Biomedical subjects

G E Nilsson

Publications and source records attributed to G E Nilsson.

At least 19 recordsLinked to original sources

PubMed2000

Brain blood flow during hypercapnia in fish: no role of nitric oxide.

Very little is known about the regulation of cerebral blood flow (CBF) in lower vertebrates, especially fish. In mammals, hypercapnia causes cerebral vasodilation and increased CBF through mechanisms that involve the production of nitric oxide (NO). We have used epi-illumination microscopy in vivo to observe effects of hypercapnia on venular erythrocyte velocity, used as an index of CBF velocity, in rainbow trout (Oncorhynchus mykiss) and crucian carp (Carassius carassius). Rainbow trout exposed to a pCO(2) of 7.5 mmHg displayed a small increase of CBF velocity in two out of five fishes, while dorsal aortic blood pressure (P(DA)) did not change. Exposing trout to a pCO(2) of 22.5 mmHg, resulted in an 80% increase in CBF velocity and a 21% increase in P(DA). Trout exposed to a pCO(2) of 75 mmHg showed an additional increase in blood pressure, while no further increase was seen in CBF velocity compared to a pCO(2) of 22. 5 mmHg. By contrast, no change in CBF velocity was seen in crucian carp, even at a pCO(2) of 75 mmHg. None of the circulatory changes seen in the trout could be blocked by superfusing the brain surface with the NO synthase blocker N(G)-nitro-L-arginine. The results point at striking species differences in the responses of CBF and P(DA) to hypercapnia in fish, and that the hypercapnia induced increase in CBF velocity seen in rainbow trout is independent of NO production.

Animals↗

PubMed2000

Effects on skin blood flow by provocation during local analgesia.

Although topical analgesia cream has been used for several years, little is known about its effects on the microcirculation. Previous studies have shown a vasoconstrictive effect after short application times and a vasodilatation after longer application. It has also been shown that vasomotion does not occur in the analgesized skin. The present study was undertaken to investigate the alterations in skin blood perfusion following local cooling, local heating and pin-pricking after the establishment of analgesia. In 11 healthy volunteers, skin analgesia was attained by use of a eutectic mixture of lidocaine and prilocaine (EMLA, Astra Pain Control AB, Sweden) applied to the skin three hours prior to provocation. The changes in skin blood perfusion, after applying three different provocation methods, were studied using the laser Doppler technique. Local cooling and heating to temperatures of +10 and +45 degrees C, respectively, were applied for 9 s by use of a copper probe (O12 mm). In the pin-prick provocation method, a combined effect of deflection and penetration of the skin to in total 3 mm was attained. Identical provocation methods were applied to placebo treated and untreated skin areas. After heat provocation, significant differences in the perfusion response between the treatments were seen (P < 0.0001). Skin areas treated with analgesia cream responded with a slow increase in perfusion that persisted beyond the four minute measurement period. Placebo and untreated areas decreased their perfusion over time. After cooling a significant reduction in skin perfusion was seen, irrespective of the treatment. Similarly, after pin-pricking a perfusion increase was seen for all treatments. The findings indicate that topical analgesia influences the myogenic control of the blood flow in those vascular plexa measured by laser Doppler following heat provocation. No differences could be seen in the response to pin-pricking and cooling for the different treatments.

Adolescent↗

PubMed1999

Relationships between sex and the size and number of forebrain gonadotropin-releasing hormone-immunoreactive neurones in the ballan wrasse (Labrus berggylta), a protogynous hermaphrodite.

This study is the first to examine the brain gonadotropin-releasing hormone (GnRH) cell population phenotype in a protogynous and monandric sequentially hermaphroditic fish. Male ballan wrasse (Labrus berggylta) had on average higher numbers of GnRH-immunoreactive (GnRH-ir) cells within the brain preoptic area (POA) than females, a difference not found in GnRH-ir cells in other brain regions. Furthermore, in males, but not females, the number of these POA GnRH-ir cells correlated with body size. Maturational state (prespawning or postspawning) had marked effects on mean profile sizes (but not numbers) of both GnRH-ir cell bodies and cell nuclei, even when existing differences in body size and allometric relationships had been taken into account. Postspawning males tended to have larger GnRH-ir profiles in all brain regions relative to both prespawning males and females. Moreover, the GnRH-ir cell number in POA, and the cell body profile size in both POA and at the level of the anterior commissure, correlated with gonad size in spermiated prespawning males, indicating a relationship between both size and number of GnRH cells and male gonadal development. These results suggest that temporary changes in the size of brain GnRH-ir neurones are coupled to the male spawning cycle, and that permanent POA GnRH-ir cell number changes are involved in the process of sex change in sequential hermaphrodites. However, smaller males had no more preoptic GnRH-ir cells than equally sized females, which may argue against a proximate inducing role of GnRH cell number changes in naturally occurring sex reversal.

