Vascular distribution of plasma catecholamines--pulmonary extraction, arterio-venous differences and effect of age

In 19 normotensive patients undergoing cardiac catheterization, plasma samples were simultaneously collected from five different sites for measuring adrenaline and noradrenaline concentrations. Mean levels (+/- SEM) in pulmonary artery and aorta were 1.70 +/- 0.13 and 1.76 +/- 0.12 nmol/l for noradrenaline and 0.35 +/- 0.05 and 0.36 +/- 0.05 nmol/l for adrenaline, respectively. Thus, no pulmonary uptake of either catecholamine was demonstrated; this was independent of ventilatory lung function. Significant peripheral extraction was only found for adrenaline, and not for noradrenaline, so we found no evidence for the necessity of arterial blood sampling for noradrenaline determinations in this static study. Finally, a significant positive correlation of venous (r = 0.56; p less than 0.01), but not arterial noradrenaline concentration with age was found, as was a negative correlation of both arterial (r = -0.55; p less than 0.01) and venous (r = -0.62; p less than 0.005) adrenaline concentrations with age. The release of adrenaline by the adrenal glands proved to be significantly decreasing with increasing age (r = -0.53; p less than 0.02).     

Increased arterial catecholamine concentrations in 50-year-old men with essential hypertension

In a recent study of 50-year-old men with long-standing, untreated essential hypertension we found increased arterial and venous plasma concentrations and arterial-venous differences of adrenaline (a-v) and noradrenaline (v-a) as compared to a matching normotensive control group. The aim of the present study was to investigate whether men of this age with hypertension of shorter duration and less severity than in the first study might also have increased plasma catecholamines. Twenty-three hypertensive and 17 age-matched normotensive control men were studied. The hypertensive ones had increased supine heart rate (P less than 0.05), arterial noradrenaline (P less than 0.01) and adrenaline (P less than 0.02) whereas venous catecholamines did not differ between the two groups. The a-v differences (means +/- SE) of adrenaline (78 +/- 14 vs 42 +/- 6 ng/l, P less than 0.05) were increased in the hypertensive compared to the normotensive group. In the hypertensive, the arterial plasma concentrations of the two catecholamines correlated positively (r = 0.71, P less than 0.001) as did the a-v differences (r = 0.54, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma adrenaline and noradrenaline during mental stress and isometric exercise in man. The role of arterial sampling

Plasma adrenaline and noradrenaline were measured in arterial blood and in forearm venous blood during isometric exercise and during a mental stress test. In both conditions arterial plasma adrenaline increased significantly, whereas arterial plasma noradrenaline remained unchanged. During isometric exercise the increase in plasma adrenaline was greater in venous blood from the exercising arm than from the resting arm. The extraction of adrenaline in the forearm was greater in the resting than in the exercising arm. Venous plasma noradrenaline showed a rebound phenomenon after isometric exercise and tended to decrease during the mental stress test. The results indicate that it is preferable to measure arterial concentrations of adrenaline as an indicator of sympathoadrenal activity rather than venous concentrations since the extraction of adrenaline in forearm might not be constant. It is suggested that a selective increase in arterial plasma adrenaline as opposed to an increase in both plasma adrenaline and noradrenaline may indicate a selective increase in sympathoadrenal activity in visceral organs.     

Influence of body weight on plasma catecholamine patterns in middle-aged, normotensive men

To study the influence of body weight on plasma catecholamine patterns, 34 healthy, normotensive men aged 51 +/- 1 years were stratified into lean (n = 22) and overweight (n = 12) subjects according to Thomas' body mass index. No significant differences on supine arterial and venous catecholamines or standing venous adrenaline and dopamine appeared. However, the lean men had an increased orthostatic venous noradrenaline response (477 +/- 38 ng/l) compared to the overweight (319 +/- 46 ng/l, P less than 0.02). The present findings may indicate an inverse relationship between the sympathetic noradrenergic responsiveness and body weight in healthy, normotensive men while no differences were found in basal catecholamine levels.     

