Endothelial dysfunction in hypertension.

Endothelial cells release both relaxing and contracting factors that modulate vascular smooth muscle tone and also participate in the pathophysiology of essential hypertension. Endothelium-dependent vasodilation is regulated primarily by nitric oxide but also by an unidentified endothelium-derived hyperpolarizing factor and by prostacyclin. Endothelium-derived contracting factors include endothelin-1, vasoconscrictor prostanoids, angiotensin II and superoxide anions. Under physiological conditions, there is a balanced release of relaxing and contracting factors. The balance can be altered in cardiovascular diseases such as hypertension, atherosclerosis, diabetes and other conditions, thereby contributing to further progression of vascular and end-organ damage. In particular, endothelial dysfunction leading to decreased bioavailability of nitric oxide impairs endothelium-dependent vasodilation in patients with essential hypertension and may also be a determinant for the premature development of atherosclerosis. Different mechanisms of reduced nitric oxide activity have been shown both in hypertensive states and several cardiovascular diseases, and endothelial dysfunction is likely to occur prior to vascular dysfunction. Thus, the strategies currently used to improve endothelial dysfunction may result in decreased morbidity and mortality in hypertensive patients.

Autonomic dysfunction and hyperdynamic circulation in cirrhosis with ascites.

Patients with advanced cirrhosis frequently show hemodynamic abnormalities. Autonomic dysfunction (AD) is also common and, owing to the importance of autonomic function in cardiovascular homeostasis, it may be involved in the pathogenesis of the hyperdynamic circulation. We, therefore, evaluated the hemodynamic status and autonomic function in 30 patients with cirrhosis, most of them with an advanced stage of the disease. Autonomic function was assessed with 7 cardiovascular tests exploring the vagal or sympathetic function. Each test was scored from 1 to 3 (normal, borderline, altered). Cardiac index (CI) was measured by an echocardiogram. Twenty-four (80%) patients showed an AD, this being definite in 14 (47%) patients. A vagal dysfunction (VD) was found in 19 patients (63%), this being definite in 11 patients (37%), and a sympathetic dysfunction (SD) in 7 patients (definite in 3 [10%] patients). The patients with AD showed a faster heart rate (P =.021), lower indicized peripheral vascular resistance (P =.013), and increased CI (P =.004) than patients without AD whereas mean arterial pressure did not differ. Similar results were seen by grouping patients according to the VD. AD score was directly correlated with heart rate (r = 0.53; P =.002) and CI (r = 0.45; P =. 016), and inversely correlated with peripheral vascular resistance (r = 0.46; P =.013). Even closer correlations were found with vagal score. AD (mainly VD) may be involved in the pathogenesis of the hyperdynamic circulatory syndrome of patients with advanced cirrhosis.

Evidence of profiled hemodialysis efficacy in the treatment of intradialytic hypotension.

In the last 10 years the percentage of dialysis patients suffering from clinical intradialytic intolerance has greatly increased. Profiled hemodialysis (PHD) is a new technical approach, alternative to standard hemodialysis (SHD) for the treatment of intradialytic symptomatic hypotension. It is based on intradialytic modulation of the dialysate sodium concentration, using a dialysate sodium concentration profile elaborated by a new mathematical kinetic model. The aim of PHD is to reduce the intradialytic blood volume decrease, thanks to a dialysate sodium profile, which allows a reduction in the plasma osmolarity decrease, thereby boosting intravascular fluid refilling. This work aims at clinically validating the PHD technique, by testing its ability against SHD, to maintain a more stable intradialytic blood volume; this evaluation was supported by monitoring some hemodynamic parameters. Twelve dialysis patients on SHD treatment were selected because of their intradialytic symptomatic hypotension. Twelve SHD (one per patient) and 12 PHD sessions (one per patient) were performed to achieve the same sodium mass removal and body weight decrease on both PHD and SHD. During these sessions we monitored the blood volume variation % by the crit-line (a non invasive blood volume monitoring device), the mean blood pressure and heart rate directly and, finally, the stroke volume and cardiac output indirectly by bidimensional doppler-echocardiography. Comparison of the results obtained with the two techniques shows PHD to achieve a significantly more stable blood volume, blood pressure and cardiovascular function than SHD, in particular during the second and the third hour of the dialysis session.

