Old and new approaches for evaluating autonomic control of circulation in man.
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Autonomic Nervous System↗
Biomedical subjects
G Grassi
Publications and source records attributed to G Grassi.
Ribozymes: structure, function, and potential therapy for dominant genetic disorders.
Some dominant genetic disorders, viral processes and neoplastic disorders base their pathogenicity on the production of protein or proteins that negatively affect cellular metabolism or environment. Thus, the inhibition of the synthesis of those proteins should prevent the biological damage. A promising approach to decreasing the level of the abnormal protein(s) is represented by specific interference with gene expression at the level of mRNA. The specific suppression of the expression of an mRNA can be achieved by using ribozymes. Ribozymes are RNA molecules able to break and form covalent bonds within a nucleic acid molecule. These molecules, with even greater potential advantages than antisense oligodeoxynucleotides, are able to bind specifically and cleave an mRNA substrate. There are advantages to using ribozymes instead of antisense oligodeoxynucleotides. Ribozymes can inactivate the target RNA without relying on the host cell's machinery and they have the capacity to cleave more than one copy of the target RNA by dissociating from the cleavage products and binding to another target molecule. Most of the studies performed to date have described the use of ribozymes as therapeutic agents for viral and cancer diseases. However, some dominant genetic disorders may also benefit from this approach. This is the case for some connective tissue disorders such as osteogenesis imperfecta, Marfan syndrome and the craniosynostotic syndromes.
Genetic Diseases, Inborn↗
Considerations on current and future trials in hypertension.
Conclusive evidence from large-scale epidemiological studies has shown that hypertension is a major risk factor for cardiovascular disease. Large-scale intervention trials have indicated that, by reducing elevated blood pressure values with antihypertensive treatment, the risk can be decreased. Despite the large body of evidence on the protective effects of the blood pressure reduction, several questions concerning the benefit of antihypertensive treatment remain unanswered. This paper briefly reviews the information provided by clinical trials on antihypertensive treatment. It also critically examines the questions that have remained partially or totally unanswered and the trials that are currently addressing them. Focus is directed on the Insight Study which addresses the benefit of antihypertensive treatment in hypertensive subjects with additional cardiovascular risk factors.
Antihypertensive Agents↗
[[Antihypertensive therapy and organ protection].
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Animals↗
[Diabetes mellitus is currently one of the most frequent causes or associated causes of uremia. Data from the Piedmont registry of dialysis and transplantation (update, December 1993)].
A regular dialytic treatment of diabetic patients is until accepted from about twenty years in many areas. Aim of this work was a retrospective analysis of main clinical and survival data of diabetic patients (diabetic nephropathy or diabetes as comorbidous factor = 659 cases) admitted for dialysis in Piedmont (Northern Italy Region about 4,400,000 inhabitants) in the period 1981-1993 (functional recovery and follow-up < 1 month excluded). A progressive increment in incidence of diabetic patients was seen mostly in the aged. At 12/31/1993, 263 of 2404 patients admitted for dialysis were diabetics (10.9%); the majority of them was treated in Hospital Centers with bicarbonate haemodialysis (54.4%), while a small group was treated with CAPD (12.9%). During the years ¿80 was seen a progressive leaving of CAPD as first choice method in this population and in the last period the orienteering is the utilization of mixed methods (diffusive-convective as first choice). As regards the survival are not prominent significant differences between this cohort and the cohort affected by vasculopathy as comorbidous factor (86.2 and 54.2% in diabetics vs 78.6 and 55.2% in patients affected by vasculopathy at 1 and 3 years--p = 0.3481; patients aged 45-64 years). In conclusion the cohort of diabetic patients represent a good marker of the clinical problems of the elder population with high clinic risk, in progressive increasing in our Region.
Adult↗
The incidence of nosocomial infections in a pneumology division and intermediate intensive care unit.
