Keizo Shiraki

Cardiovascular Responses to Lower Body Negative Pressure in the Elderly: Role of Reduced Leg Compliance

Background: It is warranted to test the hypothesis that the orthostatic tolerance does not diminish in the aging process per se in healthy individuals. Objective: The purpose of the present study was to examine the effects of aging on cardiovascular response and baroreflex sensitivity during lower body negative pressure (LBNP) with a special reference to leg compliance. Methods: Fifteen healthy old male subjects [mean age 68.2 ± (SE) 0.8 years] and 22 young male subjects [mean age 21.4 ± (SE) 0.3 years] underwent a 21-min bout of ramped LBNP (from 0 to –60 mm Hg, 10 mm Hg each for 3 min). Heart rate (HR), blood pressure, stroke volume (SV), forearm blood flow, and leg volume were measured throughout the experimental period. The arterial baroreflex sensitivity was calculated from spontaneous changes in beat-to-beat arterial pressure and HR during LBNP. Results: The leg compliance was lower, and the orthostatic tolerance index was higher in old than in young participants. The LBNP-associated increases in leg volume and HR and the decreases in SV were lower in old subjects, suggesting that the reduction of venous return was less in magnitude in old subjects during LBNP. The baseline value of baroreflex sensitivity evaluated by the sequence analysis was smaller, and no LBNP-related change was observed in old subjects, whereas a gradual LBNP-related reduction was observed in young subjects. The slope of regression between ΔSV and change in forearm vascular resistance during LBNP was identical in both age groups. Conclusions: We conclude that: (1) aging per se does not increase the intolerance to orthostatic stress induced by LBNP; (2) a low magnitude of venous return reduction during LBNP contributes to a higher tolerance in the old because of lower leg compliance, and (3) the sensitivity of baroreflex control of the HR is attenuated in the old; however, there is no deterioration of the sensitivity of the peripheral vasoconstriction during LBNP.

Whole body heating reduces the baroreflex response of sympathetic nerve activity during Valsalva straining

The present experiment was carried out to examine the possible effects of whole body heating on the baroreflex control of muscle sympathetic nerve activity (MSNA) and heart rate (HR). Nine healthy male volunteers underwent the Valsalva maneuver during exposure to heat stress using a hot water-perfused suit. To exclude an effect from the unloading of the cardiopulmonary baroreceptors during hyperthermia, the central hypovolemia was counterbalanced by head-down tilt (HDT) at 8 degrees. The baroreflex slopes of MSNA and HR against mean arterial pressure were determined by regression analysis during the early phase II (falling blood pressure period) of the Valsalva maneuver. The core temperature increased from 36.9 +/- 0.1 degrees C at thermoneutral to 37.7 +/- 0.1 degrees C during heat exposure, whereas the left atrial diameter (LAD) decreased. Both the MSNA and HR increased (P < 0.05) during hyperthermia. The baroreflex slopes of MSNA and HR in the phase II decreased 30 +/- 8% (P < 0.05) and 24 +/- 9% (P < 0.05), respectively, during hyperthermia. The HDT increased LAD, but there was no change in HR, arterial pressure and the baroreflex slopes. These results suggest that hyperthermia reduces the baroreflex responses of MSNA and HR during a transient falling period of blood pressure. These reduced baroreflex responses may not be attributable to an unloading of the cardiopulmonary baroreceptors during heat stress.

Role of cardiac‐renal neural reflex in regulating sodium excretion during water immersion in conscious dogs

The present study was undertaken to determine the role of cardiopulmonary mechanoreceptors in inducing the sustained reduction of renal sympathetic nerve activity (RSNA) and concomitant changes in sodium excretion occurring during water immersion (WI) in intact dogs. Seven cardiac‐denervated dogs were chronically instrumented for measuring RSNA, systemic arterial (Pa), central venous (Pcv) and left atrial pressures (Pla). WI initially decreased RSNA in cardiac denervated dogs by 10.0 ± 5.5 %; thereafter the RSNA fell to a nadir of 18.5 ± 5.6 % (P < 0.05) at 40–80 min of WI and then returned toward the pre‐immersion level. Renal sodium excretion increased significantly by 211 ± 69 % (P < 0.05) only during the first 20–40 min of WI. WI increased Pa, Pcv and Pla in a step manner from 94 ± 3 to 108 ± 3 mmHg (P < 0.05), from 1.4 ± 0.5 to 12.3 ± 1.0 mmHg (P < 0.05) and from 4.9 ± 0.6 to 15.4 ± 1.2 mmHg (P < 0.05), respectively. These responses in RSNA and sodium excretion to WI in the cardiac‐denervated dogs were significantly (P < 0.05) attenuated compared with those in a previous group of intact dogs. These data suggest that the attenuated responses of neural and excretory response to WI observed in cardiac‐denervated dogs can be attributed to an interruption of afferent input originating from the cardiopulmonary mechanoreceptors to the central nervous system.

