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Biomedical subjects

M Axelsson

Publications and source records attributed to M Axelsson.

At least 19 recordsLinked to original sources

A novel, fully implantable, multichannel biotelemetry system for measurement of blood flow, pressure, ECG, and temperature.

Biotelemetry provides high-quality data in awake, free-ranging animals without the effects of anesthesia and surgery. Although many biological parameters can be measured using biotelemetry, simultaneous telemetric measurements of pressure and flow have not been available. The objective of this study was to evaluate simultaneous measurements of blood flow, pressure, ECG, and temperature in a fully implantable system. This novel system allows the measurement of up to four channels of blood flow, up to three channels of pressure, and a single channel each of ECG and temperature. The system includes a bidirectional radio-frequency link that allows the implant to send data and accept commands to perform various tasks. The system is controlled by a base station decoder/controller that decodes the data stream sent by the implant into analog signals. The system also converts the data into a digital data stream that can be sent via ethernet to a remote computer for storage and/or analysis. The system was chronically implanted in swine and alligators for up to 5 wk. Both bench and in vivo animal tests were performed to evaluate system performance. Results show that this biotelemetry system is capable of long-term accurate monitoring of simultaneous blood flow and pressure. The system allows, within the room, recordings, since the implant transmission range is between 6 and 10 m, and, with a relay, backpack transmission distance of up to 500 m can be achieved. This system will have significant utility in chronic models of cardiovascular physiology and pathology.

Alligators and Crocodiles↗

Effects of hypoxia on the venous circulation in rainbow trout (Oncorhynchus mykiss).

Hypoxia in fish is generally associated with bradycardia while cardiac output (Q) remains unaltered or slightly increased due to a compensatory increase in stroke volume (SV). Rainbow trout (Oncorhynchus mykiss) were subjected to severe (P(W)O2=7.3+/-0.2 kPa) or mild (P(W)O2=11.5+/-0.2 kPa) hypoxia. Central venous pressure (P(ven)), dorsal aortic pressure (P(da)), heart rate (f(H)) and Q, were recorded in vivo. Both levels of hypoxia triggered a significant increase in P(ven). Severe hypoxia was associated with bradycardia and unaltered Q, whereas mild hypoxia was associated with a small but significant increase in Q and no bradycardia. These findings indicate that an increase in P(ven) promotes an increase in SV during hypoxia. Since mild hypoxia increased P(ven), Q and SV without bradycardia or reduced systemic resistance (R(sys)), we hypothesize that an active increase in venous tone serving to mobilize blood to the central venous compartment in order to increase cardiac preload and consequently SV, is an important cardiovascular trait associated with hypoxia. Pharmacological pre-treatment with prazosin (1 mg kg(-1)) did not conclusively reveal the underlying mechanisms to the observed changes in P(ven). This study discusses the influence of venous pooling, reduced R(sys) and altered venous tone on changes in P(ven) observed during hypoxia.

Adrenergic alpha-Antagonists↗

Computed tomographic colonography: comparison of two workstations.

PURPOSE: To compare two commercially available computed tomography (CT) colonography systems with respect to interobserver variability, the influence of level of expertise, and the gradual reduction of reviewing time for each system. MATERIAL AND METHODS: Two residents and two radiologists using Siemens CTAPP Colography software and Viatronix V3D-Colon software reviewed supine and prone CT acquisitions from 24 patients in a primary 3D endoluminal view. The observers graded each case with respect to technical quality and diagnostic value, assessed the presence of pathology, and indicated the time spent on the viewing. RESULTS: Significant differences were found in technical quality (P < 0.001) and diagnostic value (P<0.001) depending on which system was used, with higher scores for the Viatronix software. The agreement between specialists tended to be higher than that between residents (kappa=0.63 (0.30-0.95) vs. kappa=0.51 (0.21-0.81)), and the residents gave significantly (P < 0.001) higher scores of technical quality. However, the level of expertise had no significant impact on the assessments. We noted extensive variability in pathological lesions found by the different observers. The number of findings did not differ between workstations, but the viewers tended to report larger polyp sizes with the Viatronix software. The time needed for viewing decreased significantly from the first to the last examination viewed by each observer. CONCLUSION: Both the evaluated systems present trustworthy images of the human colon, but in a primary 3D setting the Viatronix software is favored owing to the user-friendly interface, higher experienced technical quality, and better diagnostic value.

