Cannula In Rats Research Articles

Corn Oil, Palm Oil and Butterfat Fractions Affect Postprandial Lipemia and Lipoprotein Lipase in Meal-Fed Rats

Our objective was to investigate the time course of postprandial lipemia and lipolytic activity in male Sprague-Dawley rats trained to eat meals containing butterfat fractions, palm oil or corn oil. Baseline and postprandial blood samples were obtained via a carotid cannula in rats fed the experimental diets for 4 wk. Rats fed saturated fats compared with corn oil showed a significantly greater peak increase in postprandial triacylglycerol concentrations. Corn oil ingestion resulted in significantly lower concentrations of cholesterol and triacylglycerol in plasma and significantly less triacylglycerol accumulation (millimoles per liter per 24 h) compared with ingestion of saturated fats. Postheparin plasma lipoprotein lipase activity and plasma insulin concentration were generally greater with ingestion of corn oil compared with palm oil or butterfat. Palm oil ingestion resulted in a biphasic plasma triacylglycerol response curve and greater postheparin plasma lipoprotein lipase activity compared with butterfat ingestion, suggesting differential effects of saturated fats on postprandial lipemia. Our results indicate that greater postprandial lipemia with ingestion of saturated fats compared with corn oil may be due in part to slower plasma triacylglycerol clearance.

Uncovering the contribution of enhanced central gain and altered cortical oscillations to tinnitus generation.

Various theories and their associated mechanisms have been proposed as the neural basis of phantom sound perception (tinnitus), including central gain enhancement and altered cortical oscillations. However, it remains unknown whether these cortical changes directly cause tinnitus, or simply coexist with the phantom percept. Using chronically-implanted electrodes and drug delivery cannulae in rats, we examined whether enhanced central gain and cortical oscillations are consistent across different tinnitus induction methods (noise exposure; salicylate), and if directly-inducing enhanced central gain or altered cortical oscillations via pharmacologic manipulation of inhibition along the auditory pathway would cause behavioral evidence of tinnitus. We show that, while there appeared to be no clear link between tinnitus and the presence of enhanced sound-evoked cortical activity or altered spontaneous cortical oscillations, pharmacologic impairment of GABAergic neurotransmission in the auditory cortex was sufficient to cause tinnitus; collective findings which further advance our understanding of the neural basis of tinnitus.

Intralesionally implanted cisplatin plus systemic carmustine for the treatment of brain tumor in rats.

The benefit of conventional chemotherapy for the treatment of malignant brain tumors, although limited, is real. A major obstacle in the treatment of these lesions is the ability to deliver drug across the blood-brain barrier (BBB). Local drug implantation, circumventing the BBB, has been a useful strategy for treatment of intracranial lesions, and may work synergistically with systemic chemotherapy. To test this hypothesis, either intraperitoneal (i.p.) carmustine or cisplatin was combined with the intracranial (i.c.) administration of polymer-delivered cisplatin in rats with intracranial tumors. 9L gliosarcoma tumor cells (5 x 10(3)) were administered through a right frontal lobe cannula in rats 7 days prior to treatments. Cisplatin-loaded biodegradable polymer was then administered via the cannula, with free cisplatin or carmustine injected i.p. Animals were monitored for 60 days post-treatment. In experiment 1, i.c. cisplatin at a dose of 0.5, 1.0, 2.0, and 4.0 mg/m2 resulted in a mean survival time of 34 +/- 3, 39 +/- 14, 47 +/- 11, and 31 +/- 20 days (MST +/- SD), respectively, compared to 26 +/- 4 days in the control group and 30 +/- 7 days in the group treated with 50 mg/m2 i.p. free cisplatin. In experiment 2, i.p. free cisplatin at 25, 40, 50, and 100 mg/m2 resulted in a MST of 28 +/- 3, 30 +/- 4, 32 +/- 3, and 14 +/- 8 days, respectively, compared to 26 +/- 1 days in the control group. In experiment 3, the MST in the groups treated with 0.5 mg/m2 of i.c. cisplatin, 25 mg/m2 of i.p. cisplatin, 10 mg/kg of i.p. carmustine, i.c. cisplatin (0.5 mg/m2) plus i.p. cisplatin (25 mg/m2), and i.c. cisplatin (0.5 mg/m2) plus i.p. carmustine (10 mg/kg) was 30 +/- 4 days (P > 0.05), 28 +/- 2 (P > 0.05), 36 +/- 4 (P < 0.01), 32 +/- 3 (P < 0.01), and 50 +/- 11 days (P < 0.01), respectively, compared to the tumor control group (26 +/- 1 days). Long-term survivors (29%) were seen only in the i.c. cisplatin plus i.p. carmustine group. Additive toxicity was not observed. Intralesional polymer-delivered (i.c.) cisplatin plus systemic (i.p.) carmustine is highly effective for the treatment of intracranial 9L gliosarcoma in tumors.

