Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effects of a daily morphine injection for 2 weeks on induction of naloxone-reversible arrhythmias in the Langendorff isolated rat heart preparation caused by dynorphin1-13 or myocardial ischemia and reperfusion. Chronic morphine treatment significantly reduced the incidence and severity of arrhythmias and increased recovery following both administration of dynorphin and myocardial ischemia and reperfusion. The results support the notion that myocardial ischemia and reperfusion induce cardiac arrhythmias via endogenous opioid peptides.
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PMID:Chronic morphine treatment reduces the incidence of ventricular arrhythmias in the isolated rat heart induced by dynorphin1-13 or myocardial ischemia and reperfusion. 288 92

It has been shown in experiments on albino rats that acute myocardial ischemia (AMI) produces a noticeable increase in excretion of adrenaline, noradrenaline, DOPA and dopamine with urine. Intraperitoneal injection of leu-enkephalin analogs (D-Ala2-Leu5-Arg6 and D-Ala2-D-Leu5-D-Arg6) to rats with AMI was accompanied by a noticeable prevention of activation of the sympathoadrenal system.
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PMID:[Enkephalins and the function of the sympathetic-adrenal system in acute myocardial ischemia]. 400 4

The endogenous opioid peptide (EOP) dynorphin and opioid receptors have been found in the heart. This opioid system plays important roles in cardiovascular regulation and is involved in the pathophysiology of shock, heart failure and myocardial ischaemia. The aim of this study was to evaluate whether the EOP dynorphin modulates or potentiates ischaemia-induced arrhythmias and whether its effects are prevented by the opiate antagonist naloxone. Following coronary artery occlusion, all rats in the control group developed ischaemia-induced arrhythmias, bradycardia and hypotension, which were significantly potentiated by pre-treatment with dynorphin and attenuated by treatment with naloxone. The results clearly indicate that EOPs may be released when myocardial ischaemia occurs, thus causing arrhythmias, bradycardia and hypotension. Dynorphin and naloxone, by virtue of their opioid agonistic and antagonistic actions, respectively, potentiate and attenuate these fatal complications secondary to myocardial ischaemia. This suggests that EOPs play an important part in ischaemic heart disease.
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PMID:Opioids in myocardial ischaemia: potentiating effects of dynorphin on ischaemic arrhythmia, bradycardia and cardiogenic shock following coronary artery occlusion in the rat. 790 Oct 21

Although the formation of oxygen-derived free radicals (or reactive oxygen species; ROS) and the release of endogenous opioid peptides (EOP) have been independently reported to be the major arrhythmogenic factors in ischemic hearts, possible relations between these two factors have seldom been investigated. Thus, we studied whether the ROS and EOP were related in the progression of ischemia-induced arrhythmias. Isolated rat hearts perfused in the Langendorff mode were treated with dynorphin A1-13 (kappa EOP receptor agonist), and/or allopurinol (xanthine oxidase inhibitor), before the onset of ischemia induced by ligating the left coronary arteries. Ischemic period lasted for 30 min, during which cardiac rhythms were recorded. At the end of ischemia, hearts were analyzed for the glutathione and ascorbate levels. Allopurinol (100 nmoles/heart) was effective in reducing the severity of arrhythmia (arrhythmia score: Mean +/- SEM 3.00 +/- 0.80 for allopurinol, 5.75 +/- 0.41 for placebo, p < 0.01), while dynorphin (10 micrograms/heart) potentiated the arrhythmia (6.71 +/- 0.52, p < 0.05 vs. placebo). Coadministration of allopurinol and dynorphin was capable of reducing arrhythmia (5.57 +/- 0.65) when compared with the administration of dynorphin alone (6.71 +/- 0.52, p < 0.05). Tissue oxidative stress was evaluated by the concentrations of glutathione (GSH) and ascorbate. Allopurinol did not significantly elevate tissue GSH concentrations (1.46 +/- 0.05 mumoles/g wet wt) in ischemic hearts, while dynorphin alone significantly decreased the GSH concentrations (0.96 +/- 0.08, p < 0.05) when compared with the placebo (1.32 +/- 0.03). The dynorphin-induced GSH decrease cannot be reversed by coadministration with allopurinol (0.90 +/- 0.104). Allopurinol significantly elevated tissue ascorbate levels (0.16 +/- 0.01) when compared with placebo (0.10 +/- 0.01, p < 0.05). Interestingly, dynorphin alone also elevated the tissue ascorbate concentrations (0.16 +/- 0.02). Coadministration of allopurinol and dynorphin further spiked the ascorbate levels (0.28 +/- 0.05, p < 0.01). In conclusion, the results suggested that ischemia-induced arrhythmia mechanisms might involve the formation of superoxide and other ROS, which were probably generated from the release of EOP (or EOP/EOP receptor interactions). Superoxide, the formation of which can be inhibited by allopurinol that exerted antiarrhythmic effect, was probably scavenged by ascorbate in myocardial ischemia. The ROS resulting from EOP/EOP receptor interactions were probably scavenged by glutathione system. Elevated ascorbate levels in dynorphin-treated hearts might result from the compensatory synthesis induced by decreased glutathione levels.
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PMID:The roles of reactive oxygen species and endogenous opioid peptides in ischemia-induced arrhythmia of isolated rat hearts. 910 Dec 52

