PubMed · 14056325
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W WALTERS. 1963. HOW TO AVOID SURGICAL DIFFICULTIES.. https://pubmed.ncbi.nlm.nih.gov/14056325/
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AIMS/HYPOTHESIS: The insulinotropic hormone, glucagon-like peptide-1 (GLP-1), is rapidly degraded in vivo as a result of the combination of extensive enzymatic degradation and renal extraction. The GLP-1 receptor agonist, exendin-4, has a longer duration of action, and has recently been approved as a new agent for the treatment of type 2 diabetes mellitus. Exendin-4 is less prone to enzymatic degradation, but it is still unclear what other factors contribute to the increased metabolic stability. MATERIALS AND METHODS: The overall metabolism of GLP-1 and exendin-4 was directly compared in anaesthetised pigs (n=9). RESULTS: Metabolism of GLP-1 (C-terminal RIA; t (1/2) 2.0+/-0.2 min, metabolic clearance rate [MCR] 23.2+/-2.8 ml min(-1) kg(-1); N-terminal RIA; t (1/2) 1.5+/-0.2 min, MCR 88.1+/-10.6 ml min(-1) kg(-1)) was significantly faster than the metabolism of exendin-4 (t (1/2) 22.0+/-2.1 min, p<0.0001; MCR 1.7+/-0.3 ml min(-1) kg(-1), p<0.01). Differences in arteriovenous concentrations revealed organ extraction of GLP-1 by the kidneys (C-terminal 56.6+/-2.6%; N-terminal 48.3+/-5.9%), liver (N-terminal 41.4+/-3.8%), and peripheral tissues (C-terminal 42.3+/-6.0%; N-terminal 33.0+/-7.8%), whereas organ extraction of exendin-4 was limited to the kidneys (21.3+/-4.9%). While the renal extraction of exendin-4 (6.9+/-2.5 pmol/min) did not differ significantly from the amount undergoing glomerular filtration (8.4+/-2.0 pmol/min), the renal extraction of C-terminal GLP-1 (9.0+/-1.1 pmol/min), exceeded the amount which could be accounted for by glomerular filtration (4.2+/-0.5 pmol/min, p<0.0005). CONCLUSIONS/INTERPRETATION: In addition to an increased resistance to enzymatic degradation, the increased stability of exendin-4 is the result of reduced differential organ extraction compared to GLP-1. The data suggest that in the anaesthetised pig, extraction occurs only in the kidney and can be fully accounted for by glomerular filtration.
In urethane-anesthetized female rats, a branch of the hypogastric nerve equivalent to the vas deferens nerve in males was shown anatomically and electrophysiologically to supply the uterine horns and we have consequently termed this the uterine nerve. Administration of p-chloroamphetamine i.v. elicited patterned bursting uterine nerve activity responses together with contractions of the uterine horns and musculature of the vaginal wall. These responses are qualitatively similar to ejaculatory responses observed following p-chloroamphetamine administration to anesthetized male rats and the urethrogenital reflex in females, suggesting they represent responses occurring during sexual processes. This response to p-chloroamphetamine was still present after complete transection of the spinal cord at T8. These data indicate that common neurophysiological and pharmacological mechanisms regulate genital reflexes at the lumbosacral spinal level in both the female and the male rat.
The systemic circulation to the lung supplies the trachea and airway walls and may be important in the pathophysiology of asthma and pulmonary oedema. An understanding of the venous drainage pathways of this bronchial blood flow may be therapeutically important. The purpose of this study was to understand the normal drainage pathways in sheep. In seven anaesthetized, ventilated sheep we injected echo contrast agents into a systemic vein or into the bronchial artery while performing echocardiography to determine whether the drainage could be observed to the right heart and/or to the left heart. During transoesophageal echo (n=5) or heart surface echo (n=2), cephalic vein injection of <8 microm diameter gelatin microballoons promptly opacified the right but never the left-sided circulation. Air in agitated saline in the seven animals showed the same result. By contrast, injection into the bronchial artery promptly opacified the left atrium, left ventricle, and aorta but not the right-sided circulation in all seven microballoon injections and all but one of the air in agitated saline injections. The failure of the echo agents to pass through the pulmonary circulation may be related to sheep pulmonary intravascular macrophages or the surface forces on air bubbles of small size promoting collapse. The main conclusion is that there are bronchopulmonary anastomoses that connect the bronchial circulation to the pulmonary venous circulation connecting distal to the pulmonary capillaries. Any bronchial venous drainage to the right-sided circulation must have been below the detection level of the instruments and would in any case appear to be much less that the post-pulmonary capillary anastomoses noted. Pulmonary venous hypertension would be expected to have a direct effect on the bronchial circulation.