Studies on left ventricular mechanical work and energetics in rat and mouse hearts are reviewed. First, left ventricular linear end-systolic pressure-volume relation (ESPVR) and curved end-diastolic pressure-volume relation (EDPVR) in canine hearts and left ventricular curved ESPVR and curved EDPVR in rat hearts are reviewed. Second, as an index for total mechanical energy per beat in rat hearts as in canine hearts, a systolic pressure-volume area (PVA) is proposed. By the use of our original system for measuring continuous oxygen consumption for rat left ventricular mechanical work, the linear left ventricular myocardial oxygen consumption per beat (VO₂)-PVA relation is obtained as in canine hearts. The slope of VO₂-PVA relation (oxygen cost of PVA) indicates a ratio of chemomechanical energy transduction. VO₂ intercept (PVA-independent VO₂) indicates the summation of oxygen consumption for Ca²⁺ handling in excitation-contraction coupling and for basal metabolism. An equivalent maximal elastance (eEmax) is proposed as a new left ventricular contractility index based on PVA at the midrange left ventricular volume. The slope of the linear relation between PVA-independent VO₂ and eEmax (oxygen cost of eEmax) indicates changes in oxygen consumption for Ca²⁺ handling in excitation-contraction coupling per unit changes in left ventricular contractility. The key framework of VO₂-PVA-eEmax can give us a better understanding for the biology and mechanisms of physiological and various failing rat heart models in terms of mechanical work and energetics.

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To study Ca²⁺ handling by the junctional sarcoplasmic reticulum (JSR), the time course of short-term mechanical restitution after varying magnitudes of twitch contractions was assessed in rat papillary muscle. Mechanical restitution consisted of a pretwitch latency period followed by a rapid and a subsequent much slower restitution of twitch force. The rate of rapid restitution was independent of the magnitude of the preceding twitch, which suggests that the rate of JSR Ca²⁺ repletion was dependent on the amount of Ca²⁺ remaining in the JSR after a twitch contraction. Based on this finding, the functions G(t) and H(t), representing the time courses of JSR Ca²⁺ repletion and release, respectively, were derived graphically from a family of the mechanical restitution curves. G(t) increased monotonically with time at a decreasing rate, while H(t) increased with time in a sigmoid manner. The mechanical alternans were simulated by using experimental values and mathematically predicted values of G(t) and H(t). A substitution of extracellular Na⁺ with Li⁺ to inhibit Na⁺/Ca²⁺ exchange resulted in an augmentation of G(t) by approximately 10%, presumably by increasing the tubular SR Ca²⁺ uptake. The inhibition of tubular SR Ca²⁺ uptake by thapsigargin (10 μM) reduced mechanical restitution by approximately 13% of the maximal twitch force, independent of the phase of mechanical restitution; the effect was greater at an earlier time point in the mechanical restitution. These results suggest that early JSR Ca²⁺ replenishment results mainly from the movement of Ca²⁺ from the tubular SR.

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Postprandial gastric myoelectrical activity recorded by electrogastrogram (EGG) with the subject in a supine position has shown to be enhanced after moderate-intensity pedaling exercise in an upright seated position, despite the suppression of vagal nerve activity. However, it is still unknown whether the effect is due to the exercise itself and/or a meal or how the position change has influenced the effects. To address this, we used a position-controllable cycle ergometer to examine the effects of the moderate-intensity exercise on EGG activity and the high-frequency (HF) component of heart rate variability (HRV), an index of vagal nerve activity. To eliminate the effect of position change, we carried out the exercise and the EGG recording in the supine position. The peak amplitude of the EGG was enhanced by prior moderate-intensity exercise with a reduced HF component of HRV, which did not differ for postexercise conditions with or without a meal. The small amount of meal itself, however, enhanced both the peak amplitude of the EGG and the HF component of HRV. The peak frequency of EGG was reduced and the instability coefficient of EGG was increased only after the exercise itself. Taken together, these results suggest that the enhanced amplitude of gastric myoelectrical activity can be induced by moderate-intensity exercise itself, even with suppressed vagal nerve activity, and that the mechanism underlying the exercise effects would differ from that underlying the effect of a meal alone.

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Effects of 9-week hindlimb suspension and 8-week recovery on air-righting reaction in response to drop from a supine position were studied in adult rats. The righting time in rats at the end of suspension (∼220 ms) was longer than the age-matched controls (∼120 ms, p < 0.05). The unloading-related change in righting time was accompanied by lowered activities of electromyogram (EMG) and altered recruitment of both neck and back muscles at a specific stage of drop. After 8 weeks of reambulation, righting time recovered toward the control level (∼153 ms, p < 0.05), but the EMG activity of back muscle was still less than controls. In contrast, the EMG of neck muscle during fall was even increased. The differences in the characteristics of the muscle fibers between two groups were minor. It is suggested that inhibition of recruitment, rather than the changes in the fiber characteristics, of neck and back muscles is one of the major causes of the slow air-righting.

