Intravenous Atropine Relieves Coronary Arterial Spasm and Hemodynamic Decompensation during Recovery after Exercise

Abstract

A 66-year-old man developed right coronary arterial spasm and hemodynamic decompensation during the early recovery phase of a treadmill exercise test. The unstable condition was corrected immediately after intravenous administration of atropine. A subsequent coronary angiographic study revealed insignificant right coronary artery stenosis. The pathophysiology of this response may be related to rapid alterations in autonomic balance during recovery after exercise. To our knowledge, this is the 1st reported case in which atropine effected immediate reversal of coronary arterial spasm and hemodynamic decompensation that were induced by exercise, rather than by pharmacologic agents. Atropine might be an effective treatment in patients who experience exercise-induced coronary arterial spasm and hemodynamic decompensation, but further investigation is warranted.

Some reports have shown that coronary arterial spasm can be induced by dynamic exercise. ^1–5 Exercise-induced coronary arterial spasm is not common, and it eludes documentation. In the late 1970s, some authors first suggested that it is caused by altered activity of the autonomic nervous system during exercise. ^1–3 Nitroglycerin is the usual treatment. We report a patient who developed exercise-induced coronary arterial spasm and hemodynamic decompensation, both of which were reversed immediately after intravenous administration of atropine.

Case Report

In August 1998, a 66-year-old man was seen in an outpatient clinic for intermittent atypical chest pain. This had been occurring for 6 months, and it was relieved by sublingual nitroglycerin. The patient had no history of cardiovascular disease, and the findings of his physical examination were unremarkable.

The patient underwent a treadmill exercise test (Bruce protocol), along with exercise thallium-201 single-photon emission-computed tomography (SPECT) at 9 a.m. His resting heart rate was 57 beats/min, and his age-predicted target heart rate was 154 beats/min. His resting blood pressure was 176/83 mmHg. After 6 minutes of exercise, his heart rate was 95 beats/min, and his incremental blood pressure was poor (126/64 mmHg). The single dose (111MBq) of tracer was injected at the peak of exercise, at which point the patient stopped exercise because of chest discomfort and dizziness.

The electrocardiogram showed horizontal ST-segment depression of 2 mm in leads II, III, aVF, and V_4–6 (Fig. 1, peak-exercise). During the early recovery period (30 seconds after stopping exercise), the patient experienced chest pain and diaphoresis concomitant with inferior ST-segment elevation (2 mm) in leads II, III, and aVF, and anterior ST-segment depression (2 mm) in lead V₄ (Fig. 1, early recovery). Meanwhile, he also developed bradycardia (34 beats/min) and hypotension (67/30 mmHg). Initial stress myocardial imaging, performed within 5 minutes of the tracer injection, showed markedly decreased uptake in the inferior wall of the left ventricle on the short axis and vertical slice (Fig. 2A, top).

Fig. 1 Electrocardiography shows changes in ST segments during treadmill exercise test. At peak exercise, depression of the ST segments was noted in leads II, III, aVF, and V₄. The ST segments became elevated in leads II, III, and aVF during early recovery phase (30 seconds after stopping exercise), and these changes were persistent for 5 minutes. The ST segments recovered within 10 seconds after intravenous administration of atropine.

Fig. 2 A) Thallium-201 single-photon emission-computed tomographic perfusion image (vertical slice) shows a filling defect of the right coronary artery territory during variant angina (top). The delayed thallium-201 image (bottom) was normal. B) Selective coronary angiography shows an insignificant plaque and 20% stenosis in the mid-portion of the right coronary artery.

Because of his hemodynamic changes, the patient was given intravenous atropine (0.6 mg) 5 minutes after stopping exercise. Within 10 seconds, his heart rate returned to 67 beats/min. His blood pressure was 129/60 mmHg, and the ST-segments from the inferior and anterior leads became normal (Fig. 1, post-atropine). The delayed thallium-201 SPECT image, performed 4 hours after administration of atropine, was normal (Fig. 2A, bottom).