Adult↗

Baroreflex mediated control of heart rate and vascular capacitance in trout.

The baroreflex was triggered by altering branchial blood pressure with pre- and post-branchial occlusions for 30 s in rainbow trout Oncorhynchus mykiss. The cardiac limb of the baroreflex was monitored by continuous heart rate (f(H)) measurements. Responses of venous capacitance vessels were assessed, immediately following either occlusion, by measuring mean circulatory filling pressure (MCFP). Arterial responses were evaluated as the change in dorsal aortic blood pressure (P(da)) before and after pre-branchial occlusion. In untreated fish pre-branchial occlusion resulted in tachycardia (62.4+/-2.4 to 69.1+/-1.7 beats min(-1)), decreased venous capacitance reflected as an increase in MCFP (0.17+/-0.03 to 0.27+/-0.03 kPa) and increased P(da) (4.0+/-0.2 kPa compared to 3.2+/-0.1 kPa before occlusion). Post-branchial occlusion somewhat reversed the responses since f(H) decreased (62.4+/-2.4 to 53.0+/-3.1 beats min(-1)), whereas MCFP remained unaltered. Treatment with the alpha-adrenergic blocker prazosin (1 mg kg(-1)) increased resting MCFP to 0.33+/-0.03 kPa and appeared to abolish both venous and arterial responses to branchial occlusion. Subsequent atropine treatment (1.2 mg kg(-1)) abolished all chronotropic responses. We present for the first time ample evidence for baroreflex-mediated control of cardiovascular homeostasis, including both the chronotropic and the vascular limb of the baroreflex in an unanaesthetized fish. Furthermore, a novel technique to cannulate and occlude the dorsal aorta, using a Fogarty thru-lumen embolectomy catheter, is explained.

Animals↗

Nitric oxide, a potent vasodilator of the aortic anastomosis in the estuarine crocodile, Crocodylus porosus.

The effects of five neuropeptides (CGRP, SOM, SP, NPY, VIP), L-NAME (nitric oxide synthase inhibitor), and adrenaline on the contractile tone of the aortic anastomosis in the estuarine crocodile, Crocodylus porosus, were investigated. None of the neuropeptides, which had previously been found to be present in the aortic anastomosis, had any direct effect on the tension developed by ring preparations. L-NAME itself significantly increased the basal tone of the vascular ring preparations, suggesting a tonic release of nitric oxide in the preparation. Adrenaline produced concentration-dependent vasoconstrictions that were counteracted by profound reflex vasodilatations that were susceptible to blockade by L-NAME. Immunohistochemistry revealed the presence of nitric oxide synthase and tyrosine hydroxylase-containing (indicating the presence of a adrenergic innervation) nerve fibres in the adventitia and adventitio-medial border of the aortic anastomosis. These data demonstrate opposing actions of adrenaline and nitric oxide on the vascular smooth muscle in the anastomosis of the C. porosus. The morphology of the anastomosis, with the extremely thick muscular vessel wall, suggests a sphincter-like function for this vessel that could be controlled mainly by adrenergic and nitrergic mechanisms.

Alligators and Crocodiles↗

The calibre of the foramen of Panizza in Crocodylus porosus is variable and under adrenergic control.

The foramen of Panizza is located within the outflow tract of the crocodilian heart, between the left and right aortas. It has been suggested that the foramen of Panizza has a variable calibre, which could explain the profound changes in the distribution of flows and pressure profiles recorded in the right and left aortas. We investigated this possibility using a modified in-situ perfused heart preparation in combination with isolated strip preparations from the outflow tract. In the perfused heart preparation, bolus injections of adrenaline increased the resistance in the foramen of Panizza, indicating a decrease in its diameter. Isolated strip preparations from the outflow tract showed a concentration-dependent increase in tension in response to adrenaline, while vasoactive intestinal polypeptide caused a relaxation in adrenaline pre-contracted strip preparations. We propose that an increase in the diameter of the foramen of Panizza may be important during pulmonary to systemic shunts to allow blood to flow from the left to right aorta (reverse foramen flow) in order to supply the carotid and coronary arteries. During non-shunting conditions, a constricted foramen may prevent excess flow from the right to left aorta during diastole.

