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Biomedical subjects

G Tallarida

Publications and source records attributed to G Tallarida.

At least 19 recordsLinked to original sources

Evaluation of spontaneous baroreflex modulation of sinus node during isometric exercise in healthy humans.

The purpose of this study was to 1) evaluate the baroreflex (BR) modulation of the sinus node during isometric exercise in humans by analyzing the variations in pulse interval (PI) in response to beat-by-beat spontaneous changes in systolic arterial pressure (SAP), thus avoiding external intervention to alter arterial pressure (AP); and to 2) evaluate the specific influence of muscle chemoreflex on the SAP-PI relationship. Sixteen healthy males were studied during rest, handgrip at 30% of maximum voluntary contraction [isometric handgrip (IHG)], post-IHG arrested forearm circulation (AFC), and recovery. AP and PI were measured continuously and noninvasively. A BR response was defined by series of at least three consecutive beats in which SAP and PI of the following beat either increased or decreased in a linear fashion. In nine subjects, forearm (FVR) and calf vascular resistances (CVR) were determined. Mean slope (by linear regression) of SAP-PI sequences did not significantly differ between rest, IHG, and AFC (14.1 +/- 2.0, 12.2 +/- 1.6, and 13.2 +/- 1.4 ms/mmHg, respectively), i.e., BR sensitivity was unchanged. IHG resulted in a rightward shift of the regression line relating SAP to PI. The shift was maintained during AFC, when PI returned to control and AP fell slightly but remained significantly elevated. CVR, which did not change during IHG, significantly increased during AFC, whereas FVR increased during both IHG and AFC, but not significantly. The data indicate that arterial BR is "reset" to a higher operating point during isometric exercise. Muscle chemoreflex appears to be partially involved in this modification.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Myocardial expression of atrial natriuretic factor gene in early stages of hamster cardiomyopathy.

Ventricular cardiomyocytes represent the most important source of atrial natriuretic factor (ANF) in pathological conditions such as congestive heart failure (CHF). It has been suggested that in cardiomyopathic Syrian hamster ventricles the ANF gene can be reactivated during the hypertrophic stage occurring before heart failure. The present study was undertaken to investigate ANF gene expression during early stages of myocardial damage and its distribution throughout atrial and ventricular myocardium in UM-X7.1 cardiomyopathic Syrian hamsters (CMPH) before hypertrophy and cardiac failure occur. Atria, right and left ventricles, and interventricular septum of hearts of 20-23 days old (young) and 90-95 days old (adult) CMPH were studied. The absence of hypertrophy and cardiac failure was preliminarly ascertained by microscopic and hemodynamic evaluation. ANF-mRNA as well as tissue and plasma immunoreactive ANF were assayed. Moreover, ANF secretion pattern was evaluated by immunocytochemical techniques. Young and adult CMPH hearts were in the necrotic stage of myocardial disease, as demonstrated by histopathological evaluation and by decreased wet weights (mg/g body weight) of different heart regions. Hemodynamic assessment showed no significant changes of left ventricular end-diastolic pressure (LVEDP) and a decrease of the left ventricular peak systolic pressure (LVSP) and +dP/dt. Plasma immunoreactive ANF (IR-ANF) levels were higher in young (3-fold) and adult (6-fold) CMPH than in age-matched normal hamsters. A reduced IR-ANF concentration (per milligram protein) was observed in both young and adult cardiomyopathic atria in respect to healthy controls, whereas a higher IR-ANF concentration was present in ventricles. A 3-fold, 6-fold and 20-fold increase of IR-ANF concentration was found in right ventricular free-wall (RV), left ventricular free-wall (LV) and interventricular septum (IVS), respectively. Northern-blot analysis confirmed that IVS was the major site of ventricular ANF-mRNA transcription in both young and adult CMPH. ANF-mRNA was increased also in atria where a faster peptide secretion can be hypothesized to lower tissue IR-ANF concentration. ANF secretion in ventricular myocardium was achieved via constitutive pathway as demonstrated by immunocytochemistry. Different patterns of ANF gene reactivation occur in CMPH myocardium before intraventricular pressure increases and structural hypertrophic modifications are detectable. The extent of ANF gene reactivation in CMPH ventricles parallels the severity of necrotic damage. Moreover, ANF gene expression is heterogeneously distributed throughout the myocardium, suggesting that interventricular septum, the ontogenically youngest heart region, might preserve foetal characters which can be rapidly reactivated in pathological conditions.

Animals↗

Effects of alpha-human atrial natriuretic peptide in guinea-pig isolated heart.