Elevated plasma noradrenaline concentrations in patients with low-output cardiac failure: dependence on increased noradrenaline secretion rates

1. Plasma noradrenaline concentrations are elevated in patients with congestive heart failure; however, the pathogenesis of these elevated noradrenaline levels is controversial. 2. Possible mechanisms for elevated noradrenaline concentrations in patients with congestive heart failure include increased noradrenaline secretion, decreased clearance of noradrenaline, and a combination of increased secretion and decreased clearance. 3. In the present study, plasma noradrenaline clearance and apparent secretion rates were determined using a whole-body steady-state radionuclide tracer method in six otherwise healthy patients with moderate degrees of low-output cardiac failure and in six normal control subjects. 4. The venous plasma noradrenaline level was elevated in the patients with congestive heart failure as compared with the control subjects (4.18 +/- 1.34 versus 1.54 +/- 0.16 nmol/l, P less than 0.05). There was no stimulation of the adrenal medulla as evident by normal plasma adrenaline levels in both groups (0.19 +/- 0.04 versus 0.18 +/- 0.02 nmol/l, not significant). The apparent secretion rate of noradrenaline was elevated in the patients with congestive heart failure (4.75 +/- 1.95 versus 1.78 +/- 0.18 nmol min-1 m-2, P less than 0.05), whereas the clearance rate of noradrenaline was similar in the two groups (1.26 +/- 0.27 versus 1.16 +/- 0.02 l min-1 m-2, not significant). 5. We conclude that the high peripheral venous plasma noradrenaline concentrations in patients with mildly decompensated low-output cardiac failure are initially due to increased secretion, rather than to decreased metabolic clearance, perhaps in response to diminished effective arterial blood volume.     

Selective imidazoline agonist moxonidine in obese hypertensive patients

Obesity is the major risk factor for the development of hypertension. This association accentuates the risk of cardiovascular disease, as it is frequently accompanied by the components of the metabolic syndrome. This randomised open parallel study evaluated the chronic effects of moxonidine--a selective imidazoline receptor agonist--on blood pressure, plasma catecholamines, leptin, insulin and components of the metabolic syndrome in obese hypertensives. Amlodipine was used as the control drug. Our results showed that moxonidine and amlodipine significantly reduced blood pressure when measured using the oscillometric method and 24-hour blood pressure monitoring. Moxonidine therapy decreased systolic blood pressure from 160.4 +/- 2.4 to 142.1 +/- 3.3 mmHg (p < 0.005) and diastolic blood pressure from 102.4 +/- 1.3 to 89.7 +/- 1.6 mmHg (p < 0.005) after 24 weeks of treatment. Moxonidine administration reduced the supine arterial plasma levels of adrenaline from 63.2 +/- 6.6 to 49.0 +/- 6.7 pg/ml (p < 0.005), the supine arterial plasma levels of noradrenaline from 187.9 +/- 10.7 to 149.7 +/- 13.2 pg/ml (p < 0.01) and the orthostatic venous plasma levels of noradrenaline from 258.6 +/- 25.0 to 190.3 +/- 16.4 pg/ml (p = 0.03). Those variables were not changed by amlodipine. The plasma levels of leptin and insulin 120 min after a glucose load decreased after moxonidine administration from 27.2 +/- 3.5 to 22.6 +/- 2.9 pg/ml (p < 0.05) and from 139.7 +/- 31.2 to 76.0 +/- 15.2 U/ml (p < 0.05), respectively. Amlodipine, however, did not modify those variables. This study showed a comparable reduction in blood pressure with both antihypertensive drugs. Moxonidine decreased sympathetic nervous activity, improved insulin resistance and reduced the plasma levels of leptin.     

