Effect of tyramine on myocardial catecholamine release in coronary heart disease

The influence of tyramine on myocardial catecholamine release and on coronary blood flow has not previously been determined in man. Therefore, the effect of tyramine was measured on coronary and systemic hemodynamics and on norepinephrine (NE) and epinephrine levels in blood from the aorta and coronary sinus in 9 patients with coronary artery disease. Tyramine produced a striking increase in coronary sinus NE, from a baseline of 344 ± 56 to a peak level of 1416 ± 310 pg/ml (p < 0.01) 2 minutes after tyramine. The increase in aortic NE was less striking, from 265 ± 32 to 421 ± 63 pg/ml (difference not significant). Therefore, the net release of NE from the heart was increased by tyramine from 12,007 ± 393 to 139,357 ± 46,156 pg/ ml/min (p < 0.03). There was no release of epinephrine across the coronary bed. There was a variable response of coronary blood flow and resistance after tyramine. Thus, the rich innervation of the heart by sympathetic nerve endings can result in marked NE release into the coronary sinus.     

Regional hemodynamic effects of beta-adrenergic blockade with propranolol in the unanesthetized primate

The effects of equal doses of d- and dl-propranolol on systemic and regional hemodynamics were studied in the unanesthetized rhesus monkey using the radioactive microsphere technique. No changes in systemic hemodynamics were seen with d-propranolol, but dl-propranolol significantly decreased the cardiac output (?25 per cent), heart rate (?18 per cent), and stroke volume (?9 per cent), and increased the total peripheral resistance (+40 per cent). During the dl-propranolol infusion the cardiac output was preferentially distributed to the brain with a small decrease in the fraction received by the liver. Flow to all organs except the brain was diminished during dl-propranolol, and the decrease was proportionate to the change in cardiac output. No change in distribution of flow was seen with d-propranolol and total flow to all organs was unchanged from control, with the exception of an increase in flow to the skin. This comparison of d- and dl-propranolol indicates that the effects of dl-propranolol are due to beta-adrenergic blockade rather than a non-specific effect of the drug.     

Clinical course of patients following the demonstration of coronary artery spasm by angiography

The clinical course of 25 patients was determined during an average of 2.7 years following the angiographic demonstration of coronary artery spasm (CAS). Seventeen patients received medical treatment after the demonstration of coronary spasm and six patients had cardiac surgery. Twenty-three patients were living and two patients had died at the time of follow-up. Twenty-one of the 23 surviving patients has either no chest pain or markedly reduced symptoms. However, the demonstration of CAS by angiography was associated with a high incidence of subsequent cardiac complications, which included myocardial infarct (four patients), cardiac arrest (four patients), and death (two patients). We concluded from this study that after the demonstration of CAS by angiography: (1) the clinical course was variable, with most patients (21 of 25 patients, 84%) having improvement of symptoms at the time of follow-up; (2) major cardiac complications were frequent (11 of 25 patients, 44%) and; (3) although clinical and coronary angiographic features were of limited use in predicting major cardiac complications, most of the patients who had an uncomplicated course (11 of 14 patients, 79%) had either < 50% fixed coronary artery luminal diameter narrowing (CAN) or coronary artery bypass graft operations, the majority of patients with < 50% fixed CAN (8 of 11 patients, 73%) had no major cardiac complications, and myocardial infarction or death usually occurred during periods of increased angina pectoris.     

Two-dimensional echocardiography in the diagnosis of carcinoid heart disease

Tricuspid valve disease accounts for significant morbidity and mortality in the carcinoid syndrome, but M-mode echocardiography is often insensitive in completely defining the tricuspid valve. We performed two-dimensional echocardiography (2DE) in seven patients with proven carcinoid syndrome. There were five males and two females whose ages ranged from 53 to 79 years. The carcinoid syndrome had been present by symptoms for 12 to 84 months and by 5-HIAA levels for 6 to 84 months prior to 2DE. Short, thickened, immobile tricuspid valve leaflets, fixed in a partially open position, were visualized in two patients and confirmed in one patient at surgery. Tricuspid regurgitation was demonstrated angiographically in one and by contrast 2DE in the other. A third patient had clinical evidence of tricuspid stenosis with a doming tricuspid valve on 2DE. The motion of the tricuspid value viewed in real time was clearly distinct in these two situations. Four patients had both normal M-mode and 2DE studies despite the fact that clinical and biochemical evidence of carcinoid disease had been present for equally long periods of time. The tricuspid valve was best visualized in the parasternal right ventricular long-axis and short-axis views. The apical four-chamber view was less helpful. Thus, 2DE demonstrated specific tricuspid valve abnormalities in the carcinoid syndrome with thickening, shortening, and immobility of the leaflets when valvular regurgitation was present and thickening and doming when the valve was stenotic. 2DE should be a useful method in the diagnosis and sequential evaluation of patients with carcinoid heart disease.     

