKCa). Direct effects of propofol in human omental arteries and veins include relaxation of vascular smooth muscle mediated via endothelium-independent hyperpolarization and attenuation of the response to contractile agents. The hyperpolarization is possibly due to propofol-induced activation of BKCa. The propofol-induced attenuation of the response to contractile agents may be explained by a decreased release of intracellularly stored calcium rather than a decreased influx of calcium from the extracellular space. Propofol at clinical concentrations seems to enhance sympathetic neurotransmission in human omental arteries, but not veins. This may be due to an increased availability of noradrenaline (NA) in the neuromuscular junction, resulting from a reduced presynaptic reuptake. Propofol at probably supraclinical concentrations, on the other hand, seems to impair the sympathetic neurotransmission in both human omental arteries and veins, possibly due to an inhibitory effect on the NA release from the sympathetic nerves.
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| 19. |
- Mellander, Stefan, et al.
(author)
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Cardiovascular regulation by endogenous nitric oxide is essential for survival after acute haemorrhage
- 1997
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In: Acta Physiologica Scandinavica. - 0001-6772. ; 160:1, s. 57-65
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Journal article (peer-reviewed)abstract
- Our previous studies have indicated that endogenous nitric oxide serves as a physiologically important inhibitor of vascular tone during acute haemorrhage. This vasodilator action attenuates the concomitant reflex adrenergic constriction and thereby prevents critical reduction of tissue blood flow. The present study aimed to evaluate the overall importance of this nitric oxide regulation for survival after acute haemorrhage. This was done by comparative observations of survival time and circulatory, metabolic and histopathological changes after an acute standardized lethal blood loss (45%) in cats exposed to nitric oxide synthase (NOS) inhibition and in matched control animals with intact nitric oxide regulation. NOS inhibition was instituted by intravenously administered N omega-nitro-L-arginine methyl ester. The survival time averaged 2 h 49 min in the NOS-blocked animals and 10 h 14 min in the control animals (P < 0.001). NOS inhibition thus reduced the posthaemorrhagic survival time to < 30% of that in the control cats. Haemorrhage in the NOS-blocked animals led to rapidly developing arterial hypotension, increased anaerobic metabolism, metabolic lactacidosis, hyperkalaemia, and morphological tissue damage especially in heart and liver, in spite of maintained arterial normoxia, which signifies tissue hypoxia caused by seriously impaired nutritional blood supply. At the time of death of the NOS-blocked cats, the control animals still exhibited a virtually normal circulatory/metabolic state. A much later, and more slowly developing circulatory/metabolic deterioration was observed in the control animals. These differences between the two groups of animals indicate that nitric oxide release, by its vasodilator action, to a significant extent helps to maintain an adequate nutritional blood supply to the tissues in acute haemorrhage.
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| 20. |
- Nygren, Jonas, et al.
(author)
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Preoperative oral carbohydrate administration reduces postoperative insulin resistance
- 1998
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In: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 17:2, s. 65-71
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Journal article (peer-reviewed)abstract
- Infusions of carbohydrates before surgery reduce postoperative insulin resistance. We investigated the effects of a carbohydrate drink, given shortly before surgery, on postoperative metabolism. Method: Insulin sensitivity, glucose turnover ([6,6, 2H2]-D-glucose) and substrate utilization were measured using hyperinsulinemic normoglycemic clamps and indirect calorimetry in two matched groups of patients before and after elective colorectal surgery. The drink group (n = 7) received 800 ml of an isoosmolar carbohydrate rich beverage the evening before the operation (100 g carbohydrates), as well as another 400 ml (50 g carbohydrates) 2 h before the initiation of anesthesia. The fasted group (n = 7) was operated after an overnight fast. Results: After surgery, energy expenditure increased in both groups. Endogenous glucose production was higher after surgery and the difference was significant during low insulin infusion rates in both groups (P < 0.05). The supressibility of endogenous glucose production by the two step insulin infusion was similar pre- and postoperatively in both groups. At the high insulin infusion rate postoperatively, whole body glucose disposal was more reduced in the fasted group (-49 ± 6% vs -26 ± 8%, P < 0.05 vs drink). Furthermore, during high insulin infusion rates, glucose oxidation decreased postoperatively only in the fasted group (P < 0.05) and postoperative levels of fat oxidation were greater in the fasted group (P < 0.05 vs drink). Only minor postoperative changes in cortisol and glucagon were found and no differences were found between the treatment groups. Conclusions: Patients given a carbohydrate drink shortly before elective colorectal surgery displayed less reduced insulin sensitivity after surgery as compared to patients who were operated after an overnight fast.
