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Nitroglycerin administration during cardiac arrest caused by coronary vasospasm secondary to misoprostol
Journal of Cardiology Cases 12 (2015) 166–168
Contents lists available at ScienceDirect
Journal of Cardiology Cases journal homepage: www.elsevier.com/locate/jccase
Case Report
Nitroglycerin administration during cardiac arrest caused by coronary vasospasm secondary to misoprostol Kent A. Owusu (PharmD, BCPS)a,*, Joseph J. Brennan (MD)b,c, Alexander Perelman (DO)c, Elise Meoli (MD)c, Jerry Altshuler (PharmD, BCPS)a,d a
Department of Pharmacy, Yale-New Haven Hospital, New-Haven, CT, USA Cardiac Intensive Care Unit, Yale-New Haven Hospital, New-Haven, CT, USA Department of Internal Medicine, Yale School of Medicine, New-Haven, CT, USA d Department of Pharmacy, Mount Sinai Beth Israel, New York, NY, USA b c
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 April 2015 Received in revised form 17 May 2015 Accepted 2 July 2015
There have been no reports of successful resuscitation using nitroglycerin (NTG) for cardiac arrest due to definitive coronary vasospasm. A 42-year-old female was brought to the Emergency Department in ventricular fibrillation after being found collapsed with the consumption of misoprostol. NTG, a potent coronary arterial dilator, not typically used in the management of cardiac arrest, was administered after 27 min of resuscitation efforts following advanced cardiac life support. NTG aided in the return of spontaneous circulation during a ventricular fibrillation cardiac arrest in the setting of prostaglandin use. ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Keywords: Nitroglycerin Cardiac arrest Coronary vasospasm Misoprostol Myocardial infarction
Introduction Cardiac arrest in the setting of coronary artery vasospasm is an uncommon phenomenon [1]. Medications, such as epinephrine and vasopressin that are included in the standard Advanced Cardiac Life Support (ACLS) algorithm for cardiac arrest, have been known to induce coronary vasospasm [2]. Nitroglycerin (NTG), on the other hand, is a potent coronary arterial dilator and is routinely used for ischemic discomfort in the setting of acute coronary syndrome (ACS) but is not typically employed in the management of cardiac arrest [2]. To our knowledge, there have been no reports of successful resuscitation using NTG for cardiac arrest due to definitive coronary vasospasm and data regarding NTG use during cardiac arrest are limited. Two reports, one from 1984, and one from 2009, document the use of intravenous NTG in the setting of cardiac arrest [3,4]. These reports however, involved patients with significant coronary atherosclerosis demonstrated by cardiac
* Corresponding author at: Yale-New Haven Hospital, 20 York Street, New Haven, CT 06510, USA. Tel.: +1 850 377 1811; fax: +1 203 688 4131. E-mail address: [email protected] (K.A. Owusu).
catheterization or undetermined coronary anatomy due to lack of catheterization entirely. Here, we report a case of successful cardiac resuscitation after administration of intravenous NTG during a prolonged cardiac arrest event secondary to coronary artery vasospasm in the setting of recent misoprostol ingestion. Case report A 42-year-old female with a medical history of hypertension was brought to the Emergency Department via Emergency Medical Services after being found collapsed with the consumption of misoprostol. A home medication list included norethindrone 0.35 mg daily and misoprostol 200 mcg sublingual once in preparation for a gynecologic procedure. Downtime to initiation of cardiopulmonary resuscitation (CPR) was approximately 5 min and the presenting rhythm was pulseless ventricular fibrillation. The patient received 1 mg epinephrine, naloxone, and was defibrillated at 200 J twice before return of circulation about 15 min after CPR was initiated. Subsequent electrocardiogram (ECG) showed ST segment elevation in the inferior and lateral leads (Fig. 2) and the patient was taken directly to the cardiac catheterization laboratory.
http://dx.doi.org/10.1016/j.jccase.2015.07.003 1878-5409/ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
K.A. Owusu et al. / Journal of Cardiology Cases 12 (2015) 166–168
167
Fig. 1.
Angiogram showing non-obstructive coronary artery disease on day of presentation. LCA, left coronary artery; RCA, right coronary artery.
Fig. 2.
Electrocardiogram showing ST-segment elevation in anteroseptal leads (V1–V5) on the day of presentation.
