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Biomedical subjects

D R Gross

Publications and source records attributed to D R Gross.

At least 55 records · Page 3Linked to original sources

Effects of naloxone in treating hemorrhagic shock in dogs with maintained baroreceptor responsiveness.

The efficacy of treating hemorrhagic shock with naloxone in conjunction with fluids, compared with fluid therapy alone, was studied. Previously instrumented dogs were anesthetized with 0.04 mg of fentanyl/kg + 2.2 mg of droperidol/kg and pentobarbital sodium (to effect). Blood was withdrawn from each animal to achieve and maintain a mean arterial blood pressure of 40 to 50 mm of Hg for the first 2 hours of the experiment (t = 0 to 120 minutes). At t = 120 minutes, IV fluid administration was begun (all dogs) and continued for 1 hour (lactated Ringer's solution at a dosage of 70 ml/kg/hr). Hypothermia was corrected. Control dogs were given no other treatment. Dogs in the naloxone plus fluids group were given an IV bolus of naloxone (1 mg/kg) at t = 120 minutes and 1 mg of naloxone/kg/hr in the fluids from t = 120 to t = 180 minutes. Treatment (either naloxone plus fluids or fluids alone) was stopped at t = 180 minutes, and measuring of response was continued for an additional hour (posttherapeutic period). Significant differences were not seen in mean arterial pressures, left ventricular peak systolic pressures, dP/dt max, time constant T (a measure of left ventricular elasticity), and mean pulmonary arterial pressures between the dogs given naloxone and fluid therapy and those given fluid therapy alone. All dogs in both groups survived the procedure.

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Contribution of the lung to total body clearance of meperidine in the dog.

The potential role of the lung in the disposition of meperidine was examined in six conscious dogs instrumented for measurement of appropriate hemodynamic parameters. Following an intravenous bolus injection of 5 mg/kg, blood samples were collected simultaneously from cannulas placed in the left ventricle and the pulmonary artery, concurrent with the hemodynamic measurements. Pulmonary clearance, calculated from concentration differences between pulmonary arterial and left ventricular blood and pulmonary blood flow, averaged 12.1 +/- 3.70 mL/min/kg, accounting for 58 +/- 13% of the total clearance of the drug. These results help resolve differences between previously reported meperidine clearance in the dog and physiological blood flows and imply that the dog may be a poor model for this drug in humans where clearance is primarily hepatic.

Animals↗

Viscoelastic behavior of the thoracic aorta of dogs and rabbits.

Data are presented which demonstrate no correlation between atrial electrical activity and diameter changes in the descending thoracic aorta of dogs or rabbits. The experiments conducted included bypassing a segment of the descending thoracic aorta in dogs, and production of a variety of arrhythmias without the bypass in dogs and rabbits. We found no evidence of electrical stimulation-induced phasic activity as suggested by other authors.

Animals↗

Plasma volume and estimated liver plasma flow during hyperbaric and hyperoxic exposures in awake dogs.

Five different experiments were conducted to determine if estimated liver plasma flow and/or plasma volume were changed as a result of exposure to 2.8 atmospheres absolute (ATA) while breathing 100% oxygen or 6 ATA while breathing compressed air. The experiments were designed to separate the relative roles of the ambient pressure, the partial pressure of oxygen, the time of high oxygen exposure or some combination of these factors on any observed changes. We found that time was not a factor in the changes seen. Hyperbaria resulted in a decrease in estimated liver plasma flow at all pressures greater than 1 ATA. There was an apparent increase in plasma volume at 1.3 ATA and a return towards 1 ATA values at higher pressures. Hyperoxia resulted in a decrease in estimated liver plasma flow at 975 mm Hg but not at 912 mm Hg. The flow was then increased again at 2128 mm Hg. Plasma volume decreased significantly at 912 mm Hg returned to baseline (152 mm Hg) values at 975 mm Hg and then decreased again at 1054 and 2128 mm Hg PO2.

