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Cardiovascular Research 2000 45(1):163-171; doi:10.1016/S0008-6363(99)00319-3
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Copyright © 2000, European Society of Cardiology

Cardiovascular reflex responses induced by epicardial chemoreceptor stimulation

Juan Cinca* and Antonio Rodrìguez-Sinovas

Experimental Cardiology Laboratory, Cardiology Service, Hospital Vall d’Hebron, Autonomous University of Barcelona, Barcelona, Spain

* Corresponding author. Tel.: +34-93-489-4031; fax: +34-93-489-4032 jcinca{at}hg.vhebron.es


   Abstract
Top
 Abstract
1 Introduction
 2 Cardiovascular reflexes...
 3 Cardiovascular reflexes...
 4 Cardiovascular reflexes...
 5 Cardiovascular reflexes...
 References
 
The cardiac mechano- and chemoreceptors are broadly distributed in the myocardium and coronary vessels. A portion of these receptors extends over the epicardium and pericardium and therefore can be excited by mechanical or chemical stimuli directly applied to the surface of the heart. Excitation of epicardial receptors by topical application of chemical compounds elicits a variety of reflex cardiovascular responses, without the vascular or systemic effects of the drug administered systemically. A considerable number of studies has used the epicardial sensory field as a tool to delineate the functional characteristics of the cardiac afferent neurones in normal as well as in pathological conditions. In this review we analyze the cardiovascular reflex responses induced by epicardial application of a variety of substances like bradykinin, nicotine, muscarine, isoprenaline, adenosine, potassium chloride, capsaicin, prostaglandins or substance P in physiological models and also in models with acute myocardial ischemia or heart failure. The data highlight the contribution of the epicardial sensory neurites to the overall control of the cardiovascular system and, on the other hand, strengthen the need for further investigations directed to better elucidate the reflex cardiovascular responses that may develop in patients with pericardial abnormalities.

KEYWORDS Autonomic nervous system; Ischemia; Vasoactive agents; Vasoconstriction/dilation


   1 Introduction
Top
 Abstract
 1 Introduction
2 Cardiovascular reflexes...
 3 Cardiovascular reflexes...
 4 Cardiovascular reflexes...
 5 Cardiovascular reflexes...
 References
 
The sensory nerve terminals extending over the surface of the heart conform a sensitive field that has been utilized by many investigators to study the interplay between the autonomic nervous system and cardiac function in normal as well as in pathological conditions. Epicardial application of chemical compounds excites local myocardial receptors without the intravascular or systemic effects of these substances administered into the circulatory system.

In the 10th volume of Cardiovascular Research, Staszewska-Barczak et al. [1] analyzed the reflex responses elicited by epicardial bradykinin, an algesic compound naturally released in the acute ischemic myocardium [2,3], to study the pathophysiology of anginal pain during acute myocardial ischemia. The study by Staszewska-Barczak et al. [1] showed that epicardial application of bradykinin to chloralose anesthetized dogs induced a reflex rise of the arterial pressure and heart rate (Fig. 1) both of which were potentiated by concurrent acute myocardial ischemia. Potentiation of the response to bradykinin during coronary occlusion was abolished by indomethacin but reappeared after treatment with prostaglandin PGE. Thus, these authors suggested that bradykinin and prostaglandins, acting in concert, may excite the nociceptors involved in ischemic anginal pain sensation [1,4].


Figure 1
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  		Fig. 1 Cardiovascular effects of increasing doses (0.02, 0.1, 1.0, and 5.0 µg) of bradykinin applied to the epicardium in an anesthetized dog. The drug induces a dose dependent increase in blood pressure, heart rate, renal vasoconstriction evidenced by a drop in renal blood flow (RBF), and femoral vasodilation manifested by an increased femoral blood flow (FBF). Modified from Staszewska-Barczak et al. [1].

 
Since the work by Staszewska-Barczak et al. [1], a substantial number of contributions in the field of neurocardiology has been made based on the study of cardiovascular reflexes induced by chemical stimulation of the epicardium. In this review we focus on the potential role of the epicardial sensory neurites in cardiovascular control in normal as well as in abnormal physiological conditions.