Animals↗

PubMed1999

Hypoxia stimulates cerebral blood flow in the estuarine crocodile (Crocodylus porosus).

The effect of N2 respiration on cerebral blood flow (CBF) velocity on the dorsal surface of cerebellum was examined in the estuarine crocodile, Crocodylus porosus, using epi-illumination microscopy. Twelve minutes of N2 respiration resulted in a 126% increase in CBF velocity. N2 respiration had no effect on blood pressure, indicating an underlying cerebral vasodilation. In addition, heart rate increased significantly. Systemic injections of aminophylline and the NO synthase (NOS) inhibitor nitro-L-arginine (L-NA) did not affect the hypoxia induced increase in CBF. We conclude that C. porosus responds to hypoxia with adenosine and nitric oxide (NO) independent cerebral vasodilation, and that this is likely to be a mechanism protecting the brain from energy deficiency during prolonged dives.

Alligators and Crocodiles↗

PubMed1999

Extracellular levels of amino acid neurotransmitters during anoxia and forced energy deficiency in crucian carp brain.

The crucian carp is one of the few vertebrates that has the ability to survive long periods of anoxia. A devastating event in the anoxic mammalian brain is a massive release of excitatory neurotransmitters, particularly glutamate. Using microdialysis to measure extracellular levels of several amino acid neurotransmitters and related compounds in the telencephalon of crucian carp in vivo, we show here that this species avoids a release of glutamate during anoxia, which is probably related to its ability to maintain energy charge. Instead, 6 h of anoxia produced a doubling of the extracellular level of GABA, the major inhibitory neurotransmitter in brain. The release of GABA may be a mechanism for lowering neuronal activity and energy use, thereby facilitating the maintenance of energy charge. Perfusing the microdialysis probe with a high-K+ Ringer showed that the telencephalon had the ability to release both glutamate and GABA. Moreover, if energy deficiency was produced during anoxia, by inhibiting glycolysis with iodoacetate (IAA), the resulting release of GABA was more rapid and profound than that of glutamate, possibly reflecting a second line of anoxia defence aimed at minimising the effect of a temporary energy failure.

Amino Acids↗

PubMed1999

Tissue-specific changes in RNA synthesis in vivo during anoxia in crucian carp.

The overall energy budget for protein synthesis (i.e., transcription plus translation) is thought to consist of fixed and variable components, with RNA synthesis accounting for the former and protein synthesis the latter. During anoxia, the downregulation of protein synthesis (i.e., the variable component), to reduce energetic demand, is an important aspect of survival in crucian carp. The present study examines RNA synthesis during anoxia by labeling with [(3)H]uridine. A novel synthesis rate calculation is presented, which allows for the tissue-specific salvage of uridine, with synthesis rates finally expressed relative to DNA. After 48 h anoxia, the decline (29%) in brain RNA synthesis and increases in the heart and liver (132 and 871%, respectively) support known RNA functions during hypoxic/anoxic survival. This study provides evidence that, in an anoxia-tolerant species, survival mechanisms involving RNA are able to operate because tissue-specific restructuring of the RNA synthesis process enables fixed synthesis costs to be maintained; this may be as vital to survival as exploiting the variable energetic demand of protein synthesis.

Animals↗

PubMed1999

Brain blood flow and blood pressure during hypoxia in the epaulette shark Hemiscyllium ocellatum, a hypoxia-tolerant elasmobranch.

