Anders Waldenström | Umeå University (original) (raw)

Papers by Anders Waldenström

Scandinavian Journal of Clinical & Laboratory Investigation, 1997

In this study, the dynamic interrelationships between myocardial functional state and changes in ... more In this study, the dynamic interrelationships between myocardial functional state and changes in the second messenger content in pressure-overloaded hypertrophied hearts were investigated. Forty-three rat hearts were used after partial clamping of the abdominal aorta. The isolated hearts were perfused with Krebs-Henseleit buffer and allocated to perfusion for 20 s or 40 min as controls (n = 12); or with noradrenaline (10(-6) mol l-1, n = 11); carbachol (3 x 10(-7) mol l-1, n = 9); or noradrenaline plus carbachol (10(-6) mol l-1 + 3 x 10(-7) mol l-1, respectively, n = 11). maxdP/dt increased more than 2-fold already after 20 s on noradrenaline stimulation, followed by a significant increase in cAMP. After 40 min, maxdP/dt was lower than the maximal value, although higher than controls. cAMP was also decreased, but still significantly higher than controls. Perfusion with noradrenaline plus carbachol produced the same changes in maxdP/dt as those seen after noradrenaline stimulation alone, but failed to increase cAMP content after both 20 s and 40 min. The inositol trisphosphate (IP3) content was increased 40 min of control perfusion (p < 0.05). Noradrenaline and carbachol, separately, produced an increase in IP3 content already after 20 s (p < 0.05). The combination of noradrenaline plus carbachol also produced an increase of IP3 (p < 0.05; compared to controls), but to a lesser extent when compared either to noradrenaline or carbachol (p < 0.05). After 40 min of perfusion, IP3 was in the same range regardless of added agonist(s) and still slightly above control level (p < 0.05). The early increase in maxdP/dt induced by noradrenaline or the combination of noradrenaline plus carbachol was not paralleled by a decrease in ATP content. This was also the case upon addition of carbachol alone. However, after 40 min of agonistic perfusion, ATP levels were substantially decreased. In conclusion, myocardial IP3 content in pressure-overloaded hypertrophied hearts was not different from that of sham-operated hearts. After agonistic stimulation, an early increase in IP3 formation was seen. Attenuation of the IP3 response by combined stimulation with noradrenaline and carbachol was initially present in pressure-overloaded hypertrophied hearts. After 40 min no attenuation was found for either IP3 or for cAMP content, suggestive of induction of a desensitization.

European Journal of Anaesthesiology, May 1, 2011

Scandinavian Journal of Rheumatology, 1999

The present study was performed to measure concentrations of plasma noradrenaline and neuropeptid... more The present study was performed to measure concentrations of plasma noradrenaline and neuropeptide-Y-like immunoreactivity in relation to cardiac function in patients with systemic sclerosis (SSc). Plasma noradrenaline was measured by high performance liquid chromatography and neuropeptide-Y by radioimmunoassay in 30 consecutive patients with SSc and 48 sex and age matched controls. Left ventricular (LV) function was evaluated by Echocardiography. There were no significant differences between patients and controls in either plasma noradrenaline or plasma neuropeptide-Y. LV dysfunction and hypertrophy were common among patients. Plasma Neuropeptide-Y was related only to systolic function, while noradrenaline was related to both systolic and diastolic function as well as to LV hypertrophy. Patients with SSc develop different forms of myocardial dysfunction without activation of the sympathetic nervous system as evaluated by plasma noradrenaline and neuropeptide-Y; leaving vascular disease of the heart to be a main candidate.

