scholarly journals Bradykinin and thromboxane A2 reciprocally interact to synergistically stimulate cardiac spinal afferents during myocardial ischemia

2010 ◽  
Vol 298 (1) ◽  
pp. H235-H244 ◽  
Author(s):  
Liang-Wu Fu ◽  
John C. Longhurst
Keyword(s):  
Myocardial Ischemia ◽  
Nerve Activity ◽  
C Fibers ◽  
First Response ◽  
Complex Process ◽  
Rami Communicantes ◽  
The Individual ◽  
Spinal Afferents ◽  
Cardiac Afferents ◽  
Afferent Response

Myocardial ischemia is a complex process leading to the simultaneous release of a number of mediators, including thromboxane A2 (TxA2) and bradykinin (BK), that activate cardiac spinal afferents. The present study tested the hypothesis that TxA2 and BK reciprocally interact to excite ischemically sensitive cardiac afferents. Nerve activity of single cardiac afferent units was recorded from the left sympathetic chain or rami communicantes (T2–T5) of anesthetized cats. Fifty-two ischemically sensitive afferents (conduction velocity = 0.27–3.35 m/s, 7 Aδ-fibers and 45 C-fibers) were identified. Repeated injections (1 μg) of BK into the left atrium (LA) 4 min after the administration of U-46619 (5 μg into the LA), a TxA2 mimetic, induced a significantly larger cardiac afferent response than the first response to BK (0.61 ± 0.14 to 1.95 ± 0.29 vs. 0.66 ± 0.09 to 2.75 ± 0.34 impulses/s, first injection vs. second injection, n = 8). Conversely, blockade of TxA2 receptors with BM-13,177 (30 mg/kg iv) attenuated the responses of eight other afferents to BK (1 μg into the LA) by 45%. In contrast, repeated BK (1 μg into the LA) induced consistent discharge activity in six separate afferents. We then observed that the coadministration of U-46619 (5 μg) and BK (1 μg into the LA) together caused a total response that was significantly higher than the predicted response by the simple addition of the individual responses. BK (1 μg) facilitated eight cardiac afferent responses to U-46619 (5 μg into the LA) by 64%. In contrast, repeated U-46619 (5 μg into the LA) without intervening BK stimulation evoked consistent responses in seven other ischemically sensitive afferents. Finally, inhibition of cyclooxygenase with indomethacin (5 mg/kg iv) eliminated the potentiating effects of BK on the cardiac afferent response to U-46619 (5 μg into the LA) but did not alter the afferent response to U-46619. These data suggest that BK and TxA2 reciprocally interact to stimulate ischemically sensitive cardiac afferent endings leading to synergistic afferent responses and that the BK sensitization effect is mediated by cyclooxygenase products.

scholarly journals A new function for ATP: activating cardiac sympathetic afferents during myocardial ischemia

2010 ◽  
Vol 299 (6) ◽  
pp. H1762-H1771 ◽  
Author(s):  
Liang-Wu Fu ◽  
John C. Longhurst
Keyword(s):  
Myocardial Ischemia ◽  
Cardiovascular Responses ◽  
P2 Receptors ◽  
Nerve Fibers ◽  
Disulfonic Acid ◽  
Dependent Manner ◽  
P2 Receptor ◽  
C Fibers ◽  
Spinal Afferents ◽  
Cardiac Afferents

