Effect of xylazine, medetomidine and dexmedetomidine on cardiac conduction in pigs

The majority of anaesthetics used in studies regarding heart arrhythmias may affect the cardiac conduction system, thus influencing the results. In veterinary medicine, xylazine, medetomidine and dexmedetomidine are commonly used for premedication in laboratory and companion animals. To date, there have been no studies assessing the effect of these substances on the cardiac conduction system. The aim of this study was to assess the effect of xylazine, medetomidine and dexmedetomidine on the parameters of the cardiac conduction system in pigs. The study was carried out on 18 Great White Polish male pigs weighing from 21 to 40 kg. The animals were divided into three equal groups. The animals from the first group received xylazine at a dose of 2 mg/kg i.v.; those from the second group received medetomidine at 40 mcg/kg i.v.; and those from the third group received dexmedetomidine at 10 mcg/kg i.v. The electrophysiological activity of the heart was analysed using an invasive electrophysiological study (EPS). During the EPS, a decrease in the heart rate after substance administration was observed in all animals, but there were no statistically significant differences in the cardiac conduction parameters. A pro-arrhythmic effect of xylazine was observed, but no statistically significant changes in the EPS parameters were noted. Our results indicate that medetomidine and dexmedetomidine may be used as standard premedication drugs in electrophysiological studies in pigs. Their use may facilitate animal preparation procedures without affecting study results..

Robert Hooke: Early Respiratory Physiologist, Polymath, and Mechanical Genius

Robert Hooke (1635–1703) was a polymath who made important contributions to respiratory physiology and many other scientific areas. With Robert Boyle, he constructed the first air pump that allowed measurements on small animals at a reduced atmospheric pressure, and this started the discipline of high-altitude physiology. He also built the first human low-pressure chamber and described his experiences when the pressure was reduced to the equivalent of an altitude of ∼2,400 m. Using artificial ventilation in an animal preparation, he demonstrated that movement of the lung was not essential for life. His book Micrographia describing early studies with a microscope remains a classic. He produced an exquisite drawing of the head of a fly, showing the elaborate compound eye. There is also a detailed drawing of a flea, and Hooke noted how the long, many-jointed legs enable the insect to jump so high. For 40 years, he was the curator of experiments for the newly founded Royal Society in London and contributed greatly to its intellectual ferment. His mechanical inventions covered an enormous range, including the watch spring, the wheel barometer, and the universal joint. Following the Great Fire of London in 1666, he designed many of the new buildings in conjunction with Christopher Wren. Unfortunately, Hooke had an abrasive personality, which was partly responsible for a lack of recognition of his work for many years. However, during the last 25 years, there has been renewed interest, and he is now recognized as a brilliant scientist and innovator.

Relationship between Biomechanical Characteristics of Spinal Manipulation and Neural Responses in an Animal Model: Effect of Linear Control of Thrust Displacement versus Force, Thrust Amplitude, Thrust Duration, and Thrust Rate

High velocity low amplitude spinal manipulation (HVLA-SM) is used frequently to treat musculoskeletal complaints. Little is known about the intervention’s biomechanical characteristics that determine its clinical benefit. Using an animal preparation, we determined how neural activity from lumbar muscle spindles during a lumbar HVLA-SM is affected by the type of thrust control and by the thrust's amplitude, duration, and rate. A mechanical device was used to apply a linear increase in thrust displacement or force and to control thrust duration. Under displacement control, neural responses during the HVLA-SM increased in a fashion graded with thrust amplitude. Under force control neural responses were similar regardless of the thrust amplitude. Decreasing thrust durations at all thrust amplitudes except the smallest thrust displacement had an overall significant effect on increasing muscle spindle activity during the HVLA-SMs. Under force control, spindle responses specifically and significantly increased between thrust durations of 75 and 150 ms suggesting the presence of a threshold value. Thrust velocities greater than 20–30 mm/s and thrust rates greater than 300 N/s tended to maximize the spindle responses. This study provides a basis for considering biomechanical characteristics of an HVLA-SM that should be measured and reported in clinical efficacy studies to help define effective clinical dosages.

Neuronal mechanisms underlying the facilitatory control of uropod steering behaviour during treadmill walking in crayfish. I. Antagonistically regulated background excitability of uropod motoneurones

One of the postural reflexes of crayfish, the uropod steering response, is elicited by specific sensory inputs while the animal is walking. It is not elicited, however, by the same inputs when the animal is at rest. To clarify the neuronal mechanisms underlying this facilitatory control of body posture in the active animals, we used intracellular recordings to analyse the synaptic activities of uropod motor system neurones in an unanaesthetized whole-animal preparation. Several uropod motoneurones were found to receive sustained depolarizing inputs during walking, whereas the walking leg motoneurones sampled always showed rhythmic activity. The membrane conductance of the uropod motoneurones increased during the sustained synaptic activity. Premotor nonspiking interneurones showed depolarizing or hyperpolarizing membrane potential changes during walking that were also accompanied by increases in membrane conductance. Some of these interneurones enhanced uropod motoneurone activity, whereas others suppressed it during walking. These results suggest that the background excitability of uropod motoneurones is kept at an intermediate level during walking by the antagonistic inputs from premotor nonspiking interneurones so that the uropod motor system can be responsive to both further excitatory and inhibitory inputs resulting from postural changes. <P>

