Year : 2009 | Volume
: 12 | Issue : 1 | Page : 67--70
Milrinone infusion: A therapeutic option in coronary vasospasm after primary percutaneous transluminal coronary angioplasty
Amarpal Singh, Rajesh Chand Arya, Bishav Mohan
Department of Cardiology, Hero DMC Heart Institute, Ludhiana, Punjab, India
Rajesh Chand Arya
Consultant Cardiac Anaesthetist, Hero DMC Heart Institute, Ludhiana, Punjab
A 42-year-old male presented to the emergency department with acute chest pain. The electrocardiogram revealed inferior wall myocardial infarction. Emergency coronary angiography revealed total occlusion of the distal right coronary artery with thrombus. Patient was taken up for primary percutaneous coronary angioplasty with stenting of distal right coronary artery. Six hours following the procedure, the patient developed re-elevation of ST-segment in inferior leads of electrocardiogram and subsequent haemodynamic instability. Repeat coronary angiography revealed patent stent and coronary artery spasm in proximal part, which was relieved by intracoronary injection of nitroglycerine. After an hour, the patient re-developed symptoms of chest pain along with bradycardia, hypotension and ST segment elevation. Intravenous infusion of nitroglycerine did not improve the condition but produced persistent hypotension. Infusion of milrinone was then started. Over time, normalisation of electrocardiogram occurred. The patient was discharged in stable condition. This case suggests that milrinone may be effective in alleviating coronary artery spasm when the use of other agents fails
|How to cite this article:|
Singh A, Arya RC, Mohan B. Milrinone infusion: A therapeutic option in coronary vasospasm after primary percutaneous transluminal coronary angioplasty.Ann Card Anaesth 2009;12:67-70
|How to cite this URL:|
Singh A, Arya RC, Mohan B. Milrinone infusion: A therapeutic option in coronary vasospasm after primary percutaneous transluminal coronary angioplasty. Ann Card Anaesth [serial online] 2009 [cited 2019 Dec 13 ];12:67-70
Available from: http://www.annals.in/text.asp?2009/12/1/67/45017
There are reports of coronary vasospasm causing acute myocardial infarction (AMI).  Spontaneous coronary vasospasm in patients with AMI is not common. Coronary spasm during cardiac catheterisation is reported to occur in 1%-5% of percutaneous coronary interventions.  The mechanism of spasm remains uncertain, but is considered to be multifactorial such as endothelial dysfunction, upregulation of rho-kinase at the site of spasm, oxidative stress or excessive smooth muscle contraction. Coronary artery spasm after stent placement has also been reported. Drug eluting stents more commonly or causitive than bare metal stents.  Nitrates and calcium antagonists are usually effective for coronary vasospasm and most patients respond to these drugs. Refractory coronary vasospasm is relieved by intracoronary administration of nicorandil.  In the presence of haemodynamic instability, intra-aortic balloon pump (IABP) has also been used. In the patient presented here, coronary vasospasm occurred 6 h after percutaneous coronary intervention (PCI) with stent placement and was recurrent causing haemodynamic instability that was relieved by milrinone. Milrinone is a known drug to relieve conduit arterial spasm in post-coronary artery bypass surgery.
A 42-year-old male, presented to medical emergency department with retrosternal chest pain along with profuse sweating 2 h prior to admission. He admitted to smoking cigarettes (20 pack years). His electrocardiogram (ECG) showed acute inferior wall myocardial infarction with posterior wall extension without right ventricular involvement. At three time of admission the patient's blood pressure 90/60 mm of Hg and heart rate was 102/min.
Mean arterial pressure was stabilised by a combination of intravenous administration of fluids and dopamine at a rate of 6 µg/kg/min. The patient was scheduled for primary percutaneous coronary angioplasty (PTCA). The coronary angiogram revealed 100% occlusion with thrombus of dominant right coronary artery (RCA) distally, with normal left circumflex and left anterior descending artery [Figure 1]. Stenting to distal RCA was performed with 3.5 × 20 mm bare metal stent. Procedure was completed without any complications and thrombolysis in myocardial infarction (TIMI) III flow was achieved [Figure 2]. Following the procedure, Abciximab (Gp IIb/IIIa inhibitor) 0.25 mg/kg followed by continuous infusion at 0.125 µg/kg/min was administered. After the procedure, the patient was asymptomatic, ECG changes settled, dopamine infusion was tapered off and intravenous fluids were continued.
Six hours apted procedure, the patient developed chest pain with ST segment elevation in inferior leads and sinus bradycardia (heart rate: 46/min). The patient's blood pressure decreased to 90/60 mm of Hg. Keeping mind the possibility of acute stent thrombosis, the patient was again taken up for emergency cardiac catheterisation. His coronary angiogram revealed coronary vasospasm in proximal RCA with TIMI I flow across the stent [Figure 3]. Coronary vasospasm was relieved by the administration of 50 µg of intracoronary nitroglycerine and TIMI III flow was re-established [Figure 4].
Administration of either intracoronary verapamil or nicorandil was deferred due to preexisting bradycardia and hypotension. Nitroglycerine infusion was restarted, but the administration had to be discontinued due to persistent hypotension. Dopamine infusion was restarted along with intravenous fluids. Despite these treatments, the patient continued to have the symptoms of ischaemia. The patient was subsequently started on milrinone infusion. Intravenous infusion of milrinone was started (25 µg/kg bolus over 20 min followed by 0.25 µg/kg/min). The authors started with half the recommended dose of milrinone with an intention to step up if required. The patient improved both symptomatically and haemodynamically. There was no recurrence of symptoms. The infusion of dopamine was stopped after tapering it and milrinone infusion was continued for 24 h. Subsequently, the patient was started on oral calcium channel blockers. He was discharged from the hospital in a stable condition with the stress for need to quit smoking.
Coronary vasospasm is defined as a transient abnormal contraction of an epicardial coronary artery that results in myocardial ischemia. Endothelial dysfunction and excessive smooth muscle contraction has been postulated to explain coronary spasm.  Rho-kinase upregulation and oxidative stress have also been given attention as an important mediator of the spasm. Predisposing factors include smoking, lipid metabolic disorders, and gene expression, all of which may be interrelated issues. 
Many agents have been used to relieve epicardial coronary vasospasm. which includes oral nifedipine, intravenous isosorbide dinitrate, nitroglycerine, diltiazem and nicorandil, intracoronary nitroglycerine, nicorandil and levosimendan. Other mechanical interventions such as multistenting, temporary left ventricular assist device, and intra-aortic counter pulsation therapy have also been tried. 
Milrinone is a positive inotrope and a potent, endothelium-independent direct vasodilator, with little chronotropic activity. It is a selective inhibitor of peak III cAMP phosphodiesterase isozyme in cardiac and vascular muscles. Although the vasorelaxant properties of milrinone are not dependent on nitric oxide release, its effect may be partly endothelium-dependent in human blood vessels in vitro . 
Milrinone is a direct vasodilator of the human conduit arteries and has been used in the perioperative treatment of internal thoracic artery spasm in cardiac surgical patients.  It has also been used therapeutically to treat cerebrovascular spasm of subarachnoid haemorrhage.  Milrinone was found to be more potent than papaverine but less potent than nitroprusside and glyceryl trinitrate. 
Smoking tobacco by the patient may have contributed to providing substrate of damaged endothelium and a state of chronic inflammation on which vasospasm occurred. We presume that milrinone may be a therapeutic intervention to treat ischemic coronary syndromes caused by coronary artery spasm. Further studies may throw more light on this issue.
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