   2 Cardiovascular reflexes stemming from the epicardium
Top
 Abstract
 1 Introduction
 2 Cardiovascular reflexes...
3 Cardiovascular reflexes...
 4 Cardiovascular reflexes...
 5 Cardiovascular reflexes...
 References
 
2.1 Anatomical background
Application of chemical compounds to the surface of the heart may stimulate afferent neurones with sensory neurites in the epicardium and pericardium. Afferent neurones with sensory neurites in the heart are located in nodose and dorsal root ganglia [5] and they influence, via central interconnecting neurones, the parasympathetic and sympathetic cardiac efferent preganglionic neurones which synapse with cardiac efferent postganglionic neurones (Fig. 2). Moreover, a population of cardiac afferent sensory neurones also exists in intrathoracic extracardiac and intrinsic cardiac ganglia [6] which interact with cardiac efferent postganglionic sympathetic and parasympathetic neurones forming feedback loops [7,8].


Figure 2
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  		Fig. 2 Diagram showing the cardiac afferent and efferent neuronal pathways involved in the reflex cardiovascular responses elicited by epicardial application of chemical compounds.

 
2.1.1 Afferent neurones
Vagal afferent axons associated with myocardial receptors ascend in the vagal nerves to the nodose ganglion [5] and reach the nucleus of tractus solitarius. From this structure, neurones interface with the nucleus ambiguus and other vasomotor center through interneurones to affect preganglionic efferent vagal and sympathetic nerves in the bulbospinal tracts.

Sympathetic afferent neurones are associated with multiple receptive fields (heart, esophagus, bronchus). These fibers course in the dorsal roots to reach dorsal root ganglion neurones which, in turn, influence neurones in the spinal cord. The latter influence neurones in the medullar vasomotor center which affect sympathetic efferent neurones.

2.1.2 Efferent neurones
Parasympathetic efferent neurones are located in the nucleus ambiguus of the medulla [9] and in the dorsal motor nucleus. They project axons to parasympathetic postganglionic neurones in the intrinsic cardiac plexus.

Sympathetic preganglionic neurones in the spinal cord connect to postganglionic neurones through the right and left cranial thoracic ganglionic chains. Sympathetic efferent postganglionic neurones are located in paravertebral ganglia, middle and superior cervical ganglia, mediastinal ganglia, and intrinsic cardiac ganglia [10].

2.1.3 Intrinsic cardiac plexus
Like canine [11] and porcine [12] hearts, the human atria and ventricles [13] contain collections of ganglia associated with nerves (ganglionated plexuses) which are consistently observed in five atrial and five ventricular regions. The most important ganglionated plexuses are located in the superior and posterior surface of the atria, in the proximity of the aortic root, and in areas close to the origin of the right and left coronary arteries [13]. The intrinsic cardiac ganglionated plexuses contain afferent neurones, efferent vagal and sympathetic fibers, and interconnecting neurones as shown by direct electrical stimulation in dogs [14]. Intrinsic cardiac afferent neurones are associated with mechano- and/or chemoreceptors some of which connect via major mediastinal nerves with the superior intrathoracic extracardiac ganglia (mediastinal, middle cervical, and stellate ganglia). Intrinsic neurones demonstrate fast Na+- and slow Ca2+-mediated action potentials [15], are sensitive to exogenous H2O2 and to locally produced oxygen-derived free radicals [16], induce pressor responses upon electrical stimulation [17], and intervene in cardiac regulation through a variety of receptors [18].

2.1.4 Local circuit neurones
These neurones intervene in much of the processing that occurs within the intrathoracic nervous system by interconnecting neurones within one ganglion as well as neurones in different intrathoracic ganglia [10]. The intrinsic cardiac nervous system also possesses neurones that project axons to neurones in other intrinsic cardiac ganglia [13].

2.2 Chemical epicardial stimulation
This section reviews the cardiovascular responses elicited by epicardial application of a variety of compounds, including chemicals like potassium chloride or specific neuroreceptor agonists.

2.2.1 Nicotine
The neural response elicited by stimulation of epicardial receptors with nicotine was described in the early 1960s by Kulaef in closed chest rabbits and cats anesthetized with urethane [19]. Using contact electrodes attached to cardiac neural branches originating in the vagus nerves, Kulaev demonstrated that epicardial application of nicotine increased both the ‘fast activity’ commonly recorded in vagal branches at the level of the azygos vein, and the ‘slow activity’ recorded close to vagal afferent fibers from the ventricles. More recently, neuronal recordings of spontaneously active in situ epicardial neurones of anesthetized dogs [20], have confirmed that these intrinsic cardiac neurones increase their activity after exposure to nicotine (Fig. 3). The neuronal response to nicotine may persist after cardiac decentralization thus suggesting that inputs from higher nervous centers are not necessary for some intrinsic neurones to generate activity [20]. The latter study also shows that neuronal responses are not influenced by tachyphylaxis to repeated epicardial administration of nicotine. However, tachyphylaxis may occur when nicotine is administered into the coronary circulation [21]. The presence of nicotinic receptors in intrinsic cardiac neurones has been demonstrated by intracellular recordings showing that hexamethonium blocked most of the spontaneous excitatory postsynaptic potential-like depolarization in dogs [22].


