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

Adenosine is a possible mediator of cardiac pain during myocardial ischemia; however, little is known about the influence of adenosine on cardiac sympathetic afferent activity and thereby on its algogenic mechanism. In 20 anaesthetized, decerebrated, curarized and artificially ventilated cats, we studied the impulse activity of 20 single afferent sympathetic fibers with a left ventricular receptive field in relation to epicardial applications of adenosine, coronary artery occlusions and arterial pressure rises. All fibers increased their impulse activity (from 1.2 +/- 0.2 to 2.6 +/- 0.5 imp/s; P < 0.001) during slight (20 +/- 8%) rises in aortic pressure, thus exhibiting low-threshold receptor characteristics. In 10 cats, epicardial applications of three different doses of adenosine (0.1, 1 and 10 mg/ml) caused a brief increase in neural activity with dose-related responses. This response was abolished by aminophylline, a P1 purinergic inhibitor. In the other group of 10 cats, four subsequent 30-s occlusions of the coronary arterial vessel supplying the receptive fields of the fibers were performed, in control conditions and 30 s, 3 and 7 min, respectively, after the end of excitation induced by adenosine (1 mg/ml) application. During the control coronary occlusion the impulse activity increased from 1.1 +/- 0.1 to 5.5 +/- 0.7 imp/s (P < 0.0001). A similar activation was present during the second occlusion initiated 30 s after the end of adenosine-induced activation. In contrast, a significant potentiation of the response was observed (8.8 +/- 1.2 vs. 5.3 +/- 0.9 imp/s; P < 0.001) during the occlusion initiated 3 min after the end of excitation by adenosine. This effect was no longer present during the last occlusion performed after 7 min. When the protocol was repeated substituting adenosine with saline (n = 5) or after i.v. administration of aminophylline (n = 5), no potentiation was observed, even though the excitatory response to coronary occlusion was preserved. These data show that adenosine can activate cardiac sympathetic afferent fibers in a dose-related manner, and potentiate their responses to coronary occlusion, while leaving unaffected the responsiveness to a hemodynamic stimulus. The excitatory effects are likely to involve the P1 purinergic receptors. The potentiation phenomenon might play a role in the genesis of an algogenic code.
 ...
PMID:Adenosine activates cardiac sympathetic afferent fibers and potentiates the excitation induced by coronary occlusion. 756 Jul 54

Adenosine has been implicated in the pathogenesis of cardiac pain through activation of cardiac sympathetic afferents. The present study was performed to assess directly the contribution of adenosine in activating ischemically sensitive cardiac sympathetic afferents. Single-unit activity of ischemically sensitive afferents located in both ventricles was recorded from the left thoracic sympathetic chain or rami communicantes of anesthetized cats during 5 min of myocardial ischemia. Intracardiac injection (5 mg) or epicardial application (1-5 mg/ml) of adenosine onto the receptive fields failed to activate 31 ischemically sensitive A delta- and C fiber afferents, which were responsive to topical application of bradykinin (10 micrograms/ml). Intracardiac injection (5 mg) or topical application (1-5 mg/ml) of an adenosine A1 receptor agonist, N6-cyclopentyladenosine, also did not increase the discharge activity of 13 other ischemically sensitive C fiber afferents. Treatment with dipyridamole (1 mg/kg iv) to inhibit the cellular uptake of adenosine did not significantly potentiate the response of 10 separate C fiber afferents to 5 min of myocardial ischemia. Furthermore, blockade of adenosine receptors with aminophylline (5 mg/kg iv) did not significantly attenuate the response of 10 other C fiber afferents to 5 min of myocardial ischemia. The results of the present study demonstrate that exogenous and endogenous adenosine do not contribute to activation of ischemically sensitive cardiac sympathetic afferents. The findings of the present study fail to support a substantial role for adenosine and its A1 receptors in activation of cardiac sympathetic afferents during myocardial ischemia.
 ...
PMID:Lack of a role of adenosine in activation of ischemically sensitive cardiac sympathetic afferents. 763 38