Myocardial ischemia activates cardiac sympathetic afferents leading to chest pain and reflex cardiovascular responses. Brief myocardial ischemia leads to ATP release in the interstitial space. Furthermore, exogenous ATP and α,β-methylene ATP (α,β-meATP), a P2X receptor agonist, stimulate cutaneous group III and IV sensory nerve fibers. The present study tested the hypothesis that endogenous ATP excites cardiac afferents during ischemia through activation of P2 receptors. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicates (T2-T5) in anesthetized cats. Single fields of 45 afferents (conduction velocities = 0.25–4.92 m/s) were identified in the left ventricle with a stimulating electrode. Five minutes of myocardial ischemia stimulated 39 of 45 cardiac afferents (8 Aδ, 37 C fibers). Epicardial application of ATP (1–4 μmol) stimulated six ischemically sensitive cardiac afferents in a dose-dependent manner. Additionally, epicardial ATP (2 μmol), ADP (2 μmol), a P2Y agonist, and α,β-meATP (0.5 μmol) significantly activated eight other ischemically sensitive afferents. Third, pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid, a P2 receptor antagonist, abolished the responses of six afferents to epicardial ATP (2 μmol) and attenuated the ischemia-related increase in activity of seven other afferents by 37%. In the absence of P2 receptor blockade, cardiac afferents responded consistently to repeated application of ATP ( n = 6) and to recurrent myocardial ischemia ( n = 6). Finally, six ischemia-insensitive cardiac spinal afferents did not respond to epicardial ATP (2–4 μmol), although these afferents did respond to epicardial bradykinin. Taken together, these data indicate that, during ischemia, endogenously released ATP activates ischemia-sensitive, but not ischemia-insensitive, cardiac spinal afferents through stimulation of P2 receptors likely located on the cardiac sensory neurites.

Histamine Contributes to Ischemia-Related Activation of Cardiac Spinal Afferents: Role of H1 Receptors and PKC

2005 ◽  
Vol 93 (2) ◽  
pp. 713-722 ◽  
Author(s):  
Liang-Wu Fu ◽  
Walter Schunack ◽  
John C. Longhurst
Keyword(s):  
Myocardial Ischemia ◽  
Receptor Agonist ◽  
Visceral Afferents ◽  
Cardiovascular Reflexes ◽  
Dependent Manner ◽  
Endogenous Histamine ◽  
Nociceptive Information ◽  
Spinal Afferents ◽  
Cardiac Afferents

Myocardial ischemia activates cardiac spinal afferents that transmit the nociceptive information leading to chest pain and elicit excitatory cardiovascular reflexes. Previous studies have shown that histamine is increased in coronary sinus blood during myocardial ischemia and that this autacoid stimulates abdominal visceral afferents. The present investigation evaluated the role of endogenous histamine in stimulation of ischemically sensitive cardiac spinal afferents. Nerve activity of single-unit cardiac afferents was recorded from the left sympathetic chain or rami communicans (T2–T5) in anesthetized cats. Sixty-four cardiac afferents were identified. Injection (5–30 μg/kg) of histamine into the left atrium (LA) stimulated 7 ischemically sensitive cardiac afferents resulting in a significant increase in their activity in a dose-dependent manner. Also, LA injection of histamine (10 μg/kg) stimulated 7 of 8 ischemically insensitive cardiac spinal afferents. Administrations of 2-(3-chlorophenyl)histamine (250 μg/kg, LA), a specific H1 receptor agonist and histamine (10 μg/kg, LA), stimulated 9 other ischemically sensitive cardiac afferents (0.48 ± 0.10 to 1.40 ± 0.20 imp/s). In contrast, dimaprit (500 μg/kg, LA), an H2 receptor agonist, stimulated only one of the 9 afferents and thus did not alter their overall activity (0.40 ± 0.09 to 0.54 ± 0.09 imp/s). ( R)α-Methyl-histamine (500 μg/kg, LA), an H3 receptor agonist, did not stimulate any of the 9 afferents. Pyrilamine (300 μg/kg, iv), a selective H1 receptor antagonist, attenuated the activity of 8 afferents during 5 min of ischemia from 3.32 ± 0.38 to 1.87 ± 0.28 imp/s and abolished the response of 9 other cardiac afferents to histamine. Finally, administration of PKC-(19–36) (30 μg/kg, iv), a selective inhibitor of protein kinase C, attenuated the response of 8 cardiac afferents to histamine by 32%. These data indicate that endogenous histamine contributes to activation of cardiac sympathetic afferents during myocardial ischemia through H1 receptors and that the action of histamine on these cardiac afferents is partially dependent on the intracellular PKC pathway.