The effects of myocardial ischemia and reperfusion on interstitial hydroxyl radical production, in the left ventricular myocardium of anesthetized cats, were investigated. Ringer's solution containing salicylic acid was perfused through an implanted microdialysis probe. Hydroxyl radical production was evaluated as the 2,3 and 2,5 dihydroxybenzoic acid (DHBA) concentrations in the microdialysates by an on-line high performance liquid chromatography system. Myocardial ischemia for 60 min, induced by ligation of the left anterior descending coronary artery, significantly increased both 2,3 and 2,5 DHBA levels when compared with the sham-operated cats. Naloxone (1 mg/kg, bolus, intravenous), an endogenous opioid peptide receptor antagonist, significantly suppressed the ischemia-induced production of hydroxyl radicals. Myocardial ischemia also induced cardiac arrhythmia. Naloxone reduced the severity of ischemia-induced arrhythmia, as observed by a significantly lower arrhythmia score (1.4 +/- 0.2 vs. 4.6 +/- 0.4 for control), and by diminished incidence of ventricular tachycardia (0/7 vs. 8/8 for control) and ventricular fibrillation (0/7 vs. 3/8 for control). Furthermore, perfusion of dynorphin (0.25 microgram, 2.5 micrograms and 25 micrograms), an endogenous opioid peptide receptor agonist, increased hydroxyl radical production. Our results suggest that, in anesthetized cats, myocardial ischemia can induce production of interstitial hydroxyl radical in left ventricular myocardium, and this production may involve the actions of released endogenous opioid peptides on their receptors.
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PMID:Increased formation of interstitial hydroxyl radical following myocardial ischemia: possible relationship to endogenous opioid peptides. 975 28

In this review we analyse the experimental and clinical findings demonstrating important regulatory significance of met-enkephalin, leu-enkephalin and their derivatives in the control of cardiovascular system activity. Enkephalin-positive immunoreactivity is revealed in the heart of different species of animals, and their cardiovascular effects are established in numerous investigations. It is determined that cardiac effects of enkephalins are essentially associated with modulatory influence at the presynaptic and postsynaptic levels on the activity of extracardiac neural regulation. Cardiovascular effects of endogenous opioid system are extremely important in developing of myocardial ischemia, cardiac arrhythmias and congestive heart failure. The cellular mechanisms of opioid effects are associated with stimulation of mu- and delta-subtypes of opiate receptors which stimulation of mu- and delta-subtypes of opiate receptors which are coupled with conductivity of ion channels, adenylate cyclase activity, phosphoinositide turnover and calcium-calmodulin-dependent protein kynases.
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PMID:[The regulatory effects of opioid peptides--enkephalins--in controlling the activities of the cardiovascular system]. 1075 29

