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)

Sixteen anesthetized New Zealand white rabbits were subjected to thoracotomy, and a reversible snare occluder was attached around a large branch of the left circumflex coronary artery. A 1.3 cm. diameter nuclear magnetic resonance (NMR) surface coil was placed adjacent to the myocardium perfused by this vessel. The animals were divided into two groups of eight animals each, treatment and control. The rabbits were studied using a 2.0 T magnetic resonance (MR) spectrometer, and baseline spectra were acquired. The treatment animals then received intravenous propranolol (1.5 mg/kg) and the control animals received an equal volume of saline. Spectra were then acquired during a 20-minute occlusion period and during subsequent reperfusion. Animals in both groups showed expected decreases in phosphocreatine and adenosine triphosphate and an increase in inorganic phosphate during occlusion; these changes reverted toward baseline values with reperfusion. There were no significant differences between the two groups. The myocardium became acidotic during occlusion in both groups, but significantly more so in the control animals: during the first 10 minutes of occlusion pH was 7.30 +/- 0.41 in the treatment group versus 6.55 +/- 0.24 for controls (p = 0.0005). During the second 10 minutes of occlusion pH was 7.05 +/- 0.65 in the treatment group versus 6.24 +/- 0.25 in controls (p = 0.0053). We conclude that attenuation of intracellular acidosis by propranolol during myocardial ischemia was evident by MR spectroscopy in this animal model.
 ...
PMID:The effects of propranolol on regional cardiac metabolism during ischemia and reperfusion assessed by magnetic resonance spectroscopy. 235 14

Components of the renin-angiotensin system (RAS) have been found in heart tissue and it is likely that angiotensin II (ANG II) is generated locally in the heart as in other organs. Pharmacological interference with converting enzyme (CE) inhibitors reduced CE activity and ANG II generation in the heart. To investigate whether local inhibition of CE in the heart with the CE inhibitor ramipril might contribute to the therapeutic effects, experiments were performed in isolated perfused working rat hearts. Acute regional myocardial ischemia was induced by occlusion of the left coronary artery followed by reperfusion. In ischemic isolated rat hearts, both single oral pretreatment with ramipril (1 mg/kg) or perfusion with the active moiety, ramiprilat (10 micrograms/ml), protected against ventricular fibrillation, which invariably occurred in control hearts during reperfusion. Reperfusion arrhythmias were aggravated by perfusion with ANG I and ANG II, but prevented by bradykinin. ANG I-enhanced ventricular fibrillations were completely eliminated during local CE inhibition with ramipril. The CE inhibitor also improved cardiodynamics. Coronary flow, left ventricular pressure, dp/dtmax, and myocardial oxygen consumption were increased in comparison to controls without changes in heart rate. In the perfusate of treated hearts, lactate dehydrogenase, and creatine kinase activities and lactate production, were reduced. Myocardial tissue levels of glycogen, ATP, and creatine phosphate were increased in ramipril-pretreated hearts whereas lactate was decreased. The results of these experiments in rat hearts suggest that local inhibition of CE by ramipril exerts protective effects after ischemia and reperfusion by reducing arrhythmias and improving cardiac function and metabolism, thus probably contributing to the therapeutic effects of CE inhibitors in cardiovascular diseases.
 ...
PMID:Beneficial effects of the converting enzyme inhibitor, ramipril, in ischemic rat hearts. 243 98

The role of cytoskeletal damage in the disruption of the plasma membrane observed during myocardial ischemia has been studied using antibodies to vinculin to identify changes in the distribution of this membrane associated cytoskeletal protein. Vinculin is a component of the cytoskeletal attachment complex between the plasma membrane and the Z-line of the underlying myofibrils. The effects of varying periods of total ischemia on the localization of vinculin were assessed by immunofluorescence and evidence of membrane disruption was evaluated by electron microscopy. Thin tissue slices prepared from the ischemic tissue were incubated in oxygenated Krebs-Ringer phosphate buffer at 37 degrees C to assess inulin permeability, ultrastructure, and any changes in the distribution of vinculin associated with incubation. The previously reported costameric pattern of vinculin staining was observed in longitudinal sections of control myocardium, myocardium subjected to 60 minutes of total ischemia, and myocardium subjected to 60 minutes of ischemia followed by 60 minutes of incubation in oxygenated media. Electron microscopy and inulin permeability measurements confirmed that plasma membrane integrity was preserved under these conditions. However, when the duration of total ischemia was extended to 120 minutes or longer, there was a progressive loss of vinculin staining along the lateral margin of myocytes. This change correlates with the appearance of subsarcolemmal blebs and breaks in the plasma membranes observed by electron microscopy and confirmed by the increase in inulin permeability observed in tissue slices.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cytoskeletal damage during myocardial ischemia: changes in vinculin immunofluorescence staining during total in vitro ischemia in canine heart. 243 27

