Ergonovine-induced Coronary Spasm Research Articles

Myocardial ischaemia secondary to intramyometrial injection of methylergonovine maleate.

Sir, Ergonovine is used in obstetric practice and as a diagnostic agent in cardiac catheterisation laboratories. This drug may precipitate acute myocardial infarction due to prolonged coronary spasm.[1] We report a case of acute myocardial ischaemia caused by intramyometrial administration of methylergonovine maleate during caesarean section. A healthy, 28-year-old woman (height 155 cm, weight 76 kg, gravida 2, para 2) at 38 weeks gestation underwent an emergency lower section caesarean section (LSCS) due to scar tenderness of previous LSCS. She had no history of preeclampsia, migraine and risk factors for coronary heart disease such as smoking, diabetes mellitus, hypertension, hyperlipidaemia and obesity. Spinal anaesthesia was administered with a 25-gauge needle at L3-L4 interspace with 12 mg of 0.5% of hyperbaric bupivacaine. After the delivery of the foetus, despite uterine massage, continuous intravenous oxytocin infusion and intramuscular carboprost (15-methyl-PGF2α) 250 μg, the uterus remained atonic. In a desperate attempt to achieve uterine contraction, the obstetrician gave a single intramyometrial injection of 0.2 mg methylergonovine maleate. Immediately, patient's blood pressure (BP) increased from 126/84 mm Hg to 164/104 mm Hg. Heart rate (HR) increased from 86/min to 104/min. Electrocardiogram (ECG) revealed sinus rhythm and oxygen saturation remained 100%. In next 5 min, patient's BP increased to 190/116 mm Hg and HR to 120/min. She started complaining of headache, substernal chest pain and developed laboured breathing. Chest auscultation revealed bilateral crepitations and ECG now showed non-specific T-wave abnormalities with ST-segment elevation. Patient was immediately intubated, and mechanical ventilation with positive end-expiratory pressure was started. Injection furosemide 20 mg was given, and nitroglycerine infusion at 5 μg/min was started. Uterus, by now, had contracted and wound closure was done. The patient was transferred to Intensive Care Unit for mechanical ventilation and monitoring of her vitals. Immediate post-operative X-ray chest showed pulmonary oedema. Subsequently, BP started stabilizing towards normal values and ECG changes reverted to normal rhythm. Chest became clear by the end of 3 h. Creatine phosphokinase and troponin levels were within normal limits. The patient was extubated after 8 h and shifted to post-operative room. Despite the frequent usage of methyl ergonovine maleate for routine management of the third stage of labour and post-partum atony, cardiac complications of this drug have rarely been reported. The risk factors for coronary artery spasm by ergot derivatives are Asian origin, age >30, smoking, family history of ischaemic heart disease and history of migraine.[2] Although other conditions such as oesophageal spasm are known to mimic angina and are accompanied by non-specific ECG changes, the onset of clinical symptoms and ECG changes immediately after intramyometrial administration of methyl ergonovine suggest cardiac aetiology (coronary vasospasm).[3] The recommended mode of administration of methylergonovine maleate in the post-partum period is intramuscular. Intravascular (IV) or intramyometrial route is not recommended. Intramyometrial injection leading to myocardial ischaemia has been reported rarely.[3] Because the myometrium is a highly vascular tissue, the intramyometrial injection of methylergonovine maleate might behave as an IV administration of drug.[3] IV injection can cause hypertension, myocardial infarction, acute heart failure, pulmonary oedema, cerebral haemorrhage and retinal detachment.[4] If IV administration is considered essential as a life-saving measure, injection should be given in incremental doses with careful monitoring of BP and ECG.[5] Nitroglycerine was successfully used to reverse ergonovine-induced coronary spasm. It also prevents subsequent development of myocardial ischaemia and infarction.[3] Thus, intramyometrial injection of ergonovine is not to be encouraged as it can cause coronary artery spasm in obstetric patients. Prompt evaluation and management may prevent or reduce the morbidity or mortality caused by this drug. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Increased circulating malondialdehyde-modified low-density lipoprotein levels in patients with ergonovine-induced coronary artery spasm