The aim of the present investigation has been to ascertain whether or not atrial natriuretic peptides (ANP) can exert a direct effect on myocardial contractility. Alpha-human ANP (alpha-hANP) concentrations ranging from 1 pM to 50 nM have been used to perfuse guinea-pig isolated hearts in a non-recirculating Langendorff apparatus. A dual concentration-related effect has been induced by alpha-hANP on myocardial function. A maximal increase of +LV dP/dtmax (+56%; P < 0.001) has been observed when guinea-pig hearts were perfused with 100 pM alpha-hANP, whereas a 25% decrease (P < 0.01) occurred with 50 nM alpha-hANP. Similar effects have also been induced by alpha-hANP on the coronary flow rate (CFR). A significant CFR increase (maximal at 10 pM alpha-hANP) was induced by picomolar concentrations of alpha-hANP, whereas a progressive decrease, which was maximal (-28%; P < 0.01) at 50 nM alpha-hANP, was observed with nanomolar concentrations of the peptide. No effects have been observed on heart rate. These results suggest that ANP has direct effects on both vascular and myocardial muscle cells. Coronary vasoconstriction induced by nanomolar concentrations of ANP can contribute to the cardiodepression, whereas ANP in picomolar concentrations can induce a coronary vasodilation which is not coupled with the enhanced myocardial contractility. The latter is the likely expression of a direct effect of the peptide on myocardial function.

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Physiological unloading of cardiopulmonary mechanoreceptors by posture change does not influence the pressor response to isometric exercise in healthy humans.

In recent studies in humans the role of cardiopulmonary baroreflexes in modulating the cardiovascular responses to isometric exercise (somatic pressor reflex) has been investigated by performing static handgrip exercise during deactivation of cardiopulmonary receptors produced by low levels of lower body negative pressure; however, findings from these studies have not been consistent. The purpose of this study was to investigate whether a more physiological unloading stimulus of cardiopulmonary baroreceptors, obtained by sequentially changing posture, could influence the pressor response to somatic afferent stimulation induced by isometric exercise. To accomplish this, ten healthy subjects performed a 2-min isometric handgrip (IHG) at 30% maximal voluntary contraction after 10 min of supine rest and, in rapid sequence, after 10 min of sitting and 10 min of standing, at the time when, owing to their transitory nature, the cardiovascular effects, due to arterial baroreceptor intervention should have been minimal. During IHG arterial pressure (BPa) was continuously and noninvasively measured to quantify accurately the blood pressure response to IHG both in magnitude and time course. Results showed that the pressor response to IHG was not significantly influenced by change in posture, either in magnitude or in time course. The mean arterial pressure increased by 17.4 (SEM 2.5), 18.6 (SEM 1.2) and 17.0 (SEM 1.3) mmHg in supine, sitting and standing [2.3 (SEM 0.3), 2.5 (SEM 0.2) and 2.3 (SEM 0.2) kPa] positions, respectively. Also the heart rate response to IHG was unaffected by change in posture.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Kinetic changes of ethanolamine base exchange activity and increase of viscosity in sarcolemmal membranes of hamster heart during development of cardiomyopathy.

The activity of the phospholipid base exchange enzyme specific for ethanolamine has been measured in cardiac sarcolemmal membrane preparations from Syrian golden and UM-X7.1 cardiomyopathic hamsters. In Syrian golden hamsters, the Km of the enzyme for ethanolamine does not change with age, whereas it almost doubles in membranes from cardiomyopathic animals, from the 30th to the 150th day of age. During the same period, the membrane cholesterol content increases by 68% in cardiomyopathic hamsters, whereas it does not change significantly in the Syrian golden hamster strain. As a consequence, in the adult animal, the cholesterol to phospholipid ratio and the viscosity of sarcolemmal membranes are higher in UM-X7.1 strain than in Syrian golden hamsters. A cause-consequence relationship between the enzymatic changes and the compositional modifications in the sarcolemma occurring in UM-X7.1 hamsters during the development of cardiomyopathy is proposed.

Animals↗

Phospholipid base exchange enzyme activity in sarcolemmal membranes from the heart of cardiomyopathic hamsters.

