G. Peruzzi

Muscle metaboreflex contribution to sinus node regulation during static exercise: insights from spectral analysis of heart rate variability.

BACKGROUND It is currently assumed that during static exercise, central command increases heart rate (HR) through a decrease in parasympathetic activity, whereas the muscle metaboreflex raises blood pressure (BP) only through an increase in sympathetic outflow to blood vessels, because when the metaboreflex activation is maintained during postexercise muscle ischemia, BP remains elevated while HR recovers. We tested the hypotheses that the muscle metaboreflex contributes to HR regulation during static exercise via sympathetic activation and that the arterial baroreflex is involved in the HR recovery of postexercise muscle ischemia. METHODS AND RESULTS Eleven healthy male volunteers performed 4-minute static leg extension (SLE) at 30% of maximal voluntary contraction, followed by 4-minute arrested leg circulation (ALC). Autonomic regulation of HR was investigated by spectral analysis of HR variability (HRV), and baroreflex control of heart period was assessed by the spontaneous baroreflex method. SLE resulted in a significant increase in the low-frequency component of HRV that remained elevated during ALC. The normalized high-frequency component of HRV was reduced during SLE and returned to control levels during ALC. Baroreflex sensitivity was significantly reduced during SLE and returned to control levels during ALC when BP was kept elevated above the resting level while HR recovered. CONCLUSIONS The muscle metaboreflex contributes to HR regulation during static exercise via a sympathetic activation. The bradycardia that occurs during postexercise muscle ischemia despite the maintained sympathetic stimulus may be explained by a baroreflex-mediated increase in parasympathetic outflow to the sinoatrial node that overpowers the metaboreflex-induced cardiac sympathetic activation.

Evaluation of reproducibility of spontaneous baroreflex sensitivity at rest and during laboratory tests

Objective The aim of the present study was to examine the reproducibility of arterial baroreflex sensitivity (BRS) provided by the spontaneous baroreflex method at rest and during laboratory tests. Methods Twenty healthy volunteers were studied 24 h apart, in the same laboratory and under the same environmental conditions, at rest, during active standing, while performing mental arithmetics and during static handgripping. Systolic blood pressure, mean arterial pressure and pulse interval were continuously and non-invasively measured by using a Finapres device. BRS was evaluated by analysing the slopes of spontaneously occurring sequences of three or more consecutive beats in which systolic blood pressure and pulse interval of the following beat both increased or decreased, in the same direction, in a linear fashion. Individual BRS were obtained by averaging all slopes computed within a given test. Results Under each test condition BRS did not differ significantly between the two consecutive days, showing strikingly similar values. The mean group coefficients of variation (CVAR), obtained by averaging individual CVAR, between the two experimental days were 15.0, 13.9, 15.3 and 19.7% for resting, standing, static hand-gripping and mental arithmetic, respectively. No relationships were found between individual CVAR and individual mean arterial pressure, pulse interval and number of baroreflex sequences under any tested condition, on both experimental days. Conclusions These results show that the spontaneous baroreflex method provides good BRS reproducibility under various stimuli that affect the neural control of circulation differently. They also suggest that BRS variability is dependent neither on haemodynamic modifications nor on the degree of baroreflex engagement, but it seems to reflect an inherent feature of the way in which arterial baroreflexes modulate the heart period.

Effects of isokinetic, isotonic and isometric submaximal exercise on heart rate and blood pressure

