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)

Theophylline-induced variations of cardiac metabolism have been investigated by determining concentrations of various energetic substrates and of high-energy phosphates in myocardial tissue, the repeated sampling of myocardium being made possible by an extracorporal circulation system. When administered in therapeutic, or even slightly higher doses, theophylline does not modify triglyceride, glycerol and free fatty acid content or phosphocreatine and ATP content in subepicardial and subendocardial layers, but it does lower glycogen and raise lactate concentration. Consequently, the changes in anaerobic glycolysis due to myocardial ischemia may be enhanced if, as is probably the case, theophylline fails to restore the supply of oxygen.
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PMID:Myocardial biochemical modifications induced by theophylline with reference to its value as antianginal drug. 48 94

Difficulties in studying myocardial metabolism with adequate time resolution have led to contradictory conclusions regarding the mechanisms causing contractile abnormalities during the early stages of ischemia. In acutely instrumented swine, we investigated whether abnormalities in subendocardial ATP, phosphocreatine, or lactate content develop rapidly enough during the first few heart beats after onset of partial myocardial ischemia to contribute to contractile failure. Within the first 15 beats of a 40-50% reduction in left anterior descending coronary artery blood flow, regional myocardial function was significantly reduced but continuing to deteriorate. Rapidly frozen transmural left ventricular biopsies obtained on the 15th heart beat (+/- 1.5 beats) after the onset of ischemia revealed significant decrements in subendocardial phosphocreatine and ATP levels to 77% (p less than 0.05) and 84% (p less than 0.005) of control values, respectively, but minimal change in lactate content. Metabolic effects as assessed by transmural averages took longer to become detectable; thus, there was a tendency to underestimate the importance of subendocardial metabolic effects on myocardial function. When left ventricular preload was assessed during this early time period, left ventricular end-diastolic wall thickness only decreased by 3%, and left ventricular end-diastolic pressure did not change significantly despite a large fall in coronary perfusion pressure. Thus, in an in vivo pig model with techniques optimized to detect subendocardial metabolic changes within the period of very early moderate myocardial ischemia, abnormalities in high energy phosphate compounds occurred rapidly enough to contribute to developing myocardial dysfunction, whereas preload-mediated mechanisms related to vascular distending pressure could not explain the functional deterioration under these conditions.
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PMID:Energy metabolism and contractile function after 15 beats of moderate myocardial ischemia. 157 34

The protective effects of exogenous phosphocreatine were evaluated in vitro on isolated perfused rat hearts during reperfusion of ischemic myocardium. The hearts were randomly allocated in 2 groups. In the first (n 6) phosphocreatine was added at a concentration of 10 mM. The latter was utilized as control (n 7). In both groups the results showed a slight decrease in the post-ischemic myocardial performance. Aortic systolic pressure and flow respectively decreased on reperfusion by 17% and 12.5% in the phosphocreatine group and by 25.6% and 35% in the control group. Coronary flow was reduced by 10% in the phosphocreatine and by 18% in the control group. No statistically relevant differences were reported within or between the groups. No changes in heart rate occurred in the same period in the phosphocreatine and in the control group. Myocardial enzyme release during reperfusion showed significant lower levels of CK and LDH in the phosphocreatine group compared to controls (p less than 0.001 after 65 min and p less than 0.025 after 75 min between the 2 groups). The occurrence of serious ventricular arrhythmias was considerably higher in controls with respect to the phosphocreatine group. The overall incidence of major rhythm disturbances was 66% in the phosphocreatine group and 100% in the control group. Irreversible ventricular fibrillation (57%) occurred only in control hearts. The present findings indicate that phosphocreatine exerts a protective effect during myocardial ischemia and reperfusion, especially by preventing serious ventricular arrhythmias and by reducing myocardial enzyme release.
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PMID:[Myocardium-protective effects of phosphocreatine in experimental ischemia-reperfusion]. 160 May 31

Brief episodes of myocardial ischemia are known to cause reversible depression of regional myocardial contraction after reperfusion. One of the mechanisms of this persistent regional dysfunction has been proposed to be depletion of high-energy phosphate compounds. Eight cats were prepared with a reversible snare occluder around the left anterior descending artery (LAD); a surface coil sutured to the epicardial surface over the LAD territory for measurement of 31-phosphorus (31P) magnetic resonance spectroscopy (MRS) spectra; and a pair of ultrasonic crystals implanted in the mid-myocardium for measurement of regional segment length shortening. The baseline value of percent segment length shortening (%SS) was 12.8 +/- 1.4%. Increased afterload did not significantly alter high-energy phosphate levels or %SS. All animals exhibited passive systolic bulging during occlusion (-8.4 +/- 3.6% systolic shortening) as well as reduced phosphocreatine (PRc, 30 +/- 3% of control) and increased inorganic phosphorus (Pi) (239 +/- 18%), but there was no change in adenosine triphosphate (ATP). During reflow, %SS did not completely recover (4.0 +/- 2.9%, P less than .05 versus baseline). PCr and Pi returned to control levels during the first 30 minutes of reperfusion. Increased afterload had no significant effect on high-energy phosphates or %SS in stunned hearts. These findings indicate a lack of correlation between recovery of high-energy phosphate stores and regional myocardial contractility in stunned myocardium. High-energy phosphate reserves are preserved in stunned myocardium and are unlikely to be a direct cause of myocardial dysfunction.
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PMID:Preservation of high-energy phosphate reserves in a cat model of post-ischemic myocardial dysfunction. 160 6

