Altered cardiac ß1 responsiveness in hyperthermic older adults.

Compared with younger adults, passive heating induced increases in cardiac output are attenuated by ∼50% in older adults. This attenuated response may be associated with older individuals' inability to maintain stroke volume through ionotropic mechanisms and/or through altered chronotropic mechanisms. The purpose of this study was to identify the interactive effect of age and hyperthermia on cardiac responsiveness to dobutamine-induced cardiac stimulation. Eleven young (26 ± 4 yr) and 8 older (68 ± 5 yr) participants underwent a normothermic and a hyperthermic (baseline core temperature +1.2°C) trial on the same day. In both thermal conditions, after baseline measurements, intravenous dobutamine was administered for 12 min at 5 µg/kg/min, followed by 12 min at 15 µg/kg/min. Primary measurements included echocardiography-based assessments of cardiac function, gastrointestinal and skin temperatures, heart rate, and mean arterial pressure. Heart rate responses to dobutamine were similar between groups in both thermal conditions (P > 0.05). The peak systolic mitral annular velocity (S'), i.e., an index of left ventricular longitudinal systolic function, was similar between groups for both thermal conditions at baseline. While normothermic, the increase in S' between groups was similar with dobutamine administration. However, while hyperthermic, the increase in S' was attenuated in the older participants with dobutamine (P < 0.001). Healthy, older individuals show attenuated inotropic, but maintained chronotropic responsiveness to dobutamine administration during hyperthermia. These data suggest that older individuals have a reduced capacity to increase cardiomyocyte contractility, estimated by changes in S', via ß1-adrenergic mechanisms while hyperthermic.

The relationship between cognitive style and sensory gating during auditory and somatosensory tasks.

Cognitive styles such as field dependence/independence and empathizing influence individual personalities. Sensory gating is conceptualized as an automatic inhibitory function related to human higher cognitive processing. The present study investigated the relationship between cognitive styles and the automatic inhibitory function using electroencephalographic evoked potentials (EPs) during auditory and somatosensory tasks with a paired stimulus. The Embedded-Figures Test (EFT) and Empathy Questionnaire (EQ) were performed to assess the cognitive styles (field dependence: FD; field independence: FI; empathizing: EM; non-empathizing: Non-EM). Sensory gating was evaluated as an amplitude ratio of EP responses to the second stimulus (S2) over responses to the first stimulus (S1). Subjects were divided into two groups based on EFT scores (FD vs. FI) or EQ scores (EM vs. Non-EM). The S2/S1 amplitude ratio of the auditory long-latency component was significantly smaller in the FD than FI group, while the S2/S1 amplitude ratio of a somatosensory long-latency component was significantly smaller in the FI than FD group. In contrast, these differences in the S2/S1 amplitude ratios of any auditory and somatosensory components were not observed between EM and Non-EM groups. Our results suggest that sensory gating conceptualized as an automatic inhibitory function is related to FD and FI cognitive styles.

Effects of acute hypoxia on human cognitive processing: a study using ERPs and SEPs.

Although hypoxia has the potential to impair the cognitive function, the effects of acute hypoxia on the high-order brain function (executive and/or inhibitory processing) and somatosensory ascending processing remain unknown. We tested the hypothesis that acute hypoxia impairs both motor executive and inhibitory processing and somatosensory ascending processing. Fifteen healthy subjects performed two sessions (sessions 1 and 2), consisting of electroencephalographic event-related potentials with somatosensory Go/No-go paradigms and somatosensory-evoked potentials (SEPs) under two conditions (hypoxia and normoxia) on different days. On 1 day, participants breathed room air in the first and second sessions of the experiment; on the other day, participants breathed room air in the first session, and 12% O2 in the second session. Acute hypoxia reduced the peak amplitudes of Go-P300 and No-go-P300, and delayed the peak latency of Go-P300. However, no significant differences were observed in the peak amplitude or latency of N140, behavioral data, or the amplitudes and latencies of individual SEP components between the two conditions. These results suggest that acute hypoxia impaired neural activity in motor executive and inhibitory processing, and delayed higher cognitive processing for motor execution, whereas neural activity in somatosensory processing was not affected by acute hypoxia.NEW & NOTEWORTHY Hypoxia has the potential to impair the cognitive function, but the effects of acute hypoxia on the cognitive function remain debatable. We investigated the effects of acute hypoxia on human cognitive processing using electroencephalographic event-related potentials and somatosensory-evoked potentials. Acute normobaric hypoxia impaired neural activity in motor executive and inhibitory processing, but no significant differences were observed in neural activity in somatosensory processing.

