Rate In Rabbits Research Articles

Selection response of growth rate in rabbits for meat production

Genetic and environmental trends in 2 lines of rabbit (B and R) selected on individual weight gain (WG) from weaning (4 wk) to slaughter (11 wk) were estimated using mixed model methodology. Line B was derived from the California breed and line R was a synthetic of stock of different origin. The data were collected from a single herd and comprised 7 718 individuals in line B and 9 391 in line R, the lines having 12 and 9 generations of selection respectively. Realized responses in the 2 lines were 2.7% and 2.2% of the initial mean per year respectively and showed that selection on WG was effective but was less than expected. Selection on slaughter weight (SW) and effects of selection on other economic traits are discussed. It is concluded that selection on either WG or SW is a simple method for improving growth rate in rabbit sire line stocks.

Selection response of growth rate in rabbits for meat production

Selection response of growth rate in rabbits for meat production

Alveolar and lung liquid clearance in anesthetized rabbits

Alveolar and lung liquid clearance were studied over 8 h in intact anesthetized ventilated rabbits by instillation of either isosmolar Ringer lactate (2 ml/kg) or autologous plasma (2 or 3 ml/kg) into one lower lobe. The half time for lung liquid clearance of the isosmolar Ringer lactate was 3.3 h and that for plasma clearance was 6 h. In the plasma experiments, the alveolar protein concentration after 1 h was 5.2 +/- 0.8 g/dl, which was significantly greater than the initial instilled protein concentration of 4.3 +/- 0.7 g/dl (P less than 0.05). Thus alveolar protein concentration increased by 21 +/- 12% over 1 h, which matched clearance from the entire lung of 19 +/- 11% of the instilled volume. Overall the rate of alveolar and lung liquid clearance in rabbits was significantly faster than in prior studies in dogs and sheep. The fast alveolar liquid clearance rate in rabbits was not due to higher endogenous catecholamine release, because intravenous and alveolar (5 x 10(-5) M) propranolol did not slow the clearance. Also, beta-adrenergic therapy with alveolar terbutaline (10(-5) or 10(-4) M) did not increase the alveolar or lung liquid clearance rates. Phloridzin (10(-3) M) did not slow alveolar liquid clearance. However, amiloride (10(-4) M) inhibited 75% of the basal alveolar liquid clearance in rabbits, thus providing evidence that alveolar liquid clearance in rabbits depends primarily on sodium-dependent transport. This rabbit study provides further evidence for important species differences in the basal rates of alveolar liquid and solute clearance as well as the response to beta-adrenergic agonists and ion transport inhibitors.

Tissue plasminogen activator mutants lacking the growth factor domain and the first kringle domain: II: Enzymatic properties in plasma and in vivo thrombolytic activity and clearance rates in rabbits

The in vitro fibrinolytic activities and fibrin specificity in human plasma as well as in vivo fibrinolytic and pharmacokinetic properties in rabbits were studied for six genetically engineered variants of human tissue-type plasminogen activator (t-PA). All variants lacked the growth factor (G) domain and the first kringle (K1) domain and varied in the presence or absence of the finger (F) domain. Additional specific site modifications were Lys 277→Val and Asn 448→Gln. The variants were denoted K2P, K2P(Val277), K2P(Gln448), FK2P, FK2P(Val277) and FK2P(G1n448). The highest specific activity in vitro in a plasma clot lysis assay was observed for the wild type t-PA and decreased in the order FK2P(Val277)≈K2P(Val277)>FK2P≈K2P>K2P(Gln448)>FK2P(Gln448). All variants displayed a time lag phase of 30–60 min before fibrinolysis was detected. This lag phase was far less pronounced for the wild type molecule. The fibrin specificity of the variants in vitro was studied by analyses of clottable fibrinogen and consumption of α 2-antiplasmin after incubating human plasma with fibrinolytically equipotent doses of the different activators. Variants K2P(Val277) and FK2P(Val277) were as fibrin specific as t-PA, whereas K2P, FK2P and the non-glycosylated K2P(Gln448) consumed more fibrinogen and α 2-antiplasmin at fibrinolytically equipotent doses. However, all t-PA variants were more fibrin specific than streptokinase. The thrombolytic and pharmacokinetic properties of t-PA and five of the variants were examined in a rabbit jugular vein thrombosis model. The thrombolytic activity in vivo following a bolus injection of 0.3mg/kg was, in order of descent, K2P>FK2P>K2P(Val277)≈FK2P(Val277)>K2P(Gln448)≈rt-PA. Two of the variants and rt-PA were investigated at two additional doses (0.6 and 1.2mg/kg). Their ED 50 (dose required to lyse 50% of the thrombus within 3h), as calculated from the dose-response curve, were 1.4, 1.25 and 0.4 mg/kg for rt-PA, K2P(Val277) and K2P, respectively. When rt-PA and the variants were compared at equivalent doses (weight) the variants were found to cause a significantly higher consumption of fibrinogen and α 2-antiplasmin. However, when the compounds were compared at a thrombolytically equivalent dose the two most potent variants, K2P and FK2P, caused the same haemostatic effect as t-PA, whereas the less potent variants were found to have a reduced fibrin specificity in vivo. All of the variants had a significantly slower clearance and a longer plasma half-life compared to rt-PA. Differences in pharmacokinetic profile were also seen among the five variants, as those containing the finger domain had a faster clearance and a shorter half-life than those without the finger.

