Anesthesia and analgesia
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Anesthesia and analgesia · Jun 2002
Ventilation with negative airway pressure induces a cytokine response in isolated mouse lung.
We tested the hypothesis that, under relatively low tidal volume (VT) mechanical ventilation, continuing lung decruitment induced by negative end-expiratory pressure (NEEP) would increase the lung cytokine response, potentially contributing to lung injury. Mouse lungs were excised and randomly assigned to one of 3 different ventilatory strategies: 1) the zero end-expiratory pressure group served as a control, 2) the NEEP7 group received a NEEP of -7.5 cm H(2)O, and 3) the NEEP15 group received a NEEP of -15 cm H(2)O. In all 3 groups, a VT of 7 mL/kg was used. After 2 h of ventilation, lung lavage fluid was collected for measurements of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and lactate dehydrogenase. Increases in plateau pressure before and after mechanical ventilation were significantly greater in the NEEP15 group compared with the zero end-expiratory pressure group or NEEP7 group. Lung compliance was decreased in the NEEP15 compared with the other two groups. Concentrations of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and lactate dehydrogenase in lung lavage were larger in the NEEP15 group than in the other groups. Atelectatic lung during repeated collapse and reopening of lung units accentuates the lung cytokine response that may contribute to lung injury even during relatively low VT mechanical ventilation. ⋯ Repeated closing and reopening of lung units induced by negative end-expiratory pressure resulted in lung inflammation and cell injury even under mechanical ventilation using a normal tidal volume. This finding may have clinical relevance in certain patients who are prone to atelectasis during mechanical ventilation.
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Anesthesia and analgesia · Jun 2002
An analysis of responses to levosimendan in the pulmonary vascular bed of the cat.
Calcium-sensitizing drugs, such as levosimendan, are a novel class of drug therapy for heart failure. We investigated the hypothesis that levosimendan is a pulmonary vasodepressor mediated through inhibition of phosphodiesterase, adenosine triphosphate (ATP)-dependent potassium channels, or both. We investigated responses to the calcium sensitizer levosimendan in the pulmonary vascular bed of the cat under conditions of controlled pulmonary blood flow and constant left atrial pressure when lobar arterial pressure was increased to a high steady level with the thromboxane A(2) analog U-46619. Under increased-tone conditions, levosimendan caused dose-related decreases in lobar arterial pressure without altering systemic arterial and left atrial pressure. Responses to levosimendan were significantly attenuated, although not completely, after the administration of U-37883A, a vascular selective nonsulfonylurea ATP-sensitive K(+)-channel-blocking drug. Responses to levosimendan were not significantly different after the administration of the nitric oxide synthase inhibitor L-N(5)-(1-iminoethyl)-ornithine or the cyclooxygenase inhibitor sodium meclofenamate or when lung ventilation was interrupted. These data show that levosimendan has significant vasodilator activity in the pulmonary vascular bed of the cat. They also suggest that pulmonary vasodilator responses to levosimendan are partially dependent on activation of ATP-sensitive K(+) channels and independent of the synthesis of nitric oxide, activation of cyclooxygenase enzyme, or changes in bronchomotor tone in the pulmonary vascular bed of the cat. ⋯ Calcium-sensitizing drugs, such as levosimendan, are a novel class of drug therapy for heart-failure treatment. The lung circulation affects both right- and left-sided heart failure. Levosimendan decreased lobar arterial pressure via a partial K(+)(ATP) (potassium channel sensitive to intracellular adenosine triphosphate levels)-dependent mechanism. These data suggest that, in addition to calcium-sensitizing activity, levosimendan decreases pulmonary resistance, which may also aid in the treatment of heart failure.
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Anesthesia and analgesia · Jun 2002
Sildenafil (Viagra) augments sodium nitroprusside-induced but not nitroglycerin-induced hypotension in dogs.
We investigated whether sildenafil citrate (Viagra) may reduce the dose of nitrovasodilators to induce deliberate hypotension. Ten mongrel dogs were acutely instrumented with a femoral artery catheter and a pulmonary artery catheter. Sodium nitroprusside (SNP; 1-16 microg. kg(-1). min(-1)) or nitroglycerin (NTG; 2-32 microg. kg(-1). min(-1)) was IV given to induce hypotension. The study consisted of two occasions, in a random order, in each animal: one with sildenafil pretreatment (1 mg/kg IV followed by 0.3 mg. kg(-1). h(-1)) and the other without to serve as a control. Hemodynamic variables were continuously monitored. Plasma cyclic guanosine monophosphate (cGMP) concentrations were measured by radioimmunoassay. Both SNP and NTG produced dose-dependent decreases in mean arterial blood pressure without affecting the heart rate in the presence as well as in the absence of sildenafil. Systemic vascular resistance index and mean pulmonary arterial pressure were also decreased. The magnitude of mean arterial blood pressure and systemic vascular resistance index reductions caused by SNP was augmented by sildenafil, whereas that caused by NTG was not affected. Neither SNP nor NTG alone altered the plasma cGMP concentrations. Sildenafil increased the plasma cGMP concentration, which was further increased by SNP but not affected by NTG. These results indicate that sildenafil may reduce the dose of SNP in producing deliberate hypotension in the dog. The potentiation of SNP-induced hypotension by sildenafil may be related to an augmented accumulation of cGMP. ⋯ Sildenafil may reduce the dose of sodium nitroprusside required to induce deliberate hypotension and hence the potential for cyanide toxicity.
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Anesthesia and analgesia · Jun 2002
The effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model.
IV prostaglandin E1 improves clinical symptoms in patients with spinal canal stenosis. In the present study, we assessed the effects of OP-1206 alpha-CD, an orally active prostaglandin E1 analog, on walking dysfunction in the rat neuropathic intermittent claudication model. To induce spinal stenosis, two pieces of silicon rubber were placed in the lumbar (L4-6) epidural space in rats. Postsurgical walking function was measured using a treadmill apparatus. Spinal cord blood flow (SCBF) and skin blood flow (SKBF) were measured using a laser-Doppler flowmeter. OP-1206 alpha-CD was administered orally bid for 11 days from postoperative Day 3. In Control nontreated rats, a significant walking dysfunction was observed from Day 1 after the induction of spinal stenosis and persisted for 14 days when compared with the Sham-Operated group. On postoperative Day 15, SCBF revealed a significant reduction in the territory of spinal stenosis, although SKBF was not affected. OP-1206 alpha-CD significantly improved walking dysfunction on postoperative Days 5 (300 microg/kg), 7 (150 and 300 microg/kg), and 14 (150 and 300 microg/kg) when compared with the Vehicle-Treated group. On postoperative Day 15, the decrease in SCBF was significantly (150 and 300 microg/kg) improved by OP-1206 alpha-CD treatment, albeit SKBF remained unaffected. These data show that oral treatment with OP-1206 alpha-CD is effective in improving walking dysfunction induced by spinal canal stenosis, and this therapeutic effect is likely mediated by improved SCBF at the territory of spinal stenosis. ⋯ Intermittent motor dysfunction is a clinical symptom associated with partial spinal compression. The present study provides evidence that oral treatment with the prostaglandin E1 analog (OP-1206 alpha-CD) is effective in improving motor dysfunction and spinal cord blood flow in rats with spinal compression.