Cardiovascular effects of gastric intubation and distension in healthy humans.

Few data exist on the effect of upper gut stimuli on the cardiovascular system. Aim of our study was to evaluate the cardiovascular effects of gastric intubation and distension. Eleven healthy subjects (eight men, aged 21-30 years) were studied and a non-invasive beat-to-beat cardiovascular monitoring system was used. After 15-min basal recording, a bag catheter was positioned in the proximal stomach and connected to a barostat. Recordings were first performed for 15 min with the bag deflated, then during inflation of air using a 100 mL per 2 min stepwise protocol until epigastric discomfort was reported, and finally for 15 min with the bag inflated at 75% of discomfort volume spared from the preceding period by 10 min with the bag deflated. Presence of the deflated bag catheter significantly increased mean arterial pressure. Stepwise distension progressively increased heart rate and cardiac index, while mean arterial pressure was affected only at discomfort volume. Peripheral resistances and systemic plasma catecholamines were unaffected. During prolonged distension, the effect on heart rate and cardiac index was transient. In conclusion, both gastric intubation and distension alter cardiovascular parameters, but the effect of distension undergoes rapid adaptation. Experimentally induced gastric distension is a valuable stimulus to study viscero-cardiovascular reflexes and their mechanisms using beat-to-beat measurements.

Effects of chronic clonidine administration on sympathetic nerve traffic and baroreflex function in heart failure.

Congestive heart failure is characterized by a sympathetic activation that is coupled with a baroreflex impairment. Whether these alterations are affected by clonidine is unknown. In 26 normotensive patients age 58.0+/-1.1 years (mean+/-SEM) affected by congestive heart failure (New York Heart Association functional class II or III) and treated with furosemide and enalapril, we measured mean arterial pressure, heart rate, venous plasma norepinephrine, and muscle sympathetic nerve traffic (microneurography) at rest and during baroreceptor stimulation and deactivation caused by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were repeated after a 2-month administration of transdermal clonidine patch (14 patients) or placebo (12 patients) according to a double-blind, randomized sequence. Clonidine caused a slight, nonsignificant reduction in mean arterial pressure and heart rate without affecting exercise capacity and echocardiographically determined left ventricular ejection fraction. In contrast, both plasma norepinephrine and sympathetic nerve traffic were significantly reduced (-46.8% and -26.7%, respectively; P<0.01 for both). This reduction was coupled with no change in cardiac and sympathetic baroreflex responses. Transdermal placebo administration for a 2-month period did not affect any of the above-mentioned variables. Thus, in congestive heart failure patients who are undergoing conventional drug treatment, chronic clonidine administration exerts marked sympathoinhibitory effects without adversely affecting cardiac functions and clinical state. Whether this leads to further therapeutic benefits remains to be tested.

Sympathetic and reflex abnormalities in heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy.

Congestive heart failure (CHF) is characterized by a sympathetic activation and a baroreflex impairment whose degree is directly related to the clinical severity of the disease. However, whether these abnormalities vary according to the ischaemic or idiopathic dilated nature of the CHF state has not been conclusively documented. In patients with a clinically stable, chronic CHF state in New York Heart Association functional class II and III, due either to ischaemic heart disease (IHD; n=22, age 60.3+/-2.4 years, means+/-S.E.M.) or to idiopathic dilated cardiomyopathy (IDC; n=20, age 58.9+/-2.8 years), and in 30 age-matched controls, we measured arterial blood pressure (using a Finapres device), heart rate (by electrocardiogram) and postganglionic muscle sympathetic nerve traffic (by microneurography) at rest and during baroreceptor manipulation induced by the vasoactive drug-infusion technique. Blood pressure values were not significantly different in CHF patients and controls. Compared with controls, heart rate was similarly increased and left ventricular ejection fraction (by echocardiography) similarly reduced in CHF patients with IHD or IDC. Muscle sympathetic nerve traffic was significantly greater in CHF patients than in controls, and did not differ between patients with IHD or IDC (67.3+/-4.2 and 67.8+/-3.8 bursts/100 heart beats respectively). This was also the case for the degree of baroreflex impairment. These data show that CHF states due to IHD or to IDC are characterized by a similar degree of peripheral sympathetic activation and by a similar impairment of the baroreflex function. Thus the neuroadrenergic and reflex abnormalities characterizing CHF are independent of its aetiology.

