Surgical removal of a telemetry system in a cynomolgus monkey (Macaca fascicularis): a 12-month observation study

Background Telemetry is a wireless implanted device that measures biological signals in conscious animals and usually requires surgery for its removal when the study is finished. After removing the device, the animals are either used for other studies or euthanatized. Case presentation Herein, we report the case of a living cynomolgus monkey (Macaca fascicularis) that was used for the entire experimental period, instead of euthanasia, after surgical removal of an implanted telemetry system. Radiography was used to determine the status of the implanted telemetry, following which, a repair surgery was performed for removing the system; clinical signs were used to preserve the life of the cynomolgus monkey. Postoperative clinical signs, food consumption, hematology, and serum biochemistry were examined during the 12-month observational period. No abnormal readings or conditions were observed in the subject after implant removal. Conclusions This study may be a useful case report for living cynomolgus monkeys in telemetry implantations used throughout the study period. We suggest minimizing the suffering and improving the welfare of these animals.

Minimizing outliers on cardiovascular signals: an open-source solution

Context: Intravenous cardiovascular recording of conscious animals is susceptible to outlier’s presence, due to freely movement and manipulations. These outliers can interfere on heart rate variability results, indicating erroneous results of sympathetic or parasympathetic modulation.Objective: Develop an automated computational approach to minimize the presence of outliers in cardiovascular recorded signals.Method: An application was developed according to the problem addressed based on free-use web frameworks.Results: The use of the proposed application detected and minimized respectively 1% and 0.97% of points outliers in signals of systolic arterial pressure (SAP) and pulse interval (PI) from a representative blood pressure recording. As until then the work of minimization of outliers was carried out manually; the use of the new application considerably reduced time spend analyzing the data.Conclusion: The proposed algorithm can detect and minimize interferent points, reducing chances of an erroneous interpretation about the cardiovascular modulation by the autonomic nervous system. The method can also significantly reduce the time of manual point-to-point screening performed by researchers.

Ritual Slaughter: The Tradition of Pilot Whale Hunting on the Faroe Islands

Faroese people consider grindadráp, the hunting of pilot whales, as a part of their cultural heritage, but from the point of view of veterinary sciences and biology, the method of killing pilot whales is a form of a ritual slaughter performed on fully conscious animals that are aware of their circumstances. Pilot whales are social, intelligent, and communicative animals that demonstrate complex social behaviors. Therefore, this traditional whaling method should be considered as a procedure in which animals are exposed to high levels of distress. In the context of contemporary civilizational development and material welfare, the practice of whaling may appear to be an inadequate and cruel relic of the past. This text explores social and cultural issues caused by pilot whale hunts and presents an understanding of the term tradition and some perspectives of how traditions change. The specificity of pilot whales as a species is presented, setting a foundation for a discussion about hunting itself. The conclusion of the text discusses different social perceptions of grindadráp by presenting arguments for and against the hunting. This analysis includes a presentation of actions undertaken bywhale hunting opponents.

Responses of Neurons in the Medullary Lateral Tegmental Field and Nucleus Tractus Solitarius to Vestibular Stimuli in Conscious Felines

Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate (increase for 60% of the neurons, decrease for 40%) of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF and RVLM neurons was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal's vigilance and alertness.

Cardiovascular and Metabolic Responses to Carbon Dioxide Euthanasia in Conscious and Anesthetized Rats

Euthanasia is a necessary component in research and must be conducted humanely. Currently, regulated CO2 exposure in conscious rats is acceptable, but data are divided on whether CO2 alone is more distressing than anesthesia prior to CO2. To evaluate distress in rats, we compared physiologic responses to CO2 euthanasia with and without isoflurane preanesthesia. Male Sprague–Dawley rats were implanted with telemetry devices to measure mean arterial pressure (MAP), heart rate (HR), and blood glucose. Animals recovered for 2 wk and were then exposed to either 5% isoflurane (n = 6) or 100% CO2 (n = 7; calculated 30% chamber volume/min displacement) in their home cages to induce loss of consciousness. Euthanasia was then completed with CO2 in both groups. MAP and HR increased when the gas delivery lids were placed on the home cages of both groups. Both MAP and HR gradually decreased with isoflurane exposure. MAP increased and HR decreased with CO2 exposure. Glucose levels remained stable throughout the procedure, except for a small drop in conscious animals initially exposed to 100% CO2. These data suggest that both gases affect the measured parameters in a similar manner, and that environmental factors, such as gas delivery lid placement, also change these measurements.

Responses of Neurons in the Medullary Lateral Tegmental Field and Nucleus Tractus Solitarius to Vestibular Stimuli in Conscious Felines

Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF neurons and RVLM was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal’s vigilance and alertness.

