Treatment of cyanide poisoning

The object of this study was to evaluate the effectiveness of five regimens in treating cyanide poisoning. A series of anesthetized adult beagle dogs were instrumented to record hemodynamic and respiratory function and given 2.5 mg/kg sodium cyanide intravenously. The 10 control animals given only cyanide died at from 5 to 7 minutes. Therapy, as described below, was given to other groups at from 2 to 3 minutes following the cyanide administration. Artificial respiration did not alter the lethal effects of cyanide nor prolong survival time in any of the 10 animals. Amyl nitrite given by inhalation or by the intravenous route allowed survival of all 15 animals. Sodium nitrite (20 mg/kg), dimethylaminophenol (DMAP) (5 mg/kg), and hydroxylamine hydrochloride (5 mg/kg) given intravenously with no artificial ventilation also allowed for 100% survival (15 animals). Amyl nitrite, sodium nitrite, and sodium thiosulfate were ineffective when given intramuscularly (I.M.) (0 of 12 dogs); however, I.M. DMAP (5 mg/kg) and I.M. hydroxylamine hydrochloride (50 mg/kg) increased heart rate and blood pressure and restored spontaneous breathing. All 15 animals treated with I.M. doses of either of these drugs survived the lethal dose of cyanide. Results of these studies indicate that intravenous sodium nitrite, DMAP, and hydroxylamine hydrochloride, and amyl nitrite by inhalation, are all effective in reversing the lethal effects of cyanide poisoning. Only DMAP and hydroxylamine hydrochloride are effective when given by the intramuscular route. These results provide data to support an approach to therapy that is more practical and applicable where expert medical care may not be available following cyanide exposure.     

The opossum as an animal model for studying radiation esophagitis.

Six opossums were evaluated as a possible animal model of radiation esophagitis. In a single exposure to the esophagus, four animals received 60Co radiation of various doses; two served as controls. Pre- and postirradiation evaluations using fiberoptic endoscopy, mucosal biopsy, barium esophagography, and manometry were performed. Esophagitis developed at one week in irradiated animals. Opossums receiving 17.5, 20, and 22.5 Gy (1,750; 2,000; and 2,250 rad) became anorexic one week postirradiation, and abnormal motility subsequently developed. The controls and the animal receiving 15 Gy (1,500 rad) remained normal. Histological changes in the irradiated opossum esophagus resembled those found in humans.     

A reproducible canine model of nonocclusive mesenteric ischemia

A technique for producing a reliable, clinically applicable, and highly reproducible canine model of nonocclusive mesenteric ischemia was developed. Following left thoracotomy in 10 dogs, a 1 mm diameter soft polyethylene tube was inserted into the pericardial space via a small puncture site. This tube was sealed in place with cyanoacrylate tissue adhesive. A solution of 10% Dextran 40 in saline was infused into the pericardial space until a 50% reduction (as monitored by electromagnetic flowmeter) in superior mesenteric artery flow (SMAQ) was obtained. Without additional intrapericardial infusion of the Dextran solution, SMAQ was reduced 51 +/- 4% to 54 +/- 3% of control values during a 60 minute post-tamponade observation period. During the same time. Cardiac output was depressed between 40 +/- 8% and 54 +/- 3%, and right atrial pressure remained elevated between 164 +/- 15% and 171 +/- 15%. Systemic arterial pressure initially dropped 28 +/- 5% but compensated to within 11 +/- 5% of pre-tamponade level at 60 minutes. The stability of this model is well suited for evaluating new experimental diagnostic and therapeutic procedures.     