Sympathetic and reflex alterations in systo-diastolic and systolic hypertension of the elderly.

BACKGROUND: Previous studies have shown that young and middle-aged essential hypertensives are characterized by a sympathetic activation coupled with an impaired baroreflex-heart rate control. The present study aimed to determine whether these neuroadrenergic and reflex alterations also characterize systo-diastolic and systolic hypertension of the elderly. SUBJECTS AND METHODS: In 20 untreated elderly essential hypertensive subjects [10 with a systo-diastolic and 10 with an isolated systolic hypertension, aged 67.2 +/- 1.5 years and 66.9 +/- 1.7 years (mean +/- SEM)], we measured beat-to-beat arterial blood pressure (finger photoplethysmographic device), heart rate (electrocardiogram) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Data were compared with those obtained in 11 age-matched normotensive control subjects. RESULTS: Compared to the elderly normotensive group, muscle sympathetic nerve activity was increased to a similar degree in the group of systo-diastolic and systolic hypertension (50.8 +/- 4.2 versus 75.2 +/- 5.2 and 70.4 +/- 5.1 bursts per 100 heart beats, respectively, P< 0.01 for both). In the control group, the stepwise increase in arterial pressure induced by phenylephrine caused progressive bradycardia and sympathoinhibition, while the stepwise decrease in arterial pressure had opposite effects. While baroreceptor-heart rate control was markedly impaired (average reduction 41.6%), in both systo-diastolic and systolic hypertensive patients, baroreceptor modulation of sympathetic nerve traffic was similar to that seen in normotensive individuals. CONCLUSIONS: These data demonstrate that sympathetic activation is not only a feature of young and middle-aged, but also of elderly hypertensives, regardless of whether both systolic and diastolic or only systolic blood pressure is increased. They also show that hypertension of the elderly is not accompanied by an impaired baroreceptor modulation of sympathetic nerve traffic.

Treatment of Helicobacter pylori and Chlamydia pneumoniae infections decreases fibrinogen plasma level in patients with ischemic heart disease.

BACKGROUND: Chronic Chlamydia pneumoniae and Helicobacter pylori infections could be a risk factor for ischemic heart disease (IHD), possibly by increasing fibrinogen levels. The aim of our study was to evaluate changes in fibrinogen level in patients with IHD and H pylori and/or C pneumoniae positivity randomly assigned to antibiotic treatment. METHODS AND RESULTS: Eighty-four patients with chronic IHD, H pylori and/or C pneumoniae antibodies, and normal acute-phase reactants were randomly assigned to treatment or no treatment. Treatment consisted of omeprazole, clarithromycin, and tinidazole in H pylori-positive patients and clarithromycin alone in C pneumoniae-positive patients. The effect of treatment and other baseline variables on fibrinogen levels, determined at 6 months, was evaluated by multivariate analysis. Treatment significantly reduced fibrinogen level at 6 months in the overall study population and in the groups of patients divided according to H pylori or C pneumoniae positivity. In the 43 treated patients, mean (+/-SD) basal fibrinogen was 3.65+/-0.58 g/L, and mean final fibrinogen was 3. 09+/-0.52 g/dL (P<0.001), whereas in the 41 untreated patients, mean basal and final fibrinogen levels were 3.45+/-0.70 and 3.61+/-0.71 g/L, respectively. The largest decrease was observed in patients with both infections. Fibrinogen changes were also significantly and negatively correlated with age. CONCLUSIONS: Our data suggest that a short, safe, and effective course of antibiotic therapy might be suggested as a means of interacting with an "emerging" risk factor.

