Exaggerated Beat-to-Beat R Amplitude Variability in Patients with Panic Disorder after Intravenous Isoproterenol

Abstract

Background: Anxiety symptoms are associated with a marked increase in sudden cardiac death, suggesting an abnormality in cardiac autonomic function. Our previous studies show a relationship between R amplitude variability and sympathetic function.Methods:We examined the effects of β-adrenergic stimulation on R and T amplitude variability in panic disorder patients by infusing the β-adrenergic agonist isoproterenol in 6 panic disorder patients and 11 normal subjects. The ECG signal was analyzed before the infusion and 5 min after the infusion was started. The outcome measures were the R and T detrended variance normalized for mean amplitudes (R_vm and T_vm) and the R_vi and T_vi, measures which are normalized for the inter-beat interval variability in addition. Results: Patients with panic disorder had significantly more variability in R and T amplitude than normal controls and the R amplitude variability was increased further by β-adrenergic stimulation with isoproterenol, which was more pronounced in the patients. Conclusions: The isoproterenol-associated increase in R amplitude variability occurred in controls in the absence of significant anxiety. However, the increase in R amplitude variability was greater in patients with panic disorder, suggesting a greater sensitivity to β-adrenergic effects of isoproterenol or to isoproterenol-induced anxiety.

Increased beat-to-beat ‘R’ amplitude variability in patients with panic disorder

“…We have also found that QRS amplitude variability was significantly higher in patients with congestive cardiac failure compared to normal controls [2]. In another study, we have shown that intravenous isoproterenol increases QRS amplitude variability much more significantly in patients with panic disorder compared to normal controls [3]. These findings are important in view of the association between anxiety disorders and an increased risk for cardiovascular mortality and sudden death [4].…”

“…The program we used automatically writes the amplitude (mV) and the time of each QRS peak (peak of "R"). This program applies a correction factor for the peak detection of QRS complex amplitude taking the baseline wander into account for each QRS complex [1][2][3]. From the 256-second segment, we obtained instantaneous heart rate and QRS amplitude series at 4 Hz using linear interpolation similar to the techniques described in our previous work [1][2][3].…”

“…This program applies a correction factor for the peak detection of QRS complex amplitude taking the baseline wander into account for each QRS complex [1][2][3]. From the 256-second segment, we obtained instantaneous heart rate and QRS amplitude series at 4 Hz using linear interpolation similar to the techniques described in our previous work [1][2][3].A normalized QRS amplitude variability index (QRSvi) was obtained from detrended "R" amplitude variance, mean "R" amplitude, detrended R-R variance, and mean R-R.The following table shows the results of the analyses. Two-tailed 't' tests were used to compare the two groups with a probability level of ≤ 0.05 to indicate significance.…”

The age of anxiety: role of animal models of anxiolytic action in drug discovery

“…Anxiety in humans can also be generated experimentally using chemical agents such as caffeine (Nardi et al, 2007), m-chlorophenylpiperazine (mCPP) (Kahn et al, 1990), yohimbine (Charney et al, 1984), CO 2 inhalation (Nardi et al, 2007), sodium lactate (Liebowitz et al, 1984; and isoproterenol (Pohl et al, 1987;Balon et al, 1988;Yeragani et al, 2007). A detailed summary of these techniques is described in Table 4.…”

“…Panic disorder patients are more vulnerable to isproterenol-induced panic attacks than healthy controls, as well as greater sensitivity to the arrhythmic effects of the drug (Pohl et al, 1987;Balon et al, 1988;Yeragani et al, 2007) ( Koszycki et al, 1991;Bradwejn and Koszycki, 2001;Rupprecht et al, 2009;Zwanzger et al, 2009) Physiological parameters, self-reported anxiety levels, attentional bias to specific word stimuli GAD patients display enhanced emotional bias towards emotional words, whereas social phobia patients display emotional bias to disorder specific (speech related) words. Non-patients with increased levels of self-reported anxiety also display higher emotional bias towards emotionally valent words.…”