Doses Of Ergonovine Research Articles

Abstract 12340: Early Restoration of Coronary Vasomotor Function Following Drug-Coated Balloon Only Angioplasty of de novo Lesions

Introduction: We evaluated whether drug-coated balloon (DCB)-treated de novo lesions are prone to vasospasm and how these segments respond to ergonovine and nitrate in comparison with angiographically normal segments and other untreated segments showing prominent vasoreactivity. Hypothesis: DCB angioplasty is an emerging treatment approach for coronary artery disease. Evidences in balloon angioplasty era, however, repeatedly reported the presence of abnormal vasomotor function at balloon-injured segment, leading to fatal spasm. Methods: 68 DCB angioplasty recipients underwent 6-months follow-up coronary angiography. Vasomotor function was assessed using intracoronary injection of incremental dose of ergonovine, followed by nitrate. Percent change of mean lumen diameter was assessed by quantitative coronary angiography at three different sites: DCB-treated segment vs. angiographically normal segment ( control ) vs. normal or mildly diseased segment (diameter stenosis < 30%) showing prominent vasomotor response ( other diseased segment ). Results: All patients were event-free during 6-month follow-up. A total of 87 DCB-treated lesions were analyzed. Significant ergonovine-induced vasospasm developed in 8 patients; however, none of them showed focal spasm involving DCB-treated lesion only. There was no significant difference in mean lumen diameter after ergonovine provocation between DCB-treated lesions vs. angiographically normal segments. However, vasoconstrictor response was greater in other diseased segments than in DCB-treated lesions. After nitrate injection, all segments dilated significantly. Vasoreactivity, defined as combined constrictor and dilator response, was comparable between DCB-treated lesions and controls (p>0.05); while significant difference was found against other diseased segment (p<0.005), implicating the restoration of vasomotor function after DCB angioplasty. Conclusions: Lesion treated by DCB did not harbor increased risk for clinically or angiographically significant vasospasm and showed vasomotor function similar to angiographically normal segments. These findings support feasibility and safety of DCB-only strategy for the treatment of de novo coronary artery disease.

Ergonovine test in angina with normal coronary arteries. Is it worth doing it?

Background Patients with angina and normal coronary arteries are often misdiagnosed with having non-cardiac pain. Although vasospasm is a well-known entity, spasm provocation is not routinely done in the majority of hospitals at present. Materials and methods One hundred and sixty two consecutive patients with thoracic pain and normal coronary arteries were retrospectively studied. The characteristics of pain were analysed. One hundred and sixty one non-invasive tests (with and without imaging) were done to 126 patients before angiography. Increasing doses of ergonovine (from 1 to 30 μg) were injected into the coronary arteries to provoke coronary spasm. The correlation between ergonovine-induced spasm and non-invasive tests was studied. Results Oppressive thoracic pain suggestive of angina was present in 144 patients. It occurred at rest in 59 patients, only at night in 14, with effort in 40, and it was mixed in 31. Non-oppressive atypical pain was reported by 18 patients. Non-invasive tests were 94 positive, 60 negative and 7 non-diagnostic. Ergonovine test elicited coronary spasm in 85 patients (52.5%). No significant correlation was found between the positivity of a non-invasive test and ergonovine-induced spasm. Conclusions More than half of the patients with angina and normal coronary arteries can be diagnosed with vasospastic angina if ergonovine test is performed. Even patients with a negative non-invasive test maybe sent to coronary angiography when vasospastic angina is suspected, in order to have an accurate diagnosis.

Decrease of nitric oxide end-products during coronary circulation reflects elevated basal coronary artery tone in patients with vasospastic angina.

The aim of this study was to investigate the role of nitric oxide (NO) in the coronary circulation and its relation to basal coronary artery tone in patients with vasospastic angina (VSA). We evaluated the level of nitric oxide end-products (NOx; nitrite + nitrate) in coronary circulation blood using an HPLC-Griess system for nine patients with VSA and nine control patients. All of the patients with VSA experienced focal spasm in the proximal to middle segments of the left anterior descending coronary artery (LAD) in response to intracoronary injection of ergonovine maleate. The luminal diameter of the coronary artery was measured in each patient by quantitative coronary arteriography. Blood samples for NOx measurement were obtained from the coronary sinus (NOxV) and the ostium of the left coronary artery (NOxA). The NOx difference, calculated from the coronary venous-arterial difference in NOx, was close to zero for the control patients whereas it was clearly negative for the patients with VSA. In addition, the NOx difference in the patients with VSA showed a negative correlation with basal coronary artery tone (r = -0.91, p < 0.01) and a positive correlation with the dose of ergonovine required for spasm provocation (r = 0.77, p < 0.05). These results indicate that increased basal coronary artery tone and higher susceptibility to ergonovine in patients with VSA would be a consequence of coronary endothelial dysfunction as is indicated by NOx.