A canine model for studying endoleak after endovascular aneurysm repair

PURPOSE: The aim of this study was to create an animal model of endoleak after stent-graft placement for abdominal aortic aneurysm (AAA) in which a large aneurysmal sac would be preserved for the testing of techniques for its percutaneous occlusion. MATERIALS AND METHODS: Infrarenal AAAs were created in nine dogs by anastomosis of an isolated segment of the inferior vena cava to the right side of the abdominal aorta in combination with a large anterior patch from the external jugular vein. One hour later, animals underwent percutaneous implantation of polytetrafluoroethylene-covered Z stent endografts with three 3-mm-diameter holes through the fabric. Aortograms were obtained before and after surgery, after endograft placement, and at the time of animal sacrifice at 1 week or 1, 2, 3, or 6 months. Pressures within the aorta and the aneurysm sac were recorded before animal sacrifice. Gross and histologic evaluations of the specimens were then carried out. RESULTS: Immediately after endograft placement, all nine animals had artificial type III endoleaks with angiographic filling of lumbar arteries and veins. One animal died of surgical complications within 2 days of surgery and is not included in our data analysis. One aneurysm ruptured at 1 week. At completion of the study, six endografts were patent and two were occluded. The aneurysm sac had enlarged by approximately 50% in seven animals. At follow-up, type I endoleak was present in three animals, type II endoleak was present in three, and the artificial type III endoleak was present in all six animals with patent endografts. The pressure differential between aorta and aneurysm sac was 36 mm Hg, with a mean aortic pressure of 87 mm Hg +/- 13.3 and a mean aneurysmal sac pressure of 51 mm Hg +/- 28.1. The aneurysmal sac exhibited early thrombus formation at 1 week, which progressed to complete thrombosis in 1-6 months. CONCLUSIONS: The model is technically feasible but would be useful in testing occlusive techniques for residual aneurysm sacs only in the acute phase after endograft placement. It would be not reliable for chronic evaluation because of rapidly progressive thrombosis in most aneurysm sacs and occasional complete thrombosis of the AAA and endograft.     

CT diagnosis of toxic brain injury in cyanide poisoning: considerations for forensic medicine

Two deaths occurred after ingestion of cyanide-containing Extra-Strength Excedrin capsules. Cranial CT scans obtained within 3 hr of each patient's collapse showed diffuse cerebral swelling and loss of gray-white differentiation. Most diffuse cerebral insults (hypoxia, ischemia) do not show such changes so soon after injury. The early onset of diffuse cerebral edema with loss of gray-white differentiation may be a clue to the diagnosis of acute cyanide poisoning.     

A dedicated animal model for mechanical thrombectomy in acute stroke

BACKGROUND: Recent studies have focused on mechanical thrombectomy as a means to reduce the time required for revascularization and increase the revascularization rate in acute stroke. To date no systematic evaluation has been made of the different mechanical devices in this novel and fast-developing field of endovascular interventions. To facilitate such evaluations, we developed a specific in vivo model for mechanical thrombectomy that allows visualization of dislocation or fragmentation of the thrombus during angiographic manipulation. METHODS: Angiography and embolization with a preformed thrombus was performed in 8 swine. The thrombus was generated by mixing 25 IU bovine thrombin and 10 mL autologous blood. For visualization during angiography, 1 g barium sulfate was added. RESULTS: The preformed thrombus exhibited mechanical stability, reproducibility, and high radiographic absorption, providing excellent visibility during angiography. The setting allowed selective embolization of targeted vessels without thrombus fragmentation. Despite the application of barium sulfate no local or systemic reaction occurred. Histologic evaluation revealed no intimal damage caused by the thrombus or contrast agent washout. CONCLUSION: The model presented here allows selective and reliable thromboembolization of vessels that reproduce the anatomic and hemodynamic situation in acute cerebrovascular stroke. It permits visualization of the thrombus during angiography and intervention, providing unique insight into the behavior of both thrombus and device, which is potentially useful in the development and evaluation of mechanical clot retrieval in acute cerebrovascular stroke.     

A cardiovascular model for studying impairment of cerebral function during +Gz stress

A digital computer model of the human cardiovascular system has been developed which can be used for studying impairment of cerebral function during +Gz stress. The model includes simulation of the arterial and venous systems, the heart, baroreceptor control of heart rate, control of venous tone, and the effect of gravity. Model predictions suggest that, for unprotected subjects, carotid pressure at eye level decreases to 50 mm Hg (beginning of peripheral light loss) at approximately 2.7 Gz. The pressure decreases to 20 mm Hg (beginning of central light loss) at approximately 3.6 Gz. An anti-G suit provides an extra 1.1 to 1.5 Gz protection. Even though blood pressure supplying retinal vessels drops significantly at the above G levels, cerebral blood flow is maintained due to protective and compensatory mechanisms. These observations compare favorably with results reported in the literature. The results suggest that this model can be used to improve our understanding of the cardiovascular system's response to +Gz stress.     