Alligators and Crocodiles↗

Large veins in the Atlantic cod (Gadus morhua) and the rainbow trout (Oncorhynchus mykiss) are innervated by neuropeptide-containing nerves.

Previous studies have shown that fish veins are reactive to several hormones known to exist in the fish circulation. Besides this humoral control, another possible means of active regulation of venous return is by autonomic nervous control of venous tone. This study therefore investigated the presence of a perivascular innervation of major veins in the Atlantic cod (Gadus morhua) and the rainbow trout (Oncorhynchus mykiss) using immunohistochemical methods. Histological staining was employed to investigate the smooth muscle distribution in the vessel walls. Vasoactive intestinal polypeptide-immunoreactive nerve fibers were found to be widespread in the venous system of G. morhua and O. mykiss, while pituitary adenylate cyclase-activating polypeptide-immunoreactive fibers were demonstrated in the duct of Cuvier of both species. Fibers containing neurokinin A and/or substance P were found in the duct of Cuvier and the posterior cardinal vein of both species and in the hepatic portal vein of O. mykiss. Calcitonin-gene related peptide-immunoreactive fibers were present in the duct of Cuvier of both species and in the hepatic portal vein of O. mykiss. Galanin-immunoreactive fibers were found in the duct of Cuvier in O. mykiss and in the hepatic portal vein of both species. Co-existence of neuropeptides in the perivascular nerve fibers was investigated by double labelling. Vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide-immunoreactive fibers were found in both species. Vasoactive intestinal polypeptide/galanin-immunoreactive fibers and vasoactive intestinal polypeptide/calcitoningene related peptide-immunoreactive fibers were found in G. morhua but not in O. mykiss. This study gives further evidence for an active venoregulation by autonomic nerves in teleost fish.

Animals↗

Gut blood flow in fish during exercise and severe hypercapnia.

This paper reviews the effects of exercise and hypercapnia on blood flow to the splanchnic circulation. Brief struggling behaviours are known to decrease blood flow to the gut (GBF). Likewise, prolonged swimming in unfed fish has been shown to reduce GBF in proportion to the increased oxygen uptake. Therefore, the normal postprandial increase in GBF theoretically should be impaired whenever fish are active. However, indirect evidence suggests that GBF is spared to some degree when fed fish swim continuously but at a cost (10-15%) to their critical swimming speed. Severe respiratory acidosis can be created by the new intensive aquaculture settings that use oxygen injection into re-circulated water. The only study so far to examine the effects of severe hypercapnia on GBF and its regulation showed that routine GBF and alpha-adrenergic control of GBF remained normal in unfed white sturgeon (Acipenser transmontanus). However, severe hypercapnia produced a hyperactive state and increased sensitivity of GBF to struggling. As a result, routine GBF was maintained for a short period of time. Thus, environmental changes such as severe hypercapnia can indirectly impact GBF through altered struggling behaviour, but the implications of the overall reduction in GBF to food assimilation have yet to be established.

Animals↗

Risk factors associated with hindlimb lameness and degenerative joint disease in the distal tarsus of Icelandic horses.

The aim of this study was to evaluate potential risk factors associated with hindlimb lameness and radiographic signs of degenerative joint disease (DJD) in the distal tarsus in Icelandic horses. The material consisted of riding horses (n = 420) age 6-12 years sired by 17 selected sires representing all major breeding lines, and of riding horses (n = 194) in the same age range sired by other sires. The examination protocol included the following: interview with owners/trainers, assessment of conformation, motion evaluation and radiographic examination. At the interview, data related to factors outside the horse (environmental variables) and data associated directly with the horse (intrinsic variables) were obtained. Data analysis was performed in 2 steps: screening using bivariate analysis, followed by testing with a multivariate logistic regression model. In the multivariate analysis, the factors of sire, age when broken to saddle and stud show participation were strongly associated with the prevalence of lameness. Height at the croup and ability to perform different gaits were also associated with the prevalence of lameness, but to a lesser degree. The risk factors of age, tarsal angle and birthplace were significantly associated with radiographic signs of DJD in the distal tarsus. Neither the variation in applied training intensity, the use of a professional or amateur trainer nor the temperament or front limb action of the individual horse was significantly associated with the prevalence of hindlimb lameness and/or radiographic signs of DJD in the distal tarsus in the Icelandic horse.