Role of activated platelets in excitation of cardiac afferents during myocardial ischemia in cats

2002 ◽  
Vol 282 (1) ◽  
pp. H100-H109 ◽  
Author(s):  
Liang-Wu Fu ◽  
John C. Longhurst
Keyword(s):  
Myocardial Ischemia ◽  
Polymorphonuclear Leukocytes ◽  
Platelet Rich Plasma ◽  
Cardiovascular Responses ◽  
Immune Serum ◽  
Activated Platelets ◽  
Spinal Afferents ◽  
Cardiac Afferents ◽  
Related Increase

Myocardial ischemia activates cardiac spinal afferents that mediate chest pain and excitatory reflex cardiovascular responses. Platelets are activated during myocardial ischemia and release 5-hydroxytryptamine, which stimulates abdominal spinal afferents. This study investigated the role of activated platelets in excitation of cardiac spinal afferents during ischemia. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from cats and incubated with collagen (2 mg/ml) or thrombin (5 U/ml). We observed reduction of platelets in PRP indicative of platelet activation by collagen and thrombin, respectively. Activity of single-unit, ischemia-sensitive cardiac spinal afferents was recorded from the left sympathetic chain in anesthetized cats. Injection of 1.5 ml PRP + collagen (activated platelets) into the left atrium (LA) stimulated 12 of 13 cardiac afferents. PRP + saline (nonactivated platelets, LA) and PPP + collagen did not alter activity of these afferents. PRP + thrombin (1.5 ml, LA) stimulated eight of nine other cardiac afferents, whereas PPP + thrombin did not stimulate any of the nine afferents. Antiplatelet immune serum (1 ml/kg iv) significantly decreased circulating platelets as well as neutrophils (polymorphonuclear leukocytes, PMNs) in eight other cats, and in each animal, attenuated the ischemia-related increase in activity of cardiac afferents. Conversely, responses of five separate cardiac afferents to ischemia were not diminished after treatment with anti-PMN immune serum when concentration of circulating platelets was maintained by infusion of donated PRP despite the decrease in circulating PMNs. These data indicate activated platelets stimulate ischemia-sensitive cardiac spinal afferents and contribute to activation of these afferents during ischemia.

scholarly journals Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

2013 ◽  
Vol 305 (1) ◽  
pp. H76-H85 ◽  
Author(s):  
Liang-Wu Fu ◽  
John C. Longhurst
Keyword(s):  
Myocardial Ischemia ◽  
Opioid Receptors ◽  
Opioid Peptides ◽  
Nerve Fibers ◽  
Afferent Nerve ◽  
Nerve Activity ◽  
Afferent Nerves ◽  
Peripheral Opioid Receptors ◽  
Cardiac Afferents

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP ( n = 7) or bradykinin ( n = 7). These data suggest that peripheral opioid peptides suppress the responses of cardiac sympathetic afferent nerves to myocardial ischemia and ischemic mediators like ATP and bradykinin.

Myocardial Ischemia Recruits Mechanically Insensitive Cardiac Sympathetic Afferents in Cats

2002 ◽  
Vol 87 (2) ◽  
pp. 660-668 ◽  
Author(s):  
Hui-Lin Pan ◽  
Shao-Rui Chen
Keyword(s):  
Lactic Acid ◽  
Myocardial Ischemia ◽  
Receptive Field ◽  
Topical Application ◽  
Dependent Manner ◽  
Mechanical Stimuli ◽  
Concentration Dependent Manner ◽  
C Fibers ◽  
Cardiac Afferents ◽  
New Evidence

