Changes in plasma catecholamine concentrations in patients with coronary heart disease during pacing and physical exercise

To study the difference in sympathetic activity during pacing the right atrium or during physical exercise in patients with coronary heart disease, we investigated circulating plasma catecholamine concentrations in the coronary sinus and brachial artery radioenzymatically in 11 male patients with well documented coronary artery disease. Heart rate was increased stepwise 20 beats/min from 90 beats/min up to 150 beats/min by pacing the right atrium and physical exercise was performed by increasing work load stepwise by 25 from 25 up to 100 W on an ergometric bicycle. Plasma noradrenaline and adrenaline concentrations were increased significantly only during physical exercise. In addition, there was an increase in arterial-coronary sinus noradrenaline difference during graded physical exercise, whereas no further release of noradrenaline from the myocardium occurred during pacing. An enhanced cardiac sympathetic tone in patients with coronary heart disease is discussed. It is suggested that atrial pacing is not an adequate stimulus evoking an overall increase of cardiac and peripheral sympathetic tone.     

A comparison of sympathoadrenal activity and cardiac performance at rest and during exercise in patients with ventricular demand or atrial synchronous pacing

Cardiac sympathetic function was assessed by measuring the coronary sinus overflow of noradrenaline and dopamine at rest and during supine exercise in eight patients with high degree atrioventricular block treated with dual chamber pacemakers (DDD). Patients exercised (30-60 W) during both ventricular inhibited (VVI) and atrial synchronous (VAT) pacing. During exercise cardiac output increased less markedly in the VVI mode than in the VAT mode. The cardiac output response was entirely stroke volume dependent in the VVI mode and mainly heart rate dependent in the VAT mode. Coronary sinus noradrenaline concentrations were higher in the VVI mode at rest and during exercise. Noradrenaline overflow from the heart was enhanced during VVI pacing and increased from about 100 pmol/min (17 ng/min) at rest to 1087 pmol/min during exercise (60 W) in the VVI mode and 545 pmol/min in the VAT mode. Dopamine overflow from the heart was less than 5 pmol/at rest but increased 2-5 fold during exercise. Also arterial concentrations of catecholamine increased more during exercise in the VVI mode, but the differences between pacing modes were less pronounced. Circulating adrenaline seems to be of little importance for cardiac function under these conditions; in healthy individuals the arterial concentrations of adrenaline attained in this study have small effects. Cardiac noradrenaline overflow correlated with pulmonary capillary venous pressures and atrial rates in both pacing modes, indicating a relation between cardiac sympathetic activity and cardiac function. Enhanced cardiac release of noradrenaline may increase cardiac contractility and thereby partially compensate for the lack of heart rate responsiveness to exercise during VVI pacing.     

A comparison of sympathoadrenal activity and cardiac performance at rest and during exercise in patients with ventricular demand or atrial synchronous pacing.

Cardiac sympathetic function was assessed by measuring the coronary sinus overflow of noradrenaline and dopamine at rest and during supine exercise in eight patients with high degree atrioventricular block treated with dual chamber pacemakers (DDD). Patients exercised (30-60 W) during both ventricular inhibited (VVI) and atrial synchronous (VAT) pacing. During exercise cardiac output increased less markedly in the VVI mode than in the VAT mode. The cardiac output response was entirely stroke volume dependent in the VVI mode and mainly heart rate dependent in the VAT mode. Coronary sinus noradrenaline concentrations were higher in the VVI mode at rest and during exercise. Noradrenaline overflow from the heart was enhanced during VVI pacing and increased from about 100 pmol/min (17 ng/min) at rest to 1087 pmol/min during exercise (60 W) in the VVI mode and 545 pmol/min in the VAT mode. Dopamine overflow from the heart was less than 5 pmol/at rest but increased 2-5 fold during exercise. Also arterial concentrations of catecholamine increased more during exercise in the VVI mode, but the differences between pacing modes were less pronounced. Circulating adrenaline seems to be of little importance for cardiac function under these conditions; in healthy individuals the arterial concentrations of adrenaline attained in this study have small effects. Cardiac noradrenaline overflow correlated with pulmonary capillary venous pressures and atrial rates in both pacing modes, indicating a relation between cardiac sympathetic activity and cardiac function. Enhanced cardiac release of noradrenaline may increase cardiac contractility and thereby partially compensate for the lack of heart rate responsiveness to exercise during VVI pacing.     