The aim of this work was to ascertain whether free radicals play a causal role in the injury occurring in myocardial ischemia and reperfusion. To this purpose we observed whether spin-trapping compounds protect the heart when used at a concentration capable of reacting with free radicals. The lipophilic spin trap alpha-phenyl-t-butyl nitrone (PBN) was used because it is taken up by the myocites. Isolated Langendorff rat hearts were subjected to ischemia according to two schemes: "Model A" = 30 min zero-flow ischemia followed by 30 min reperfusion; "Model B" = 60 min of low-flow ischemia (10% of the individual value; N2 saturated) followed by 30 min reperfusion. Treated groups received in addition 5.0 mM PBN which was supplied continuously. The following parameters were measured throughout the experiment: contractile performance (RPP); coronary flow (CF); CPK; phosphocreatine (PCr), ATP, inorganic phosphate (Pi), intracellular pH (pHi). The pathology obtained by "Model A" is more severe than that of Model B, and partly irreversible. During the ischemic phase in "Model A", contractility, PCr and ATP dropped to near zero; during initial reflow CPK rose about 13-fold and Pi rose 2.5-fold, while pHi decreased to 6.1. During reperfusion, a partial recovery of PCr, Pi and pHi was observed, while RPP and ATP did not increase; PBN treatment improved significantly PCr and CPK, while the other parameters were unaffected. During ischemia, "Model B" hearts showed a drop of contractility to near zero, of PCr to 35%, of ATP to 50%; CPK rose 7-fold and Pi 1.5-fold; pHi was not modified. During reperfusion, all parameters recovered in part, with exception of Pi. PBN developed a marked protective activity on all tested parameters, which gained a nearly normal value. The results of the present investigations show that the lipophilic spin trap PBN partly protects the heart from the ischemia/reperfusion injury, thus confirming that free radicals play a causal role in this pathology; the continuous loading of the tissue with the drug can be an important factor for obtaining the protective effect.
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PMID:Protective activity of the spin trap tert-butyl-alpha-phenyl nitrone (PBN) in reperfused rat heart. 161 68

Phosphocreatine (PC) has been widely used in cardiac surgery as a component of cardioplegic solutions because of its positive effects in preventing ischemic heart damage; we have researched the efficacy of PC in cardiac surgery when infused through the intravenous route before and after cardiac arrest. Two groups of patients who had undergone aortocoronary by-pass grafts were matched: group A (20 patients) did not receive any particular treatment; PC was administered intravenously to patients in group B after the induction of anaesthesia, immediately prior to cardiac arrest and after the release of aortic cross-clamp. To test the efficacy of the drug, the following parameters were evaluated: the recovery as the incidence of low cardiac output and/or need of inotropic drugs; dysrhythmias; electrocardiographic signs of myocardial ischemia or infarction; release of cardiac necrosis enzymes. Treated patients were found to have a better recovery, a lower incidence of dysrhythmias, an easier resumption of normal sinus rhythm with a lower number of electric defibrillations and a significantly lower release of cardiac enzymes. It can be therefore said that PC has a marked protective effect on myocardial anoxia in cardiac surgery, even when administered intravenously.
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PMID:[The use of systemic phosphocreatine in heart surgery]. 162 Apr 16

The three techniques allowing the noninvasive study of cardiac metabolism, namely magnetic resonance spectroscopy (MRS), positron emission tomography (PET) and single photon emission computed tomography (SPET), all use external detection with stable or radioactive isotopes. These techniques yield different information. PET is quantitative and very sensitive, and therefore only tracer amounts of molecules need to be injected. It allows neurotransmitters and receptors to be studied and a global view of metabolism (oxygen consumption, glucose and fatty acid utilization) to be obtained. SPET also has good sensitivity, but uses gamma-emitting isotopes of heteroatoms. Their longer half-lives allow follow-up for hours or days. MRS is based on stable elements with high (hydrogen 1, phosphorus 31, fluorine 19...) or low (carbon 13, Deuterium) natural abundance. It has very low sensitivity and only millimolar concentrations of substrates can be detected, but various parts of metabolism can be studied. The in vivo measurement of myocardial concentration of substances has many problems that are common to all three techniques (measurement of the volume, measurement of the quantity of each molecule, resolution, partial volume effect, improvement of the signal-to-noise ratio, movement of the organ). The complementarity of the techniques is illustrated by their applications to the study of cardiac metabolism. For instance, the energy metabolism can be studied by 31P-MRS, which detects the high-energy compounds ATP and phosphocreatine, and 13C-MRS yields information on the tricarboxylic acid cycle activity. PET and SPET allow the utilization of fatty acids, the normal fuels of the heart, to be studied. During ischaemia, PET with 18F-fluorodeoxyglucose (18FDG) can determine the glucose consumption and 1H-MRS shows the increase in lactic acid, reflecting anaerobic glycolysis. Comparison of the use of acetate labelled with 11C for PET or 13C for MRS shows the potentials and limitations of each technique. Myocardial perfusion can be evaluated directly with various PET tracers or indirectly with thallium 201 or various technetium-99m-labelled tracers by SPET. No MRS marker of perfusion is so far clinically available. Mainly SPET and PET are used clinically for the investigation of ischaemic heart disease as well as cardiomyopathies, but some initial results using 31P-MRS are being obtained.
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PMID:Complementarity of magnetic resonance spectroscopy, positron emission tomography and single photon emission tomography for the in vivo investigation of human cardiac metabolism and neurotransmission. 166 Dec 37