Abstract The purpose of the present study was to compare arterial pressure (AP) and heart rate (HR) responses to submaximal isokinetic, isotonic and isometric exercises currently employed in physical rehabilitation therapy in terms of both magnitude and time-course. To this aim AP and HR were continuously and noninvasively measured in ten healthy subjects performing isokinetic, isotonic and isometric exercises at the same relative intensity. Isokinetic and isotonic exercises consisted of 30 knee extension/flexion repetitions at 40% of maximal effort. Isokinetic speed was set at 180° · s−1. Isometric exercise consisted of a 60-s knee extension at 40% maximal voluntary contraction. The AP showed a rapid and marked increase from the onset of all types of exercise progressing throughout the exercises. Peak systolic (SAP) and diastolic (DAP) arterial pressure were 190.7 (SEM 8.9) and 121.6 (SEM 7.8) mmHg during isokinetic and 197.6 (SEM 11.2) and 128.3 (SEM 7.7) mmHg during isotonic exercise, respectively. During isometric exercise peak SAP and DAP were 168.1 (SEM 6.3) and 102.1 (SEM 3.7) mmHg, respectively [both lower compared to isokinetic and isotonic exercise (P < 0.05)]. The HR rose abruptly and after five isokinetic and isotonic repetitions it had already increased by about 30 beats · min−1, continuing to rise throughout the exercises. The HR response to isometric exercise was significantly less (P < 0.05) at all times. An immediate fall in AP, undershooting resting levels, was observed at the cessation of all types of exercise, being more marked after isokinetic and isotonic exercise. These results indicate that submaximal exercise of a dynamic type induces greater AP responses than intensity-matched isometric exercise and that even submaximal endurance-type rehabilitation exercise yields an elevated functional stress on the cardiovascular system which could precipitate hazardous events particularly in subjects with unrecognized cardiac diseases.

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.

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.

Effect of postural changes on cardiovascular responses to static exercise in hypertensive human beings.

OBJECTIVE In hypertensive patients, exaggerated increases in vascular resistance and arterial blood pressure have been reported on changing posture from supine to upright. In this study we tested the hypothesis that in hypertensive subjects, upright posture induces an increase in the vasoconstrictor and pressor responses to physical exercise. SUBJECTS AND METHODS We studied 17 males with mild hypertension and 10 sex- and age-matched normotensives. Each performed three bouts of static handgrip at 30% maximum voluntary contraction for 2 min after 10 min of supine rest and, in sequence, after 10 min of sitting and 10 min of standing. Arterial pressure, heart rate and forearm vascular resistance were measured by Finapres and plethysmography, respectively. RESULTS Exercise posture did not affect the mean arterial pressure and heart rate responses to static handgrip. No significant differences in these responses were observed between the hypertensives and the normotensives in any posture. In the hypertensives (n = 12), forearm vascular resistance did not change significantly from resting values during supine and sitting static handgrip but increased significantly during standing static handgrip. In the normotensives, forearm vascular resistance did not change significantly from resting values during static handgrip in any posture. The forearm vascular resistance response to the standing static handgrip was significantly greater in the hypertensives than the normotensives. The algebraic sum of forearm vascular resistance responses to postural change from sitting to standing plus that induced by sitting static handgrip (i.e. additive reflexes) was significantly less than the forearm vascular resistance response to the standing static handgrip (i.e. combined relexes), indicating a facilitatory interaction between exercise and orthostatic stimuli in hypertensives. In contrast, the algebraic sum of the heart rate responses to postural change from sitting to standing plus that induced by sitting static handgrip was significantly greater than the response to standing static handgrip, indicating an inhibitory interaction. CONCLUSIONS In hypertensive patients, physiological orthostasis causes an increased vasoconstrictor response to static exercise, but this is opposed by an inhibitory influence on the heart rate response, with the result that the pressor response to static exercise is unaffected by upright posture.

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

SummaryIn 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 hand-grip 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. Most important, the sum of the separate BPa responses induced by supine IHG and by posture change from supine to sitting (summation of reflexes) was not significantly different from the pressor response observed during sitting IHG (interaction of reflexes). Likewise, the sum of the separate BPa. responses induced by sitting IHG and by changing postures from sitting to standing was not significantly different from the pressor response to standing IHG. These data indicate that, under physiological conditions, cardiopulmonary baroreflexes do not exert a significant role in modulating the reflex pressor drive from muscles during isometric exercise in healthy humans.

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.

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

Abstract 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 (α-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 α-hANP on myocardial function. A maximal increase of +LV dPdtmax (+56%; P P P