Figure 3
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  		Fig. 3 Effects of local application of nicotine to a neurally intact preparation of an anesthetized dog. (A) Baseline recording of the ECG, left ventricular pressure (LVP) and neuronal activity. (B) Nicotine induced a slowing of heart rate accompanied by an increase in neuronal activity (the neural unit generates 2–4 action potentials/cardiac cycle. Modified from Huang et al. [20].

 
In association with the neuroexcitatory action, epicardial application of nicotine induces a decrease of blood pressure [19,23] which is greatest when the compound is applied to midposterior regions of the left ventricle [23]. The vasodepressor response was inhibited either by bilateral vagotomy or, as shown by Staszewska-Barczak et al. [1], by blocking epicardial neural fiber transmission with local infiltration with lignocaine. The latter observations are consistent with previous studies suggesting that receptors excited by nicotine are subserved by vagal afferent axons coursing centrally in epicardial tissues [24].

2.2.2 Bradykinin
Application of bradykinin to the epicardium excites cardiac sympathetic afferent fibers [25,26] as well as vagal afferent neurones [27]. Extracellular recordings of neuronal activity have evidenced that bradykinin increases the activity of afferent sensory neurones located in the dorsal root ganglia [26,28] and also afferent sensory neurones located in the nodose ganglion [29]. Most of sympathetic dorsal root ganglion neurones with epicardial neurites respond to both mechanical and chemical stimuli with bradykinin, substance P or purinergic compounds [28]. By contrast, cardiac afferent neurones in the nodose ganglion respond more actively to chemical than to mechanical stimulation [10].

The cardiovascular response induced by epicardial application of bradykinin is not unique. A rise in systemic arterial pressure and an increase in heart rate was observed in dogs [1] as well as in cats with sinoaortic denervation and vagotomy [30]. By contrast, a decrease in blood pressure, a slowing of heart rate, and a reduction of renal sympathetic nerve activity was observed in dogs submitted to vagotomy and sinoaortic denervation [31]. The rise in systemic pressure induced by epicardial bradykinin is subserved by cardiac sympathetic, capsaicin-sensitive afferent neurones [32] since this pressor response was inhibited by chronic administration of capsaicin in anesthetized guinea pigs [32]. Moreover, Staszewska-Woolley et al. [33,34] have demonstrated that the reflex tachycardia and pressor effects induced by epicardial application of bradykinin in dogs are inhibited by superfusion of the epicardium with selective bradykinin B2 receptor antagonist. Thus, these authors suggest that excitation of cardiac sympathetic afferent neurones by bradykinin is mediated by specific type B2 kinin receptors.

The nonuniform reflex response to epicardial bradykinin may be the result of a simultaneous activation of cardiac vagal and sympathetic afferent neurones because vagotomy increases the hemodynamic effects induced by intracoronary administration of bradykinin [35]. It is unlikely that differences in the cardiovascular reflex response induced by bradykinin were due to an heterogeneous distribution of the bradykinin sensitive afferent neurones in the left ventricle because the vasopressor effect of bradykinin was comparable in all left ventricular sites explored in anesthetized dogs [23,36].

The increase in sympathetic renal nerve activity induced by epicardial bradykinin may impair glomerular filtration rate and excretion of sodium and potassium [37]. Thus it has been suggested that in certain pathophysiological conditions associated with the release of bradykinin, such as occurs during acute myocardial ischemia, the cardiac sympathetic afferent axons can influence central neuronal control of blood volume and pressure.

2.2.3 Muscarinic agonists
The existence of muscarinic synapses in the intrinsic cardiac plexus was suggested by the observation that microinjection of the muscarinic agonist bethanechol chloride in atrial ventral ganglionated plexus of dogs [20], modified the activity of in situ epicardial neurones (Fig. 4). Further evidence for muscarinic modulation in intrinsic neurones is afforded by studies showing that stimulation of pericoronary nerves with topical application of metacholine induces a drop in systolic left ventricular pressure and dP/dt in chloralose anesthetized pigs [38]. This effect was inhibited by previous disruption of pericoronary nerve transmission with phenol or by pretreatment with atropine [38]. In the same porcine model, stimulation of epicardial neurites by topical application of metacholine also induced a reflex cardiac depressor response accompanied by bradycardia, AV nodal conduction block, and salivary secretion.