A new animal model for testing renal tolerance of contrast agents

RATIONALE AND OBJECTIVES: To develop a new animal model for the evaluation of the renal tolerance of contrast agent and its application to diatrizoate and iotrolan injections in comparison to saline and mannitol solution. MATERIALS AND METHODS: The nephrotoxic potential of intravenously injected contrast agents in Beagle dogs was determined from the effects on the pharmacokinetics of creatinine injected immediately after these agents in comparison with the kinetics of creatinine injected alone. The kinetic parameters evaluated included plasma half-life, volume of distribution, and clearance. In a series of studies, the experimental conditions were optimized in terms of creatinine dose and the effects of diatrizoate, iotrolan, saline, and mannitol solution on the pharmacokinetic parameters of creatinine were determined. RESULTS: Bolus injection of creatinine into dogs followed a dose-linear pharmacokinetic behavior with a terminal half-life of 90 minutes (10 mg/kg) and 108 minutes (20 mg/kg), respectively, and a clearance of 5 mL/min/kg. Injection of diatrizoate decreased the clearance and the half-life of creatinine significantly. A mannitol solution with the same osmolality as diatrizoate showed the same effect whereas physiological saline did not affect pharmacokinetic parameters of creatinine. The isotonic iotrolan was intermediate between saline and diatrizoate in its effects on creatinine clearance. CONCLUSION: The effect of contrast agents on pharmacokinetic parameters of creatinine injected immediately after the administration of the agents in dogs might be a useful model for the evaluation of renal tolerance. In a cross-over study, iotrolan was not statistically separable from diatrizoate.     

一种建立门脉高压动物模型的新方法

目的：探索一条新的、更迅速和有效地建立门脉高压和肝纤维化动物模型的途径。材料和方法：采取前瞻性研究方法，在１５只大耳白兔通上静脉主干注入不同稀释度的白芨混悬液，栓塞门静脉末梢血管而升高门脉压，术后３－４周采取同法复查测量门脉压，作肝活检病理切片及血管铸形。结果：通过兔门静脉注入０．４％白芨混悬液４ｍｌ，能使门脉压升高约４０％，３周后门脉压仍维持较高水平，病理切征示被白芨栓塞部位出现典型的肝纤维化改     

脑静脉窦栓塞动物模型的建立方法

目的:探讨经皮穿刺静脉插管静脉窦内弹簧圈或/和明胶海绵植入致脑静脉窦急性栓塞动物模型的建立方法,评价其有效性、可行性、优缺点。方法:采用经静脉插管的介入方法将弹簧圈和/或明胶海绵放置在实验小型猪脑静脉窦的不同位置达到静脉窦完全或不完全栓塞的效果。结果:9例实验动物均成功的完全或不完全栓塞上矢状窦、直窦、乙状窦。右侧乙状窦栓塞1例,上矢状窦中后1/3 Rolandic静脉前1~2cm处1例,Rolandic静脉处栓塞3例,Rolandic静脉后1~2cm处栓塞2例,直窦栓塞1例,窦汇和直窦栓塞1例。结论:经皮穿刺静脉插管脑静脉窦内弹簧圈、明胶海绵植入致脑静脉窦急性栓塞动物模型的实验方法有效可行,此方法不开颅,脑组织无人为损伤,更加接近实际发病状况。     

A reproducible radionuclide procedure for measurement of cerebrospinal fluid shunt flow

A radionuclide technique was developed to obtain reproducible measurements of cerebrospinal fluid flow in Rickham-Holter type shunt systems. In attempting to reproduce previously described radionuclide procedures, we found that different flow rate measurements can be obtained simply by chaning the radiotracer injection technique or the method of analysis of the time activity curves which are generated. The importance of these technical pitfalls cannot be over-emphasized, since there is no gold standard to evaluate cerebrospinal fluid flow in vivo. An experimental model with a calibrated Harvard pump and a shunt system filled with normal saline was constructed. Aliquots of 500 Ci of pertechnetate in 0.05 ml of saline were injected serially into the center of the Rickham reservoir using a size 28 needle. Time-activity curves were obtained after waiting five min to reach equilibrium, and standard curves of radiotracer clearance vs actual flow for each system used clinically in our institution were generated. In addition, a technique to quantify and thus correct for the small but significant leak of radiotracer which occurs at the site of injection in the reservoir is described. Excellent correlation was obtained between our results and the clinical and radiological findings in a preliminary clinical evaluation.     

