Toru Yazawa

Alteration in dopamine metabolism in the thermoregulatory center of exercising rats.

To examine the role of monoamines and amino acids in thermoregulation, we measured their concentrations in the preoptic area and anterior hypothalamus (PO/AH) in exercising rats, using an in vivo microdialysis technique. Body temperature (Tb) was monitored using a telemetry system. Tb increase by about 1.0 degrees C in the first 15 min of treadmill exercise (10 m/min; for 60 min), and was maintained thereafter at a steady high level possibly due to activation of the heat loss system. The levels of dopamine metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) in the PO/AH significantly increased during exercise. However, exercise did not induce an increase in the level of either serotonergic substances (5-hydroxytryptamine and 5-hydroxyindoleacetic acid) or amino acids (aspartate and glutamate). Our data indicate that dopamine breakdown processes in the PO/AH are activated during exercise. Dopamine in the PO/AH may be involved in the heat loss mechanisms for thermoregulation when Tb rises during exercise.

Changes of body temperature and thermoregulatory responses of freely moving rats during GABAergic pharmacological stimulation to the preoptic area and anterior hypothalamus in several ambient temperatures.

Action of gamma-aminobutyric acid (GABA) in the preoptic area and anterior hypothalamus (PO/AH) has been implicated to regulate body temperature (T(b)). However, its precise role in thermoregulation remains unclear. Moreover, little is known about its release pattern in the PO/AH during active thermoregulation. Using microdialysis and telemetry techniques, we measured several parameters related to thermoregulation of freely moving rats during pharmacological stimulation of GABA in normal (23 degrees C), cold (5 degrees C), and hot (35 degrees C) ambient temperatures. We also measured extracellular GABA levels in the PO/AH during cold (5 degrees C) and heat (35 degrees C) exposure combined with microdialysis and high performance liquid chromatography (HPLC). Perfusion of GABA(A) agonist muscimol into the PO/AH increased T(b), which is associated with increased heart rate (HR), as an index of heat production in all ambient temperatures. Although tail skin temperature (T(tail)) as an index of heat loss increased only under normal ambient temperatures, its response was relatively delayed in comparison with HR and T(b), suggesting that the increase in T(tail) was a secondary response to increased HR and T(b). Locomotor activity also increased in all ambient temperatures, but its response was not extraordinary. Interestingly, thermoregulatory responses were different after perfusion of GABA(A) antagonist bicuculline at each ambient temperature. In normal ambient temperature conditions, perfusion of bicuculline had no effect on any parameter. However, under cold ambient temperature, the procedure induced significant hypothermia concomitant with a decrease in HR in spite of hyperactivity and increase of T(tail). It induced hyperthermia with the increase of HR but no additional change of T(tail) in hot ambient temperature conditions. Furthermore, the extracellular GABA level increased significantly during cold exposure. Its release was lower during heat exposure than in a normal environment. These results indicate that GABA in the PO/AH is an important neurotransmitter for disinhibition of heat production and inhibition of heat loss under cold ambient temperature. It is a neurotransmitter for inhibition of heat production under hot ambient temperature.

Functional role of the preoptic area and anterior hypothalamus in thermoregulation in freely moving rats

We recently reported that perfusion of tetrodotoxin (TTX) into the preoptic area and anterior hypothalamus (PO/AH), by using a microdialysis technique, induced an increase in body temperature (Tb) under normal and hot ambient temperatures (23 and 35 degrees C) in freely moving rats. However, the procedure had no effect on Tb under a cold ambient temperature (5 degrees C). The present study was designed to determine the mechanism(s) of increases in Tb after perfusion of TTX into the PO/AH, by measuring tail skin temperature (Ttail) as an index of heat loss, and heart rate (HR) and locomotor activity (Act) as indexes of heat production, under three ambient temperatures. Under normal ambient temperature (23 degrees C), perfusion of TTX induced significant hyperthermia with increased HR, Act and Ttail. In a hot environment (35 degrees C), perfusion of TTX induced a greater increase in Tb with increased HR but no change in Ttail and Act. In a cold environment (5 degrees C), perfusion of TTX had no effect on Tb with a slight increase in Act but no change in HR and Ttail. Our results suggest that the PO/AH may be involved in inhibition of heat production and excitation/inhibition of the tail vasomotor tone.