Hypovolemic intolerance to lower body negative pressure in female runners

PURPOSE An attenuated baroreflex response and orthostatic intolerance have been reported in endurance-trained male athletes; however, it is still unknown whether this occurs also in females. The purpose of the present study was to examine whether endurance exercise-trained women had a predisposition to orthostatic compromise, and if so, what causative factor(s) may induce orthostatic intolerance. METHODS We studied cardiovascular and hormonal responses to graded lower body negative pressure (LBNP) (0 to -60 mm Hg) in 26 middle-distance female runners (18.6 +/- 0.1 yr) as the exercise-trained (ET) subjects and 23 age-matched untrained (UT) control subjects. On the basis of the occurrence of syncope episodes during LBNP, ET and UT subjects were further allocated to two groups; ET with presyncope (ET+syncope) and without presyncope (ET-syncope) and UT with presyncope (UT+syncope) and without presyncope (UT-syncope). RESULTS Occurrence of presyncope episodes during LBNP was higher in ET (65.4%, P < 0.05) than that for UT (34.8%). Leg compliance was higher (P < 0.05) in ET than in UT. LBNP reduced stroke volume (SV) more (P < 0.05), increased heart rate (HR) higher (P < 0.05), and increased forearm vascular resistance (FVR) more in ET+syncope as compared with the other groups. Response of vasoactive hormones to LBNP was higher in ET+syncope (P < 0.05) than that of the other groups except for norepinephrine (NE); high in both ET+syncope and UT+syncope. The relationship between SV and NE, an index of sympathetic neuronal response, had no training-related changes during LBNP. CONCLUSION We conclude that exercise-trained females have a high incidence of orthostatic intolerance during LBNP, with a greater reduction of SV independent of changes in baroreflex and neurohumoral function. A lower incidence of LBNP intolerance in UT may be accounted for by a lower reduction of SV during LBNP. An increase in leg compliance in the exercise-trained females may play an important role in inducing pronounced reduction of SV and hence the intolerance to LBNP.

Quantitative and sustained suppression of renal sympathetic nerve activity by left atrial distension in conscious dogs.

In order to investigate the interrelations between left atrial pressure (Pla) and renal sympathetic nerve activity (RSNA) and heart rate (HR), Pla was increased by a balloon both in conscious sham-operated and cardiac-denervated dogs. RSNA was decreased and HR was increased with increasing Pla in sham-operated dogs. The reflex changes in RSNA and HR induced by the stimulation of atrial receptors persisted for at least 15 min. There was a consistent relationship between Pla and RSNA which could be described by a single exponential equation: % Δ RSNA = 80.0(1−e−0.395 Δ Pla), or by a linear equation when ΔPla was less than 6 mmHg; %ΔRSNA=-13.5ΔPla−2.25. The relationship between Pla and HR can be described by a single exponential equation: Δ HR = 86.5(1−e−0.125 Δ Pla). A significant linear relationship between RSNA and HR was obtained during a graded left atrial distention (%ΔRSNA=-1.08ΔHR−17.7). In cardiac-denervated dogs, RSNA tended to increase and HR remained constant during the left atrial distention. These results indicate that left atrial receptors regulate RSNA and HR in both a quantitative and sustained manner in conscious sham-operated dogs.

Role of cardiopulmonary and carotid sinus baroreceptors in regulating renal sympathetic nerve activity during water immersion in conscious dogs.

The aim of the present study was to investigate how loading of cardiopulmonary baroreceptors induced by water immersion (WI) modifies baroreflex control of renal sympathetic nerve activity (RSNA) in conscious dogs. Nine dogs were chronically instrumented for measuring carotid sinus nerve activity (CSNA), RSNA, carotid arterial (Pca), and central venous (Pcv) pressures. The stimulus-response relationships of Pca-CSNA and Pca-RSNA were determined simultaneously in the same dog by changing Pca using rapid intravenous infusions vasoactive drugs during pre-WI and WI. WI increased central venous pressure significantly (P < 0.05) by 10.4 mmHg. WI shifted the Pca-RSNA curve acutely leftward compared with the pre-WI period, which was associated with significant (P < 0.05) decreases in the saturation pressure by 39.0 mmHg and operating range by 43.1 mmHg. WI relocated the operating pressure to near the saturation pressure, where the gain was low. The Pca-CSNA curve obtained during WI was identical to that obtained during pre-WI period. These results suggest that the shift in baroreflex control of RSNA could be attributed to the inhibitory influence of the cardiopulmonary mechanoreceptor loading and not by the resetting of carotid baroreceptors per se.

Muscle Sympathetic Nerve Activity During Acute Increase in Core Temperature in Humans

The effect of heat stress on muscle sympathetic nerve activity was studied in nine men. Transient heat loading was given through water-perfused suits for 40 min. Esophageal temperature (Tes), blood pressure (BP), cardiac output (CO), forearm blood flow (FBF), and sympathetic nerve activity in the peroneal muscle nerve fascicles (MSNA) were measured throughout the experimental period. The average Tes increased to 38.73° ± 0.10°C (P < 0.05) at the termination of the experiment. MSNA rose linearly in proportion to the rise in Tes. FBF increased to about 20 m1/100 ml/min (P < 0.05) with the increase in Tes up to 37.6°C and plateaued thereafter. CO increased by 20% (P < 0.05) 15 min after heat exposure and remained elevated at 8.3 1/min toward the termination of the experiment while leaving BP unchanged. Based on the fact of a constant muscle blood flow during heat stress and a plateaued increment of FBF, we conclude that the Tes-dependent increase in MSNA is an indicator for the evaluation of peripheral sympathetic nerve activities in regions other than the skin.