Magnesium sulphate infusion suppresses the cardiac release of noradrenaline during a handgrip stress test

BACKGROUND: Magnesium has several important cardiovascular effects, but its effect on cardiac sympathetic efferent neuron activity has not been clarified. Objectives: To examine the effect of magnesium sulphate infusion on cardiac sympathetic efferent postganglionic neuronal liberation of noradrenaline. PATIENTS AND METHODS: Twenty-two patients who underwent cardiac catheterization were randomly allocated to the control group or the magnesium group. Plasma noradrenaline and adrenaline concentrations in the aorta and the coronary sinus were measured. Noradrenaline or adrenaline release from the heart was calculated by dividing the difference in noradrenaline or adrenaline concentration between the aorta and the coronary sinus by that of the aorta. After baseline blood sampling, the control patients and the patients in the magnesium group received intravenous infusion of saline or magnesium sulphate (10 mmol). All patients were then subjected to 3 min of handgrip exercise stress test to augment sympathetic efferent neuronal activity, and the blood sampling was repeated. RESULTS: Although blood pressure was increased by the handgrip stress test, there were no differences in heart rate and blood pressure between the two groups, both at baseline and during the handgrip stress test. The plasma noradrenaline and adrenaline concentrations and noradrenaline or adrenaline release from the heart did not differ between the two groups in the baseline condition. However, the handgrip stress increased plasma noradrenaline concentrations and the cardiac noradrenaline release was increased in the control group, whereas the cardiac noradrenaline release was not increased by the handgrip stress in the magnesium group (P<0.02). CONCLUSIONS: These data indicate that magnesium sulphate infusion suppresses the release of catecholamines by the heart, which is an indirect index of sympathetic efferent neuronal activity.     

Low-dose atropine attenuates muscle sympathetic nerve activity in healthy humans.

Central muscarinic receptors play an important role in the regulation of cardiac vagal nerve activity. We studied the inhibition of central muscarinic receptors and sympathetic nerve function in humans, since very little information is currently available on this subject. We examined the effects of graded doses of atropine (five doses, range 0.001 to 0.016 mg/kg) on heart rate, arterial pressure, heart rate variability, and muscle sympathetic nerve activity in 13 healthy young volunteers. Atropine caused biphasic effects on heart rate and the high-frequency (HF) power of R-R interval variability. At lower doses (< or =0.002 mg/kg for heart rate, 0.001 mg/kg for HF power), atropine decreased heart rate and increased HF power. In contrast, at higher doses, atropine increased heart rate and decreased HF power. Low-dose atropine significantly attenuated muscle sympathetic nerve activity, burst rate (bursts/min) by -30.5 +/- 6.0% and burst incidence (bursts/100 heart beats) by -23.8 +/- 6.9% at 0.002 mg/kg. Systolic and diastolic arterial pressure did not change with atropine infusion. Low-dose atropine (< or =0.002 mg/kg) did not significantly affect either low frequency (LF) power or LF/HF. These results suggest that central muscarinic receptors may modulate not only cardiac vagal nerve activity but also sympathetic nerve activity in the skeletal muscle vasculature.     

Function of the autonomic nervous system in young, untreated hypertensive patients

The reactivity of the sympathetic nervous system was studied in 10 young, adult patients with labile hypertension and compared with a normotensive age-matched control group. Upon graded exercise on a constant speed bicycle ergometer, the hypertensive subjects reacted with an exaggerated blood pressure response and a significantly greater increase in the plasma adrenaline and noradrenaline levels. The basal catecholamine levels, however, were similar in both observation groups. This was in spite of an intact baroreceptor reflex in the hypertensives as indicated by a normal hemodynamic response to angiotensin II. This apparent discrepancy may be explained by an enhanced uptake of adrenaline during stress into the neuron, where it acts as a cotransmitter and facilitates the release of noradrenaline via presynaptic beta 2-adrenoceptors. Similar blood pressure and heart rate responses to isoproterenol and atropine were observed in both groups. This indicates normal beta-adrenoceptor sensitivity and vagal nerve activity in the hypertensive subjects.     