High energy phosphate levels are depressed following global ischemia and require several days to completely recover. Short-term methods to enhance ATP recovery have included infusion of ATP precursors, inhibition of enzymes that catabolize AMP, and membrane transport stabilization. Several precursors have been used to augment adenine nucleotide synthesis including adenosine, inosine, adenine, and ribose. Because of the short-term nature of previous experiments, recovery had been incomplete and the effects in the intact animal unknown. The purpose of this study was to determine the effects of ribose infusion in a long-term model of global ischemia and attempt to identify the precursor which limits myocardial ATP regeneration in the intact animal. Global myocardial ischemia (20 min, 37 degrees C) was produced in dogs on cardiopulmonary bypass. With reperfusion either ribose (80 mM) in normal saline or normal saline alone was infused at 1 ml/min into the right atrium and the animals were followed for 24 hr. Ventricular biopsies were obtained through an indwelling ventricular cannula prior to ischemia, at the end of ischemia, and 4 and 24 hr postischemia and analyzed for adenine nucleotides and creatine phosphate levels. Radiolabeled microspheres were used to measure myocardial and renal blood flows and no significant difference was found between ribose-treated control groups. In both groups, myocardial ATP levels fell by at least 50% at the end of ischemia. No significant ATP recovery occurred after 24 hr in the control dogs, but in the ribose-treated animals, ATP levels rebounded to 85% of control by 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Enhanced high energy phosphate recovery with ribose infusion after global myocardial ischemia in a canine model. 249 8

Nine adult rats underwent occlusion of the left coronary artery (LCA) to assess the ability of a manganese chelate of N, N'-Bis (pyridoxal-5-phosphate) ethylenediamine-N, N'-diacetic acid (Mn-DPDP), to delineate acute myocardial ischemia. Hemodynamic effects of the contrast medium were tested in the isolated rat heart. Gated transaxial images of the heart at the mid-ventricular level were obtained using a 2 Tesla magnet. A TE of 20 msec and a TR of 1 R-R interval (approximately 250 msec) were used. Images were taken prior to injection of 400 mumol/kg of Mn-DPDP, 2 minutes after injection, and then at 15 minute intervals for one hour. The time between LCA occlusion and injection of contrast averaged 95 minutes. The signal intensity (SI) of normal myocardium was increased by 125 +/- 9% immediately after injection, and did not significantly vary over one hour. SI of ischemic myocardium increased by only 16 +/- 14% immediately after injection, gradually rising to 44 +/- 13% after one hour. Visual discrimination between normal and ischemic myocardium was obtained throughout the study. The percent contrast between normal and ischemic myocardium was 47.2 +/- 6% at 2 minutes after injection, gradually decreasing to a final value of 31.3 +/- 4%. No hemodynamic effects were produced in the isolated heart using concentrations in the perfusate several-fold higher than those expected to be produced by the intravenous injection of 400 mumol/kg Mn-DPDP. Mn-DPDP shows the potential for delineation of the jeopardy area resulting from coronary occlusion for at least one hour after injection of the agent.
 ...
PMID:Magnetic resonance imaging of acute myocardial ischemia using a manganese chelate, Mn-DPDP. 250 2

Recent work has now clearly established that coronary arterial thrombosis is the direct cause of acute myocardial infarction. This thrombotic event occurs when a pre-existing atherosclerotic plaque ruptures or fissures, thereby exposing underlying thrombogenic material to the circulation. Platelets are thus activated and the clotting cascade is initiated. It is as yet unclear why a previously stable atherosclerotic plaque should fissure or rupture. However, suggested mechanisms include release of vasoactive substances from activated platelets, coronary arterial vasomotion, mechanical stress fatigue of the atherosclerotic plaque, and rupture of vasa vasorum within the atherosclerotic plaque. The resultant cessation of myocardial blood flow produces specific biochemical and physiological alterations secondary to myocardial ischemia. Intracellular acidosis, loss of high-energy phosphates, reduced sensitivity of contractile proteins to calcium, and accumulation of inorganic phosphate and lipid, all occur within the ischemic myocyte. Diastolic compliance is markedly reduced by ischemia followed by cessation of systolic contractile activity. Most of these alterations are reversible if ischemia is relieved promptly. Prolonged ischemia leads to delayed biochemical and physiological recovery and/or cell necrosis.
 ...
PMID:The pathophysiology of acute myocardial infarction. 266 57

Nuclear magnetic resonance spectroscopy has great potential for defining noninvasively the metabolic status of the heart and skeletal muscle. This technique uses the spin properties of certain nuclei (such as phosphorus-31, hydrogen-1 and carbon-13) to measure high energy phosphates, intracellular pH, lactate and glycogen. Animal studies have formed the basis for human investigations and have demonstrated well-defined changes in high energy phosphates during myocardial ischemia and reperfusion, as well as in cardiomyopathies. Human studies have been limited by issues of sensitivity and localization, although techniques such as rotating frame, depth-resolved surface coil spectroscopy, image-selected in vivo spectroscopy and spectroscopic imaging have been used to acquire phosphorus-31 spectra from the human heart. The few human studies of patients with disease have demonstrated elevated inorganic phosphate peaks after myocardial infarction and abnormal phosphodiester peaks in patients with hypertrophic cardiomyopathy. Studies of patients with heart failure have shown that these patients acidify their peripheral muscles with exercise more easily than do control subjects. Clinical application of nuclear magnetic resonance spectroscopy will depend on technical advances and the demonstration of sensitivity of metabolic changes with disease.
 ...
PMID:Cardiovascular applications of nuclear magnetic resonance spectroscopy. 267 66