The effect of adrenaline upon cardiovascular and metabolic functions in man

On three separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline, 50 ng min-1 kg-1 (high A), adrenaline, 10 ng min-1 kg-1 (low A) or sodium chloride solution (saline: 154 mmol of NaCl/l) plus ascorbic acid, 1 mg/ml (control), over 30 min. Venous adrenaline concentrations of 2.19 +/- 0.15 nmol/l, 0.73 +/- 0.08 nmol/l and 0.15 +/- 0.03 nmol/l were achieved during the high A, low A and control infusions respectively. Heart rate rose significantly by 19 +/- 3 beats/min (high A) and by 6 +/- 1 beats/min (low A). Heart rate remained significantly elevated 30 min after cessation of the high A infusion, despite venous plasma adrenaline concentration having fallen to control levels. The diastolic blood pressure fell during the high A and low A infusions, but the systolic blood pressure rose only during the high A infusion. Vasodilatation occurred in the calf vascular bed during both high A and low A infusions. The changes in hand blood flow and hand vascular resistance were not statistically significant, although there was a tendency to vasoconstriction during the infusion of adrenaline. Metabolic rate rose significantly by 23.5 +/- 1.8% (high A) and by 11.8 +/- 1.6% (low A). Metabolic rate remained elevated between 15 and 30 min after termination of the high A infusion. There was an initial transient increase in respiratory exchange ratio (RER) during the adrenaline infusions. During the later stages of the adrenaline infusions and after their cessation, RER fell, probably reflecting increased fat oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of eprosartan on catecholamines and peripheral haemodynamics in subjects with insulin-induced hypoglycaemia

ANG II (angiotensin II) facilitates catecholamine release from the adrenal medulla and neuronal NE (noradrenaline) release. Since animal experiments point to specific sympatho-inhibitory properties of the AT1 (ANG II type 1)-receptor blocker EPRO (eprosartan), the primary aim of this study was to clarify if EPRO inhibits sympathetic reactivity in humans as determined by the effect of EPRO on insulin-induced catecholamine release. Sixteen healthy male volunteers were randomized in a double-blind cross-over study to receive a single dose of EPRO (600 mg) compared with placebo, followed by insulin-induced hypoglycaemia [0.15 IU (international unit)/kg of body weight; intravenous bolus] on two study days 1 week apart. From baseline to the end of hypoglycaemia (170 min), the sympatho-adrenal reactivity was mapped by invasive continuous blood pressure monitoring and repeated measurements of FBF (forearm blood flow), arterial and venous concentrations of glucose, catecholamines [EPI (adrenaline) and NE (noradrenaline)], renin, ANG II and aldosterone. EPRO induced an 8-10-fold increase in plasma renin and ANG II concentrations compared with placebo. Plasma glucose decreased equally during placebo and EPRO from baseline 5.9 mmol/l to 1.9 mmol/l and 2.1 mmol/l respectively, inducing a 17-fold increase in arterial EPI concentration at peak. The AUC (area under the curve) during hypoglycaemia for arterial EPI concentrations was 314+/-48 nmol.min.l-1 in placebo compared with 254+/-26 nmol.min.l-1 following EPRO treatment (P=0.14). EPRO attenuated the corresponding AUC for the EPI-induced pulse pressure response (4670+/-219 mmHg.min in EPRO compared with 5004+/-266 mmHg.min in placebo; P=0.02). Moreover, EPRO caused a less pronounced increase in FBF compared with placebo (402+/-30 compared with 479+/-46 ml.100 g-1 of body weight; P=0.04). Musculocutaneous NE release was not affected by EPRO and the AUC for NE release was 51.69+/-15.5 pmol.min-1.100 g-1 of body weight in placebo compared with 39.35+/-18.2 pmol.min-1.100 g-1 of body weight after EPRO treatment (P=0.57). In conclusion, EPRO did not significantly inhibit sympathetic reactivity compared with placebo; however, it blunted the haemodynamic responses elicited by the sympatho-adrenal stimulation which only tended to be attenuated by this drug.     

