Real-time analysis ambulatory electrocardiography--clinical evaluation of cardiac arrhythmias by the Aegis system

To evaluate the technical reliability, clinical applicability, and arrhythmia accuracy of one manufacturer's real-time analysis ambulatory ECG instrument (Aegis Medical Systems), 164 patients were simultaneously examined through a "Y" cable by both a real-time analyzer and a conventional Holter recorder. Technical failure was similar for both recorders (2% in each), and the real-time analyzer was applicable to all patients encountered. Using a randomly selected hand-counted database of 799 hours as the standard of truth, accuracy of the real-time analyzer for hourly mean heart rate, isolated ventricular ectopic beats, ventricular couplets, ventricular tachycardia, isolated supraventricular ectopic beats and supraventricular tachycardia was determined. Mean heart rate showed 96% agreement and a high correlation (r = .986) to hand-counted values. Real-time analysis overall sensitivity, positive predictive accuracy, and false positive rate for the Aegis Medical System were (a) for isolated ventricular ectopic beats--92%, 92%, and 8%, (b) for ventricular couplets--80%, 97%, and 3%, (c) ventricular tachycardia--81%, 92%, and 8%, (d) supraventricular ectopic beats--81%, 82%, and 18%, and (e) for supraventricular tachycardia--75%, 89%, and 11%. Arrhythmia analysis was valid for mean heart rate and ventricular arrhythmias, but showed lower sensitivities in detection of low prevalence (1-60 b/Hr) ventricular couplets (72%) and ventricular tachycardia (43%). Significant inaccuracies for some densities of supraventricular arrhythmia were also found. This study found the real-time analysis ambulatory ECG similar to conventional Holter recording for technical reliability and patient applicability. Given the limitations of currently available real-time analysis ambulatory ECG systems, it is a promising technology.     

Hypertension and sudden death: Increased ventricular ectopic activity in left ventricular hypertrophy

The present study was designed to detect and quantify cardiac arrhythmias in hypertensive patients with left ventricular hypertrophy. Continuous ambulatory electrocardiographic tracings and arterial pressure were recorded for 24 hours in 14 normotensive subjects, 10 patients with established essential hypertension without left ventricular hypertrophy, and 16 hypertensive patients with left ventricular hypertrophy by electrocardiographic criteria. Urinary excretion of norepinephrine was simultaneously measured over four successive four-hour and one eight-hour period. Patients with left ventricular hypertrophy had significantly more ventricular (but not atrial) premature contractions than those without left ventricular hypertrophy or than normotensive subjects. Five patients with left ventricular hypertrophy had episodes of more than 30 premature ventricular contractions per minute. Higher-grade ventricular ectopic activity such as coupled premature ventricular contractions was seen in two, and multifocal premature ventricular contractions were seen in three in the group with left ventricular hypertrophy. No difference in urinary catecholamine excretion rates among the three groups was seen. Left ventricular hypertrophy has been shown to be an independent risk factor for sudden death and acute myocardial infarction. Electrocardiographic monitoring of patients with left ventricular hypertrophy allows identification of those who have the highest risk and, therefore, require the most aggressive therapeutic intervention.     

Ventricular arrhythmias in the elderly: prevalence, mechanisms, and therapeutic implications

Aging is associated with an increase in both the prevalence and complexity of ventricular ectopic beats (VEB), whether detected by resting ECG, 24-hour ambulatory monitoring, or exercise testing. Frequent and/or multiform VEB, ventricular couplets, and short runs of ventricular tachycardia have been detected by these techniques in a sizeable percentage of apparently healthy subjects in the seventh decade and beyond. Although the mechanism for the increase in VEB with advancing age is uncertain, possibilities include latent coronary artery disease, left ventricular hypertrophy or dilatation, elevated plasma catecholamines, and a relative prolongation of the QT interval. Because the age-related increase in VEB does not appear to increase cardiac mortality in older subjects without demonstrable heart disease, and given the significant likelihood of adverse effects from antiarrhythmic drugs in their age group, these drugs should be reserved for elderly patients with organic heart disease and frequent or complex VEB.     