Spontaneously hypertensive rats (SHR) have functional defects in purinergic neurotransmission. Because adenosine is antiaarrhythmic, the adenosine probably has lesser antiarrhythmic potency in SHR. We tested this hypothesis by comparing the antiarrhythmic effects of adenosine against arrhythmias induced by global myocardial ischemia/reperfusion in isolated perfused heart of SHR and its normotensive counterparts: Wistar Kyoto rats (WKY) and Sprague-Dawley rats (SD). The Langendorff isolated perfused heart preparation was used. Ventricular fibrillation (VF) was induced by global myocardial ischemia/reperfusion. Ischemia/reperfusion-induced VF was most severe in SD. The severity of VF in WKY was similar to that in SHR. Adenosine 75 micrograms/heart had significant antiarrhythmic effect in both types of normotensive rats; a much higher dose of adenosine (150 micrograms/heart) was required to attenuate cardiac arrhythmias in SHR, suggesting reduced responsiveness to adenosine in genetically hypertensive rats. The mechanisms of action responsible for reduced responsiveness to adenosine in SHR require further study.
 ...
PMID:Differential antiarrhythmic potency of adenosine in normotensive and spontaneously hypertensive rats. 776 17

Adenosine released by ischemic myocardial cells stimulates coronary artery vasodilation. Measurement of adenosine concentrations in pericardial fluid in animal models of myocardial ischemia has been used to study the process of adenosine release. To determine whether pericardial fluid adenosine concentrations are increased in human ischemic heart disease, adenosine concentrations were measured in pericardial fluid in 23 subjects undergoing open-heart surgery for coronary artery disease. The results were compared with adenosine concentrations measured in pericardial fluid obtained from 20 subjects undergoing surgery for valvular heart disease. Adenosine concentrations also were measured in pleural fluid obtained during internal mammary artery bypass grafting. Adenosine concentrations were significantly increased in subjects with coronary artery disease compared with fluid obtained from subjects with valvular heart disease (2.47 +/- 0.24 vs 1.36 +/- 0.21 [SEM] microM [p = 0.0013]). Adenosine concentrations were higher in pleural fluid than pericardial fluid from the same individuals. Adenosine concentrations were significantly correlated with pericardial fluid cell counts and lactate dehydrogenase concentrations (r = 0.48; p = 0.0012 and r = 0.77, p = 0.0001, respectively). The results are consistent with myocardial release of adenosine in ischemic heart disease. If adenosine concentrations in pericardial fluid approximate those in myocardial interstitial fluid, sufficient adenosine is present to stimulate adenosine receptor activation in coronary artery smooth muscle.
 ...
PMID:Pericardial fluid adenosine in ischemic and valvular heart disease. 784 59

Adenosine infusion is accompanied by increases in coronary blood flow and myocardial blood volume. Myocardial blood volume may produce changes in diastolic left ventricular (LV) performance by increasing myocardial turgor. Diastolic dysfunction may also be the result of myocardial ischemia. The relation between changes in LV mass and diastolic function has not been previously investigated. This study examined the relation between changes in LV mass during adenosine-induced coronary hyperemia and LV diastolic function. Serial two-dimensional and Doppler echocardiographic measurements were made before, during, and after adenosine infusion (140 micrograms/min for 6 min) in 21 patients with (group 1) and 10 patients without (group 2) coronary artery disease (CAD). The LV mass and transmitral diastolic filling indexes were determined from digitized images from apical four-chamber view. Adenosine infusion produced a greater increase in LV mass in group 2 than in group 1 (29% +/- 11% vs 9% +/- 6%, p < 0.0002). The ratio of transmitral early (E) to atrial (A) filling velocity (E/A) increased 10% +/- 16% in group 2 and decreased 8% +/- 20% in group 1 (p < 0.02), and the velocity time integral of early filling increased 11% +/- 52% in group 2 and decreased 20% +/- 31% in group 1 (p < 0.04). There was a correlation between the change in E/A ratio and the LV mass (r = 0.53, p < 0.003). Thus adenosine infusion caused a greater increase in LV mass in normal subjects than in patients with CAD. There were also changes in Doppler-derived indexes of diastolic LV function.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Relation between diastolic left ventricular function and myocardial blood volume during adenosine-induced coronary hyperemia. 790 Jun 20

