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Biomedical subjects

G Grassi

Publications and source records attributed to G Grassi.

At least 55 records · Page 3Linked to original sources

Effects of ageing on the cardiopulmonary receptor reflex in normotensive humans.

This study examined the effects of ageing on the cardiopulmonary receptor regulation of vasomotor tone in skeletal muscle and renin release by the kidney. To this end, the changes in forearm vascular resistance (mean arterial pressure divided by plethysmographically measured forearm blood flow), plasma noradrenaline concentration and plasma renin activity were measured in eight young (23 +/- 2 years, mean +/- s.e.m.) and seven elderly healthy subjects (69 +/- 2 years) during manoeuvres which altered cardiopulmonary receptor activity. The cardiopulmonary receptors were stimulated by increasing central venous pressure through passive leg-raising and deactivated by reducing central venous pressure through non-hypotensive (-15 mmHg) and hypotensive (-40 mmHg) levels of lower body negative pressure. During either manoeuvre, central venous pressure changed by the same amount in both groups, but the reflex changes in forearm vascular resistance, plasma noradrenaline and plasma renin activity were significantly less in elderly subjects. Since the increase in forearm vascular resistance induced by a cold pressor test was comparable in young and elderly subjects, a non-specific depression of cardiovascular responsiveness to neural stimuli can be excluded. Thus, healthy normotensive elderly subjects show an impairment of both vascular and neurohumoral influences exerted by cardiopulmonary receptors. This may be involved in the decreased ability of the elderly to cope with gravity challenges.

Adult

Cardiopulmonary receptor modulation of plasma renin activity in normotensive and hypertensive subjects.

Cardiopulmonary receptors modulate renin release in several animals species. However, their involvement in reflex control of this humoral substance in humans is controversial. Furthermore, no information is available on the alteration of this control in hypertension. We studied the modulation of plasma renin activity (radioimmunoassay) in 12 normotensive subjects and in 12 age-matched subjects with untreated hypertension of mild or moderate degree. Cardiopulmonary receptors were stimulated by increasing central venous pressure (right atrial catheter) and cardiac volume (echocardiographic measurement) through passive leg raising and deactivated by reducing central venous pressure and cardiac volume through lower body negative pressure. The stimuli were maintained for 20 to 30 minutes, and their degree was set to avoid changes in blood pressure (indirect or direct measurements) and heart rate, thus avoiding involvement of arterial baroreceptors. In normotensive subjects, deactivation of cardiopulmonary receptors induced a progressive rise in plasma renin activity and stimulation of cardiopulmonary receptors induced a progressive fall. The reflex gain (ratio between plasma renin activity and central venous pressure or cardiac volume changes) was similar for deactivation and stimulation. During cardiopulmonary receptor deactivation, the gain corresponded to that obtained by dividing the increase in plasma renin by the reduction in central venous pressure induced by tilting. Cardiopulmonary receptor deactivation and stimulation also induced clear-cut changes in plasma renin activity in hypertensive subjects, but the percent magnitude of the reflex plasma renin activity excursion was less than that in normotensive subjects. These observations indicate that cardiopulmonary receptors modulate plasma renin activity in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Cardiopulmonary reflex before and after regression of left ventricular hypertrophy in essential hypertension.

Studies that have examined the cardiopulmonary receptor control of circulation in hypertension have produced conflicting results. In 10 normotensive subjects and in age-matched essential hypertensive subjects without (n = 10) or with left ventricular hypertrophy (n = 12), as well as in seven subjects of the latter group restudied after 1 year of treatment that induced regression of cardiac hypertrophy, we examined the cardiopulmonary reflex by increasing central venous pressure and stimulating cardiopulmonary receptors through passive leg raising and by reducing central venous pressure and deactivating cardiopulmonary receptors through nonhypotensive lower body negative pressure. Reflex responses were measured as changes in forearm vascular resistance (mean blood pressure divided by plethysmographically measured blood flow), plasma norepinephrine concentration, and plasma renin activity. In hypertensive subjects without left ventricular hypertrophy, stimulation and deactivation of cardiopulmonary receptors caused changes in forearm vascular resistance, norepinephrine concentration, and plasma renin activity that were modestly reduced as compared with those in normotensive subjects. However, all these changes were markedly reduced in hypertensive subjects with left ventricular hypertrophy. Following regression of left ventricular hypertrophy, the changes in vascular resistance, plasma norepinephrine, and plasma renin activity induced by cardiopulmonary receptor manipulation all improved markedly. These results demonstrate that cardiopulmonary receptor regulation of peripheral vascular resistance and of neurohumoral variables is impaired in essential hypertension and that the impairment is much more pronounced when this condition is associated with cardiac structural alterations. Therapeutic regression of these alterations, however, leads to a marked improvement of this reflex, with consequent favorable effects on circulatory homeostasis.