The pharmacokinetics and liver metabolism of N-hydroxy-3, 4-methylenedioxyamphetamine (NOH MDA) in rats

The metabolism and disposition of N-hydroxy- 3, 4-methylenedioxyamphetamine (NOH MDA) was studied by utilizing rat liver slices as well as by intravenous pharmacokinetic studies in rats. In the liver slice experiments, NOH MDA (16 μg/ml) was incubated with rat liver slices and the disappearance of NOH MDA and the appearance of MDA were observed over 2 hours. Drug and metabolites were assayed by a reverse phase high performance liquid chromatographic procedure including a C8 column and UV detection. NOH MDA disappeared from the plasma at an apparent first-order rate with a t1 2 of 36.3+/− 8.4 min. By the end of 2 hours, approximately 85% of the NOH MDA was biotransformed to MDA. Following placement of jugular cannulas in rats, a dose of 15 mg/kg of NOH MDA was administered intravenously. With rapid blood sampling, a t1 2 of 0.86+/−0.12 min was observed for NOH MDA. A total body clearance of 9.09+/−2.06 L/hr/kg and a volume of distribution of 0.184+/−0.022 L/kg were noted. Plasma concentrations of MDA were observed after the NOH MDA dose to rats. The MDA t1 2 after NOH MDA dosing was 1.68+/−0.29 hours with peak plasma concentrations at 8 min. No other major metabolites could be detected in liver slice, plasma, or urine samples. Both sets of studies demonstrate the rapid conversion of NOH MDA to MDA in rats.

Pharmacological evidence for involvement of the sympathetic nervous system in the increase in renin secretion produced by a low sodium diet in rats

To determine the degree to which increased sympathetic activity contributes to the increase in renin secretion produced by a low sodium diet, the β-adrenergic blocking drug propranolol or saline vehicle was injected through indwelling jugular cannulas in rats fed a normal diet and rats fed a low sodium diet for 9 days. Plasma renin activity (PRA) and plasma renin concentration (PRC) were elevated by the low sodium diet, and these values were reduced 42–45% by propranolol, although they were still higher than in the normal diet controls. Plasma corticosterone was moderately elevated in cannulated rats on regular diet, compared to decapitated controls, but corticosterone did not differ between cannulated and decapitated rats on low salt diet; propranolol reduced plasma corticosterone. However, PRA and PRC were comparable in cannulated rats and decapitated controls on both the normal and the low sodium diets, and propranolol did not produce a significant reduction in PRA and PRC in rats fed the normal diet. This indicates that the effects of propranolol on PRA and PRC in the low sodium rats were not simply due to reduction of a stress-induced increase in renin secretion. The results indicate that increased sympathetic activity makes a substantial contribution to the increase in renin secretion produced by 9 days of dietary sodium restriction.

The use of a silastic shield to protect an externalized biliary cannula

A simple shield made of a folded silastic sheet is described for the protection of the externalized portion of a permanent biliary cannula in rats. Advantages of this shield are its light weight, flexibility, transparency, and ease of resealing for repeated interruption of hepatobiliary circulation. Since the shield is positioned around rather than being a segment of the cannula, a single length of tubing can be used.

A technique for collecting cerebrospinal fluid using an intraventricular cannula in rats

The difficulty in obtaining cerebrospinal fluid (CSF) in an efficient and simple manner in rats prompts us to introduce a new technique that makes use of a cannula placed in the lateral ventricle. The cannula is implanted with a stereotaxic apparatus and the CSF is collected with a glass capillary tube. The technique has proved to work well for experiments in which the CSF must be free of blood. It also permits the collection of volumes of CSF sufficient for radioimmunoassays, and may be used in chronic experiments.

