Radiotelemetry Transmitters Research Articles

Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

Increased plasma osmolality elevates mean arterial pressure (MAP) through activation of the sympathetic nervous system, but the neurotransmitters released in the spinal cord to regulate MAP during osmotic stress remain unresolved. Glutamatergic neurons of the rostral ventrolateral medulla project to sympathetic preganglionic neurons in the spinal cord and are likely activated during conditions of osmotic stress; however, this has not been examined in conscious rats. This study investigated whether increased MAP during chronic osmotic stress depends on activation of spinal glutamate receptors. Rats were chronically instrumented with an indwelling intrathecal (i.t.) catheter for antagonist delivery to the spinal cord and a radiotelemetry transmitter for continuous monitoring of MAP and heart rate. Osmotic stress induced by 48 h of water deprivation (WD) increased MAP by ~15 mmHg. Intrathecal kynurenic acid, a nonspecific antagonist of ionotropic glutamate receptors, decreased MAP significantly more after 48 h of WD compared with the water-replete state. Water-deprived rats also showed a greater fall in MAP in response to i.t. 2-amino-5-phosphonovalerate. Finally, i.t. kynurenic acid also decreased MAP more in an osmotically driven model of neurogenic hypertension, the DOCA-salt rat, compared with normotensive controls. Our results suggest that spinally released glutamate mediates increased MAP during 48-h WD and DOCA-salt hypertension.

Abstract 635: Knockdown Of Tyrosine Hydroxylase In The Nucleus Of The Solitary Tract (NTS) Reduces Persistent Increase In Blood Pressure During Chronic Intermittent Hypoxia (CIH)

A2 neurons in caudal NTS express tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and respond to stressors such as hypoxia. We tested the hypothesis that TH knockdown in NTS reduces cardiovascular responses to CIH, an animal model that mimics the arterial hypoxemia observed during sleep apnea in humans. Adult male Sprague-Dawley rats were implanted with radiotelemetry transmitters and adeno-associated viral constructs (GeneDetect, Inc) with a GFP reporter having either short hair-pin RNA for TH (shRNA) or scrambled virus (scRNA) were injected into caudal NTS. A group of no injection, no CIH (control) rats were also used. Baseline mean arterial pressure (MAP) and heart rate (HR) were collected from all 3 groups for at least 4 days after which the virus injected rats were exposed to 7 days CIH (alternating 3 min periods of 10% O2 and 21% O2 from 8am to 4pm; from 4pm to 8am the rats were exposed to 21% O2). In shRNA injected rats (n=9) 7 day exposure to CIH increased MAP and HR during the day by 6.6±1.8 mmHg and 49.9±7.7 bpm and during the night by 0.3±1.8 mmHg and -4.5±1.3 bpm compared to baseline. In scRNA injected rats (n=10) 7 day exposure to CIH increased MAP and HR during the day by 7.7±1.2 mmHg and 65.3±7.9 bpm and during the night by 4.8±1.5 mmHg and 0.0±4.9 bpm compared to baseline. In control rats (n=8) MAP and HR were 1.5±1.0 mmHg and -8.4±3.8 bpm during the day and 1.8±0.9 mmHg and -10.8±2.9 bpm during the night compared to baseline. CIH induced significant changes in MAP and HR during the day in both the scRNA (p=.006 MAP; p<.001 HR) and shRNA (p=.007 MAP; p<.001 HR) groups. Compared to control rats, during the night CIH induced significant changes in MAP in the scRNA rats (p=0.02) but not in the shRNA group and no significant changes in HR in either group. The number of TH-immunoreactive neurons was reduced by 20% in sections with GFP fluorescence; shRNA 28±1 cells/section compared to scRNA 35±1 cells/section (p=.005). CIH induces an increase in MAP that persists beyond the period of exposure to CIH. Knockdown of TH in the NTS reduces this persistent increase in MAP induced by exposure to CIH. This indicates that NTS A2 neurons play a role in the cardiovascular responses to CIH and suggests they may play a similar role in the pathology of sleep apnea in humans.

