The Lack of a Growth-Promoting Effect of Orally Administered Bovine Somatotropin in the Rat Body-Weight-Gain Bioassay

The Lack of a Growth Promoting Effect of Orally AdministeredBovine Somatotropin in the Rat Body-Weight-Gain Bioassay. SEAMAN,W. J., NAPPIER, J. L., OLSEN, R. F., CHARLTON, M. D., SKINNER,P. J., WEAVER, R. J., AND HOFFMAN, G. A. (1988). Fundam. Appl.Toxicol. 10, 287-294. Bovine somatotropin (bSt) was given eitherorally or subcutaneously to groups of female hypophysectomizedrats daily for 9 days. Ten rats per dose group were given oraldosages of 0 (buffered-water vehicle control), 40,400, 2000,and 4000 µg of bSt per day. Similar groups often ratseach received subcutaneous doses of 0 (buffered-water vehiclecontrol), 15, 30, and 60 µg of bSt per day. Rats wereweighed daily to observe their body-weight gain, which is ameasure of the biological activity of bSt in the hypophysectomizedrat. At study termination, serum of treated rats was monitoredfor the presence of bSt and antibody to bSt. Bovine somatotropinwas detected in the serum of the subcutaneously treated rats,but not in those rats treated orally. Of 18 rats treated subcutaneouslywith bSt, 14 developed antibodies to bSt, whereas of 38 ratstreated orally with bSt, 11 developed antibodies. Subcutaneouslytreated rats grew in a dose-related manner as expected in thisassay. Orally administered bSt failed to elicit a growth responseat any dose in this sensitive bioassay system. The data suggestthat neither bSt nor growth-promoting fragments of bSt are absorbedafter oral administration of doses up to 40,000 Mg/kg/day inthe hypophysectomized rat.     

Toxicity of Methylenedioxymethamphetamine (MDMA) in the Dog and the Rat

Toxicity of Methylenedioxymethamphetamine (MDMA) in the Dogand the Rat. FRITH, C. H., CHANG, L. W., LATTIN, D. L., WALLS,R. C., HAMM, J., AND DOBLIN, R. (1987). Fundam. Appl Toxicol.9, 110–119. Methylenedioxymethamphetamine (MDMA) was administeredto dogs and rats orally once a day for a 28-day period to evaluatethe morphological and neuropathological effects. Major clinicalsigns associated with the administration of MDMA in the dogincluded circling, depression, dilated pupils, hyperactivity,rapid breathing, and salivation. Major clinical signs in therat included hyperactivity, excitability, piloerection, exophthalmos,and salivation. Gross observations at necropsy in the dog possiblyrelated to administration of the test article included reducedtesticular size (one high and one medium dose) and prostaticenlargement in two high-dose animals. No gross lesions wereseen in the rats at necropsy. The medium-and the high-dose groupsin both sexes in both the rats and the dogs gained significantlyless weight than the control and low-dose groups. Food consumptiondecreased the first week for the high-and medium-dose groups,but a significant reversal toward more normal consumption wasnoted in the following weeks in both the rats and the dogs.Hematologic, clinical chemistry, and urinalysis values did notappear to be affected by the administration of the test articlein the dog. in the rat clinical pathology variables showinga trend to decrease with dose included urinary pH, blood ureanitrogen, glucose, creatinine (females), lactate dehydrogenase(LDH) (females), and chloride. Clinical pathology variablesshowing a trend to increase with dose included total white bloodcell count and phosphorus. Microscopically, testicular atrophywas present in one medium-dose and two high-dose male dogs.Prostatic hyperplasia was present in two high-dose male dogs.No test article-related lesions were seen in the brains of eitherspecies.     

Electrophysiological Effect of the Maze Procedure on Canine Sinoatrial Node Function

The maze procedure is an operation that has had great initial success in curing atrial fibrillation. This procedure includes several right atrial incisions that may interrupt the integrity of the sinoatrial node or its arterial supply. To assess the effect of the maze procedure on sinus node function (SNF), the following studies were performed: sinus node recovery times (SNRT), corrected SNRT (CSNRT), CSNRT under autonomic blockade maximal heart rate and intrinsic heart rates. Thirty-four dogs underwent a right thoracotomy with cardiopulmonary bypass (CPB). The dogs were divided into three groups. Group I (n = 9), the sham group, underwent CPB without any incisions. Group 2 (n = 8) underwent CPB and one of the right atria] incisions. Group 3 (n = 18) underwent CPB and all three of the right atrial incisions. SNF was determined before and after the procedure. Groups 1 and 2 had no significant difference in measured SNF acutely after the procedure. In Group 3 the mean SNRT increased from 552 msec to 1,984 msec (P = 0.005). Sinus node dysfunction was corroborated by all studies. In the chronic studies, a trend toward recovery of SNF was observed. The maze procedure results in significant acute sinus node dysfunction. This dysfunction may resolve spontaneously over the ensuing months. Modifications of the maze procedure that avoid the sinus node or its blood supply area may reduce procedure related sinus node dysfunction.     

