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Biomedical subjects

M Pagani

Publications and source records attributed to M Pagani.

At least 181 records · Page 10Linked to original sources
PubMed1985

Characterization of alpha 2-adrenoceptor binding properties of imidazoline-like drugs, azoloazepine derivatives and beta-phenethylamine-like drugs in human platelet membranes.

To characterize the agonist profile of alpha 2-adrenoceptor agonists (imidazoline-like drugs, azoloazepine derivatives, beta-phenethylamines-like drugs) on human platelets, the characteristics of alpha 2-adrenoceptors (KD, Bmax) have been evaluated and the affinity constants measured by displacement technique and computer-assisted analysis of the curves. Furthermore, since alpha 2-adrenoceptor agonists interact with the post-synaptic receptors in a calcium-operated channel, whether the effect of calcium-entry inhibitors (verapamil, nifedipine, diltiazem) is related to a competition with alpha 2-receptors has also been examined. By Scatchard analysis, it was calculated that in human platelets alpha 2-adrenoceptors have KD = 3.45 nM and Bmax = 247 fmol (mg protein)-1. As far as the potency is concerned, imidazoline-like drugs were the most potent agonists in human platelet alpha 2-adrenoceptors (guanabenz IC50 = 8.6 +/- 0.8 X 10(-8), B-HT 920 IC50 = 2.9 +/- 0.3 X 10(-7), (-)-adrenaline IC50 = 3.4 +/- 0.5 X 10(-7)). Among the calcium-entry inhibitors only verapamil antagonized [3H]rauwolscine binding: the effect was stereospecific, (-)-D 600 being more potent than (+)-D 600. Nifedipine and diltiazem did not affect alpha 2-receptor binding. It is concluded that human platelets alpha 2-receptors share the agonist potency profile of other tissues containing alpha 2-receptors (brain, pre-synaptic junction), and that among calcium-entry blockers only verapamil can antagonize alpha 2-agonists. Nifedipine and diltiazem do not appear to interact stereospecifically with alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1985

Analysis of the pressor sympathetic reflex produced by intracoronary injections of bradykinin in conscious dogs.

The reflex hemodynamic effects of intracoronary bradykinin were tested in 20 conscious instrumented dogs. When the experiments were performed after full recovery from surgery and anesthesia, graded doses (10-300 ng/kg) of bradykinin always produced graded pressor responses, in the absence of any pain reaction. At the maximum pressor response obtained with 100 ng/kg, mean arterial pressure rose 28 +/- 3% from 89 +/- 4 mm Hg, left ventricular pressure 20 +/- 3% from 121 +/- 2 mm Hg, heart rate 30 +/- 4% from 88 +/- 5 beats/min, rate of change of left ventricular pressure 18 +/- 3% from 2812 +/- 65 mm Hg/sec (P less than 0.01). Higher doses of bradykinin did not produce greater responses. The magnitude of the response was similar when the injection was performed in either the left anterior descending (change in mean arterial pressure 29 +/- 3%) or circumflex (change in mean arterial pressure 27 +/- 2%) coronary artery. The reflex nature of the response was proved by its disappearance after appropriate pharmacological blockades; moreover, after vagotomy, the pressor rise was maintained, the heart rate response was reduced (change in heart rate 10 +/- 2%), and the inotropic response was enhanced (rate of change of left ventricular pressure 24 +/- 3%). This suggested that the afferent pathway of the pressor reflex was in the sympathetic nerves and that a subordinate vagal depressor reflex was also operative. No pain reaction was obtained even when injecting very large amounts (1000-2000 ng/kg) of bradykinin, which, instead, induced arterial hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1985

Simultaneous analysis of beat by beat systemic arterial pressure and heart rate variabilities in ambulatory patients.