It has been shown that the problem of nosocomial infections is different in each specialist hospital division, and it is important to be aware of the local situation and to identify the specific problems. In order to set up an effective prevention programme and in the setting of a general system of control of nosocomial infection, we studied the incidence of infections and correlated the pathogenic organisms appearing during hospitalization in patients admitted to our Pneumology Division and Intermediate Intensive Care Unit over a period of 12 months. A nosocomial infections incidence of 13% was observed and 75% of these were respiratory, 21% urinary and 4% other infections. Seventy two percent of pathogenic agents were Gram-negative bacilli and 28% Gram-positive cocci. The site-specific rates of infections observed are related to intrinsic (host dependent) and extrinsic (non-host-dependent) risk factors that have not been exhaustively evaluated in the present study. However, the data so far collected will allow us to redirect the resources used in the control of nosocomial infections by targeting efforts at the surveillance of better defined groups of patients and by achieving data more suitable for comparisons between hospitals.
Cross Infection↗
Obesity and the sympathetic nervous system.
Several epidemiological studies have shown that obesity represents an independent risk factor for development of cardiovascular diseases, including hypertension, myocardial ischaemia, and cardiac arrhythmias. Although the metabolic and the haemodynamic alterations occurring in the obese state have been well defined for several years, our knowledge on the sympathetic alterations occurring in this condition is more scarce and controversial. This paper reviews the evidence that human obesity is characterized by abnormalities in sympathetic cardiovascular control, in the light of the results of recent studies performed by employing a sensitive technique to assess sympathetic activity in humans, i.e. microneurography. Evidence is provided that sympathetic overactivity is a common hallmark of the obese state, even when blood pressure levels are within the normal range. It will also discuss the potential mechanisms responsible for this sympathetic activation, suggesting that overweight-related metabolic alterations, such as the insulin resistance state, and abnormalities in sympathetic cardiovascular control exerted by arterial baroreceptors may play a pathogenetic role. Finally, the effects of body weight reduction on the sympathetic overactivity which characterizes the obese state will also be examined.
Energy Intake↗
Sympathetic activation and loss of reflex sympathetic control in mild congestive heart failure.
BACKGROUND: Baroreflex control of sympathetic activity is impaired in severe congestive heart failure (CHF), probably causing the marked sympathetic activation typical of this condition. Little information exists, however, as to whether baroreflex impairment and related sympathetic activation also occur in mild CHF. METHODS AND RESULTS: We studied 19 patients (age, 57.5 +/- 2.2 years, mean +/- SEM) with CHF in New York Heart Association (NYHA) class III or IV and with a marked reduction in left ventricular ejection fraction (LVEF, 30.1 +/- 1.5% from echocardiography) and 17 age-matched patients with CHF in NYHA class I or II and with an only slightly reduced LVEF (44.9 +/- 3.3%) that never was < 40%. Seventeen age-matched healthy subjects served as control subjects. Primary measurements included beat-to-beat arterial blood pressure (with the Finapres technique), heart rate (from ECG), and postganglionic muscle sympathetic nerve activity (MSNA, from microneurography at the peroneal nerve). Measurements were performed at baseline and during baroreceptor stimulation (intravenous phenylephrine infusion), baroreceptor deactivation (intravenous nitroprusside infusion), and cold-pressor test. Baseline blood pressure was similar in the three groups, whereas heart rate was progressively greater from control subjects to patients with mild and severe CHF, MSNA (bursts per 100 heart beats) increased significantly and markedly from control subjects to patients with mild and severe CHF (47.1 +/- 2.9 versus 64.4 +/- 6.2 and 82.1 +/- 3.4, P < .05 and P < .01, respectively). Heart rate and MSNA were progressively reduced by phenylephrine infusion and progressively increased by nitroprusside infusion. Compared with control subjects, the responses were strikingly impaired in severe CHF patients, but a marked impairment also was seen in mild CHF patients. On average, baroreflex sensitivity in mild CHF patients was reduced by 59.1 +/- 5.5% (MSNA) and 64.8 +/- 4.8% (heart rate). In contrast, reflex responses to the cold-pressor test were similar in the three groups. CONCLUSIONS: These results demonstrate that in mild CHF patients the baroreceptor inhibitor influence on heart rate and MSNA is already markedly impaired. This impairment may be responsible for the early sympathetic activation that occurs in the course of CHF.