The key to surviving hypoxia is to protect the brain from energy depletion. The epaulette shark (Hemiscyllium ocellatum) is an elasmobranch able to resist energy depletion and to survive hypoxia. Using epi-illumination microscopy in vivo to observe cerebral blood flow velocity on the brain surface, we show that cerebral blood flow in the epaulette shark is unaffected by 2 h of severe hypoxia (0.35 mg O2 l-1 in the respiratory water, 24 C). Thus, the epaulette shark differs from other hypoxia- and anoxia-tolerant species studied: there is no adenosine-mediated increase in cerebral blood flow such as that occurring in freshwater turtles and cyprinid fish. However, blood pressure showed a 50 % decrease in the epaulette shark during hypoxia, indicating that a compensatory cerebral vasodilatation occurs to maintain cerebral blood flow. We observed an increase in cerebral blood flow velocity when superfusing the normoxic brain with adenosine (making sharks the oldest vertebrate group in which this mechanism has been found). The adenosine-induced increase in cerebral blood flow velocity was reduced by the adenosine receptor antagonist aminophylline. Aminophylline had no effect upon the maintenance of cerebral blood flow during hypoxia, however, indicating that adenosine is not involved in maintaining cerebral blood flow in the epaulette shark during hypoxic hypotension.

Adenosine↗

PubMed1999

Principles and practice of the laser-Doppler perfusion technique.

This paper reviews the development and use of laser-Doppler perfusion monitors and imagers over the past two decades. The enormous interest in microvascular blood perfusion coupled with the 'ease of use' of the technique has led to 1500+ publications citing its use. However, useful results can only be achieved with an understanding of the basic principles of the instrumentation and its application in the various clinical disciplines. The basic theoretical background is explored and definitions of blood perfusion and laser-Doppler perfusion are established. The calibration method is then described together with potential routes to standardisation. A guide to the limitations in application of the technique gives the user a clear indication of what can be achieved in new studies as well as possible inadequacy in some published investigations.

Artifacts↗

PubMed1998

A mathematical analysis on the biological zero problem in laser Doppler flowmetry.

The biological zero (BZ) problem is a critical issue inherent in laser Doppler flowmetry (LDF). It causes confusion when measuring low tissue blood flows. Many experimental studies have been done on the question of whether the BZ flux should be subtracted from the normally measured flux in various situations. However this problem can only be solved after a proper mathematical analysis. Only then can we clearly define and formulate what flux is truly meaningful in blood perfusion measurement and what movement generates the BZ flux and how can we correctly remove it. Following this motivation, the movement of moving blood cells (MBC's) is decomposed into a net translation and a random wondering based on in vivo observations. This important step leads to a clear definition of the BZ and net perfusion flux and reveals that subtraction of BZ flux from the normal flux will certainly cause an underestimation of the net flux. Using this decomposition, the relationship between the net, BZ and normal flux is established which leads to the correct formula to recover the net flux from the BZ and normal fluxes. This recovered net flux is shown to be bounded by the normal flux and the normal flux minus the BZ flux. Numerical studies, preliminary phantom model and clinical evaluations manifest that the new approach is more accurate and reasonable at measuring low net fluxes. In contrast, subtracting BZ flux causes a systematic underestimation of perfusion and is apparently inappropriate even from a methodological point of view. In addition to the novel BZ solution, a general density function of the speed of MBC's is given which is more faithful than the Maxwell density used in [4]. This general density function offers new possibilities for further theoretical developments in LDF.

Capillaries↗

PubMed1998

A note on the compartmental analysis and related issues in laser Doppler flowmetry.

Compartmental analysis (CA) in laser Doppler flowmetry (LDF) means deciphering the nutritional and thermoregulating flows from the measured perfusion flux. Based on the new theories proposed in [1] and [2], the CA is formulated here as an optimal approximation without directly involving the geometric information of the vessel network. It is seen that this approximation approach could also solve the biological zero (BZ) problem simultaneously, therefore, it actually provides a systematic solution to the BZ problem without estimating the BZ flux experimentally. In addition, the BZ problem with compartmental differences is reformulated, and the condition under which multiple compartments can be treated as a single one is investigated. The result, together with some computer simulations, showed that the theory in [2] is still an easy and useful approximation in practice. This note serves as an useful supplement to [1] and [2] and may help to solve and clarify some critical problems in LDF.

Body Fluid Compartments↗

PubMed1998

Acute defense mechanisms against hemorrhage from mechanical gill injury in rainbow trout.