Stress levels of adrenaline amplify the blood pressure response to sympathetic stimulation

The possibility that sympathetic pressor responses are modulated by adrenaline-mediated facilitation of neuronal noradrenaline release was explored in 17 subjects with borderline hypertension. Infusion of adrenaline, which raised plasma adrenaline by a factor of 8 to 9, augmented the rise in systolic and diastolic arterial pressure induced by standardized cold pressor and isometric exercise tests. The heart rate response to these tests was not affected. When a low dose of propranolol was given on top of the adrenaline infusion before the cold pressor test, the blood pressure response to cold exposure was not different from the response observed when the test was performed during saline infusion. Plasma noradrenaline was higher during adrenaline infusion then during saline infusion, both before and after the cold pressor and isometric exercise tests, and the effect of adrenaline on plasma noradrenaline was antagonized by propranolol. These observations are consistent with the hypothesis that stress levels of circulating adrenaline may amplify sympathetic pressor responses by facilitation of the release of transmitter noradrenaline.     

Endogenous and exogenous catecholamines can accentuate myocardial ischemia only when coronary blood flow is below a critical level

Seventy-eight dogs with graded constriction of the left main coronary artery were studied to determine the coronary blood flow at which the heart is vulnerable to catecholamine induced ischemia. The left main coronary artery was cannulated with a Griggs' type self-perfusing cannula. The coronary blood flow (CBF) was reduced by graded constriction of the extra-corporeal circuit connected with this cannula. Blood flow rates between 12 and 117 ml/min/100 g were studied. Cardiac activation was achieved by either intracoronary administration of a physiological dose of catecholamine (noradrenaline; 0.4 microgram/kg/min or adrenaline; 0.2 microgram/kg/min), or by electrical stimulation of the left stellate ganglion (4 Hz, 2 msec, 10 V for 5 min). When CBF was below 30 ml/min/100 g, accentuated myocardial ischemia was always indicated by lactate production, myocardial creatine phosphate depletion, ischemic ST segment changes, and elevated left ventricular end diastolic pressure (LVEDP) during these stimulations. When CBF was above 50 ml/min/100 g, catecholamine clearly accelerated the cardiac function and myocardial metabolism with no signs of ischemia. When CBF was between 30 and 50 ml/min/100 g signs of accentuated myocardial ischemia appeared during catecholamine activation in only 1/2 of the dogs. This study indicated that the critical level for CBF at which endogenous or exogenous catecholamine can produce ischemia is between 30 and 50 ml/min/100 g.     

Enhanced vagal activity and normal arginine vasopressin response in carotid sinus syndrome: implications for a central abnormality in carotid sinus hypersensitivity

The relation between arginine vasopressin and vagal activity in carotid sinus syndrome was studied in 10 patients and 17 age matched controls using head up tilt as a stimulus. Of the controls, seven had unexplained syncope and 10 were healthy elderly subjects with no previous history of syncope. Subjects were studied supine for 45 min and thereafter during 120 min head up tilt to 40 degrees. Phasic arterial pressure and heart rate were monitored throughout. Serum was sampled at frequent intervals to measure arginine vasopressin, noradrenaline, and adrenaline concentrations. Seventy per cent of carotid sinus patients had vasovagal syncope at (mean(SD)) 25(4) min after tilt compared with 43% of subjects with unexplained syncope and one healthy elderly control. The maximum (mean(SD)) fall in systolic blood pressure and heart rate was 70(20) mmHg and 20(7) beats.min-1 (p less than 0.001 and p less than 0.01 respectively). Arginine vasopressin, noradrenaline, and adrenaline concentrations rose significantly in syncopal subjects (p less than 0.001, p less than 0.01, and p less than 0.05 respectively). Changes in systolic blood pressure, heart rate, and hormone concentrations were similar for patients with carotid sinus syndrome and control subjects. For those who completed the tilt period without the development of symptoms, systolic blood pressure and arginine vasopressin and adrenaline concentrations were unchanged, whereas noradrenaline concentrations and heart rate rose significantly. Vasovagal activity is thus appreciably increased in carotid sinus syndrome. Furthermore, the afferent limb of the carotid sinus reflex appears to be intact in patients with carotid sinus syndrome since the pattern of arginine vasopressin release was not different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenaline infusion in man increases muscle sympathetic nerve activity and noradrenaline overflow to plasma