Effect of repetitive stunning on myocardial metabolism in pig hearts

Recent animal and clinical studies have suggested that chronic hibernation, a condition of depressed mechanical function and enhanced glycolysis in viable but downregulated myocardium, may result from chronic repetitive ischemia and reperfusion. The present study was conducted to test whether similar trends could be reproduced in an acute animal preparation of repetitive stunning. Eight intact pig hearts were extracorporeally perfused for 115 min and subjected to four cycles of ischemia [60% decrease in anterior descending flow for 5 min each, interspersed with 15 min of aerobic reperfusion]. Each bout of ischemia caused a progressive decline in regional systolic shortening such that systolic shortening was 37% lower at end-reperfusion (P < 0.05 vs. initial conditions). Regional myocardial O2 consumption was reduced during ischemia but was not significantly lower at end-reperfusion compared with that under initial conditions. Fatty acid oxidation was unchanged at any point during the trials. Although glucose utilization was increased by an average of 264% during the four ischemic periods, it was not significantly or progressively increased during the reperfusion periods. Therefore, although this acute stunning protocol depressed mechanical function, it did not cumulatively increase glycolysis during reperfusion. This absence of accelerated glycolysis is at variance with the metabolic findings reported in clinical hibernation and raises concerns regarding this protocol in animal studies designed to simulate short-term hibernation.

Synaptic plasticity in the thalamo-cortical pathway as one of the neurobiological correlates of forelimb flexion conditioning: electrophysiological investigation in the cat

1. In a previous study, using a chronic cat preparation subjected to an associative conditioning procedure, we described the plasticity of the thalamo-cortical pathway by qualitatively and quantitatively analyzing the motor responses induced by stimulating each of the relays on the cerebello-thalamo-cortical pathway. In the present study, it was proposed to analyze the effects on the synapses located between thalamic endings and cortical neurones, using a twofold behavioral and electrophysiological approach, with a view to correlating the patterns of synaptic plasticity with the changes in the motor responses recorded. 2. For this purpose, a reduced, functionally organized sensorimotor circuit, which can be taken to be a neuronal analog of associative conditioning, was studied in an awake chronic animal preparation. This circuit was defined on the basis of the sites at which conditioned (CS) and unconditioned stimuli (UCS) were applied: the CS was applied at a site on the cerebellar interpositus nucleus which activated the forepaw musculature so as to induce flexion movements and the UCS was applied to the skin of the distal part of that paw so as to induce reflex flexion movements. By repetitively activating the central nervous pathways by the associated CS and UCS according to a predefined temporal pattern, the efficiency of the thalamo-cortical pathway's contribution to the movement production was enhanced, and its capacity to convey the cerebellar inputs to neurons in the motor cortex increased. 3. The associative nature of the conditioning was tested using previously established criteria. The setting up of motor and central changes in response to the repetitive presentation of paired CS and UCS, the fact that these changes were reversible because they could be abolished by applying extinction procedures, and the consistency of their occurrence whenever the CS was applied repeatedly alone for several days to naive animals, all showed that the stimuli of both kinds (CS and UCS) had to be applied together for the plasticity of the thalamo-cortical pathway to be expressed. 4. By determining whether the waves constituting the cerebello-cortical responses were excitatory or inhibitory, the nature of the changes in the transmission of the cerebellar impulses to neurons in the motor cortex was established.(ABSTRACT TRUNCATED AT 400 WORDS)

Ventilatory afterdischarge and central respiratory drive interactions in the awake goat

We have previously established the existence of ventilatory afterdischarge (VAD) in the awake goat by means of an isolated perfused carotid body (CB) technique. In the present series of experiments we used this animal preparation to examine the effects of systemic (central nervous system) hypoxia, mild hypercapnia, and hypocapnia on the manifestation of VAD in ventilatory variables and respiratory muscle electromyogram activity after hypoxic stimulation of the isolated CB. With systemic isocapnic normoxia, inspired minute ventilation remains above control for 30–40 s (time constant = 16.8 s) after termination of CB hypoxia; however, with systemic hypocapnia, VAD is short (time constant = 5.5 s) and hypoventilation is common after removal of CB stimulation. During mild systemic hypercapnia, VAD is prolonged (time constant = 39.9 s). However, systemic (central nervous system) hypoxia did not decrease VAD (time constant = 17.0 s). These results indicate that the manifestation of VAD is more sensitive to the level of arterial PCO2 and central chemoreceptor activity than it is to the state of central oxygenation. Inspiratory and expiratory muscle electromyogram activities qualitatively tracked ventilation during CB stimulation and during the VAD period in all conditions.