By cutting gill filaments in anesthetized rainbow trout (Oncorhynchus mykiss), observing the bleeding through a stereomicroscope, and using blockers of various known endogenous filament artery vasoconstrictors, we have here attempted to characterize hemostatic mechanisms in gills. The immediate hemostatic response to a cut in a gill filament artery was a local vasoconstriction, stopping the hemorrhage within approximately 20 s. In heparinized fish, the hemorrhage recommenced after approximately 8 min, suggesting that the vasoconstriction soon subsides and blood clotting becomes responsible for the hemostasis. Antagonists of acetylcholine, adenosine, and serotonin receptors were unable to block the hemostatic vasoconstriction. Also, tetrodotoxin was without effect, indicating a nonnervous origin. By contrast, indomethacin significantly affected the measured bleeding times, suggesting that eicosanoids play a significant role in this process (possibly by stimulating vasoconstriction and/or by inducing local thrombocyte aggregation). By possessing several hundred virtually identical filaments with readily observable vasculature, the fish gill appears to be a good experimental model for studying hemostatic mechanisms.

Animals↗

PubMed1997

Anoxic depression of light-evoked potentials in retina and optic tectum of crucian carp.

The crucian carp is an exceptionally anoxia-tolerant vertebrate. For the brain, with its very high rate of ATP use, depression of energy use is likely to be an important strategy for anoxic survival. This study shows that the light-evoked response of the retina and the corresponding evoked potential in optic tectum decrease in amplitude by 69 and 75%, respectively, during 38 min of anoxia, and by about 90% after 1 h in anoxia. Both responses were restored upon reoxygenation. The length of light exposure (5 s or 100 ms) did not affect the degree of anoxic depression. These results are the first to show an anoxia-induced depression of central nervous system (CNS) activity in vivo in this species, and indicate that the crucian carp temporarily turns off its visual sense in order to reduce neural energy use during anoxic condition.

Animals↗

PubMed1997

Brain Na+/K+-ATPase activity in two anoxia tolerant vertebrates: crucian carp and freshwater turtle.

The crucian carp (Carassius carassius) and freshwater turtles (Trachemys scripta) are among the very few vertebrates that can survive extended periods of anoxia. The major problem for an anoxic brain is energy deficiency. In the brain, the Na+/K+-ATPase is the single most ATP consuming enzyme, being responsible for maintaining ion gradients. We here show that the Na+/K+-ATPase activity in the turtle brain is reduced by 31% in telencephalon and by 34% in cerebellum after 24 h of anoxia. Both changes were reversed upon reoxygenation. By contrast, the Na+/K+-ATPase activities were maintained in the anoxic crucian carp brain. These results support the notion that crucian carp and turtles use divergent strategies for anoxic survival. The fall in Na+/K+-ATPase activities displayed by the turtle is likely to be related to the strong depression of brain electric and metabolic activity utilized as an anoxic survival strategy by this species.

Animals↗

PubMed1997

Serotonin as a regulator of hypothalamic-pituitary-interrenal activity in teleost fish.

Evidence for the presence of a serotonin1A (5-HT1A) receptor subtype in the salmonid fish brain has recently been presented. In the present study the potent 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) was tested for its effect on plasma cortisol concentrations in rainbow trout (Oncorhynchus mykiss). Blood was sampled and 8-OH-DPAT administered through a catheter in the dorsal aorta. Thirty minutes after the injection of 40 microg of 8-OH-DPAT/kg, plasma cortisol levels had increased from 12 to 149 ng/ml, whereupon they fell, reaching baseline levels after 4 h. The effect of 1-40 microg 8-OH-DPAT/kg on plasma cortisol concentrations was dose-dependent. The results lends further support to the hypothesis that the brain serotonergic system plays a key role in integrating autonomic, behavioral and neuroendocrine stress-responses in fish as well as mammals, suggesting that not only the structural and biochemical organization, but also the function of the serotonergic system has been conserved during vertebrate evolution.

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

PubMed1997

Effects of L-thyroxine on brain monoamines during parr-smolt transformation of Atlantic salmon (Salmo salar L.).

During spring, seaward migrating juvenile Atlantic salmon (Salmo salar) undergo parr-smolt transformation (PST) which involves changes in physiology, including one or two peaks in plasma thyroxine (T4). To investigate if changes in plasma T4 influence neural function, we measured levels of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and also measured serotonin (5-hydroxytryptamine, 5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in brain regions of two groups of Atlantic salmon parr on an 8:16 h light/dark photoperiod. One group was treated with ambient T4 to simulate the natural smolt peak in plasma T4. T4 treatment depressed DOPAC levels as well as DOPAC/DA and 5-HIAA/5-HT ratios in the olfactory system but with no changes in the optic tectum. We conclude that during PST monoaminergic functions in specific brain regions of juvenile Atlantic salmon are affected by T4 treatment.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Comparative aspects on nitric oxide in brain and its role as a cerebral vasodilator.

