Considerable controversy regarding the effects of hypoxia on the pulmonary vasculature has arisen over the past few decades. The literature has been extensively reviewed by Fishman (1), and it is now generally accepted that hypoxia is a pulmonary vasoconstrictor. Much of the controversy has centered around the interpretation of a small elevation of pulmonary arterial pressure in the face of an increase in cardiac output related to the hypoxic stimulus. Some investigators calculated a small increase of pulmonary vascular resistance, whereas others could not confirm this observation. Most studies were performed in adult animals, or in adult humans, but more recently attention has been directed to hypoxic responses in the newborn animal, in view of the greater responsiveness of the pulmonary vasculature at this age.The relationship between the degree of pulmonary vascular response and the level of hypoxia has received only little attention, and usually a constrictor response to a single low oxygen gas inhalation has been reported. Recently Thilenius, Hoffer, Fitzgerald, and Perkins (2) attempted to relate pulmonary vascular resistance change to the level of inspired gas oxygen tension, but no obvious relationship could be demonstrated. Liljestrand (3) in 1958 suggested that the pulmonary vascular response to hypoxia may be related to the production of local Ho ion concentration changes in the lung. More recently Enson and as-* Submitted for publication June 25, 1965; accepted December 2, 1965. Supported by U. S. Public Health Service National Heart Institute grants HTS5532 and HE08378, and by a grant-in-aid from the Westchester Heart Association. sociates (4) described a relationship between the response to hypoxia and the level of H+ ion concentration.The purpose of the present study was 1 ) to attempt to delineate the effects of varying degrees of hypoxia induced by breathing low oxygen gas mixtures on the pulmonary vasculature of the newborn calf; 2) to study possible interrelationships between pulmonary vascular response, hypoxia, and H+ ion concentration; 3) to assess the mechanism of the hypoxic response; and 4) to study the general hemodynamic effects of hypoxia in the newborn animal. MethodsNaturally born Holstein calves aged 9 to 36 hours were anesthetized with sodium Pentothal in doses of 15 to 20 ml of a 2.5% solution given intravenously. An endotracheal tube with an inflatable cuff was inserted perorally, and anesthesia was then maintained with a gas mixture containing i to 1% Fluothane and approximately 30% oxygen and 70% nitrous oxide. Spontaneous breathing was first allowed, while an incision was made through skin and muscle down to parietal pleura in the fourth left intercostal space. Positive pressure breathing was then administered with a Harvard respiratory pump by using a tidal volume of 350 to 500 ml and a frequency of 16 to 18 per minute. The expiratory tube from the pump was placed under 2 to 3 cm of water to slightly elevate endexpiratory pressure and so help to maintain expansion of the...

The purpose of this study was to characterize the trophic effect of pancreatic duct cells on the islets of Langerhans. Ductal epithelium and islets were isolated from hamster pancreata. In addition, duct-conditioned medium (DCM) was prepared from primary duct cultures that had been passaged twice to remove other cellular elements. Three experimental groups were then established: Group 1, 100 islets alone; Group 2, 100 islets+80 duct fragments; and Group 3, 100 islets in 25% DCM. All tissues were embedded in rat tail collagen for up to 12 days and the influence of pancreatic ductal epithelium on islet cell survival was examined. By day 12, 20·6 3·0% (...) of the islets cultured alone developed central necrosis, compared with 6·7 2·0% of the islets co-cultured with ducts and 5·6 1·5% of the islets cultured in DCM (P<0·05). The presence of apoptotic cell death was determined by a TdT-mediated dUTP-biotin nick end labelling (TUNEL) assay and by a specific cell death ELISA. DNA fragmentation in islets cultured alone was significantly increased compared with islets cultured either in the presence of duct epithelium or in DCM (P<0·05). More than 80% of TUNEL-positive cells were situated in the inner 80% of the islet area, suggesting that most were -cells. DCM was analysed for known growth factors. The presence of a large amount of IGF-II (34 ng/ml) and a much smaller quantity of nerve growth factor (4 ng/ml) was identified. When the apoptosis studies were repeated to compare islets alone, islets+DCM and islets+IGF-II, the cell death ELISA indicated that IGF-II produced the same beneficial result as DCM when compared with islets cultured alone.We conclude that pancreatic ductal epithelium promotes islet cell survival. This effect appears to be mediated in a paracrine manner by the release of IGF-II from cells in the ductal epithelium.

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ExtractCardiac output, renal blood flow, and intrinsic renal vascular resistance were measured in piglets ranging in age from 6 h to 45 days. During this period of time the mean cardiac output increased from 0.9 to 6.5 liters/min/m . These data demonstrate that the large increase in renal blood flow in the pig during the first 6 weeks of life was due to both an increase in cardiac output as well as a decrease in renal vascular resistance. By 6 weeks of age, cardiac output was at adult levels. Since in the adult pig the kidney receives 20 % of the cardiac output, increases in renal blood flow beyond 6 weeks of age must result from further decreases in renal vascular resistance. SpeculationIn the human infant, cardiac index is comparable to values observed in the adult. It appears, therefore, that the entire increase in renal blood flow observed during year 1 of life is due to steadily decreasing renal vascular resistance. Since glomerular filtration rate is modified by the relative resistances in the glomerular afferent and efferent arterioles, the parallel increases in filtration rate during infancy may be related to the same mechanism.Introduction mates renal plasma flow by not more than 30-40%. Rates of flow reach mature levels (1,200 ml/min/1.73 Numerous studies have shown that renal blood flow m