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)

Despite the use of cold blood potassium (CBK) cardioplegia, the severely impaired myocardium and/or long ischemia time continue to be a challenge. Because of the association of Ca++ with cell injury and death, the use of Ca++ entry blockers is logical. Investigation of cold blood diltiazem (CBD) revealed no advantages over CBK cardioplegia. The combination of potassium and diltiazem is appropriate because of their different mechanisms of action. Ten dogs had 1 hour of myocardial ischemia with topical ice (temperature 7 degrees +/- 2 degrees C) after coronary perfusion with 200 ml of cold blood (5 degrees +/- 1 degree C) containing potassium (30 mEq/L) and diltiazem (400 micrograms/kg). Eight dogs had 2 hours of ischemia after perfusion with 200 ml of cold blood containing potassium (30 mEq/L) and diltiazem (200 micrograms/kg) and reperfusion every 30 minutes with 100 ml of cold blood containing KCl (30 mEq/L) and diltiazem (100 micrograms/kg). Six dogs received the same treatment as the previous group except that diltiazem was increased to 1,600 micrograms/kg for all four perfusions. Baseline studies were repeated after 60 minutes of reperfusion without the use of Ca++ or inotropic agents. Heart rate, peak systolic pressure, velocity of the contractile element (Vce), maximum velocity of contractile element (Vmax), peak +dp/dt, peak -dp/dt, dp/dt over common peak isovolumic pressure, left ventricular compliance, stiffness and elasticity, and heart water were unchanged from control. Coronary vascular resistance was unchanged in Groups 1 and 2 but declined in Group 3. Creatine phosphate was preserved during ischemia; adenosine triphosphate (ATP) declined. With reperfusion there was continued fall in ATP, ADP, and the adenosine pool. Ultrastructure was well preserved. In 16 of 24 dogs defibrillation was not required, whereas all 48 dogs with CBK and all 13 with CBD required defibrillation. These data suggest that the addition of diltiazem to CBK provides more effective cardioplegia (preservation of creatine phosphate), although ATP and the adenosine pool continued to decline with reperfusion.
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PMID:Cold blood potassium diltiazem cardioplegia. 669 11

High energy phosphates [phosphocreatine (PCr) and adenosine triphosphate (ATP)] are maintained in the heart under conditions of altered myocardial contractility and under certain conditions of maintained in the heart under conditions of altered myocardial contractility and under certain conditions of myocardial ischemia (such as hibernating myocardium). However, the metabolic consequences of reduced regional contractility have not been investigated. This study was designed to test the hypotheses that (1) under conditions of normal blood flow, reduction in regional contractility does not result in changes in PCr or ATP and (2) under conditions of reduced blood flow, reduction in regional contractility prevents the expected decline in high energy phosphates usually seen in regional ischemia. An in situ open chest swine preparation was used in which regional contractility was reduced with the administration of intracoronary lidocaine. High energy phosphates were measured using phosphorus-31 magnetic resonance spectroscopy (NMR) under conditions of normal flow and reduced flow. Intracoronary lidocaine infusion in 9 animals did not change blood flow from basal levels, but significantly reduced regional segment shortening from 0.16 +/- 0.02 to 0.02 +/- 0.01. The ratio of PCr/ATP did not change with lidocaine infusion (control: 1.53 +/- 0.09; lidocaine: 1.59 +/- 0.11), but oxygen content in the anterior interventricular vein increased from 8.25 +/- 0.69 to 9.83 +/- 0.91 ml/O2/100 ml blood in parallel studies (P = 0.04). While the lidocaine infusion was maintained, subsequent coronary stenosis significantly reduced subendocardial blood flow from 0.91 +/- 0.06 to 0.41 +/- 0.06 ml/min/g without significantly altering high energy phosphates (PCr/ATP = 1.51 +/- 0.15). In contrast to the 29% decline in PCr previously seen with regional ischemia, PCr was unchanged with this degree of flow reduction in the presence of lidocaine. Thus, PCr and ATP are unchanged under conditions of reduced contractility, consistent with equilibrium of energy synthesis and utilization. In addition, factors which reduce myocardial contractility, either pharmacologically or endogenously, protect against the metabolic consequences of reduced flow by reducing MVO2.
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PMID:Effects of regional myocardial lidocaine infusion on high energy phosphates. 773 Oct 55