Catecholamines in plasma from artery, cubital vein, and femoral vein in patients with cirrhosis. Significance of sampling site

The concentration of noradrenaline (NA) and adrenaline (A) was measured in arterial, cubital venous and femoral venous plasma in order to determine possible differences in different vascular beds in the peripheral circulation. In patients with cirrhosis, arterial plasma NA (median 2.54 nmol/l, n = 40) was significantly increased compared to controls (median 1.42 nmol/l, n = 17, p less than 0.001). Arterial plasma A was not significantly different (0.41 vs. 0.38 nmol/l). Cubital and femoral venous NA and A were positively correlated to the arterial values in both cirrhosis and controls (r = 0.86 to 0.97, p less than 0.01). In cirrhosis, median cubital venous:arterial NA ratio was significantly above unity (1.14, n = 36, p less than 0.001) as compared to unity in controls (1.00, n = 8), whereas the femoral venous:arterial NA ratio was similar in cirrhosis and controls, and significantly below unity (median 0.86 and 0.87). Cubital venous:arterial and femoral venous:arterial A ratios were significantly below unity in cirrhosis as well as in controls. The results point towards an enhanced sympathetic nervous activity in cirrhosis which may involve, among other organs, the upper limb (especially the skin of forearm and hand). To assess circulating levels of catecholamines, the importance of arterial sampling is stressed as peripheral venous samples may also reflect local factors.     

Plasma catecholamines in pregnancy induced hypertension

Increased activity of the sympathetic nervous system has been implicated in the genesis of early hypertension in young people. Studies in pregnancy allow observations to be made on evolving, recently established and resolving hypertension in the human. We describe the results of two studies involving women who developed hypertension during pregnancy. In the first study, plasma concentrations of noradrenaline and adrenaline were measured in 17 women with pregnancy induced hypertension (PIH) and 17 normotensive pregnant control subjects. Plasma noradrenaline (nmol/l) was lower in the PIH group compared with control patients in both semi-recumbent (1.11 +/- 0.53 vs 1.98 +/- 0.96, P less than 0.001) and standing positions (1.31 +/- 0.65 vs 2.57 +/- 1.27, P less than 0.005). Five days post partum, plasma noradrenaline had risen in the PIH group compared with pregnant values in semi-recumbent (1.65 +/- 1.0 vs 1.11 +/- 0.52, P less than 0.05) and standing positions (2.46 +/- 1.5 vs 1.31 +/- 0.65, P less than 0.05). In the normotensive patients plasma noradrenaline did not differ between post partum and pregnant values (1.51 +/- 0.73 vs 1.98 +/- 0.96 semi-recumbent; 2.00 +/- 1.16 vs 2.57 +/- 1.7 standing). Logarithmic transformation of the noradrenaline concentration data resulted in a significant (P less than 0.02) negative correlation with diastolic blood pressure in the pregnant patients but not post partum. Plasma adrenaline concentration was the same in both groups. In the second study, plasma concentrations of noradrenaline and adrenaline were measured sequentially through pregnancy in five women who developed PIH and five control subjects who remained normotensive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alanine and glutamine release from the human forearm: effects of glucose administration

The effect of glucose infusion alone (175 mg/kg bolus dose followed by 4 mg min-1 kg-1 for 70 min) and in combination with forearm exercise on the exchange of glucose, alanine, glutamine and other metabolites and amino acids across forearm muscle was studied in six healthy individuals after an overnight fast. Arterial and deep venous blood was sampled and a mercury strain gauge plethysmograph was used to measure forearm blood flow. Total body energy expenditure and net glucose and fat oxidation were assessed by indirect calorimetry. The infusion of glucose increased the mean arterial blood glucose concentration from 4.95 +/- 0.19 (SEM) to a plateau of 9.6-9.9 mmol/l (P less than 0.01). The arterial blood concentrations of alanine and glutamine were not significantly altered but that of lactate increased from 0.50 +/- 0.02 to 0.65 +/- 0.05 mmol/l (P less than 0.02) and that of pyruvate increased from 46 +/- 5 to 72 +/- 6 mumol/l (P less than 0.01). In the resting state glucose administration did not significantly affect the lactate/pyruvate ratio in arterial or venous blood. Arterial plasma insulin concentration increased four-fold and total ketone body concentration decreased two- to three-fold. After glucose administration, alanine release was suppressed (in all subjects) from a mean value of 153 +/- 22 to 57 +/- 16 nmol min-1 100 ml-1 of forearm (P less than 0.02) whereas that of glutamine was not significantly affected (160 +/- 30 to 143 +/- 29 nmol min-1 100 ml-1 of forearm). Lactate release, like that of alanine, decreased, whereas pyruvate was slowly released in the basal state and was taken up during glucose administration (P less than 0.01). These changes were associated with a decrease in the uptake of total ketone bodies to one-fifth to one-tenth of that in the basal state. The net amino acid balance across the forearm muscle bed was negative throughout the study but decreased from a mean value of -567 in the basal state to -300 nmol min-1 100 ml-1 of forearm after glucose administration for 60 min. This was predominantly due to decreased release of effluxing amino acids, particularly alanine.(ABSTRACT TRUNCATED AT 400 WORDS)     