Adult↗
Alterations of radial artery compliance in patients with congestive heart failure.
Congestive heart failure is accompanied by several hemodynamic alterations. To investigate whether these alterations include reduced arterial compliance, we studied 25 patients (age 57 +/- 2 years, mean +/- SE) with a mild or severe congestive heart failure based on clinical symptoms (New York Heart Association class II vs III or IV) and on echocardiographic alterations of left ventricular diastolic diameter and ejection fraction. Radial artery diameter and blood pressure were continuously measured by Doppler ultrasonography and a finger pressure device, respectively. Compliance was calculated by the Langewouters formula, and compliance values were derived throughout the systolic-diastolic pressure range. The area under the compliance-pressure curve normalized for pulse pressure was used to compare compliance values in the various groups. Data were obtained both in baseline condition and at the release from a 12-minute brachial artery occlusion. Fourteen healthy, age-matched subjects served as controls. Compared with the control group, patients with severe congestive heart failure showed a reduction of baseline compliance index (-48%, p < 0.01). Furthermore, while in control subjects compliance markedly increased after brachial artery occlusion (+43%, p < 0.01), in patients with severe congestive heart failure no increase occurred. No baseline compliance alteration was seen in patients with mild congestive heart failure in whom, however, the postischemic increase in compliance was also significantly blunted (-50% vs controls, p < 0.05). Thus, arterial compliance and arterial compliance modulation are impaired in congestive heart failure. Although more marked in severe congestive heart failure, the impairment is manifest in mild congestive heart failure as well.
Blood Pressure Determination↗
Blood pressure variability and reflex control in the elderly.
Several lines of experimental and clinical evidence collected over the past ten years suggest that the aging process is characterized not only by profound structural cardiovascular alterations, but also by marked functional changes in the reflex mechanisms involved in the homeostatic control of the circulation. This paper will examine how aging affects baroreceptor control of the heart and sympathetic nerve traffic, providing evidence that while the former is markedly impaired in the elderly, the latter is virtually preserved. It will also discuss the age-related alterations in cardiopulmonary receptor function that, under physiological conditions, tonically inhibit sympathetic vasoconstriction tone and renin release from the kidney. Finally, evidence will be provided showing that short- and long-term blood pressure variabilities (and the different components of blood pressure variability) over 24 hours undergo major changes in the elderly. All these alterations in neural cardiovascular control mechanisms have clearcut clinical implications representing a potential marker of the increased cardiovascular risk which characterizes elderly people.
Aged↗
Quantitative analysis of hepatitis C virus RNA in liver biopsies by competitive reverse transcription and polymerase chain reaction.
BACKGROUND/AIMS: The determination of HCV-RNA concentration in liver samples is likely to provide interesting insights for the study of disease progression and for evaluation of the efficacy of anti-viral therapy. METHODS: A procedure was developed for the precise quantification of HCV-RNA in liver biopsies, based on the competitive reverse transcription-polymerase chain reaction technology. This competitive assay consists of the co-amplification of the target RNA with known amounts of a competitor RNA molecule containing the same sequence as the target plus an insertion in the middle, allowing resolution of the two amplification products by gel electrophoresis. RESULTS: The amounts of HCV-genomic-RNA and beta-actin mRNA (the latter being used as an internal standard to overcome the problem of reproducibility of quantitative RNA extraction) were evaluated in liver biopsies of 15 patients affected by hepatitis C virus-positive chronic liver disease at the time of diagnosis. All the patients underwent alpha-interferon therapy for 6 months and were subsequently followed for at least 1 further year after the end of treatment. Viral RNA concentration (which ranged from 2 to 2.7 x 10(5) HCV-RNA molecules per 10(6) beta-actin molecules) directly correlated with the efficacy of treatment, indicating that low levels of viral replication in the liver are associated with a poor response to therapy. CONCLUSIONS: This study suggests that the determination of viral load in the liver is an important prognostic tool for the prediction of the efficacy of alpha-interferon therapy.