CNS Regulation of Cardiac Rhythm and the Potential for Pain-Induced Arrhythmia

CNS Control of Cardiac Rhythm. The purpose of our studies was to determine brain areas that influence cardiac rhythm. Studies were performed in anesthetized cats and indicate that a yet undetermined site in the hindbrain involving GABAergic mechanisms has a major influence over cardiac rhythm. In addition, a serotonergic mechanism involving 5-HT₂ receptors in the subretrofacial nucleus is responsible for selective activation of sympathetic neurons to the ventricle of the heart. Our data also indicate that neurons in the area postrema exert a major effect on cardiac rhythm. Finally, the question of whether pain-induced changes in cardiovascular function involves neurons in the subretrofacial nucleus is also addressed.     

A Packaged Solution to the Problems of Testing Arrhythmia Control Devices at Implant

A composite implantable arrhythmia control device (ACD) implements the functions of a bradycardia pacemaker, an antitachycardia pacemaker, a cardioverter, and a defibrillator in an integrated fashion. Given this broad spectrum of functionality, the implant testing for these devices can become a formidable endeavor requiring a large ensemble of expensive, complex support equipment, and a significant amount of time. However, if this procedure is not carried out correctly, the device might later fail to defibrillate. This article presents a unique packaging system for an ACD that allows the device to be used while it is still in its sterile package. The device may then be used during implant testing as the defibrillation test unit. This collapses the amount of support equipment that is required to just the ACD, its programmer, and an optional switch box. By providing additional support specifically for implant testing through the ACD programmer, implant testing may be reduced to a quick, easy-to-manage procedure. Since the device used during implant testing is the same device that will be implanted, this packaging system offers the further advantage that the physician can be confident that, once implanted, the ACD will function correctly.     

Case Report: Pneumomediastinum and pneumothorax complicating colonoscopy

Colonic perforation is potentially the most serious complication of colonoscopy. Both the clinical manifestation and rapidity of onset of symptoms can vary depending on whether the perforation occurs directly into the peritoneal cavity or into the retroperitoneal space. Colonic perforation is often associated with abdominal pain, although more uncommon presentations have been documented. A case report of a unilateral pneumothorax and pneumomediastinum complicating colonoscopy is described, which responded well to conservative measures without recourse to surgical intervention, antibiotic therapy or parenteral alimentation.     

Safety of External Cardioversion/Defibrillation in Patients with Internal Defibrillation Patches and No Device

Placement of prophylactic epicardial defibrillation patches at time of open-heart surgery in patients at risk for postoperative arrhythmias has been strongly questioned. Concern has centered on the ability to safely perform subsequent external defibrillation if needed. From 61 patients who were treated with a two-stage strategy we identified 17 who, while wearing epicardial patches and no generator, received external cardioversion/defibrillation for 20 episodes of hemodynamically unstable ventricular arrhythmias. All the patients had one small and one large patch. Eighteen of the episodes were induced during electrophysiological testing (with transthoracic shocks delivered via pad electrodes oriented in an apex-posterior configuration) and two were spontaneous. The episodes occurred at 21 +/- 27 days from patch implant. Thirteen episodes (65%) were converted with one shock at an energy level of 185 +/- 65 J. Seven (35%) required a second shock at 351 +/- 22 J. The accumulated energy requirement was 286 +/- 205 J. No adverse outcomes were noted. The number of episodes requiring more than one shock and the energy requirements were not different from those in a control group of 20 similar arrhythmias treated with the same equipment. Under these conditions, external cardioversion/defibrillation in patients with one large and one small epicardial defibrillation patch was uniformly successful. Further data is needed in the out-of-hospital setting and on the results of external defibrillation in patients with two large patches.     

Dose-dependent effects of a nitric oxide biosynthesis inhibitor on hyperdynamic circulation in two models of portal hypertension in conscious rats

The role of nitric oxide (NO) in the hyperkinetic circulation in portal hypertension has not been clearly elucidated. Different doses of NO inhibitors, haemodynamic values and experimental conditions might explain the discrepant results. The aim of the present study was to investigate the acute effects of a specific biosynthesis inhibitor of NO, Nω-nitro-L-arginine (L-NNA), on the systemic and splanchnic circulation in normal conscious rats and rats with portal hypertension due to either partial portal vein stenosis or secondary biliary cirrhosis. The administration of L-NNA (15 to 960 (μg.kg^-1.min^-1) induced a significant dose dependent increase in arterial pressure which was not different among the three groups of rats. Following an acute and maximal vasopressive dose of L-NNA (1 mg.kg^-1.min^-1) cardiac index decreased more in portal vein stenosed and cirrhotic rats (-45 ± 3% and -45 ± 2%, respectively) than in normal rats (-31 ± 2%), and systemic vascular resistance increased more in the two groups of portal hypertensive rats than in normals (+161 ± 13% and + 154 ± 10% vs + 85 ± 6%, respectively). L-NNA caused a greater decrease in portal tributary blood flow in portal vein stenosed and cirrhotic rats (-63 ± 4% and -55 ± 4%, respectively) than in normal rats (-45 ± 6%). Similarly, the increase in portal territory vascular resistance was significantly more marked in portal vein stenosed and cirrhotic rats (+ 337 ± 62% and +214 ± 24%, respectively) than in normal rats (+153 ± 23%). Portal pressure did not change. Following the acute administration of L-NNA, no significant difference in splanchnic and systemic haemodynamics were noted between portal vein stenosed and normal rats, except for portal pressure. In cirrhotic rats, splanchnic and systemic values remained different from normal rats. This study confirms that NO plays a role in the haemodynamic changes in portal hypertension, and shows that NO inhibitors have a dose-dependent effect in conscious portal hypertensive rats.