Acta Physiologica Scandinavica, 1997

Adenine nucleotides, lactate and pyruvate were monitored by microdialysis in pig hearts, comprisi... more Adenine nucleotides, lactate and pyruvate were monitored by microdialysis in pig hearts, comprising four experimental groups. Two preconditioned groups, one β-blocked by metoprolol (0n3 mg kg -1 body wt ; n l 6) and the other (n l 7) without β-blockade. Two groups were not preconditioned, one β-blocked (n l 6) and one without β-blockade (n l 7). Probes were inserted into ischaemic and non-ischaemic myocardium. Preconditioning consisted of four consecutive 10 min periods of ischaemia each separated by 20 min of reperfusion. All animals were subjected to 40 min of index ischaemia followed by 25 min of reperfusion. Myocardial cAMP content was determined in biopsies after the final reperfusion and was found low in the β-blocked groups. Lactate levels during index ischaemia exceeded the basal level 4-6-fold in dialysate. Adenosine concentration reached 12 µmol  -1 during the first preconditioning period while an attenuation was typical for the following three preconditioning periods. The sum of the concentrations of adenosine, inosine and hypoxanthine was significantly lower during index ischaemia in the preconditioned groups displaying a peak value of 115 µmol  -1 . The corresponding value for unpreconditioned hearts was 230 µmol  -1 . The part of adenosine was 5 % and less than 1 %, respectively. Pyruvate concentration decreased during each brief ischaemic period of preconditioning rising to a higher level of reperfusion. The decrease in pyruvate was smaller in the controls during index ischaemia. The effects of β-blockade and preconditioning on ischaemic metabolism were comparable and the results of the two treatments were not additive in this respect.

Acta Physiologica Scandinavica, Oct 9, 2001

During pre-conditioning the interstitial concentration of adenosine, in contrast to lactate, pres... more During pre-conditioning the interstitial concentration of adenosine, in contrast to lactate, presents a die-away curve-pattern for every successive episode of ischaemia. This die-away pattern might not necessarily be attributed to diminished adenosine production. The present study was undertaken to investigate whether pre-conditioning alters the metabolic turnover of adenosine as observed by the lactate production during ischaemia. Interstitial levels of metabolites in pre-conditioned (n=21) and non-preconditioned (n=21) porcine hearts were monitored with microdialysis probes inserted in both ischaemic and non-ischaemic tissue in an open chest heart model. Three subgroups perturbated with either plain microdialysis buffer (control), buffer containing adenosine (375 microM), or buffer containing deoxyadenosine (375 microM) were studied. All animals were subjected to 90 min of equilibrium microdialysis before 40 min of regional myocardial ischaemia and 120 min of reperfusion. Pre-conditioning consisted of four repetitive episodes of 10 min of ischaemia and 20 min of reperfusion. Significantly higher levels of inosine and lactate were found in the ischaemic tissue of the pre-conditioned subgroup receiving adenosine (P < 0.05) compared with the other two subgroups receiving deoxyadenosine and plain buffer, respectively. This difference was only valid for pre-conditioned ischaemic myocardium, and hence equal amounts of inosine and lactate were produced in the non-preconditioned ischaemic myocardium regardless of the presence of adenosine or deoxyadenosine. In the non-ischaemic myocardium baseline levels of metabolites were measured in all subgroups. Pre-conditioning favoured degradation of exogenous adenosine to inosine successively ending up in enhanced lactate production. This was probably because of the involvement of the hexose monophosphate pathway in the pre-conditioned ischaemic myocardium. This route may therefore be supplementary in energy metabolism as a metabolic flow can be started by adenosine ending up in lactate without initial adenosine 5'-triphosphate (ATP) investment. Utilization of adenosine in this way may also explain the successive die-away pattern of adenosine seen in consecutive pre-conditioning cycles.

Acta Physiologica Scandinavica, Aug 26, 2003

The validity of the microdialysis technique for experimental in vivo studies of myocardial energy... more The validity of the microdialysis technique for experimental in vivo studies of myocardial energy metabolism is not known. To address this question interstitial levels of energy-related metabolites (lactate, adenosine, inosine and hypoxanthine) obtained by the microdialysis technique were compared with corresponding metabolites from myocardial biopsies at given intervals in a porcine heart model using different protocols of ischaemia and reperfusion. In an open chest porcine heart model, interstitial levels of energy-related metabolites were monitored using the microdialysis technique. All animals (n = 23) were subjected to 120-min pretreatment followed by 40 min of regional ischaemia and 120 min of reperfusion. Tissue biopsies were obtained in the beginning, middle and at the end of the 40-min ischaemic period and at the end of the reperfusion period. Pretreatment consisted of either rest (group 1, n = 7), or rest for 90 min and one ischaemia/reperfusion (10 + 20 min) cycle (group 2, n = 9), or four ischaemia/reperfusion cycles (10 + 20 min each) (group 3, n = 7). Interstitial levels of energy-related metabolites monitored by the microdialysis technique correlated with tissue biopsy levels of lactate (r = 0.90, P < 0.001), adenosine (r = 0.89, P < 0.001), inosine (r = 0.88, P < 0.001) and hypoxanthine (r = 0.91, P < 0.001), respectively, which were obtained by tissue biopsies at given time intervals. These significant correlations were valid regardless of the functional state of the myocardium. We observed significant correlations between microdialysis probe levels and tissue biopsy levels of energy-related metabolites in both ischaemic and non-ischaemic tissue. These data assess the validity of the microdialysis technique (in the current setting) for studying dynamic changes of myocardial energy metabolism.