The analysis of power spectral density (PSD) or RR variability in the electrocardiogram (ECG) has suggested that, in the early phase of essential hypertension, sympatho-vagal interaction is characterized by a sympathetic predominance. Recently, we have developed a high fidelity, direct arterial pressure ambulatory recording system which allows a beat by beat computer analysis of arterial pressure and heart rate. A microminiature tip transducer (Millar, diameter 0.8 mm) is inserted percutaneously into the radial artery and connected to a Holter two-channel magnetic tape recorder. The tip transducer has a wide band pass (> 1 kHz), excellent stability (congruent to 2 mmHg/24 h) and does not require a perfusion line. The overall frequency response of the entire recording-reproducing system is better than 20 Hz (-3 dB). The ECG and pressure signals are analysed with automatic autoregressive modelling algorithms to provide a quantitative estimate of blood pressure and heart rate variability through the computation of the PSD. In seven hypertensive patients, systolic arterial pressure and variance were higher during the day (157 +/- 9 mmHg and 122 +/- 9 mmHg2) than during the night (122 +/- 4 mmHg and 30 +/- 3 mmHg2). The PSD of RR and of systolic arterial pressure consisted of a predominant low frequency peak (congruent to 0.09 cycles/beat) during the day, and two peaks at low and high (congruent to 0.25 cycles/beat) frequency during the night. While RR variance was similar during both day- and night-time, a predominant low frequency peak was observed during the day.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1984

Global versus regional myocardial ischaemia: differences in cardiovascular and sympathetic responses in cats.

The cardiovascular and sympathetic responses to occlusions of the left main ("global" ischaemia) or distal left anterior descending ("regional" ischaemia) coronary artery were studied in 19 anaesthetised cats with chronic sinoaortic baroreceptor denervation. "Global" ischaemia, before vagotomy, resulted in a significant reduction of mean arterial pressure (MAP), left ventricular pressure (LVP), and LVdP/dtmax while sympathetic efferent impulse activity was significantly augmented during the initial 15 +/- 2 s of occlusion (early phase) and, vice versa inhibited during the subsequent 20 +/- 2 s of occlusion (late phase). Vagotomy did not modify the haemodynamic responses, however, a significant increase in sympathetic discharge was detectable during the whole occlusion period (early and late phases). "Regional" ischaemia, before vagotomy, resulted in a significant increase in sympathetic neural discharge and MAP, with no changes in left ventricular function. After vagotomy the occlusion elicited a significant increase in MAP, LVP, LVdP/dtmax and efferent sympathetic neural activity. These excitatory responses were abolished after the interruption of a large part of the cardiac sympathetic afferents. Thus coronary artery occlusion induced haemodynamic and sympathetic reflex responses that were dependent upon the interaction of opposite influences mediated by the simultaneous activation of cardiac vagal and sympathetic afferents. The extent of "ischaemic myocardium" represented a determinant factor for the prevailing type of neural response.

Action Potentials↗
PubMed1984

Power spectral density of heart rate variability as an index of sympatho-vagal interaction in normal and hypertensive subjects.

Instantaneous heart rate reflects sympatho-vagal influences on pace-maker activity. Hence computer analysis of heart rate variability might provide a quantitative index of that interaction. The power spectral density (PSD) estimate of heart rate variability was obtained in normal controls and in uncomplicated hypertensives, both at rest and during a non-hypotensive sympathetic stimulus (tilting). In normal controls PSD shows three major peaks of frequencies P1 = 0.07, P2 = 0.12, P3 = 0.25 cycles/beat. P1, which is associated with sympathetic activity, represents only a minor portion of total variability at rest, while becoming predominant with tilting. P2 and P3 are associated with vagal activity, and represent the major part of variability at rest, while they are reduced by tilting. In hypertensive patients PSD is altered, as P1 is already predominant at rest and increases only slightly with tilting. Thus PSD of heart rate variability is capable of detecting an early alteration in sympatho-vagal balance of cardiac control present in uncomplicated hypertension.

Adult↗
PubMed1983

The role of the sympathetic nervous system in congestive heart failure.