Cardiac Arrest After Mesenteric Manipulation in a Patient Undergoing Abdominal Surgery

Cardiac Arrest After Mesenteric Manipulation in a Patient Undergoing Abdominal Surgery

Hypersensitivity of human coronary segments to ergonovine 6 months after injury by coronary angioplasty: a quantitative angiographic study in consecutive patients undergoing single-vessel angioplasty.

Multiple studies have been designed to analyse restenosis angiographically but few have studied the vasoreactivity of coronary segments subjected to angioplasty a few months before. In the present study we analysed, with use of quantitative angiography, the vasoreactivity of previously dilated segments to graded doses of ergonovine and of isosorbide dinitrate. Fifty consecutive patients undergoing follow-up angiography 6 months after a single coronary angioplasty procedure were studied. The vasoconstrictor response at dilated segments (-19.3 +/- 3.0%) was significantly greater than at control proximal and distal sites in dilated (-7.3 +/- 1.1%, -11.0 +/- 2.9%) and non-dilated (-9.1 +/- 1.3%, -8.3 +/- 2.2%) vessels for the lowest dose of ergonovine (100 micrograms). The constrictor response to 100 micrograms ergonovine (-20.2 +/- 5.3%) at restenosed segments (> 50% stenosis, n = 18) was similar to that (-18.8 +/- 3.8%) at non-restenosed sites (n = 32). In contrast, the degree of constrictor response was similar in all segments including dilated segments for the highest dose of ergonovine used. All segments dilated significantly after intracoronary injection of isosorbide dinitrate. Our results demonstrate hypersensitivity of the dilated site to ergonovine 6 months after angioplasty at both restenosed and non-restenosed sites. This response may reflect partial dysfunction of endothelium that has regenerated after injury or hypersensitivity of vascular smooth muscle cells at the site of arterial injury.

Effects of intracoronary ergonovine on the contralateral coronary artery in patients with atypical chest pain

Ergonovine has become an accepted agent for the provocation of coronary artery spasm. Standard testing protocols generally use either cumulative or single intravenous bolus doses of ergonovine. A disadvantage of such protocols is that spasm may occur in both coronary arteries simultaneously, or during catheter exchange and, if severe, may be difficult to document and manage in some patients with severe myocardial ischemia, especially if using the Judkins technique. Recently, some investigators 1,2 have begun to administer intracoronary ergonovine to allow selective provocation of spasm in a single coronary artery. It has been postulated that this method might offer more precise control of the vasoconstrictor stimulus and a wider margin of safety than is possible with intravenous administration of ergonovine. In addition, this approach may avoid systemic hypertension and occasional systemic adverse effects that may be seen with intravenous ergonovine. Despite increasing use of intracoronary ergonovine administration in patients, it has not been determined whether such administration causes a truly selective vasoconstrictor effect. The present study determines whether intracoronary ergonovine administration causes selective unilateral coronary artery constriction or whether the contralateral coronary artery is affected as well.

Circadian Influence in Cardiovascular Disease (Part 1)

This department will offer stylized clinical presentations of current cardiovascular issues. Questions raised as a case history evolves highlight key elements that are elaborated upon in the discussions which follow.

The dynamic changes of plasma tissue-type plasminogen activator level and the activity of its inhibitor during coronary vasospasm.

This study aimed to examine the dynamic changes of the fibrinolytic system during coronary vasospasm. Tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) and fibrinopeptide A (FPA) levels were measured in the great cardiac venous and arterial blood of 9 patients with clinically and angiographically proven vasospastic angina and 11 controls. Before ergonovine provocation, although there was no difference between the above 2 groups in t-PA levels in the aorta or the great cardiac vein, the PAI level in patients with variant angina was lower than in the controls both in the aorta (4.2 +/- 3.5 IU/ml vs 10.9 +/- 5.2 IU/ml) and in the great cardiac vein (2.3 +/- 2.9 IU/ml vs. 11.9 +/- 4.9 IU/ml). During ergonovine-induced coronary vasospasm in patients with variant angina, the t-PA level in the great cardiac vein significantly increased from 3.4 +/- 0.7 ng/ml to 4.4 +/- 0.5 ng/ml (p less than 0.05), but it did not change in the aorta. The maximal dose of ergonovine (0.4 mg) induced mild diffuse coronary vasoconstriction in the controls, and this diffuse coronary vasoconstriction induced a reduction of PAI levels in the great cardiac vein from 11.9 +/- 4.9 IU/ml to 9.5 +/- 4.8 IU/ml (p less than 0.05). FPA levels in the great cardiac vein did not change during ergonovine-induced coronary vasospasm in either group. Thus, the coronary vasospasm induced the release of t-PA from endothelial cells of coronary vessels and resulted in the reduction in the PAI activity in the great cardiac vein.(ABSTRACT TRUNCATED AT 250 WORDS)