European Journal of Obstetrics & Gynecology and Reproductive Biology, Oct 1, 1995

To study the energy metabolite pattern in term pregnant myometrium and to compare it with that of... more To study the energy metabolite pattern in term pregnant myometrium and to compare it with that of a striated skeletal muscle. Metabolites of carbohydrates, triglycerides and nucleotides were determined in biopsies from myometrium and rectus abdominis muscle from ten healthy term pregnant women before onset of labour. The metabolite concentrations in the two types of muscle were compared by two tailed Student's t-test for paired values and correlations were calculated by Pearsson's correlation test. Comparison of the two muscle types revealed a higher concentration of glucose and a higher lactate/pyruvate ratio in the myometrium but a lower concentration of triglyceride metabolites. Adenosine was found in 36-fold higher concentration in the uterine compared with the rectus muscle and an inverse relationship between adenosine and glucose concentrations was observed in the myometrium. The results indicated that the pregnant uterine smooth muscle utilized glucose as the principal nutritive metabolite rather than lipids and that the anaerobic pathway of the glucose metabolism was more active in the myometrium compared with the striated rectus muscle. Also, it is suggested that glucose has a critical role as the principal fuel for ATP formation and the involvement of the adenylate kinase and 5'-nucleotidase reactions in any event of glucose shortage.

European Journal of Clinical Investigation, Nov 1, 1996

Left ventricular hypertrophy is a condition with high mortality. An association with insulin resi... more Left ventricular hypertrophy is a condition with high mortality. An association with insulin resistance and hyperinsulinaemia has recently been suggested. The aim of this study was to examine the effects of isolated hyperinsulinaemia on cardiac weight and haemodynamic regulation. Rats were exposed to hyperinsulinaemia for 7 weeks after adrenalectomy with corticosterone substitution and continuous infusion of propranolol to control counter‐regulatory mechanism (n=15) (AIP group). Hypoglycaemia was prevented by glucose in the drinking water. Hyperinsulinaemic (AIP) rats were heavier and had increased relative masses of the myocardium (left ventricle 17% and right ventricle 20%), kidneys and adipose tissues in comparison with normoinsulinaemic adrenalectomized, corticosterone‐ and propranolol‐treated controls (AP) (n=10). Blood pressure in the insulin‐exposed animals, measured weekly by the tail‐cuff method in conscious rats, was not different from (AP) controls over 5 weeks, but increased in the sixth week. At the end of the seventh experimental week, blood pressure measured intra‐arterially was also found to be elevated. Heart rate was not changed but total peripheral resistance was about twice that of controls (P<0.001). Cardiac output and stroke volume was 30–40% lower in the AIP rats (P<0.05). It is concluded that exposure to elevated insulin levels with control of counter‐regulating mechanisms from β‐adrenergic mechanisms and adrenals is not immediately followed by blood pressure elevation. It is, therefore, suggested that early onset of blood pressure elevation after insulin exposure might be caused by insulin counter‐regulatory events, causing both insulin resistance and blood pressure elevation. The long‐term adaptations may involve a direct influence by insulin as a ‘trophic factor’ on myocardial and on peripheral resistance vessels, followed by increased blood pressure, decreased cardiac output and stroke volume.

Journal of International Medical Research, Aug 1, 2004

We aimed to develop a model for studying membrane leakiness. A microdialysis technique was used t... more We aimed to develop a model for studying membrane leakiness. A microdialysis technique was used to investigate rubidium-86 ( 86 Rb) uptake in suspended human erythrocytes in vitro, with the aim of later applying the technique to in vivo studies. Suspensions were prepared from washed erythrocytes and 86 Rb administered directly or via the microdialysis probe. The effects on 86 Rb uptake of varying the haematocrit were measured. Erythrocytes were also treated with the K + ionophore valinomycin or the Na + / K + -ATPase inhibitor ouabain. The effects on 86 Rb uptake, microdialysate content of lactate and pyruvate, and erythrocyte content of 2,3-bisphosphoglycerate (2,3-BPG) were measured. Valinomycin dissipates the potassium gradient and activates Na + /K + -ATPase, demonstrated by decreased erythrocyte 86 Rb uptake with increasing concentrations of valinomycin. This increased ion pump activity enhanced glycolysis, which was demonstrated by accumulation of pyruvate and lactate due to enhanced consumption of 2,3-BPG. The microdialysis technique is appropriate for in vitro studies of ion fluxes across cellular membranes.

