Case Report

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A 32-year-old woman, gravida 7, para 7, had an uncomplicated pregnancy and a full-term spontaneous vaginal delivery. The patient was given oral bromocriptine mesylate (Parlodel, Sandoz Pharmaceuticals, Ruell-Malmaison, France; 1.25 mg four times a day) to suppress lactation. When discharged on the fifth postpartum day, she continued taking bromocriptine (2.5-mg tablets twice daily). Then she developed visual hallucinations and severe headache. All these symptoms disappeared when she withheld the drug for 1 day. She took bromocriptine again on day 9 and developed the same symptoms. On day 10 she had an episode of severe chest pain. Her electrocardiogram showed marked ST-segment elevation in leads II, III, and aVF, a Q wave in lead III, and anterior ST depression. Electrocardiogram (ECG) abnormalities did not change after intravenous nitroglycerin. Thrombolytic therapy was not administered because she had recently given birth. Coronary angiography was done 5 hours after the onset of symptoms, and it showed a total occlusion of the midportion of the right coronary artery; the left coronary artery was normal. Test results from ventriculography showed a limited zone of akinesia of the inferior wall. Percutaneous transluminal coronary angioplasty was immediately done, and the right coronary artery was reopened. Serial test results of myocardial enzymes and serial electrocardiograms confirmed acute inferior transmural infarction. The peak serum creatine phosphokinase level was 1100 IU.

The patient's past history was not significant. She never used bromocriptine before. She smoked 1 pack per day. Blood glucose and lipid profile test results were within normal limits. The patient was discharged on calcium-antagonists, nitrates, and aspirin. One month later, she was tested with bromocriptine, after informed consent, to elucidate the mechanism of her previous myocardial infarction. Calcium-antagonists and nitrates were withdrawn 36 hours before the test. Smoking was prohibited during the test day.

With the patient in a supine position, bromocriptine was given orally, at a dose of 2.5 mg. Two hours later, at the peak of action of bromocriptine, she had coronary angiography. A severe narrowing [> 70%] of the right coronary artery occurred; the constriction was 2 cm distal from the tip of the catheter Figure 1, left). After intracoronary nitroglycerin was administered, this constriction disappeared Figure 1, right), which indicated that bromocriptine might have caused the vasospasm. The patient said she did not have chest pain during the test. Her ECG remained unchanged compared with the basal ECG, which showed a Q wave in leads III and aVF. The patient was discharged on calcium antagonists, and the subsequent clinical course was uneventful.

View larger version (66K): [in this window] [in a new window]   Figure 1. Coronary angiogram of the right coronary artery. Left. Bromocriptine-induced spasm of the artery (arrow). Right. The arterial constriction disappears after intracoronary nitroglycerin.

Discussion

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Postpartum myocardial infarction is a rare event. Only 24 reports including our case have been found in the literature. In 11 cases, this life-threatening complication appeared after treatment with ergot derivatives and in 5 cases, with bromocriptine treatment (2-4, and our study). A reasonable mechanism for the myocardial infarction in our patient would be coronary artery spasm with possible thrombus formation at the site of spasm. However, coronary atherosclerosis on angiogram was not evident. Additionally, the patient did not have conditions such as mitral stenosis, cardiomyopathy, patent foramen ovale, endocarditis, or atrial fibrillation, which might have caused coronary embolization.

To our knowledge, direct evidence of bromocriptine-induced coronary spasm has not been previously reported. The spasm seen after bromocriptine was distinct from "catheter tip" spasm, for several reasons. We used a soft-tip Schneider JR4 catheter (Schneider AG, Pfizer Hospital Products Group, Zurich, Switzerland), and the operator was careful not to intubate deeply the right coronary artery. The spasm was clearly distal to the catheter tip, and it was 1.5 cm long; catheter-induced spasms usually involve a shorter arterial length. The fact that the spasm was not accompanied by chest pain and electrocardiographic changes is not surprising because it involved an artery supplying an infarcted area.

The mechanism whereby bromocriptine could have precipitated coronary artery spasm is not clear. Bromocriptine activates D2-dopamine receptors. D2 receptors are associated with inhibition of adenylate cyclase, and they are located on postganglionic sympathetic nerve terminals [5] where they mediate inhibition of norepinephrine release. There is some evidence [6] that D2 receptors are also located postsynaptically on the arterial wall; however, the properties of these postsynaptic D2 receptors are not known.

In normal conditions, bromocriptine does not have serotoninergic or -adrenergic agonist properties, in contrast to other ergot derivatives such as ergonovine maleate commonly used as a provocative agent for coronary spasm. It is possible that in our patient the stimulation of D2-dopaminergic receptors could have resulted in a paradoxical constrictive response as shown with exogenous dopamine in a previous study or that a decreased sensitivity of peripheral dopaminergic receptors could have unmasked the vasoconstrictor effects of bromocriptine that are mediated by other receptors [7]. This might be due to an unusual pathologic reactivity of the arterial coronary wall present in our patient. Vasospasm could have been provoked by both activation of -adrenergic and serotoninergic receptors as previously described [7] in a patient with dopamine-induced coronary spasm. Our study suggests that bromocriptine should be considered as a possible etiologic agent causing postpartum myocardial infarction and should be used with caution in patients with predisposing factors.