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| 21. |
- Bergenfelz, A, et al.
(author)
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Side localization of parathyroid adenomas by simplified intraoperative venous sampling for parathyroid hormone
- 1996
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 20:3, s. 60-358
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Journal article (peer-reviewed)abstract
- Side localization of parathyroid adenomas was performed by venous sampling for intact parathyroid hormone (PTH) in 20 consecutive patients with primary hyperparathyroidism (pHPT) after induction of anesthesia. The results were thus available during surgery. Nineteen of the patients had solitary parathyroid adenoma, and one had hyperplasia. There was no complication to the procedure. A lateralizing PTH gradient for a parathyroid adenoma was obtained in 13 patients. At surgery 12 of them (92%) were proved correct; that is, the adenoma was localized on the same side. Thus the technique correctly lateralized the adenoma in 12 of 19 patients (63%). We therefore conclude that the method of intraoperative venous sampling for intact PTH is safe, and the predictive value of a lateralizing gradient is high. It could therefore be used as an adjunct to surgical skill and noninvasive localization procedures in selected cases, for instance in patients with prior neck surgery and hypercalcemic crisis.
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| 22. |
- De Kanter, M., et al.
(author)
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A prospective study of orthostatic blood pressure in diabetic patients
- 1998
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In: Clinical Autonomic Research. - 0959-9851. ; 8:4, s. 189-193
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Journal article (peer-reviewed)abstract
- To clarify whether orthostatic blood pressure is affected by the type of diabetes, cardiac autonomic neuropathy, and the duration of diabetes, orthostatic blood pressure (passive 90°tilt) was evaluated in 102 patients with insulin dependent diabetes mellitus (IDDM), 51 patients with non-insulin dependent diabetes mellitus (NIDDM), and in 238 control subjects in a first study followed up after 8 to 17 years. The heart rate reaction during deep breathing (E/I ratio) and to tilt (acceleration and brake indices) assessed cardiac autonomic function. In the first study, the lowest systolic blood pressure (LSBP) and the lowest diastolic blood pressure (LDBP) after tilt were significantly lower in IDDM patients compared with NIDDM patients (p < 0.001 for LSBP and p < 0.05 for LDBP) and controls (p < 0.001). LDBP was, however, also significantly lower (p < 0.05) in NIDDM patients than in controls. Hence, although most severe in IDDM, LDBP was disturbed in both types of diabetes. In IDDM, a low E/I ratio was associated with disturbed orthostatic blood pressure. At follow-up examinations, orthostatic blood pressure deteriorated in NIDDM but not in IDDM patients. In conclusion, LSBP and LDBP were impaired in IDDM patients compared with NIDDM and control subjects; however, LDBP was also impaired in NIDDM patients compared with controls. When the duration of diabetes increased, orthostatic blood pressure deteriorated in NIDDM but not in IDDM patients.
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| 23. |
- Gannedahl, Per E., et al.