The role of preoptic area and anterior hypothalamus and median raphe nucleus on thermoregulatory system in freely moving rats

To clarify the role of the preoptic area and anterior hypothalamus (PO/AH) on thermoregulatory system and the effects of serotonergic innervation from the median raphe nucleus (MRN) on body temperature (Tb), we perfused tetrodotoxin (TTX) solution into the PO/AH or MRN by using a microdialysis technique at different ambient temperatures (5, 23 and 35 degrees C) in freely moving rats. Tb was continuously monitored by using a telemetry system. In the MRN, perfusion of TTX solution induced significant hypothermia in the normal environment, a greater decrease in Tb during cold exposure and had no effect on Tb during heat exposure. In the PO/AH, perfusion of TTX solution induced significant hyperthermia in normal environment, a greater increase in Tb during heat exposure and had no effect on Tb during cold exposure. Our results indicate that the PO/AH regulates mainly heat loss or inhibits the loci regulating heat production. Furthermore, heat production appears to be regulated by other loci receiving serotonergic innervation from the MRN.

Effects of ambient light on body temperature regulation in resting and exercising rats.

We investigated the effects of environmental light and darkness on thermoregulation during both daytime and nighttime by monitoring body temperature (T(b)) and physical activity of rats using a telemetry system. Experiments were performed in both resting and exercising rats. In resting rats, lights-off during the daytime resulted in an increase in both T(b) and activity. Conversely, during the nighttime, T(b) decreased with the lights-on stimulus despite the fact that the activity was left unchanged. Treadmill exercise (10 m/min) always increased T(b) from the basal resting level. In both daytime and nighttime, exercising rats exhibited a persistent T(b)-rise when lights were on. However, in the lights-off condition at nighttime, the T(b) of exercising rats increased to a level significantly higher than that of exercising rats with the lights-on. Our results suggest that light at nighttime causes the suppression of T(b) in both resting and exercising rats.

Neurodynamical Control of the Heart of Healthy and Dying Crustacean Animals

We analyzed the heartbeat-interval recorded from crustacean animals, using detrended fluctuation analysis (DFA) and delayed-time embedding method. EKG was obtained from freely moving animals in normal condition and then in terminal condition; we kept recording until the life was coming to an end. Our experimental purpose was to know whether DFA and embedding methods characterize quantitatively conditions of the cardiac control network, either in the brain or in the heart, or both, the brain and heart. We concluded that DFA exponents represent whether the subjects are under sick or healthy conditions. Here we show how the controller conditions of the brain changed and how pacemaker neural network in the heart deteriorated from time to time. This report demonstrates relationship between DFA and electro-physiological of the heart.Copyright

Cardioacceleratory reflexes triggered by mechanoproprioceptors of the swimmerets in the stomatopod crustacean Squilla oratoria

Abstract The heart of Squilla oratoria is innervated by processes arising from the cardiac ganglion, which lies on the outer surface of the heart wall. The ganglion is regulated by one pair of cardioinhibitory nerves and two pairs of cardioacceleratory nerves. Cardiac acceleration accompanied activation of the five pairs of swimmerets in the first to the fifth abdominal segments. The cardioacceleratory nerves were activated when swimmerets beat strongly. Activation of the cardioacceleratory nerves was caused by electrical stimuli to a nerve branch extending to the swimmerets from the first nerve root of the abdominal ganglion. Bursts of afferent impulses were recorded from the nerve branch of the first nerve root corresponding to periods of protractive and retractive swimmeret movements. Afferent impulses were recorded from the nerve branch when the articular membrane was artificially boosted up. Cardiac acceleration during active swimmeret movements in Squilla is attributable to a reflexive response triggered by the movements. Putative mechanoproprioceptors on the articular membrane between the sterna and basipodite in the swimmerets may be responsible for the cardioacceleratory reflex.