Long-term prognostic significance of ambulatory electrocardiographic findings in apparently healthy subjects greater than or equal to 60 years of age.

To determine the long-term prognostic significance of frequent or complex ectopic beats and ST-segment changes on 24-hour ambulatory electrocardiogram (ECG) in apparently healthy older subjects, 98 volunteers were followed up from the Baltimore Longitudinal Study of Aging who were 60 to 85 years old and free of cardiac disease by history, physical examination and maximal treadmill testing at the time of ambulatory ECG between 1978 and 1980. Over a mean follow-up period of 10 years, coronary events developed in 14 subjects: angina pectoris in 7, nonfatal myocardial infarction in 3 and sudden cardiac death in 4. The incidence of coronary events did not differ significantly between subjects who developed the following arrhythmias and those who did not, respectively: greater than or equal to 30 supraventricular ectopic beats in any hour, 18 vs 13%; greater than or equal to 100 supraventricular ectopic beats in 24 hours, 20 vs 12%; paroxysmal atrial tachycardia, 15 vs 14%; greater than or equal to 30 ventricular ectopic complexes (VECs) in any hour, 17 vs 14%; greater than or equal to 100 VECs in 24 hours, 18 vs 14%; or repetitive VECs, 20 vs 13%. The mean 24-hour heart rate (75 +/- 8 vs 72 +/- 9 beats/min) as well as the maximal (116 +/- 20 vs 111 +/- 18 beats/min) and minimal (51 +/- 6 vs 53 +/- 7 beats/min) heart rate also did not differ between the coronary event and non-event groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical significance of pressor responses to laboratory stressor testing in hypertension.

We investigated the relation between pressor responses to laboratory stressors and 24-hour blood pressure (BP) variability or left ventricular mass. Mental arithmetic tests, isometric hand grip exercise, and bicycle ergometer exercise were carried out in middle-aged normotensive subjects (n=10) and in age-matched WHO stage I (n=23) and stage II (n=11) patients with essential hypertension. Mental arithmetic was associated with a greater rate of increase in plasma epinephrine than in norepinephrine, and handgrip exercise was associated with a greater rate of increase in plasma norepinephrine than in epinephrine in all three groups. Bicycle ergometer exercise caused a remarkable increase in plasma norepinephrine and a mild increase in plasma epinephrine in all three groups. In mental arithmetic tests, pressor responses of hypertensive patients were significantly greater than those of normotensives. The pressor response during mental tests was significantly correlated with the value of 24-hour BP variability in all subjects (r=0.56, p< 0.01). The pressor response to handgrip increased with the stage of hypertension. A good correlation existed between the pressor response to handgrip and the left ventricular mass index in the subjects (r=0.73, p < 0.001). There was no difference in the pressor response to ergometer exercise between any of the groups. The findings suggest that the pressor response to mental stress reflects BP variability and that the response to handgrip is correlated with target-organ disease associated with hypertension, especially the degree of cardiac hypertrophy.     

Long-term cardiovascular safety of salmeterol powder pharmacotherapy in adolescent and adult patients with chronic persistent asthma: a randomized clinical trial

STUDY OBJECTIVES: This study investigates the long-term cardiovascular safety of salmeterol powder vs placebo in adolescent and adult patients with mild persistent asthma. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Eighteen US clinical centers. PATIENTS: Three hundred fifty-two patients (> or = 12 years) with mild persistent asthma (duration > or = 6 months) requiring pharmacotherapy; with FEV1 of 70 to 90% of predicted and without abnormal ECG/continuous ambulatory ECG (Holter). INTERVENTIONS: Randomized to twice-daily salmeterol powder (50 microg) or placebo via breath-actuated device for 52 weeks. Backup albuterol was available to control asthma symptoms. MEASUREMENTS AND RESULTS: Cardiovascular safety was regularly assessed by 12-lead ECG with a 15-s lead II rhythm strip, 24-h continuous ambulatory ECG (Holter) monitoring, serial vital sign measurements, and review of adverse cardiovascular events. No deaths occurred during the study. No clinically significant between-group differences were observed in pulse rate, ECG QTc interval, median number of ventricular or supraventricular ectopic events, incidence of ventricular ectopic couplets and runs, or incidence of > 100 ventricular or supraventricular ectopic events in 24 h. No clinically significant between-group differences were observed in arterial BP or incidence of adverse cardiovascular events. Salmeterol was well tolerated throughout the 52-week study period, with a cardiovascular safety profile similar to that of placebo. CONCLUSIONS: Long-term, twice-daily pharmacotherapy with salmeterol powder is safe and is not associated with unfavorable clinically significant changes in cardiac function or increases in cardiovascular adverse effects.     