Abstract 291: Antihypertensive Effect Of Bia 5-1058 a New Selective Peripheral Dopamine β-hydroxylase Inhibitor

The sympathetic nervous system can alter blood pressure by modulation of cardiac output, peripheral vascular resistance and renal function. One strategy for controlling sympathetic nerve function is to reduce the biosynthesis of norepinephrine (NE) via inhibition of dopamine β-hydroxylase (DβH; EC 1.14.17.1 ), the enzyme that catalyses the conversion of dopamine (DA) to NE in sympathetic nerves. BIA 5-1058 is a reversible DβH inhibitor that decreases NE levels in peripheral sympathetically innervated tissues slowing down sympathetic nervous system drive, without effect in brain tissues. In freely moving SHR implanted with radio-telemetry transmitters single administration of BIA 5-1058 showed a dose (3, 30 and 100 mg/Kg) and time dependent effect on blood pressure with no significant effect on heart rate (HR) and total activity monitored over a 96-hour period. The maximum reduction on systolic blood pressure (SBP) was -10.8, -21.1 and -35.2 mmHg for 3, 30 and 100 mg/Kg, respectively and the maximum reduction on diastolic blood pressure (DBP) was -9.9, -18.4 and -24.8 mmHg for 3, 30 and 100 mg/Kg, respectively. The antihypertensive effect of BIA 5-1058 (30 mg/Kg) was further evaluated in combination with efficacious doses of well-known antihypertensive drugs, like the ACE inhibitor captopril, the AT1 receptor antagonist losartan, the diuretic hydrochlorothiazide, beta-blocker metoprolol, the alpha-1 receptor antagonist prazosin, and the calcium channel blocker diltiazem. All drugs were administered orally (single dose) in a cross-over design and the effect was monitored for 72 hours. The combination of BIA 5-1058 with any of the tested antihypertensive drugs caused a stronger and prolonged blood pressure decrease than any of the compounds alone.In conclusion, peripheral DβH inhibitors can be used, alone or in combination with others antihypertensive drugs, to reduce blood pressure.

Effect of global and regional sympathetic blockade on arterial pressure during water deprivation in conscious rats

Forty-eight hours of water deprivation (WD) in conscious rats results in a paradoxical increase in mean arterial pressure (MAP). Previous studies suggest this may be due to increased sympathetic nerve activity (SNA). However, this remains to be investigated in conscious, freely behaving animals. The purpose of this study was to determine, in conscious rats, the role of the sympathetic nervous system (SNS) in mediating WD-induced increases in MAP and to identify which vascular beds are targeted by increased SNA. Each rat was chronically instrumented with a radiotelemetry transmitter to measure MAP and heart rate (HR) and an indwelling venous catheter for plasma sampling and/or drug delivery. MAP and HR were continuously measured during a 2-day baseline period followed by 48 h of WD and then a recovery period. By the end of the WD period, MAP increased by ∼15 mmHg in control groups, whereas HR did not change significantly. Chronic blockade of α(1)/β(1)-adrenergic receptors significantly attenuated the WD-induced increase in MAP, suggesting a role for global activation of the SNS. However, the MAP response to WD was unaffected by selective denervations of the hindlimb, renal, or splanchnic vascular beds, or by adrenal demedullation. In contrast, complete adrenalectomy (with corticosterone and aldosterone replaced) significantly attenuated the MAP response to WD in the same time frame as α(1)/β(1)-adrenergic receptor blockade. These results suggest that, in conscious water-deprived rats, the SNS contributes to the MAP response and may be linked to release of adrenocortical hormones. Finally, this sympathetically mediated response is not dependent on increased SNA to one specific vascular bed.

Investigating the contribution of the adrenal medulla and sympathetic nerves in the regulation of dexamethasone‐induced hypertension

Chronic treatment with dexamethasone (DEX), a synthetic glucocorticoid produces hypertension in humans. Our studies show that DEX treatment in Fisher 344 rats increases mean arterial pressure (MAP) and reduces heart rate (HR) (+16 ± 2 mmHg, and −39±15 beats/min). We tested the hypothesis that these effects are caused by sympathoadrenal activation. Our aim was to determine whether combined adrenal medullectomy (ADMX) and chemical sympathectomy with 6‐hydroxydopamine (6‐OHDA) reduces the cardiovascular effect of DEX. Fischer 344 male rats were implanted with radiotelemetry transmitters and MAP was recorded continuously during the study. After MAP baseline recording, animals were subjected to ADMX surgery, followed by treatment with 6‐OHDA (20 mg/kg, i.p.) and DEX (0.1 mg/day, in drinking water for 7 days). The results indicate that combined ADMX and 6‐OHDA decreased baseline MAP by −14 ± 3 mmHg, and increased HR by 85 ± 8 beats/min. Subsequent DEX treatment increased MAP from post ADMX and 6‐OHDA level by 22 ± 2 mmHg. HR increased by 49 ± 7 beats/min. These results indicate that the adrenal medulla and peripheral sympathetic nerves are involved in the maintenance of baseline blood pressure, but they may not be required for the elevation of blood pressure induced by DEX. Funding support: Department of Veterans Affairs and American Heart Association.