Chest pain caused by myocardial ischemia is mediated by cardiac sympathetic afferents. Although silent nociceptors exist in somatic structures and some visceral organs, their presence in the heart remains uncertain. The present study examined the presence and the functional characteristics of mechanically insensitive cardiac sympathetic afferents using an electrical search technique. Single-unit activity of afferents innervating the left ventricle was recorded from the sympathetic chain in anesthetized cats. Cardiac afferents were identified initially with a stimulating electrode placed on the surface of the heart. Responses of cardiac afferents to mechanical stimuli, 5 min of myocardial ischemia, and topical application of bradykinin (1–10 μg/ml) and lactic acid (10–50 μg/ml) were then determined. Ischemia activated all 38 mechanically insensitive afferents and 17 of 25 mechanically sensitive afferents. The mechanically sensitive afferents typically were spontaneously active and had a smaller receptive field and a slightly faster conduction velocity. On the other hand, the mechanically insensitive afferents were slow conducting C fibers and had a large electrical receptive field on the epicardium. The response of 38 mechanically insensitive afferents to ischemia [2.83 ± 0.14 (SD) imp/s] was significantly greater than that of 17 mechanically sensitive afferents (from 0.41 ± 0.05 to 0.74 ± 0.15 imp/s). The mechanically insensitive afferents also exhibited a greater response to topical application of bradykinin or lactic acid in a concentration-dependent manner. This study provides important new evidence that the heart is innervated by silent sympathetic afferents, which are activated profoundly by myocardial ischemia. These data also suggest that the mechanically insensitive sympathetic afferents may function as cardiac nociceptors.

CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents

2005 ◽  
Vol 289 (3) ◽  
pp. R695-R703 ◽  
Author(s):  
E. H. E. M. van de Wall ◽  
P. Duffy ◽  
R. C. Ritter
Keyword(s):  
Vagal Afferents ◽  
Gastric Distension ◽  
Solitary Tract ◽  
C Fibers ◽  
Balloon Distension ◽  
Electrophysiological Responses ◽  
Vagal Afferent ◽  
Fos Expression ◽  
Afferent Response ◽  
And Control

Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhances behavioral and electrophysiological responses to gastric distension in rats and people, we hypothesized that CCK might enhance the vagal afferent response to gastric distension via an action on capsaicin-insensitive vagal afferents. To test this hypothesis, we quantified expression of Fos-like immunoreactivity (Fos) in the dorsal vagal complex (DVC) of capsaicin-treated (Cap) and control rats (Veh), following gastric balloon distension alone and in combination with CCK injection. In Veh rats, intraperitoneal CCK significantly increased DVC Fos, especially in nucleus of the solitary tract (NTS), whereas in Cap rats, CCK did not significantly increase DVC Fos. In contrast to CCK, gastric distension did significantly increase Fos expression in the NTS of both Veh and Cap rats, although distension-induced Fos was attenuated in Cap rats. When CCK was administered during gastric distension, it significantly enhanced NTS Fos expression in response to distension in Cap rats. Furthermore, CCK's enhancement of distension-induced Fos in Cap rats was reversed by the selective CCK-A receptor antagonist lorglumide. We conclude that CCK directly activates capsaicin-sensitive C-type vagal afferents. However, in capsaicin-resistant A-type afferents, CCK's principal action may be facilitation of responses to gastric distension.

scholarly journals Functions of Sleep

2021 ◽  
pp. 177-182
Author(s):  
E Miletínová ◽  
J Bušková
Keyword(s):  
Neuronal Development ◽  
Well Being ◽  
Main Function ◽  
Complex Issue ◽  
Complex Process ◽  
Scientific Papers ◽  
System Functioning ◽  
Function Of Sleep ◽  
The Individual

Sleep is essential component of life. Even though the research in this field develops constantly, there are still many aspects of this rather complex process that remains to be fully clarified. One of these aspects, reason why we actually sleep, is perhaps the most crucial. In this mini review we aim to address this question and discuss potential functions of sleep. Many recent scientific papers are currently available that covers similar topic. We tried to summarize these recent findings. There are certainly many ways how to approach this rather complex issue. Our article will specifically focus on role of sleep in neuronal development, synaptic plasticity, memory consolidation or mental health in general. Its role in immune system functioning will also be mentioned. Moreover, we will also consider more general functions of sleep, such as well-being of the organisms or securing survival of the individual. In conclusion, we will highlight possible main function of sleep.