Congestive heart failure in childhood and adolescence: recognition and management

Clinical, coronary arteriographic, and hemodynamic studies were performed in 55 patients with left bundle branch block (LBBB) and coronary artery disease and were compared with 110 patients consecutively matched for age and sex with ischemic heart disease but without LBBB. No significant differences were found in duration of symptoms or frequency of prior myocardial infarction, hypertension, or diabetes mellitus; however, the LBBB patients had a significantly (p < 0.001) higher frequency of congestive heart failure (38.2% vs 11.8%) and cardiomegaly (63.6% vs 25.5%). An evaluation of severity of the coronary disease on the basis of subtotal vs total obstructive lesions, number of vessels involved, total coronary score, and individual coronary arteries involved revealed no significant differences between the groups. The LBBB patients had significantly (p < 0.001) greater impairment of left ventricular function as reflected by the end-diastolic volume (107 ± 43 vs 79 ± 30 ml/m²), ejection fraction (0.35 ± 0.19 vs 0.59 ± 0.18), and frequency of an abnormal contractile pattern (91% vs 61%). Evaluating the LBBB patients on the basis of the QRS width and axis revealed no significant intragroup differences in clinical profile, severity of coronary disease, or left ventricular dysfunction. A prolonged PR interval (≥0.20 second) was associated with more severe coronary artery disease and an enlarged heart. This study indicates that coronary artery disease associated with LBBB identifies patients with severe left ventricular dysfunction.     

Three-vessel coronary artery spasm in a patient with variant angina and normal coronary arteries

Variant angina with two or more electrocardiographic or angiographic localizations has seldom been reported [1-4]. We present a case of variant angina pectoris and normal coronary arteries with three different and independent electrocardiographic localizations.     

Use of droperidol-fentanyl sedation for cardiac catheterization in children

Droperidol-fentanyl sedation for cardiac catheterization was evaluated in 106 consecutive children ≥ two years of age. The dose of 0.025 c.c. per kilogram of body weight (maximum 1 c.c.) produced adequate sedation in all but two patients without producing significant hypoventilation or heart rate changes. In patients without left heart volume overload or myocardial disease, left ventricular volume studies and pressurevelocity indices of contractile state were normal. Side effects were rarely encountered and easily controlled or reversed with diphenhydramine. Although we recommend this combination for cardiac catheterization sedation, we would not recommend exceeding our dosage schedule.     

Myocardial infarction in patients with coronary artery spasm demonstrated by angiography

Twelve cases of myocardial infarction (MI) were documented in 11 of 39 patients who had coronary artery spasm (CAS) that was observed by angiography either before MI (3 patients), after MI (5 patients), or both before and after MI (3 patients). MI corresponded in location to sites of ECG changes of myocardial ischemia during spontaneous angina pectoris in 7 of 7 patients and to the region of myocardium supplied by the vessel in which CAS was observed by angiography in each patient. MI occurred in the distribution of the right coronary artery in 8 patients and of the left coronary artery in 4 patients. Of 12 vessels that supplled infarcted regions of myocardium, 7 vessels had ≥50% diameter fixed coronary artery narrowing (CAN), but the remaining 5 vessels had minimal (10%) or no fixed CAN. In those patients who were studied after MI, coronary angiography demonstrated that only 3 of 9 vessels in the distribution of infarcted regions of myocardium were completely occluded. Clinical follow-up for an average of 1.3 years after MI showed that 7 patients continued to have chest pain, 2 patients were asymptomatic, and 2 patients died suddenly 9 weeks and 1 year, respectively, after MI. Therefore, among our patients with CAS demonstrated by angiography, Mis (1) were frequent (28%), (2) occurred in the distribution of observed coronary spasm, (3) were frequently (5 of 12 arteries) in the distribution of vessels having minimal or no fixed narrowing, and (4) were often (6 of 9 arteries) in the distribution of vessels that were demonstrated to be patent after MI.     