Effect of Castration on Cardiac Index in the Spontaneously Hypertensive Rat

Androgens amplify the development of hypertension in the spontaneously hypertensive rat (SHR). We showed that androgens increase venous tone, an important contributor to cardiac filling in SHR. The current study tested the hypothesis that castration of SHR would alter the hemodynamic profile during hypertension development in the SHR.SHR were subjected to sham operation, castration or castration+testosterone replacement at 4 weeks of age. Cardiac output was tracked longitudinally using echocardiography. At 6 weeks of age the rats were implanted with radiotelemetry transmitters to monitor arterial pressure and heart rate. These variables were monitored to 13 weeks of age.At 5 weeks of age cardiac index was slightly higher in sham operated (51±5 ml/min/100g) compared to the castrated SHR (40±4 ml/min/100g). Testosterone treatment of castrated SHR partially restored cardiac index (49±8 ml/min/100g). Cardiac index decreased rapidly as the rats aged. At 13 weeks of age there were no differences in cardiac index amongst the groups (Sham: 25±1 ml/min/100g; Castrated 24±2 ml/min/100g; Castrated+testosterone 27±4 ml/min/100g)Collectively, these data are consistent with the possibility that androgens amplify the development of hypertension, at least in part, by increasing cardiac index during the very early stages of hypertension. Supported by NIH #2RO1HL63053‐ARRA (DM).

Implantation of Radiotelemetry Transmitters Yielding Data on ECG, Heart Rate, Core Body Temperature and Activity in Free-moving Laboratory Mice

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a manageable size and relatively easy to house. These factors, together with the availability of a wealth of spontaneous and experimentally induced mutants, make laboratory mice ideally suited to a wide variety of research areas. In cardiovascular, pharmacological and toxicological research, accurate measurement of parameters relating to the circulatory system of laboratory animals is often required. Determination of heart rate, heart rate variability, and duration of PQ and QT intervals are based on electrocardiogram (ECG) recordings. However, obtaining reliable ECG curves as well as physiological data such as core body temperature in mice can be difficult using conventional measurement techniques, which require connecting sensors and lead wires to a restrained, tethered, or even anaesthetized animal. Data obtained in this fashion must be interpreted with caution, as it is well known that restraining and anesthesia can have a major artifactual influence on physiological parameters1, 2. Radiotelemetry enables data to be collected from conscious and untethered animals. Measurements can be conducted even in freely moving animals, and without requiring the investigator to be in the proximity of the animal. Thus, known sources of artifacts are avoided, and accurate and reliable measurements are assured. This methodology also reduces interanimal variability, thus reducing the number of animals used, rendering this technology the most humane method of monitoring physiological parameters in laboratory animals3, 4. Constant advancements in data acquisition technology and implant miniaturization mean that it is now possible to record physiological parameters and locomotor activity continuously and in realtime over longer periods such as hours, days or even weeks3, 5. Here, we describe a surgical technique for implantation of a commercially available telemetry transmitter used for continuous measurements of core body temperature, locomotor activity and biopotential (i.e. onelead ECG), from which heart rate, heart rate variability, and PQ and QT intervals can be established in freeroaming, untethered mice. We also present pre-operative procedures and protocols for post-operative intensive care and pain treatment that improve recovery, well-being and survival rates in implanted mice5, 6.