Abnormal constriction of coronary resistive vessels can induce angina and myocardial ischemia. The possibility that a microvascular vasomotor dysfunction could cause ischemia is in contrast with the well-known traditional notion that a metabolically induced vasodilation could compensate for the effect of an epicardial coronary stenosis. Vasoconstrictor stimuli can plausibly act on vessels situated immediately proximal (prearterioles) to those that can be dilated by ischemia metabolites (arterioles). This functional 2-compartment model of resistive vessels is based on the ability of different substances to cause opposite actions on resistive vessels with different sizes. The possible mechanisms of prearteriolar dysfunction, observed in patients with syndrome X, single vessel disease after a successful PTCA and in a subset of chronic stable patients include: an organic reduction of total vascular section; vascular smooth muscle hyperreactivity to heterogeneous constrictor stimuli; an impaired flow-mediated endothelium-dependent vasodilation (possibly due to a reduced NO and/or EDHF synthesis). The first and third hypothesis can only account for anginal episodes at effort while the second model could explain episodes occurring at rest and without an increase in heart rate. Those mechanisms causing an imbalance between myocardial oxygen supply and demand, induce an increased release of adenosine in order to promote a compensating vasodilation. Adenosine can possibly avoid the occurrence of ischemia but, being a powerful algogenic stimulus, causes pain. It is worth noting that the presence of patchy prearteriolar dysfunction induces areas with excessive release of adenosine. Since total vascular section is extremely large a massive adenosine spill-over can occur with a consequential boosting of algogenic and vasodilatory effect.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Mechanisms of coronary microvascular dysfunction]. 802 13

Dynamic exercise echocardiography is sensitive and specific in detection and evaluation of coronary artery disease. Frequently, however, patients cannot achieve maximum exercise because of various factors. The aims of this study were to compare usefulness of adenosine infusion and dynamic exercise to induce myocardial ischemia detected with 2-D echocardiography and standard electrocardiography; to determine the sensitivity of the adenosine echo test; and to evaluate the safety and tolerability of adenosine infusion. In 31 men with clinical diagnosis of stable angina pectoris, myocardial ischemia was induced by: a) symptom-limited exercise test on a bicycle, and b) intravenous adenosine infusion. The two tests were performed with an average interval of 24 hours. Coronary angiography was performed in 29 of 31 patients and significant coronary artery disease (diameter narrowing > 50%) was documented in 26 of these (12 single, 6 two- and 8 three-vessel disease). The criterion for echo positivity was a transient impairment of contraction as compared to the baseline examination in any of 10 segments, with an increase of left ventricular score index of 0.3 or more. ECG positivity was considered as ST60 segment depression of 0.1 mV or more from the reference level in any lead. Adenosine echo test was positive in 22 out of 26 patients and exercise echo in 19 (sensitivity 85% and 73%, respectively, p = NS). Adenosine ECG test was positive in 14 of 26 patients and exercise ECG test in 21 (sensitivity 54% and 81% respectively, p = NS). In three patients with normal coronary arteriography adenosine echo was negative in all three, exercise echo, adenosine ECG and exercise ECG in two.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adenosine echocardiography--an alternative to dynamic stress echocardiography. 810 95