Variability of electrocardiographic responses to repeated ergonovine provocation in variant angina patients with coronary artery spasm

We reviewed our experience with serial ergonovine provocative tests for coronary artery spasm (CAS) in ten variant angina patients with angiographically proved CAS. Of the 26 ergonovine tests performed in the ten patients, only four patients exhibited reproducible ECG response to ergonovine. The remaining six patients had variable and unpredictable ECG responses to ergonovine. All patients were in an active phase of their disease. The variability of ST segment directional response to ergonovine is considered to be on the basis of disparate sensitivity of the coronary circulation to intravenous ergonovine. Because of this variable response, the ECG response alone should not be considered as the standard indicator for CAS presence but should be utilized with other hemodynamic and angiographic criteria.     

Histamine provocation of clinical coronary artery spasm: Implications concerning pathogenesis of variant angina pectoris

Twelve patients with nonexertional chest pain and nonobstructive fixed coronary disease (< 50% luminal diameter narrowing) were given histamine to investigate the potential role (coronary artery H₁ receptor agonism) of the endogenous agent in producing coronary artery spasm (CAS). Histamine, at intravenous dose of 0.5 to 1.0 μg/kg/min, provoked CAS in four patients. In six patients neither histamine nor ergonovine provoked spasm, and these patients were considered by chronic follow-up evaluation to have noncardiac etiology for their chest pain syndrome. In one patient CAS was provoked with ergonovine but not by histamine, and one ergonovine-positive patient had an equivocally positive histamine result. Pretreatment with cimetidine (H₂ receptor antagonism) was necessary to avoid unpleasant side effects of histamine. Thus these observations indicate that histamine should be included among the specific agents capable of inducing CAS and provide new insight concerning the mechanism(s) causing variant angina pectoris.     

Randomized double-blind comparison of nifedipine and isosorbide dinitrate therapy in variant angina pectoris due to coronary artery spasm

Twelve patients were entered prospectively into a randomized double-blind study comparing the efficacy of nifedipine and isosorbide dinitrate (ISDN) in the treatment of variant angina pectoris due to coronary artery spasm. Using the diary technique, both anginal episodes and nitroglycerin tablets consumed were recorded during the pretrial, no drug period, and both active drug phases. During the baseline pretrial period, an average of 1.1 anginal episodes/day occurred with reduction to 0.28/day during nifedipine treatment and 0.39/day during ISDN treatment. Headache was the major side effect during ISDN treatment, occurring in 9 of 11 (81%) patients; and nonheart failure related pedal edema during nifedipine treatment, occurring in 4 of 12 (33%) patients. Intolerable side effects necessitating cessation of treatment occurred in two patients during nifedipine treatment and in three patients during ISDN treatment. Patients preferred nifedipine over ISDN because of increased efficacy and fewer uncomfortable side effects. We conclude that both nifedipine and ISDN are effective therapy for coronary spasm, but that nifedipine was more effective and was preferred by the majority of patients.     

Coronary artery spasm as the cause of myocardial infarction during coronary arteriogarphy.

Catheter-induced coronary artery spasm has been observed frequently. It is usually transient, reacts to the administration of nitroglycerin, and its distribution is generally confined to an area in proximity ot the intubated catheter. A 43-year-old woman with recurrent chest pain was found to have a rather long segment of tight proximal obstruction of the right coronary artery and experienced a myocardial infarction during coronary catheterization. Because of recurrent attacks of severe chest pain, coronary artery bypass surgery was performed which failed to result in significant improvement of her symptoms. Two repeat coronary cineangiograms seven weeks and three years after surgery revealed the proximal right coronary artery to be free of stenotic lesions or of luminal irregularities. After considering possible mechanisms of myocardial necrosis in the presence of normal coronary arteries it is concluded that myocardial necrosis can result from catheter-induced coronary artery spasm in spite of administration of nitroglycerin.