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)

Alterations in myocardial and plasma levels of adenosine 3':5'-cyclic phosphate (cyclic AMP) were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic APM levels increased markedly after thoracotomy but returned to control levels two hours later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham-occlusion. After localized coronary occlusion, only modest and insignificant changes occurred in plasma cyclic AMP levels in anesthetized animals and also in conscious dogs. The present study suggests that adrenergically mediated changes in tissue cyclic AMP content are an early manifestation of both generalized and local myocardial ischemia, while the plasma cyclic AMP level is a relatively insensitive indicator of small coronary occlusions.
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PMID:Myocardial and plasma levels of adenosine 3':5'-cyclic phosphate. Studies in experimental myocardial ischemia. 16 37

Alterations in myocardial and plasma cyclic adenosine monophosphate (cyclic AMP) levels were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic AMP levels increased markedly after thoracotomy but returned to control levels 2 hr later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham occlusion. Localized coronary occlusion tended to increase plasma cAMP levels in anesthetized animals and also in concious dogs. The present study suggests that adrenergically mediated changes in tissue and plasma cyclic AMP content are early manifestations of both generalized and local myocardial ischemia and tend to reflect the magnitude of the insult.
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PMID:Alterations in myocardial and plasma cyclic adenosine monophosphate in experimental myocardial ischemia. 17 14

After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either 14C-adenine or 14C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 3'5'-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady state conditions the SA of adenosine and cAMP in the perfusate were of the same order of magnitude and proved to be many times higher than the SA of the respective precursor adenine nucleotides. This difference was observed regardless whether adenine or adenosine was used as prelabeling substances. The SA of inosine and hypoxanthine in the perfusate were constantly lower than the SA of adenosine. Cardiac ischemia of 6 min, which resulted in a markedly increased formation of adenosine, led to a pronounced decrease in the SA of adenosine released from the heart. Our findings provide evidence that at least two different adenine nucleotide compartments of the heart severe as precursors for the formation of adenosine and cAMP, one characterized by a high, the other by a lower SA. Under normoxic conditions adenosine and cAMP released into the cardiac perfusate are derived mainly from a nucleotide fraction of high SA, which appears to be rather small. During ischemia a second compartment of much lower SA in addition contributes to the formation of adenosine.
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PMID:Compartmentation of cardiac adenine nucleotides and formation of adenosine. 18 85

Continuously recorded bipolar electrograms were obtained simultaneously from epi-, endo-, and mid-myocardial regions of the ischemic and normal zones of cat left ventricle in vivo after coronary occlusion, analyzed by computer, and compared to regional cyclic AMP levels. Regional cyclic AMP content was used as an index of the combined local effects of: (a) efferent sympathetic nerve discharge; (b) release of myocardial catecholamines due to ischemia; and (c) circulating catecholamines. Ischemia resulted in a progressive increase in pulse width and rise time and a decrease in rate of rise of voltage (dV/dt) of the local electrograms from ischemic zones reaching a maximum within 2.4+/-0.3 min (mean+/-SE) at the time of onset of severe ventricular dysrhythmias, all of which returned toward control before the cessation of the dysrhythmia (33.5+/-1.5 min after coronary occlusion). Increases in cyclic AMP in ischemic zones preceded corresponding increases in the frequency of premature ventricular complexes (PVCs). Propranolol inhibited the increases in cyclic AMP and reduced the frequency of PVCs in animals without ventricular fibrillation. In animals with ventricular fibrillation, cyclic AMP was significantly elevated in normal and ischemic zones compared to animals with PVCs only. Electrical induction of PVCs or ventricular fibrillation in ischemic and nonischemic hearts failed to increase cyclic AMP. The results suggest that the changes in regional adrenergic stimulation of the heart may contribute to perpetuation of ventricular dysrhythmia and the genesis of ventricular fibrillation early after the onset of myocardial ischemia.
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PMID:Mechanisms contributing to malignant dysrhythmias induced by ischemia in the cat. 20 67