Plasma catecholamine responses to change of posture in alcoholics during withdrawal and after continued abstinence from alcohol

Plasma catecholamine, blood pressure and heart rate responses to standing were measured in ten alcoholics during withdrawal, ten alcoholics after 2-7 weeks of abstinence from alcohol, six abstinent alcoholics with orthostatic hypotension and ten normal control subjects. Withdrawing alcoholics had supine and standing heart rates and plasma noradrenaline and adrenaline concentrations that were higher than in abstinent alcoholics or control subjects. Supine blood pressures were also higher in withdrawing alcoholics than in abstinent alcoholics or control subjects, but on standing blood pressures in withdrawing alcoholics fell, four patients having a fall of more than 30/5 mmHg. Abstinent alcoholics without orthostatic hypotension had higher basal and standing concentrations of noradrenaline than control subjects but normal heart rates and adrenaline concentrations. Abstinent alcoholics with orthostatic hypotension showed a wide range of basal plasma noradrenaline concentrations and were found to have variable plasma noradrenaline responses to standing, three subjects having normal responses and three subjects having no or little increase in plasma noradrenaline on standing. It is concluded that alcohol withdrawal is associated with increased sympathetic nervous activity, as reflected by raised supine and standing plasma concentrations of catecholamines, and that even after 2-7 weeks of abstinence from alcohol plasma noradrenaline concentrations may be higher than in control subjects. Despite increased sympathetic nervous responses to standing, alcoholics during withdrawal have impaired blood pressure control and some may exhibit orthostatic hypotension. Orthostatic hypotension may also be observed in alcoholics during continuing abstinence from alcohol; in some of these patients failure of reflex noradrenaline release in response to standing may contribute to orthostatic hypotension.     

Does dopamine regulate aldosterone secretion in the rat?

This study investigated the role of dopamine in the control of adrenal steroidogenesis. Adrenaline, noradrenaline and dopamine have been measured in plasma and in the adrenal zona glomerulosa and medulla of rats fed low, normal and high sodium diets and in zona glomerulosa tissue of rats with adrenal regeneration hypertension (ARH). Adrenal concentrations (means +/- SE) of adrenaline, noradrenaline and dopamine in rats fed a normal diet were 1471 +/- 335, 527 +/- 75 and 51 +/- 12 nmol/g in the medulla, and 66 +/- 17, 18 +/- 9 and 6 +/- 1 nmol/g in the zona glomerulosa. The dopamine content of the zona glomerulosa was greater than could be accounted for by simple contamination from the medullary catecholamines and is commensurate with that of tissue with dopaminergic innervation. Adrenal noradrenaline and adrenaline concentrations and plasma catecholamine and corticosterone concentrations were not affected by dietary sodium intake. Plasma aldosterone concentrations were greater than 3030.4, 339.8 +/- 41.5 and 55.2 +/- 11.0 pmol/l in rats fed low, normal and high sodium diets respectively. Five weeks after right adrenalectomy and nephrectomy and left adrenal enucleation, ARH rat systolic blood pressure had increased by 47 mmHg. In the regenerated gland, the concentrations of noradrenaline and adrenaline were negligible but dopamine was present in amounts similar to that of a normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebrospinal fluid levels of catechols in patients with neurogenic orthostatic hypotension