Figure 4
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  		Fig. 4 Local application of bethanechol to a neurally intact preparation of an anesthetized dog. As compared with control (A) the drug (B) induces suppression of neuronal activity an a slight decrease of the heart rate without appreciable variations in left ventricular pressure (LVP). Modified from Huang et al. [20].

 
Muscarinic receptors have been found overlapping the cholinergic nerve fibers in intrinsic cardiac ganglia, AV conduction system, and vena cava and pulmonary veins in rat heart [39,40]. M1 muscarinic receptor agonists depolarize the cell membrane [41] and modulate spontaneous release of acetylcholine in rat basal forebrain [42]. By contrast, M2 muscarinic receptor agonists induce hyperpolarization of neuronal cell membrane [43] and modulate the Ca2+ current of central neurones [44]. An extensive review of the muscarinic receptor mechanisms involved in regulation of neuronal ionic currents has been recently published [45].

2.2.4 Adrenoceptor agonists
Intrinsic cardiac neurones contain {alpha}-adrenoceptors [46] and β-adrenoceptors [47] and are capable of synthesizing and degrading catecholamines [48]. Microinjection of isoproterenol in cardiac ganglionated plexus of dogs modified the activity of about half of explored in situ epicardial neurones and this was associated with increases in heart rate and LV pressure. Likewise, dobutamine administered to intrinsic cardiac neurones within the ventral right atrial ganglionated plexus also resulted in prolonged enhancement of cardiac contractility in anesthetized dogs [49]. The cardiodynamic responses elicited by β-adrenoceptor stimulation of intrinsic cardiac neurones are presumably due to direct or indirect activation of efferent cardiac sympathetic neurones. The capability of intrinsic cardiac neurones to directly generate responses to β-adrenergic stimulation (i.e. without the need for inputs from higher neural centers) is suggested by the fact that even after cardiac decentralization, a substantial number of intrinsic cardiac neurones still respond to isoproterenol [20]. Ventricular arrhythmias may develop in association with the increase in activity of intrinsic neurones exposed to isoprenaline [50]. Likewise, we have observed that application of isoprenaline to the pericoronary nerves in chloralose anesthetized pigs induces a positive inotropic effect and triggers ventricular arrhythmias (Fig. 5, personal unpublished data).


Figure 5
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  		Fig. 5 Effects of topical application of isoprenaline to the pericoronary nerves of the left anterior descending coronary artery on ECG, regional myocardial shortening (ultrasonomicrometry), left ventricular pressure (LVP), LV dP/dt, and coronary blood flow in a chloralose anesthetized pig. The drug induces an increase in LVP, LV dP/dt, and coronary blood flow which is immediately followed by the occurrence of a ventricular tachycardia 90 s after isoprenaline application (personal data).

 
2.2.5 Capsaicin
Staszewska-Woolley et al. [33] have reported that epicardial application of capsaicin in anesthetized dogs induces reflex increases in arterial pressure and heart rate which in contrast to bradykinin are not inhibited by selective bradykinin B1 or B2 receptor antagonists. The same authors also showed that the response to epicardial capsaicin was abolished by sectioning the upper thoracic white rami communicans and stellectomy, being unaffected by bilateral vagotomy [51]. These data indicate that canine capsaicin sensitive afferent neurones may be spinal sympathetic in origin.

2.2.6 Other compounds
Epicardial application of potassium chloride induces reflex increase in blood pressure and heart rate in anesthetized dogs [33] and also excitatory cardiac responses associated with an increased renal nerve activity in chloralose anesthetized cats with sinoaortic denervation and vagotomy [30]. However, when the cardiac sympathetic and vagal cardiac nerves are intact, potassium chloride may produce excitation, inhibition or no change in sympathetic outflow [30].

Afferent neurones with sensory neurites in the epicardium that are located in nodose and dorsal root ganglia increase their activity after exposure to substance P [28,52]. Some of these neurites contain substance P receptors because neuronal activity is suppressed by substance P antagonist spantide [28] and, moreover, specific binding sites of substance P have been found by in vitro autoradiography in cardiac parasympathetic ganglia [53]. Substance P receptors also exist in some coronary arteries in guinea-pig hearts which mediate the vasodilator response induced by this compound [53].