Effects of face/head and whole body cooling during passive heat stress on human somatosensory processing.

We herein investigated the effects of face/head and whole body cooling during passive heat stress on human somatosensory processing recorded by somatosensory-evoked potentials (SEPs) at C4' and Fz electrodes. Fourteen healthy subjects received a median nerve stimulation at the left wrist. SEPs were recorded at normothermic baseline (Rest), when esophageal temperature had increased by ~1.2°C (heat stress: HS) during passive heating, face/head cooling during passive heating (face/head cooling: FHC), and after HS (whole body cooling: WBC). The latencies and amplitudes of P14, N20, P25, N35, P45, and N60 at C4' and P14, N18, P22, and N30 at Fz were evaluated. Latency indicated speed of the subcortical and cortical somatosensory processing, while amplitude reflected the strength of neural activity. Blood flow in the internal and common carotid arteries (ICA and CCA, respectively) and psychological comfort were recorded in each session. Increases in esophageal temperature due to HS significantly decreased the amplitude of N60, psychological comfort, and ICA blood flow in the HS session, and also shortened the latencies of SEPs (all, P < 0.05). While esophageal temperature remained elevated, FHC recovered the peak amplitude of N60, psychological comfort, and ICA blood flow toward preheat baseline levels as well as WBC. However, the latencies of SEPs did not recover in the FHC and WBC sessions. These results suggest that impaired neural activity in cortical somatosensory processing during passive HS was recovered by FHC, whereas conduction velocity in the ascending somatosensory input was accelerated by increases in body temperature.

The effect of elevations in internal temperature on event-related potentials during a simple cognitive task in humans.

The effect of hyperthermia on cognitive function remains equivocal, perhaps because of methodological discrepancy. Using electroencephalographic event-related potentials (ERPs), we tested the hypothesis that a passive heat stress impairs cognitive processing. Thirteen volunteers performed repeated auditory oddball paradigms under two thermal conditions, normothermic time control and heat stress, on different days. For the heat stress trial, these paradigms were performed at preheat stress (i.e., normothermic) baseline, when esophageal temperature had increased by ∼0.8°C, when esophageal temperature had increased by ∼2.0°C, and during cooling following the heat stress. The reaction time and ERPs were recorded in each session. For the time control trial, subjects performed the auditory oddball paradigms at approximately the same time interval as they did in the heat stress trial. The peak latency and amplitude of an indicator of auditory processing (N100) were not altered regardless of thermal conditions. An indicator of stimulus classification/evaluation time (latency of P300) and the reaction time were shortened during heat stress; moreover an indicator of cognitive processing (the amplitude of P300) was significantly reduced during severe heat stress (8.3 ± 1.3 µV) relative to the baseline (12.2 ± 1.0 µV, P < 0.01). No changes in these indexes occurred during the time control trial. During subsequent whole body cooling, the amplitude of P300 remained reduced, and the reaction time and latency of P300 remained shortened. These results suggest that excessive elevations in internal temperature reduce cognitive processing but promote classification time.

Effects of passive heat stress on human somatosensory processing.

