Acta physiologica
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To evaluate the haemodynamic effects of the dual endothelin receptor antagonist tezosentan, both alone and combined with hypertonic saline/dextran (HSD), on porcine endotoxin shock, with focus on cardiopulmonary circulation. The effects on gas exchange and short-term survival were also studied. ⋯ Tezosentan, alone and in combination with HSD, improved cardiac index and arterial oxygenation. The addition of HSD to tezosentan treatment did not improve the endotoxin-induced hypotension, but beneficial effects on microcirculation and systemic oxygenation were seen despite low perfusion pressure, as indicated by increased SvO(2) and reduced metabolic acidosis.
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Recently a family of O(2)-dependent prolyl hydroxylase domain-containing enzymes (PHD) has been identified as a cellular oxygen-sensing mechanism. Reduced prolyl hydroxylase activity initiates a signalling cascade that includes the accumulation, as well as the activation, of hypoxia-inducible factor (HIF-1alpha). In turn the transcription factor HIF-1alpha, and other targets of the PHD, elicit a myriad of incompletely understood cellular responses. In these studies we have tested: (1) whether a small-molecule prolyl hydroxylase inhibitor (PHI) can effectively activate the oxygen-sensing pathway when administered systemically to mice, and (2) whether the activation of the PHD signalling pathway at the cellular level results in whole-animal hypoxic tolerance. ⋯ These results demonstrate a novel pharmacological strategy to induce hypoxic tolerance and are the first to demonstrate that the activation of the PHD oxygen-sensing pathway at the cellular level is sufficient to produce a hypoxic-tolerant phenotype at the physiological level of the whole animal.
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Effects of intermittent lower limb ischaemia on coronary blood flow and coronary resistance in pigs.
Intermittent limb ischaemia prior to cardiac ischaemia is a cardioprotective stimulus. This study was to investigate whether this peripheral stimulus had any effects on basal coronary blood flow and resistance, and to explore its potential mechanisms by studying the effect of femoral nerve transection and Katp blockade by glibenclamide. ⋯ The rIPC stimulus leads to reduced coronary resistance and increased flow. This effect, while modified by glibenclamide appears to be a generic effect of remote ischaemia rather than a direct preconditioning effect.
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Recovery of voluntary movements after partial spinal cord injury depends, in part, on a take-over of function via unlesioned pathways. Using precise forelimb movements in the cat as model, spinal pathways contributing to motor restitution have been investigated in more detail. The food-taking movement by which the cat graSPS a morsel of food with the digits and brings it to the mouth is governed by interneurones in the forelimb segments (C6-Th1) and is normally controlled via the cortico- and rubrospinal tracts. ⋯ Deficits in preshaping during the final approach to the morsel as well as lack of force were observed. A C5 DLF lesion spares corticofugal pathways to the brainstem and upper cervical segments. It is suggested that indirect corticomotoneuronal pathways may provide for recovery of dexterous finger movements and that the role of CM pathways for such movements should be broadened to include not only the monosynaptic connexion.
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Throughout normal life, activity-dependent plasticity occurs in the spinal cord as well as in brain. Like other central nervous system (CNS) plasticity, spinal cord plasticity can occur at numerous neuronal and synaptic sites and through a variety of mechanisms. Spinal cord plasticity is prominent early in life and contributes to mastery of standard behaviours like locomotion and rapid withdrawal from pain. ⋯ Explorations of spinal cord plasticity are necessary for understanding motor skills. Furthermore, the spinal cord's comparative simplicity and accessibility makes it a logical starting point for studying skill acquisition. Induction and guidance of activity-dependent spinal cord plasticity will probably play an important role in realization of effective new rehabilitation methods for spinal cord injuries, cerebral palsy and other motor disorders.