Diagnostic angiography demonstrated a normal left main coronary artery, a 60% left anterior descending (LAD) artery stenosis and a 70% right coronary arterial (RCA) ostial stenosis (Fig. 1). The LAD and RCA lesions were interrogated by fractional flow reserve and found to be 0.84 and 0.86 respectively, consistent with non-obstructive coronary disease. An initial transthoracic echocardiogram (TTE) immediately post-arrest demonstrated global hypokinesis with relative sparing of the inferior and inferoseptal walls and an ejection fraction of 25–30%. Drastic ST elevations on ECG without culprit lesions on diagnostic coronary angiography performed suggested coronary spasm. Provocative testing was not pursued in this case given additional associated risks including sustained ventricular tachycardia and cardiac tamponade in up to 1.3% of patients [5]. Pertinent laboratory parameters were within normal limits (Table 1). The patient was transferred to the cardiac intensive care unit (CICU) for initiation of therapeutic hypothermia (TH). Shortly upon transfer to the CICU, prior to initiation of TH, she experienced another episode of ventricular fibrillation cardiac arrest. Following the ACLS algorithm, resuscitation efforts were performed with chest compressions, delivery of two shocks at 200 J, administration of 300 mg of amiodarone, 4 mg of epinephrine (in 1 mg increments at 3 to 5-minute intervals), 40 units of vasopressin (administered 3 min after the initial 1 mg epinephrine dose), and 150 total milliequivalents of sodium bicarbonate. After delivery of the second shock, rhythm transitioned to pulseless electrical activity with continuation of resuscitation efforts. After 27 min of resuscitation efforts without return of spontaneous circulation,
we decided to administer 200 mcg of NTG as an i.v. bolus as a last resort. A second i.v. bolus of NTG 400 mcg was administered within 1 min of the initial NTG bolus, while resuscitation efforts were continued. Within 6 min of the second i.v. NTG bolus administration, return of spontaneous circulation was achieved. A NTG i.v. infusion was initiated at 0.15 mcg/kg/min to control vasospasm, norepinephrine i.v. infusion at 0.4 mcg/kg/min to maintain mean arterial pressure >60 mmHg, and amiodarone i.v. infusion at 1 mg/ min for recurring ventricular arrhythmia.
Table 1
Pertinent laboratory findings.
Laboratory parameter (units)
Day 0 (on arrival)
Day 0 (prior to 2nd cardiac arrest)
Sodium (mmol/l) Potassium (mmol/l) Chloride (mmol/l) Bicarbonate (meq/l) pH Creatinine (mg/dl) Glucose (mg/dl) Calcium (mg/dl) Magnesium (mg/dl) Phosphorous (mg/dl) Troponin T (ng/ml) Lactate (mmol/l) INR Hemoglobin (g/dl) Hematocrit (%) Platelet (1000/ul)
138 3.9 101 13.7
142 4.0 112 12.4 7.22 0.6 226 7.3 2.2 3.3
0.9 327 8.9 2.0 0.3 1.05 14.8 45.9 209
5.5 1.13 14.3 42.8 189
K.A. Owusu et al. / Journal of Cardiology Cases 12 (2015) 166–168
168
Fig. 3.
Electrocardiogram showing resolution of ST-segment elevation on day #2 of hospitalization.