The activity of phospholipid base exchange enzymes has been evaluated in cardiac sarcolemmal membranes from Syrian Golden hamsters and from a hamster strain (UM-X7.1) characterized by a genetic form of hypertrophic cardiomyopathy. No choline base exchange activity and only a little serine base exchange activity were detected, whereas the ethanolamine base exchange enzyme was found highly active in membranes from both strains. For this reason, the present study is focussed on the ethanolamine base exchange enzyme. The apparent Km for ethanolamine of ethanolamine base exchange enzyme from Syrian Golden membranes and from UM-X7.1 strain membranes are 18 and 32 microM, respectively. The specific activity of the sarcolemmal ethanolamine base exchange enzyme is lower in the UM-X7.1 strain than in Syrian Golden hamsters. The calcium-dependence of the enzyme appears different when the membranes from the two strains are compared. Indeed, after removal of the membrane-bound divalent cations, comparable activities are found in both membrane preparations, whereas, upon addition of Ca2+ to the incubation mixtures, the activity of the enzyme is enhanced in the membranes from Syrian Golden strain more than in those from UM-X7.1 strain. The cholesterol content of sarcolemmal membranes is higher in the cardiomyopathic strain than in the Syrian Golden hamsters. A possible relation between changes of the membrane lipid composition and of the ethanolamine base exchange activity is discussed.

Animals↗

On the role of neural mechanisms in the cardiocirculatory inhibitory action of alpha-human atrial natriuretic peptide in the anesthetized rabbit.

The effects induced by alpha-human 28-amino acid residue atrial natriuretic peptide (alpha-hANP) on arterial pressure, heart rate and vascular resistance, measured as hindlimb perfusion pressure (HPP), were examined in anesthetized rabbits. In particular, the involvement of the autonomic nervous system in mediating the cardiocirculatory effects of alpha-hANP was investigated. Intravenous alpha-hANP (8 micrograms/kg, bolus injection) in anesthetized rabbits caused a sustained decrease in atrial pressure, a transient decrease in HPP and no significant changes in heart rate. After sinoaortic denervation, alpha-hANP produced a greater decrease in arterial pressure and in hindlimb vascular resistance and also a consistent decrease in heart rate. Bilateral vagotomy did not significantly alter the cardiocirculatory responses to alpha-hANP in either normal or in sinoaortic denervated rabbits. Intravenous infusion of alpha-hANP (2 micrograms/kg bolus + 0.2 micrograms/kg per min) did not substantially change the baroreflex cardiocirculatory responses to loading and unloading carotid and aortic baroreceptors with bilateral carotid occlusion and phenylephrine or nitroglycerin bolus injection. In addition, alpha-hANP infusion did not modify the cardiovascular reflex responses to chemical stimulation of neural receptors (sensory endings of group III and IV somatic afferents) in the hindlimb muscles which are primarily mediated by sympathetic nerves in the anesthetized rabbit. Pharmacological blockade of the autonomic nervous system with atropine and guanethidine did not reduce the hypotensive and bradycardic effects caused by alpha-hANP in sinoaortic denervated animals. The results indicate that in anesthetized rabbits: (1) alpha-hANP can induce inhibitory cardiocirculatory responses (hypotension, bradycardia, musculocutaneous vasodilation) which are consistently offset by the sinoaortic baroreceptor system; (2) alpha-hANP does not alter the reflex control of arterial pressure and heart rate by arterial baroreceptors and muscle chemosensitive receptors; (3) activation of cardiopulmonary vagally-mediated depressor reflexes does not contribute to the inhibitory cardiovascular action of alpha-hANP; and (4) inhibitory effects on sympathetic activity do not constitute a significant component of the cardiocirculatory action of alpha-hANP.

Anesthesia↗

[A comparison of the parameters used in determining the anaerobic threshold by a computerized analysis of the indices of breath-by-breath gas exchange].

Anaerobic threshold (AT) determination by gas exchange measurements has to date been performed mostly by visual inspection from plots of ventilatory and gas exchange indexes. Owing to its subjective nature, this approach appears to be somehow arbitrary. Moreover, it still remains undetermined which of the commonly used gas exchange indexes is most reliable in detecting the anaerobic threshold. In the present study we have compared the AT values provided by the gas exchange indexes in common use, each one processed by a computerized method, based on a 2-segments linear regression model. A quantitative analysis of their reproducibility has also been performed. By comparison, the same has been done by using the conventional technique based on visual inspection of plots of the same gas exchange indexes, made by 2 independent observers. The aim of the study was to evaluate whether an objective method of AT detection improves the reliability of anaerobic threshold determination by gas exchange measurements. Eight healthy male subjects performed 2 incremental exercise tests at exhaustion with a 2-week interval. Respiratory exchange data were collected on a breath-by-breath basis. The following gas exchange indexes have been employed: V-slope; VE vs VO2; VE/VO2 vs VO2 or time; PetO2 vs VO2 or time. The latter 2 have been examined coupled with the VE/VCO2 and PetCO2 curves, respectively. By employing the computerized method, there were no significant differences in AT detection among the 4 indexes. The best agreement was between V-slope and VE vs VO2 (delta 15.8 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The role of chemosensitive muscle receptors in cardiorespiratory regulation during exercise.