Herein, we investigated the effects of passive heat stress on human somatosensory processing recorded by somatosensory-evoked potentials (SEPs). Fifteen healthy subjects received a median nerve stimulation at the left wrist under two thermal conditions: Heat Stress and normothermic Time Control. The latencies and amplitudes of P14, N20, P25, N35, P45, and N60 at C4' and P14, N18, P22, and N30 at Fz were evaluated. Under the Heat Stress condition, SEPs were recorded at normothermic baseline (1st), early in heat stress (2nd), when esophageal temperature had increased by ~1.0°C (3rd) and ~2.0°C (4th), and after heat stress (5th). In the Time Control condition, SEPs were measured at the same time intervals as those in the Heat Stress condition. The peak latencies and amplitudes of SEPs did not change early in heat stress. However, the latencies of P14, N20, and N60 at C4' and P14, N18, and P22 at Fz were significantly shorter in the 4th session than in the 1st session. Furthermore, the peak amplitudes of P25 and N60 at C4', and P22 and N30 at Fz decreased with increases in body temperature. On the other hand, under the Time Control condition, no significant differences were observed in the amplitudes or latencies of any component of SEPs. These results suggested that the conduction velocity of the ascending somatosensory input was accelerated by increases in body temperature, and hyperthermia impaired the neural activity of cortical somatosensory processing.

Blood flow distribution during heat stress: cerebral and systemic blood flow.

The purpose of the present study was to assess the effect of heat stress-induced changes in systemic circulation on intra- and extracranial blood flows and its distribution. Twelve healthy subjects with a mean age of 22±2 (s.d.) years dressed in a tube-lined suit and rested in a supine position. Cardiac output (Q), internal carotid artery (ICA), external carotid artery (ECA), and vertebral artery (VA) blood flows were measured by ultrasonography before and during whole body heating. Esophageal temperature increased from 37.0±0.2°C to 38.4±0.2°C during whole body heating. Despite an increase in Q (59±31%, P<0.001), ICA and VA decreased to 83±15% (P=0.001) and 87±8% (P=0.002), respectively, whereas ECA blood flow gradually increased from 188±72 to 422±189 mL/minute (+135%, P<0.001). These findings indicate that heat stress modified the effect of Q on blood flows at each artery; the increased Q due to heat stress was redistributed to extracranial vascular beds.

Macrophage-derived matrix vesicles: an alternative novel mechanism for microcalcification in atherosclerotic plaques.

RATIONALE: We previously showed that early calcification of atherosclerotic plaques associates with macrophage accumulation. Chronic renal disease and mineral imbalance accelerate calcification and the subsequent release of matrix vesicles (MVs), precursors of microcalcification. OBJECTIVE: We tested the hypothesis that macrophage-derived MVs contribute directly to microcalcification. METHODS AND RESULTS: Macrophages associated with regions of calcified vesicular structures in human carotid plaques (n=136 patients). In vitro, macrophages released MVs with high calcification and aggregation potential. MVs expressed exosomal markers (CD9 and TSG101) and contained S100A9 and annexin V. Silencing S100A9 in vitro and genetic deficiency in S100A9-/- mice reduced MV calcification, whereas stimulation with S100A9 increased calcification potential. Externalization of phosphatidylserine after Ca/P stimulation and interaction of S100A9 and annexin V indicated that a phosphatidylserine-annexin V-S100A9 membrane complex facilitates hydroxyapatite nucleation within the macrophage-derived MV membrane. CONCLUSIONS: Our results support the novel concept that macrophages release calcifying MVs enriched in S100A9 and annexin V, which contribute to accelerated microcalcification in chronic renal disease.

Mechanisms and controllers of eccrine sweating in humans.

Human body temperature is regulated within a very narrow range. When exposed to hyperthermic conditions, via environmental factors and/or increased metabolism, heat dissipation becomes vital for survival. In humans, the primary mechanism of heat dissipation, particularly when ambient temperature is higher than skin temperature, is evaporative heat loss secondary to sweat secretion from eccrine glands. While the primary controller of sweating is the integration between internal and skin temperatures, a number of non-thermal factors modulate the sweating response. In addition to summarizing the current understanding of the neural pathways from the brain to the sweat gland, as well as responses at the sweat gland, this review will highlight findings pertaining to studies of proposed non-thermal modifiers of sweating, namely, exercise, baroreceptor loading state, and body fluid status. Information from these studies not only provides important insight pertaining to the basic mechanisms of sweating, but also perhaps could be useful towards a greater understanding of potential mechanisms and consequences of disease states as well as aging in altering sweating responses and thus temperature regulation.