A quantitative evaluation of stress associated with indwelling superior vena cava cannulae in rats

“Nonrestraining” superior vena cava (SVC) cannulae are commonly used in rat metabolic studies. The objective of this study was to evaluate the level of stress and metabolic alterations associated with surgical placement and subsequent maintenance and use of an indwelling intravenous cannula as measured by resting energy expenditure (REE), respiratory quotient (RQ), urinary nitrogen excretion, and substrate utilization pattern. Nine rats underwent SVC cannulation and six rats underwent sham operation. Postoperatively, animals were starved for 48 hr and then refed either parenterally or orally for 48 hr. Sham-operated animals adapted appropriately to starvation within 24 hr by decreasing REE 14% and increasing utilization of fat (RQ:0.89 → 0.78). Hypometabolic adaptation to starvation was delayed in cannulated animals until the second postoperative day, but appropriate alterations in energy substrate utilization were not affected by the presence of cannulae. Cannulae did not affect the metabolic response to oral refeeding with similar increases in REE and similar patterns of substrate utilization in sham-operated and cannulated animals. Animals refed parenterally demonstrated higher REE and apparent fat deposition (RQ > 1) consistent with continuous hypercaloric glucose administration. Urinary nitrogen excretion was not affected by the presence of cannulae. Cannula-associated metabolic alterations are minimal and transient and do not preclude detection and quantification of alterations associated with composition or utilization of exogenous substrates.

Chronic arterial and venous catheterization of conscious, unrestrained rats.

A method is described for implanting arterial and venous cannulas in rats that requires only minor surgery. Catheters are introduced into the abdominal aorta through the ventral tail artery and into the vena cava through a lateral tail vein. The wounds are covered with an acrylic cuff and the catheters are brought out through a stainless steel spiral connected to the cuff and then attached to top of a metabolism cage used to house the rat. This method makes possible continuous access to the catheters in undisturbed, mobile animals. Using this model we compared mean arterial pressure, heart rate, plasma renin activity, and plasma catecholamine levels in freely moving Long-Evans rats and in Brattleboro homozygous rats.

Comparative features of Starling-lymphatic interaction at the pleural level in mammals.

Pleural liquid pressure was measured with saline-filled cannulas in rats, rabbits, cats, pups (4-5 days and 2 mo), small and large dogs, and pigs. On both the costal and mediastinal sides pleural liquid pressure at a level corresponding to the tricuspid valve decreased with increasing body mass; because this behavior was more marked on the mediastinal than on the costal side, a horizontal costomediastinal pleural liquid pressure gradient developed. No differences in liquid pressure were found in animals of different age but of similar size. The protein concentration and the volume-to-body weight ratio of the collected pleural liquid were also found to decrease with increasing body mass. For plasma colloid osmotic pressure, no size-related differences in the Starling balance seem to occur on costal side, whereas such balance shifts toward filtration at mediastinal level with increasing body mass. The lower liquid pressure found with increasing body mass is discussed in terms of lower conductance of the mesothelia and possibly greater lymphatic action. In terms of the Starling-lymphatic interaction we suggest that lymphatics can generate a pressure only slightly lower than that reflecting the equilibrium of the Starling balance of forces.

Stimulation of rat pancreatic enzyme secretion by diet components.

The stimulation of pancreatic enzymesecretion by diet components was investigated with a pancreatic duct cannula in rats. The infusion of casein into the duodenumresulted in a marked stimulation of the enzymesecretion. Onthe contrary, an aminoacid mixture simulated casein composition had no effect. Someoligopeptides, starch, sucrose, glucose, soybean oil and other commondiet componentsalso did not stimulate pancreatic enzymesecretion. A dose-response relationship was observed between the protein infusion level and the stimulation intensity of pancreatic enzyme secretion. Synthetic substrates for trypsin, tosyl-arginine methyl ester and benzoyl-arginine-p-nitroanilide, and for chymotrypsin, benzoyl-tyrosine ethyl ester, stimulated the enzyme secretion as well as casein; however, a typical substrate for aminopeptidase, leucine-p- nitroanilide, had no effect. These findings suggest that the substrates for pancreatic proteases can act primarily as secretagogues amongmanydiet components. The ability as a secretagogue was more potent in casein than a-lactalbumin. Native ovalbumin was hardly digested by pancreatin in vitro. However, mild heat-denaturation of this protein considerably improved both its digestibility and ability as a secretagogue. It can be explained that mild heat-denaturation of the protein improves its availability as a substrate for pancreatic protease. Based on these results, a mechanismby which substrate protein is recognized for pancreatic enzymesecretion in the rat intestine is discussed.