The effects of stimulation of the A5 region on blood pressure and heart rate in rabbits

The effects of stimulation of the A5 cell group of the caudal ventrolateral pons electrically or with L-glutamate on heart rate and blood pressure were determined in rabbits. Electrical stimulation caused blood pressure increases and reflex bradycardia. L-glutamate caused decreases in blood pressure and heart rate which were blocked by the L-glutamate antagonist aminophosphoheptanoic acid. Transection of the brainstem at the level of the midbrain did not alter the effects of either electrical or chemical stimulation. Lesions of the nucleus and tractus solitarius (NTS) attenuated the effects of L-glutamate, but did not change the effectiveness electrical stimulation. Injections of 6-hydroxydopamine three to four weeks before the experiments blocked the effects of electrical stimulation but only reduced the effects of L-glutamate injection. The A5 group may have two functional subdivisions. Some A5 cells may produce blood pressure depressor and bradycardiac effects by means of projections to the NTS and the spinal cord. Other A5 cells may produce blood pressure presser effects by means of projections to the spinal cord.

Corticosteroid action on choroid plexus: Reduction in Na+?K+-ATPase activity, choline transport capacity, and rate of CSF formation

Glucocorticoids have a well-known clinical effect on brain edema and intracranial hypertension, but the mechanism of action is still poorly understood. In the present report the effect of beta-methasone on choroid plexus transport and CSF formation was studied. Following 5 days of daily treatment with betamethasone the CSF production rate in rabbits was reduced by 43% as measured by ventriculo-cisternal perfusion with radioactive inulin. Accordingly, the transport capacity in the choroid plexus, measured in terms of choline uptake and accumulation in vitro, and the activity of Na+--K+-ATPase decreased in both rabbit (in the lateral ventricles by 31 and 31%, respectively) and rat (by 16 and 24%, respectively). Thus, the demonstrated influence of glucocorticoids on these functions of the choroid plexus seem to be important components in their therapeutic effect on intracranial hypertension.

Influence of antibiotic dose, dosing interval, and duration of therapy on outcome in experimental pneumococcal meningitis in rabbits.

We examined the influence of several pharmacokinetic parameters on cure rates in rabbits with experimental pneumococcal meningitis. When the duration of treatment was kept constant, cure rates improved as the individual dose of ampicillin was increased. On the other hand, when four doses of ampicillin at 60 mg/kg of body weight, producing peak concentrations in cerebrospinal fluid (CSF) of approximately 40 times the MBC, were administered at intervals of 24 instead of 4 h and the duration of therapy was thus prolonged from 12 to 72 h, cure rates also increased (85 versus 25%; P less than 0.01). These high cure rates were achieved even though bacterial titers in CSF 24 h after the first dose had reached levels similar to those present at the beginning of therapy. Cure in these animals was explained by the fact that the second ampicillin dose reduced bacterial titers in CSF significantly more than did the first dose (5.2 versus 2.5 log10 CFU/ml; P less than 0.02). The clinical relevance of these observations remains to be determined.

Comparison between rabbits and beagle dogs of sustained-release effect of gelatin microcapsules containing piretanide

To use piretanide, a commercially available loop diuretic, as a long-acting antihypertensiue agent, we attempted to prepare it in sustained-release form by microencapsulation using gelatin. Gelatin microcapsules of piretanide were administered to rabbits and beagle dogs for pharmacokinetic evaluation, taking the gastrointestinal transit rate into consideration. Commercial piretanide tablets were used as control and treated in the same manner. The rate-determining steps were the gastrointestinal absorption process for the tablets and the drug-release process for the microcapsules in both animal species. Drug mobility in the gastrointestinal tract was considerably faster in dogs than in rabbits, but there was almost no difference between the two species in the amount of drug which remained unabsorbed in the gastrointestinal tract. As a result, gelatin microcapsules of piretanide showed satisfactory sustained-release properties in beagle dogs, although control of the drug release rate in rabbits could not be clearly evaluated.