Age Factors↗

The transmembrane domain and the proton channel in proton-pumping transhydrogenases.

Proton-pumping nicotinamide nucleotide transhydrogenases are composed of three main domains, the NAD(H)-binding and NADP(H)-binding hydrophilic domains I (dI) and III (dIII), respectively, and the hydrophobic domain II (dII) containing the assumed proton channel. dII in the Escherichia coli enzyme has recently been characterised with regard to topology and a packing model of the helix bundle in dII is proposed. Extensive mutagenesis of conserved charged residues of this domain showed that important residues are betaHis91 and betaAsn222. The pH dependence of betaH91D, as well as betaH91C (unpublished), when compared to that of wild type shows that reduction of 3-acetylpyridine-NAD(+) by NADPH, i.e., the reverse reaction, is optimal at a pH essentially coinciding with the pK(a) of the residue in the beta91 position. It is therefore concluded that the wild-type transhydrogenase is regulated by the degree of protonation of betaHis91. The mechanisms of the interactions between dI+dIII and dII are suggested to involve pronounced conformational changes in a 'hinge' region around betaR265.

Amino Acid Sequence↗

Proton translocating nicotinamide nucleotide transhydrogenase from E. coli. Mechanism of action deduced from its structural and catalytic properties.

Transhydrogenase couples the stereospecific and reversible transfer of hydride equivalents from NADH to NADP(+) to the translocation of proton across the inner membrane in mitochondria and the cytoplasmic membrane in bacteria. Like all transhydrogenases, the Escherichia coli enzyme is composed of three domains. Domains I and III protrude from the membrane and contain the binding site for NAD(H) and NADP(H), respectively. Domain II spans the membrane and constitutes at least partly the proton translocating pathway. Three-dimensional models of the hydrophilic domains I and III deduced from crystallographic and NMR data and a new topology of domain II are presented. The new information obtained from the structures and the numerous mutation studies strengthen the proposition of a binding change mechanism, as a way to couple the reduction of NADP(+) by NADH to proton translocation and occurring mainly at the level of the NADP(H) binding site.

Amino Acid Sequence↗

Gastrointestinal blood flow in the red Irish lord, Hemilepidotus hemilepidotus: long-term effects of feeding and adrenergic control.

Cardiac output, blood flow to the coeliac and mesenteric arteries, dorsal aortic blood pressure and heart rate were recorded simultaneously at rest and postprandial for 6 days in a teleost, the red Irish lord (Hemilepidotus hemilepidotus). We anticipated that gastrointestinal blood flow would increase postprandially, supported by an increase in cardiac output. However, we had no predictions for either the exact time-course of this response, or for the regional distribution of blood flow between to the two major arteries comprising the splanchnic circulation. In resting, unfed animals, blood flow to the coeliac artery and mesenteric artery was 4.1 +/- 0.6 ml min(-1) kg(-1) and 4.9 +/-1.3 ml min(-1) kg(-1), respectively (mean +/- SEM, n = 7), which together represented 34% of cardiac output. Feeding increased blood flow to the coeliac and mesenteric arteries in a time-dependent manner. The increase in coeliac artery blood flow preceded that in the mesenteric artery, a finding that is consistent with the coeliac artery supplying blood to the liver and stomach, while the mesenteric artery supplies blood to the stomach and intestine. Coeliac blood flow had increased by 84 +/- 18% after 1 day and had a peak increase of 112 +/- 40% at day 4 postprandial. Mesenteric blood flow was not significantly elevated at day 1, but had increased by 94 +/- 19% at day 4 postprandial. Cardiac output also increased progressively, increasing by a maximum of 90 +/- 30% at day 4. Because the increase in cardiac output was adequate to meet the postprandial increase in gut blood flow, the postprandial decreases in vascular resistance for the coeliac and mesenteric circulations mirrored the increases in blood flow. Intra-arterial injections of adrenaline and noradrenaline into resting fish more than doubled coeliac and mesenteric vascular resistances, and blood flow decreased proportionately. This adrenergic vasoconstriction was totally abolished by pretreatment with the alpha-adrenoceptor antagonist phentolamine, which in itself approximately halved coeliac and mesenteric vascular resistances. These observations indicate a significant alpha-adrenergic tone in the gastrointestinal circulation of the red Irish lord, the loss of which could not entirely account for the post-prandial increase in gastrointestinal blood flow. Other control mechanisms are suggested.