A rapid and convenient freehand method for the implantation of cerebroventricular cannulae in rats

The technique of implantation of permanent cannulae, allowing the acute or chronic infusion of solutions into the ventricular system of animals, has been widely used in studies of central nervous system function. Many methods have been published describing the manufacture of cannula systems suitable for intraventricular or intracerebral drug administration in the rat (Myers, 1971; Sparkes and Spencer, 1971; Ott et al., 1974; Rezek and Havlicek, 1975; Malkinson et al., 1977; Crane and Click, 1979). Although such systems can be economical and simple to manufacture, they all suffer from the disadvantage that the implantation technique, generally using conventional stereotaxic methods, is very time-consuming. This greatly limits the number of animals that can readily be prepared by a single worker, which can seriously restrict the application of intracerebroventricular (icv) administration techniques in experiments requiring relatively large numbers of animals. The procedure for implantation of cannulae actually practiced varies from laboratory to laboratory and it is hard to find useful tips and hints. Rather, the details of technique are determined by tradition and acquired by word of mouth; some methods practiced involve the totally freehand implantation of cannula guides, with accuracy being sacrificed for volume of output. In order to ensure the regular production of a sufficiently large number of cannulated animals for behavioral studies, we have created a simple, semifreehand cannulation method which offers the advantages of good accuracy and reproducibility, while taking much less time than more thorough techniques. In the present paper, we describe this rapid technique in sufficient detail to enable its easy implementation. Results of histological studies are also presented.

Metabolism of 3H-dopamine continuously perfused through push-pull cannulas in rats' brains: Modification by amphetamine or prostaglandin F 2α

Using perfusion cannulas implanted in the lateral cerebroventricles, the metabolism of a trace concentration of 3H-dopamine, continuously presented, was investigated in rats performing an operant for food reinforcement. The subjects were mature, drug-naive, male Long-Evans rats. Perfusate contained measurable quantities of 3H-3,4-dihydroxyphenylacetic acid ( 3H-DOPAC), 3H-3-methoxy-4-hydroxyphenylacetic acid ( 3H-homovanillic acid, 3H-HVA), 3H-3-methoxytyramine ( 3H-3-MT) and the 3H-noradrenaline metabolite, 3H-3-methoxy-4-hydroxyphenylethyleneglycol ( 3H-MHPG). Systemic injection of d-(1.5 mg/kg) or 1-(3.0 mg/kg) amphetamine resulted in decreased quantities of 3H-DOPAC, 3H-HVA and 3H-MHPG in perfusate with a concurrent decrease in fixed-ratio 20 behavior. Addition of prostaglandin F 2α (10 ng/μl perfused at a rate of 10 μl/minute) had no effect on the rats' fixed-ratio 20 behavior or rectal temperature, but resulted in decreased quantities of 3H-DOPAC, 3H-HVA and 3H-MHPG in perfusate. It is concluded that this methodology allowed us to monitor drug-induced changes in CNS dopaminergic and noradrenergic function in conscious rats engaged in schedule-controlled operant behavior. Furthermore, a trace concentration of PGF 2α in perfusion medium caused changes in 3H-dopamine metabolism in a manner similar to that of systemically administered amphetamines.

A technique for multiple, high-rate blood samplings via an external cannula in rats

A method for obtaining multiple, high-rate blood sample collections from rats without the use of anesthesia and anticoagulant is described. The surgical procedure consists of a bypass of the carotid via a cannula; this cannula forms a loop above the rat's head and is available for blood sampling. The method permits the investigation of high-frequency oscillations in blood components of rat.

Regional distribution of ethanol in rat brain

The cerebral distribution of a low ip dose of ethanol (ETOH) was studied using a double-barrelled, membrane-tipped perfusion cannula in rats. The cannulas were perfused with physiological solution in freely-moving animals at a rate of 19 μl/min for 5 min at 5, 10, and 15 min and subsequently at 15 min intervals for the remainder of 2 hrs after 1 g/kg ETOH. Peak blood ETOH levels (in mg/ 100 ml) after the single dose were 4 times those found in the lateral ventricle, 6–7 times those found in the reticular formation, cerebral cortex, and amygdala, and 9–11 times those found in the caudate and lateral hypothalamus. Peak levels were reached earliest in the lateral ventricle and reticular formation. In a related study, homogenized (“whole”) brain ETOH levels were found to be similar to blood levels while flushed (“bloodless”) brain ETOH levels were approximately 20% lower than those found in blood and “whole” brain. It is concluded that there is a significant differential distribution of ETOH in the rat brain after a low dose of ETOH, and that this unequal brain ETOH distribution may influence the behavioral effects of the drug.