Anesthesia and analgesia
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Anesthesia and analgesia · Oct 2002
Beta-adrenergic stimulation restores oxygen extraction reserve during acute normovolemic hemodilution.
Compensatory increases in oxygen extraction (EO(2)) during acute normovolemic hemodilution (ANH) have the effect of decreasing tissue oxygen tension values, thus increasing the threat of tissue hypoxia. We hypothesized that if the beta-adrenergic agonist isoproterenol (ISOP) could augment cardiac output (CO) during ANH, it could reverse the increases in EO(2) and restore the margin of safety for tissue oxygenation. Studies were performed in seven anesthetized (isoflurane) dogs. CO was measured by using thermodilution, and regional blood flow (RBF) was measured by using radioactive microspheres. Systemic oxygen delivery (DO(2)), oxygen consumption (OV0312;O(2)), and EO(2), as well as regional DO(2), were calculated. Measurements were obtained under the following conditions in each dog: 1) baseline-1, 2) ISOP (0.1 micro g. kg(-1). min(-1) IV), 3) baseline-2, 4) ANH, and 5) ISOP during ANH. Hematocrit was 45% +/- 3% under baseline conditions and 18% +/- 3% during ANH. Before ANH, ISOP caused parallel increases in CO and systemic DO(2), which, in the presence of an unchanged OV0312;O(2), reduced EO(2). RBF increased in myocardium and spleen, decreased in pancreas, and did not change in brain, spinal cord, or other tissues. ANH caused increases in CO, which were insufficient to offset the decrease in arterial oxygen content, and thus systemic DO(2) declined; systemic OV0312;O(2) was maintained by an increase in EO(2). ANH-related increases in RBF maintained DO(2) in myocardium, brain, duodenum, and pancreas, whereas DO(2) declined in kidney and spleen. ISOP during ANH increased CO and systemic DO(2), which returned systemic EO(2) to baseline, and it increased RBF in myocardium, kidney, duodenum, and spleen. We conclude that 1) beta-adrenergic stimulation with ISOP restored the systemic EO(2) reserve during ANH, without apparent adverse effects in the individual body tissues, and that 2) the use of inotropic drugs, such as ISOP, may extend the limit to which hematocrit can be reduced safely during ANH. ⋯ By restoring the oxygen extraction reserve, isoproterenol and other inotropic drugs can enhance the margin of safety and extend the limit to which hematocrit can be reduced safely during acute normovolemic hemodilution. The use of this approach will depend on the degree of hemodilution, the extent of mixed venous oxygen desaturation, and whether increases in cardiac output are possible or desirable.
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Anesthesia and analgesia · Oct 2002
Vocalization responses after intrathecal administration of ionotropic glutamate receptor agonists in rats.
Inotropic glutamate receptors in the spinal cord (N-methyl-D-aspartic acid [NMDA], alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA], and kainate receptors) seem to play a key role in acute pain transmission and the neuronal plasticity in chronic pain states. Vocalization responses produced by activation of these receptors on the pain pathways can be quantified semiautomatically and thus could be used as a research tool. We studied vocalization responses induced by intrathecal administration of various agonists acting at the glutamate receptors in normal rats and in the presence of peripheral inflammation and a chronic constriction injury model of neuropathic pain. The nonselective endogenous agonist, glutamate, and the NMDA receptor glycine site agonist D-serine did not produce vocalization, whereas selective agonists acting at AMPA, NMDA, and kainate receptors produced dose-related vocalization responses. The vocalization response evoked by the administration of AMPA was significantly increased in the neuropathic pain model. In conclusion, spinal administration of ionotropic glutamate receptor agonists produce short-lasting, dose-related vocalization responses that can be used as a basic research and screening tool for analgesic studies. However, peripheral inflammation or nerve injury did not substantially alter vocalization responses overall, possibly indicating that the vocalization test is not a good tool for studying the role of excitatory amino acids in these pathological pain conditions. ⋯ Vocalization responses evoked by spinal administration of ionotropic glutamate receptor agonists can be used for experimental analgesic studies. However, pathological pain models did not substantially alter vocalization responses, possibly indicating that this test is not suitable for studying the role of spinal excitatory amino acids in central sensitization.
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Anesthesia and analgesia · Oct 2002
Hyperalgesia during opioid abstinence: mediation by glutamate and substance p.
Opioid-abstinence hyperalgesia (OAH) is a phenomenon characterized by thermal and mechanical hyperalgesia that occurs between intermittent doses of opioids or after the chronic administration of these drugs when administration is abruptly stopped. In these studies we attempted to determine whether the activation of spinal cord dorsal horn neurons was greater in mice with OAH than in control mice in response to the intrathecal administration of the primary neurotransmitters glutamate and substance P. After mice were treated with an established protocol consisting of the implantation of morphine pellets followed by removal after 6 days, the mice were hyperalgesic as assessed with the hotplate and Hargreaves thermal paw withdrawal assays. Mechanical allodynia was also demonstrated. The intrathecal injection of either glutamate (5-25 micro g) or substance P (0.02-0.1 nmol) caused greater pain behaviors in mice with OAH than in control mice. Likewise, it was observed that the dorsal horn regions of OAH mice had more Fos-positive nuclei after either glutamate or substance P administration than did control mice. We conclude that mice with OAH exhibit increased pain behaviors and have increased numbers of Fos-positive nuclei in response to intrathecal glutamate and substance P administration when compared with control mice. Thus, spinal sensitization to primary neurotransmitters may be responsible in part for the manifestation of OAH. ⋯ Opioids are a mainstay of treatment for many types of chronic pain. These studies provide evidence that the hyperalgesia induced by chronic opioid administration may be in part to spinal neuroplastic changes.