Effects of amlodipine on sympathetic nerve traffic and baroreflex control of circulation in heart failure.

Short-acting calcium antagonists exert a sympathoexcitation that in heart failure further enhances an already elevated sympathetic activity. Whether this is also the case for long-acting formulations is not yet established, despite the prognostic importance of sympathetic activation in heart failure. It is also undetermined whether in this condition long-acting calcium antagonists favorably affect a mechanism potentially responsible for the sympathetic activation, ie, the baroreflex impairment. In 28 heart failure patients (NYHA functional class II) under conventional treatment we measured plasma norepinephrine and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during arterial baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were performed at baseline and after 8 weeks of daily oral amlodipine administration (10 mg/d, 14 patients) or before and after an 8-week period without calcium antagonist administration (14 patients). Amlodipine caused a small and insignificant blood pressure reduction. Heart rate, left ventricular ejection fraction, and plasma renin and aldosterone concentrations were not affected. This was the case also for plasma norepinephrine (from 2.43+/-0.41 to 2.50+/-0.34 nmol/L, mean+/-SEM), muscle sympathetic nerve activity (from 54.4+/-5.9 to 51.0+/-4.3 bursts/min), and arterial baroreflex responses. No change in the above-mentioned variables was seen in the control group. Thus, in mild heart failure amlodipine treatment does not adversely affect sympathetic activity and baroreflex control of the heart and sympathetic tone. This implies that in this condition long-acting calcium antagonists can be administered without untoward neurohumoral effects anytime conventional treatment needs to be complemented by drugs causing additional vasodilatation.

Heart rate as marker of sympathetic activity.

OBJECTIVE: To determine the value of the supine heart rate as a marker of sympathetic tone by assessing, in a large group of subjects, the relationships between this parameter and two other indices of sympathetic activity, plasma norepinephrine and sympathetic nerve traffic. PATIENTS AND METHODS: We studied 243 subjects aged 50.0+/-12.1 years (mean +/- SD). Of these, 38 were normotensive healthy controls, 113 subjects had untreated essential hypertension, 27 were obese normotensives and 65 had congestive heart failure. In each subject, over a 10 min supine period, we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), venous plasma norepinephrine (high-performance liquid chromatography) and efferent postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). RESULTS: In the whole study group, supine heart rate was correlated with both plasma norepinephrine (r = 0.32, P < 0.0001) and muscle sympathetic nerve activity (r = 0.38, P < 0.0001). This was also the case in the normotensive obese subjects and the heart failure subjects considered separately. Heart rate values were greater in the obese and the heart failure patients than in controls (75.1+/-13.0 and 78.2+/-13.0 versus 69.2+/-11.6 beats/min; P < 0.05 and P < 0.001, respectively), as were plasma norepinephrine (362.7+/-202 and 400.3+/-217 versus 230.4+/-126 pg/ml; P < 0.01 and P < 0.001, respectively) and muscle sympathetic nerve activity (44.1+/-14.7 and 55.3+/-14.3 versus 27.8+/-11.0 bursts/min; P < 0.001 for both). In contrast, in the essential hypertensive subjects, no significant relationship was found between these three indices of sympathetic activity. Furthermore, in the hypertensives, the heart rate was not increased, at variance with the sympathetic nerve traffic, which was greater than in controls (36.2+/-10.0 versus 27.8+/-11.0 bursts/min, P < 0.001). CONCLUSIONS: These data suggest that the supine heart rate can be regarded as a marker of intersubject differences in sympathetic tone, and that this is the case both in the general population and in those with cardiovascular diseases. Its value for this purpose is limited, however, and the limitations may be more evident in essential hypertension than in conditions such as obesity and heart failure.

Calcium antagonists and sympathetic activity in congestive heart failure.