The application of cyclic AMP as a marker of myocardial ischemia in humans with coronary artery disease has been investigated during pacing-induced angina. Cyclic AMP was determined by a radioimmunoassay. In 15 patients myocardial lactate extraction at rest (20 +/- 12%) converted to production levels (-30 +/- 23%) during angina (p less than 0.0005). Insignificant changes occurred in coronary venous plasma cyclic-AMP levels. The mean myocardial cyclic-AMP extraction at rest (0.3 +/- 8.7%) converted to small release values (-6.0 +/-11%) during angina (= n.s.). No significant correlation was found between myocardial lactate and cyclic-AMP uptake or release. Therefore, cyclic AMP is an insensitive marker in the evaluation of myocardial ischemia.
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PMID:Myocardial extraction of cyclic AMP during pacing-induced angina. 22 57

Experimental myocardial ischemia produced in dogs by proximal left anterior descending coronary artery ligation is accompanied by relatively rapid (1 h) increases in the number of (-) [3H]dihydroalprenolol binding sites without changing their dissociation constants in ischemic left ventricular tissue. The changes, persist for at least 8 h and are accompanied by marked decreases in myocardial tissue ischemic region norepinephrine content. In contrast, in the same canine model 1 h of proximal left anterior descending coronary artery ligation did not result in a significant change in the number of [3H]quinuclidynl benzilate binding sites of their dissociation constants. However, the number of [3H]quinuclidynl benzilate binding sites (muscarinic cholinergic receptors) are 50--70% greater than (-) [3H]dihydroalprenolol binding sites (beta adrenergic receptors) in canine left ventricular tissue. Thus, the data suggest that proximal left anterior descending coronary artery occlusion for 1 h significantly increases the number of beta adrenergic receptors in ischemic left ventricular tissue without changing the number of muscarinic cholinergic receptors. Whether the ischemia-produced increase in cardiac beta-receptor content is causally related to increased cyclic AMP levels that develop in ischemic tissue and/or an etiologic factor in arrhythmias originating from ischemic myocardial tissue will have to be determined in additional studies.
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PMID:Beta adrenergic and muscarinic cholinergic receptors in canine myocardium. Effects of ischemia. 22 35

Insertion of a flow pump into the Langendorff retrograde perfusion apparatus has permitted the production of stable, graded ischemia in hearts whose hemodynamic and metabolic response may be evaluated. Ventricular pressures were monitored with a modified balloon and catheter-tip manometer system, and oxygen consumption , lactate and glucose metabolism, and tissue high-energy phosphate stores measured. A 15-min stabilization period in 56 paced hearts was followed by 15 min of either full, 40, 30, 20, or 10% coronary flow, after which the ventricular tissue was freeze-clamped for tissue assay. Tissue creatine phosphate fell progressively from 23.7 in full flow hearts to 9.9 mumol/g dry wt after 90% reduction in flow. This was accompanied by a graded reduction in ATP from 20.3 to 14.0 mumol/g dry wt and a rise in AMP from 1.1 to 2.6 mumol/g dry wt. Tissue lactate rose progressively from 22.3 to 60.1 mumol/g dry wt. Hemodynamic function correlated with coronary flow. This preparation offers an opportunity to study pharmacological and metabolic interventions in ischemic heart disease.
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PMID:A model of graded ischemia in the isolated perfused rat heart. 93 18