Animals↗

Hemodynamic effects of 10% dextrose and of dextran 70 on hemorrhagic shock during exposure to hyperbaric air and hyperbaric hyperoxia.

Six groups of six conditioned dogs each were instrumented with an electromagnetic flow-meter transducer around the pulmonary artery, and indwelling silastic cannulae in the pulmonary artery, the left ventricle, the ascending aorta, and the right atrium. After allowing a minimum of 5 d for recovery, the dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA), breathing 100% oxygen (PO2 2128 mm Hg) and at 6 ATA breathing air (PO2 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Mean aortic pressure was maintained between 40-50 mm Hg for 30 min. This required a rather constant 40 +/- 4.5 ml X kg-1 body weight of total blood removed. Three groups, one at each depth perturbation, were then given Dextran 70, the other three groups 10% dextrose. Fluids were administered at a constant rate until the mean aortic pressure rose to within 90% of its original 1 ATA baseline value. At this point, the infusion was stopped and the total amount of fluid administered was recorded. Hemodynamic parameters were measured or calculated for eight different time periods during each experiment. The amount of Dextran 70 required did not change with hyperbaric exposure but only half as much 10% dextrose was required at depth. Dextran 70 held the cardiovascular parameters constant for 30 min following administration but after 10% dextrose, cardiac output tended to decrease at 15 and 30 min posttreatment. There were no significant differences in the cardiovascular effects of hemorrhage between or among the dogs exposed to the three different environmental conditions.

Animals↗

An evaluation of plasma volume expanders in the treatment of decompression sickness.

Each of 29 goats was instrumented with an ultrasonic flowmeter transducer around the left common carotid artery and a silastic catheter in the anterior vena cava. Following recovery from the surgery the goats were subjected to a dive protocol designed to elicit symptoms of decompression sickness (DCS). The goats were returned to the surface and, following a 20-min observation period, were either left untreated (controls) or treated with one of five different plasma volume expanders. The plasma volume expanders were evaluated based on their ability to decrease the severity of DCS and the number of arterial bubbles that could be counted. Analysis of the results shows that all of the five plasma volume expanders used appeared to reduce the severity of the signs of DCS and to decrease the number of arterial bubbles detected but that these tendencies were not statistically significantly except for Mannitol and Dextran 40. Animals that did not develop arterial bubbles tended to respond better to fluid therapy than did those that did develop bubbles.

Animals↗

Hemodynamic effects of Dextran 40 on hemorrhagic shock during hyperbaria and hyperbaric hyperoxia.

Three groups of six dogs each were instrumented with an electromagnetic flow-meter around the pulmonary artery, and indwelling silastic cannulas in the pulmonary artery, the left ventricle, the ascending aorta and the right atrium. After 7-10 d, dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA) breathing 100% oxygen (PO2 approximately equal to 2128 mm Hg), and at 6 ATA breathing air (PO2 approximately equal to 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Pressure was maintained between 40-50 mm Hg for 30 min. Enough Dextran 40 was then infused to stabilize the aortic pressure to within 90% of its original 1 ATA baseline value. Hemodynamic parameters were measured or calculated at eight different times. More than twice the amount of Dextran 40 was required at depth than at 1 ATA. There were statistically significant differences due to the effects of hemorrhage but no differences between the three groups attributable to either of the hyperbaric conditions or the effects of Dextran 40.

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Simultaneous cystometry and uroflowmetry (micturition study) for evaluation of the caudal part of the urinary tract in dogs: studies of the technique.

