Anesthesia and analgesia
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Anesthesia and analgesia · May 2004
Intraarterial pulmonary pentoxifylline improves cardiac performance and oxygen utilization after hemorrhagic shock: a novel resuscitation strategy.
The role of pentoxifylline (PTX) as a resuscitation adjunct in hemorrhagic shock is unclear. PTX infusion into the pulmonary artery and its effects on cardiac performance and oxygen utilization have not been defined. We hypothesized that pulmonary PTX is superior to systemic PTX or lactated Ringer's (LR) solution alone. The effects of LR solution, systemic PTX, and pulmonary PTX on cardiac performance and oxygen utilization in a hemorrhagic shock model in dogs were compared. Animals were bled to a mean arterial blood pressure (MAP) of 40 mm Hg maintained for 30 min and randomized into 3 resuscitation groups: LR solution (2x shed blood), systemic PTX (10 mg/kg bolus i.v.) in addition to LR solution (2x shed blood) + PTX (5 mg/kg for 45 min i.v.), and pulmonary PTX (10 mg/kg bolus + 5 mg/kg for 45 min via a pulmonary artery catheter) plus LR solution (2x shed blood, i.v.). Arterial blood gases, hemoglobin levels, MAP, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, oxygen delivery, oxygen consumption, and oxygen extraction ratio (O(2)ER) were measured serially. No differences in blood loss, hemoglobin, and MAP were observed. Pulmonary PTX increased cardiac index to levels more than baseline (P = 0.012) and decreased systemic vascular resistance index and pulmonary vascular resistance index to levels less than baseline (P < 0.0001). Pulmonary PTX increased oxygen delivery and oxygen consumption to baseline levels. Postresuscitation O(2)ER levels in LR-treated animals remained more than baseline (P < 0.0001). Systemic and pulmonary PTX significantly decreased O(2)ER compared with shock levels. PTX resuscitation is superior compared with LR solution alone. Intraarterial pulmonary PTX administration is safe, and improves cardiac performance as well as O(2) utilization. ⋯ This study shows that a novel route (via the pulmonary circulation) used to administer pentoxifylline after hemorrhagic shock leads to superior cardiac performance in comparison with administration via lactated Ringer's solution or i.v. systemic pentoxifylline.
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Anesthesia and analgesia · May 2004
The monoamine reuptake inhibitor milnacipran does not affect nociception to acute visceral distension in rats.
The role of antidepressants in the treatment of visceral pain has not been extensively examined. Milnacipran, an antidepressant that inhibits monoamine reuptake, is widely used in the treatment of depression and fibromyalgia. In this study, we sought to determine the activity of milnacipran against acute visceral nociception. Female virgin rats were studied 7 days after bilateral ovariectomy. For uterine cervical distension (UCD), two metal rods were inserted into the cervical osses under general anesthesia for manual distension. Colorectal distension (CRD) was performed by insertion of a balloon catheter into the descending colon and rectum, followed by manual inflation. Two electrodes were inserted into the rectus abdominus muscle for recording UCD- or CRD-induced reflex contraction, which was quantified by electromyography (EMG). A dose response for milnacipran, administered intrathecally or i.v., was obtained for UCD and CRD stimulation. Milnacipran failed to inhibit the UCD-induced EMG response, whether administered i.v. or intrathecally. Similarly, i.v. milnacipran, administered either acutely or chronically, failed to inhibit the CRD-induced EMG response. CRD and UCD are well established animal models for the study of acute visceral pain. Milnacipran, although it provides some unique advantages compared with other antidepressants, is unlikely to produce analgesia after acute administration in the setting of acute visceral pain. ⋯ Neither intrathecal nor i.v. milnacipran, a monoamine reuptake inhibitor, inhibits an acute visceral pain response induced by colorectal or uterine cervical distension.
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Anesthesia and analgesia · May 2004
Characteristic of interactions between intrathecal gabapentin and either clonidine or neostigmine in the formalin test.
Intrathecal gabapentin is effective for phase 2 of the formalin response but not for acute pain. Unlike gabapentin, intrathecal clonidine and neostigmine attenuate both acute pain and phase 2 of the formalin response. We evaluated gabapentin's interactions with either clonidine or neostigmine in the formalin test. Male Sprague-Dawley rats were used. For the formalin test, 50 microL of 5% formalin solution was injected into the hindpaw. The interaction of drugs was investigated by a fixed-dose analysis or an isobolographic analysis. Intrathecal gabapentin produced a suppression of the phase 2 flinching response, but not the phase 1 response, in the formalin test. Intrathecal clonidine and neostigmine resulted in a reduction of the pain behavior in both phases. A fixed-dose analysis in phase 1 showed that gabapentin potentiated the antinociceptive effect of clonidine and neostigmine. An isobolographic analysis in phase 2 revealed a synergistic interaction after intrathecal administration of gabapentin-clonidine or gabapentin-neostigmine mixture. We conclude that the combination of gabapentin with either clonidine or neostigmine at the level of the spinal cord could play a major role not only in acute pain, but also in phase 2 of the formalin response. ⋯ We determined the pharmacological properties of gabapentin combined with either clonidine or neostigmine in the formalin test. Spinal gabapentin reinforced the effects of clonidine and neostigmine in the formalin test. The hitherto unreported action of gabapentin on acute nociceptive stimulus could be of considerable significance.
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Anesthesia and analgesia · May 2004
Metoclopramide causes airway smooth muscle relaxation through inhibition of muscarinic M3 receptor in the rat trachea.
Although metoclopramide, often used as an antiemetic, is reported to have an anticholinesterase action, the effect on airway smooth muscle remains unclear. We investigated the effect of metoclopramide on the contraction, phosphatidylinositol response, and binding affinity of muscarinic M(3) receptors in rat trachea preparations. Male Wistar rats were anesthetized and their tracheas excised and chopped into 3-mm-wide rings, 1-mm-wide slices, or frozen 10- microm-thick sections. Contraction was induced with 0.55 microM carbachol (CCh) and, 30 min later, metoclopramide (10 microM to 1 mM) was added. The slices were incubated with (3)[H]myo-inositol, 0.55 microM CCh, and metoclopramide, and the formation of (3)[H] inositol monophosphate was measured. A radioligand binding study was conducted to examine the effects of metoclopramide using [(3)H] 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), a muscarinic M(3) receptor antagonist, in sections of the trachea. Metoclopramide concentration dependently attenuated CCh-induced contraction and inositol monophosphate accumulation, and also attenuated the binding affinity of 4-DAMP to muscarinic M(3) receptors. The 50% inhibitory concentration of metoclopramide against the binding affinity of 4-DAMP to muscarinic M(3) receptors of rat trachea was 24 micro M. These findings suggest that the attenuation by metoclopramide of CCh-induced contraction and phosphatidylinositol response may be mediated through the muscarinic M(3) receptors. ⋯ We investigated the effect of metoclopramide on the contraction, phosphatidylinositol response, and binding affinity of muscarinic M(3) receptors in rat trachea preparations. Our findings suggest that the attenuation by metoclopramide of carbachol-induced contraction and phosphatidylinositol response may be mediated through the muscarinic M(3) receptors.