Histological studies have detected nitric oxide (NO) synthase in the central nervous system of all vertebrates examined, from lampreys to mammals. However, there are still very few comparative physiological studies on the function of NO synthase in the brain of non-mammalian vertebrates. So far, we know that acetylcholine can cause an NO-dependent increase in brain blood flow in turtles and some fish species (crucian carp and rainbow trout), whereas some other fishes appear to lack such a mechanism. Hypercapnia can induce NO-dependent cerebral vasodilation in mammals, but such a mechanism appears to be lacking in the ectothermic vertebrates examined. The number of species studied needs to be expanded before we can draw any firm conclusions about the origin of NO-dependent brain blood flow regulation: if it has evolved more than once or if it has been occasionally lost during evolution. We conclude that NO synthase may be present in all vertebrate brains but that its functions can vary, as judged from its role in cerebral blood flow regulation. The diversity of functions that NO has proven to have within the mammalian brain is likely to be paralleled by the same degree of diversity of function between vertebrate groups.

Animals↗

PubMed1997

A role for adenosine in metabolic depression in the marine invertebrate Sipunculus nudus.

Involvement of neurotransmitters in metabolic depression under hypoxia and hypercapnia was examined in Sipunculus nudus. Concentration changes of several putative neurotransmitters in nervous tissue during anoxic or hypercapnic exposure or during combined anoxia and hypercapnia were determined. Among amino acids (gamma-aminobutyric acid, glutamate, glycine, taurine, serine, and aspartate) and monoamines (serotonin, dopamine, and norepinephrine), some changes were significant, but none were consistent with metabolic depression under all experimental conditions applied. Only the neuromodulator adenosine displayed concentration changes in accordance with metabolic depression under all experimental conditions. Levels increased during anoxia, during hypercapnia, and to an even greater extent during anoxic hypercapnia. Adenosine infusions into coelomic fluid via an indwelling catheter induced a significant depression of the normocapnic rate of O2 consumption from 0.36 +/- 0.04 to a minimum of 0.24 +/- 0.02 (SE) mumol.g-1.h-1 after 90 min (n = 6). Application of the adenosine antagonist theophylline caused a transient rise in O2 consumption 30 min after infusion during hypercapnia but not during normocapnia. Effects of adenosine and theophylline were observed in intact individuals but not in isolated body wall musculature. The results provide evidence for a role of adenosine in inducing metabolic depression in S. nudus, probably through the established effects of decreasing neuronal excitability and neurotransmitter release. In consideration of our previous finding that metabolic depression in isolated body wall musculature was elicited by extracellular acidosis, it is concluded that central and cellular mechanisms combine to contribute to the overall reduction in metabolic rate in S. nudus.

Adenosine↗

PubMed1997

Neurochemical mechanisms behind gill microcirculatory responses to hypoxia in trout: in vivo microscopy study.

In vivo microscopy combined with systemic blood flow and pressure measurements were used to examine the hemodynamic and microcirculatory responses to hypoxia in gills of rainbow trout and to clarify if the underlying mechanisms are adrenergic, cholinergic, serotonergic, or adenosinergic. Hypoxia (P(O2) 1.07-1.33 kPa) reduced, halted, or reversed the blood flow in the distal portion of the efferent filamental artery (EFA). Simultaneously, a large overflow to the central venous system appeared, allowing a continuous flow through many of the secondary lamellae. No vasoconstriction could be observed in this portion of the filament, showing that a vasoconstriction occurred elsewhere, possibly at the EFA sphincter, because the gill resistance (R(G)) increased. These effects were mimicked by prebranchial injection of acetylcholine, a treatment that also strongly constricted the distal efferent filamental vasculature. Atropine blocked most of the hypoxia-induced hemodynamic changes, although a minor increase in R(G) remained. The latter appeared to be of a nonadrenergic noncholinergic origin, being unaffected by additional treatment with an alpha-adrenoreceptor antagonist. It was also unaffected by blockers of serotonin and adenosine-A1 receptors. Other responses seen included a cholinergic maintenance of the systemic resistance during hypoxia and an alpha-adrenoceptor-mediated posthypoxic hypertension. This study demonstrates that hypoxia evoked a cholinergic reflex vasoconstriction located at proximal parts of the efferent filamental vasculature.

Acetylcholine↗