Prevalence of left ventricular hypertrophy and cardiac arrhythmias in borderline hypertension.

Seventy-eight men with borderline hypertension according to the World Health Organization criteria underwent echocardiographic examination, followed by simultaneous ambulatory blood pressure and electrocardiographic monitorings for 24 h. The prevalence of echocardiographic left ventricular hypertrophy was 16.6% (13/78). Borderline hypertensives with left ventricular hypertrophy had more supraventricular (P less than .001) and ventricular ectopic beats (P less than .001) than normotensive controls and borderline hypertensives without cardiac involvement. Furthermore, ventricular ectopic activity was significantly related to left ventricular mass (r = 0.58, P less than .05) in borderline hypertensives showing echocardiographic evidence of left ventricular hypertrophy. Our findings suggest that noninvasive assessment of target organ status, including echocardiography, should be employed to optimize risk stratification in borderline hypertension.     

The heart in hypertension and arrhythmias

Antihypertensive management reduces the incidence of congestive heart failure, malignant hypertension and stroke; however, the overall incidence of events due to ischemic heart disease was not influenced by antihypertensive treatment. One of the possible explanations might be some negative metabolic effects of antihypertensive drugs. Hypokalemia develops in 20 to 50% patients who receive a thiazide diuretic. An association between hypokalemia and malignant arrhythmias (including ventricular fibrillation), in acute myocardial infarction, has been observed. 24-hour ambulatory electrocardiographic monitoring demonstrated a higher frequency of ventricular ectopic beats in hypertensive patients taking thiazides. There is, however, no convincing evidence of a simple causative relation between ventricular extrasystoles and low concentrations of serum potassium. Hypertensives with left ventricular hypertrophy (ECG criteria) had significantly more premature ventricular contractions than patients with established hypertension without left ventricular hypertrophy or normotensive subjects. These data could provide an electrophysiologic substrate for the epidemiologic findings of increased morbidity and mortality in patients with left ventricular hypertrophy.     

Effects of psychologic stress on repolarization and relationship to autonomic and hemodynamic factors

INTRODUCTION: Psychological stress can precipitate ventricular arrhythmias in patients with ICDs, as well as sudden death. However, the physiologic pathways remain unknown. We sought to determine whether psychological stress induced in the laboratory setting alters indices of repolarization associated with arrhythmogenesis. METHODS AND RESULTS: Patients with ICDs and a history of ventricular arrhythmia underwent ambulatory ECG monitoring during a laboratory mental stress protocol (anger recall and mental arithmetic). Continuous changes in repolarization indices which have correlated with temporal and spatial myocardial heterogeneity of repolarization, including T-wave alternans (TWA), T-wave amplitude (Tamp), and T-wave area (Tarea) were analyzed in the time domain. In the 33 patients (85% male, 88% with coronary artery disease, mean ejection fraction 30%), norepinephrine, epinephrine, BP, and HR increased during mental stress. TWA increased from 22 (interquartile range 16-27) at baseline to 29 (21-38) uV during mental stress (P < 0.001). Changes in TWA correlated with changes in HR, systolic BP, and catecholamines. Tamp and Tarea also increased with mental stress (P < 0.01) but did not correlate with changes in other variables. CONCLUSION: Psychological stress increased TWA, Tamp, and Tarea. Autonomically mediated repolarization changes may be a pathophysiologic link between emotion and arrhythmia in susceptible patients.     