This study was conducted to determine if muscle sympathetic nerve activity (MSA) and/or the neuronal release of noradrenaline per impulse are modulated by adrenaline in the physiological plasma concentration range. We gave step-wise infusions of adrenaline (0.05-0.6 nmol/kg per min) to 10 healthy young men and measured: intra-arterial blood pressure; heart rate; central venous pressure (CVP); efferent MSA (microneurography in the peroneal nerve); arterial (brachial artery) and femoral venous plasma concentrations of noradrenaline, and the spillover of noradrenaline to arterial and venous plasma (radiotracer infusion). The infusion of adrenaline caused a fall in diastolic blood pressure and tachycardia, and was associated with increases in MSA and noradrenaline spillover. These observations suggest that part of the adrenaline-induced increase in transmitter release is due to enhanced nerve impulse activity, but such a conclusion rests on the absence of diffusion limitations from the site of noradrenaline infusion into the blood stream. After termination of adrenaline infusion the tachycardia and elevated plasma noradrenaline levels persisted, but these changes were probably due mainly to a profound increase in nerve activity. Concurrently, there was a reduction in CVP which may have triggered the increase in efferent sympathetic nerve activity. Infusions of adrenaline did not influence the clearance of noradrenaline from arterial plasma, but the fractional extraction over the leg was moderately reduced, indicating that more arterial noradrenaline is recovered in venous plasma during adrenaline infusion. The present data suggest that the reasons for the adrenaline-induced increase in noradrenaline release are complex, but they are consistent with the hypothesis that stress levels of adrenaline enhance sympathetic nerve activity, and that circulating adrenaline may modulate both haemodynamic and neural responses to stress.     

Circulating and tissue catecholamines in rats with chronic neurogenic hypertension

Summary To study the role of peripheral catecholamines in plasma and different tissues in neurogenic hypertension we measured directly blood pressure, maximum rate of left ventricular pressure rise (dp/dt_max) and heart rate through an aortic catheter 5 weeks after total sino-aortic baroreceptor deafferentation in male Sprague-Dawley rats. Blood samples were collected through the same catheter to determine plasma catecholamine concentrations. Blood pressure and dp/dt_max were significantly higher in neurogenic-hypertensive rats when compared with sham operated rats. Plasma noradrenaline concentrations and plasma adrenaline concentrations reached significantly higher levels in neurogenic-hypertensive rats. In the heart noradrenaline content was lower (when calculated per g wet weight) and in the adrenal medulla adrenaline content was higher in neurogenic-hypertensive rats, when compared with sham operated controls. A significant positive correlation was found between dp/dt_max and plasma noradrenaline concentrations.It is concluded that sino-aortic baroreceptor deafferentation produces a significant chronic hypertension, probably supported by elevated plasma catecholamine concentrations and enhanced synthesis and release of adrenaline from adrenal medulla.     

Myocardial ischaemia and ventricular arrhythmias precipitated by physiological concentrations of adrenaline in patients with coronary heart disease.

The clinical and haemodynamic effects of adrenaline infusion (30 ng kg-1 min-1) producing plasma adrenaline concentrations in the range seen during acute myocardial infarction and of placebo were investigated in a crossover design in 14 patients with stable coronary heart disease. Adrenaline infusion resulted in electrocardiographic evidence of myocardial ischaemia (greater than or equal to 1 mm (0.1 mV) horizontal or downsloping ST segment depression) in 10 patients and angina in four, although the mean (SEM) increase in heart rate was modest (14 (2) beats/min) and mean coronary vascular resistance fell from 1.56 (0.21) to 1.16 (0.14) mm Hg min ml-1 (p less than 0.005). New or increasingly frequent or complex ventricular arrhythmias occurred in five patients. Placebo infusion had no effect on the variables measured. Supine bicycle exercise during infusion of the saline placebo was associated with a similar degree of ST segment depression (0.9 (0.2) mm) as adrenaline infusion at rest (0.9 (0.1) mm) but exercise performed during adrenaline infusion (10 patients) resulted in more pronounced ST segment depression (1.9 (0.3) mm) (p less than 0.005) than either intervention alone. Angina occurred in three of 11 patients during control exercise and in six of 10 during the combination of adrenaline infusion and exercise. Such potentially adverse consequences of low dose adrenaline infusion in patients with stable coronary heart disease are consistent with the suggestion that adrenal activation is detrimental during acute myocardial infarction, being both arrhythmogenic and proischaemic.     