OBJECTIVE: To review the sympathetic abnormalities occurring in heart failure, their pathophysiological importance and clinical relevance, and the effects of drug treatment, with particular reference to calcium antagonists. SYMPATHETIC ACTIVATION IN HEART FAILURE: Indirect and direct approaches to study sympathetic function in humans have documented conclusively that sympathetic activation represents a hallmark of cardiac failure syndrome. Evidence indicates that sympathetic overactivity is associated with, and probably caused by, a baroreflex impairment and that it has adverse effects on patients' prognosis and survival. GOALS OF DRUG TREATMENT IN CONGESTIVE HEART FAILURE: In the past, drug treatment in heart failure was aimed at improving patients' survival by ameliorating cardiac hemodynamics. It is now established that a major goal of therapeutic intervention is also to reduce sympathetic activation characterizing heart failure. CALCIUM ANTAGONISTS IN HEART FAILURE: Studies with short-acting calcium antagonists show that they enhance sympathetic activation and that this has an adverse effect on patients' survival. In contrast, third generation calcium antagonists such as amlodipine, which have a slow onset and long duration of action, do not adversely affect sympathetic function and reflex cardiovascular control. Indeed, evidence suggests calcium antagonists with this profile may exert favorable clinical effects.

Hemodilution reduces clinic and ambulatory blood pressure in polycythemic patients.

Limited information is available for humans on whether blood viscosity affects total peripheral resistance and, hence, blood pressure. Our study was aimed at assessing the effects of acute changes in blood viscosity on both clinic and 24-hour ambulatory blood pressure (BP) values. In 22 normotensive and hypertensive patients with polycythemia, clinic and 24-hour ambulatory BPs were measured before and 7 to 10 days after isovolumic hemodilution; this was performed through the withdrawal of 400 to 700 mL of blood, with concomitant infusion of an equivalent volume of saline-albumin solution. Hematocrit, plasma renin activity, plasma endothelin-1, right atrial diameter (echocardiography), and blood viscosity were measured under both conditions. Plasma renin activity and right atrial diameter were used as indirect markers of blood volume changes. Plasma endothelin-1 was used to obtain information on a vasomotor substance possibly stimulated by our intervention, which could counteract vasomotor effects. Isovolumic hemodilution reduced hematocrit from 0.53+/-0.05 to 0.49+/-0.05 (P<.01). Plasma renin activity, plasma endothelin-1 and right atrial diameter were unchanged. Clinic blood pressure was reduced by hemodilution (systolic, 144.3+/-5.4 to 136.0+/-3.9 mm Hg[mean+/-SEM]; diastolic, 87.0+/-2.8 to 82.1+/-2.6 mm Hg, P<.05 for both) and a reduction was observed also for 24-hour average ABP (systolic, 133.6+/-2.9 to 129.5+/-2.7 mm Hg; diastolic, 80.0+/-2.0 to 77.3+/-1.7 mm Hg, P<.05 for both). The reduction was consistent in hypertensive patients (n = 12), whereas in normotensive patients (n = 10) it was small and not significant. Both clinic and 24-hour average heart rates were unaffected by the hemodilution. Thus, in polycythemia, reduction in blood viscosity without changing blood volume causes a significant fall in both clinic and 24-hour ambulatory BPs; this is particularly true when, as can often happen, blood pressure is elevated. This emphasizes the importance this variable may have in the determination of blood pressure and the potential therapeutic value of its correction when altered.

Evaluation of the baroreceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring in humans.