Effect of 24-hour blood pressure and heart rate variations on left ventricular hypertrophy and dilatation in essential hypertension

This study correlates variables derived from blood pressure (BP) and heart rate (HR) monitoring with the degree of left ventricular structural changes in essential hypertension. Forty patients with mild-to-moderate hypertension according to World Health Organization criteria underwent 24-hour ambulatory monitoring. Echocardiographic (posterior wall and interventricular septum thickness, left ventricular mass) or ECG (SV1 + RV5) indices of hypertrophy were significantly (p less than 0.01) correlated (positive correlations) with derivatives of BP monitoring (mean systolic and diastolic BP values) but not with HR derivatives. Echocardiographic indices of dilatation (left ventricular end-diastolic volume and diameter) were significantly (p less than 0.01 to less than 0.001) correlated (negative correlations) with derivatives of HR monitoring (mean HR values, mainly during the night) but not with BP derivatives. It is concluded that in essential hypertension, left ventricular hypertrophy depends on mean 24-hour systolic and diastolic BP values, whereas left ventricular dilatation appears to be more prominent in patients with bradycardia mainly during the night.     

Noninvasive evaluation of cardiac dysrhythmias, and their relationship with multisystemic symptoms, in progressive systemic sclerosis patients

Fifty-three patients (34 who had diffuse scleroderma, and 19 who had CREST syndrome [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias]) were studied by noninvasive procedures, including resting electrocardiogram (ECG), continuous 24-hour Holter ECG monitoring, M-mode echocardiography, and 2-dimensional echocardiography. Only 22 patients (42%) had abnormalities such as conduction defects, supraventricular or ventricular arrhythmias, or ST-T changes detected on resting ECG. In contrast, using Holter monitoring, the number of conduction abnormalities seen increased from 10 to 16 patients and transient ST-T changes increased from 2 to 18 patients. Forty-eight patients had ventricular arrhythmias, with multiform ventricular premature beats in 21 (40%), pairs of runs of ventricular tachycardia in 15 patients (28%), and 1 or more runs of ventricular tachycardia in 7 (13%). Echocardiography detected asymmetric septal hypertrophy in 10 patients, impaired ventricular function in 9 patients, congestive cardiomyopathy in 2, mitral prolapse in 4, and pericardial effusion in 3 patients. Multiform and/or repetitive ventricular premature beats occurred more frequently in patients with echocardiographic abnormalities, but were also present in patients who had normal findings on echocardiographic examination. Cardiac involvement was not correlated with clinical variants of scleroderma (CREST syndrome or diffuse scleroderma), nor with other signs and symptoms of the disease. Thus, cardiac involvement is found much more frequently than would be expected from clinical symptoms or from results of resting ECG alone; therefore, Holter monitoring and echocardiography should be included in the routine workup of patients who have scleroderma.     

Catecholamine effects on blood pressure and heart rate in the American bullfrog, Rana catesbeiana

The effects of catecholamines and adrenergic blocking agents were studied in vivo on the blood pressure and heart rate of the unanaesthetized American bullfrog, Rana catesbeiana. Bullfrogs were chronically cannulated with a T cannula in the right sciatic artery. The mean systemic arterial blood pressure prior to the infusion of catecholamines was 18.5 ± 1.5 mm Hg. Mean preinfusion heart rate was 30.9 ± 2.0 beats/min. Epinephrine elicited the largest increase in blood pressure, with an accompanying decrease in heart rate. Norepinephrine and phenylephrine were less effective. Isoproterenol was the only catecholamine tested which elevated heart rate in a dose-dependent manner. It had no effect on blood pressure. The beta adrenergic antagonist, propranolol, blocked the increase in heart rate elicited by isoproterenol but had no effect on the blood pressure increases elecited by the other catecholamines. The alpha adrenergic antagonist, phentolamine, partially blocked the blood pressure increase by epinephrine, norepinephrine, and phenylephrine as well as the elevation of heart rate by isoproterenol. Atropine alone elevated heart rate 19 ± 3 beats/min, and prevented slowing of the heart due to epinephrine, norepinephrine, and phenylephrine. Stimulatory effects of epinephrine on heart rate were observed only after atropine had been administered. Beta adrenergic receptors, therefore, appear to function in heart rate regulation; however, the predominant effect of catecholamines is reflex slowing of the heart due to stimulation of the vagus nerve. In contrast, the alpha receptor, stimulated by epinephrine, appears to be the main adrenergic receptor controlling blood pressure changes.     