Correlations of hemodynamic parameters with plasma catecholamines in patients with congestive cardiomyopathy

Noradrenaline and adrenaline blood levels, as well as central hemodynamics (Swan-Ganz semi-floating balloon-tipped catheter), were measured at rest and during moderate exercise in 8 male patients suffering with idiopathic congestive cardiomyopathy (COCM), and in 12 healthy male control subjects. The stroke volume and the cardiac output in COCM were, on the average, one-half that of the control subjects; adrenaline, noradrenaline, pulmonary capillary wedge pressure, as well as the roentgenographically determined heart volume (at rest) in COCM were, on the average, increased more than twice the control values. The noradrenaline and adrenaline responses in COCM reached at the 25-W exercise level the response of controls at the 150-W level. Direct correlations were observed between the cate-cholamine responses and the capillary wedge pressure as well as the heart volume; inverse correlations existed between the catecholamines and the stroke volume or the cardiac output. The results may be indicative of a causal relationship between the reduced function of the left heart and a compensatorily increased sympathetic activity, but they are not at all conclusive for a definite cause-effect response. The differences in catecholamine levels and the correlations are more significant for noradrenaline during both exercise and rest, whereas for adrenaline significance only occurred during exercise. The noradrenaline and adrenaline levels may serve as indicators (especially in the chronic stage) in the diagnosis of reduced left ventricular function.     

Myocardial ischaemia and ventricular arrhythmias precipitated by physiological concentrations of adrenaline in patients with coronary heart disease.

The clinical and haemodynamic effects of adrenaline infusion (30 ng kg-1 min-1) producing plasma adrenaline concentrations in the range seen during acute myocardial infarction and of placebo were investigated in a crossover design in 14 patients with stable coronary heart disease. Adrenaline infusion resulted in electrocardiographic evidence of myocardial ischaemia (greater than or equal to 1 mm (0.1 mV) horizontal or downsloping ST segment depression) in 10 patients and angina in four, although the mean (SEM) increase in heart rate was modest (14 (2) beats/min) and mean coronary vascular resistance fell from 1.56 (0.21) to 1.16 (0.14) mm Hg min ml-1 (p less than 0.005). New or increasingly frequent or complex ventricular arrhythmias occurred in five patients. Placebo infusion had no effect on the variables measured. Supine bicycle exercise during infusion of the saline placebo was associated with a similar degree of ST segment depression (0.9 (0.2) mm) as adrenaline infusion at rest (0.9 (0.1) mm) but exercise performed during adrenaline infusion (10 patients) resulted in more pronounced ST segment depression (1.9 (0.3) mm) (p less than 0.005) than either intervention alone. Angina occurred in three of 11 patients during control exercise and in six of 10 during the combination of adrenaline infusion and exercise. Such potentially adverse consequences of low dose adrenaline infusion in patients with stable coronary heart disease are consistent with the suggestion that adrenal activation is detrimental during acute myocardial infarction, being both arrhythmogenic and proischaemic.     

Metabolic effects of adrenaline and noradrenaline in man: studies with somatostatin

