Low-dose Aspirin Inhibits Cardiac Sympathetic Activation and Vagal Withdrawal Response to Morning Rising.

Aspirin is known to interfere with platelet function and can protect individuals at risk of sudden death. However, this property of aspirin is less defined for cardiac autonomic activity. We assessed pulse rate variability by spectral analysis and measured plasma eicosanoid levels before and after administration of 81-mg aspirin to 12 healthy subjects over a 60-degree head-up tilt test in the morning. In upright posture, low-dose aspirin decreased both the normalized unit value of low-frequency (normalized LF) power (mean ± SD, 82.5 ± 4.5 vs. 77.5 ± 6.5 nu, P = 0.01) and LF/HF ratio (6.0 ± 2.1 vs. 4.7 ± 2.7, P = 0.02) and augmented the normalized unit value of high-frequency power (15.0 ± 4.4 vs. 19.8 ± 6.4 nu, P = 0.004). It simultaneously upregulated plasma 6-keto-PGF1α level (13.4 ± 6.8 vs. 19.7 ± 12.8 pg/mL, P = 0.04) and inhibited plasma thromboxane B2 (TXB2) level (11.6 ± 7.3 vs. 6.3 ± 4.2 pg/mL, P = 0.003). In the upright posture, both before and after aspirin, there was a significant direct correlation between plasma TXB2 levels and the normalized LF power (r = 0.42, P = 0.04) as well as between the plasma TXB2/6-keto-PGF1α ratio and the normalized LF power (r = 0.50, P = 0.01). Administration of low-dose aspirin in healthy people inhibits cardiac sympathetic activation and vagal withdrawal response to morning rising through an alternation of the TXA2/PGI2 balance.

Influence of hyperoxia on skin vasomotor control in normothermic and heat-stressed humans.

Hyperoxia induces skin vasoconstriction in humans, but the mechanism is still unclear. In the present study we examined whether the vasoconstrictor response to hyperoxia is through activated adrenergic function (protocol 1) or through inhibitory effects on nitric oxide synthase (NOS) and/or cyclooxygenase (COX) (protocol 2). We also tested whether any such vasoconstrictor effect is altered by body heating. In protocol 1 (n = 11 male subjects), release of norepinephrine from adrenergic terminals in the forearm skin was blocked locally by iontophoresis of bretylium (BT). In protocol 2, the NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) and the nonselective COX antagonist ketorolac (Keto) were separately administered by intradermal microdialysis in 11 male subjects. In the two protocols, subjects breathed 21% (room air) or 100% O(2) in both normothermia and hyperthermia. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure measured by Finapres. In protocol 1, breathing 100% O(2) decreased (P < 0.05) CVC at the BT-treated and at untreated sites from the levels of CVC during 21% O(2) breathing both in normothermia and hyperthermia. In protocol 2, the administration of l-NAME inhibited (P < 0.05) the reduction of CVC during 100% O(2) breathing in both thermal conditions. The administration of Keto inhibited (P < 0.05) the reduction of CVC during 100% O(2) breathing in hyperthermia but not in normothermia. These results suggest that skin vasoconstriction with hyperoxia is partly due to the decreased activity of functional NOS in normothermia and hyperthermia. We found no significant role for adrenergic mechanisms in hyperoxic vasoconstriction. Decreased production of vasodilator prostaglandins may play a role in hyperoxia-induced cutaneous vasoconstriction in heat-stressed humans.

Reduced baroreflex cardiac sensitivity predicts increased cognitive performance.

Abstract This study evaluated the relationship between baroreceptor reflex sensitivity and cognitive performance. Twenty normal subjects performed the Uchida-Kraepelin test, a serial arithmetic task. Baroreceptor reflex sensitivity during a 5-min Uchida-Kraepelin test was assessed in minute periods by spectral analysis using the maximum-entropy method. During the task, baroreceptor reflex sensitivity was significantly reduced. There was an inverse between-subjects association between baroreceptor reflex sensitivity and the level of performance (number of additions completed) both at different time periods of the Uchida-Kraepelin test and during the whole task (r=-.51). This finding supports the existence of a pathway mediating mutual cardiovascular-central nervous system influences through the baroreceptors, establishing an essential mechanism facilitating adaptive reactions to stressful conditions.

Assessment of cardiac baroreflex function during fixed atrioventricular pacing using baroreceptor-stroke volume reflex sensitivity.

UNLABELLED: Baroreflex sensitivity in paced patients. INTRODUCTION: The baroreceptor-heart rate (HR) reflex has prognostic value in cardiovascular medicine. However, it cannot be used in chronotropically incompetent or paced patients. In healthy subjects, the baroreceptor-stroke volume (SV) reflex, with power spectral analysis of SV and blood pressure (BP) variations in the low-frequency band, serves as an alternate measure of the baroreceptor-cardiac reflex. This study examined the baroreceptor-stroke volume (SV) reflex sensitivity in the supine and 60 degrees upright positions in paced patients. METHODS AND RESULTS: We studied 16 recipients of dual-chamber pacemakers paced at a fixed rate. The hemodynamics and baroreceptor-SV reflex sensitivity were measured during atrioventricular (AV) sequential pacing every 5 minute in the supine and 60 degrees upright positions. Mean SV decreased from 42.0+/-20.1 mL in the supine to 36.6+/-16.1 mL in the upright position (P<0.05), whereas BP and total peripheral resistance did not change. A significant fall in baroreceptor-SV reflex sensitivity from 29.2+/-18.0%/mmHg to 19.5+/-15.5%/mmHg was observed during upright tilt (P<0.005). CONCLUSION: Fixed-rate AV sequential pacing did not blunt the decrease in baroreceptor-SV reflex sensitivity consistent with the arterial baroreflex gain response to upright posture. The decreased baroreceptor-SV reflex sensitivity occurring with the upright posture may reflect a baroreflex-induced inotropic effect secondary to vagal withdrawal and sympathetic activation.