Adult

Neural control of circulation before and after intravenous urapidil in essential hypertension.

Drugs interfering with sympathetic influences on the cardiovascular system have been shown to effectively lower blood pressure in hypertension. However, sympathetic cardiovascular control is involved in blood pressure homeostasis, which means that these drugs may produce potential adverse haemodynamic effects that may reduce the benefit of their antihypertensive action. This paper summarises the results of a study in which we examined the effects of urapidil on the arterial baroreflex and the cardiopulmonary reflex in 6 essential hypertensive patients given 25 mg of the drug intravenously. The dose of the drug used caused a marked reduction in arterial blood pressure (direct measurement). However, pressor and depressor responses to carotid baroreceptor deactivation and stimulation (neck chamber device), respectively, were not modified when compared with those observed in the placebo period. This was also the case for increases and reductions in both forearm vascular resistance and plasma noradrenaline (norepinephrine) concentrations induced by deactivating and stimulating cardiopulmonary receptors, respectively. The pressor and tachycardic responses to handgrip and cold exposure were also unaffected by the drug. It is concluded that when administered at a clinically effective dose urapidil does not adversely affect major reflex mechanisms involved in neural cardiovascular regulation. This has favourable implications for the use of the drug in clinical practice.

Antihypertensive Agents

Treatment of allergy to heterologous monocomponent insulin with human semisynthetic insulin. Long-term study.

Eight type II (non-insulin-dependent) diabetic subjects (7 women, 1 man, aged 42-61 yr), initially treated with oral hypoglycemic agents and intermittently treated with conventional insulins, were identified as developing allergic reactions to porcine and mixed-species monocomponent insulin. Allergy was systemic (urticaria and nonthrombocytopenic purpura) and local delayed in two subjects and local immediate or biphasic in six subjects. Lipoatrophy was present in two subjects. After treatment with human semisynthetic insulin (Monotard HM and Actrapid HM), systemic allergy disappeared. Local allergy disappeared in five subjects and was reduced in three subjects. No lipoatrophy occurred in new injection areas. The clinical results were accompanied by a significant decrease in serum insulin-specific IgE after 6, 12, 18, 24, 30, and 36 mo. Insulin-specific IgG showed an evident decrease in five of eight patients, but the difference in mean values was not significant after 6, 18, 24, 30, and 36 mo. With one exception, intradermal skin tests were positive to human, bovine, and porcine insulin before and after human insulin treatment.

Adult

[Analysis and evaluation of blood alcohol values found in victims of fatal traffic accidents in the Parma region (1982-1986)].

The Authors examined the relationship between blood alcohol levels and traffic accident incidence in 340 cases which came under the observation of the Institute of Forensic Medicine from 1982 to 1986. Positive blood alcohol (31.2% of cases) were correlated to age, sex, type of vehicle driven, day and hour of the accident and to influence upon behaviour (greater than or equal to 0.50 g%) and to drunkenness (greater than or equal to 1.50 g%). Positive blood alcohol resulted to be correlated to, in the following order, passengers, drivers, pedestrians, motorcyclists and cyclists. The incidence was also related to evening and night hours, and to the days Saturday, Sunday and Monday. Our results, even if not completely superimposable, from a statistical point of view, do permit a comparison between them and those found in the Literature regarding the casuistry of other forensic anatomo-pathologic studies that define the risk factors related to alcohol consumption and traffic accident risk.

Accidents, Traffic

Reflex control of circulation and angiotensin converting enzyme inhibition in man.