The baroreceptor control of the sinus node was evaluated in 10 normotensive and 10 age-matched essential hypertensive subjects in whom ambulatory blood pressure was recorded intra-arterially for 24 hours and scanned by a computer to identify the sequences of three or more consecutive beats in which systolic blood pressure (SBP) and pulse interval (PI) progressively rose (+PI/+SBP) or fell (-PI/-SBP) in a linear fashion, according to a method validated in cats. In normotensive subjects, several hundred +PI/+SBP and -PI/-SBP sequences of 3 beats were found whereas the number of sequences of 4, 5, and more than 5 beats showed a progressive drastic reduction. The mean slopes of +PI/+SBP (7.6 +/- 2.0 msec/mm Hg) and -PI/-SBP (6.4 +/- 1.5 msec/mm Hg) sequences were similar, but in both instances there was a large scattering of the values around the mean (variation coefficients: 64.2 +/- 4.7 and 62.6 +/- 2.4%). The slopes decreased as a function of the sequence length and baseline heart rate and increased to a marked extent during the night as compared with daytime values. All sequences were more rare (-33.2% for +PI/+SBP and -31.7% for -PI/-SBP) and less steep in hypertensive subjects (-40.3 and -36.2%, respectively), who failed to show the marked nighttime increase in slope observed in normotensive subjects. To our knowledge, these observations provide the first description in humans of the baroreceptor-heart rate reflex in daily life. This reflex is characterized by marked within-subject variations in sensitivity due in part to hemodynamic, temporal, and behavioral factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of baroreceptor reflex by blood pressure monitoring in unanesthetized cats.

The arterial baroreceptor control of the sinus node operating in unanesthetized conditions was evaluated in 10 cats in which blood pressure was recorded intra-arterially and scanned by a computer to identify the "spontaneous" sequences of three or more consecutive beats in which systolic blood pressure (SBP) progressively rose and pulse interval (PI) progressively lengthened (type 1 sequences) or SBP progressively fell and PI progressively shortened (type 2 sequences). Many type 1 and 2 three-beat sequences were found; four-, five-, and six-beat sequences of either type were progressively less common, and sequences longer than six beats were almost never identified. The regression coefficient was 30% greater for type 1 than for type 2 sequences. However a prominent feature of either regression coefficient was a wide scattering in each cat (average variation coefficient 50.9 +/- 5.5%). The regression coefficient values were related to some extent to the PI but not to the SBP existing at the beginning of the sequence. Sinoaortic denervation dramatically reduced the number of sequences of either type. These data validate a method for collecting a large number of observations on the baroreceptor-heart rate reflex in physiological conditions. This method may improve understanding of baroreflex involvement in integrated cardiovascular regulation.

[The emergency service physician and acute abdominal pathology. Comparative study on 1500 cases]. / Il medico di Pronto Soccorso di fronte alla patologia addominale acuta. Studio comparativo su 1500 casi.

1436 cases of recent abdominal pain encountered in the Casualty Department of Biella Hospital over 18 consecutive months are examined. The incidence of the various abdominal pathologies, the diagnostic and therapeutic procedures adopted in the first hours after admission and any differences between original diagnosis by the general practitioner of the First Aid post, diagnosis on admission and diagnosis on release from hospital are examined.

[Miocamycin in the prevention and treatment of cutaneous infections in the emergency service]. / La miocamicina nella profilassi e nel trattamento delle infezioni cutanee in Pronto Soccorso.

The efficacy and tolerability of a new macrolide, Myocamycine, were assessed in the anti-infectious prophylaxis of lacerations and contusions and in the treatment of already infected wounds or phlegmons. A total of 175 patients were treated. Side effects induced the suspension of treatment in 8% of cases while the drug proved effective in preventing the infection of wounds at risk in 98% and curing existing infections in 100%.

Differential control of blood pressure and heart rate by carotid and aortic baroreceptors in unanaesthetized cats.