A procedure similar to one used for urodynamic evaluation of persons was adapted for simultaneous cystometry and uroflowmetry in dogs. Percutaneous transabdominal urinary bladder catheterizations were used for bladder infusion and cystometry, so that urine flow during voiding would not be altered by urethra instrumentation. The technique was evaluated twice in each of 12 healthy dogs (6 males and 6 females). Studies of individual dogs were performed 1 week apart. Comparisons were made between xylazine and oxymorphone for sedation to accomplish the procedure. Although the 2 drugs provided adequate sedation, oxymorphone was unsatisfactory because it interfered with micturition, whereas xylazine generally did not. Adverse consequences of the procedure occurred infrequently and were minor. According to results of urinalyses, hematuria or pyuria, or both, appeared during the week after the procedure was done in a few dogs, and staphylococcal bacteriuria was induced in 4 dogs. Fluid leakage from urinary bladders was not demonstrated by abdominal paracentesis immediately after each procedure or by contrast radiography performed the day after the 2nd study for each animal. Micturition studies were concluded to be reasonably safe to do, especially when performed by experienced individuals. The studies were judged to have considerable potential value as a means to evaluate lower urinary tract function in dogs.

Anesthesia↗

Simultaneous cystometry and uroflowmetry (micturition study) for evaluation of the caudal part of the urinary tract in dogs: reference values for healthy animals sedated with xylazine.

Micturition studies were performed in 12 healthy dogs (6 females and 6 males). The animals were sedated with xylazine given either IV (1.1 mg/kg) or IM (2.2 mg/kg). Separate antepubic catheters were used to perform bladder infusions and record intravesical pressures. Instantaneous urine flow measurements were obtained, using an apparatus specially designed and constructed for small animals. A total of 45 simultaneous cystometric and uroflowmetric recordings were obtained, and numerical values for 16 different micturition variables were tabulated. The variables were analyzed separately on the basis of sex of the animal, route of administration of the sedative, and the fact of having had a previous bladder instrumentation-micturition study performed. Significant differences within individual dogs were not seen in these analyses. Intravesical pressures, urine flow rates, compliances, and urethral resistance were significantly different (P less than 0.05) between male and female dogs. The micturition study was a simple and reliable urodynamic testing method that could be clinically useful in dogs. In contrast to urodynamic tests previously described in veterinary medicine, this method provided evaluation of the bladder and urethra as a functional unit during both the filling and the emptying phases of micturition. A micturition study should not be regarded as an absolute measure of the physiologic activity of the caudal part of the urinary tract. However, it can provide important additional information for clinical assessment when the lower part of the urinary tract is affected by disease, injury, or drugs.

Animals↗

Salicylate pharmacokinetics in the dog at 6 ATA in air and at 2.8 ATA in 100% oxygen.

Hyperbaric air and hyperbaric hyperoxia, which have been shown to decrease both liver plasma flow and plasma volume in dogs, may potentially affect the disposition of drugs whose distribution and/or elimination are dependent upon those actions. This study examined the effects of those conditions on the disposition of salicylic acid, using the dog as a model. The drug was administered to six mixed-breed dogs as a 10 mg sodium salicylate/kg i.v. bolus at 1 ATA breathing air (control), at 2.8 ATA breathing 100% O2, and at 6 ATA breathing air, followed by serial blood sampling for 8 h. Statistical analysis showed a significant increase (p less than 0.05) in salicylate clearance at 2.8 ATA compared to control with a subsequent, although not statistically significant, increase in elimination half-life. There were no significant differences between the values observed at 6 ATA and either control or 2.8 ATA. As 100% O2 at 2.8 ATA is used during hyperbaric oxygen medical therapy and during decompression, this change in disposition of this commonly used agent may have implications in man. Studies in man must be conducted, however, to determine if the same conclusions apply.

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Hemodynamic effects of lactated Ringer's solution on hemorrhagic shock during exposure to hyperbaric air and hyperbaric hyperoxia.

Three groups of six dogs each were instrumented with an electromagnetic flow-meter around the pulmonary artery, and indwelling silastic cannulas in the pulmonary artery, the left ventricle, the ascending aorta and the right atrium. After allowing 5-7 d for recovery the dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA) breathing 100% oxygen (PO2 approximately equal to 2128 mm Hg) and at 6 ATA breathing air (PO2 approximately equal to 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Mean aortic pressure was maintained between 40-50 mm Hg for 30 min. Enough lactated Ringer's solution was then infused to stabilize the aortic pressure to within 90% of its original 1 ATA baseline value. Hemodynamic parameters were measured or calculated at eight different times. There were statistically significant differences in some of the measured parameters due to the effects of hemorrhage but no differences between the three groups attributable to either of the hyperbaric conditions or the effects of lactated Ringer's solution.