Several possible mechanisms leading to the cardiorespiratory adjustments to muscular exercise can be considered. Activation of the cardiovascular and respiratory centers may result from: (1) direct or reflex action of circulating metabolites (humoral control); (2) cortical influxes (central drive); (3) nervous impulses from receptors in the contracting muscles (peripheral drive). Information presently available focuses most of the interest upon the muscular drive. Our studies on anesthetized animals (rabbits, dogs) have demonstrated that different types of exercise (dynamic and static) produce two different types of adjustments reflexly elicited by activation of sensory endings of somatic afferents in muscles. Dynamic exercise produces a vasodilatory effect with a decrease in blood pressure and heart rate and an increase in breathing frequency; static exercise provokes an increase in blood pressure, heart rate and depth of breathing. These two patterns of adjustments to exercise are also reproducible, in anesthetized animals, by injecting chemical substances into muscular arteries. Injections of bradykinin, K+ ions and acid solutions evoke cardiorespiratory responses analogous to those produced by dynamic contractions; injections of hypertonic NaCl or glucose evoke an excitatory pattern closely similar to that elicited by isometric contractions. These research studies lead to the hypothesis that two functionally distinct types of chemosensitive receptors (K and P) exist in the skeletal muscles which are activated in proportionally different measures during different types of muscular activity, thus evoking coordinated changes in the cardiovascular and respiratory functions. These studies also strongly support the important role of the peripheral reflex mechanism in governing the circulatory and respiratory systems to perfectly match cardiorespiratory changes to the muscular metabolic needs during exercise.

Animals↗

[Study of the interactions of atrial natriuretic peptides with the autonomic nervous system. Effects on cardiocirculatory and respiratory reflexes caused by activation of chemosensitive muscle receptors].

In order to verify the hypothesis that possible interactions with the autonomic nervous system may contribute to the cardiovascular effects of atrial natriuretic factor (ANF), 9 rabbits were anesthetized to study the effect of the infusion of synthetic human ANP (2 mcg/kg in bolus followed by 0.2 mcg/kg/min for 20 min iv) on the reflex responses induced by intra-arterially injected BK (250 ng) and hypertonic NaCl (10%) or glucose (40%). The infusion of ANP provoked a decrease in systolic (SBP, 14%) and diastolic (DBP, 8%) pressure without any significant changes in heart rate (HR). The injection of BK and hypertonic NaCl into femoral arteries carried out during ANP infusion produced cardiorespiratory response patterns similar to those observed in control conditions. After injecting BK, a fall in SBP (25%), DBP (50%) and HR (16%), and an increase in breathing frequency were observed. After injecting NaCl, an increase occurred in SBP (20%), DBP (25%), HR (10%) and in depth of breathing. In the present experimental conditions, ANP has not been found to be capable of significantly interfering with the reflex pattern of cardiorespiratory responses either from the inhibition or activation of the sympathetic nervous system induced by chemical stimulation of muscle receptors.

Animals↗

[Cardiocirculatory and respiratory reflexes of muscular origin during prolonged experimental dynamic exercise. Effects of sectioning of the sino-carotid and aortic nerves and bilateral vagotomy].

In anesthetized rabbits we have evaluated the effects of denervation of sino-aortic areas and vagotomy on the reflex cardiorespiratory responses during 2 min of contractions of gastrocnemius muscle induced by electrical stimulation of tibial nerve. The following parameters were examined: blood pressure (BP), heart rate (HR), respiratory frequency (f), tidal volume (Vt) and pulmonary ventilation (Ve) while arterial pH, pCO2 and pO2 and end-tidal CO2 (petCO2) were monitored. During steady state of rhythmic contractions we observed a decrease of BP, a slight decrease in HR and marked rise of Ve due to an increase of f with a slight increase of Vt. The sectioning of carotid-sinus, aortic and vagus nerves does not substantially modify the cardiorespiratory responses to muscular exercise; all the responses are abolished from the sectioning of somatic nerves in exercising limbs. The importance of the role of the peripheral nervous control by muscles (peripheral drive) is confirmed in the regulation of cardiorespiratory participation in motory activity, also in the steady state phase of muscular exercise in which components of a chemometabolic or hemodynamic nature could be more effective.

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