Implantation of Radiotelemetry Transmitters Yielding Data on ECG, Heart Rate, Core Body Temperature and Activity in Free-moving Laboratory Mice

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a manageable size and relatively easy to house. These factors, together with the availability of a wealth of spontaneous and experimentally induced mutants, make laboratory mice ideally suited to a wide variety of research areas.In cardiovascular, pharmacological and toxicological research, accurate measurement of parameters relating to the circulatory system of laboratory animals is often required. Determination of heart rate, heart rate variability, and duration of PQ and QT intervals are based on electrocardiogram (ECG) recordings. However, obtaining reliable ECG curves as well as physiological data such as core body temperature in mice can be difficult using conventional measurement techniques, which require connecting sensors and lead wires to a restrained, tethered, or even anaesthetized animal. Data obtained in this fashion must be interpreted with caution, as it is well known that restraining and anesthesia can have a major artifactual influence on physiological parameters1, 2.Radiotelemetry enables data to be collected from conscious and untethered animals. Measurements can be conducted even in freely moving animals, and without requiring the investigator to be in the proximity of the animal. Thus, known sources of artifacts are avoided, and accurate and reliable measurements are assured. This methodology also reduces interanimal variability, thus reducing the number of animals used, rendering this technology the most humane method of monitoring physiological parameters in laboratory animals3, 4. Constant advancements in data acquisition technology and implant miniaturization mean that it is now possible to record physiological parameters and locomotor activity continuously and in realtime over longer periods such as hours, days or even weeks3, 5.Here, we describe a surgical technique for implantation of a commercially available telemetry transmitter used for continuous measurements of core body temperature, locomotor activity and biopotential (i.e. onelead ECG), from which heart rate, heart rate variability, and PQ and QT intervals can be established in freeroaming, untethered mice. We also present pre-operative procedures and protocols for post-operative intensive care and pain treatment that improve recovery, well-being and survival rates in implanted mice5, 6.

An anti-hypertensive role for the GPR182 orphan receptor in the rostral ventrolateral medulla of hypertensive rats?

s / Autonomic Neuroscience: Basic and Clinical 163 (2011) 1–133 76 P.092 An anti-hypertensive role for the GPR182 orphan receptor in the rostral ventrolateral medulla of hypertensive rats? S. Milosavljevic (University of Bristol, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, United Kingdom), N. Japundzic-Zigon (University of Belgrade, Institue of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, Serbia), J.F.R. Paton (University of Bristol — Physiology & Pharmacology, United Kingdom), D. Murphy (University of Bristol, Henry Wellcome L.I.N.E, United Kingdom) Affymetrix microarray studies have suggested that the expression of the gene encoding the orphan G protein-coupled receptor GPR182 is up-regulated in the rostral ventrolateral medulla (RVLM) of adult spontaneously hypertensive (SHR) rats in comparison with matched normotensive Wistar control rats. We thus hypothesized that RVLM GPR182 may have a role in the aetiology of high blood pressure in the SHR. To test this hypothesis, we suppressed the expression of GPR182 in the RVLM using Adenoviral vectors expressing specific short hairpin RNAs (shRNAs). Animals were first implanted with radiotelemetry transmitters for chronic MAP and HR registration. Following recovery, rats (SHR, n=6; WKY, n=5) were subjected to bilateral microinjections of Adenoviral vectors (2x10E9 pfu/ml) into the RVLM. In SHRs, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) increased (40±9 mm Hg (p<0.01) and 37±7 mm Hg (p<0.01), respectively) five days after GPR182 knockdown. Heart rate (HR) increased by 69±16 bpm (p<0.01). Similarly, an increase in both SBP and DBP of WKY rats reached a peak five days after the adenoviral vectors administration (29±12 mm Hg (p<0.001) and 22±7 mm Hg (p<0.01), respectively). HR did not exhibit significant changes. A virus expressing enhanced green fluorescent protein had no effect on blood pressure in either strain. These results suggest that GPR182 has a protective, anti-hypertensive role in regulation of blood pressure. GPR182 up-regulation in the SHR maybe a futile attempt by the autonomic nervous system to compensate for the harmful increase in blood pressure.