Determination of baroreceptor-stroke volume reflex sensitivity by power spectral analysis: a quantitative probe of baroreceptor-cardiac reflex.

Baroreceptor-cardiac reflex, which consists of baroreceptor-induced chronotropic and inotropic actions, is a very useful index of cardiac sympathovagal balance. Baroreceptor-heart rate reflex sensitivity, which reflects baroreceptor-induced chronotropic action, has been used as a marker of baroreceptor-cardiac reflex. However, it cannot be used in patients with chronotropic incompetence and/or implanted cardiac pacemaker. We hypothesized that baroreceptor-stroke volume (SV) reflex sensitivity, which reflects baroreceptor-induced inotropic action, may also be a useful method for measurement of baroreceptor-cardiac reflex, similar to the baroreceptor-heart rate reflex sensitivity. To test this hypothesis, we measured baroreceptor-SV reflex sensitivity expressed as ratio of low frequency (LF) power to total power of SV fluctuation (LF/TP(SV): %/mmHg) by spectral analysis of mean blood pressure and SV fluctuations, the gain in low-frequency band between two signals in supine and 60 degrees upright positions, and compared these values to baroreceptor-heart rate reflex sensitivity in 14 healthy subjects. Baroreceptor-SV reflex sensitivity correlated significantly with baroreceptor-heart rate reflex sensitivity (r = 0.73, p < 0.0001). In addition, baroreceptor-SV reflex sensitivity correlated significantly and positively with high frequency (HF) power (r = 0.57, p < 0.005) and negatively with LF/HF ratio (r = -0.57, p < 0.005) in power spectral analysis of R-R interval variability. Moreover, baroreceptor-SV reflex sensitivity in LF/TP(SV) correlated positively with the R-R interval (r = 0.70, p < 0.0001) and negatively with diastolic blood pressure (r = -0.50, p < 0.01). We conclude that baroreceptor-SV reflex sensitivity in LF/TP(SV) can be used as a quantitative probe of baroreceptor-cardiac reflex, similar to the baroreceptor-heart rate reflex sensitivity in healthy subjects, and it may enable us to estimate inotropic aspect in baroreceptor-cardiac reflex in patients with chronotropic incompetence and/or implanted pacemaker.

Influence of coronary artery disease risk factors on baroreflex sensitivity in the elderly.

In this study, we assessed whether baroreflex sensitivity (BRS) is influenced by risk factors of cardiovascular disease. Subjects of this study were 95 elderly people (40 males and 55 females; mean age +/- SD, 66.6+/-1.6 years) who underwent a medical check-up. BRS was determined as the gain of transfer function in baroreflex arc by spectral analysis of mean blood pressure and R-R interval variabilities in low-frequency band (0.04-0.15 Hz). Gender-related differences in BRS and relationships between BRS and various risk factors of cardiovascular disease were investigated. The value of BRS was significantly higher in males [10.7+/-3.7 (SD) ms/mmHg] than in females [9.0+/-4.0 ms/mmHg, p< 0.05]. However, this gender-related difference disappeared when other variables were taken into account in the multivariate model. Multiple regression analyses showed independent inverse relationships between BRS and heart rate [b=-0.016+/-0.004 (SE) bpm, beta=-0.39], and between BRS and platelet count [b=-0.002+/-0.001 x 103/ micro l, beta=-0.22]. Our results indicated that BRS is inversely related to platelet count in the elderly population. The precise mechanism of this correlation is unknown, but platelet factors released from platelet aggregates can potentially influence vascular function and modify BRS, or there is a common underlying determinant responsible for the covariation.

Effect of plasma lipoproteins on natural killer cell activity in the elderly population.

BACKGROUND: Natural killer (NK) cells possess spontaneous cytotoxicity against tumors and virus-infected cells to play a major role in immunosurveillance and defense against the development of cancer, as well as bacterial and viral infections. The role of plasma lipoproteins in atherogenesis is well recognized, but the physiological relevance of their immunoregulatory properties is still questioned. In particular, it is unknown whether hypercholesterolemia should be considered a risk factor for diminished immunity in old age. METHODS: To evaluate effects of plasma lipoprotein levels on immune function, we assessed the relation between plasma lipoprotein profiles and NK cell activity. NK cell activity was assayed by release of (51)Cr from K562 target cells, and concurrent plasma lipoprotein levels were measured in 47 samples of elderly males (mean age +/- SD, 66.6 +/- 1.7 years). RESULTS: Univariate regression analyses revealed direct relations between NK cell activity and high-density lipoprotein cholesterol (r=.46, p<.001), apolipoprotein (Apo) A-1 (r=.48, p<.001), and Apo A-2 (r=.46, p<.005). In addition, multiple regression analyses showed a direct independent relation between NK cell activity and Apo A-1 (b=0.32+/-0.09 mg/dl, beta=0.48, and p <.001). CONCLUSION: NK cell activity is related directly to plasma Apo A-1 levels in elderly subjects. The mechanisms of this interaction are unknown, but Apo A-1 contributes to the composition of the antiatherogenic fraction of high-density lipoprotein and could also defend against infectious and malignant disease through a potential for NK cell activity.