Adult↗
Structural cardiovascular alterations and blood pressure variability in human hypertension.
AIM: To evaluate the cardiovascular risk of hypertensive patients in relation to left ventricular hypertrophy, arteriolar hypertrophy and blood pressure variability, and the effects of antihypertensive treatment. LEFT VENTRICULAR HYPERTROPHY: In hypertensive subjects with marked left ventricular hypertrophy, cardiovascular problems are about three times more frequent than in hypertensives who do not have left ventricular hypertrophy. The evidence suggests, however, that a moderate degree of left ventricular hypertrophy may be compensatory and that regression of mild hypertrophy should not necessarily be pursued. ARTERIOLAR HYPERTROPHY: An increased wall to lumen ratio leads to an increase in vascular resistance and thus promotes hypertension. Regression of this alteration with antihypertensive treatment appears to be both beneficial and achievable, although it is not clear whether all antihypertensive agents have the same effect. Moreover, there are methodological problems in determining whether a regression has actually been achieved. BLOOD PRESSURE VARIABILITY: There is evidence to suggest that end-organ damage is more frequent and more marked in hypertensives with greater 24 h blood pressure variability. It appears that antihypertensive treatment does not easily reduce this variability, although the intermittent measurements taken by automatic monitoring devices do not fully reflect patterns of blood pressure variation. It may be that hypertensives with a greater degree of blood pressure variability can obtain a reduction in the magnitude of this variability with antihypertensive treatment.
Antihypertensive Agents↗
Sympathetic activation in obese normotensive subjects.
Human obesity is characterized by profound alterations in the hemodynamic and metabolic states. Whether these alterations involve sympathetic drive is controversial. In 10 young obese subjects (body mass index, 40.5 +/- 1.2 kg/m2, mean +/- SEM) with normal blood pressure and 8 age-matched lean normotensive control subjects, we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (electrocardiogram), postganglionic muscle sympathetic nerve activity (microneurography at the peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography). The measurements were performed in baseline conditions and, with the exception of plasma norepinephrine, during baroreceptor stimulation and deactivation caused by increases and reductions of blood pressure via intravenous infusions of phenylephrine and nitroprusside. Baseline blood pressure and heart rate were similar in obese and control subjects. Plasma norepinephrine was also similar in the two groups. Muscle sympathetic nerve activity, however, was 38.6 +/- 5.1 bursts per minute in obese subjects and less than half that level in control subjects (18.7 +/- 1.3 bursts per minute), the difference being highly statistically significant (P < .02). Muscle sympathetic nerve activity and heart rate were reduced during phenylephrine infusion and increased during nitroprusside infusion, but the changes were about half as great in obese subjects as in control subjects. Thus, even in the absence of any blood pressure alteration, human obesity is characterized by a marked sympathetic activation, possibly because of an impairment of reflex sympathetic restraint. This may be involved in the high rate of hypertension and cardiovascular complications seen in obesity.
Adult↗
Sympathetic modulation of radial artery compliance in congestive heart failure.