Evaluation of a novel ECG lead placement method in telemetered freely moving cynomolgus monkeys: Assessment of an intravascular biopotential lead

Introduction ECG is considered as a critical biomarker of cardiac safety pharmacology. ECG signal quality is essential for accurate interval quantification and automated arrhythmia detection. Methods We evaluated ECG signal quality over a 6 month period from 15 cynomolgus monkeys with radiotelemetry transmitters using biopotential leads where the negative lead was inserted in the jugular vein and advanced to the superior vena cava (intravascular lead) and the positive lead was placed on the diaphragm at the apex of the heart (diaphragmatic lead). Signal noise and signal-to-noise ratio from this implantation methodology were compared with signals obtained from animals with subcutaneous ECG lead. Macroscopic pathology and histopathology associated with the intravascular lead were evaluated at 6 months post-implantation in six monkeys. Results The ECG morphology obtained with the intravascular/diaphragmatic lead placement was comparable to conventional subcutaneous ECG (emulating Lead II) but presented higher amplitudes (P-wave + 50.0%; R-wave + 30.0%). Signal noise showed a circadian cycle of changes in magnitude for subcutaneous ECG leads that was not observed with this method. The intravascular/diaphragmatic lead placement presented a higher signal-to-noise ratio than subcutaneous ECG leads. No macroscopic abnormality was observed to be associated with the intravascular lead. Mild thickening of the intima/subintima with mild intimal proliferation of the cranial vena cava surrounding the intravascular lead were noted at histopathological examination. Discussion The intravascular/diaphragmatic ECG lead placement in cynomolgus monkeys provided reduced signal noise and elevated P–QRS–T amplitudes. The intravascular lead was well tolerated and appeared suitable for chronically instrumented cardiovascular safety pharmacology studies. Further assessments would be warranted to evaluate the potential of this methodology in other species.

Heart rate correction models to detect QT interval prolongation in novel pharmaceutical development

IntroductionThe QT interval of the electrocardiogram (ECG) reflects the duration of ventricular depolarization and repolarization. A drug-induced prolongation of ventricular repolarization, and thereby QT prolongation, is recognized to be a marker for an enhanced risk for ventricular arrhythmia. The assessment of a drug's effect on the QT interval has therefore become routine within pharmaceutical research and development. However, the heart rate has a major influence on the QT interval; the QT interval shortens as heart rate increases such that one needs to account for such heart rate-dependent changes when evaluating possible drug-induced effects on the QT interval. The relationship between the QT interval and heart rate can be modeled mathematically and using this function a so-called “corrected” QT interval (QTc) can be generated to assess drug-induced effects independent from heart rate-dependent effects. In the past few years, a large number of mathematical relationship have been described that supposedly best describe the heart rate–QT relationship. In this paper we describe a novel approach for selecting the optimal mathematical function for this purpose for a given individual. MethodsMongrel, purpose-bred dogs (16, males and females) were instrumented with radiotelemetry transmitters (ITS) for measurement of aortic pressure (AP), left ventricular pressure (LVP), the lead II ECG and body temperature. ECGs were recorded continuously without drug treatment and include a range of HRs due to spontaneous, physiological changes over the 24h of data acquisition. Various mathematical models (>20) were then used to evaluate the HR–QT relationship and these were compared statistically to objectively select the model best fitting the data set of each individual animal. ResultsIn this study a dynamic analysis algorithm was developed to find the optimal descriptor of the HR–QT relationship for a given individual animal under control conditions. The use of this optimal relationship provides the best possible approach for detecting drug-induced effects on the QT interval for compounds that also affect the heart rate. DiscussionSeveral numerical methods to optimize the correction functions and statistical procedures to perform significance tests were discussed and implemented in a QT/RR relationship analysis system, named QTana. Given a sample data set, QTana searches the best correction model(s) from the integrated 11 QT/RR relationship modeling functions.

Nicotine-induced Perturbations on Heart Rate, Body Temperature and Locomotor Activity Daily Rhythms in Rats

The aim of this study was to evaluate the influence of nicotine on the daily rhythms of heart rate, body temperature and locomotor activity in unrestrained rats by use of implanted radiotelemetry transmitters. The study was divided into three seven-day periods: a control period, a treatment period and a recovery period. The control period was used for baseline measurement of heart rate, body temperature and locomotor activity. During the treatment period three rats received nicotine (1 mg kg(-1), s.c.) at 0900 h. Three rats received saline under the same experimental conditions. Heart rate, body temperature and locomotor activity were continuously monitored and plotted every 10 min. During the three periods a power spectrum analysis was used to determine the dominant period of rhythmicity. If daily rhythms of heart rate, body temperature and locomotor activity were detected, the characteristics of these rhythms, i.e. the mesors, amplitudes and acrophases, were determined by cosinor analysis, expressed as means +/- s.e.m. and compared by analysis of variance. Nicotine did not suppress daily rhythmicity but induced decreases of amplitudes and phase-advances of acrophases for heart rate, body temperature and locomotor activity. These perturbations might result from the effects of nicotine on the suprachiasmatic nucleus, the hypothalamic clock that co-ordinates biological rhythms.