Following return of spontaneous circulation, the patient was noted to have bloody secretions from her endotracheal tube and required airway pressure release ventilation settings to maintain oxygenation. Due to the need to avoid paralysis with this ventilator mode, wanting to avoid coagulopathy in the setting of the bloody secretions, and concern that moderate hypothermia (32–34 8C) could exacerbate coronary vasospasm, the decision was made to start modified (mild) TH with a target temperature of 36 8C. On day 2 of admission, ECG showed resolution of ST-segment elevation (Fig. 3). After 24 h of NTG i.v. infusion, she was transitioned to a nicardipine i.v. infusion at 2.5 mg/h and later transitioned to oral nifedipine 10 mg every 8 h. Prior to discharge, she was transitioned from oral nifedipine to amlodipine 5 mg once daily. The patient had no episodes of hypertension. However, she was optimized for coronary artery disease and cardiomyopathy with aspirin 81 mg daily, atorvastatin 40 mg daily, lisinopril 5 mg daily, and extendedrelease metoprolol 25 mg daily. She had no recurrent episodes of ventricular fibrillation. Within 48 h of her presentation, she was showing signs of meaningful neurologic activity and by the end of her hospitalization, her mental status had returned to baseline. Prior to discharge, she had a cardiac magnetic resonance imaging, which did not show any evidence of infiltrative disease and showed similar wall motion abnormalities as the aforementioned TTE. She received a single lead automatic implantable cardioverter defibrillator given the possibility of future recurrence and depressed ejection fraction. The patient was successfully discharged on day 14 of hospitalization. Discussion Cardiac arrest secondary to myocardial ischemia as a result of coronary vasospasm has been well documented in the clinical literature [6]. In our case, TTE demonstrated regional wall motion abnormalities but the absence of obstructive coronary disease was confirmed with diagnostic angiography. Coronary vasospasm has been attributed to either the hyperreactivity of vascular smooth muscle cells (VSMCs) or a vasoconstrictor stimulus acting on the hyper-reactive VSMCs [6]. Vasodilators including nitrates and calcium channel antagonists are the standard treatment for coronary vasospasm [6]. While relatively uncommon, misoprostol was likely the vasoconstrictor stimulus culpable for the hyper-reactive VSMCs in this case. A 2009 case report described an incidence of acute myocardial infarction due to coronary vasospasm induced by misoprostol, a synthetic prostaglandin E (PGE)1 analog administered intravaginally,
and sulprostone, a synthetic PGE2 analog [7]. Eight hours after administration of 5 intravaginal doses of misoprostol and an i.v. dose of sulprostone, the patient complained of acute left-sided chest pain and nausea [7]. An ECG was performed and ST elevation was reported in inferior electrocardiographic leads (II, III, and aVF) with reciprocal ST depression in the anterior leads [7]. Coronary angiography demonstrated stenosis in the RCA, which subsequently resolved after administration of 400 mcg intracoronary NTG [7]. A follow-up ECG showed complete resolution of ST elevation [7]. In our case, reported use of misoprostol was within hours of cardiac arrest. The mechanism for prostaglandin-mediated contractility of coronary arteries remains unclear although probable mechanisms include activation of G protein-coupled receptor, specifically subtypes EP1 and EP3, responsible for vasoconstriction [7,8]. In the present case, high-dose i.v. NTG during a ventricular fibrillation cardiac arrest in the setting of prostaglandin use, aided in the return of spontaneous circulation. Conflict of interest All the authors included in this manuscript have no conflicts of interest to disclose with respect to any financial and personal relationships with other people or organizations that could inappropriately influence this case. References [1] Myerburg RJ, Kessler KM, Mallon SM. Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary artery spasm. N Engl J Med 1992;326:1451–5. [2] O’Connor RE, Brady W, Brooks SC, Diercks D, Egan J, Ghaemmaghami C, Menon V, O’Neil BJ, Travers AH, Yannopoulos D. Part 10: acute coronary syndromes. 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2010;122(Suppl. 3):S787–817. [3] Guglin M, Postler G. High dose nitroglycerin treatment in a patient with cardiac arrest: a case report. J Med Case Rep 2009;3:8782. [4] Ward WG, Reid RL. High-dose intravenous nitroglycerin during cardiopulmonary resuscitation for refractory cardiac arrest. Am J Cardiol 1984;53:1725. [5] Sueda S, Ochi N, Kawada H, Matsuda S, Hayashi Y, Tsuruoka T, Uraoka T. Frequency of provoked coronary vasospasm in patients undergoing coronary arteriography with spasm provocation test of acetylcholine. Am J Cardiol 1999;83:1186–90. [6] Niccoli G, Scalone G, Crea F. Acute myocardial infarction with no obstructive coronary atherosclerosis: mechanisms and management. Eur Heart J 2015;36:475–81. [7] Sung CW, Jung J-H, Lee S-H, Lee S-H, Lee KM, Ahn BM, Choi S, Cho JR, Lee N, Lee K-Y. Acute myocardial infarction due to vasospasm induced by prostaglandin. Can J Cardiol 2009;25:e359–60. [8] Qian YM, Jones RL, Chan KM, Stock AI, Ho JK. Potent contractile actions of prostanoid EP3-receptor agonists on human isolated pulmonary artery. Br J Pharmacol 1994;113:369–74.