Diuretic-induced ventricular ectopic activity

The need to avoid hypokalemia during diuretic therapy in nondigitalized patients has been questioned. Twenty-one patients with (1) mild essential hypertension, (2) plasma potassium of < 3.5 meq/liter during previous diuretic treatment, and (3) normal findings {< 6 unifocal ventricular premature beats/hour} on 24-hour ambulatory electrocardiographic monitoring and exercise testing were treated with hydrochlorothiazide (50 mg twice a day) for four weeks and then ambulatory electrocardiographic monitoring and exercise testing were repeated. Ambulatory electrocardiographic monitoring revealed that ventricular ectopic activity developed in seven patients and complex ventricular ectopic activity (multifocal ventricular premature beats, ventricular couplets and/or ventricular tachycardia) in four. Only two of these seven had ventricular ectopic activity during exercise testing while they were hypokalemic. Potassium repletion in these seven patients with spironolactone abolished complex ventricular ectopic activity and reduced unifocal ventricular premature beats significantly (p < 0.01) from an average of 71.2 ventricular premature beats/hour/patient during hydrochlorothiazide treatment to 5.4 ventricular premature beats/hour/patient after potassium repletion. Although complex ventricular ectopic activity was more likely to occur with plasma potassium < 3.0 meq/ liter, restoration of normokalemia was required in several patients to abolish residual ventricular ectopic activity. Persistent ventricular ectopic activity in one patient suggested that myocardial injury sustained during hypokalemia may initiate chronic ventricular ectopic activity. Even in nondigitalized patients, the hazard of diuretic-induced ventricular ectopic activity warrants correction of hypokalemia.     

Differences in left ventricular structural and functional changes between pheochromocytoma and essential hypertension. Role of elevated circulating catecholamines.

Experimental findings suggest that catecholamines increase protein synthesis and play a role in cardiac hypertrophy. We hypothesize that elevated circulating plasma catecholamines in pheochromocytoma influence cardiac structural and functional remodeling. We compared 15 patients with surgically proven pheochromocytoma and 15 with untreated essential hypertension; we matched the patients for age, sex, body surface area, and blood pressure (BP) levels. Left ventricular hypertrophy (LVH) was identified by M-mode echocardiography in six patients with pheochromocytoma and in four with essential hypertension. Among both groups there were no differences in cardiac structure, no correlation between left ventricular mass and BP, no significant differences in mitral E-F slope, no correlation between either plasma norepinephrine or plasma epinephrine levels, and no differences in the left ventricular structural indices measured. In the pheochromocytoma group, left ventricular end systolic stress and end systolic diameter were significantly lower and left ventricular percent fractional shortening was higher. Plasma norepinephrine levels were higher in the pheochromocytoma group, but did not differ among patients of that group with and without LVH. We conclude that in both pheochromocytoma and essential hypertension, only a subset of patients develop evidence of LVH, and that in pheochromocytoma, the elevation of circulating plasma catecholamines is not necessarily associated with LVH. These results indicate that factors other than catecholamines and BP determine the development of LVH in pheochromocytoma.     