Janus Kinase 2/Signal Transducers of Activated Transcription (JAK/STAT) pathway in angiotensin II (ANG II)‐mediated elevations in blood pressure: peripheral vs. centrally mediated effects

ANG II mediates both central and peripheral effects on blood pressure. ANGII activates the JAK2/STAT signaling pathway in peripheral blood vessels and kidney cortex and is critical for ANG II-induced hypertension. AG490, a JAK2 inhibitor can theoretically cross the blood brain barrier, thus we inquired whether Ang II-mediated effects via JAK2/STAT centrally or peripherally to modulate blood pressure. In male Sprague Dawley rats radiotelemetry transmitters, or intravenous (iv) catheters were implanted for MAP and HR measures. Rats were placed on a 2% salt diet 7 days prior to ICV cannulae to administer AG490 (1nmol/L; or aCSF) or iv infusion (10ng/kg/min) and peripheral Ang II infusion (150 ng/kg/min;minipump) for 14 days. In a separate study iv catheters peripherally delivered ANG II and AG490 (10 ng/kg/min) as well as an arterial catheter to measure mean arterial pressure (MAP). Centrally AG490 had no effect on mean arterial pressure (MAP) compared to aCSF/Ang II control rats. However, peripheral AG490 significantly reduced the MAP (160 +9 mm Hg ANG II vs 121 +5 mm Hg ANG II/AG490). Western analyses confirmed no central activation of JAK2, however, there was significant activation of JAK2 in thoracic aorta and kidney cortex homogenates. In conclusion, JAK2 mediates Ang II-mediated increases in blood pressure via a peripheral not centrally mediated mechanism. Funded by: NIH R00HL087927 (CAN) and R00HL91177 (ABB).

Non‐permanent radiotelemetry leg harness for small birds

AbstractI developed a modified leg harness for mounting radiotelemetry transmitters to small birds, which includes a weak link that allows telemetry equipment to be shed. Over 4 years, I mounted 62 transmitters on 49 Tuamotu kingfishers (Todiramphus gambieri) using weak‐link harnesses. Kingfishers retained 86% of transmitters for the duration of monitoring periods (23–66 days) whereas 22 of 23 transmitters were shed from birds resighted after 6–15 months. Apparent mortality was no higher for radio‐marked birds than for birds without transmitters. The weak‐link harness is an improvement to existing transmitter attachment techniques and provides a useful, effective, and ethical means of studying bird movements. © 2011 The Wildlife Society.

Cardiovascular Assessment in Radiotelemetry-Implanted Pregnant Rats

ABSTRACTObjective: The aim of this study was to assess the potential adverse effects of the chronic use of surgically implanted radiotelemetry transmitters and femoral catheters on embryo–fetal development in rats. Methods: Two groups of 10 female rats were implanted with femoral catheters and radiotelemetry transmitters. Ten additional rats were implanted with femoral catheters alone. The females were then time mated with male rats and pregnancy confirmed. Saline was continuously infused from gestation days 6–17. Saline infusion was replaced with 0.8 μg/ml angiotensin II in one group of animals, on gestation days 6, 9, 12, and 15 in order to demonstrate the validity of the system to detect changes in hemodynamic function by a pharmacologically active agent. Embryo–fetal development was assessed by examination of the number and location of the fetuses, early and late resorptions, and number of implantation sites. Parameters evaluated included postimplantation loss, live litter size, mean fetal body weights, and fetal sex ratios. Results: Intrauterine survival was unaffected in all groups. Mean numbers of corpora lutea and implantation sites and the mean litter proportions of preimplantation loss were similar across all groups. Infusion of angiotensin II elicited the expected hemodynamic response, i.e., increased arterial blood pressure with a concomitant decrease in heart rate. Conclusion: Radiotelemetry can be used in combination with continuous intravenous infusion as a viable methodology for detecting test article induced changes in cardiovascular function in pregnant rats, with no effects on intrauterine growth and survival or fetal morphology.