ObjectiveCoronary endothelial dysfunction is thought to underlie the development of coronary artery spasms. Malondialdehyde-modified low-density lipoprotein (MDA-LDL) was suggested as a marker of endothelial damage. This study investigated the diagnostic impact of MDA-LDL on ergonovine-induced coronary spasms. MethodsWe included 152 patients with suspected coronary spastic angina. MDA-LDL levels were measured before an ergonovine provocation test. Coronary spasm was defined as total or subtotal occlusion, compared to the relaxed state after nitroglycerin, associated with ischemic ECG changes and concurrent chest pain. Changes in vessel diameter in response to ergonovine were evaluated with quantitative coronary angiography. ResultsCoronary spasms were observed in 41 patients (27%). MDA-LDL levels were significantly higher in patients with spasms compared to those without spasms (139.9±45.9U/L vs. 109.6±36.6U/L, p<0.01). Univariate logistic regression analyses indicated significant relationships between coronary spasms and MDA-LDL (per 10U/L, odds ratio (OR): 1.20; p<0.01), high-density lipoprotein (per 10mg/dL, OR: 0.76; p=0.03), smoking (OR: 3.04; p<0.01), and male gender (OR: 3.51; p<0.01). In the multivariate model, MDA-LDL (per 10U/L, OR: 1.17; p<0.01) remained a significant predictor of coronary spasm. Regression analysis showed a positive correlation between MDA-LDL levels and coronary luminal diameter changes induced by ergonovine (r=0.57, p<0.01). The optimal MDA-LDL threshold for predicting coronary spasm was 121.3U/L, identified with a receiver operating characteristic curve. ConclusionsIncreased circulating MDA-LDL levels were associated with ergonovine-induced coronary artery spasm.

Action of Steroid Sex Hormones on the Isolated Rabbit Heart

Steroid sex hormones, testosterone, progesterone and diethylstilbestrol, have been tested on the isolated rabbit heart. These hormones produced a negative inotropic effect (1-10 mumol/l) and an inhibitory effect on the vasopressin- or ergonovine-induced coronary spasm (0.1-10 mumol/l). Basal coronary tone was increased by testosterone and progesterone, while diethylstilbestrol induced a slight reduction of coronary perfusion pressure. The negative inotropic effect was reversed by calcium and isoprenaline, thus resembling the calcium entry blocker activity. The activation of myocardial and coronary contractility by the calcium agonist, Bay K 8644, was antagonized by all these hormones. These observations demonstrated an influence of steroid sex hormones with calcium fluxes in the isolated rabbit heart.

Inhibitory actions of amiodarone on the isolated rabbit heart and aorta

1. 1. The inhibitory actions of amiodarone on the isolated rabbit heart and aorta have been studied. 2. 2. Amiodarone inhibited vasopressin- and ergonovine-induced coronary spasm, starting from a concentration of 10 −7 M which did not affect myocardial contractility to 10 −4 M, which decreased myocardial contractility. 3. 3. Sinus node activity was largely unaffected even when the highest dose of 10 −4 M was used. 4. 4. Amiodarone did not modify the smooth muscle contraction in rabbit aorta strips precontracted with noradrenaline or potassium. 5. 5. Comparison with other inhibitors of the cardiovascular system (α- and β-blockers, nitrates, calcium entry blockers) points out a peculiar pharmacological profile of amiodarone and indicates some doubts about its presumed anti-adrenergic properties.

The Nature of ventricular arrhythmias during ergonovine‐induced vasospastic angina pectoris

The peak incidence of ventricular fibrillation in acute myocardial infarction usually occurs during the first hours after the onset. Electrophysiological changes immediately after the onset have been studied in animal models, but are still incompletely understood in humans. For clarification of the characteristic features of ventricular arrhythmias during acute myocardial ischemia, ventricular arrhythmias were studied in 81 patients with vasospastic angina pectoris induced by ergonovine. Ventricular arrhythmias occurred in 45 of these patients, including ventricular tachycardia in 15, and ventricular fibrillation requiring repeated DC defibrillation in two patients. Most ventricular extrasystoles occurred before the ST segment reached maximum elevation, while reperfusion arrhythmias were less common. In many patients the coupling intervals varied, and the configuration was multiform. It is concluded that ventricular arrhythmias occurring during ergonovine-induced coronary spasm show different characteristics from those occurring during chronic ischemia. As the arrhythmias in this study seem, in some ways, to resemble arrhythmias occurring at the onset of myocardial infarction, the results might provide useful information on ventricular arrhythmias in myocardial ischemia in humans.

