Clinical science
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Comparative Study
Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury.
Massive cutaneous burn combined with smoke inhalation causes high mortality in fire victims. Cyclo-oxygenase (COX) and inducible nitric oxide (NO) synthase (iNOS) have been shown to be up-regulated in burn injury. Ketorolac, a non-steroidal, anti-inflammatory agent (NSAID), inhibits prostaglandin and thromboxane synthesis through inhibition of COX. ⋯ Treatment with ketorolac prevented all of these morbidities. Post-treatment with ketorolac also resulted in significant inhibition of elevated plasma nitrite/nitrate levels in control animals. These results suggest that ketorolac may ameliorate cardiopulmonary morbidity, at least in part, by inhibiting excessive NO.
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Interleukin-2 (IL-2), a cytokine that induces natural killer cells termed lymphokine-activated killer (LAK) cells, is in use as an anticancer agent. During IL-2 therapy, adverse effects, such as vasodilatation and hypotension, are common. Previous studies suggest that these effects are due to nitric oxide (NO). ⋯ The sham group showed no changes in any of the parameters. Scavenging NO by PHP prevented the hyperdynamic reaction induced by IL-2 administration in sheep. This activity of PHP may prevent the early discontinuation of IL-2 therapy that results because of these adverse events.
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In patients with recurrent unexplained syncope, exaggerated peripheral venous pooling and impaired circulatory adjustment is thought to contribute to the outcome of a head-up tilt (HUT) test. The present study investigated the role of leg volume changes during venous congestion in the haemodynamic response of patients with recurrent unexplained syncope and the ability to predict the outcome of a HUT test. Changes in calf volume (strain gauge plethysmography), heart rate and arterial blood pressure were recorded in 60 patients with history of unexplained syncope (without postural tachycardia symptom) during venous congestion provoked by pneumatic thigh cuffs while supine at rest and during the initial 10 min of a 45 min 70 degrees HUT test. ⋯ Calf volume changes did not correlate with a symptomatic outcome to a 70 degrees HUT. The lack of exaggerated venous pooling during venous congestion and the inability of calf volume changes to predict a positive HUT suggest that excessive venous pooling does not contribute to the outcome of HUT. Attenuated changes in arterial pressure during venous congestion while supine suggest impaired adjustment of peripheral resistance to leg venous occlusion.
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Accumulation of neutrophils in the lung contributes to the endothelial damage in the tissue associated with acute respiratory distress syndrome. This initial recruitment of neutrophils within the pulmonary microvasculature may involve P-selectin. Thus we hypothesized that an antibody against P-selectin would reduce pulmonary damage. ⋯ The lymph conjugated dienes were significantly lower in the treated animals. However, lung myeloperoxidase activity and lung tissue conjugated dienes were significantly increased in the treated animals compared with the non-treated injured controls. In conclusion, although the anti-(P-selectin) antibody did not protect against lung injury during the initial 48 h of burn and smoke, it decreased some aspects of injury in the peripheral microcirculation.
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The effects of gas mixtures comprising supplementary 3% carbon dioxide, 35% oxygen or a combination of 3% CO(2) plus 35% O(2) in ambient air have been compared on arterial blood gases, peripheral and cerebral oxygenation and middle cerebral artery velocity (MCAV) at 150 m and on acute exposure to 3459 m in 12 healthy subjects. Breathing 3% CO(2) or 35% O(2) increased arterial blood oxygen at both altitudes, and the CO(2)/O(2) combination resulted in the most marked rise. MCAV increased on ascent to 3459 m, increasing further with 3% CO(2) and decreasing with 35% O(2) at both altitudes. ⋯ Breathing 3% CO(2) or 35% O(2) increased cerebral oxygenation at both altitudes, and the CO(2)/O(2) combination resulted in the greatest rise at both altitudes. The combination also resulted in significant rises in cutaneous and muscle oxygenation at 3459 m. The key role of carbon dioxide in oxygenation at altitude is confirmed, and the importance of this gas for tissue oxygenation is demonstrated.