An in situ working swine heart preparation is described in which total coronary perfusion was controlled. At normal rates of coronary flow, oxygen, glucose, and fatty acid utilization were stable for at least a 60-min perfusion period. With a 50% reduction in coronary flow, oxygen and glucose consumption were reduced during 30 min of perfusion and fatty acid extraction was lower at the end of 30 min. Glycogen utilization was increased, but tissue levels of creatine phosphate, ATP, and lactate were similar to those in hearts receiving normal flow. With a 60% reduction in coronary flow, uptake of oxygen, glucose, and fatty acids were further decreased. Tissue levels of high-energy phosphates and glycogen were decreased and ADP, AMP, and lactate increased. Mechanical performance progressively deteriorated in these hearts, and ventricular fibrillation developed after about 20 min (19.8 plus or minus 3.0 min). The data indicate that this preparation is suitable for the study of myocardial metabolism during mild and severe ischemia and may be useful for the evaluation of pharmacological interventions designed for the treatment of myocardial ischemia.
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PMID:Metabolic responses to varying restrictions of coronary blood flow in swine. 111 86

Catecholamines mediate their effects in the heart through beta 1- and beta 2-receptors. Beta 1-receptors mediate the effects of sympathetic nerve stimulation. Alpha-receptors may have a role but, unlike the beta-receptor mediated responses, act without producing any increase in cyclic AMP. Prolonged receptor stimulation results in a reduction in beta-receptor sensitivity. In contrast blockade with a non-agonist agent is associated with an increase in catecholamine sensitivity which may be responsible for the withdrawal reactions that can occur when beta-blocking drugs are rapidly withdrawn in patients with ischaemic heart disease. Experimentally, prolonged noradrenaline infusions result in ventricular hypertrophy. Catecholamines have been implicated in several pathologies. High and rising catecholamine levels are associated with worsening of prognosis in patients with heart failure. These patients show a decreased beta-receptor number and cellular concentration of catecholamines. On the other hand cardiomyopathy is associated with an increased sensitivity to catecholamines. Catecholamines aggravate cardiac damage in ischaemia. Excessively high catecholamine loads cause myocardial damage in otherwise normal hearts, for example in patients with a phaeochromocytoma and those with various forms of cerebral damage such as subarachnoid haemorrhage, cerebrovascular accidents, and head injury.
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PMID:Heart and catecholamines. 168 38

We tested the hypothesis that loss of mitochondrial adenine nucleotides during myocardial ischemia is induced by the accumulation of inorganic phosphate (Pi) and a decrease in cytosolic ATP. In the isolated perfused rat heart, loss of mitochondrial adenine nucleotides (ATP + ADP + AMP) was preceded by the rise in tissue Pi and the loss of tissue ATP. After 30 min ischemia, the average rate of loss of mitochondrial adenine nucleotides was c. 1.5% of the initial pool/min. In isolated heart mitochondria, there are two pathways for adenine nucleotide release: a 'fast', phosphate-dependent pathway, which is inhibited by atractyloside; and a 'slow', phosphate-independent pathway, which is insensitive to atractyloside. Decreasing the pH from 7.4 to 6.5 significantly decreased the rate of release by the phosphate-dependent pathway (but not the phosphate-independent pathway). Analysis of release rates indicated that HPO4-2 is responsible for the phosphate-induced release; Vmax = 53.8% of the pool/per minute, Km = 7.5 mM. In vitro, extramitochondrial ATP inhibited adenine nucleotide release in the presence of Pi such that the rate of release was inversely proportional to the extramitochondrial [ATP]; extrapolation to zero ATP indicated a release rate of 2 to 3% of the pool/per minute, which is approximately equal to the rate of the 'slow' phosphate-independent pathway. Moreover, increasing the Pi concentration did not increase the rate of adenine nucleotide release in the presence of extramitochondrial ATP. Accumulation of mitochondrial adenine nucleotides was observed when the mitochondria were incubated in the presence of 4 mM or greater ATP. The results suggest that the rise in intracellular Pi during myocardial ischemia does not induce the loss of adenine nucleotides from the mitochondrial compartment, but rather that degradation of cytosolic ATP results in a slowing of ATP influx such that the rate of efflux (phosphate-independent) exceeds the rate of influx.
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PMID:Mechanism of loss of adenine nucleotides from mitochondria during myocardial ischemia. 181 Oct 58


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