The metabolic responses to infusion of adrenaline (6 micrograms/min) and of noradrenaline (5 micrograms/min) for 120 minutes have each been studied in five normal males with and without concurrent somatostatin (250 micrograms/h). Adrenaline induced marked and sustained hyperglycaemia (maximal blood glucose at 75 min, 9.0 +/- 0.4 mmol/l) while noradrenaline induced only a mild and transient blood glucose rise. Blood lactate was elevated by adrenaline (2.57 +/- 0.47 mmol/l with adrenaline, 0.62 +/- 0.06 mmol/l with saline at 120 min, p less than 0.02). Pyruvate levels rose proportionately less so that the circulating lactate:pyruvate ratio was increased (16.6 +/- 1.3 with adrenaline, 11.4 +/- 0.9 with saline at 120 min, p less than 0.05). Lactate and pyruvate levels were unaffected by noradrenaline. Both catecholamines increased circulating non-esterified fatty acid (NEFA) and glycerol to peak at 30 min, while maximal 3-hydroxybutyrate concentrations were achieved at 50 min (0.26 +/- 0.07 mmol/l with adrenaline; 0.23 +/- 0.06 mmol/l with noradrenaline; 0.03 +/- 0.01 mol/l with saline, both p less than 0.05). Insulin levels were partially suppressed by noradrenaline, while a small rise in circulating insulin was observed with adrenaline which was also associated with a large rebound rise in insulin secretion on cessation of the infusion. Mild and transient hyperglucagonaemia was observed with adrenaline while stimulation of glucagon secretion was more sustained with noradrenaline. Somatostatin suppressed insulin, glucagon and growth hormone secretion and both magnified and prolonged the hyperglycaemic effect of adrenaline (maximal at 105 min, 11.3 +/- 0.5 mmol/l, p less than 0.01 versus adrenaline alone).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrine, metabolic and cardiovascular responses to adrenaline after abdominal surgery

Adrenaline-induced changes in heart rate, blood pressure, plasma adrenaline and noradrenaline, cortisol, glucagon, insulin, cAMP, glucose lactate, glycerol and beta-hydroxybutyrate were studied preoperatively and 4 and 24 h after skin incision in 8 patients undergoing elective cholecystectomy. Late postoperative responses of blood glucose, plasma cAMP, lactate and glycerol to adrenaline infusion were reduced, whereas other responses were unaffected. Blood glucose appearance and disappearance rate as assessed by [3H]3-glucose infusion was unchanged pre- and postoperatively. The increase in glucose appearance rate following adrenaline was similar pre- and postoperatively. These findings suggest that several beta-receptor-mediated responses to adrenaline are reduced after abdominal surgery.     

Loss of nocturnal decline of blood pressure in patients with nasal polyposis

The objective of this study was to assess the blood pressure pattern in patients with nasal polyposis. Twenty-seven patients with nasal polyposis (18 males and 9 females), ranging in age from 15 to 72 years (mean 37.1 years) were eligible for inclusion in the study. All patients were hospitalized overnight before surgery. After the basal blood pressure measurements were taken, non-invasive ambulatory blood pressure monitoring was carried out. Oxygen saturation was measured via a finger probe and venous blood sampling was taken for catecholamine level during the full night. All measurements were repeated 4 months after nasal surgery. Mean values for nocturnal decline in blood pressure and heart rate before surgery were less marked than those measured after surgery. Mean decline values (+/- SD) were; 4.6 +/- 2.4 mmHg for systolic blood pressure, 5.8 +/- 3.8 mmHg for diastolic blood pressure, and 7.9 +/- 3.9 beats/min for heart rate before surgery, 9.3 +/- 2.8 mmHg, 8.5 +/- 4.1 mmHg and 10.4 +/- 4.3 beats/min after surgery (p < 0.01), respectively. Whereas mean and minimum SaO2 (%) significantly increased (p < 0.01), catecholamine levels decreased (p < 0.05 for adrenaline, p < 0.01 for noradrenaline) after surgery. A correlation was found between BMI and blood pressure as well as between duration of obstruction and blood pressure. Patients who snored had higher blood pressure values than those who did not. Our data show that in cases of nasal polyposis, hypoxia, hypercapnia, snoring, and sleep disorders may develop and persons with nasal polyposis and snoring have an increased risk of hypertension and loss of nocturnal decline in blood pressure.     

Neural and humoral mechanisms involved in blood pressure variability

In order to study blood pressure variability we have measured blood pressure, heart rate, plasma noradrenaline and adrenaline concentration and plasma renin activity during sleep and during the waking process in 20 subjects with borderline hypertension. The responses to a number of standardized tests were also measured. These were reading, mental arithmetic, change in posture, physical exercise and the response to intravenously injected phenylephrine and noradrenaline. The sensitivity of the baroreflex for heart rate control was also determined from the relationship between heart period (R-R interval) and change in systolic pressure after the injection of phenylephrine. Blood pressure was also recorded continuously for 24 hours. From the lowest levels achieved during sleep, blood pressure rose as the subjects regained consciousness but was not restored to its baseline value until mental activity was also restored by reading. Blood pressure rose further with mental arithmetic. These changes were accompanied by a greater proportional rise in plasma adrenaline than in plasma noradrenaline concentrations. Plasma renin activity changed little. The pressor responses to phenylephrine and noradrenaline were inversely related to baroreceptor sensitivity. The fall in blood pressure with sleep and the rise with mental arithmetic was also inversely related to the sensitivity of the reflex. Systolic pressure recorded throughout the day was inversely related to the R-R interval in each subject. The slope of this relationship and range of R-R interval was greatest in the subjects with the most sensitive baroreflexes.     

