Acetylsalicylic acid and autonomic modulation

Abstract

Loss of autonomic balance characterized by increased sympathetic activity and decreased vagal activity has been implicated as a major cardiovascular risk factor. Aspirin's cardioprotective abilities involve a multitude of physiologic processes. However, the effects of aspirin on cardiac autonomic activity are unknown. In a double-blind crossover study, 22 subjects randomly received either aspirin or placebo in the amounts of 325 mg with each meal (three times per day) over a 2.5-day period. The total amount of aspirin ingested was 2,275 mg, which resulted in plasma levels of 3.3 mg/dl. At the conclusion of each treatment, subjects were evaluated for autonomic physiology activity using standard autonomic tests. Power spectral analyses of the electrocardiograms were used to delineate autonomic function. A 2 x 4 repeated measures analysis of variance revealed significant and favorable changes in autonomic activity after the use of aspirin. Specifically, at rest high-frequency (HF) power was significantly higher (mean, 1,090 + 1,463.5 msec2) compared with the placebo (mean, 692 742 msec2) (p<0.05). Low-frequency (LF) power was significantly reduced (mean, 963 745 msec2) after aspirin compared with placebo (mean, 1,100 906 msec2). After the aspirin treatment, a significantly lower LF-to-HF power ratio (mean, 1.7 2 msec2) was noted at rest when compared with the placebo (mean, 2.5 2.7 msec2) (p <0.05). Similar significant trends were seen during the sustained isometric contraction after aspirin therapy for HF power (mean 210 2.15 msec2) compared with placebo (mean, 213 184 msec2) (p <0.05). Accordingly, the LF-to-HF power ratio was lower as well when compared to placebo treatment (mean, 2.3 3.5 msec2) (mean, 5.3 8.4 msec2) (p <0.05). No differences were found in breathing rates for hemodynamic variables between any of the protocols. The significant reduction of LF-to-HF ratio, a marker of sympathovagal balance, for both protocols appeared to be largely due to a withdrawal of LF modulation and concomitant but lesser increase in HF modulation. Favorable alterations in autonomic outflow through prostaglandin inhibition may be one of the mechanisms by which low therapeutic amounts of aspirin provide prophylactic cardioprotection.

Low-Dose Aspirin for Prevention of Cardiovascular Risk in Bereavement: Results from a Feasibility Study

“…It targets the main cardiovascular risk factors during bereavement, is inexpensive, is widely available, does not require a prescription, and is feasible in other short-term interventions. Low-dose aspirin is widely used for its antiplatelet effect, has anti-inflammatory properties, and positively influences depressed mood [4], HRV [5], and blood pressure [6].To investigate aspirin as a feasible preventive intervention, acutely bereaved participants (n = 10) were recruited on average within 30 days (SD = 14.67) of the death of their spouse; nonbereaved controls (n = 12) were also recruited. We assessed hemodynamic markers (blood pressure, heart rate, HRV) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CES-D) during 2 laboratory visits.…”

The brain as a target for development of new class of drugs for the treatment of somatic diseases

“…In addition, measurement of autonomic nervous system activity in patients receiving aspirin showed significant increases in heart rate variability, a marker of sympatho-vagal balance. These data indicate that inducement of favorable autonomic activity may participate in acetylsalicylic acid's cardioprotective effects [12]. Acetylsalicylic acid also exerts prophylactic effects on the development and progression of certain types of cancer [13].…”

Cyclooxygenase inhibitors and the exercise-induced stress response

“…The pathways through which prostaglandins are involved in the cortisol stress response include a direct influence on the release of corticotropin-releasing hormone (CRH) and/or antidiuretic hormone (ADH) from the paraventricular nucleus (PVN), and indirect stimulation of the PVN via the central noradrenergic neurons. 8,14 Prostaglandins are further involved in the exercise-induced autonomic nervous system response 7 and in the increase in body temperature and other metabolic adaptations. 14 Several other aspects of the exercise-related neuroendocrine response, which are under control of the hypothalamus and the hypothalamo-pituitary axis, are also influenced by prostaglandins and other eicosanoids.…”

“…13 NSAIDs may theoretically also influence the adaptive exercise-induced stress response through suppression of the synthesis of those prostaglandins that stimulate the fever response, the sympathetic nervous system and the hypothalamo-pituitary-adrenocortical axis. 7,8,18 The frequent use of COX inhibitors by athletes is a wellknown occurrence. In view of their role in the development of the exercise-induced stress response, COX inhibitors could theoretically also be expected to have an effect on the performance of athletes.…”

“…The plasma half-life of naproxen is 12 -15 hours and peak plasma concentrations are seen in about 2 hours. 7,20 Rofecoxib is 50 times more selective in inhibiting the COX-2 isoenzyme. The plasma half-life is 10 -17 hours and peak plasma concentrations are seen in 2 -3 hours.…”