Echocardiographic Estimation of Left Atrial Pressure in Beagle Dogs with Experimentally-Induced Mitral Valve Regurgitation

Non-invasive and immediate estimation of left atrial pressure (LAP) is very useful for the management of mitral regurgitation (MR), and many reports have assessed echocardiographic estimations of LAP to date. However, it has been unclear of which examination and evaluate article possess the best accuracy for the MR severity. The present research aims to establish the echocardiographic estimation equation of LAP that is well applicable for clinical MR dogs. After the chordae tendineae rupture was experimentally induced via left atriotomy in six healthy beagle dogs (three males and three females, two years old, weighing between 9.8 to 12.8 kg), a radio telemetry transmitter catheter was inserted, which allows the continuous recordings of LAP without the use of sedation. Approximately 5 weeks after the surgery, echocardiographic examination, indirect blood pressure measurement, measurement of plasma atrial natriuretic peptide (ANP) and LAP measurement by way of the radio telemetry system was performed simultaneously. Subsequently, simple linear regression equations between LAP and each variable were obtained, and the equations were evaluated whether to be applicable for clinical MR dogs. As a result, the ratio of early diastolic mitral flow to early diastolic lateral mitral annulus velocity (E/Ea) had the strongest correlation as maximum LAP=7.03*(E/Ea)-54.86 (r=0.74), and as mean LAP=4.94*(E/Ea)-40.37 (r=0.70) among the all variables. Therefore, these two equations associated with E/Ea should bring more precise and instant estimations of maximum and mean LAP in clinical MR dogs.

An introduction to the practical and ethical perspectives on the need to advance and standardize the intracoelomic surgical implantation of electronic tags in fish

The intracoelomic surgical implantation of electronic tags (including radio and acoustic telemetry transmitters, passive integrated transponders and archival biologgers) is frequently used for conducting studies on fish. Electronic tagging studies provide information on the spatial ecology, behavior and survival of fish in marine and freshwater systems. However, any surgical procedure, particularly one where a laparotomy is performed and the coelomic cavity is opened, has the potential to alter the survival, behavior or condition of the animal which can impair welfare and introduce bias. Given that management, regulatory and conservation decisions are based on the assumption that fish implanted with electronic tags have similar fates and behavior relative to untagged conspecifics, it is critical to ensure that best surgical practices are being used. Also, the current lack of standardized surgical procedures and reporting of specific methodological details precludes cross-study and cross-year analyses which would further progress the field of fisheries science. This compilation of papers seeks to identify the best practices for the entire intracoelomic tagging procedure including pre- and post-operative care, anesthesia, wound closure, and use of antibiotics. Although there is a particular focus on salmonid smolts given the large body of literature available on that group, other life-stages and species of fish are discussed where there is sufficient knowledge. Additional papers explore the role of the veterinarian in fish surgeries, the need for minimal standards in the training of fish surgeons, providing a call for more complete and transparent procedures, and identifying trends in procedures and research needs. Collectively, this body of knowledge should help to improve data quality (including comparability and repeatability), enhance management and conservation strategies, and maintain the welfare status of tagged fish.

The consequences of angling, beach seining, and confinement on the physiology, post-release behaviour and survival of adult sockeye salmon during upriver migration

Few studies have examined the effects of fisheries capture on wild fish, particularly in the context of evaluating the sustainability of capture and release methods for Pacific salmon ( Oncorhynchus spp.) during upriver migration. This study examined the physiological condition, post-release behaviour and survival of adult migrating sockeye salmon ( O. nerka) in the Fraser River, British Columbia, Canada. Fish were captured by either beach seine or angling and released immediately, or were captured by angling and released following a 24-h recovery period in a net pen. Before release, all salmon were biopsied or tagged with radio telemetry transmitters. Capture by either angling or beach seine with immediate release resulted in >95% survival 24 h after release, whereas net pen recovery after angling resulted in ∼80% survival. This differential in survival was similarly expressed in the percentage of released fish reaching natal sub-watersheds, with 52.2% and 36.3% of fish immediately released by beach seine and angling reaching natal sub-watersheds, respectively, compared with 2.9% of fish released after angling and net pen recovery. Blood plasma stress indices reflected the 10-fold difference in survival, with a ∼4-fold higher plasma cortisol, a ∼2-fold higher plasma glucose and significantly depressed plasma ions and osmolality relative to fish sampled upon capture. Plasma lactate did not differ among groups. Collectively, these results suggest that a 24 h recovery in net pen following angling failed to promote post-release survival experienced with immediate release after angling or beach seining.

