Determination of the renal concentration capacity following intravenous administration of dDAVP in healthy humans

The synthetic AVP analogue 1-desamino-8-d-arginine-vasopressin (dDAVP) is used for treatment of polyuric disorders. Lack of commercially available assays limits the usefulness of dDAVP as a diagnostic tool in the assessment of renal concentrating capacity. We aimed to develop a specific radioimmunoassay (RIA) for determination of plasma dDAVP (pdDAVP) in order to investigate the relationship between pdDAVP levels and urine osmolality (Uosm). Further, we aimed to determine the onset, duration, and maximum concentrating capacity following intravenous (i.v.) bolus dDAVP injection. The dDAVP assay was based on a well-established RIA for measurements of AVP. Fourteen healthy subjects (aged 15–18 years) participated. Blood and urine samples were collected prior to and after i.v. bolus of 0.03?µg/kg dDAVP. Diuresis and Uosm was measured for nine hours following dDAVP administration. PdDAVP and Uosm were analyzed.We established a specific RIA for the measurement of pdDAVP. All subjects reached maximal pdDAVP concentration (C_max) 30 minutes following infusion, and a rise in Uosm after 60 minutes. Maximal Uosm varied between subjects, with no direct correlation to the achieved pdDAVP levels. We found no significant intra-individual variation between two dDAVP infusions and the effect was reproducible in terms of C_max and maximal Uosm. We characterized the relationship between pdDAVP and Uosm after dDAVP bolus injection in healthy adolescents using our dDAVP assay. Maximal Uosm achieved correlated with the baseline Uosm levels and seemed unrelated to achieved pdDAVP levels. The urine concentrating response was maintained at least eight hours.     

Abnormalities of pulmonary artery wedge pressures in sleep-induced apnea

Six patients with sleep apnea syndrome were studied with continuous hemodynamic monitoring during sleep. Sleep apnea had been previously documented with an average number of apneas per hour of sleep ranging from 23 to 93 (mean 63). There was a significant decrease in heart rate during sleep (82 ± 5 to 69 ± 6, P < 0.01). There was a significant rise in systemic blood pressure (103 ± 2 mm Hg to 116 ± 6 mm Hg, P < 0.05) and pulmonary artery pressure (20 ± 1 mm Hg to 32 ± 5 mm Hg) during sleep. In addition, pulmonary artery wedge pressure increased (12 ± 2 mm Hg to 20 ± 3 mm Hg, P < 0.05) during sleep and 5 of the 6 patients developed an abnormal pulmonary wedge pressure. There was a significant decrease in P_O2 during sleep (71 ± 3 mm Hg to 49 ± 2 mm Hg, P < 0.005). These findings suggest that increases in pulmonary wedge pressures may be contributing to increase in pulmonary artery pressures in these patients during sleep.     

FVB/N: an inbred mouse strain preferable for transgenic analyses.

FVB/N mice offer a system suitable for most transgenic experiments and subsequent genetic analyses. The inbred FVB/N strain is characterized by vigorous reproductive performance and consistently large litters. Moreover, fertilized FVB/N eggs contain large and prominent pronuclei, which facilitate microinjection of DNA. The phenotype of large pronuclei in the zygote is a dominant trait associated with the FVB/N oocyte but not the FVB/N sperm. In experiments to generate transgenic mice, the same DNA constructs were injected into three different types of zygotes: FVB/N, C57BL/6J, and (C57BL/6J x SJL/J)F1. FVB/N zygotes survived well after injection, and transgenic animals were obtained with efficiencies similar to the F1 zygotes and much better than the C57BL/6J zygotes. Genetic markers of the FVB/N strain have been analyzed for 44 loci that cover 15 chromosomes and were compared with those of commonly used inbred strains. In addition to the albino FVB/N strain, pigmented congenic strains of FVB/N are being constructed. These features make the FVB/N strain advantageous to use for research with transgenic mice.     

Effect of ventilation by high-frequency oscillation on lung and chest wall mechanics in the dog

High-frequency oscillation (HFO) has been shown to be effective in maintaining gas exchange, but the effects of high-frequency, small-volume ventilation on the mechanical properties of the respiratory system are unknown. A volume displacement plethysmograph was used to study lung volumes and static pressure-volume (PV) curves during HFO in pentobarbital-anesthetized dogs. During long-term studies, adequate gas exchange was maintained with a stroke volume of 2.5 ml/kg and frequencies between 15 and 30 Hz. The effect of 5–7 hours of HFO on lung and chest wall mechanics was studied in 8 dogs. In another 8 dogs the relationship of volume history and respiratory muscle tone to occlusion airway pressure and lung volume during short-term HFO was investigated. With prolonged HFO, a small but significant decrease in total lung capacity occurred by 5 hours and the static respiratory system PV curve shifted slightly to the right. These changes were reversed by muscle paralysis and may be explained by a change in respiratory muscle tone. Static lung compliance and the hysteresis ratio (an index of tissue properties) remained unchanged. The relationship of occlusion airway pressure and lung volume during short-term HFO was dependent on the lung volume history and was influenced by respiratory muscle tone only at low airway pressures. These findings suggest that during prolonged HFO a small increase in chest wall stiffness may result. However, occlusion airway pressure and lung volume at the onset of HFO are mainly dependent on the volume history of the lung. Presented in part at the Fall Meeting of the American Physiological Society, Toronto, Canada, October 12–17, 1980