Depending on its duration, temporary myocardial ischemia leads to a disturbance of myocardial function before irreversible cellular necrosis is developed. Mechanical, electrical, and metabolic disturbances were suggested to be possible mechanisms accounting for the altered mechanical performance in ischemic hearts. To further investigate the alteration of myocardial energy metabolism on the subcellular level, we determined, by means of nonaqueous fractionation, the cytosolic-mitochondrial distribution of high-energy phosphates and other metabolites (ATP, ADP, phosphocreatine, creatine, and inorganic phosphate) in ischemic (zero-flow) guinea pig hearts after isolated perfused working heart preparation. Additional experiments using 31P nuclear magnetic resonance spectroscopy were performed to determine pHi and [Mg2+]i changes during global ischemia. The total ATP content of myocardial tissue dropped only slowly to 76% of control ATP at 10 minutes and to 51% at 30 minutes and reached almost zero at 60 minutes of ischemia. However, striking differences were observed on the subcellular level: While cytosolic phosphocreatine was almost completely consumed after 3 minutes of ischemia (from 19.1 +/- 1.6 to 3.3 +/- 0.5 mmol/L), ATP concentration in the cytosol decreased within 30 minutes from 8.4 +/- 0.6 to only 5.4 +/- 0.9 mmol/L. Mitochondrial ATP was rapidly and linearly reduced to 60% after 5 minutes of ischemia and was nearly unmeasurable after a further 20 minutes. Thus, in contrast to the breakdown of phosphocreatine in cytosol, the only slight alteration of cytosolic ATP reveals a reduction in cytosolic ATP utilization. Moreover, the unaffected cytosolic-mitochondrial difference in the phosphorylation potential of ATP demonstrates the intact function of the ADP/ATP carrier during early ischemia. These results might indicate a disturbance of the functional coupling between carrier and phosphocreatine kinase (phosphocreatine shuttle), which could be of importance for the early contractile failure in myocardial ischemia.
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PMID:Alteration of the cytosolic-mitochondrial distribution of high-energy phosphates during global myocardial ischemia may contribute to early contractile failure. 792 21

Thirty-seven men with angiography or ultrasound confirmed peripheral arterial occlusive disease were divided into two groups. Group 1 included 24 patients treated with one daily infusion of 10 g of phosphocreatine in 200 ml of solvent for 10 days. Group 2 included 13 patients who were given 0.9% NaCl in the same scheme. Groups were comparable in: duration of intermittent claudication, maximal walking distance, Ketle index, cholesterol, triglycerides, frequency of ischemic heart disease, hypertension, diabetes, smoking. Patients were examined 4 times: before starting, on second day, after treatment period, and 1 month after. Treadmill-test; ADP-, PAF-, 5-HT-induced platelet aggregation; D-dimer; PAI-1 activity; blood viscosity at high and low shear rate; hematocrit were performed. After treatment maximal walking distance significantly increased in patients of Group 1. Mechanisms of this effects include positive influence of phosphocreatine on platelet aggregation, blood rheology, coagulation and fibrinolytic systems.
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PMID:The effect of exogenous phosphocreatine on maximal walking distance, blood rheology, platelet aggregation, and fibrinolysis in patients with intermittent claudication. 807