Electroacupuncture (EA) is used in traditional Chinese medicine to treat arrhythmias, hypertension and myocardial ischemia. Our previous work suggests that the inhibitory effect of EA on the pressor reflex induced by bradykinin (BK) applied to the gallbladder is due, in part, to the activation of opioid receptors, most likely located in the rostral ventrolateral medulla (rVLM). However, specific opioid receptor subtypes, and hence the neurotransmitters. responsible for this inhibition are unknown. Therefore, in anesthetized cats, BK (10 microg/ml) was applied to the gallbladder to induce transient reflex increases in arterial blood pressure (BP). EA (1-2 mA, 5 Hz, 0.5 ms pulses) was delivered through acupuncture needles inserted bilaterally into Neiguan and Jianshi acupoints on forelimbs, overlying the median nerves. EA attenuated the BK-induced pressor response by 39%. Opioid receptor subtype antagonists or agonists were microinjected unilaterally into the rVLM. The mu- and delta-receptor antagonists CTOP and ICI 174,864, respectively, significantly attenuated the EA-induced inhibition for at least 30 min. The K-receptor antagonist (nor-BNI) was less effective and was shorter acting. Like EA, microinjection of mu- and delta-opioid agonists, DAGO and DADLE, respectively, into the rVLM significantly decreased the pressor responses. In contrast, the kappa-opioid agonist, U50,488, failed to alter the BK-induced pressor response. We conclude that a significant portion of inhibition of the gallbladder pressor response by EA is related to activation of mu- and delta-opioid receptors in the rVLM. The endogenous neurotransmitters for mu- and delta-opioid receptors, beta-endorphins and enkephalins, in the rVLM, therefore appear to play a role in the EA-related modulation of cardiovascular reflex responses. Conversely, dynorphin is less likely to be involved in this response.
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PMID:Rostral ventrolateral medullary opioid receptor subtypes in the inhibitory effect of electroacupuncture on reflex autonomic response in cats. 1147 45

There is evidence that the myocytes produce dynorphin and dynorphin-like peptides, which are kappa opioid receptor (kappa-OR) agonists. Activation of kappa-OR, a dominant opioid receptor in the heart, alters the cardiac function in vivo and in vitro. The observations suggest that the endogenous kappa-opioid peptides may act as autocrines or paracrine in regulation of cardiac functions. Myocardial ischemia is a common cause of heart disorders, which is manifested in decreased myocardial performance, arrhythmia and infarct. When myocardial ischemia occurs, the sympathetic discharge increases, which in turn increases the work-load and oxygen consumption. This exacerbates the situation induced by ischemia. One of the mechanisms with which the body protects against ischemia-induced injury/arrhythmia is inhibition of stimulation of beta-adrenoceptor (beta-AR), the receptor mediating the actions of sympathetic stimulation. kappa-Opioids inhibit the beta-AR activation. The inhibition of the beta-AR activation is due to inhibition of Gs-protein and to a lesser extent the adenylyl cyclase of the signaling pathway mediating beta-AR stimulation by a pertussis sensitive G-protein that mediates kappa-OR activation. Another mechanism against ischemia-induced injury is preconditioning, which is defined as prior exposures to ischemia or other insults make the heart more tolerant to subsequent and more severe insults. Protection occurs immediately or 1-3 days after preconditioning. kappa-OR mediates protection of preconditioning with ischemia or metabolic inhibition, one of the consequences of ischemia, in the heart. Activation of kappa-OR by U50488H, a selective kappa-OR agonist (pharmacological preconditioning with U50488H, UP), activates protein kinase C (PKC), opens K(ATP) channels and increases the production of heat shock proteins. Blockade of PKC, or closing of the K(ATP) channels or inhibition of the synthesis of the heat shock protein abolishes the cardioprotection of UP. The findings indicate the important roles of PKC, the K(ATP) channels and the heat shock protein in cardioprotection of UP. In addition, UP also attenuates the Ca(2+) overload, a precipitating cause of cardiac injury, induced by ischemic insults, indicating that UP may confer cardioprotection via at least partly attenuating the Ca(2+) overload. Most interestingly, blockade of the K(ATP) channels with channel blockers, that abolishes the delayed cardioprotection of UP, also attenuates the inhibitory effect of UP on Ca(2+) overload, suggesting that the cardioprotective effect of opening of the K(ATP) channels may be due at least partly to the prevention/attenuation of Ca(2+) overload.
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PMID:Roles of kappa opioid receptors in cardioprotection against ischemia: the signaling mechanisms. 1271 97

