The Journal of clinical investigation
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Recent studies have shown that effective pulmonary ventilation is possible with tidal volumes (VT) less than the anatomic dead-space if the oscillatory frequency (f) is sufficiently large. We systematically studied the effect on pulmonary CO2 elimination (VCO2) of varying f (2-30 Hz) and VT (1-7 ml/kg) as well as lung volume (VL) in 13 anesthetized, paralyzed dogs in order to examine the contribution of those variables that are thought to be important in determining gas exchange by high frequency ventilation. All experiments were performed when the alveolar PCO2 was 40 +/- 1.5 mm Hg. ⋯ The mean values of a, b, and c for all dogs were 2.12 X 10(-3), 0.49, and 0.08, respectively. The most important variable in determining VCO2 was VOSC; however, there was considerable variability among dogs in the independent effect of VT and f on VCO2, with a doubling of VT at a constant VOSC causing changes in VCO2 ranging from -13 to +110% (mean = +35%). Increasing VL from functional residual capacity (FRC) to the lung volume at an airway opening minus body surface pressure of 25 cm H2O had no significant effect on VCO2.
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Experiments were made to investigate the effect of four anesthetic drugs that are commonly used in surgical practice on the postoperative growth of mouse tumors in syngeneic recipients. These experiments revealed that some of the anesthetics when applied for surgical excision of the local tumor, strongly accelerated postoperative progression of spontaneous lung metastases produced by the 3LL Lewis lung carcinoma and by the B16 melanoma. Some of the drugs caused the appearance of metastases in organs, such as the liver, in which spontaneous metastases are not usually produced by these tumors. A T10 sarcoma clone that does not produce detectable metastases in immune intact mice even following intravenous injection, did produce metastases when injected into animals treated with pentothal sodium.
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Neutrophils are a characteristic feature of the alveolitis of idiopathic pulmonary fibrosis (IPF). a chronic disorder limited to lung. One mechanism by which neutrophils may be selectively attracted to lung and not other tissues is via the secretion of the neutrophil-specific chemotactic factor by alveolar macrophages. To evaluate the role of alveolar macrophages in modulating the migration of neutrophils to he lung in IPF, alveolar macrophages, obtained by bronchoalveolar lavage of patients with IPF, were evaluated for their ability to release a chemotactic factor for neutrophils. ⋯ Fourth, IPF alveolar macrophages that released large amounts of the chemotactic factor had an apparent suppression of their immunoglobulin (Ig)G Fc receptor function, suggesting that immune complexes were bound to their surface. In contrast, the IgG Fc receptor function of IPF alveolar macrophages that released only small amounts of the factor was similar to that of normal macrophages. These studies suggest that neutrophils are attracted to the lung in patients with IPF by a potent chemotactic factor released by alveolar macrophages that have been stimulated, in vivo, via their IgG Fc receptor by immune complexes.
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Although numerous agents have been shown experimentally to protect ischemic myocardium, a critical unanswered question is whether function is preserved in the salvaged tissue. Accordingly, 38 openchest dogs had measurements of percent segment length shortening (%SS) and velocity of segment length shortening either in midmyocardial or subepicardial and subendocardial ischemic segments before and after 60 min of left anterior descending coronary artery occlusion during 5 h of reperfusion; 10 additional dogs were subjected to 3 h of coronary occlusion followed by 72 h of reperfusion. 15 min after coronary artery occlusion, radiolabeled microspheres were injected into the left atrium for measurement of regional myocardial blood flow, and dogs were treated with 1 mg/kg i.v. (n = 23) of an anti-inflammatory drug, flurbiprofen or an equal volume of saline (n = 25). The ischemic myocardium-at-risk for necrosis was determined by injecting methylene blue dye into the left atrium with the coronary artery reoccluded at the end of the reperfusion period, slicing the left ventricle into thin transverse sections, and measuring the areas of each slice that were not perfused (pink unstained tissue) by methylene blue. ⋯ In dogs subjected to 3 h of coronary occlusion and 72 h of reperfusion, the administration of flurbiprofen was also associated with significantly smaller infarcts and a significantly more rapid rate of functional recovery than in control dogs. Thus, it appears that flurbiprofen not only decreased the quantity of necrosis in tissue made ischemic after coronary occlusion and then reperfused, but also allowed more rapid recovery of segmental function in ischemic but nonnecrotic tissue and in tissue with patchy necrosis; such recovery did not occur in equally ischemic myocardium in untreated control dogs. Earlier functional recovery of reversibly injured tissue following prolonged periods of ischemia is an additional important role for agents that protect ischemic myocardium from necrosis.
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The effects of methoxamine and nitroglycerin on measurements of large vessel (left circumflex) coronary dimensions were examined in eight conscious dogs using an ultrasonic dimension gauge, and total coronary resistance was calculated from measurements of arterial pressure and coronary blood flow. Methoxamine (50 mug/kg per min), after transiently increasing left circumflex coronary dimensions, induced sustained reductions in left circumflex diameter (9+/-2%) and external (18+/-4%) and internal (27+/-5%) cross-sectional areas, at a time when mean arterial pressure rose by 65+/-5%, left ventricular dP/dt had decreased only slightly, and heart rate and mean coronary blood flow remained at control levels. Calculated large vessel and total coronary resistances rose similarly, i.e., by 108+/-29 and 92+/-14%, respectively. ⋯ At this time, significantly different effects were observed on large vessel coronary resistance, which fell by 18+/-2%, and on total coronary resistance, which rose by 11+/-4%. Thus, in the conscious dog, large coronary vessels not only react passively to changes in aortic pressure but also undergo substantial active changes. Alpha adrenergic stimulation is sufficiently powerful to reduce cross-sectional area, despite the opposing elevation of distending pressure.