Acta Physiologica Scandinavica, Feb 1, 1994

Journal of Internal Medicine, 2001

To establish by flow cytometry and fluorophores an increased calcium ion load in erythrocytes of ... more To establish by flow cytometry and fluorophores an increased calcium ion load in erythrocytes of four patients with Tarui's disease. Calcium ion levels were determined in erythrocytes of patients and controls under normal and energy-deprived conditions. Adenylates were measured to assess energy status of incubated erythrocytes. The experiments were carried out at the Department of Clinical Chemistry of the University Hospital of Uppsala, Sweden. Four family members with Tarui's disease participated in the study. The proband (patient 1) was a 39-year-old male; patients (male, aged 46 years) 2 and 3 (female, 30 years) were his two siblings. Patient 4 (male, 16 years) was the son of patient 2. None. Calcium ion homeostasis was measured under basic conditions and under energy-deprived conditions and related to cellular adenylate content. All patients showed enhanced erythrocyte calcium ion loading compared to controls under energy-deprived conditions. Under normal conditions, however, three out of the four patients showed an increased erythrocyte calcium ion level compared to controls. We conclude that erythrocytes from patients with Tarui's disease have an increased Ca2+ permeability, initiating compensatory mechanisms involving increased Ca2+ pump activity and increased glycolytic flux, which are not always sufficient to keep erythrocyte calcium ion concentration within physiological range.

Acta Physiologica Scandinavica, Feb 1, 1993

European Journal of Clinical Investigation, Sep 1, 1997

The purpose of the study was to investigate by in vitro and in vivo methods the phosphocreatine (... more The purpose of the study was to investigate by in vitro and in vivo methods the phosphocreatine (PCr)/ ATP ratio as an expression of the energy metabolic state of human myometrium in comparison with striated skeletal muscle. The contents of PCr and adenylates in biopsies of uterine smooth muscle and m. rectus abdominis from seven term pregnant women were determined in vitro and compared with results obtained in vivo by phosphorus magnetic resonance spectroscopy (31P-MRS) in the uterus and m. gastrocnemius of eight non-pregnant women. The PCr/ATP ratio in the striated skeletal muscle was about three times higher than that of the myometrium. The results of the in vitro biopsy part of the study and the in vivo 31P-MRS part conformed with each other. In the biopsies both PCr and ATP concentrations were significantly lower in the myometrium than in the rectus muscle, but the difference for PCr was more pronounced, accounting for the significantly lower PCr/ATP ratio in the uterine smooth muscle. The energy metabolic pattern of uterine smooth muscle differs from that of striated skeletal muscle regarding the contents of high-energy phosphocompounds and the PCr/ATP ratio. This in vivo finding is the first report on human smooth muscle using 31P-MRS.

Clinica Chimica Acta, Dec 1, 1993

We determined the concentrations of adenosine and some of its catabolic products in biopsy specim... more We determined the concentrations of adenosine and some of its catabolic products in biopsy specimens from predetermined loci of human myometrium under different functional conditions to compare uterine muscle with rectus abdominis muscle from the same individuals. In order to achieve a good resolution in the separation of nucleosides and purine bases, a preseparation procedure was developed prior to analysis of these compounds on high performance liquid chromatography. Adenosine occurred in a nearly 70-fold higher concentration in smooth uterine muscle in comparison with striated skeletal muscle. Similarly, myometrial inosine and hypoxanthine were 7- and 2.4-times in excess over the rectus muscle, whereas xanthine was scarcely and rather evenly represented in the two types of muscles. The uterine content of adenosine and inosine was distinctly higher in pregnant women compared to non-pregnant ones. A regional difference existed for adenosine, with 3.3 times higher concentration in fundus uteri compared to the isthmic part. A reverse pattern was observed for hypoxanthine and inosine, being 2-3 times more frequent in the isthmic part. The orthophosphate concentration was not stoichiometrically related to the adenosine concentration in a simple way, being 2-3 times lower in uterine muscle compared to the skeletal muscle. A significant correlation existed between uterine contents of AMP and adenosine and similarly, significant inverse correlations were apparent between uterine ATP and ADP contents and energy charge on one hand and adenosine content on the other.

