Per Svendsen

Oral cadmium chloride intoxication in mice: effects of dose on tissue damage, intestinal absorption and relative organ distribution

The acute toxicity of soluble cadmium salts has almost exclusively been studied experimentally after parenteral exposures, where acute mortality is caused by hepatic necrosis. This report describes an alternative experimental model using oral exposure. A single oral toxic dose of CdCl2 to mice induced toxic gastroenteritis; subsequent hepatic and renal lesions were also observed. Whole-body gamma-counting after a single oral toxic 109CdCl2 dose to mice showed a dose-dependent delay of the fecal excretion of non-absorbed cadmium. This delay was absent when a low, non-toxic dose was administered. This effect is most likely due to decreased peristalsis and, at higher doses, intestinal atony due to oral cadmium toxicity. After fecal elimination of non-absorbed cadmium, the residual body burden of cadmium expressed as percent of initial dose reflects the fractional intestinal cadmium absorption due to slow reexcretion of absorbed cadmium. The fractional absorption increased with increasing doses of cadmium. The relative cadmium deposition in brain, testes and intestines decreased with increasing dose, whereas the relative liver deposition increased with dose. The delayed fecal elimination and increased fractional absorption of cadmium may significantly contribute to the development of both local and systemic toxicity in oral cadmium intoxication.

Oral cadmium chloride intoxication in mice: Effects of chelation

In acute oral cadmium intoxication, the immediate target organ is the gastrointestinal tract. In this study, toxic effects following oral administration of CdCl2 to mice by stomach tube included intestinal paralysis, constipation and necrosis of the gastrointestinal epithelia. Tissue damage in liver, kidneys and testes developed in survivors due to the systemic toxicity of absorbed cadmium. Chelation of the Cd2+ ion by STPP, EDTA or DTPA prior to oral administration reduced mortality, tissue damage and whole body retention of cadmium. Other chelators (cysteine, NTA, DDC) only marginally affected the whole-body retention. DDC even enhanced the inhibition of intestinal motility caused by cadmium. DTPA and DDC decreased the relative deposition in the liver and increased the relative renal deposition. DDC also increased the relative cadmium deposition in brain, lung, spleen and testes. Among the chelators tested, DTPA was most efficient in preventing toxic effects of oral cadmium.

Vertebral artery flow and cervical manipulation: An experimental study☆

BACKGROUND Spinal manipulation therapy is used by millions of patients each year to relieve symptoms caused by biomechanical dysfunction of the spine. Cerebrovascular accidents in the posterior cerebral circulation are a feared complication, but little research has been done on vertebral artery hemodynamics during cervical manipulation. OBJECTIVE The purpose of this study was to develop an experimental model for investigations of volume blood flow changes in the vertebral arteries during premanipulative testing of these vessels and during spinal manipulation therapy of the cervical spine. DESIGN AND SETTING An experimental study in a university biomedical laboratory. MATERIAL AND METHODS The vertebral arteries were exposed in 8 adult pigs after extensive mediastinal dissection. Volume blood flow was measured on both sides simultaneously by advanced transit-time flowmetry. RESULTS After cervical manipulation, the vertebral artery volume blood flow increased significantly for 40 seconds before returning to baseline values in less than 3 minutes. We found no significant changes in volume flow during premanipulative testing of the vertebral arteries (DeKleyns test). CONCLUSION We present an experimental model for investigations of vertebral artery hemodynamics during biomechanical interventions. We found a modest and transient effect of cervical manipulation on vertebral artery volume flow. The model may have further applications in future biomechanical research, for example, to determine whether any of several spinal manipulative techniques imposes less strain on the vertebral artery, thereby reducing possible future cerebrovascular accidents after such treatment.

Oral cadmium chloride intoxication in mice: diethyldithiocarbamate enhances rather than alleviates acute toxicity.

Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect. Thus, orally administered DDC enhanced cadmium-induced duodenal and ileal tissue damage and inhibition of peristalsis, as indicated by an increased intestinal transit time. At low cadmium doses, the whole-body retention of cadmium was increased by oral DDC administration. Intraperitoneally administered DDC increased cadmium-induced acute mortality and testicular necrosis, and it enhanced cadmium-induced reduction of intestinal motility and increased the whole-body retention of cadmium, indicating increased intestinal cadmium absorption. Also, DDC changed the organ distribution of absorbed cadmium: after i.p. administration of DDC, the relative hepatic deposition was reduced, whereas the relative deposition in other organs, in particular the brain, was increased. This study indicates that medical use of DDC should be avoided in individuals with current exposure to cadmium.

Calibration of a reflectance pulse oximeter in fetal lambs for arterial oxygen saturations below 70

Objective: To calibrate a reflectance pulse oximeter developed at the Division of Perinatal Physiology, University Hospital of Zurich, for monitoring of oxygen saturations below 70%. Methods: Oxygen saturation measured monivasively with the reflectance pulse oximeter in fetal sheep was compared with oxygen saturation of arterial blood samples measured by a conventional two-wavelength oximeter. Oxygen saturation was varied by stepwise reduction of the inspired oxygen concentration of the ewe. Results: A total of 58 data pairs was obtained from five fetuses, with a range of 10.9-73.5% for the reference method and 6.8-69.2% for the pulse oximetry oxygen saturation values. There was good correlation between the results obtained by the two methods (r2 = .89, P < .0001), with a 95% confidence interval of ± 12.5%. The pulse oximeter showed a precision of 6.2% oxygen saturation. Conclusion: The Zurich reflectance pulse oximeter offers valid measurements of oxygen saturation levels down to 10% oxygen saturation, and is therefore suitable for monitoring the fetus during delivery.

Vasodilator response to exogenous adrenocorticotropic hormone in fetal adrenal cortex precedes increased steroidogenesis in sheep at 105-112 days gestation

OBJECTIVE To examine whether the increase in adrenal cortical blood flow induced by adrenocorticotropic hormone (ACTH) is linked to steroidogenesis, or if these effects can be separated. STUDY DESIGN Adrenal cortical responses to ACTH were measured in ovine fetuses at 105-112 days gestation, when the adrenal is hyporesponsive. Fetuses were given an intravenous infusion of ACTH(1-24) or of vehicle. We measured regional adrenal blood flows by the microsphere technique and plasma ACTH and cortisol levels by radioimmunoassay. RESULTS After 3 and 24 h of ACTH infusion, plasma cortisol concentrations had risen from 2.8+/-0.8 ng/ml to 8.4+/-0.3 and 78.0+/-15.8 ng/ml (means+/-S.E.M.). Adrenal cortical blood flow increased from 108+/-25 ml/min/100 g to 319+/-33 and 518+/-51 ml/min/100 g. Plasma cortisol levels and adrenal blood flow did not change in control fetuses. CONCLUSION Since there was a rapid blood flow response to ACTH, despite the expected delay in the rise of plasma cortisol, we suggest that vascular responses to ACTH are not tightly linked to adrenal metabolic activity in the ovine fetus at 0.7 gestation.