Autonomic nervous system influences on QT interval in normal subjects

OBJECTIVES: We sought to determine whether the relationship between heart rate (HR) and QT interval (QT) differs as HR increases in response to exercise, atropine and isoproterenol. BACKGROUND: Autonomic nervous system influences on repolarization are poorly understood and may complicate the interpretation of QT measurements. METHODS: Twenty-five normal subjects sequentially underwent graded-intensity bicycle exercise, atropine injection and isoproterenol infusion. Serial 12-lead electrocardiograms were recorded at steady state during each condition and analyzed using interactive computer software. The HR-QT data were modeled linearly and the slopes (quantifying QT adaptation to HR) as well as the QT intervals at 100 beats/min for each intervention were compared by repeated-measures analysis of variance. RESULTS: As HR increased, QT was longer for isoproterenol in comparison to exercise or atropine, which were similar. The HR-QT slope (ms/beats/min) was less steep for isoproterenol (-0.83 +/- 0.53) than for atropine (-1.45 +/- 0.21) or exercise (-1.37 +/- 0.23) (p < 0.0001). In comparison to men, women had more negative HR-QT slopes during all interventions. At 100 beats/min, the QT was 364 ms during isoproterenol, which was significantly longer than that during exercise (330 ms) or atropine (339 ms) (p < 0.0001). Isoproterenol produced a dose-dependent increase in U-wave amplitude that was not observed during exercise or atropine. CONCLUSIONS: In comparison to exercise and atropine, isoproterenol is associated with much less QT shortening for a given increase in HR and, therefore, greater absolute QT intervals. Our findings demonstrate that autonomic conditions directly affect the ventricular myocardium of healthy subjects, causing differences in QT that are independent of HR.     

Myocardial potassium uptake and catecholamine release during cardiac sympathetic nerve stimulation

To determine whether sympathetic nerve stimulation induces a significant potassium uptake in the myocardium, the changes in myocardial potassium balance, catecholamine release, lactate uptake, and oxygen consumption were recorded in eight anaesthetised open chest pigs during electrical stimulation of the right intermediate cardiac nerve at 10 Hz. Potassium concentrations were continuously measured by polyvinylchloride valinomycin minielectrodes in arterial and coronary sinus blood. Potassium concentration in coronary sinus blood fell to a nadir 0.42(0.21-0.61) mmol.litre-1 below control values (median and 95% confidence interval) and resulted in a peak potassium uptake of 65(38-102) mumol.min-1 100 g-1 after 2.5(2.0-3.0) min, which correlated (r = 0.94, p less than 0.001) with cardiac noradrenaline release. Accumulated myocardial potassium uptake amounted to 139(82-241) mumol.100 g-1 when a stable potassium concentration difference between arterial and coronary sinus blood was reached after 5.5(4.25-6.50) min. Cardiac contractility (LV dP/dt), myocardial oxygen consumption, and lactate uptake rose from control to peak potassium uptake (p less than 0.001) by 140%, 158%, and 92% respectively. Coronary sinus blood noradrenaline and adrenaline concentrations rose significantly (p less than 0.01) from 58(44-87) pg.ml-1 at control to 2208(1159-5627) pg.ml-1 at peak uptake and from 15(11-19) pg.ml-1 to 85(64-230) pg.ml-1 respectively. Arterial noradrenaline increased from 29(19-41) pg.ml-1 to 374(176-640) pg.ml-1 and arterial adrenaline rose from 15(11-23) pg.ml-1 to 31(24-52) pg.ml-1 (p less than 0.001). It is concluded that sympathetic nerve stimulation induces a substantial myocardial potassium uptake in a dose dependent relation to cardiac noradrenaline release and alters the contractile and metabolic state of the heart substantially with only minor changes in arterial catecholamine concentration.