Planning of Material Handling : Literature Review

2019 ◽  
Vol 13 (2) ◽  
pp. 29-44
Author(s):  
Péter Telek ◽  
Ákos Cservenák
Keyword(s):  
Literature Review ◽  
Material Handling ◽  
State Of The Art ◽  
The State ◽  
Integrated Planning ◽  
Complex Process ◽  
Individual Planning ◽  
The Individual ◽  
The University

Nowadays, there are many well proved, effective processes to solve planning tasks in the field of material handling used advanced calculations forms and software. Unfortunately, most of them are used for individual tasks, so the applicability of their results is limited. The Institute of Logistics of the University of Miskolc has been working on integrated planning of handling machines for decades, where the individual planning tasks have to be solved together in a complex process. The main aim of this paper to give an overview about the state of the art of the planning of material handling, based on a literature review of the Science Direct publication database. As a result of this research we can determine some new direction for the planning of material handling.

Interaction of bradykinin and prostaglandin E1 on cardiac pressor reflex and sympathetic afferents

1986 ◽  
Vol 250 (5) ◽  
pp. R815-R822 ◽  
Author(s):  
T. Nerdrum ◽  
D. G. Baker ◽  
H. M. Coleridge ◽  
J. C. Coleridge
Keyword(s):  
Blood Pressure ◽  
Prostaglandin E1 ◽  
Pressor Response ◽  
Interactive Effect ◽  
Small Reduction ◽  
Arterial Blood ◽  
Repeated Applications ◽  
Pressor Reflex ◽  
Cardiac Afferents ◽  
Afferent Response

Bradykinin applied to the epicardium stimulates cardiac sympathetic afferents and evokes a reflex increase in arterial blood pressure. In anesthetized cats we examined the potentiation of these effects by prostaglandin E1 (PGE1) applied to the ventricular epicardium. We recorded cardiac afferent impulses from the second to the fifth left thoracic sympathetic rami. PGE1 (0.1 microgram/ml) alone had little effect on blood pressure, but it significantly increased the pressor response to bradykinin, and it reduced or abolished tachyphylaxis to repeated applications of bradykinin. Both mechanosensitive and chemosensitive sympathetic cardiac afferents were stimulated by bradykinin. Indomethacin (intravenous) caused a small reduction in the afferent response to bradykinin. Epicardial application of PGE1 significantly increased the response (magnitude and duration) of chemosensitive endings to bradykinin but not that of mechanosensitive endings; however, PGE1 abolished the tachyphylaxis of both chemosensitive and mechanosensitive endings to repeated applications of bradykinin. Because both bradykinin and prostaglandins are released in the ischemic myocardium, their interactive effect on cardiac sympathetic afferents could play a part in the sensory and reflex responses to myocardial ischemia.

“Time's Up”: The Experience of Entering Residential Aged Care for Young People with Acquired Neurological Disorders and Their Families

2018 ◽  
Vol 20 (1) ◽  
pp. 37-48 ◽  
Author(s):  
Sandra Barry ◽  
Lucy Knox ◽  
Jacinta M. Douglas
Keyword(s):  
Young People ◽  
Lived Experience ◽  
Neurological Disorders ◽  
Healthcare Setting ◽  
Aged Care ◽  
Residential Aged Care ◽  
Health Crisis ◽  
Complex Process ◽  
The Individual ◽  
Key Events

Background and aims: Previous research has highlighted that living in residential aged care (RAC) is associated with a range of negative outcomes for adults with acquired neurological disorders. This study sought to understand the lived experience of entering RAC for young people and their family members and characterise their needs during this process.Method: Data included 64 written and verbal submissions to the 2015 Senate Inquiry into the Adequacy of existing residential care arrangements available for young people with severe physical, mental or intellectual disabilities in Australia. In line with hermeneutic tradition, text was analysed using thematic analysis.Results: Entry to RAC was experienced as a complex process that coalesced around three key events: an unexpected health crisis, a directive that time's up and the individual is required to leave the healthcare setting, with a subsequent decision to move into RAC. This decision was made in the absence of time, knowledge of options or adequate support.Conclusions: Findings suggest that there are both immediate practice changes and longer term policy responses that can support the health and disability systems to uphold the rights of people with acquired disability to choose where and how they will live their lives.

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