Contents lists available at ScienceDirect
Journal of Cardiology Cases journal homepage: www.elsevier.com/locate/jccase
Case Report
Nitroglycerin administration during cardiac arrest caused by coronary vasospasm secondary to misoprostol Kent A. Owusu (PharmD, BCPS)a,*, Joseph J. Brennan (MD)b,c, Alexander Perelman (DO)c, Elise Meoli (MD)c, Jerry Altshuler (PharmD, BCPS)a,d a
Department of Pharmacy, Yale-New Haven Hospital, New-Haven, CT, USA Cardiac Intensive Care Unit, Yale-New Haven Hospital, New-Haven, CT, USA Department of Internal Medicine, Yale School of Medicine, New-Haven, CT, USA d Department of Pharmacy, Mount Sinai Beth Israel, New York, NY, USA b c
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 April 2015 Received in revised form 17 May 2015 Accepted 2 July 2015
There have been no reports of successful resuscitation using nitroglycerin (NTG) for cardiac arrest due to definitive coronary vasospasm. A 42-year-old female was brought to the Emergency Department in ventricular fibrillation after being found collapsed with the consumption of misoprostol. NTG, a potent coronary arterial dilator, not typically used in the management of cardiac arrest, was administered after 27 min of resuscitation efforts following advanced cardiac life support. NTG aided in the return of spontaneous circulation during a ventricular fibrillation cardiac arrest in the setting of prostaglandin use.
Keywords: Nitroglycerin Cardiac arrest Coronary vasospasm Misoprostol Myocardial infarction
Introduction Cardiac arrest in the setting of coronary artery vasospasm is an uncommon phenomenon [1]. Medications, such as epinephrine and vasopressin that are included in the standard Advanced Cardiac Life Support (ACLS) algorithm for cardiac arrest, have been known to induce coronary vasospasm [2]. Nitroglycerin (NTG), on the other hand, is a potent coronary arterial dilator and is routinely used for ischemic discomfort in the setting of acute coronary syndrome (ACS) but is not typically employed in the management of cardiac arrest [2]. To our knowledge, there have been no reports of successful resuscitation using NTG for cardiac arrest due to definitive coronary vasospasm and data regarding NTG use during cardiac arrest are limited. Two reports, one from 1984, and one from 2009, document the use of intravenous NTG in the setting of cardiac arrest [3,4]. These reports however, involved patients with significant coronary atherosclerosis demonstrated by cardiac
* Corresponding author at: Yale-New Haven Hospital, 20 York Street, New Haven, CT 06510, USA. Tel.: +1 850 377 1811; fax: +1 203 688 4131. E-mail address: [email protected] (K.A. Owusu).
catheterization or undetermined coronary anatomy due to lack of catheterization entirely. Here, we report a case of successful cardiac resuscitation after administration of intravenous NTG during a prolonged cardiac arrest event secondary to coronary artery vasospasm in the setting of recent misoprostol ingestion. Case report A 42-year-old female with a medical history of hypertension was brought to the Emergency Department via Emergency Medical Services after being found collapsed with the consumption of misoprostol. A home medication list included norethindrone 0.35 mg daily and misoprostol 200 mcg sublingual once in preparation for a gynecologic procedure. Downtime to initiation of cardiopulmonary resuscitation (CPR) was approximately 5 min and the presenting rhythm was pulseless ventricular fibrillation. The patient received 1 mg epinephrine, naloxone, and was defibrillated at 200 J twice before return of circulation about 15 min after CPR was initiated. Subsequent electrocardiogram (ECG) showed ST segment elevation in the inferior and lateral leads (Fig. 2) and the patient was taken directly to the cardiac catheterization laboratory.
http://dx.doi.org/10.1016/j.jccase.2015.07.003 1878-5409/ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
K.A. Owusu et al. / Journal of Cardiology Cases 12 (2015) 166–168
167
Fig. 1.
Angiogram showing non-obstructive coronary artery disease on day of presentation. LCA, left coronary artery; RCA, right coronary artery.
Fig. 2.
Electrocardiogram showing ST-segment elevation in anteroseptal leads (V1–V5) on the day of presentation.