Hyperdynamic circulation of advanced cirrhosis: a re-appraisal based on posture-induced changes in hemodynamics.

Little is known about the effect of posture on the circulatory abnormalities of advanced cirrhosis. We evaluated the systemic hemodynamics, measured by Doppler-echocardiography, atrial natriuretic factor, plasma renin activity and plasma norepinephrine, in 10 patients with cirrhosis and ascites and 10 healthy controls, after 2 h of standing and during lying down for a further 2 h. Standing hemodynamic patterns of controls and patients with cirrhosis did not differ significantly. The latter, however, showed higher plasma renin activity, norepinephrine and atrial natriuretic factor. The assumption of the supine position led to greater increases in cardiac index and atrial natriuretic factor, and reduction in systemic vascular resistance in patients with cirrhosis. Norepinephrine and plasma renin activity declined in both groups to a similar extent, while heart rate only slowed in controls. Thus, after 2 h in the supine position, patients with cirrhosis showed hyperdynamic circulation with increased cardiac index and heart rate and reduced systemic vascular resistance. Norepinephrine, plasma renin activity and atrial natriuretic factor were also elevated. The hyperdynamic circulation in advanced cirrhosis appears during or is enhanced by lying down. This finding suggests that this syndrome is, at least in part, attributable to excessive blood volume translocation towards the central area. However, the persistent activation of renin-angiotensin and sympathoadrenergic systems suggests that a concomitant reduced vascular sensitivity to vasoconstrictors concurs in its development.

[Late thrombolysis in acute myocardial infarct: short and long term effects on left ventricular function]. / La trombolisi tardiva nell'infarto acuto del miocardio: effetti a breve e lungo termine sulla funzione ventricolare sinistra.

Although the efficacy of intravenous thrombolysis in the treatment of acute myocardial infarction has been widely proved, some uncertainty concerning the "temporal window" of administration still persists. The aim of the present investigation was to study whether the late administration of a thrombolytic agent (6 or more hours after the onset of symptoms of acute myocardial infarction) offers any short or long-term advantages with regards to left ventricular function and clinical outcome. We studied 100 consecutive patients at their first episode of myocardial infarction, admitted to Coronary Unit within 24 hours of the onset of symptoms. Of these patients, 62 were administered rt-PA (44 patients within the 6th hour, and 18 between the 6th and 24th hour after the onset of symptoms) and the 38 remaining patients, who did not receive the thrombolytic agent (due to concerns with respect to possible complications), constituted the control group (18 admitted within 6 hours and 20 between 6 and 24 hours). All patients underwent serial electrocardiograms, and echocardiograms upon admission and at discharge to assess the ejection fraction, the asynergy score and the percentage of ischemic area. Furthermore, the survivors were invited for a follow-up examination one year after their acute initial episode. Seven cases of heart failure occurred, before discharge, among the control patients admitted 6 to 24 hours after onset of symptoms, compared with no cases in the subgroup of patients treated with rt-PA during the same time period (p = 0.0068).(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term cardiac adaptation to severe haemodilution: an echocardiographic study in normal and hypertensive subjects.