Myocardial ischemia is characterized by a decrease in phosphocreatine (PCr) and Mg(2+)-ATP contents as well as an accumulation of myosin ATPase reaction products (inorganic phosphate [P(i)], protons, and Mg(2+)-ADP). The possibility that these metabolites play a role in rigor tension development was checked in rat ventricular Triton X-100-skinned fibers. Rigor tension was induced by stepwise decreasing [Mg(2+)-ATP] in the presence or in the absence of 12 mmol/L PCr. To mimic the diastolic ionic environment of the myofibrils, [free Ca2+] was set at 100 nmol/L (pCa 7); [free Mg2+], at 1 mmol/L; and ionic strength, at 160 mmol/L. In control conditions (pH 7.1, with no added P(i) or Mg(2+)-ADP), the pMg(2+)-ATP for half-maximal rigor tension (pMg(2+)-ATP50) was 5.07 +/- 0.03 in the presence of PCr. After withdrawal of PCr, the pMg2+)-ATP50 value was shifted toward higher Mg(2+)-ATP values (3.57 +/- 0.03). Addition of 20 mmol/L P(i) shifted the pMg(2+)-ATP50 to 3.71 +/- 0.04 (P < .05) in the absence of PCr and in the opposite direction to 4.98 +/- 0.02 (P < .01) in the presence of PCr. Acidic pH (6.6) strongly increased pMg(2+)-ATP50 in both the absence (3.90 +/- 0.03, P < .001) and presence (5.44 +/- 0.02, P < .001) of PCr. Conversely, Mg(2+)-ADP (250 mumol/L) decreased pMg(2+)-ATP50 to 3.26 +/- 0.06 (P < .001) in the absence of PCr; at pMg(2+)-ATP 4, no rigor tension was observed until PCr concentration was decreased to < 2 mmol/L. At acidic pH, maximal rigor tension was lower by 29% compared with control conditions, whereas in the presence of Mg(2+)-ADP, maximal rigor tension developed to 143% of the control value; P(i) had no effect. The tension-to-stiffness (measured by the quick length-change technique) ratio was lower in rigor (no PCr and pMg(2+)-ATP 6) than during Ca2+ activation in the presence of both PCr and ATP. Compared with control rigor conditions, this parameter was unchanged by Mg(2+)-ADP and decreased by acidic pH, suggesting a proton-induced decrease in the amount of force per crossbridge. In addition to their known effects on active tension, Mg(2+)-ADP and protons affect rigor tension and influence ischemic contracture development. It is concluded that ischemic contracture and increased myocardial stiffness may be mediated by a decreased PCr and local Mg(2+)-ADP accumulation. This emphasizes the importance of myofibrillar creatine kinase activity in preventing ischemic contracture.
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PMID:Myocardial ischemic contracture. Metabolites affect rigor tension development and stiffness. 815 39

Noninvasive measurements of high-energy phosphate metabolism in the anterior myocardium of heart patients are now possible with image-guided, localized nuclear magnetic resonance (MR) spectroscopy. The results, reviewed herein, are largely consistent with those of prior animal studies. Quantification with phosphorus-31 MR yields normal phosphocreatine (PCr) and adenosine triphosphate (ATP) concentrations of about 11 and 6 mumol per gram wet weight, respectively, with a PCr/ATP ratio of around 1.8. Studies of patients with hypertrophic and dilated cardiomyopathy, left ventricular hypertrophy, valve disease, transplanted hearts, myocardial infarction, or reversible ischemia reveal abnormalities in the PCr/ATP ratio and/or the metabolite concentrations. Differences in reported findings for cardiomyopathies might be attributable to statistical sensitivity and the presence of heart failure. The technique might find use in the clinic for identifying failure when other factors complicate diagnosis. The PCr/ATP ratio is often reduced in transplanted hearts but is not a reliable predictor of histologic rejection involving myocyte necrosis. In myocardial infarction, metabolite levels may be reduced while the remaining PCr and ATP signals likely reflect surrounding surviving tissue. Stress-test studies of anterior myocardial ischemia produce transient reductions in the PCr/ATP ratio, which appear to be specific for ischemic disease. This may lead to a new way of assessing ischemia, particularly if the technology can gain access to a larger portion of the heart. Cardiac spectroscopy with nuclei other than P-31 shows promise.
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PMID:MR spectroscopy of the human heart: the status and the challenges. 818 33

Interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectra were continuously collected on perfused rat hearts subjected to low-flow ischemia (30 min, 10% flow) or zero-flow ischemia (21 min) followed by reperfusion. During untreated low-flow and zero-flow ischemia, intracellular Na+ (Nai+) increased by 53 +/- 11 (+/- SE) and 78 +/- 8%, respectively, and remained elevated for zero-flow hearts. However, during both low- and zero-flow ischemia, Nai+ did not increase in hearts treated with the Na(+)-H+ exchange inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). The pH decreases during ischemia were unchanged. EIPA treatment reduced ATP depletion during ischemia. During reperfusion from zero-flow ischemia, EIPA-treated hearts displayed more rapid and extensive recoveries of phosphocreatine and ATP. Recovery of left ventricular developed pressure was improved for zero-flow hearts treated with EIPA during the ischemic period exclusively (104 +/- 13%) compared with untreated hearts (36 +/- 21%). These data indicate that Na(+)-H+ exchange is an important mechanism for Nai+ accumulation, but not for pH regulation, during myocardial ischemia. Additionally, Nai+ homeostasis plays an important role in the postischemic recovery of cellular energy and ventricular function.
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PMID:NMR measurements of Na+ and cellular energy in ischemic rat heart: role of Na(+)-H+ exchange. 828 40