Magnetic resonance spectroscopy (MRS) has been used effectively in the evaluation of cardiac physiology. Studies have been done at various levels of complexity extending from isolated hearts to man. Correlation of high-energy phosphate compounds with contractile function is achieved by simultaneous or immediate sequential measurement of ventricular contractile function and the phosphorus-31 MR spectra. Studies in isolated hearts have monitored the response to ischemia of normal and hypertrophic hearts and the preservation of myocardial function and high- energy phosphate stores by drugs administered prior to the ischemic event. Regional myocardial ischemia has been evaluated by simultaneous monitoring of myocardial regional segment length by sonomicrometry and regional myocardial 31P MRS in the intact heart of larger animal models. Function and metabolism have been assessed in man by the combined application of cine MRI and 31P MRS acquired with a surface coil.
 ...
PMID:Magnetic resonance spectroscopy of the heart. Overview of studies in animals and man. 269 42

Seventy-eight dogs with graded constriction of the left main coronary artery were studied to determine the coronary blood flow at which the heart is vulnerable to catecholamine induced ischemia. The left main coronary artery was cannulated with a Griggs' type self-perfusing cannula. The coronary blood flow (CBF) was reduced by graded constriction of the extra-corporeal circuit connected with this cannula. Blood flow rates between 12 and 117 ml/min/100 g were studied. Cardiac activation was achieved by either intracoronary administration of a physiological dose of catecholamine (noradrenaline; 0.4 microgram/kg/min or adrenaline; 0.2 microgram/kg/min), or by electrical stimulation of the left stellate ganglion (4 Hz, 2 msec, 10 V for 5 min). When CBF was below 30 ml/min/100 g, accentuated myocardial ischemia was always indicated by lactate production, myocardial creatine phosphate depletion, ischemic ST segment changes, and elevated left ventricular end diastolic pressure (LVEDP) during these stimulations. When CBF was above 50 ml/min/100 g, catecholamine clearly accelerated the cardiac function and myocardial metabolism with no signs of ischemia. When CBF was between 30 and 50 ml/min/100 g signs of accentuated myocardial ischemia appeared during catecholamine activation in only 1/2 of the dogs. This study indicated that the critical level for CBF at which endogenous or exogenous catecholamine can produce ischemia is between 30 and 50 ml/min/100 g.
 ...
PMID:Endogenous and exogenous catecholamines can accentuate myocardial ischemia only when coronary blood flow is below a critical level. 271 69

Six hours of coronary occlusion has been thought to produce extensive and irreversible transmural damage and no possibility of salvage by reperfusion. This has been based on findings of adenosine triphosphate depletion and histochemical (triphenyltetrazolium chloride nonstaining) and ultrastructural changes (conventional preparatory techniques). This study tests the hypothesis that, in contrast to conventional wisdom, considerable structural and mitochondrial functional integrity remains in cardiac muscle subjected to 6 hours of regional ischemia. Twenty open-chest anesthetized dogs underwent isolation of the left anterior descending coronary artery and were observed for 6 hours. Eight of the 20 did not undergo ischemia and served as controls. Twelve underwent 6 hours of proximal ligation of the left anterior descending coronary artery (30% +/- 2% area at risk). Transmural biopsy specimens were analyzed. Coronary occlusion reduced regional blood flow (radioactive microspheres) to less than 10 ml/100 gm/min (p less than 0.05) and dyskinesia persisted in the area at risk for 6 hours. High-energy phosphates (adenosine triphosphate and creatine phosphate) declined to negligible levels and histochemical damage occurred (49% +/- 12% triphenyltetrazolium chloride non-staining). Mitochondrial ultrastructural changes (low protein denaturation embedding technique) were mild (the integrity of the inner and outer mitochondrial surface membranes and crystal membranes was maintained and myofibrillar degeneration did not occur). Mitochondrial oxidative phosphorylation rate remained at 63% of control levels, respiratory control index remained at 77%, and adenosine diphosphate/oxygen ratio was maintained at 96%. Mitochondrial Ca++ increased with lanthanum (from 26 to 46 nmol/mg protein, p less than 0.05), but irreversible calcium precipitation did not occur; calcium could be mobilized to normal levels (i.e., 13 nmol/mg protein) by ethylenediaminetetraacetic acid chelation. These data support our inference that necrosis does not occur after 6 hours of coronary occlusion and suggest that muscle salvage by reperfusion is possible after at least 6 hours of regional myocardial ischemia.
 ...
PMID:Studies on prolonged acute regional ischemia. I. Evidence for preserved cellular viability after 6 hours of coronary occlusion. 281 16


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