In order to avoid transfusion risks and optimize blood bank resources, in recent years many blood sparing techniques have been proposed, including severe haemodilution. The aim of this study is to assess the pattern of normal haemodynamic and cardiac adaptation to severe haemodilution in patients undergoing major orthopaedic surgery and refusing blood transfusions for religious reasons (the patients were Jehovah's Witnesses). Two-dimensionally guided M-mode echocardiograms were performed at baseline and 4 days after major orthopaedic surgery in 26 Jehovah's Witnesses (age 61 +/- 11 years), with normal regional and global baseline left ventricular function and no valvular disease. Left ventricular (LV) volumes were estimated by using the Teichholz formula. From the latter, we calculated ejection fraction and stroke volume, cardiac output (stroke volume x heart rate), and total peripheral resistance estimated as mean arterial pressure by cuff sphygmomanometer x 80/cardiac output. On the basis of LV mass (ASE-cube corrected by Devereux), two groups were identified: non-hypertrophic (LV mass index < 110 g.m-2 in women and < 130 g.m-2 in males) and hypertrophic. In the 19 patients without LV hypertrophy, haemoglobin decreased from 13.5 +/- 1.6 (mean +/- standard deviation) g.dl-1 (at baseline) to 8.7 +/- 1.3 post-operation (P < 0.01), and peripheral vascular resistances fell from 2131 +/- 450 to 1278 +/- 310 (dyne.s.cm-5) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The hemodynamic status of preascitic cirrhosis: an evaluation under steady-state conditions and after postural change.

To assess the hemodynamic status of patients with compensated cirrhosis, mean arterial pressure, cardiac index and peripheral vascular resistance and markers of central (plasma concentrations of atrial natriuretic factor) and arterial volemia (plasma norepinephrine concentration, plasma renin activity) were studied in 10 patients and 10 healthy control subjects under steady-state conditions (after 2 hr of standing) and after assumption of the supine position (30, 60, and 120 min). After standing, neither hemodynamics nor markers of effective volemia differed significantly between controls and patients. By evaluating the areas under the curve during the 2 hr of supine posture, the increase in cardiac output and plasma natriuretic factor and the decrease in peripheral vascular resistance were greater in patients (2.59 +/- 0.43 [S.E.M.] L/min/hr; 32.8 +/- 7.2 pg/ml/hr -1,103 +/- 248.4 dyn.sec/cm5/hr, respectively) than in controls (0.53 +/- 0.24 L/min/hr, p = 0.005; 17.4 +/- 4.7 pg/ml/hr, p = 0.005; -265.5 +/- 206.2 dyn.sec/cm5/hr, p = 0.02). The declines in heart rate, plasma norepinephrine concentration and plasma renin activity did not differ significantly. Mean arterial pressure did not significantly change. Our results suggest that during periods of upright posture, cirrhotic patients in the preascitic stage, who are known to have expanded blood volume, compensate for dilatation of the splanchnic vascular bed through total hypervolemia. The latter becomes excessive during recumbency, leading to supernormal increases in venous return, central volemia and cardiac index. The decline in peripheral vascular resistance appears to be a compensatory mechanism to maintain steady arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

[Mexiletine in patients with progressive infarction and reduced ventricular function: anti-arrhythmic efficacy and hemodynamic effects]. / Mexiletina per os in pazienti con pregresso infarto e ridotta funzione ventricolare: efficacia antiaritmica ed effetti emodinamici.

Reduced left ventricular function and ventricular arrhythmias are the main risk factors associated with sudden death in patients with previous acute myocardial infarction. Antiarrhythmic therapy may have side-effects on myocardial contractility and sometimes makes the arrhythmia itself worse, especially when the pump function is seriously compromised. The aim of this study was to evaluate the efficacy of oral mexiletine as well as any modifications in left ventricular function by means of ambulatory ECG monitoring and angiocardiography with Tc 99m, at rest and after the handgrip test, in 20 patients with previous myocardial infarction and ventricular arrhythmias who were grouped into NYHA class II and class III. The mexiletine therapy lasted three weeks. Both classes showed a significant decrease in the number of ventricular extrasystoles/hour and in the number of couples (p less than 0.01). The decrease in the number of the ventricular runs proved to be higher in the general analysis (p less than 0.01) than in each NYHA class (p less than 0.05). At the end of the study, significant modifications were not observed either in the end-diastolic and end-systolic volumes, or in the ventricular ejection fraction.