Comparative effects of catecholamines in cardiac tamponade: Experimental and clinical studies

In experimental cardiac tamponade, catecholamines improve hemodynamic variables. To determine whether hemodynamic changes result in increased blood flow to critical organs, tamponade was produced in nine spontaneously breathing, anesthetized dogs. Infusion of dopamine, isoproterenol or norepinephrine doubled cardiac output, but only norepinephrine increased mean arterial pressure. All catecholamines increased blood flow to the myocardium, but not to the brain or kidney. Isoproterenol caused a significant decrease in the endocardial/epicardial blood flow ratio, which was shown to be due to tachycardia.To determine whether catecholamines increase cardiac output and mean arterial pressure in patients with tamponade, eight patients with tamponade due to neoplasms were studied before therapeutic pericardiocentesis. Cardiac output increased only 50 percent with dopamine and isoproterenol and not at all with norepinephrine. Cardiac filling pressure did not decrease with isoproterenol or dopamine, as in experimental tamponade. Only norepinephrine increased mean arterial pressure.Thus, although catecholamines improve hemodynamics in experimental tamponade, the heart is the only critical organ to which blood flow is improved. The hemodynamic benefits of catecholamine administration to patients may be more limited than previous experimental studies have suggested.     

Myocardial catecholamine content after heart transplantation

Myocardial catecholamine levels have not yet been determined in the transplanted human heart. We measured norepinephrine, epinephrine, and dopamine in endomyocardial biopsies from 19 short-term (organ age, 6.6 +/- 6 months) and five long-term (organ age, 62 +/- 2 months) heart transplant patients. Results were compared with those from 10 normal control subjects. In 17 of 19 short-term heart transplant patients, myocardial catecholamines were undetectable, indicating values below 0.1 pg/micrograms noncollagen protein, which was the detection threshold of our assay. In the remaining two patients, myocardial catecholamines (pg/microgram noncollagen protein) were norepinephrine (1.4 and 3.2), epinephrine (0.8 and 1.9), and dopamine (0.9 and 2.3), respectively. In the five long-term heart transplant patients, myocardial catecholamines were not detected. Catecholamine concentrations in 10 healthy control subjects were norepinephrine (10.3 +/- 2.9), epinephrine (0.36 +/- 0.51), and dopamine (0.52 +/- 0.40). Low myocardial norepinephrine levels (less than 20% of control values) with unexplained high levels of epinephrine and dopamine were found in single transplant patients. In most heart transplant patients, however, myocardial catecholamines were undetectable up to five years after transplantation, indicating that the adrenergic response of these hearts probably depends on variations in plasma catecholamines or cardiac beta-receptor density.     

Cardiac arrhythmias and heart rate in hyperthyroidism

The arrhythmia profile and heart rate (HR) were analyzed by 24-hour Holter monitoring in 37 hyperthyroid patients before (triiodothyronine [T3] hormone level = 331 +/- 108 ng/dl), during (T3 level = 202 +/- 98 ng/dl) and after an antihyperthyroid therapy of 8 to 89 weeks' duration (T3 level = 149 +/- 41 ng/dl). The data were compared with those of 50 control subjects free from cardiac disease. Only 12 hyperthyroid patients (32%) had complex ventricular arrhythmias (Lown grade 3 or 4) as compared with 6 normal subjects (12%, p greater than 0.05). Three patients (8%) had repetitive ventricular arrhythmias (Lown grade 4A/B) as compared with 4 normal subjects (8%, p greater than 0.05). Supraventricular premature complexes occurred more often in hyperthyroid patients than in normal subjects before and after therapy (p less than 0.001). The prevalence of supraventricular tachycardia decreased from 8 patients to 1 during therapy (p less than 0.002). The HR decreased from 95 +/- 13 to 79 +/- 9 beats/min after therapy, but was still increased as compared with the normal subjects (72 +/- 8 beats/min, p less than 0.001). A day/night difference in HR greater than 10% was found in 32 patients (86%) and was more pronounced than in the normal group (p less than 0.001). Compared with the normal HR profile, the HR curve of hyperthyroid patients was shifted to a higher level (about 20 beats/min). Serum T3 level correlated best with HR at night in hyperthyroid patients (r = 0.74, p less than 0.001). Thus, hyperthyroid patients show frequent supraventricular arrhythmias that might be reversible during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heart rate and QT-interval dispersion with consideration of left ventricular geometry in a population study of men and women aged 35-59 years