Clinical characteristics: Angina pectoris represents a visceral pain caused by reversible myocardial ischemia. The majority of ischemic attacks are symptomless. When pain is manifested, it appears late during the ischemic event. The pain is complex in its quality and bears little relation to the region of myocardial ischemia. Pain shows a sensitive dependence on initial conditions suggesting a mechanism with deterministic chaotic dynamics for the association between myocardial ischemia and pain. Neurophysiological substrate: Ganglia are present within the heart, particularly in epicardial fat. The blood supply of intrinsic cardiac ganglia arises primarily from branches of the proximal coronary arteries. Both afferent and efferent neurons within the intrinsic cardiac nervous system exist, while the majority of neurons in that location may be local circuit neurons. Integration takes place not only in the intrinsic cardiac nervous system, but also in mediastinal, middle cervical, and stellate ganglia. Cardiac afferent receptors are also connected to cell bodies in dorsal root and nodose ganglia, as well as intrathoracic ganglia. Myocardial regions have no spatial representation in these ganglia. Adenosine, among a number of substances, can modulate the activity generated by cardiac afferent nerve endings and intrinsic cardiac neurons. Such effects appear to be exerted at A1 receptors. Adenosine as a pain messenger: During myocardial ischemia adenosine is released in large quantities into the interstitial space. The endothelium takes up the major amount of adenosine. Thus only small increments of adenosine are detected in the blood-stream. Given as an intravenous bolus to healthy volunteers or to patients with ischemic heart disease and angina pectoris, adenosine provokes angina pectorislike pain, which is similar to habitual angina pectoris with regard to quality and location. Pain is provoked in the absence of ECG signs of ischemia. Patients with asymptomatic myocardial ischemia are less sensitive to adenosine, whereas patients with Syndrome X are more sensitive with respect to adenosine-provoked pain. When adenosine is given intraarterially, including into the coronary arteries, pain is provoked in the corresponding vascular bed. Adenosine-provoked pain and ischemic pain are counteracted by previous administration of the adenosine receptor antagonist theophylline.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Mechanisms of pain in angina pectoris--a critical review of the adenosine hypothesis. 811 Jun 16

Adenosine methylene diphosphate (AMPCP), a 5'-nucleotidase inhibitor, was evaluated as an adjunct to cold crystalloid cardioplegic myocardial protection. Cardiopulmonary bypass (CPB) was instituted at 28 degrees C in two groups of mongrel dogs (each, n = 6). Myocardial ischemia was induced for 150 min by aortic cross clamping. Crystalloid cardioplegia (4 degrees C) was infused into the aortic root at 15 ml/kg/20 min in the control group (CP). The experimental group (CP + AMPCP) received identical doses of cardioplegia supplemented with 250 microM AMPCP. While on CPB, the mean arterial pressure was 70 mm Hg and the myocardial temperature ranged from 16 to 22 degrees C. Hemodynamic parameters were recorded prior to institution of CPB and at 15 and 45 min following the termination of CPB. Starling curves were constructed for cardiac index (CI), mean arterial pressure (MAP), mean left ventricular pressure (LVP), +dP/dt and -dP/dt at each time point for left atrial pressures between 5 and 12.5 mm Hg. The area under each curve was calculated and expressed as a percentage of prebypass values. Statistical analysis was performed with Student's two-tailed t test. The data demonstrate that although recovery of CI, MAP, heart rate, and LVP was similar in both groups, statistically significant improvement in recovery of myocardial compliance (-dP/dt) and systolic function (+dP/dt) was seen with AMPCP. The addition of the 5'-nucleotidase inhibitor, AMPCP, to cold crystalloid cardioplegia enhances postischemic myocardial performance in vivo and may be useful during prolonged periods of global myocardial ischemia.
 ...
PMID:5'-Nucleotidase inhibition enhances postischemic myocardial performance. 815 30

The use of adenosine-echocardiography to detect coronary artery disease was evaluated in 39 patients. Adenosine was infused intravenously at 0.14 mg/kg/min for 6 minutes with continuous recordings of two-dimensional echocardiography. Three minutes after the start of adenosine infusion, thallium (201Tl) was administered into a separate vein. Myocardial single photon emission computed tomography (SPECT) images were obtained 10 minutes and 3 hours after the 201Tl injection. Transient reduction of systolic wall motion after adenosine infusion was considered an abnormal ischemic response. Echocardiography detected a wall motion abnormality after adenosine infusion in 17 of 39 patients. 201Tl redistribution was observed in 28 patients. Agreements for the presence of myocardial ischemia or infarction between 201Tl SPECT and echocardiography were 62% (24/39). The sensitivity of echocardiography in patients with single-vessel disease was 21%, but 76% with multi-vessel disease (p < 0.01 vs single-vessel disease). All side effects were tolerated well and disappeared within 1 or 2 minutes after stopping adenosine infusion. Adenosine-echocardiography was particularly useful for the detection of multiple-vessel coronary disease. Simultaneous evaluation of wall motion and myocardial perfusion during adenosine-induced maximal coronary vasodilation may improve the functional description of diseased myocardial segments.
 ...
PMID:Adenosine-echocardiography for the detection of coronary artery disease. 815 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>