Recent studies have improved our understanding of the beneficial actions of calcium antagonists on myocardial microcirculation and metabolism. The effect of calcium antagonists on the microcirculation of the left ventricular rat myocardium was studied using in vivo microscopic techniques. Intravenous verapamil 0.3 mg/kg and nifedipine 75 micrograms/kg produced a 15 to 18% increase in the diameter of larger A1 and A2 coronary arterioles (range 31 to 300 microns); diameters of terminal (A4) arterioles and capillaries did not change significantly. Furthermore, verapamil significantly (p less than 0.001) increased the ratio of capillaries filled with red cells to those containing plasma alone. Verapamil pretreatment produced a similarly selective dilatation of larger coronary arterioles and protected against the ischaemia-induced fall in capillary red cell content. Spectroscopic data show that verapamil also produces an increase in myocardial phosphocreatine and preservation of adenosine triphosphate (ATP) during ischaemia in the Langendorff-perfused heart. In patients with exercise-induced angina, gallopamil decreased global myocardial 201Tl and 123I phenylpentadecanoic acid (IPPA) uptake due to a reduction in myocardial oxygen consumption. Regional 201Tl and IPPA uptake as well as IPPA clearance in post-stenotic areas tended to rise after gallopamil treatment. Thus, the beneficial effects of calcium antagonists such as verapamil or gallopamil in patients with ischaemic heart disease may result from dilatation of predominantly larger arterioles. Consequently, there is an improvement in regional perfusion and free fatty acid utilisation in reversibly ischaemic regions.
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PMID:Calcium antagonists and myocardial microperfusion. 171 89

To determine the possible application of exogenous phosphocreatine (ePC) to protect the ischemic myocardium from reperfusion abnormalities in cardiac rhythm, the antiarrhythmic and antifibrillatory activities of the agent were studied in an acute myocardial ischemia model and reperfusion-induced cardiac damage. It was shown that ePC produced a pronounced antifibrillatory effect in acute coronary occlusion and subsequent reperfusion. The agent substantially increased the threshold of electric ventricular fibrillation and the frequency of spontaneous defibrillation. The highest activity was shown by ePC in ischemic myocardial reperfusion. The agent suppressed both rapid inward Na+ current and slow inward Ca2+ current. The effects of ePC on transmembrane ion currents suggest that the agent has a unique electrophysiological mechanism of action involving the properties of Classes I and IV antiarrhythmics, making ePC promising in clinical application in patients with impaired conduction and automatism.
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PMID:[Electrophysiologic study of the anti-arrhythmic mechanism of action of phosphocreatine in acute myocardial ischemia and reperfusion]. 180 69

The effects of phosphocreatine and tocopheryl phosphate and their combined use in ischemia and reperfusion of the heart were studied in anesthetized dogs. The investigation focused on the size of myocardial infarction and left ventricular contractility, ischemic and reperfusion arrhythmias were assessed using Holter monitoring. Phosphocreatine was found to reduce the number of arrhythmias and to prevent the fatal outcomes in myocardial ischemia animals but not to influence the reperfusion rhythm disturbances. Combined administration of tocopheryl phosphate and phosphocreatine, in contrast to their isolated use, completely prevented the development of ventricular fibrillations and fatal outcomes in the animals with reconstructed coronary flow. Administration of phosphocreatine restricted the infarction size, combined use of the drugs facilitated its further reduction, while the group with isolated administration of tocopheryl phosphate showed the infarction size to differ insignificantly from the control values. Combined administration of the drugs, unlike their use alone, improved left ventricular contractility in reperfusion of ischemic myocardium. The cardioprotective effect observed in combined administration of the drugs was attended with depressed lipid peroxidation in reperfused myocardium.
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PMID:[Phosphocreatine, tocopheryl phosphate and their combination in acute ischemia and myocardial reperfusion in dogs: the effect on rhythm disorders, left ventricle contractility and infarct size]. 188 38


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