Interrelationships between heart rate (HR), parameters of QT interval dispersion on resting ECG and four variants of echocardiographically defined left ventricular geometry were elucidated in 723 participants of a population study of inhabitants of Tallinn aged 35-59 years. Examination included anthropometry, blood pressure (BP) measurement, registration of ECG and echocardiography. None of normotensive examinees had concentric left ventricular hypertrophy. Among men with normal BP eccentric left ventricular hypertrophy was very rare (0.88%) and contrary to normal left ventricular geometry was associated with highest values of HR and QTD, QTc, QTDc. Among normotensive women eccentric left ventricular hypertrophy was found in 35.3% of cases and was associated with lowest values of HR while parameters of QT interval dispersion were similar to those observed in other variants of left ventricular geometry. Both men and women with hypertension and left ventricular hypertrophy had significantly lower HR and higher values of QT interval dispersion compared with hypertensives with normal left ventricular geometry. In men HR was positively related to age, systolic and diastolic BP and left ventricular myocardial mass index. In women relationship between HR, BP and age was very weak. Relation of HR to left ventricular myocardial mass index was more noticeable although turned out to be inverse.     

beta-Endorphin-induced stimulation of central sympathetic outflow: beta-endorphin increases plasma concentrations of epinephrine, norepinephrine, and dopamine in rats

Intracisternal administration of synthetic human beta-endorphin (0.058-7.25 nmol) in chronically cannulated, conscious, freely moving, adult male rats increased plasma concentrations of epinephrine, norepinephrine, and dopamine in a dose-related manner. Epinephrine secretion was the most sensitive to the stimulatory effect of intracerebral beta-endorphin; plasma epinephrine increased transiently in response to 0.058 nmol. Of the three catecholamines, plasma epinephrine showed the greatest and most rapid response to the largest dose (7.25 nmol) studied. Plasma norepinephrine increased significantly in response to 1.45 nmol, peaking later than plasma epinephrine. Plasma dopamine increased only in response to the highest dose examined. These beta-endorphin effects on plasma catecholamines were inhibited by intraarterial naloxone (1.1 mumol/kg), supporting mediation at opioid receptors. Pretreatment with the ganglionic blocking agent chlorisondamine inhibited the responses of all three catecholamines to intracisternal beta-endorphin. Bilateral adrenal denervation completely prevented the plasma epinephrine response to beta-endorphin and blunted the plasma norepinephrine and dopamine responses. Prior intracisternal administration of hemicholinium-3 blocked the plasma responses of all three catecholamines to intracisternal beta-endorphin, providing evidence for the involvement of central cholinergic neurons in the mechanism mediating beta-endorphin-induced increases in plasma catecholamines. The data are consistent with the hypothesis that endorphins act at a presently unknown brain site(s) to increase the central sympathetic outflow to adrenal medulla and peripheral sympathetic nerve endings, thus stimulating peripheral catecholamine release and increasing plasma concentrations of epinephrine, norepinephrine, and dopamine.     

Free and conjugated plasma catecholamines in pheochromocytoma patients with and without sustained hypertension

Ten pheochromocytoma patients, five with paroxysmal hypertension (Group 1), five with sustained hypertension (Group 2) and 15 normals were studied to determine the relationship between differential secretion of the catecholamines (CA) or differences in their sulphoconjugation and the hypertension patterns in these patients. Group 1 patients were studied in the normotensive period. A consistent finding in this study is that permanent hypertensive patients showed the highest free and conjugated norepinephrine (NE) levels while paroxysmal patients studied during the normotensive period showed the highest conjugated epinephrine (E) levels. Although no significant difference was found in levels of free plasma epinephrine in the Group 1 patients, in the ratio of total plasma E/NE, E was clearly predominant. No significant differences could be found in the degree of the per cent conjugation of individual catecholamines between both groups of patients. Group 1 showed a higher (P less than 0.05) E and a lower dopamine (DA) per cent conjugation than controls. In conclusion, although the dominant type of CA secreted seems to be the main factor in determining the hypertension pattern, sulphoconjugation ability may also play an important role.