Diagnostic angiography demonstrated a normal left main coronary artery, a 60% left anterior descending (LAD) artery stenosis and a 70% right coronary arterial (RCA) ostial stenosis (Fig. 1). The LAD and RCA lesions were interrogated by fractional flow reserve and found to be 0.84 and 0.86 respectively, consistent with non-obstructive coronary disease. An initial transthoracic echocardiogram (TTE) immediately post-arrest demonstrated global hypokinesis with relative sparing of the inferior and inferoseptal walls and an ejection fraction of 25–30%. Drastic ST elevations on ECG without culprit lesions on diagnostic coronary angiography performed suggested coronary spasm. Provocative testing was not pursued in this case given additional associated risks including sustained ventricular tachycardia and cardiac tamponade in up to 1.3% of patients [5]. Pertinent laboratory parameters were within normal limits (Table 1). The patient was transferred to the cardiac intensive care unit (CICU) for initiation of therapeutic hypothermia (TH). Shortly upon transfer to the CICU, prior to initiation of TH, she experienced another episode of ventricular fibrillation cardiac arrest. Following the ACLS algorithm, resuscitation efforts were performed with chest compressions, delivery of two shocks at 200 J, administration of 300 mg of amiodarone, 4 mg of epinephrine (in 1 mg increments at 3 to 5-minute intervals), 40 units of vasopressin (administered 3 min after the initial 1 mg epinephrine dose), and 150 total milliequivalents of sodium bicarbonate. After delivery of the second shock, rhythm transitioned to pulseless electrical activity with continuation of resuscitation efforts. After 27 min of resuscitation efforts without return of spontaneous circulation,
we decided to administer 200 mcg of NTG as an i.v. bolus as a last resort. A second i.v. bolus of NTG 400 mcg was administered within 1 min of the initial NTG bolus, while resuscitation efforts were continued. Within 6 min of the second i.v. NTG bolus administration, return of spontaneous circulation was achieved. A NTG i.v. infusion was initiated at 0.15 mcg/kg/min to control vasospasm, norepinephrine i.v. infusion at 0.4 mcg/kg/min to maintain mean arterial pressure >60 mmHg, and amiodarone i.v. infusion at 1 mg/ min for recurring ventricular arrhythmia.
Table 1
Pertinent laboratory findings.
Laboratory parameter (units)
Day 0 (on arrival)
Day 0 (prior to 2nd cardiac arrest)
Sodium (mmol/l) Potassium (mmol/l) Chloride (mmol/l) Bicarbonate (meq/l) pH Creatinine (mg/dl) Glucose (mg/dl) Calcium (mg/dl) Magnesium (mg/dl) Phosphorous (mg/dl) Troponin T (ng/ml) Lactate (mmol/l) INR Hemoglobin (g/dl) Hematocrit (%) Platelet (1000/ul)
138 3.9 101 13.7
142 4.0 112 12.4 7.22 0.6 226 7.3 2.2 3.3
0.9 327 8.9 2.0 0.3 1.05 14.8 45.9 209
5.5 1.13 14.3 42.8 189
K.A. Owusu et al. / Journal of Cardiology Cases 12 (2015) 166–168
168
Fig. 3.
Electrocardiogram showing resolution of ST-segment elevation on day #2 of hospitalization.
