Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BACKGROUND. Acute closure remains a significant limitation of percutaneous transluminal coronary angioplasty (PTCA) and underlies the majority of ischemic complications. This study details the clinical and angiographic characteristics of a series of patients receiving an intracoronary stent device to manage acute and threatened closure and presents the early clinical results. METHODS AND RESULTS. From October 1989 through June 1991, 115 patients undergoing PTCA received intracoronary stents to treat acute or threatened closure in 119 vessels. Sixty-three percent had multivessel coronary disease, 33 (29%) had undergone prior coronary artery bypass grafting (CABG), and 52 (45%) had had previous PTCA. Using the American College of Cardiology/American Heart Association (ACC/AHA) classification, 15% of lesions were class A, 55% were class B, and 30% were class C. Eight patients were referred with severe coronary dissection and unstable angina after PTCA at other institutions. Acute closure was defined as occlusion of the vessel with TIMI (Thrombolysis in Myocardial Infarction) 0 or 1 flow immediately before stent placement. Threatened closure required two or more of the following criteria: 1) a residual stenosis greater than 50%, 2) TIMI grade 2 flow, 3) angiographic dissection comprising extraluminal dye extravasation and/or a length of greater than 15 mm, 4) evidence of clinical ischemia (either typical angina or ECG changes). Twelve vessels (10%) met the criteria for acute closure, and 87 vessels (73%) satisfied the criteria for threatened closure. Twenty vessels (17%) failed to meet two criteria. Stenting produced optimal angiographic results in 111 vessels (93%), with mean diameter stenosis (+/- 1 SD) reduced from 83 +/- 12% before to 18 +/- 29% after stenting. Overall, in-hospital mortality was 1.7% and CABG was required in 4.2%; Q wave myocardial infarction (MI) occurred in 7% and non-Q wave MI in 9%. Stent thrombosis occurred in nine patients (7.6%). For the 108 patients who presented to the catheterization laboratory without evolving MI, Q wave MI occurred in 4% and non-Q wave MI occurred in 7%. Angiographic follow-up has been performed in 81 eligible patients (76%), and 34 patients (41%) had a lesion of greater than or equal to 50%. CONCLUSIONS. This stent may be a useful adjunct to balloon dilatation in acute or threatened closure. Randomized studies comparing this stent with alternative technologies are required.
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PMID:Intracoronary stenting for acute and threatened closure complicating percutaneous transluminal coronary angioplasty. 153 28

We determined whether high fatty acid oxidation rates during aerobic reperfusion of ischemic hearts could be explained by a decrease in malonyl-CoA levels, which would relieve inhibition of carnitine palmitoyl-transferase 1, the rate-limiting enzyme involved in mitochondrial uptake of fatty acids. Isolated working rat hearts perfused with 1.2 mM palmitate were subjected to 30 min of global ischemia, followed by 60 min of aerobic reperfusion. Fatty acid oxidation rates during reperfusion were 136% higher than rates seen in aerobically perfused control hearts, despite the fact that cardiac work recovered to only 16% of pre-ischemic values. Neither the activity of carnitine palmitoyltransferase 1, or the IC50 value of malonyl-CoA for carnitine palmitoyl-transferase 1 were altered in mitochondria isolated from aerobic, ischemic, or reperfused ischemic hearts. Levels of malonyl-CoA were extremely low at the end of reperfusion compared to levels seen in aerobic controls, as was the activity of acetyl-CoA carboxylase, the enzyme which produces malonyl-CoA. The activity of 5'-AMP-activated protein kinase, which has been shown to phosphorylate and inactivate acetyl-CoA carboxylase in other tissues, was significantly increased at the end of ischemia, and remained elevated throughout reperfusion. These results suggest that accumulation of 5'-AMP during ischemia results in an activation of AMP-activated protein kinase, which phosphorylates and inactivates ACC during reperfusion. The subsequent decrease in malonyl-CoA levels wil result in accelerated fatty acid oxidation rates during reperfusion of ischemic hearts.
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PMID:High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5'-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. 761 56

Cerebral edema is one of the major consequences of head trauma (HT); its evolution may cause secondary ischemia and neuronal damage. In a closed head injury model in rats, we have shown BBB disruption and edema formation during the post traumatic period. We have previously shown that chronic exposure to moderate heat improves clinical outcome of rats subjected to HT. Long term exposure to heat results in the achievement of a stable acclimated state, characterized by a lower metabolic rate and improved heat tolerance. In the present study, we investigated the effect of chronic exposure to heat on edema formation after HT. Rats were held at 24 degrees C (CON) or 34 degrees C (ACC) for one month. Injury was then induced under ether anesthesia by a weight drop device. Four or 48 hours later, they were sacrificed for evaluation of BBB integrity (Evans blue, EB, extravasation) or edema formation (specific gravity, SG, or percent water). We found that EB uptake by the contused hemisphere was 6 fold lower in the ACC rats as compared to CON (p < 0.001). Furthermore, edema measured at 48 h by both SG and percent water methods was significantly lower in the acclimated rats (p < 0.01). We suggest that heat acclimation offers protection to rats subjected to head injury, possibly by reduction of plasma proteins extravasation.
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PMID:Long term exposure to heat reduces edema formation after closed head injury in the rat. 797 14