Adrenergic alpha-Agonists↗

Interactions between the soluble domain I of nicotinamide nucleotide transhydrogenase from Rhodospirillum rubrum and transhydrogenase from Escherichia coli. Effects on catalytic and H+-pumping activities.

Nicotinamide nucleotide transhydrogenase from Escherichia coli is composed of two subunits, the alpha and the beta subunits, each of which contains a hydrophilic domain, domain I and III, respectively, as well as several transmembrane helices, collectively denoted domain II. The interactions between domain I from Rhodospirillum rubrum (rrI) and the intact or the protease-treated enzyme from E. coli was investigated using the separately expressed and purified domain I from R. rubrum, and His-tagged intact and trypsin-treated E. coli transhydrogenase. Despite harsh treatments with, e.g. detergents and denaturing agents, the alpha and beta subunits remained tightly associated. A monoclonal antibody directed towards the alpha subunit was strongly inhibitory, an effect that was relieved by added rrI. In addition, rrI also reactivated the trypsin-digested E. coli enzyme in which domain I had been partly removed. This suggests that the hydrophilic domains I and III are not in permanent contact but are mobile during catalysis while being anchored to domain II. Replacement of domain I of intact, as well as trypsin-digested, E. coli transhydrogenase with rrI resulted in a markedly different pH dependence of the cyclic reduction of 3-acetyl-pyridine-NAD+ by NADH in the presence of NADP(H), suggesting that the protonation of one or more protonable groups in domain I is controlling this reaction. The reverse reaction and proton pumping showed a less pronounced change in pH dependence, demonstrating the regulatory role of domain II in these reactions.

Amino Acid Sequence↗

Cardiovascular actions of python bradykinin and substance P in the anesthetized python, Python regius.

The cardiovascular actions of python bradykinin (BK) and substance P (SP) have been investigated in the anesthetized ball python, Python regius. Bolus intra-arterial injections of python BK (0.03-3 nmol/kg) produced concentration-dependent increases in arterial blood pressure, heart rate (HR), and cardiac output concomitant with small decreases in systemic resistance and stroke volume. Intra-arterial injection of 3 nmol/kg python BK produced a tenfold increase in circulating concentration of norepinephrine, but epinephrine levels did not change. BK-induced tachycardia was attenuated (>90%) by the beta-adrenergic receptor antagonist sotalol, and the hypertensive response was attenuated (>70%) by the alpha-adrenergic receptor antagonist prazosin, indicating that effects of python BK are mediated at least in part by activation of the extensive network of adrenergic neurons present in vascular tissues. Bolus intra-arterial injections of python SP in the range 0. 01-30 pmol/kg produced concentration-dependent decreases in arterial blood pressure and systemic peripheral resistance concomitant with increases in cardiac output and stroke volume but with only minor effects on HR. The data suggest that kinins play a physiologically important role in cardiovascular regulation in the python.

Adrenergic alpha-Antagonists↗

The emetic reflex in a reptile (Crocodylus porosus).

The emetic (vomiting) reflex in a crocodilian, Crocodylus porosus, was characterised for the first time using the plant alkaloid veratrine (5 mg kg(-)(1) i.v. or i.p.) as an emetic stimulus. The latency to the onset of vomiting was 8.0+/-0.9 min (mean +/- s.e.m., N=5 animals). Vomiting was preceded by a clearly defined set of prodromal behaviours including, in temporal sequence, rhythmic contraction of the pharynx, sneezing and jaw snapping. Expulsion of vomitus was not particularly forceful and was accompanied by lateral shaking of the head. Physiological studies revealed that vomiting was accompanied by oscillatory (9.1+/-0.7 oscillations over 29.7+/-3. 6 s, N=9 episodes in three animals) increases in intraperitoneal pressure (7.0+/-0.9 kPa, cf. 0.7+/-0.1 kPa during respiration). The significance of these results is discussed in the context of the role(s) of vomiting as a protective reflex and as a mechanism for removal of indigestible food residues (e.g. fur, claws) from the gut.

Abdomen↗