Clinica Chimica Acta, Oct 1, 1993

Clinical Physiology and Functional Imaging, Nov 22, 2010

Scandinavian Journal of Clinical & Laboratory Investigation, 1994

It has long been known that high concentrations of catecholamines may induce myocardial damage, a... more It has long been known that high concentrations of catecholamines may induce myocardial damage, and aggravate ischaemic injury. It has also been shown that beta-blockade may protect the myocardium from ischaemic damage. Stimulation of muscarinic receptors modulates beta-adrenergic receptor affinity for isoproterenol and attenuates isoproterenol induced adenylyl cyclase activation. Effects of muscarinic receptor stimulation were therefore investigated in isolated anterogradely perfused rat hearts under different experimental conditions. One group of hearts was perfused with noradrenaline, 10(-6) mol l-1 for 45 min, and another group was perfused with different carbachol concentrations (3 x 10(-7)-10(-5) mol l-1) with or without noradrenaline 10(-6) mol l-1, for 45 min. Release of creatine kinase to the perfusion buffer was taken as a sign of cell damage. Heart rate, left ventricular maxdP/dt and left ventricular pressure were measured throughout the perfusion time by insertion of a 20 gauge cannula through the left ventricular wall near the base. Carbachol (3 x 10(-7) mol l-1) alone induced a decrease of heart rate by 25% and maxdP/dt by 13%. Noradrenaline produced a 20% increase in heart rate, whereas the combination of noradrenaline plus carbachol induced a minor decrease in heart rate. Muscarinic receptor stimulation alone decreased myocardial contractility. However, when combined with noradrenaline no decrease in contractility was seen. Also, the release of creatine kinase to the perfusion buffer containing the combination of carbachol plus noradrenaline was reduced. Thus, muscarinic receptor stimulation protected the myocardium from catecholamine induced damage at concentrations where no change in contractility was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Gynecologic and Obstetric Investigation, 1999

Glycogen, glucose, some nucleosides and purine base derivatives were determined in biopsies from ... more Glycogen, glucose, some nucleosides and purine base derivatives were determined in biopsies from 10 term pregnant women undergoing elective cesarean sections before labor. The concentrations were compared in the biopsies which were cut from isthmus and fundus of the uterus and m. rectus abdominis. M. rectus biopsies had 1.5 and 2 times higher concentration of glycogen than the isthmic and fundal uterine biopsies, respectively. The glucose concentration in the striated muscle was on the other hand only half that in the myometrium. The uterus displayed regional differences in concentrations of glycogen (higher in isthmus). A relatively low glycogen content in term pregnant uterine smooth muscle compared with striated muscle signifies the restricted energy demands of pregnant myometrium.

Journal of Cardiovascular Pharmacology, May 1, 1996

The concentrations of lactate, pyruvate, and adenosine, together with some of their derivatives, ... more The concentrations of lactate, pyruvate, and adenosine, together with some of their derivatives, were determined in microdialysates from 12 pig hearts, 6 of which were subjected to preconditioning and 40 min of ischemia (index ischemia) and 6 of which were subjected to only 40 min of index ischemia. Two microdialysis probes were inserted in ischemic myocardium. Glyburide (10 mu M) in a modified isotonic Krebs-Ringer phosphate buffer was administered through one of the probes and plain isotonic phosphate buffer was administered through the other. Accordingly, the experimental setup permitted us to study the metabolic effects of glyburide on ischemic myocardium constituting two groups that were either preconditioned or unpreconditioned. The preconditioning effect was validated with area at risk and infarction area measurements in 12 other pigs. We noted no functional differences between the groups. In the unpreconditioned group glyburide infusion resulted in enhanced 60% lactate production during index ischemia. However, preconditioning attenuated the enhancing effect of glyburide on lactate production. The interplay between the effects of glyburide and preconditioning on ischemic myocardium is suggested to be dependent on the different modes of action on the K(+)(ATP) channel.