Effects of opiate manipulations on latent inhibition in rabbits: Sensitivity of the medial septal region to intracranial treatments.

The effects of opiate manipulations were examined on latent inhibition of classically conditioned heart rate in rabbits. Animals were exposed to an auditory stimulus that was later used as a conditioned stimulus (CS). Administration of the agonist levorphanol into the medial septal region either preceding or immediately following CS preexposure sessions attenuated latent inhibition of the conditioned response. This effect was observed in animals that showed no change in long-term retention of habituation. Administration of levorphanol into the central nucleus of the amygdala, a sensitive site for opiate manipulations on aversive conditioning tasks, was ineffective. Further analysis of the effect obtained within the septal region revealed pharmacological specificity. The effect of posttraining levorphanol was also time dependent and exhibited neuroanatomical specificity. Posttraining opiate antagonist administration into the medial septum produced a modest augmentation of latent inhibition. The medial septal region appears to provide a site where opiate manipulations alter some aspect of retention for events that occur in the absence of reinforcement.

生体の電気的諸現象に及ぼすキンドリンク効果の影響(第3報)

An electrophysiological study was made on the change of heart rate in rabbits which were experimentally kindled either in amygdaloid nucleus, hippocampus, septal nucleus or cerebral cortex. The results obtained were as follows.(1) After each stimulation, heart r ate decreased in every kindled group. The decrease of heart rate was most clearly seen in the amygdaloid nucleus-kindled group, followed by the hippocampus-, the cerebral cortex- and the septal nucleus-kindled group in that order.(2) Heart rate between stimulations remained unchanged in the amygdaloid- an d the septal nucleus-kindled group, while it increased in the hippocampus-kindled group. Namely, there was observed permanent change of the heart rate in the hippocampus- and cerebral cortexkindled groups.(3) B ased on the above results, it can be concluded that kindling phenomena produce permanent changes on the autonomic nervous system and the cardiac function as well. Accordingly, kindling phenomena are suggested to be eligible for an experimental model for cardiovascular symptoms caused by imbalance of the autonomic nervous system.

Effects of intravenous infusion of doxorubicin on blood chemistry, blood pressure and heart rate in rabbits.

The effects of a 1 h continuous infusion of doxorubicin (12.5 mg kg-1, 200 mg M-2) on blood chemistry was examined in rabbits over a 6-h period. Plasma glucose levels remained unchanged while insulin levels were significantly decreased to 39, 45 and 61% of the zero time value (12.8 +/- 2.9 ng ml-1) at 30, 60 and 120 min, respectively, after starting the drug infusion. Plasma cortisol levels were increased to 141, 140 and 131% of the initial zero time value (12.3 +/- 2.2 ng ml-1) at 120, 240 and 360 min, respectively. Doxorubicin had no effect on plasma electrolytes, osmolality and urea nitrogen but significantly increased plasma creatinine over the corresponding control value (2.2 +/- 0.8 micrograms ml-1 to 4.9 +/- 0.7 micrograms ml-1) at 120 min and the level remained elevated for the remaining period of the study. Systolic and diastolic pressure, and heart rate were also depressed at 240 and 360 min. The data collected in the present study indicate that the doxorubicin infusion might have a direct effect on beta cells in the pancreas as well as muscle tissue. Changes in cortisol, blood pressure and heart rate appear to be secondary to other effects produced by doxorubicin.

In vitro and in vivo release of levonorgestrel from poly(ortho esters) : I. Linear polymers

The in vitro and in vivo release of levonorgestrel from linear poly(ortho ester) cylindrical devices containing 30 wt.% drug and 2 wt.% calcium lactate was studied. The in vitro release rate was a relatively constant 20 μg/day for about one year at which time the experiment was discontinued. The in vivo release rate in rabbits was about 33 μg/day. In both studies rate of polymer erosion is about the same and significantly leads rate of drug release. Therefore, factors other than polymer erosion determine rate of drug release. SEM studies of devices explanted from rabbits show the formation of a foamed drug layer surrounding the device. The formation of this layer is caused by polymer erosion around undissolved drug. Rate of drug delivery from the device is controlled by dissolution of levonorgestrel from the outside of the foamed drug layer. The higher in vivo release is attributed to the presence of lipophilic species that facilitate dissolution of levonorgestrel.