A reproducible radionuclide procedure for measurement of cerebrospinal fluid shunt flow

A radionuclide technique was developed to obtain reproducible measurements of cerebrospinal fluid flow in Rickham-Holter type shunt systems. In attempting to reproduce previously described radionuclide procedures, we found that different flow rate measurements can be obtained simply by changing the radiotracer injection technique or the method of analysis of the time activity curves which are generated. The importance of these technical pitfalls cannot be over-emphasized, since there is no gold standard to evaluate cerebrospinal fluid flow in vivo. An experimental model with a calibrated Harvard pump and a shunt system filled with normal saline was constructed. Aliquots of 500 microCi of pertechnetate in 0.05 ml of saline were injected serially into the center of Rickham reservoir using a size 28 needle. Time-activity curves were obtained after waiting five min to reach equilibrium, and standard curves of radiotracer clearance vs actual flow for each system used clinically in our institution were generated. In addition, a technique to quantify and thus correct for the small but significant leak of radiotracer which occurs at the site of injection in the reservoir is described. Excellent correlation was obtained between our results and the clinical and radiological findings in a preliminary clinical evaluation.     

A reproducible and variable intensity cycling performance protocol for warm conditions

This study was undertaken to assess the reproducibility of a variable intensitycycling protocol using subjects of varying abilities, under warm humid conditions.Eleven subjects (Age 21.4+/-2.6 years; VO2peak 3.30+/-0.9 l x min(-1); peak power 322.8+/-86.3 W; mean+/-SD) performed a 60 min cycling trial punctuated with six one-min "all-out" sprints at 10-min intervals on three occasions 5-14 days apart. Ambient temperature and relative humidity were set at 33+/-0.7 degrees C and 63+/-2.0%, respectively. Subjects used their own bicycle mounted to an electromagnetic trainer and were only permitted to monitor elapsed time and heart rate. Repeatability was assessed using the limits of agreement which were best between trials 2 and 3 where the distance cycled was -0.54 km below and 1.34 km above the distance cycled for trial 2. The co-efficient of variation (CV) for distance for three trials was 3.58%. For trials 1 and 2 the CV was 3.54% (r = 0.97, p< 0.001) decreasing to 1.34% (r = 0.99, p< 0.001) for trials 2 and 3. The intra-class correlation for three trials was 0.93. Distance for trial 1 (26.3+/-5.0 km; p< 0.05) was less than trials 2 (27.7+/-5.7 km) and 3 (28.1+/-5.6 km). It was concluded that repeatability for this performance protocol with cyclists of varying abilities In warm humid conditions was acceptable given at least one familiarisation trial. However, it is not yet known whether other protocols designed for moderate environments are applicable to less favorable conditions. Further studies are needed before results of treatment effects under differing ambient conditions can be fully understood and assigned appropriate significance.     

An animal model for radiologic biliary interventional procedures

Procedural development, in vivo evaluation, and professional training in interventional biliary radiology require an animal model that provides easy and safe access to the gallbladder and bile ducts. A porcine model was used successfully for catheterization of the biliary system under fluoroscopic control. Permanent access to the gallbladder of ten pigs was achieved with a large-bore cholecystostomy catheter. Catheterization of the common bile duct through the cystic duct was feasible in all animals. Repeated interventional radiologic procedures were performed with intramuscular sedation of the animals, which made this model particularly useful for studies requiring multiple procedures or serial follow-up over several weeks. This article describes the technical aspects of the animal model and the radiographic anatomy of the extrahepatic biliary system in 27 domestic pigs.     

Some vitreous humour cardiorenal biochemical parameters as an indicator of acute carbon monoxide poisoning death: an animal model

In this study, acute carbon monoxide (CO) was used to cause the death of experimental animals through inhalation. The sample size of the study was made up of 18 rabbits divided into the control group (CG), disguised death (DD) and carbon monoxide death (CD) groups respectively. Vitreous humours were extracted using standard methodologies and biochemical parameters estimated using WHO approved methods and procedures. The findings showed a significant decrease (P < 0.05) in vitreous humour chloride ion, calcium ion, pH, uric acid and total calcium in the CDs. However, vitreous lactate dehydrogenase (LDH) of the experimental animals significantly increased (P < 0.05) only in the CD group, while creatine kinase (CK) and creatine significantly increased in both the DD and CD animal groups, although they were markedly higher in the CD. Therefore, decreases in concentrations of vitreous humour uric acid, chloride and calcium profile, and an increase in vitreous LDH could serve as possible indicators of CO poisoning, especially in scenarios of impracticable use of blood, as in rigor mortis, livor mortis or decomposition.