To demonstrate the usefulness of in vivo 31P nuclear magnetic resonance spectroscopy (MRS) in the diagnosis of ischemic heart disease, major findings from three clinical cardiac MRS investigations performed at our institute are summarized. The first study investigated whether 31P MRS with handgrip exercise testing could detect myocardial ischemia demonstrated by exercise 201Tl scintigraphy. Contrary to findings in normal subjects or patients with fixed thallium defects, the ratio of phosphocreatine (PCr) to ATP decreased significantly during exercise in patients with reversible thallium defects. In the second study, PCr and ATP content was measured by 31P MRS and compared in human myocardium with reversible ischemia or scar diagnosed by exercise thallium scintigraphy. Although the PCr content decreased in patients with either reversible or fixed thallium defects, the ATP content decreased only in the latter group. In the third study, postischemic myocardium with chronic mechanical dysfunction that exhibits recovery after revascularization in left ventriculography was metabolically characterized using quantitative cardiac 31P MRS. Postischemic myocardium with reversible mechanical dysfunction demonstrated reduced PCr but normal ATP content. These results suggest that 31P MRS is a clinically important method both for the detection of myocardial ischemia and in the evaluation of myocardial viability.
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PMID:[Diagnosis of myocardial ischemia and viability by 31P nuclear magnetic resonance spectroscopy]. 959 25

Endothelin-1 (ET-1) is the most potent vasoconstrictor known to date, and it was proposed that this peptide plays a major role in myocardial ischemia/reperfusion injury. ET-1 could increase myocardial susceptibility to ischemia by two mechanisms: via coronary flow reduction and/or via direct, metabolic effects on the heart. In isolated, buffer-perfused rat hearts, function was measured with a left ventricular balloon, and energy metabolism (ATP, phosphocreatine, inorganic phosphate, intracellular pH) was estimated by 31NMR-spectroscopy. Under constant pressure perfusion, hearts were subjected to 15 min of control perfusion, 15 ("moderate injury") or 30 ("severe injury") min of global ischemia, followed by 30 min of reperfusion. Hearts were pre-treated with ET-1 (boluses of 0.04, 4, 40 of 400 pmol) 5 min prior to ischemia. In the control period, ET-1 reduced coronary flow, ventricular function, phosphocreatine and intracellular pH dose-dependently: during ischemia/reperfusion, coronary flow, functional recovery and high-energy phosphate metabolism were adversely affected by ET-1 in a dose-related manner. To study effects of ET-1 not related to coronary flow reduction, additional hearts were perfused under constant flow conditions (ET-1 0 or 400 pmol) during 15 min of control, 15 min of ischemia and 30 min of reperfusion. When coronary flow was held constant, functional and energetic parameters were similar for untreated and ET-1 treated hearts during the entire protocol, i.e. the adverse effects of ET-1 on function and energy metabolism during ischemia/reperfusion were completely abolished. In both constant pressure and constant flow protocols, 400 pmol ET-1 reduced the extent of ischemic intracellular acidosis. The authors conclude that ET-1 increases the susceptibility of isolated hearts to ischemia/reperfusion injury via reduction of coronary flow.
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PMID:Endothelin-1 increases susceptibility of isolated rat hearts to ischemia/reperfusion injury by reducing coronary flow. 999 May 37

The value of magnetic resonance (MR) imaging and 31P spectroscopy is reported for evaluating the anatomy, function, and high-energy phosphate metabolism of the heart in patients with cardiovascular disease. Recent developments include the evaluation of myocardial contraction under pharmacologic stress and direct tracking of wall motion with myocardial tagging, assessment of first-pass myocardial perfusion with ultrafast MR in conjunction with MR contrast agents, and MR velocity mapping to determine flow velocity and volume in medium-sized vascular structures. The clinical significance of 31P spectroscopy is expanding, as shown in several studies in patients with ischemic heart disease and cardiomyopathy. The phosphocreatine to ATP ratio proved to be a sensitive marker for regional ischemia in patients with critical coronary artery stenoses. Changes in high-energy phosphate metabolism may be detected in patients with dilated cardiomyopathy, which may be useful to differentiate primary and secondary cardiomyopathies. MR imaging and 31P spectroscopy may be combined for a complete evaluation of patients with cardiovascular disease.
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PMID:Magnetic resonance imaging and spectroscopy of the heart. 1014 2


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