   3 Cardiovascular reflexes stemming from the pericardium
Top
 Abstract
 1 Introduction
 2 Cardiovascular reflexes...
 3 Cardiovascular reflexes...
4 Cardiovascular reflexes...
 5 Cardiovascular reflexes...
 References
 
The pericardium may be involved in various reflex cardiovascular responses because it possesses a rich sensory network which can be excited by compounds released in the pericardial space. On the other hand, the pericardium may attenuate the activity of the left ventricular mechanoreceptors in pathophysiological situations of ventricular overload [54]. The sensory receptors in the pericardium associated with nodose ganglion afferent neurones possess 5-hydroxytryptamine type 3 (5-HT3) receptors [55,56] and, as shown by Staszewska-Woolley et al. [57], the pericardial sensory neurites associated with sympathetic afferent axons display capsaicin sensitivity. The pericardial sensory neurites do not respond to local application of atrial natriuretic peptide [56], substance P, or calcitonin gene-related peptide [57].

Studies conducted in different animal species have disclosed the ability of the pericardium to produce substances like prostanoids, especially 6-keto-PGF1 alpha, and prostacyclin [58,59]. Release of these substances in the pericardial space can stimulate the intrinsic cardiac neurones thereby giving rise to local reflex hemodynamic responses which might modulate cardiac function in pathophysiological conditions. The neural effects of prostaglandins released into the pericardial fluid may result either from stimulation of receptors in the sympathetic and vagal afferents or from inhibition of presynaptic noradrenaline release from postganglionic sympathetic nerves [60]. The inhibitory effect of PGE1 on the release of noradrenaline induced by electrical stimulation of sympathetic efferent neurones was more marked at low stimulating frequencies [61] and was not affected by activating prostaglandin synthesis [62]. The substances released in the pericardial space may theoretically excite both epicardial and pericardial chemoreceptors, but studies comparing the cardiovascular responses elicited by separate stimulation of these two sensory fields have shown that differences may exist [63]. Indeed, the reflex drop in blood pressure and heart rate induced by activating parasympathetic afferent neurones with nicotine occurs only when epicardial but not pericardial sensory neurites are stimulated. By contrast, application of bradykinin on either of these two regions stimulates sympathetic afferent neurones giving rise to a reflex increase in blood pressure and heart rate. The reflex hemodynamic response elicited by pericardial stimulation with bradykinin can be inhibited by local superfusion with the bradykinin B2 receptor antagonist Hoe 140 [64] or, on the contrary, can be enhanced by locally formed prostanoids [65]. Inflammatory pericardial diseases may be associated with a local release of bradykinin and thereby a sympathetic pressor reflex can develop [63]. On the other hand, formation of prostanoids to various pericardial stimuli may exert a negative effect on efferent cardiac sympathetic neural drive [66] and affect the tone of epicardial arteries [67]. The effects of neural interventions may be also affected by intrapericardial administration of extraneous substances (i.e. hexamethonium or tetrodotoxin) [68,69] or by the application of defibrillating shocks via implantable patches [70].

The type of anesthesia may influence the reflex responses to pericardial chemoreceptor stimulation since it has been reported that pericardial application of bradykinin induces a cardioexcitatory reflex in awake and in chloralose anesthetized rats, whereas a cardiodepressor response is seen in barbiturate anesthetized animals [71]. General anesthesia is used in most of the studies reviewed in this manuscript thus it is noteworthy that reflex responses induced by stimulation of epicardial sensory neurites in experimental models cannot be entirely extrapolated to the clinical situation.


   4 Cardiovascular reflexes subserved by epicardial chemoreceptors in heart failure
Top
 Abstract
 1 Introduction
 2 Cardiovascular reflexes...
 3 Cardiovascular reflexes...
 4 Cardiovascular reflexes...
5 Cardiovascular reflexes...
 References
 
Intraneural recordings (microneurography) in patients with heart failure have revealed an increased sympathetic nerve activity [72–74] which is associated with a low efferent parasympathetic nerve tone [75]. Cardiac afferent sympathetic neurones appear to mediate both the reflex sympathetic excitation and the inhibition of vagal efferent activity in heart failure [76]. A positive correlation between the increased sympathetic efferent neural activity and the plasmatic levels of norepinephrine has been found in patients with heart failure [72,73]. Thus, the increased sympathetic nerve firing in congestive heart failure largely accounts for the marked increase in norepinephrine spillover from the heart [77], although a reduction in NO in the central nervous system may contribute as well [78].