In unanaesthetized cats the most striking effects of sino-aortic denervation (SAD) consist of a marked increase in blood pressure variability and a concomitant marked reduction in heart rate variability. Because the relative contribution of carotid and aortic baroreceptors to these phenomena has never been assessed, blood pressure (intra-arterial catheter) and heart rate were measured in unanaesthetized, unrestrained cats for 8-10 h under three conditions: intact animals, 1 week after section of the carotid sinus or the aortic nerves and 1 week after SAD. Blood pressure and heart rate signals were analysed by a computer to provide mean values and variation coefficients of variation i.e. blood pressure and heart rate variabilities, for each recording period. In the intact cats the coefficient of variation was 6.6 +/- 0.6% (mean +/- s.e.) for mean blood pressure and 11.2 +/- 1.7% for heart rate. The coefficient of variation for mean blood pressure was not altered by either the aortic or the carotid sinus nerve section, a marked increase being observed only after SAD (11.5 +/- 1.3%, P less than 0.01). On the other hand, the coefficient of variation for heart rate was reduced either by the carotid or by the aortic nerve section. The reduction observed following the carotid baroreceptor denervation accounted for the greater fraction of the overall reduction (74 versus 26%) in coefficient of variation for heart rate observed after SAD (4.8 +/- 0.9%, P less than 0.01). These data show that the carotid sinus and aortic nerves are similarly involved in control of blood pressure variability.(ABSTRACT TRUNCATED AT 250 WORDS)

A new approach to analysis of the arterial baroreflex.

The arterial baroreflex is commonly evaluated by measuring the lengthening and shortening in pulse interval in response to changes in systolic (S) blood pressure (BP) induced by infusion of vasopressor and vasodepressor drugs. This method is simple but has important limitations: only a few observations can be made, reproducibility of the responses is far from optimal, interference by direct drug action on the sinus node and the baroreceptors cannot be excluded and the artificially induced stimuli only poorly mimic the naturally occurring pressor and depressor transients. A new approach was therefore pursued. Blood pressure was recorded intra-arterially for 3 +/- 0.4 h (mean +/- s.d) in 10 unanaesthetized, unrestrained cats and the recording was scanned by a computer to identify the spontaneous sequences of three or more consecutive beats in which SBP progressively rose and pulse interval progressively lengthened (type 1 sequence) or SBP progressively fell and pulse interval progressively shortened (type 2 sequences). Accurate beat-to-beat measurements of SBP and pulse interval were obtained by adopting a very narrow sampling interval of the BP trace, i.e. 1.6 ms real time. For each sequence the regression between the SBP values and the pulse internal values of the following cycle was calculated. In each cat a large number of three-beat sequences were found, the four-, five- and six-beat sequences being, however, progressively less common. All sequences had a high correlation coefficient (r > 0.9), type 1 having a greater slope than type 2 (14.1 +/- 2.5 versus 10.3 +/- 7.6 ms/mmHg, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Reflex control of blood pressure and heart rate by arterial baroreceptors and by cardiopulmonary receptors in the unanaesthetized cat.

Studies in unanaesthetized animals have reported that section of the carotid sinus and aortic nerves is accompanied by an increased blood pressure variability but not by a sustained blood pressure rise, thus questioning the role of arterial baroreceptors in the long term control of mean blood pressure values. However, sino-aortic denervation (SAD) does not produce denervation of all baroreceptor areas, and it has been suggested that aortic baroreceptor fibres in the vagus and cardiopulmonary vagal afferents that restrain sympathetic vasoconstrictor tone prevent blood pressure from permanently rising. In unanaesthetized cats we recorded blood pressure intra-arterially for 8-12 h when baroreflexes were intact, 7 days after SAD and 1-2 days additional bilateral cervical vagotomy. Blood pressure signals were analysed by computer to provide means and coefficients of variation (CV, variabilities) for each recording period. In intact cats, mean blood pressure was 99 +/- 7 mmHg (average +/- s.e.) and CV 6 +/- 1%. SAD did not alter mean blood pressure but markedly increased CV (12 +/- 2%; P less than 0.01). Additional vagotomy did not alter mean blood pressure (104 +/- 6 mmHg), nor did it alter the increased CV observed after SAD alone. Vagotomy failed to affect mean blood pressure and CV even when performed in cats with intact carotid and aortic nerves. The lack of effect of vagotomy did not depend on simultaneous section of afferent and efferent fibres, because selective blockade of the latter by atropine also failed to affect mean blood pressure and CV.(ABSTRACT TRUNCATED AT 250 WORDS)