Animal studies have suggested that arterial compliance can be modulated by adrenergic influences. Whether this adrenergic modulation also occurs in humans is still a matter of debate. In the present article we address this issue by examining the relationships between sympathetic tone and arterial compliance in a variety of physiological and pathophysiological conditions. We have found that cigarette smoking, ie, an action that produces a marked sympathetic activation, causes a significant reduction in radial artery compliance, as measured by an echotracking device capable of providing continuous beat-to-beat evaluation of this hemodynamic variable. When expressed as compliance index, ie, as the ratio between the area under the compliance-pressure curve and pulse pressure, the reduction amounted to 35.7 +/- 4.8% (mean +/- SEM) and was independent of the smoking-related blood pressure increase. Furthermore, pharmacological stimulation of adrenergic receptors located in the arterial wall was also shown to affect arterial compliance because the radial artery compliance index was markedly reduced (- 29.5 +/- 3.9%) during phenylephrine infusion in the brachial artery at doses devoid of any systemic blood pressure effect. Evidence was also obtained that the relationship between sympathetic activation and arterial compliance has pathophysiological relevance, because in 17 patients with congestive heart failure (New York Heart Association classes II through IV) there was a significant inverse correlation (r = .62, P < .01) between muscle sympathetic nerve activity (directly measured by microneurography in the peroneal nerve) and radial artery compliance.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Angiotensin-converting enzyme inhibition and radial artery compliance in patients with congestive heart failure.
Congestive heart failure is characterized by a clear-cut impairment of arterial compliance of medium-sized arteries, but whether this alteration is irreversible or can be favorably affected by cardiovascular drugs currently used in congestive heart failure treatment is unknown. We studied 9 congestive heart failure patients (New York Heart Association class II; age, [mean +/- SEM] 60.7 +/- 3.3 years) receiving diuretic and digitalis treatment in whom arterial compliance was assessed at the level of the radial artery by an echotracking device capable of measuring the arterial diameter along the entire cardiac cycle. Beat-to-beat arterial blood pressure was concomitantly measured by a Finapres device that allowed diameter-pressure curves and compliance-pressure curves (Langewouters' formula) to be calculated for the entire systolic-diastolic blood pressure range. Arterial compliance was expressed as the area under the compliance-pressure curve normalized for pulse pressure (compliance index). Data were collected before and after 4 and 8 weeks of oral administration of benazepril (10 mg/day). Ten healthy subjects were studied before and after an observational period of 4 weeks (5 subjects) or 8 weeks (5 subjects), and 9 age-matched mildly essential hypertensive subjects studied before and after 4 to 12 weeks of benazepril administration served as control subjects. In congestive heart failure patients, baseline compliance index was significantly less than in normotensive and hypertensive subjects. However, the compliance index showed a marked increase after 4 weeks of benazepril administration (+95.7 +/- 24.9%, P < .05); the increase was also marked after 8 weeks of angiotensin-converting enzyme inhibitor treatment (+77.7 +/- 4.2%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Radial artery compliance in young, obese, normotensive subjects.
Obesity is characterized by a number of cardiovascular alterations, and whether these alterations involve arterial compliance is unknown. In 12 young, obese, normotensive subjects (age, 23.9 +/- 1.3 years; mean +/- SEM) and 12 age- and sex-matched lean control subjects we measured blood pressure, radial artery diameter, and radial artery compliance continuously over the systodiastolic pressure range with a Finapres device and recently developed echo-tracking device. Measurements were obtained at baseline and after prolonged ischemia, that is, when diameter and compliance are increased. Blood pressure values were normal in both groups (obese subjects: 109.2 +/- 4.9/68.2 +/- 2.7 mm Hg; lean control subjects: 108.2 +/- 4.1/60.7 +/- 3.8 mm Hg), but in addition to a marked increase in body mass index (38.5 +/- 0.8 versus 23.1 +/- 0.9 kg/m2, P < .01), obese subjects showed a slight and nonsignificant increase in heart rate (71.1 +/- 3.2 versus 66.7 +/- 3.3 beats per minute, P = NS), increases in left ventricular wall thickness and left ventricular mass index (121.5 +/- 4.8 versus 103.4 +/- 3.3 kg/m2, P < .01), no changes in plasma renin activity and plasma norepinephrine (compared with normal values), and a marked reduction in total body glucose uptake (glucose clamp technique). Obese subjects showed radial artery diameter and compliance values that were greater than those seen in control subjects throughout the systodiastolic pressure range. The differences were 13% (P < .05) and 96% (P < .01), respectively, and both diameter and compliance remained higher in obese than lean subjects after forearm ischemia. In obese and lean subjects baseline radial artery diameter values correlated highly with body weight, body surface area, and body mass index.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Cardiac and vascular structural changes in normotensive subjects with parental hypertension.
