Although chest pain is symptomatic of myocardial ischaemia, up to 50 % of patients who present with pains in the chest have angiographically normal coronary arteries and are diagnosed with ‘non-cardiac’ chest pain (Mayou, 1998). Psychiatric examination of this patient group has revealed a high incidence of anxiety states such as panic disorder (e.g. Fleet et al. 1996). Panic attacks are characterised by extreme fear and intense autonomic disturbances that are often accompanied by chest pain (DSMIV). In animals, stimulation in the dorsal part of the periaqueductal grey matter (dPAG) evokes panic-like behaviour with intense autonomic activation (Lovick, 2000) and changes in the ST segment of the ECG (Lovick & Drew, 1998). We have now explored the possibility that a coronary constriction may underlie the changes in the ECG waveform that occur during stimulation in the dPAG.

Male Wistar rats (300Ð390 g body weight) were anaesthetised with 20 % urethane (0.7 ml 100 g^-1, I.P.) and instrumented to record blood pressure, heart rate, ECG (approximately V4 position), femoral arterial blood flow and tracheal air flow. Rectal temperature was maintained at 37 °C. Experiments were carried out in accordance with the Animals (Scientific Procedures) Act, 1986. Stimulation in the dPAG (50Ð120 mA, 1 ms pulses, 80 Hz for 10 s) produced a pressor response (50.0 ± 2.7 mmHg, mean ± S.E.M.), tachycardia (47.4 ± 4.4 beats min^-1), an increase in femoral arterial conductance (58.2 ± 6.5 %) and hyperpnoea (60.3 ± 7.5 breaths min^-1). In all rats (n = 15), the duration of the interval between the peak of the S and T waves (ST_int) increased significantly from 18.2 ± 0.6 to 22.0 ± 0.6 ms (P < 0.005, paired t test) and the ST segment of the ECG waveform (ST_seg) was depressed by 0.052 ± 0.01 mV. Administration of the slow calcium channel antagonist amlodipine (1, 2 and 3 mg kg^-1 I.V., n = 5 for each dose) produced a dose-related attenuation of the PAG-evoked cardiovascular changes and the PAG-evoked increase in ST_int and ST_seg of the ECG waveform. At the highest dose used (3 mg kg^-1), the dPAG-evoked increase in ST_int (from 18.55 ± 1.36 to 23.13 ± 1.4 ms) was attenuated significantly by 86.4 % (from 19.52 ± 1.39 to 20.14 ± 1.28 ms) (P < 0.05, n = 5) and the PAG-evoked depression of ST_seg was reduced by 80 % from 0.082 ± 0.023 to 0.0163 ± 0.0018 mV (P < 0.01). The effect was maximal 120 min after drug administration and recovery had not occurred after 3 h when the experiment was terminated by an overdose of anaesthetic.

We suggest that during activation of the dPAG, localised coronary spasm may give rise to regional ischaemic changes in the heart that are reflected by changes in the waveform of the ECG. Such a regional ischaemia could contribute to episodes of chest pain in patients with ‘non-cardiac’ chest pain and panic disorder.

This work was supported by The Wellcome Trust. We thank Pfizer Ltd for a gift of amlodipine.

All procedures accord with current UK guidelines.