Relative roles of preload increase and coronary constriction in ergonovine-induced myocardial ischemia in stable angina pectoris

To assess the relative role of increased ventricular preload and critical coronary lesions in ergonovine-induced myocardial ischemia, 9 normal subjects (group A), 7 patients with stable angina (group B) and 5 with variant angina (group C) were studied. In all patients, the 12-lead electrocardiogram, blood pressure and left ventricular (LV) volume (technetium-99m blood pool) were continuously recorded before and during administration of incremental doses of ergonovine given at 5-minute intervals. In all subjects, an initial LV dilatation developed; in group B and C patients, this was followed by a decrease in stroke volume and ejection fraction with subsequent onset of electrocardiographic changes and angina. The interval between these events was significantly shorter in group C and in 3 group B patients; in these patients, signs of ischemia appeared with smaller ergonovine doses and at minimal preload increase, coronary constriction being the likely mechanism of ischemia. In the remaining 4 group B patients, the onset of stroke volume, ejection fraction, electrocardiographic changes and angina was significantly delayed, occurring after administration of larger ergonovine doses when LV volume was already considerably increased. This finding suggests that the loading effect of ergonovine on LV volume, rather than on coronary constriction, could be the prevailing mechanism of ergonovine-induced ischemia in these patients.

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.

Response of the coronary artery to a small dose of ergonovine in variant angina

The response of the coronary artery to a small dose (0.01 mg) of ergonovine was observed in nine patients without variant angina and in 10 patients with variant angina. Coronary angiograms were obtained before and after small and larger (routinely used) doses of ergonovine. With the larger dose, all 10 patients with variant angina had total or subtotal spastic occlusion accompanied by angina and ECG changes. Excluding the site of spastic occlusion produced by the larger dose of ergonovine, diameters of proximal, middle, and distal segments in each major coronary artery were measured before and after a small dose of ergonovine. The mean percentage of change in diameter (diameter before — diameter after a small dose of ergonovine)/diameter before a small dose of ergonovine × 100% in patients without variant angina was not significantly different from that in patients with variant angina (5.2 ± 9.5% vs 7.0 ± 11.9%, respectively). However, in patients with variant angina, a small dose of ergonovine produced a percentage of change in diameter of 39.8 ± 15.3% at the site of spastic occlusion incuded by a larger dose of ergonovine, compared with that of 7.0 ± 11.9% in the remaining nonspastic coronary arteries ( p < 0.05). These results indicate that patients with variant angina have local segments which respond differently to ergonovine from the remaining segments of coronary arteries. Clinically, this observation might be helpful in determining the angiographic positivity to ergonovine.

Ergonovine-induced myocardial ischemia: no role for serotonergic receptors?

Because ergonovine appears to produce coronary contractions by a serotonergic (5-HT) mechanism, we attempted to prevent ergonovine-induced ischemia in patients with vasospastic angina by pretreatment with ketanserin, a new selective 5-HT blocker. We studied seven patients with consistently positive results of ergonovine testing (ST segment elevation in three and ST segment depression in four). Ergonovine testing was performed before and after a bolus of 10 mg of ketanserin (all patients) and infusion of 2 to 4 mg/hr for 8 hr (six patients). To assess 5-HT blockade during ketanserin infusion, the constrictor response of hand veins to 5-HT was tested before and after ketanserin. Despite evidence of 5-HT blockade in hand veins, ergonovine-induced ischemia was not prevented by ketanserin in any patient, and there was no significant change in the dose of ergonovine required to provoke ischemia. In one patient, four spontaneous episodes of ST segment elevation occurred during infusion of ketanserin. The plasma concentrations of ketanserin at the time of ergonovine testing ranged from 61 to 127 ng/ml (mean 102) and were well above those that completely inhibit canine coronary 5-HT contractions in vitro. Although human coronary arteries may differ in their responsiveness to 5-HT or ketanserin, these data suggest that ischemia from ergonovine-induced coronary vasospasm is not mediated by 5-HT receptors.