In multiple system atrophy (MSA) and pure autonomic failure (PAF), orthostatic hypotension (OH) results from deficient noradrenaline release from sympathetic nerves during standing. Post-mortem findings have indicated loss of central noradrenergic cells in both diseases. The present study sought in vivo neurochemical evidence for central noradrenergic deficiency in patients with OH due to MSA or PAF. A total of 28 patients with OH (18 with MSA; 10 with PAF) had cerebrospinal fluid and blood sampled for levels of noradrenaline and its neuronal metabolite dihydroxyphenylglycol. A control group of 44 subjects included 10 elderly normal volunteers, 10 patients with Alzheimer's disease, 18 patients with dysautonomia (postural tachycardia syndrome or neurocardiogenic syncope) and six patients with MSA in the absence of OH. Patients with OH had lower cerebrospinal fluid concentrations of noradrenaline (0.53+/-0.07 nmol/l) and dihydroxyphenylglycol (6.52+/-0.46 nmol/l) than did control subjects (0.90+/-0.09 and 9.64+/-0.46 nmol/l respectively; P =0.0001). The MSA+OH group had higher plasma levels of both catechols (noradrenaline, 1.31+/-0.16 nmol/l; dihydroxyphenylglycol, 5.08+/-0.43 nmol/l) than did the PAF group (noradrenaline, 0.38+/-0.08 nmol/l; dihydroxyphenylglycol, 2.53+/-0.30 nmol/l; P <0.001), despite similarly low cerebrospinal fluid levels. Among MSA patients, those with OH had lower cerebrospinal fluid levels of noradrenaline and dihydroxyphenylglycol than those without OH (noradrenaline, 1.71+/-0.64 nmol/l; dihydroxyphenylglycol, 10.41+/-1.77 nmol/l respectively; P =0.006). The findings are consistent with central noradrenergic deficiency in both MSA+OH and PAF. In MSA, central noradrenergic deficiency seems to relate specifically to OH.     

Ionized calcium and acid-base status in arterial and venous whole blood during general anaesthesia

Ionized calcium, pH, pCO2 and base excess (BE) have been measured in paired samples of anaerobically collected arterial (aB) and venous whole blood (vB) from patients under general anaesthesia and during recovery. A statistically significant decrease was found in the concentration of ionized calcium in anaerobic arterial and venous blood during induction of anaesthesia and during surgery partly due to variations in pH. Statistically significant correlations were found between logcCa2+ and pH (r = -0.67, p less than 0.001), and between cCa2+ and pCO2 (r = 0.66, p less than 0.001) in anaerobic arterial blood. The in vivo slope (dlogcCa2+/dpH) was found to be -0.15 +/- 0.08 and -0.14 +/- 0.06 for arterial and venous blood, respectively (mean +/- SE). The in vitro slope estimated by equilibrating arterial and venous serum at two pCO2 values was -0.22 +/- 0.03, and -0.21 +/- 0.03, respectively (mean +/- SE). Because of a considerable variability in slope we believe that the best clinical evaluation of ionized calcium is achieved by taking measurements from anaerobically collected whole blood. Interpolating or extrapolating ionized calcium to a standard pH of 7.40 on the basis of a standard slope may introduce unnecessary errors.     

Cardiac and whole-body [3H]noradrenaline kinetics during adrenaline infusion in man.