Removal of the facilitating effect of angiotensin II on sympathetic cardiovascular influences may enhance the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors but may also disturb reflexes involved in blood pressure homeostasis. To test this hypothesis in essential hypertensive subjects, the forearm vasomotor response to cardiopulmonary receptor deactivation (lower body negative pressure) was studied before and after acute or prolonged administration of captopril at doses capable of lowering blood pressure and blocking the formation of angiotensin II. After either acute or prolonged captopril administration there was less response (i.e. forearm vasoconstriction) than in the no-drug state. However, in the same subjects, another reflex response to cardiopulmonary receptor deactivation, the increase in plasma renin activity, was not blunted by the drug. Furthermore, the other major reflex responsible for blood pressure homeostasis, the arterial baroreflex, was left unchanged or was even favoured by administration of clinically effective doses of captopril. This finding applied to both the heart rate and the blood pressure modulating ability of the reflex (vasoactive drug and neck chamber techniques, respectively). Thus, reflex control of circulation may be adversely affected by ACE inhibition. However, this does not include all reflex targets and at least one major reflex is preserved following this pharmacological intervention. This may explain why our patients showed no orthostatic hypotension during chronic treatment with ACE inhibitors.

Blood Pressure

Selective cytotoxicity of an oxygen-radical-generating enzyme conjugated to a monoclonal antibody.

The monoclonal antibody 8A, which recognizes a human plasma cell-associated antigen, was covalently linked to xanthine oxidase in a conjugate maintaining both immunological and enzymatic properties. A significant degree of target cell lysis was obtained at an enzyme concentration that was ineffective on non-target cells and on myeloid staminal cells (CFU-GM). The cytotoxic activity was abolished by an excess of antibody, by allopurinol and by superoxide dismutase and catalase. A possible use of the conjugate for bone marrow purging in multiple myeloma patients is suggested.

Antibodies, Monoclonal

Influence of cardiopulmonary receptors on the bradycardic responses to carotid baroreceptor stimulation in man.

Animal studies have shown that arterial baroreflexes are modulated by reflexes originating from the cardiopulmonary volume receptors, and that this modulation consists of a reduction of the inhibitory influence exerted by arterial baroreceptors on the heart and peripheral circulation. This has not been confirmed in man, however, in whom no reduction in the bradycardic response to carotid baroreceptor stimulation has been observed after the mild increase in central venous pressure (right atrial catheter) and cardiopulmonary receptor activity provided by passive leg raising. In seven normotensive subjects carotid baroreceptors were gradedly stimulated by progressively increasing carotid transmural pressure through a neck chamber device, the resulting reflex lengthening in R-R interval being measured in the two-three cardiac cycles immediately after the baroreceptor stimulus. This manoeuvre was performed in control conditions and repeated during a head-out water immersion which increased central venous pressure (right atrial catheter) from 1.5 +/- 0.2 to 12.0 +/- 0.9 mmHg (mean +/- SE), thereby providing a marked increase in the cardiopulmonary receptor stimulus. In the control condition graded stimulation of the baroreceptors caused a progressive lengthening in R-R interval, the maximal effect being + 477.4 +/- 57.2 ms. Immersion increased the R-R interval from 774.2 +/- 3.2 to 961.6 +/- 5.8 ms (P less than 0.01) and reduced mean arterial pressure (cuff measurement) from 96.0 +/- 1.0 to 82.3 +/- 0.9 mmHg. The changes in R-R interval induced by carotid baroreceptor stimulation were virtually identical with those observed in the absence of immersion.

Adult

Calcium antagonists and neural control of circulation in essential hypertension.