(author)
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Minimal influence of anaesthesia and abdominal surgery on computerized vectorcardiography recordings
- 1995
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In: Acta Anaesthesiologica Scandinavica. - : Elsevier. - 0001-5172 .- 1399-6576. ; 39:1, s. 71-78
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Journal article (peer-reviewed)abstract
- Myocardial infarction still represents a major cause of morbidity and mortality following surgical procedures. Continuous computerized on‐line vector‐ECG has previously been shown to be useful in the detection of myocardial ischaemia, in acute myocardial infarction and unstable angina pectoris and for ischaemia monitoring after PTCA procedures. This method was presently tested for the possible influence of anaesthesia and surgery during cholecystectomy under general anaesthesia (n = 9), and during inguinal hernia repairs using a spinal block (n = 5). The patients had no history, symptoms or signs of ischaemic heart disease. Analyses of vectorcardiographic changes were made in relation to predefined standardized anaesthetic and surgical procedures, all of which potentially could influence the vector‐ECG. Three vectorcardiographic trend parameters were studied: QRS‐vector difference, ST‐vector magnitude and ST‐change vector magnitude. The overall vectorcardiographic changes were minimal and smaller than vectorcardiographic changes previously reported during myocardial ischaemia and infarction. Since anaesthetic and surgical procedures per se had only minor effects on the vector ECG recordings, it is concluded that continuous computerized on‐line vectorcardiography will not be skewed by these procedures. Hence, vectorcardiography has the potential of becoming a new monitor for the detection of perioperative myocardial ischaemia.
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| 24. |
- Jönsson, Anders, 1959, et al.
(author)
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Effects of amide local anaesthetics on eicosanoid formation in burned skin.
- 1999
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In: Acta anaesthesiologica Scandinavica. - 0001-5172. ; 43:6, s. 618-22
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Journal article (peer-reviewed)abstract
- Previous studies have demonstrated potent inhibition of burn oedema and progressive ischaemia by local anaesthetics. Since eicosanoids have been suggested to play an important role in the pathophysiology of burns, we compared in the present ex vivo study the effects of topical lidocaine/prilocaine cream (EMLA, ASTRA, Sweden) and intravenous lidocaine with that of saline on eicosanoid formation by normal and burned rat skin.
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| 25. |
- Jönsson, Anders, 1959, et al.
(author)
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Local anesthetics improve dermal perfusion after burn injury.
- 1998
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In: The Journal of burn care & rehabilitation. - 0273-8481. ; 19:1 Pt 1, s. 50-6
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Journal article (peer-reviewed)abstract
- Deep partial-thickness burn injury was induced in the abdominal skin of anesthetized rats. Dermal perfusion was assessed by laser Doppler flowmetry. In the first set of experiments, one group of rats (n = 15) was topically treated with a lidocaine-prilocaine cream 5% (25 mg of each in 1 g) for 6 hours, starting 5 minutes after inducing the burn injury. In one control group (n = 14), the thermal injury was treated with placebo cream. Results showed a markedly reduced perfusion in the skin of the control animals within the first hour after burn injury, with further decrease during the following 5 hours of observation. In animals treated with the lidocaine-prilocaine cream, skin perfusion in the burned area was significantly increased during the first 30 minutes after the burn injury compared to before the burn (p < 0.01), followed by a decrease to a level below the preburn stage but significantly higher than that of control animals during the first hour after burn injury (p < 0.05). As opposed to burned control animals, skin perfusion gradually recovered toward preburn levels at the end of the experiment in local anesthetic-treated animals. In the second experimental set, four groups of animals were burned and subsequently treated with a bolus dose of lidocaine intravenously (2 mg/kg), followed by continuous intravenous lidocaine infusions at a rate of 50 (n = 10), 100 (n = 11), or 150 (n = 10) micrograms.kg-1.min-1. The infusions were started 5 minutes after the burn injury and lasted for 6 hours. Corresponding volumes of saline solution were given to burned control animals (n = 10). Results showed a significantly improved skin perfusion in the lidocaine-treated group in a dose-response fashion as compared to control animals. A maximum improvement of dermal perfusion in the burned area was induced by intravenous lidocaine at an infusion rate of 150 micrograms.kg-1.min-1 as compared to burned controls treated with isotonic saline solution infusions (p < 0.01). Results showed that topical or systemic administration of local anesthetics can prevent progressive dermal ischemia after thermal injury.
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