1. To investigate the possible role of adrenaline as a modulator of noradrenaline release from the sympathetic nervous system, the responses of cardiac and whole-body noradrenaline kinetics to intravenous infusions of adrenaline (30 ng min-1 kg-1) and matching saline placebo were determined at rest and during supine bicycle exercise in 16 patients undergoing cardiac catheterization, in whom beta-adrenoceptor antagonists had been discontinued for 72 h. 2. At rest and compared with placebo, infusion of adrenaline was associated with a small increase in arterial plasma noradrenaline from 211 +/- 29 pg/ml to 245 +/- 29 pg/ml (P less than 0.05). Increases in whole-body noradrenaline spillover to arterial plasma were larger (from 282 +/- 40 ng min-1 m-2 to 358 +/- 41 ng min-1 m-2, P less than 0.01) and there was a trend towards an increase in whole-body noradrenaline clearance. Cardiac noradrenaline clearance was modestly increased during adrenaline infusion, but cardiac noradrenaline spillover was not altered despite increases in heart rate and coronary sinus plasma flow. Adrenaline infusion was associated with symptomatic myocardial ischaemia in four of 14 patients with coronary heart disease. 3. Supine bicycle exercise was associated with significant increases in peripheral noradrenaline concentrations and in cardiac and whole-body noradrenaline spillover. The increases on exercise were not significantly different for these variables during saline and adrenaline infusions. 4. Infusion of adrenaline to produce 'physiological' increases in plasma adrenaline concentration was associated with an increase in total noradrenaline release, as assessed by whole-body noradrenaline spillover to plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of euglycaemic and hypoglycaemic hyperinsulinaemia on sympathetic and parasympathetic regulation of haemodynamics in healthy subjects

The effects of hypoglycaemia during hyperinsulinaemia, occurring under various pathophysiological conditions, on the cardiovascular regulatory system and vasculature are largely unknown. The aim of the present study was to investigate regulatory and haemodynamic responses to acute hyperinsulinaemia and consequent hypoglycaemia in 18 healthy subjects. Blood sampling and 5 min ECG and blood pressure recordings were performed at baseline and during the euglycaemic and hypoglycaemic phases of a hyperinsulinaemic clamp. Heart rate variability (HRV) and blood pressure variability (BPV) were assessed by using power spectral analysis, and baroreflex sensitivity (BRS) was assessed using the cross-spectral method. Stroke volume was assessed from the non-invasive blood pressure signal by the arterial pulse contour method. Euglycaemic hyperinsulinaemia did not change plasma catecholamine concentrations, HRV, BPV, BRS, heart rate, blood pressure, stroke volume, cardiac output or peripheral resistance. However, hyperinsulinaemic hypoglycaemia resulted in an 11.7-fold increase in the plasma adrenaline concentration (from 0.19+/-0.03 to 1.68+/-0.32 nmol/l; P <0.001), and a modest 1.3-fold increase in the plasma noradrenaline concentration (from 1.74+/-0.22 to 2.02+/-0.19 nmol/l; P <0.05) compared with baseline. Furthermore, we observed significant decreases in diastolic blood pressure (from 68+/-3 to 60+/-3 mmHg; P <0.05) and peripheral resistance (from 24.1+/-1.2 to 18.5+/-1.1 mmHg.min(-1) x l(-1); P <0.01). Stroke volume and cardiac output increased markedly from the euglycaemic to the hypoglycaemic period only ( P <0.01 for both). Hypoglycaemia did not influence HRV, BPV or BRS. Our findings indicate that hyperinsulinaemic hypoglycaemia is characterized by a significant increase in the plasma adrenaline concentration and by decreases in peripheral resistance and blood pressure. Counter-regulation during hyperinsulinaemic hypoglycaemia involves selective adrenomedullary sympathetic activation, and does not influence cardiac parasympathetic regulation or baroreflex control of heart rate.     

Physiological responses to the early mobilisation of the intubated, ventilated abdominal surgery patient