[Clinical indications for performing Doppler ultrasonography of the extracranial carotid vessels. A series of 805 subjects]. / Indicazioni cliniche all'esecuzione dell'ecografia associata a Doppler dei vasi carotidei extracranici. Una casistica di 805 soggetti.

Duplex scanning of the extracranial carotid vessels is a highly reliable medical investigation for identifying atherosclerotic or other pathology in this vascular region. The introduction of this technique into hospital practice has posed the problem of when it is indicated. The present study has shown that almost half the examinations carried out (45.2%) were requested on the basis of what were defined as "general" symptoms (vertigo, lipothymia, migraine, etc.); this group showed a low prevalence of atheromatous plaques. 22.7% of the examinations were requested as a control in the presence of atherosclerosis in another vascular region (coronaries, arteries of the lower extremities, etc.) and in these patients the prevalence of carotid stenosis was high or very high. Patients examined subsequently to a neurological episode came to 15.3% of the total. There was a high prevalence of carotid atheromatous lesions. Numerous controls were requested in subjects with type 2A and 2B hyperlipoproteinaemia (6.7% of the total) with a prevalence of atheromatous lesions higher than the homogeneous-for-age group. A limited number of patients (2%) underwent the study following visual disturbances of presumable ischaemic origin. The prevalence of carotid stenoses in these subjects is high. Patients who underwent carotid TEA (8.1%) represent a special group in whom intervention brings a general improvement although the percentage of vessel restenosis exceeds 20%.

Association of serum IgA and C4 with severe atherosclerosis.

To assess the possible involvement of humoral immunity in diffuse atherosclerosis, IgG, IgA, IgM, C3 and C4 were measured in the sera of 23 atherosclerotic subjects (at least 3 stenoses greater than 75% in the arteries of the limbs and neck, as assessed by panangiography) and of 20 controls (possible stenoses less than 40% documented by arteriography of the aortic arch and epi-aortic branches and "normal" response to exercise stress testing and Doppler ultrasonography of the arteries of the lower limbs). Age (59-69) and sex distribution did not differ significantly in the 2 groups. The following serum concentrations were higher in the atherosclerotic subjects than in the controls: C4 (28.7 +/- 6.5 (1 SD) vs. 23.4 +/- 3.8 mg/dl; P = 0.0013); IgA (323.3 +/- 155.0 vs. 210.3 +/- 87.9 mg/dl; P = 0.0020); and C3 (126.3 +/- 16.9 vs. 111.0 +/- 18.9 mg/dl; P = 0.0109). To assess whether these parameters were independently associated with atherosclerosis, a multiple logistic regression was performed, also including other variables which differed between the atherosclerotic group and the control group with P values less than 0.20 (cigarette smoking, arterial hypertension, body mass index, serum HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, serum triglycerides, IgG and IgM). In multivariate analysis only IgA (P = 0.0012), C4 (P = 0.0072), cigarette smoking (P = 0.0141) and serum triglycerides (P = 0.0177) were independently associated with atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial infarction and histamine release.

On the basis of previous data suggesting the involvement of cardiac histamine in ischemic heart disease (IHD), we evaluated plasma histamine (H) and creatine-kinase isoenzyme (CK-MB) level in cardiac and healthy subjects. 20 patients with acute myocardial infarction (AMI) (10 developing AMI in Hospital, thus making possible the detection of plasma H level before acute event), 10 patients with IHD not developing AMI and 10 presumably healthy subjects were admitted to the study. 15 of all patients with AMI showed a correlated H and CK-MB trend during AMI reaching the highest peak 24 hours after onset of pain. 7 of the patients with IHD who developed AMI in Hospital showed a slightly higher plasma H level, before AMI, than those with IHD who did not develop AMI. A possible role of histamine in the pathogenesis of AMI is discussed.