Muscle sympathetic nerve activity in women and men following acute myocardial infarction: a meaningful difference?

Awareness of an apparent excess of mortality in women, as compared with men, in the days subsequent to acute myocardial infarction (AMI) prompted Hogarth and colleagues to investigate whether there exist sex-related differences in the magnitude of post-infarct efferent sympathetic nerve discharge. In a remarkable technical tour de force, these investigators quantified the frequency of fibular nerve muscle sympathetic singleand multifibre discharge [muscle sympathetic nerve activity (MSNA)]in a cohort of 72 carefully assembled Caucasian subjects, divided equally between women and men suffering an uncomplicated acute infarct, and well-matched healthy non-medicated female and male control subjects. Patients were screened by history and laboratory examination to exclude the potential confounding influence of known stimuli to sympathetic excitation or autonomic neuropathy. In study patients, MSNA and pre-specified haemodynamic and autonomic variables were acquired on four separate occasions: 2–4 days, and 3, 6, and 9 months after their AMI. Remarkably, complete microneurographic data were acquired over this time period from 35 of the 36 patients. Equally noteworthy is the investigators’ success in their efforts to match patients and control subjects for age, body mass index, waist circumference, smoking history, creatinine, and fasting glucose and lipids, to match male and female patients and their respective controls for blood pressure (BP) and heart rate (HR), and to minimize the effect of other potential confounding variables. The influence of endogenous oestrogen was effectively excluded by age, and that of exogenous oestrogen by subject selection. What did they find? In healthy control subjects, sympathetic burst incidence (quantified as the number of impulses per hundred cardiac cycles) was 37% higher in men than in women with similar systolic arterial pressure (P ,0.001). When studied 2–4 days after their AMI, sympathetic burst incidence was augmented significantly, relative to control subjects, in both males (P ,0.01) and females (P ,0.001), with no difference between sexes with respect to the magnitude of sympathetic nerve discharge attained. In the months following infarction, there was a gradual decline in sympathetic burst incidence in both men and women, to levels similar to those in control subjects. On the basis of these findings, the authors concluded that women develop relatively greater sympathetic excitation immediately following uncomplicated AMI that is sustained for 6–9 months. They proposed that such augmentation contributes to the vulnerability of women to adverse events over this period. These observations confirm previous reports involving healthy subjects of between-sex differences in muscle sympathetic nerve firing rates. The uniqueness of the present investigation lies in its comparison of healthy subject data with MSNA of men and women studied longitudinally at pre-specified time intervals following an uncomplicated AMI. This study, however, is essentially descriptive. The authors do not offer or investigate mechanisms responsible for this relatively greater sympathetic activation in the post-infarct period in women, or provide evidence for its functional importance. Continuous pulse synchronous outflow from central sympathetic motoneurons is entrained and inhibited by input from baroreceptor afferents whose discharge is stimulated by stretch of mechanically sensitive nerve endings situated in the aorta, carotid sinus, atria, and ventricles. Input from arterial baroreceptors ordinarily ceases when pressure, during diastole, drifts below the threshold for nerve firing. Consequently, sympathetic nerve firing tracks diastolic rather than systolic BP. Relative to control subjects of similar sex, patients studied 2–4 days after their AMI exhibited lower diastolic BP (P ,0.01 for both groups). There was no