Refractory ergonovine-induced coronary vasospasm: Importance of intracoronary nitroglycerin

Recent experience has suggested that the ergonovine maleate test is a safe procedure for the diagnosis of variant angina pectoris, because ergonovine-induced coronary vasospasm has generally been reversible by sublingual nitroglycerin. This report describes five cases of ergonovine-induced coronary vasospasm that were refractory to sublingual nitroglycerin. Four of these patients had cardiac arrest. In two patients the vasospasm was responsive to intracoronary nitroglycerin administration. Three patients died as a result of the test. The two survivors differed from the nonsurvivors in the total dose of ergonovine given (0.1 and 0.15 mg versus 0.17, 0.3 and 0.3 mg, respectively) and in the method of administration of ergonovine. The survivors were given serial doses of 0.05 mg each, whereas the three nonsurvivors received either larger initial doses (0.1 followed by 0.07 mg) or progressive incremental doses (0.05, 0.1 and 0.15 mg serially). Sublingual nitroglycerin, given to all five patients, and intravenous nitroglycerin, given to three of the five, were ineffective in reversing vasospasm. Intracoronary nitroglycerin favorably altered the course of the survivors. Thus, the ergonovine maleate test is not benign and may cause severe coronary vasospasm that is unresponsive to sublingual and intravenous nitroglycerin, but may be reversed by intracoronary nitroglycerin.

Observations on the action of ergonovine on the coronary circulation and its use in the diagnosis of coronary artery insufficiency

The clinical and electrocardiographic findings indicate that ergonovine, intravenously, has a definite action on the coronary circulation. The symptoms produced are typically those of angina pectoris, and the electrocardiograms correspond to the expected picture of coronary insufficiency, 17,18,19 including the pattern observed during positive anoxemia 7,8,9 and exercise tolerance tests, 1,5 and consist mainly of RS-T depression and T-wave inversion. Since ergonovine maleate rarely produced tachycardia, the changes induced were not due to an increase in heart rate. Nitroglycerin is effective in preventing the ergonovine-produced angina and in shortening the duration of the electrocardiographic abnormalities. In view of the small series of patients studied, further investigation is warranted before any final statements can be made as to the general utility of ergonovine maleate as a measure of the functional status of the coronary circulation. Further study is also indicated to determine the minimum dose of ergonovine that will produce electrocardiographic effects without causing the symptoms of angina. Knowledge of the circulatory action of this drug is essential in view of its widespread use in obstetrics. While no untoward reactions were noted in our subjects, caution must be exercised to avoid excessive dosage and to have available for immediate use vasodilator drugs such as amyl nitrite and nitroglycerin.

THE PHARMACODYNAMICS OF THE DOMESTIC FOWL WITH RESPECT TO ERGONOVINE AND ERGOTAMINE

1. The practicability of the chicken as a laboratory animal is reaffirmed.2. The alkaloids ergonovine and ergotamine are about equally effective in their action upon the circulatory system of the chicken as judged by the magnitude of the blood‐pressure response, but the effects of ergonovine are more transitory.3. Much smaller doses of ergonovine are required to produce pressor responses in chickens than in cats or in other laboratory animals.4. In doses of about 10–20 mg. ergonovine and ergotamine are effective in inhibiting but not reversing the blood‐pressure response to epinephrine in the chicken.5. After moderate doses of ergonovine and ergotamine electrocardiograms show only a slowing of the heart. With excessive doses minor changes in the T‐wave are observed.6. In experiments on the perfused hearts of the fowl, cat, and rabbit small amounts of ergonovine and ergotamine give a striking reduction in the coronary flow. Ergotamine is some ten times more potent than ergonovine in this respect and also more persistent.7. The response of the oviduct to these alkaloids is irregular except in the case of the uterine portion, which is always stimulated by ergonovine. Epinephrine inhibits all segments.8. Studies on the isolated chicken intestine show a reduction in tone from ergonovine and ergotamine, the former being more effective. The response to both substances decreases from duodenum to colon.It is a pleasure to acknowledge the helpful guidance of Professor E. M. K. Geiling throughout this investigation. A portion of the expenses of this work has been met by a grant from the Biological Research Fund of the University of Chicago.