In vitro and in vivo release of levonorgestrel from poly(ortho esters) : II. Crosslinked polymers

The in vitro and in vivo release of levonorgestrel from crosslinked poly(ortho ester) cylindrical devices containing 30 wt.% drug and 7.1 wt.% Mg(OH) 2 was studied. For reasons not entirely understood, hydrolysis rates of crosslinked poly(ortho ester) are faster than hydrolysis of linear polymers. The in vitro release rate of levonorgestrel was about 10 μg/day for 160 days at which point the experiment was discontinued. The in vivo levonorgestrel release rate in rabbits from identical devices was about 20 μg/day. In the in vitro studies polymer erosion leads drug release but in vivo release of levonorgestrel is fast enough so that concomitant polymer erosion and drug release take place. SEM examination of devices explanted from rabbits are consistent with a surface erosion process.

Effects of prostaglandins on intraocular pressure recovery rate in rabbits

The actions of a number of prostaglandins (PGs) were studied in unanesthetized rabbits using an intraocular pressure (IOP) recovery-rate method. In topical doses of 0.1 to 10 μg, these compounds accelerated the rate at which IOP returned to control levels after an infusion of hypertonic saline. In general, PGE 1 appeared more potent than the other PGs at these doses. Arachidonic acid also increased the IOP recovery rate. The effect of arachidonic acid was completely blocked by the cyclooxygenase inhibitor indomethacin. Recovery rate responses to arachidonic acid were increased further after pretreatment with the lipoxygenase inhibitor phenidone. When administered alone, phenidone itself accelerated IOP recovery; this action was also blocked by indomethacin. The IOP recovery rate method appears to be a useful tool for studying ocular effects of PGs and other products or inhibitors of arachidonic acid metabolism.

Increased numbers of sperm in the oviducts and improved fertilization rates in rabbits after administration of phenylephrine or ergonovine near the time of insemination.

Phenylephrine, an alpha-adrenoceptor agonist, was administered im to does near the time of mating or insemination. The treatment increased sperm numbers in the oviducts by about 50-fold and in the uterus by about 10-fold at 2 or 2.5 h after insemination. Methoxamine, another alpha-adrenoceptor agonist that was given im, did not increase sperm numbers, although both phenylephrine' and methoxamine significantly increased the number and amplitude of uterine contractions when contractions were measured by strain gauge force transducers attached to the uterus of conscious does. Ergonovine, an ergot derivative given im, increased sperm numbers more than 10-fold in the oviducts and five to 10-fold in the uterus at 2 or 2.5 h after insemination. Ergonovine increased the frequency and amplitude of uterine contractions when given iv but not when given im. In tests with a range of doses of phenylephrine and ergonovine, 5 mg of phenylephrine and .6 mg of ergonovine appeared to be near optimal for maximizing the number of sperm in the uterus and oviducts at 2.5 h after insemination. Phenoxybenzamine, an alpha-adrenoceptor blocking agent, prevented the phenylephrine-induced increases in both uterine contractions and sperm numbers in the oviducts and uterus. Phenoxybenzamine also prevented the effect of ergonovine on sperm numbers. In does inseminated with low numbers of sperm (92,000; an inseminate selected to result in a low fertilization rate in control does), the administration of phenylephrine or ergonovine significantly increased ovum fertilization rates (16% for control does, 52 and 63%, respectively, for phenylephrine- and ergonovine-treated does).

Effect of prostaglandin inhibition on glomerular filtration rate in normal and uremic rabbits

Studies were performed to assess the effect of alterations in prostaglandin biosynthesis on glomerular filtration rate in rabbits with normal renal function and after surgical reduction of renal mass. In normal animals, the administration of either of two cyclo-oxygenase inhibitors resulted in a 53% reduction in urine prostaglandin E excretion, but no change in creatinine clearance. Creatinine clearance rates were almost 71% lower in the uremic animals when compared to the animals with normal renal function. Despite the reduction in renal mass, urine prostaglandin E excretion rates in the uremic animals were over twice that seen in normal rabbits. When factored by either glomerular filtration rate or remaining renal mass, urine prostaglandin E excretion rates in uremic rabbits when compared to normal animals were increased more than 9-times and 4-times respectively. Administration of cyclo-oxygenase inhibitors in the uremic animals resulted in a 71% decrease in urine prostaglandin E excretion and, unlike the non-uremic animals, a 53% fall in creatinine clearance. These findings suggest that intact renal prostaglandin biosynthesis is a necessary factor in the homeostatic adaptive mechanisms which maintain the glomerular filtration rate in animals with decreased renal mass.