The patient subsequently underwent cardiac catheterization and coronary angiography. Left ventriculography was normal. Coronary angiography showed a 20% stenosis in the mid-portion of the right coronary artery (Fig. 2B). Exercise-induced right coronary arterial spasm was diagnosed. The patient has been managed with diltiazem (30 mg 3 times daily) and has experienced no recurrence of chest pain during a follow-up period of 20 months.

Discussion

In patients who have variant angina, anginal attacks are generally caused by coronary arterial spasm at rest. Exercise-induced coronary arterial spasm has been reported occasionally in patients who have insignificant atherosclerotic coronary artery disease. ^1–6 In our patient, exercise-induced coronary arterial spasm was diagnosed on the basis of the clinical presentation, electrocardiographic findings, and thallium-201 SPECT imaging. The SPECT images revealed a myocardial perfusion defect in the area supplied by the right coronary artery. We hypothesized that treatment with atropine might result in complete reperfusion of the defect.

This unusual case of exercise-induced coronary arterial spasm is of clinical interest because the patient's hemodynamic decompensation, which developed during the exercise recovery phase, was relieved immediately after intravenous administration of atropine, a parasympatholytic agent. Previously, Yasue and colleagues ⁷ found that pretreatment with intravenous atropine blocked acetylcholine-induced coronary spasms, and they suggested that parasympathetic tone might play a role in the pathogenesis of coronary arterial spasm. Wang and associates ⁸ reported that the isoproterenol head-up tilt test could provoke coronary arterial spasm, and they speculated that both increased basal parasympathetic tone and strong sympathetic stimulation are important in causing coronary arterial spasms. In our patient, the poor response of heart rate and blood pressure during exercise suggested strong basal parasympathetic tone.

During strenuous exercise, sympathetic discharge is maximal, and parasympathetic stimulation is withdrawn. In our patient, sinus bradycardia and hypotension in the presence of ongoing ischemia due to coronary arterial spasm occurred during the early recovery phase. The ability of atropine to abolish these effects suggests that they result from sudden parasympathetic hyperactivity immediately after exercise.

An alternative explanation, suggested by the ST changes during exercise, could be that the spasm was induced by the exercise itself and not by recovery after exercise. The spasm continued to progress even after the exercise stopped, resulting in ST elevation in leads II, III, and aVF in the first 30 seconds of recovery. Intense pain may have triggered a vasovagal reaction that, in turn, caused the bradycardia and hypotension. The atropine may have corrected only the bradycardia and hypotension, and the rest of the sequence may have just followed. We could not demonstrate that the atropine caused the ST elevation to subside prior to correction of blood pressure and heart rate; however, we found that the bradycardia and elevated ST segments were corrected concurrently after atropine injection.

The response to dynamic exercise consists of a complex series of cardiovascular adjustments to provide active muscles with enough blood for metabolic needs, while maintaining adequate blood supply to essential organs such as the brain and heart. As cardiac output increases with dynamic exercise, vascular resistance decreases in active muscles (as, for example, in dilation of the coronary vessels) but increases in tissues that are not functional during exercise. Because of its vasodilator actions, nitroglycerin can relieve myocardial ischemia within minutes and should be used promptly in patients who have coronary arterial spasm and myocardial ischemia. The side effects of nitroglycerin include hypotension and associated reflex tachycardia, headaches, facial flushing, and occasional profound bradycardia, presumably related to vagal stimulation. Nitroglycerin has been given sublingually to patients who have exercise-induced coronary arterial spasm and hypotension. However, in consideration of its possible side effects and of the cardiovascular response to dynamic exercise, nitroglycerin might not be suitable for patients who experience exercise-induced coronary arterial spasm, bradycardia, and hypotension.

To our knowledge, this is the 1st reported case in which atropine effected immediate reversal of coronary arterial spasm and hemodynamic decompensation that were induced by exercise, rather than by pharmacologic agents. From this case, we suggest that atropine might be the treatment of choice for patients who develop exercise-induced coronary arterial spasm associated with hemodynamic decompensation. Further investigation is warranted, however.