Following return of spontaneous circulation, the patient was noted to have bloody secretions from her endotracheal tube and required airway pressure release ventilation settings to maintain oxygenation. Due to the need to avoid paralysis with this ventilator mode, wanting to avoid coagulopathy in the setting of the bloody secretions, and concern that moderate hypothermia (32–34 8C) could exacerbate coronary vasospasm, the decision was made to start modified (mild) TH with a target temperature of 36 8C. On day 2 of admission, ECG showed resolution of ST-segment elevation (Fig. 3). After 24 h of NTG i.v. infusion, she was transitioned to a nicardipine i.v. infusion at 2.5 mg/h and later transitioned to oral nifedipine 10 mg every 8 h. Prior to discharge, she was transitioned from oral nifedipine to amlodipine 5 mg once daily. The patient had no episodes of hypertension. However, she was optimized for coronary artery disease and cardiomyopathy with aspirin 81 mg daily, atorvastatin 40 mg daily, lisinopril 5 mg daily, and extendedrelease metoprolol 25 mg daily. She had no recurrent episodes of ventricular fibrillation. Within 48 h of her presentation, she was showing signs of meaningful neurologic activity and by the end of her hospitalization, her mental status had returned to baseline. Prior to discharge, she had a cardiac magnetic resonance imaging, which did not show any evidence of infiltrative disease and showed similar wall motion abnormalities as the aforementioned TTE. She received a single lead automatic implantable cardioverter defibrillator given the possibility of future recurrence and depressed ejection fraction. The patient was successfully discharged on day 14 of hospitalization. Discussion Cardiac arrest secondary to myocardial ischemia as a result of coronary vasospasm has been well documented in the clinical literature [6]. In our case, TTE demonstrated regional wall motion abnormalities but the absence of obstructive coronary disease was confirmed with diagnostic angiography. Coronary vasospasm has been attributed to either the hyperreactivity of vascular smooth muscle cells (VSMCs) or a vasoconstrictor stimulus acting on the hyper-reactive VSMCs [6]. Vasodilators including nitrates and calcium channel antagonists are the standard treatment for coronary vasospasm [6]. While relatively uncommon, misoprostol was likely the vasoconstrictor stimulus culpable for the hyper-reactive VSMCs in this case. A 2009 case report described an incidence of acute myocardial infarction due to coronary vasospasm induced by misoprostol, a synthetic prostaglandin E (PGE)1 analog administered intravaginally,
and sulprostone, a synthetic PGE2 analog [7]. Eight hours after administration of 5 intravaginal doses of misoprostol and an i.v. dose of sulprostone, the patient complained of acute left-sided chest pain and nausea [7]. An ECG was performed and ST elevation was reported in inferior electrocardiographic leads (II, III, and aVF) with reciprocal ST depression in the anterior leads [7]. Coronary angiography demonstrated stenosis in the RCA, which subsequently resolved after administration of 400 mcg intracoronary NTG [7]. A follow-up ECG showed complete resolution of ST elevation [7]. In our case, reported use of misoprostol was within hours of cardiac arrest. The mechanism for prostaglandin-mediated contractility of coronary arteries remains unclear although probable mechanisms include activation of G protein-coupled receptor, specifically subtypes EP1 and EP3, responsible for vasoconstriction [7,8]. In the present case, high-dose i.v. NTG during a ventricular fibrillation cardiac arrest in the setting of prostaglandin use, aided in the return of spontaneous circulation. Conflict of interest All the authors included in this manuscript have no conflicts of interest to disclose with respect to any financial and personal relationships with other people or organizations that could inappropriately influence this case. References [1] Myerburg RJ, Kessler KM, Mallon SM. Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary artery spasm. N Engl J Med 1992;326:1451–5. [2] O’Connor RE, Brady W, Brooks SC, Diercks D, Egan J, Ghaemmaghami C, Menon V, O’Neil BJ, Travers AH, Yannopoulos D. Part 10: acute coronary syndromes. 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2010;122(Suppl. 3):S787–817. [3] Guglin M, Postler G. High dose nitroglycerin treatment in a patient with cardiac arrest: a case report. J Med Case Rep 2009;3:8782. [4] Ward WG, Reid RL. High-dose intravenous nitroglycerin during cardiopulmonary resuscitation for refractory cardiac arrest. Am J Cardiol 1984;53:1725. [5] Sueda S, Ochi N, Kawada H, Matsuda S, Hayashi Y, Tsuruoka T, Uraoka T. Frequency of provoked coronary vasospasm in patients undergoing coronary arteriography with spasm provocation test of acetylcholine. Am J Cardiol 1999;83:1186–90. [6] Niccoli G, Scalone G, Crea F. Acute myocardial infarction with no obstructive coronary atherosclerosis: mechanisms and management. Eur Heart J 2015;36:475–81. [7] Sung CW, Jung J-H, Lee S-H, Lee S-H, Lee KM, Ahn BM, Choi S, Cho JR, Lee N, Lee K-Y. Acute myocardial infarction due to vasospasm induced by prostaglandin. Can J Cardiol 2009;25:e359–60. [8] Qian YM, Jones RL, Chan KM, Stock AI, Ho JK. Potent contractile actions of prostanoid EP3-receptor agonists on human isolated pulmonary artery. Br J Pharmacol 1994;113:369–74.