We tested the hypothesis that the selective kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) improves recovery from myocardial stunning. Ten dogs were chronically instrumented for measurement of heart rate, left atrial, aortic and left ventricular pressure (LVP), and the maximum rate of LVP increase (LV dP/dt(max)) and decrease (LV dP/dt(max)), coronary blood flow velocity and myocardial wall-thickening fraction. Regional myocardial blood flow was determined with fluorescent microspheres. Catecholamine plasma levels were measured by high-performance liquid chromatography, and beta-endorphin and dynorphin plasma levels by radioimmunoassay. An occluder around the left anterior descending artery (LAD) allowed induction of a reversible LAD-ischemia. Animals underwent two experiments in a randomized crossover fashion on separate days: (a) 10 min LAD-occlusion (control experiment), (b) second ischemic episode 24 h after nor-BNI (2.5 mg/kg IV) (intervention). Dogs receiving nor-BNI showed an increase in wall-thickening fraction, LV dP/dt(max) and LV dP/dt(min) before ischemia and during the whole reperfusion (P < 0.05 versus control experiment). After nor-BNI pretreatment, dynorphin levels increased after induction of ischemia to a peak level of 15.1 +/- 3.6 pg/mL (P < 0.05 versus control experiment). The increase in plasma beta-endorphin during ischemia and early reperfusion was attenuated after nor-BNI. Compared with the control experiment, nor-BNI left global hemodynamics, regional myocardial blood flow, and catecholamine levels unchanged. In conclusion, nor-BNI improves recovery from myocardial stunning after regional myocardial ischemia in chronically instrumented dogs.
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PMID:Kappa-opioid receptor antagonism improves recovery from myocardial stunning in chronically instrumented dogs. 1700 Jul 88

During myocardial ischemia, the cranial cervical spinal cord (C1-C2) modulates the central processing of the cardiac nociceptive signal. This study was done to determine 1) whether C2 SCS-induced release of an analgesic neuropeptide in the dorsal horn of the thoracic (T4) spinal cord; 2) if one of the sources of this analgesic peptide was cervical propriospinal neurons, and 3) if chemical inactivation of C2 neurons altered local T4 substance P (SP) release during concurrent C2 SCS and cardiac ischemia. Ischemia was induced by intermittent occlusion of the left anterior descending coronary artery (CoAO) in urethane-anesthetized Sprague-Dawley rats. Release of dynorphin A (1-13), (DYN) and SP was determined using antibody-coated microprobes inserted into T4. SCS alone induced DYN release from laminae I-V in T4, and this release was maintained during CoAO. C2 injection of the excitotoxin, ibotenic acid, prior to SCS, inhibited T4 DYN release during SCS and ischemia; it also reversed the inhibition of SP release from T4 dorsal laminae during C2 SCS and CoAO. Injection of the kappa-opioid antagonist, nor-binaltorphimine, into T4 also allowed an increased SP release during SCS and CoAO. CoAO increased the number of Fos-positive neurons in T4 dorsal horns but not in the intermediolateral columns (IML), while SCS (either alone or during CoAO) minimized this dorsal horn response to CoAO alone, while inducing T4 IML neuronal recruitment. These results suggest that activation of cervical propriospinal pathways induces DYN release in the thoracic spinal cord, thereby modulating nociceptive signals from the ischemic heart.
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PMID:C2 spinal cord stimulation induces dynorphin release from rat T4 spinal cord: potential modulation of myocardial ischemia-sensitive neurons. 1875 68


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