Heart Rate Responses To A Survival Swim Test In Mice

Understanding cardiovascular regulation could have important implications in reducing the incidence of cardiovascular diseases. However, relatively little is known about the genetic regulation of cardiac function as dissecting the complexity of genetic cardiac control can be challenging. Further, it is not known if similar sets of genes control heart rate (HR) at baseline compared to stress induced changes in HR. PURPOSE: To test the hypothesis that differences in genetic background influence HR changes during a survival swim test. METHODS: Five inbred mouse strains (NZB/B1NJ, DBA2/J, C57L/J, 129Sv1m/J and SWR/J; 4-8 mice per strain) were instrumented with an ETA-F20 radio telemetry transmitter for ECG recording at baseline and during the survival swim test. Following 24 hours of continuous baseline ECG recording, mice were forced to swim in 30°C water until they were unable or unwilling to avoid 2 full seconds of complete submersion in the water. ECG was also recorded continuously during the survival test. RESULTS: Baseline HRs between strains were not different except when comparing the 129Sv1m/J and NZB/B1nJ strains (650.9 vs. 585.4 respectively; P= 0.05). Moreover, the average swim time between strains was significantly different with DBA2/J mice swimming for the longest period (10.3 mins) and 129/Sv1mJ mice for the shortest (2.4 mins; P= <0.05). Regression analysis did not reveal significant relationships between the change in HR during the survival test and baseline HR (R = -0.399) or change in HR during the swim test and swim time (R = 0.392). CONCLUSIONS: The limited differences in baseline HR between strains in this study, which differed from previous reports, may be due to the conditions under which baseline HR was assessed (24 hour mean vs. quiescence). The lack of a relationship between baseline HR and HR responses to the swim test suggests different set genes controlled HR in the different conditions. However, the between strain differences in baseline HR, in addition to HR responses and tolerance to the swim test, suggests these phenotypes are in part genetically controlled. Furthermore, the decline in HR during the survival swim test suggests that this is a useful model for investigating genetic control of HR, but it may not be a useful for assessing human HR responses to swimming.

Cannabinoid-induced reduction in antral pacemaker frequency: a telemetric study in the ferret

The gastric myoelectric activity (GMA) is the electrical pacesetter potential, which drives gastric motility. Cannabinoids have broad-spectrum antiemetic and antinauseant activity. Paradoxically, they inhibit intestinal peristalsis and reduce gastric motility but their effect on GMA remains unknown. Ferrets were surgically implanted with radiotelemetry transmitters to record GMA, body temperature and heart rate. The effect of WIN 55,212-2 (1 mg kg(-1), i.p.), an agonist at the cannabinoid type 1 and 2 receptors was examined in conscious, unrestrained ferrets. WIN 55,212-2 was also compared to the anandamide upregulator URB 597 (5 mg kg(-1), i.p.) for a potential to modulate the emetic response and behavioral changes induced by apomorphine (0.25 mg kg(-1), s.c.). WIN 55,212-2 decreased GMA frequency (8.1 ± 0.4 cpm, compared to 9.6 ± 0.1 cpm in vehicle-treated animals, n = 6, P < 0.01). Apomorphine induced 9.0 ± 1.6 emetic episodes, WIN 55,212-2 inhibited the emetic response (3.3 ± 1.0 episodes, n = 6, P < 0.05) but URB 597 had no effect (9.0 ± 1.5 episodes). Apomorphine-induced hyperactivity in vehicle-treated animals (6.5 ± 3.6-16.6 ± 4.9 active behavior counts, n = 6, P < 0.01), which was reduced by WIN 55,212-2 (5.0 ± 1.5 counts, n = 6, P < 0.05). WIN 55,212-2 demonstrated clear antiemetic efficacy, which extends the broad-spectrum antiemetic efficacy of cannabinoids to dopamine receptor agonists in the ferret. Our results, however, suggest a more limited spectrum of action for URB 597. WIN 55,212-2 decreased the frequency of the antral electrical pacemaker, which reveals new insights into the mechanism regulating the decrease in motility induced by cannabinoids.