Diving into the brain: deep-brain imaging techniques in conscious animals

In most species, survival relies on the hypothalamic control of endocrine axes that regulate critical functions such as reproduction, growth, and metabolism. For decades, the complexity and inaccessibility of the hypothalamic–pituitary axis has prevented researchers from elucidating the relationship between the activity of endocrine hypothalamic neurons and pituitary hormone secretion. Indeed, the study of central control of endocrine function has been largely dominated by ‘traditional’ techniques that consist of studying in vitro or ex vivo isolated cell types without taking into account the complexity of regulatory mechanisms at the level of the brain, pituitary and periphery. Nowadays, by exploiting modern neuronal transfection and imaging techniques, it is possible to study hypothalamic neuron activity in situ, in real time, and in conscious animals. Deep-brain imaging of calcium activity can be performed through gradient-index lenses that are chronically implanted and offer a ‘window into the brain’ to image multiple neurons at single-cell resolution. With this review, we aim to highlight deep-brain imaging techniques that enable the study of neuroendocrine neurons in awake animals whilst maintaining the integrity of regulatory loops between the brain, pituitary and peripheral glands. Furthermore, to assist researchers in setting up these techniques, we discuss the equipment required and include a practical step-by-step guide to performing these deep-brain imaging studies.

Responses of neurons in the rostral ventrolateral medulla of conscious cats to anticipated and passive movements

The vestibular system contributes to regulating sympathetic nerve activity and blood pressure. Initial studies in decerebrate animals showed that neurons in the rostral ventrolateral medulla (RVLM) respond to small-amplitude (<10°) rotations of the body, as in other brain areas that process vestibular signals, although such movements do not affect blood distribution in the body. However, a subsequent experiment in conscious animals showed that few RVLM neurons respond to small-amplitude movements. This study tested the hypothesis that RVLM neurons in conscious animals respond to signals from the vestibular otolith organs elicited by large-amplitude static tilts. The activity of approximately one-third of RVLM neurons whose firing rate was related to the cardiac cycle, and thus likely received baroreceptor inputs, was modulated by vestibular inputs elicited by 40° head-up tilts in conscious cats, but not during 10° sinusoidal rotations in the pitch plane that affected the activity of neurons in brain regions providing inputs to the RVLM. These data suggest the existence of brain circuitry that suppresses vestibular influences on the activity of RVLM neurons and the sympathetic nervous system unless these inputs are physiologically warranted. We also determined that RVLM neurons failed to respond to a light cue signaling the movement, suggesting that feedforward cardiovascular responses do not occur before passive movements that require cardiovascular adjustments.

BP Fluctuations and the Real-Time Dynamics of Renal Blood Flow Responses in Conscious Rats

BackgroundRenal autoregulation maintains stable renal function despite BP fluctuations and protects glomerular capillaries from hypertensive injury. However, real-time dynamics of renal autoregulation in conscious animals have not been characterized.MethodsTo develop novel analytic methods for assessing renal autoregulation, we recorded concurrent BP and renal blood flow in conscious rats, comparing animals with renal autoregulation that was intact versus impaired (from 3/4 nephrectomy), before and after additional impairment (from the calcium channel blocker amlodipine). We calculated autoregulatory indices for adjacent short segments of increasing length (0.5, 1, 2.5, 5, 10, and 20 seconds) that exhibited a mean BP difference of at least 5 mm Hg.ResultsAutoregulatory restoration of renal blood flow to baseline after BP changes in conscious rats occurs rapidly, in 5–10 seconds. The response is significantly slower in states of impaired renal autoregulation, enhancing glomerular pressure exposure. However, in rats with severe renal autoregulation impairment (3/4 nephrectomy plus amlodipine), renal blood flow in conscious animals (but not anesthetized animals) was still restored to baseline, but took longer (15–20 seconds). Consequently, the ability to maintain overall renal blood flow stability is not compromised in conscious rats with impaired renal autoregulation.ConclusionsThese novel findings show the feasibility of renal autoregulation assessment in conscious animals with spontaneous BP fluctuations and indicate that transient increases in glomerular pressure may play a greater role in the pathogenesis of hypertensive glomerulosclerosis than previously thought. These data also show that unidentified mechanosensitive mechanisms independent of known renal autoregulation mechanisms and voltage-gated calcium channels can maintain overall renal blood flow and GFR stability despite severely impaired renal autoregulation.

Classical and controlled auditory mismatch responses to multiple physical deviances in anaesthetised and conscious mice

Human mismatch negativity (MMN) is modelled in rodents and other non-human species to examine its underlying neurological mechanisms, primarily described in terms of deviance-detection and adaptation. Using the mouse model, we aim to elucidate subtle dependencies between the mismatch response (MMR) and different physical properties of sound. Epidural field potentials were recorded from urethane-anaesthetised and conscious mice during oddball and many-standards control paradigms; with stimuli varying in duration, frequency, intensity, and inter-stimulus interval. Resulting auditory evoked potentials, classical MMR (oddball – standard), and controlled MMR (oddball – control) waveforms were analysed. Stimulus duration correlated with stimulus-off response peak latency (p < 0.0001). Frequency (p < 0.0001), intensity (p < 0.0001), and inter-stimulus interval (p < 0.0001) correlated with stimulu-son N1 and P1 (conscious only) peak amplitudes. These relationships were instrumental in shaping classical MMR morphology in both anaesthetised and conscious animals, suggesting these waveforms reflect modification of normal auditory processing by different physical properties of stimuli. Controlled MMR waveforms appeared to exhibit habituation to auditory stimulation over time, which was equally observed in response to oddball and standard stimuli. These observations are not consistent with the mechanisms thought to underlie human MMN, which currently do not address differences due to specific physical features of auditory deviance. Thus, no evidence was found to objectively support the deviance-detection or adaptation hypotheses of MMN in relation to anaesthetised or conscious mice.