Microwave Radiation and Heat-Beat Rate of Rabbits

Each of three adult New Zealand rabbits, 2 male and 1 female albinos, was exposed dorsally or ventrally, to 2450-MHz plane waves for 20 min under each of several field conditions: 1) to continuous waves (CW) at 5 mW/cm2; 2) to pulsed waves (PW) of 1-microsecond width that recurred 700 pps at an average of 5 mW/cm2 and at a peak of 7.1 W/cm2; 3) to PW of 10-microseconds width at a peak of 13.7 W/cm2 that were synchronized with and triggered by the R wave of the electrocardiogram (EKG) at various delay times (0, 100, and 200 ms; and 4) to CW at 80 mW/cm2. Carbon-loaded Teflon electrodes were used to record the EKG from forelimbs of an animal before, during, and after irradiation whilst it was maintained in a constant exposure geometry in a wooden squeeze box. Field induced changes in the heart-beat rate were observed at 80 mW/cm2 but not a lower average power densities, although a peak positive chronotropic effect might have been occasioned by PM introduced at 100 and 200 ms after the R wave peak. No cumulative effect was observed over a period of four months. Thermographic analysis revealed relatively little absorption of microwave energy by the myocardium irrespective of anatomical aspect of exposure.

Effect of Dibenzyline on Blood Pressure, Heart Rate snd Respiratory Rate in Rabbits During Increased Intraeranial Pressure

Effect of Dibenzyline on Blood Pressure, Heart Rate snd Respiratory Rate in Rabbits During Increased Intraeranial Pressure

Turnover of Sodium and Water by Free-Living Rabbits, Oryctolagus Cuniculus.

Four places in New South Wales were chosen that had a permanent water supply and vegetation with very low or very high Na content, or no surface water during the study and medium, or low to medium, Na content. Wild rabbits (Oryctolagus cuniculus) were caught in those places, given 22NaCl and 3H2O by intraperitoneal injection and held for 4 to 5 h, then blood samples were taken and the rabbits were weighed, marked and released at the point of capture. After another 8 to 23 days they were recaptured and weighed, and blood samples were taken. Between the 7 or 8 values for different places and dates, mean bodyweight ranged from 937 to 1650 g, exchangeable Na from 37.37 to 50.10 mEq/kg bodyweight or 48.78 to 67.93 mEq/litre body water, Na turnover from 0.51 to 13.95 mEq/kg bodyweight daily, Na biological half-life from 2.3 to 55.0 days, total body water 677 to 777 ml/kg, water turnover 88 to 375 ml/kg daily and water half-life 1.4 to 5.6 days. Mean values are for groups of 4 to 25 rabbits. Between the 4 places, water content of vegetation ranged from 142 to 832 mg/kg fresh vegetation and, including 2 sites at one of the 4 places, Na content ranged from 0.51 to 20.98 mEq/kg fresh and 2.41 to 124.9 mEq/kg dry matter. There was a positive linear relation between Na in fresh vegetation and Na turnover rate in rabbits. The relation between water content of vegetation and water turnover in rabbits was not precise, because probably of such factors as diet selection, rain and accessibility and use of water. Lactation may have a strong effect on rabbits when water or Na is scarce, because rabbits may not ingest the faeces and urine of their young like other animals.Low rate of water turnover, especially after metabolic weight correction, demonstrated the efficiency of water conservation of rabbits and partly explained their success in dry places. Published values for other species are compared. Food items were not identified in the present work, but identification and analysis of their Na content would allow qualitative calculation of the food intake of free-living herbivores from their Na turnover.

Effect of diazepam on properties of the erythrocyte-plasma proteins complex and the development of shock after heterologous blood transfusion

Preliminary injection of 2 mg/kg diazepam abolishes the pyrogenic reaction and increases the survival rate of rabbits after intravenous injection of cat blood. A study of the physicochemical properties of the blood by measurement of the ionization equilibrium during thermal denaturation showed that injection of heterologous blood into rabbits and suspending rabbit's erythrocytes in cat's plasma in vitro lead to a sharp decrease in the rate of proton binding by the plasma protein in the presence of the foreign erythrocytes. Preliminary injection of diazepam to the rabbits and addition of diazepam to the cat's plasma in vitro prevent these changes and enable the blood to retain its native properties. Addition of diazepam in a concentration of about 10−4 M to heterologous plasma considerably reduces erythrocyte agglutination.