Bigger et al. showed that measures of RR variability are reduced to about 25% of normal two to three weeks after myocardial infarction (46). Several small studies have studied the recovery of-RR variability after myocardial infarction. Both early and late phases of recovery have been studied.
The Early Phase of Recovery. Flapan et al. (47) studied the recovery of a time domain measure of high frequency power in 20 highly selected patients who experienced their first myocardial infarction. Cardiac parasympathetic activity was measured using the counts of the number of times that successive RR intervals differed by >50 ms (NN50) in a 24-hour period. The NN50 is strongly correlated with high frequency power.
The study by Flapan et al. excluded patients with previous infarction, age >70, history of diabetes, renal failure, alcohol abuse, hypertension, prior treatment with or contraindication to treatment with beta-adrenergic blocking drugs or with antihypertensive drugs. Patients with arrhythmias or heart failure on admission to the coronary care unit also were excluded. All patients were treated with streptokinase and aspirin acutely and continued to receive atenolol and aspirin over the three-month follow-up period. Continuous 24-hour ECG recordings were made at <l.5, 7, 42, and 140 days after myocardial infarction. For the 20 patients overall, NN50 doubled between 1.5 days and six weeks after infarction and tripled between 1.5 days and three months. Flapan et al. found a striking difference in the pattern of recovery of NN50 depending on the site of infarction. For the 9 patients with inferior myocardial infarction, NN50 was within normal limits for age at 1.5 days after infarction and did not change significantly over the three-month follow-up. For the 11 patients with anterior myocardial infarction, NN50 was 20%) of normal at 1.5 days and recovered progressively to 6770 of normal by three months after infarction. By six weeks after myocardial infarction, there was no significant difference in NN50 between patients with anterior and inferior infracts. In anterior infracts, there was a striking difference in the recovery of bean rate, which stabilized by day 7, and RR variability, which continued to increase for six weeks to three months. These workers postulated that stimulation of vagal afferent nerves by ischemia and prostaglandins preserved the efferent vagal activity in inferior infarction.
The patients in the study by Flapan et al. are highly selected and small in number. Therefore, the study needs to be confirmed and extended before the fascinating findings are considered established. If confirmed, the mechanism for the difference between vagal activity for inferior and anterior myocardial infarction needs further exploration. Flapan et al. postulate that the infract process, especially prostaglandins release, causes increased vagal afferent nerve traffic which is responsible for preserving efferent vagal activity. However, it is not clear why increased afferent vagal nerve traffic should produce NN50 values above normal rather than Just preserve normal values. Also, their explanation does not account for the marked decrease in cardiac vagal activity in anterior myocardial infarction. Bigger et al. explained the decrease in cardiac vagal activity in anterior infarction by postulating an increase in afferent sympathetic nerve traffic, an effect which has been shown to decrease efferent vagal nerve traffic in experimental myocardial ischemia (48). Surely, we have much more to learn about the mechanisms accounting for changes in cardiac neural activity that occur during acute myocardial infarction.
The Late Phase of Recovery. Bigger et al. (46) studied recovery of RR variability in the placebo cohort in the Cardiac Arrhythmia Pilot Study (CAPS) using the CHRONOS algorithms. The 68 patients who had 24-hour electrocardiographic recordings at baseline, 3, 6, and 12 months after - myocardial infarction were studied. The 24-hour power spectral density was computed using fast Fourier transforms and divided into four components of the RR power spectrum - ultra low frequency (<0.0033 Hz), very low frequency (0.0033 to <0.04 Hz), low frequency (0.04 to <0.15 Hz), and high frequency power (0.15 to 0.40 Hz). Total power ( I. 157 x IO-5 to 0.40 Hz) also was calculated. The mean baseline values (25±17 days after myocardial infarction) for the five frequency domain measures of RR variability in the CAPS patients were similar to those found in 715 patients who participated in the Multicenter Post infarction Program (MPIP), indicating that the CAPS sample is generally representative of post-infarction patients with respect to these measures. The values for the five measures were one-third to one-half of those found in 95 normal persons of similar age and gender (xx). There was a substantial increase in all measures of RR variability between the baseline 24-hour ECG recording and the 3 month recording (p <0.001). Figure 10 shows the time course of recovery of RR variability over the year after myocardial infarction. Between 3 months and 12 months, the values were quite stable for the group as a whole as well as for individuals (intraclass correlation coefficients *0.66). Even 12 months after infarction, full recovery values for the five measures of RR variability were only one-half to two-thirds the values found in the sample of 95 normal age and sex matched persons.