EVALUATION OF SLEEP BY DETRENDED FLUCTUATION ANALYSIS OF THE HEARTBEAT

There are already‐established methods for investigating biological signals such as rhythmic heartbeats. We used detrended fluctuation analysis (DFA), originally developed by Peng et al. (1995) to check power‐law characteristics, because the method can quantify the heart condition numerically. In this article, we studied the heartbeat of sleeping subjects. Our purpose was to test whether DFA is useful to evaluate the subject’s wellness of both during being awake and sleeping. This is a challenge to measure sleep without complex/expensive machine, an electro encephalography (EEG). We conducted electrophysiological recording to measure heartbeats during sleep using electrocardiograph with three‐leads, one ground electrode and two active electrodes attached to chest. For good recording, a stable baseline must be maintained even when subjects move their body. We needed a tool to ensure long‐term steady recording. We thus invented a new electric‐circuit designed to produce this desired result. This gadget allow...

Low Scaling Exponent during Arrhythmia: Detrended Fluctuation Analysis is a Beneficial Biomedical Computation Tool

Cardiovascular disease is one of the major social health problems. Heart attacks, in particular, are a major social concern because of the unpredictable and silent way they develop. Recently, it was reported that the incidence of myocardial infarction has decreased significantly (Yeh et al., 2010). However, some unlucky patients are unaware that they are at risk for the life threatening disease. We must acknowledge that while the default setting is good health, there is always an onset to a disease and never to a return to good health. This onset results in “silent“ angina, and finally a “silent“ attack can happen. In fact, Dutch researchers estimated that 43% of heart attacks went unrecognized (de Torbal et al., 2006). Our ultimate aim was to predict a heart attack, or at least to quantitatively analyze the heart condition, based on the belief that it is possible to predict a heart attack by observing fluctuations in heartbeat intervals. Fluctuation analysis first appeared in the physical literature a long time ago (Peng et al., 1995). However, strong empirical evidence of its accuracy and usefulness must still be collected. Traditionally, cardiac studies have employed heart rate variability (HRV) to detect the onset of cardiac problems, including disorders of the autonomic nervous system. Problems arise, however, when patients are previously assumed to be healthy before the appearance of symptoms associated with HRV. An earlier marker is necessary because the early identification of symptoms aids in the prevention of the onset of chronic diseases. Detrended fluctuation analysis (DFA) (Peng et al., 1995) was proposed as a potentially useful method for detecting the signs of cardiovascular disease (See Stanley et al., 1999); although DFA has not yet been developed as a practical medical tool, such as the electrocardiogram (EKG). (We prefer the abbreviation “EKG” to “ECG,” with due respect to the inventor, Dutch physiologist, Nobel laureate, Willem Einthoven.) We recently tested the practical usefulness of DFA by using the heart of crustacean-animal models. In the test, we successfully showed that DFA could distinguish between intact and isolated hearts (Yazawa et al., 2004). In that study, we found out that the scaling exponent of the isolated hearts shifted and approached to 0.5 without exception. In turn, the scaling exponent of the intact hearts showed a value of about 1.0 without exception. As a result, we realized that DFA was reliable and useful because DFA was likely able to accurately reflect

Generation Mechanism of Alternans in Luo–Rudy Model

Electrical alternans is the alternating amplitude from beat to beat in the action potential of the cardiac cell. It has been associated with ventricular arrhythmias in many clinical studies; however, its dynamical mechanisms remain unknown. The reason is that we do not have realistic network models of the heart system. Recently, Yazawa clarified the network structure of the heart and the central nerve system in the crustacean heart. In this study, we construct a simple model of the heart system based on Yazawa’s experimental data. Using this model, we clarify that two parameters (the conductance of sodium ions and free concentration of potassium ions in the extracellular compartment) play the key roles of generating alternans. In particular, we clarify that the inactivation gate of the time-independent potassium channel is the most important parameter. Moreover, interaction between the membrane potential and potassium ionic currents is significant for generating alternate rhythms. This result indicates th...