Epicardial application of chemical stimuli has been used in experimental models of heart failure to assess the integrity of various cardiopulmonary reflexes. Stimulation of sympathetic afferent neurones associated with epicardial sensory neurites by bradykinin in dogs with pacing-induced heart failure has shown that failing hearts display greater increases in renal sympathetic nerve activity, higher arterial pressure, and faster heart rate than nonfailing hearts [79]. The enhancement of sympathetic efferent neuronal activity in response to epicardial bradykinin in dogs with heart failure was attenuated by treatment with indomethacin [79] thus suggesting that prostaglandins released in heart failure [80] may potentially mediate the enhanced responsiveness to epicardial bradykinin. Baseline renal sympathetic nerve activity is also increased in dogs with pacing-induced heart failure [81]. By contrast, resting discharge of cardiac vagal chemosensitive endings is preserved in dogs with heart failure [82].


   5 Cardiovascular reflexes subserved by epicardial chemoreceptors in myocardial ischemia
Top
 Abstract
 1 Introduction
 2 Cardiovascular reflexes...
 3 Cardiovascular reflexes...
 4 Cardiovascular reflexes...
 5 Cardiovascular reflexes...
References
 
Acute myocardial ischemia activates local mechano- and chemoreceptors subserved by vagal and sympathetic afferent neurones, resulting, respectively, in reflex inhibition or excitation of sympathetic activity and cardiovascular function [83–85]. The complex reflex responses induced by acute myocardial ischemia have been extensively reviewed elsewhere [10,86].

Epicardial application of adenosine potentiated the increase in afferent sympathetic nerve activity induced by the coronary artery occlusion in cats, thus suggesting that adenosine is a possible mediator of the ischemic cardiac pain [87,88]. The increase in sympathetic afferent nerve activity by adenosine [28,89] is likely mediated by adenosine A1 receptors [86,90]. However, other studies performed in ischemically sensitive afferent neurones located in both ventricles of anesthetized cats have failed to show activation of afferent sympathetic neurones by epicardial application of adenosine [91]. The allogenic effect of adenosine is potentiated by substance P [92] and this may explain the severity of cardiac ischemic pain during acute myocardial infarction since substance P is released in the infarction region. The ischemic cardiac pain is perceived when the activity from the afferent sensory neurones reaches the hypothalamus and projects bilaterally to specific cortical areas [93]. For this reason, anginal pain may be attenuated by interfering the spinothalamic tract activity with direct electrical stimulation of spinal cord [94]. Afferent fibers with mechanosensitive endings in or near the coronary arteries appear to subserve cardiac pain during intraluminal coronary catheter balloon angioplasty [95].

During the acute phase of coronary artery occlusion, a series of experiments in dogs have shown that epicardial application of bradykinin or nicotine over the ischemic area and also over areas distal to the infarction, failed to induce, respectively, the reflex increase or the reflex decrease in arterial pressure [96,97]. Likewise, brief periods of ischemia attenuated the response of ischemia-sensitive sympathetic afferent fibers to epicardial stimulation with adenosine in cats [98]. By contrast, no abnormalities on conduction in the intrinsic cardiac nerves overlying and distal to an acute transmural infarction were seen during electrical stimulation of the epicardium for at least 12 h postinfarction in dogs [99]. Therefore, altered responsiveness to epicardial application of chemical compounds may be due to primary receptor alterations than to an absence of epicardial axonal function. Chronic transmural myocardial infarction is associated with alterations in autonomic neural innervation of the bordering noninfarcted myocardium in dogs [96], pigs [100] and humans [101]. In addition to chemoreceptors, the mechanosensitive neurites are also damaged in areas of myocardial infarction as indicated by the impairment of the reflex responses induced by changes in left ventricular filling pressures in dogs [102].


   Acknowledgements
 
Supported by grants from Fondo de Inversiones Sanitarias (FIS 98/0430), Mataró TV3, and from our institution (PRHG 38/99).


   References
Top
 Abstract
 1 Introduction
 2 Cardiovascular reflexes...
 3 Cardiovascular reflexes...
 4 Cardiovascular reflexes...
 5 Cardiovascular reflexes...
 References
 

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