Data from animals and from man suggest that calcium antagonists interfere with alpha-adrenergic receptors and that this mechanism may be responsible for some of the vasodilation induced by these drugs. However, alpha-adrenergic receptors play a primary role in baroreceptor regulation of the cardiovascular system and blood pressure homeostasis, which might therefore be adversely affected by calcium antagonist treatment. We addressed this question in 14 essential hypertensives studied before treatment, 1 h after 20 mg oral nitrendipine and 5-7 days after daily administration of 20 mg oral nitrendipine. Blood pressure was measured by an intra-arterial catheter, heart rate by an electrocardiogram, cardiac output by thermodilution and forearm blood flow by venous occlusion plethysmography. Total peripheral and forearm vascular resistances were calculated by dividing mean blood pressure by blood flow values. Plasma norepinephrine was also measured (high performance liquid chromatography) in blood taken from the right atrium. Compared with the pretreatment values, acute nitrendipine administration caused a fall in resting blood pressure, an increase in the resting heart rate and cardiac output, and a fall in resting peripheral and forearm vascular resistance. The resting hypotension and vasodilation were also evident during the prolonged nitrendipine administration, which was, however, accompanied by much less resting cardiac stimulation than that observed in the acute condition. Baroreceptor control of the heart rate (vasoactive drug method) was similar before and after acute and prolonged nitrendipine treatment. This was also the case for carotid baroreceptor control of blood pressure (neck chamber technique) and for control of forearm vascular resistance as exerted by receptors in the cardiopulmonary region (lower-body negative-pressure and passive leg-raising techniques).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Hemodynamic effects of acute and prolonged administration of nitrendipine in essential hypertension.

In six hospitalized subjects with mild or moderate and untreated essential hypertension, we measured mean blood pressure (MBP, brachial artery catheter), heart rate (HR, electrocardiogram), cardiac output (CO, thermodilution), and total peripheral resistance (TPR, MBP divided by CO) at rest and during a cold pressor test (CPT, 60 s), a hand-grip exercise (HG, 40% maximum strength for 90 s), and a cyclette exercise (CE, 50 W for 5 min). The study was performed in a no-drug condition, 1 h after 20 mg oral nitrendipine (aN) and 1 week after daily administration of 20 mg oral nitrendipine (pN). Compared with the no-drug condition, aN reduced resting MBP from 137.3 +/- 7.3 (mean +/- SEM) to 112.3 +/- 9 mm Hg (p less than 0.05), increased resting HR from 72.3 +/- 6.9 to 85.3 +/- 8.8 beats/min) (p less than 0.05), increased resting CO from 6,191 +/- 508, to 8,700 +/- 1,050 ml/min (p less than 0.05), and reduced resting TPR from 1,807 +/- 119 to 1,140 +/- 228 dynes/s/cm5 (p less than 0.05). The reduction in resting MBP and TPR were unchanged by pN, whereas the increase in HR and CO were attenuated by 47 and 42%, respectively (p less than 0.05). Neither aN nor pN altered the hemodynamic responses to CPT, HG, and CE. As a result, the peak MBP and TPR values that were measured during these maneuvers were always lower (p less than 0.05) during aN and pN than in the no-drug condition. Thus, nitrendipine exerts marked antihypertensive and vasodilatatory effects that are evident at rest and during conditions elevating BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Normal and neoplastic plasma cell membrane phenotype: studies with new monoclonal antibodies.

Three monoclonal antibodies (MoAb), named 8A, 8F6 and 62B1, reacting with plasma cell-associated antigens, were characterized. 8A was found to be positive throughout the B cell lineage maturation steps from the immature B-committed CD10+ cell to the plasma cells. 8F6 and 62B1 reactivity is restricted to more mature cells and related lymphoid malignancies. In particular 62B1 appears to be limited to hairy cells and plasma cells. The results show that it is possible to obtain reagents reacting with plasma cells by immunizing mice with cells derived from human multiple myelomas. Furthermore, the obtained results suggest that it is possible to elicit antibodies against antigens which are present throughout all the differentiation steps of the B cell lineage. These new MoAb could help in elucidating the phenotype of the plasma cells and the relationships of multiple myelomas with other B cell proliferative disorders.

Animals

Family study of schizophrenia: exploratory analysis for relevant factors.

Two hundred twenty-nine schizophrenic patients, diagnosed according to DSM-III criteria, and their first degree relatives (except children) were studied. HLA A1 and CRAG A1 antigens were used as markers of probable dopaminergic pathology and, therefore, as possible indicators of genetic homogeneity that might identify subgroups of families with a specific and recognizable liability. Data were subjected to a logistic analysis in which the dependent variable was the presence of schizophrenia spectrum disorders in relatives, and the independent variables were the presence or absence of HLA A1 and CRAG A1 antigens, the sex of the proband, the sex of the relative, the severity of illness in the proband, and the type of relationship. The results for the entire sample demonstrate that the type of relationship, the sex of the proband, and the sex of the relative have significant effects on the risk of disorder in the relatives. In addition, the presence in the proband of one of the CRAG A1 antigens is a valid classification criterion for identifying a relatively homogeneous subgroup of families of schizophrenic patients.