Comparison of electrocardiography and thallium-201 myocardial scintigraphy for the detection of ergonovine-induced coronary artery spasm: Angiographic correlation

This study was performed to determine the sensitivity of thallium imaging vs ECG monitoring for detecting coronary artery spasm noninvasively following intravenous ergonovine administration as compared to simultaneous coronary angiography. Thirty-two patients with insignificant coronary artery disease and chest paln underwent 12-lead ECG monitoring, thallium imaging, and coronary arteriography following the administration of 0.05, 0.1, 0.2, and 0.3 mg of ergonovine given 5 minutes apart or until chest pain occurred. One minute following the last dose of ergonovine, 2.5 mCi of thallium-201 was injected intravenously, and a final ECG was recorded and repeat coronary arteriography performed. Within 10 minutes following the injection of thallium, imaging was performed in the 40-degree and 70-degree left anterior oblique and anterior projections. The ECG, thallium study, and coronary arteriogram were read blindly and results were compared. The ECG, anglogram, and thallium study were read as positive if the following occurred, respectively: ≥1 mm ST segment elevation, depression, or T wave reversal; greater than 50% vessel narrowing; and reversible perfusion defect. Five patients were excluded from analysis because of either catheter-induced spasm, suboptimal thallium studies, or protocol violations. Of the 27 patients included for analysis, six had chest pain, five had a positive angiogram, five had a positive thallium study, and one had a positive ECG. The sensitivity of thallium vs ECG monitoring was 80% vs 25%, and the accuracy was 92% vs 80%. We conclude that thallium imaging greatly increases the noninvasive detection of ergonovine-induced coronary spasm as compared with the ECG with no loss of accuracy.

Ergonovine-induced coronary spasm refractory to intracoronary nitroglycerin but responsive to nitroprusside

Ergonovine-induced coronary spasm refractory to intracoronary nitroglycerin but responsive to nitroprusside

Influence of nifedipine on left ventricular systolic and diastolic function: Relationships to manifestations of ischemia and congestive failure

In addition to the favorable effects of calcium antagonists on symptoms related to coronary spasm, we recently documented preclusion of ergonovine-induced coronary spasm angiographically in four patients with proved Prinzmetal's angina. To determine whether nifedipine has similar “relaxing” or negative inotropic actions on left ventricular myocardial function, we studied 19 patients with various degrees of left ventricular dysfunction before and after nifedipine (20 mg sublingually) during cardiac catheterization. Left ventricular afterload was reduced, with a significant (13 percent) decline in arterial pressure; left ventricular diastolic pressures were unchanged. Left ventricular ejection function was augmented, with significant increases in ejection fraction (14 percent), mean velocity of circumferential fiber shortening (41 percent), systolic ejection rate (25 percent), and end-systolic pressure volume ratio (19 percent). Cardiac index increased significantly by 16 percent. Early diastolic relaxation, diastolic pressure-volume relations and end diastolic stiffness remained unchanged after nifedipine. When patients were categorized (Group I: left ventricular end-diastolic volume ≤ 90 ml/m 2, end-diastolic pressure ≤ 20 mm Hg; Group II: end-diastolic volume > 90 ml/m 2, end-diastolic pressure > 20 mm Hg), highly pertinent differences were apparent. Nifedipine significantly reduced left ventricular preload and end-diastolic pressures in Group II but not in Group I patients. Enhancement of left ventricular ejection function in Group II patients was significantly more prominent than that in patients with normal baseline function. Although diastolic properties were insignificantly changed overall, the left ventricular diastolic pressure-volume relation was displaced downward by nifedipine in Group II, but not in Group I patients. Both systemic and pulmonary vascular resistance declined significantly more in Group II patients, whereas cardiac index was increased 25 percent compared with a negligible change in group I patients. These results indicate beneficial effects of nifedipine on myocardial oxygen requirements, particularly in patients with impaired left ventricular function in whom left ventricular preload and afterload were both significantly reduced, cardiac index augmented and the pressure-volume relation shifted downward. To confirm predicted symptomatic benefits in 13 other patients with fixed coronary, disease, incremental atrial pacing to anginal threshold was performed before and 30 minutes after nifedipine (20 mg sublingually). Mean paced heart rate at onset of angina increased 19.3 percent after nifedipine. Concomitantly, aortic pressure decreased significantly by 22.1 percent at the onset of angina; double product was unchanged at the anginal threshold. Thus, although left ventricular afterload was reduced by nifedipine, the anginal threshold was unchanged in terms of myocardial oxygen requirements. In concert, these results indicate that therapeutically effective influences of nifedipine in patients with fixed coronary disease are attributable basically to hemodynamic alterations consequent upon left ventricular afterload reduction. Nevertheless, such effects imply therapeutic benefit, the reduced afterload concomitantly permitting greater exercise-induced tachycardia before the anginal threshold is reached.