Congestive heart failure is usually accompanied by cardiovascular signs of an increased sympathetic and a decreased parasympathetic efferent activity. A current hypothesis for these autonomic changes holds the baroreceptor mechanisms mainly responsible for this complex neural reflex pattern together with a decreased responsiveness of cardiac vagal afferent ffibers. An alternative hypothesis is proposed here. Afferent sympathetic fibers with sensory endings in the atria and in the pulmonary veins are progressively excited by volume load. In cats with a chronic spinal section at C8, breathing spontaneously, an infusion of saline induces a reflex tachycardia through a sympatho-sympathetic neural circuit. In chronic dogs with intact cardiovascular innervation, the stimulation of aortic or cardiac sympathetic afferent fibers elicits an excitatory sympathetic reflex leading to hypertension and tachycardia; in addition, the sensitivity of baroreflexes is markedly reduced. Therefore, in congestive heart failure, especially in the absence of hypotension, the reflex excitation of the sympathetic outflow and the inhibition of the vagal efferent activity directed to the heart could be due to reflex mechanisms mediated by sympathetic cardiovascular afferents.

Animals↗
PubMed1982

A positive feedback sympathetic pressor reflex during stretch of the thoracic aorta in conscious dogs.

The role of pressor sympathetic reflexes in circulatory control was investigated in conscious dogs. Animals were previously instrumented with a 6- to 8-cm rigid core cannula covered by an inflatable rubber cylinder in the thoracic aorta, a pressure catheter implanted in the aorta above the cannula, and a second catheter inserted into the aorta below the cannula through a femoral artery. Two piezoelectric crystals were positioned at opposing adventitial sites to measure aortic distension with ultrasound techniques. After recovery from surgery, the diameter of the aortic segment surrounding the cannula was increased by 9.6 +/- 0.4% from 16 +/- 1 mm by inflating the rubber cylinder, without obstructing blood flow. Mean aortic pressure rose 31 +/- 3% from 100 +/- 3 mm Hg and heart rate 20 +/- 3% from 91 +/- 3 beats/min (P less than 0.01). The pressor response was abolished by alpha-adrenergic blockade (phentolamine 1 mg/kg, iv). The heart rate response was reduced either by beta-blockade (propranolol 1 mg/kg, iv) or muscarinic blockade (atropine 0.2 mg/kg, iv) and abolished by their combination. During aortic stretch, the sensitivity of the baroreflex was reduced 57 +/- 7% from 18 +/- 2 msec/mm Hg (P less than 0.01). The pressor response was increased by 49 +/- 8% after bilateral carotid sinus nerve section and vagotomy. These excitatory reflex responses were obtained in absence of any pain reaction. Thus, in the conscious dog, aortic distension within physiological ranges induces a potent pressor sympathetic reflex with positive feedback characteristics. Such a pressor reflex not only occurs in the presence of functioning baroreflexes, but is also capable of reducing their sensitivity.

Adrenergic alpha-Antagonists↗
PubMed1981

Functions of afferents in cardiovascular sympathetic nerves.

This paper contains data and discussion of the role of afferents in the sympathetic trunks from the cardiovascular complex that evoke autonomic reflex action. A description is given of these cardiovascular reflexes induced by afferents of the sympathetic trunks in neurally intact as well as spinal animals. A positive feedback hypothesis is also proposed.

Afferent Pathways↗
PubMed1981

A sympathetic hypertensive reflex from the heart of conscious dogs.

1. The aim of the present experiment was to study in conscious animals the effect of chemical stimulation of cardiac sensory innervation by bradykinin, a physiological substance known to activate both vagal and sympathetic cardiac sensory nerve endings, at doses devoid of systemic haemodynamic effects. 2. In conscious dogs with implanted catheters bradykinin (100 ng/kg) injected into a cannulated branch of the left coronary artery induced significant (P less than 0.01, n = 5) reflex increases in mean arterial pressure and heart rate as well as increases in left ventricular pressure, left ventricular dP/dt max. and coronary blood flow. 3. These changes were obtained in the absence of pain reactions. 4. The concept, derived from experiments on anaesthetized animals, that chemical stimulation of the intact sensory supply of the heart always elicits a cardiovascular depressor reflex mediated by cardiac vagal afferents has to be modified, as pressor sympathetic reflexes may occur after an appropriate stimulus to the fully innervated heart of conscious dogs.

Animals↗
PubMed1980

Alpha adrenergic vasoconstriction and nitroglycerin vasodilation of large coronary arteries in the conscious dog.