Adolescent

Effects of celiprolol on reflex control of the cardiovascular system in essential hypertension.

We have previously shown that baroreceptor control of the cardiovascular system and the cardiopulmonary receptor control of peripheral circulation are preserved or only moderately reduced during antihypertensive treatment with acebutolol or nadolol, which indicates that treatment with beta blockers with or without intrinsic sympathomimetic activity does not impair fundamental neural mechanisms involved in circulatory homeostasis. In the present study we have investigated the reflex control of circulation before and during antihypertensive treatment with celiprolol, which, in addition to its beta-blocking action, has vasodilator properties that may stem from interference with neural cardiovascular control. In six essential hypertensive subjects we measured blood pressure (intraarterial catheter), heart rate (ECG recording), central venous pressure (right atrial catheter), and forearm blood flow and resistance (plethysmography) before and during alterations in the activity of the arterial baroreceptors obtained by means of lower body suction and passive leg raising. The study was performed before and after 5-7 days of oral administration of celiprolol at 200-400 mg once a day. Compared to the values obtained in the control, condition celiprolol caused a reduction in blood pressure, a slight change in heart rate, and an increase in forearm blood flow, which indicated the occurrence of a clear-cut forearm vasodilatation. The heart rate responses to arterial baroreceptor manipulation were unchanged by celiprolol which reset the carotid baroreflex so that its tonic restraint on blood pressure increased despite the hypotension induced by the drug. The inhibitory restraint tonically exerted by the cardiopulmonary receptors on peripheral circulation was also increased by celiprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Acebutolol

Control of circulation by arterial baroreceptors and cardiopulmonary receptors in hypertension.

This article reviews observations made on reflex control of circulation in essential hypertension and in a few models of experimental hypertension. It is emphasized that a wide consensus exists on the fact that baroreceptor control of heart rate is impaired in essential hypertension and that this occurs not only in severe but also in mild and borderline hypertensive conditions. On the other hand, baroreceptor control of blood pressure is much less affected by chronic elevations in arterial blood pressure due to central or peripheral factors that differentially affect cardiac and vascular responses to the vagus and the sympathetic drive, respectively. Cardiopulmonary receptor control of peripheral circulation and renin release is also little affected by hypertension, and the suggestion has been made that its sensitivity may even be enhanced in early hypertensive stages and then undergoes a subsequent reduction as cardiac hypertrophy develops. Finally, the possible consequences of preservation of reflex control of circulation in hypertension are discussed. It is speculated that this phenomenon may be in part responsible for the similar percentage of blood pressure oscillations that can be observed in normotensive and borderline, moderate, and severe hypertensive subjects.

Animals

[Maternal drug dependence and infections. Perinatal mortality].

Some toxic and infectious factors affecting pregnant drug addicts are analysed. Harmful effects on the foetus and the newborn are assessed. The problem of perinatal mortality as a result of maternal drug addiction is examined. A review of the literature reveals the mortality rate to be high.

Antigens, Viral

Reflex cardiovascular regulation in humans.

Although studies of the cardiovascular control exerted by arterial baroreceptors in man are limited by technical and ethical problems, the variable-pressure neck-chamber technique has provided a considerable amount of information about this topic. This paper focuses on the carotid baroreceptor reflex as evaluated by studies using the neck-chamber technique and examines this control in a number of physiological and pathophysiological states. The results of these studies suggest that in normotensive subjects the set-point of the reflex is located eccentrically toward its saturation, which makes this homeostatic mechanism more effective in counteracting a blood-pressure fall than a blood-pressure rise. They also suggest that the concept of an impairment of the arterial baroreflex in aging, exercise, and hypertension, though valid for the baroreceptor control of heart rate, is no longer tenable for the baroreceptor control of arterial pressure. The paper also reviews in humans the effects of arterial baroreceptors on regional circulations and on the excretion of humoral substances such as renin, and compares them with those of the cardiopulmonary receptors. It is suggested that the latter predominate over the former in the reflex modulation of plasma-renin activity, and that this is part of a homeostatic mechanism for blood-volume control.

Blood Pressure