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We studied the effects of non-pain transcutaneous electrical stimulation (TES) and pain-eliciting TES on vibration-induced finger flexion reflex (VFR) in 12 healthy volunteers. Tonic finger flexion reflex in the upper limb was induced by the application of vibratory stimulation on the volar side of the middle fingertip in the right hand before and after TES. Non-pain TES or pain-eliciting TES was applied on the skin between the bases of the first and second metacarpals in the right hand dorsal area in a crossover design. Pain-eliciting TES inhibited VFRs significantly (Fisher's PLSD, p < 0.01), compared to those of the time-control group during and after TES. VFRs were reduced approximately to 63.8% and 78.6% of prestimulation flexion force during and after pain-eliciting TES, respectively. Nonpain TES did not inhibit VFR. These results suggest that pain-conducting afferent fibers have inhibitory neuronal connection over the ipsilateral reflex circuits of VFR in the upper limb.

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The differential role of Na⁺/Ca²⁺ exchange in the regulation of intracellular ionized calcium ([Ca²⁺]i) in immunological and pharmacologically identified type 1 astrocytes and Purkinje cells was studied in rat cerebellar culture, using Ca²⁺ (Fluo-3, Fura-2) and Na⁺ (SBFI) fluorescence measurements. The mean resting [Ca²⁺]_i was significantly higher (191 ± 8 nM, n = 25) in type 1 astrocytes than in Purkinje cells (92 ± 2.5 nM, n = 35). In contrast to Purkinje cells, in unstimulated cerebellar type 1 astrocytes, forward and reverse Na⁺/Ca²⁺ modes operate under resting physiological conditions, being responsible for most of the total Ca²⁺ transplasma membrane fluxes. Four observations support this hypothesis: (1) under resting conditions of temperature and ionic composition, Na⁺_o removal causes a remarkable increase in [Ca²⁺]_i, being inhibited by 2',4' dichlorobenzamil (DCB), and 2-[2-[4-(nitrobenzilloxiphenyl ethyl] isothiourea metanesulfonate (KB-R7943); (2) Ca²⁺_o removal in the presence of Na⁺_o causes an important drop in [Ca²⁺]_i, which is absent in Li+o or NMG+o (N-methyl-D-glucamine) containing medium; (3) the reverse mode exchange inhibitor KB-R7943 mimics the removal of Ca²⁺_o only in the presence of Na⁺_o; and (4) under loaded [Na⁺]_i conditions (ouabain or the activation of taurine-Na⁺-cotransport), reverse mode exchange increases in both astrocytes and Purkinje cells. In type 1 astrocytes stimulated with endothelin-3 (ET-3), the recovery of the Ca²⁺_i signal occurs largely through the Na⁺/Ca²⁺ exchanger. Genistein, a tyrosine kinase inhibitor, completely and reversibly blocks all exchange activity, but not its inactive analogue daidzein, thus suggesting that the Na⁺/Ca²⁺ exchanger of cerebellar type 1 astrocytes may be modulated by phosphorylation. Our main conclusion is that in rat cerebellar type 1 astrocytes under resting physiological conditions, most of the total transplasma membrane Ca²⁺ fluxes take place through the Na⁺/Ca²⁺ exchanger, thus accounting for the resting [Ca²⁺]_i.

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The effects of heat-stress on proliferative potential in vivo were studied in rat skeletal muscle. Male Wistar rats (7-weeks-old) were divided into two groups: control (n = 24) and heat-stressed (n = 24). Rats in the experimental group were exposed to environmental heat-stress (41°C for 60 min) in a heat chamber without anesthesia. The soleus muscles were dissected 1, 7, and 14 days after the heat exposure. The wet and dry weights of soleus muscle relative to body weight in the heat-stressed group were significantly higher than controls 7 days after the exposure (10.1% and 17.5%, respectively, p < 0.05). The distribution of 5-bromo-2'-deoxyuridine and proliferating cell nuclear antigen-positive nuclei, that are the indicators for the cell proliferation, were increased by 2.2 and 5.1 times, respectively 1 day after heating (p < 0.05). The expressions of heat shock protein 72 (58.0%) and phosphorylated p70S6 kinase (52.3%) were increased 1 day following heat exposure (p < 0.05). These results suggest that heat-stress could promote the cell proliferation and induce muscular hypertrophy.