OBJECTIVE: To evaluate whether a predisposition to hypertension is associated with early cardiac and vascular alterations. SUBJECTS: Twenty-five normotensive subjects with both parents hypertensive (group 1) and 28 age- and sex-matched control subjects with both parents normotensive (group 2). METHODS: In the two groups the measurements included: clinic blood pressure; left ventricular end-diastolic diameter, septal wall thickness and posterior wall thickness (by echocardiography); minimal forearm and calf vascular resistances (i.e. resistance assessed immediately after prolonged ischaemia, which depends on arteriolar wall thickness); and baseline and postischaemic radial artery compliance-pressure curves over the systolodiastolic pressure range (by echotracking device and finger blood pressure). RESULTS: Group 1 had a slightly higher clinic blood pressure, and septal and posterior wall thickness, than group 2. Minimal forearm vascular resistance was clearly greater in group 1 than in group 2, whereas minimal calf vascular resistance was not significantly different in the two groups. Radial artery compliance was also similar in the two groups. CONCLUSIONS: Parental predisposition to hypertension is accompanied by cardiac and arteriolar structural changes qualitatively similar to those found in hypertensive patients, although arteriolar structural changes do not involve all vascular beds. Arterial compliance is not altered in this condition. Vascular changes may be determined by mechanisms other than blood pressure elevation.
Adult↗
[Changes in the compliance of the radial artery in normotensive subjects with familial hypercholesterolemia].
BACKGROUND: Recent studies have shown that in normotensive hypercholesterolemic subjects endothelial dependent dilatation of arterioles is impaired. METHODS: We studied the effects of hypercholesterolemia on arterial compliance in normotensive subjects of both sexes, with a normal serum cholesterol (n = 8, total serum cholesterol = 209 +/- 7 mg/dl, means +/- SEM), an elevated serum cholesterol (n = 8, 285 +/- 8 mg/dl) and familial hypercholesterolemia (n = 8, 393 +/- 20 mg/dl). All subjects were normotensive and devoid of clinical and laboratory evidence of atherosclerotic lesions. The mean age of the 3 groups was 46.7 +/- 2.5, 51.5 +/- 2.9 and 49.8 +/- 2.9 years respectively. In hypercholesterolemic subjects use of hypolipidemic drugs was stopped 2 months before the study. Arterial compliance was measured from the radial artery by an echo-tracking device capable of providing radial artery diameter and, with the addition of a Finapres device, diameter/pressure and compliance/pressure curves continuously over the systolic-diastolic blood pressure range. RESULTS: Mean arterial pressure was similar in the three groups (84.5 +/- 6.1, 79.8 +/- 2.4 and 73.1 +/- 4.4 mm Hg). Arterial compliance was similar in normocholesterolemic and non familial hypercholesterolemic subjects but it was strikingly reduced (50%) in familial hypercholesterolemic subjects. The reduction was even more evident following prolonged local ischemia because while in the first two groups arterial compliance increased after ischemia, in familial hypercholesterolemia no increase occurred. CONCLUSIONS: Thus, familial hypercholesterolemia is accompanied by a striking CONCLUSIONS: Thus, familial hypercholesterolemia is accompanied by a striking reduction in radial artery compliance, i.e. a marked increase in arterial wall stiffness. This may increase the traumatic effect of blood pressure on the arterial wall, favouring atherosclerosis. The lack of compliance alterations in non familial hypercholesterolemia suggests that this hemodynamic disturbance either occurs when serum cholesterol is more markedly increased or it has a genetic origin.
Analysis of Variance↗