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Pharmacokinetics of pentobarbital under hyperbaric and hyperbaric hyperoxic conditions in the dog.

High hydrostatic pressure has been shown to reverse the anesthetic effects of barbiturates. However, attempts to distinguish between two possible causes of this reversal, changes in drug disposition or changes in drug-receptor interaction, have not been reported. This study examined the possible effects of hyperbaria and hyperbaric hyperoxia on the distribution and clearance of pentobarbital in the dog. The drug was administered to six mixed-breed dogs as a 30 mg/kg i.v. bolus at 1 ATA breathing air, 6 ATA breathing air, and 2.8 ATA breathing 100% oxygen, with serial blood sampling for 12 h. Pharmacokinetic and statistical analyses showed no significant effects of hyperbaria or hyperbaric hyperoxia on the total plasma clearance, volume of distribution or elimination half-life. If pressure reversal of barbiturate anesthesia occurs at these pressures, changes in the disposition of the drug are not the causative factors.

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Drug disposition under hyperbaric and hyperbaric hyperoxic conditions: meperidine in the dog.

Patients being treated for a variety of conditions with hyperbaria or hyperbaric hyperoxia, and ill or injured deep sea divers being decompressed, may require concomitant drug therapy. This study examined the possible effects of those conditions on the distribution and elimination of meperidine, using the dog as a model. The drug was administered to six mixed-breed dogs as a 1.4 mg/kg i.v. bolus at 1 ATA breathing air, at 2.8 ATA breathing 100% O2, and at 6 ATA breathing air, and followed by serial blood sampling for 3 h. Statistical analysis showed no effects of hyperbaria or hyperbaric hyperoxia on the elimination half-life, total plasma clearance, or volume of distribution. These studies demonstrated marked differences between man and the dog in the elimination of meperidine. This probably means these results cannot be extrapolated to man.

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Adverse cardiovascular effects of oxytetracycline preparations and vehicles in intact awake calves.

Comparisons were made of cardiovascular effects in intact, awake, previously instrumented calves given the following oxytetracycline (OXY) preparations and components: polyvinylpyrrolidine vehicle (PVP), OXY HCl in PVP (OXY-PVP), OXY HCl (USP) in saline solution, propylene glycol, 77.8% (PG), propylene glycol vehicle (PGV), and OXY HCl in PGV (OXY-PGV). The 3 preparations containing PG caused significant increases in pulmonary arterial pressures and significant decreases in cardiac output and stroke volume. Aortic pressures were significantly decreased, as were heart rates. Both pulmonic and systemic resistances were significantly increased. There were no direct effects measured on left ventricular contractility. The aqueous OXY caused no significant changes. The PVP preparation and vehicle caused no changes in pulmonary pressures, pulmonary resistance, cardiac output, or stroke volume. Significant increases were observed in aortic pressure, heart rate, and systemic resistance. Left ventricular contractility was not changed. Seemingly, the PG-induced changes were a result of histamine release which did not appear to be dependent on prior sensitization of the calves.

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Theophylline pharmacokinetics during hyperbaria and hyperbaric hyperoxia in the dog.

The effect of hyperbaria and hyperbaric hyperoxia on the disposition kinetics of theophylline were investigated in the dog. The drug was administered as a 5 mg/kg iv bolus at 1 atmospheres absolute (ATA), 2.8 ATA and 6 ATA. Serial blood samples were collected over an eight hour period and analyzed for theophylline concentration using a gas chromatographic method. From the resultant data, elimination half-life, volume of distribution and total body clearance were calculated. There were no apparent effects of hyperbaria or hyperbaric hyperoxia on any of the parameters describing theophylline disposition, implying that, in the animal model studied, distribution, elimination and effect should remain constant.

Animals↗