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To better understand the neural mechanism of heart rate (HR) regulation during dynamic exercise, the responses of HR and the magnitude of respiratory R-R interval variation were examined during exercise and recovery at mild intensities in humans. Eight subjects performed 3-min constant load cycle exercises in a semi-supine position at work rates of 25, 50, and 100 W. The respiratory interval was fixed at 4 s. Peak-to-valley variation in R-R interval caused by respiration was measured breath-by-breath and standardized for tidal volume (ΔRRst, a noninvasive index of the degree of parasympathetic cardiac control). At all work rates the HR increased significantly from 2.5 s after the beginning of exercise (p < 0.05) and decreased temporarily and slightly at around 15 s, and the ΔRRst varied almost inversely. The HR and the ΔRRst until 12.5 s after the beginning of exercise changed independently of work rate (ANOVA, p = 0.27 and p = 0.08). The HR – ΔRRst relationship at the initial phase of exercise (for 12.5 s) was almost the same at all work rates. These results suggest that the initial HR response to exercise is strongly parasympathetically regulated independently of work rate. The HR recovered slower than the ΔRRst at 50 and 100 W. On the HR – ΔRRst relationship, the HR during recovery was significantly higher than during exercise at 1/3, 1/2, and 2/3 levels of pre-exercise ΔRRst at 50 and 100 W and at the 1/3 level at 25 W (p < 0.05). At 25 W, the difference in HR at the 1/3 level was 5.5 beats·min⁻¹, and the HR increase to exercise was 21.2 beats·min⁻¹. We suggest that a HR regulatory system responds slower than a cardiac parasympathetic system to exercise, a cardiac sympathetic system, is activated even during mild exercise in humans.

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Effects of heat stress on the recovery of atrophied soleus muscle were studied in rats. Ten-week-old male Wistar rats were randomly divided into cage control (CC) and 5-day hindlimb suspension group (HS). The half of the rats in group HS was exposed to heat stress (41°C for 60 min) in an incubator immediately after the hindlimb suspension (HS-H) and the other group of rats was not heat stressed (HS-C) prior to 10 days of ambulation recovery. One group of cage control rats (CH) was also exposed to heat similarly. The soleus muscles were dissected at four time points, i.e., immediately after the suspension (or heat stress), and 3, 5, and 10 days after the recovery (n = 8 per group at each time point). The absolute wet weight and water and protein content of whole soleus muscle in group HS-C were ∼36, 27, and 8 mg less than CC (p < 0.05). Thus, the percentage contribution of water and protein loss to the decrease in muscle weight was 75 and 22%, respectively. Although water content, as well as muscle weight, was elevated within 3 days, the increase of protein was delayed. Heat exposure prior to recovery accelerated the increase in protein content even in the control group. These phenomena were closely associated with 72-kD heat shock protein (HSP72) content. It is suggested that heat stress applied at the end of hindlimb unloading facilitated the recovery of atrophied soleus muscle of rat, through possibly HSP72-related events of protein metabolism. The data also indicated that the combination of heat and mechanical stress evoked larger and long lasting HSP72 response than does heat or mechanical stress alone.

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This study measured in vivo synthesis of total RNA and protein from cortex, cerebellum and midbrain/brainstem and 6 major organs from Syrian hamsters (Mesocricetus auratus) during (a) 33 h of torpor (body temperature 5–6°C); (b) 90 min of the early arousal; (c) 90 min of the middle arousal; (d) 90 min in cold adapted cenothermic (CEN) hamsters of the same circannual period. Appropriate physiological parameters were used to confirm the phase of the hibernation cycle during infusion and incorporation of [³H]-uridine and [¹⁴C]-leucine. In torpor, RNA synthesis was 5–25% of CEN levels depending upon tissue. In brain and heart mRNA was not preferentially synthesized. Protein was synthesized at low, tissue specific levels during torpor. Initiation of arousal and the warming of anterior organs via non-shivering thermogenesis during the early arousal occurred without measurable synthesis of RNA or proteins. Tissue specific levels of RNA and protein synthesis occurred later after shivering thermogenesis had been recruited and was strongly influenced by thermal gradients in the body. In the middle arousal phase, protein synthesis is most active in the brain despite modest synthesis of RNA and mRNA. The majority of molecular processing required for the induction and maintenance of torpor and the arousal from torpor up until the onset of shivering thermogenesis occurs during the cenothermic period before the hamster initiates the hibernation cycle.

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