The effects of methoxamine and nitroglycerin on measurements of large vessel (left circumflex) coronary dimensions were examined in eight conscious dogs using an ultrasonic dimension gauge, and total coronary resistance was calculated from measurements of arterial pressure and coronary blood flow. Methoxamine (50 mug/kg per min), after transiently increasing left circumflex coronary dimensions, induced sustained reductions in left circumflex diameter (9+/-2%) and external (18+/-4%) and internal (27+/-5%) cross-sectional areas, at a time when mean arterial pressure rose by 65+/-5%, left ventricular dP/dt had decreased only slightly, and heart rate and mean coronary blood flow remained at control levels. Calculated large vessel and total coronary resistances rose similarly, i.e., by 108+/-29 and 92+/-14%, respectively. Methoxamine reduced coronary arterial wall stiffness from control at comparable stress levels, although at any common radius, wall stiffness was augmented substantially. Nitroglycerin (25 mug/kg) induced an initial decrease in coronary dimensions along with the fall in arterial pressure. However, left circumflex coronary dimensions then rose, reaching a maximum 5 min later at a time when left circumflex coronary blood flow was reduced and heart rate and left ventricular dP/dt were at control levels. At this time, significantly different effects were observed on large vessel coronary resistance, which fell by 18+/-2%, and on total coronary resistance, which rose by 11+/-4%. Thus, in the conscious dog, large coronary vessels not only react passively to changes in aortic pressure but also undergo substantial active changes. Alpha adrenergic stimulation is sufficiently powerful to reduce cross-sectional area, despite the opposing elevation of distending pressure.

Animals↗
PubMed1979

Positive feedback sympathetic reflexes and hypertension.

A pressor reflex that can be elicited from the thoracic aorta in conscious dogs is described. Distension of the aorta excites sympathetic afferent fibers and results in an increase in arterial blood pressure because of increased sympathetic outflow to the heart and blood vessels. The reflex center for this positive feedback mechanism is located in the spinal cord and, when the reflex is activated, it can modulate other negative feedback control systems.

Animals↗
PubMed1979

A sympathetic pressor reflex in the conscious dog.

1. The effects of mechanical activation of aortic sympathetic sensory fibres have been studied in conscious dogs. 2. A cannula covered by an inflatable rubber balloon, previously implanted in the descending thoracic aorta, was used to stretch the aortic walls without obstructing blood flow. 3. Aortic stretch significantly increased mean arterial blood pressure and heart rate from control values in the absence of pseudo-affective reactions. 4. This response indicates that positive feedback sympathetic reflexes are operative in the conscious, fully innervated animal.

Animals↗
PubMed1979

Depressed responsiveness to vasoconstrictor and dilator agents and baroreflex sensitivity in conscious, newborn lambs.

The effects of vasoconstrictors and vasodilators were compared in conscious, newborn lambs and adult sheep instrumented with electromagnetic flow probes on the ascending aorta and catheters in the thoracic aorta. Methoxamine, angiotensin II, norepinephrine, nitroglycerin and isoproterenol were administered intravenously to evaluate their effects on arterial pressure, cardiac output and systemic vascular resistance (SVR). The difference in response between adults and newborns was most apparent with methoxamine. Methoxamine, 400 micrograms/kg, i.v., which increased mean arterial pressure by 57 +/- 6% and SVR by 278 +/- 27% in newborn lambs, caused greater increases (p less than 0.01) of 81 +/- 8% and 1418 +/- 141%, respectively, in the adults. Responses also differed significantly between newborn and adult animals to norepinephrine, angiotensin II, nitroglycerin and isoproterenol. In a second group of animals in which smaller amounts of methoxamine and isoproterenol were injected directly into the terminal aorta, changes in terminal aortic flow and resistance were examined. Again, both vasoconstrictor and vasodilator responses were more marked in adults than in newborns. Finally, the sensitivity of the arterial baroreceptor reflex was evaluated by comparing the regression of pulse interval (PI) on systolic arterial pressure (SAP) after an intravenous dose of methoxamine in conscious, adult and newborn animals. The PI/SAP slopes in adult sheep, 45.4 +/- 3.5 msec/mm Hg, were significantly greater (p less than 0.01) than in newborn lambs, 11.7 +/- 2.2 msec/mm Hg.

Angiotensin II↗