The aim of this study was to investigate the effects of mobilisation on respiratory and haemodynamic variables in the intubated, ventilated abdominal surgical patient. Mobilisation was defined as the progression of activity from supine, to sitting over the edge of the bed, standing, walking on the spot for one minute, sitting out of bed initially, and sitting out of bed for 20 minutes. Seventeen patients with age (mean +/- SD) 71.4 +/- 7.1 years satisfied inclusion criteria. Respiratory and haemodynamic parameters were measured in each of the above positions and compared with supine. In the 15 subjects who completed the protocol, standing resulted in significant increases in minute ventilation (VE) from 15.1 +/- 3.1 l/min in supine to 21.3 +/- 3.6 l/min in standing (p < 0.001). The increase in VE in standing was achieved by significant increases in tidal volume (VT) from 712.7 +/- 172.8 ml to 883.4 +/- 196.3 ml (p = 0.008) and in respiratory rate (fR) from 21.4 +/- 5.0 breaths/min to 24.9 +/- 4.5 breaths/min (p = 0.03). No further increases were observed in these parameters beyond standing when activity was progressed to walking on the spot for one minute. When supine values were compared with walking on the spot for one minute, inspiratory flow rates (VT/TI) increased significantly from 683 +/- 131.8 ml/sec to 985.1 +/- 162.3 ml/sec (p = 0.001) with significant increases in rib cage displacement (p = 0.001) and no significant increase in abdominal displacement (p = 0.23). Arterial blood gases displayed no improvements following mobilisation. Changes in VT, fR, and VE were largely due to positional changes when moving from supine to standing.     

Effect of intravenous infusion of adrenaline on the cardiovascular responses to distal body subatmospheric pressure in man

1. On two separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline [0.27 nmol (50 ng) min-1 kg-1] or saline (154 mmol/l NaCl), plus ascorbic acid (5.68 mmol/l), over 30 min. 2. On each occasion, the subjects were exposed to distal body subatmospheric pressure (DBSP), 0 to 50 mmHg (0 to 6.65 kPa) in 10 mmHg (1.33 kPa) steps, before infusion, during the final 15 min of the infusion, and at 15 min and 30 min after the cessation of the infusion. 3. Venous adrenaline concentrations of 2.85 +/- 0.22 nmol/l were achieved during the adrenaline infusion, compared with 0.49 +/- 0.07 nmol/l during the saline infusion (P less than 0.001). At 15 min and at 30 min after cessation of the adrenaline infusion, venous adrenaline concentrations had fallen to levels similar to those achieved after the cessation of the saline infusion. 4. Heart rate rose significantly from 58 +/- 4 beats/min to 67 +/- 4 beats/min during the adrenaline infusion (P less than 0.05), but there was no further significant change in response to 50 mmHg (6.65 kPa) DBSP. At 30 min after the cessation of the adrenaline infusion, heart rate rose from 60 +/- 4 beats/min to 78 +/- 7 beats/min in response to 50 mmHg DBSP. This increase was significantly greater than that observed before the adrenaline infusion [58 +/- 4 beats/min to 69 +/- 7 beats/min during 50 mmHg (6.65 kPa) DBSP; P less than 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)     

Should a VVIR Pacemaker Increase the Heart Rate with Standing?

To assess the usefulness of incorporating a posture sensor into a ventricular inhibited rate modulated pacemaker, the hemodynamic effects of increasing the ventricular pacing rate with standing were studied in 15 pacemaker dependent patients aged 55 +/- 3.5 years. In a randomized cross-over design, the pacing rate remained at 70 or was increased to 100 beats/min immediately prior to standing. Blood pressure was monitored continuously and forearm blood flow was measured by venous occlusion plethysmography. There was no difference in supine blood pressure (117 +/- 4/63 +/- 3 compared to 118 +/- 5/64 +/- 4 mmHg) or forearm blood flow (2.88 +/- 0.36 vs 2.94 +/- 0.32 mL/100 mL/min) before the 70 or 100 pacing rate intervention. With standing, blood pressure fell to an equivalent degree at the two pacing rates (fall in mean blood pressure at 70 beats/min 6 +/- 4 and at 100 beats/min 8 +/- 2 mmHg, P = 0.7). After 1 minute of standing differences in blood pressure were similar, but after 2.5 minutes of standing the increase in mean blood pressure was less at 70 than at 100 beats/min (increase from control 28 +/- 2 compared to 36 +/- 3 mmHg, P = 0.002). Forearm blood flow decreased after standing for 1 and 2.5 minutes but there was no difference between the 70 and 100 pacing rates (fall in forearm blood flow at 2.5 minutes 0.50 +/- 0.24 and 0.59 +/- 0.25 mL/100 mL/cm2).(ABSTRACT TRUNCATED AT 250 WORDS)