Although rotational ablation has been successful in the treatment of complex coronary lesions, periprocedural complications of microvascular-mediated ischemia (slow flow or no reflow) and coronary vasospasm may occur. In an attempt to reduce such complications, a drug cocktail consisting of a combination of verapamil 10 micrograms/ml, nitroglycerin 4 micrograms/ml, and heparin 20 U/ml was infused in 21 consecutive patients with AHA/ACC Type B2 and C lesion morphology. A total of 27 lesions were treated, with a procedural success rate of 95%. One patient required emergency bypass surgery. Coronary vasospasm occurred in 7% (2/27 lesions). Only one lesion (3.7%) was associated with a transient reduction in TIMI flow that resolved within 5 min, and none had classical no-reflow. No patient developed intraluminal thrombus, and none had hypotension requiring inotropic support. All patients had prophylactic temporary pacemakers inserted. All RCA and circumflex lesions and 50% of LAD stenoses required transient pacing. A "cocktail" infusion of verapamil, nitroglycerin, and heparin mixed in pressurized saline delivered through the 4-French Teflon sheath of the Rotablator system during rotational ablation is associated with high success and low complication rates. Transient AV block is frequent, especially when treating RCA and circumflex arteries; therefore, prophylactic pacing is indicated.
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PMID:Cocktail attenuation of rotational ablation flow effects (CARAFE) study: pilot. 887 32

The evaluation and management of heart disease in patients about to undergo noncardiac surgery begins with a careful history and physical examination, including an assessment of clinical risk for perioperative myocardial infarction and/or death. Patients can be categorized into major, intermediate, minor or low clinical risk groups, based on clinical markers such as past myocardial infarction, congestive heart failure, angina or diabetes. Additional evaluation includes estimation of surgery-specific risk, prior coronary evaluation and/or revascularization, and level of functional capacity. Based on these parameters, physicians can decide to engage in further noninvasive testing to assess left ventricular function and/or risk of perioperative ischemia in a small, selected group of patients. Rarely, patients may meet criteria for perioperative coronary revascularization followed by noncardiac surgery. Perioperative medical therapy relies heavily on the use of beta blockers. Postoperative cardiac surveillance must be tailored to the individual patient. The use of pulmonary arterial catheters, the type of anesthesia and the assessment of long-term cardiac risk are also discussed in this summary of the ACC/AHA Guidelines.
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PMID:Surgical patients with heart disease: summary of the ACC/AHA guidelines. American College of Cardiology/American Heart Association. 930 74

Internists are frequently asked to do preoperative consultations and to manage perioperative complications. Realistic goals are to identify patient factors that increase the risk of surgery, to quantify this risk in order to make decisions about the appropriateness of and timing of the surgery, to provide recommendations on how to minimize the risk, to identify and manage coexisting medical conditions and their associated medication requirements, to monitor the patient for perioperative problems, and to make recommendations to deal with these problems when they occur. With few exceptions, nonselective imaging and laboratory screening tests have repeatedly been shown to be of little value when the history and physical do not suggest a problem. The risk associated with the planned surgery can be estimated, with the most common serious complications being cardiac events. Updated versions of Goldman's risk indices are particularly helpful for this. Clinical variables are optimally combined with selective stress testing to discern which patients will benefit from preoperative revascularization. This has been studied best in the setting of vascular surgery. A critical guiding principle is that the value of revascularization must be judged in terms of long term gains rather than just immediate perioperative benefit. Other interventions include the selective use of beta blockers, adequate analgesia for all, control of hypertension, and appropriate volume management, especially in the settings of preexisting CHF or valvular disease. It must also be recognized that perioperative ischemia and CHF often present atypically. An approach that combines aspects of both the ACC/AHA and the ACP guidelines seems optimal. A variety of noncardiac issues must also be addressed. Postoperative pulmonary complications are common, especially with preexisting pulmonary disease, thoracic and upper abdominal surgery, and obesity. PFTs and ABGs are indicated in selected patients. Stopping smoking, incentive spirometry, and selective use of bronchodilators and antibiotics are helpful. Patients with rheumatologic diseases have specific concerns based on systemic manifestations of disease including anemia, thrombocytopenia, pulmonary fibrosis, pericarditis, and hypercoagulability; medication effects particularly from steroids and nonsteroidal anti-inflammatory drugs; and specific joint problems including contractures and atlantoaxial joint instability. Diabetes increases the risk of infection and cardiac complications. Prevention of ketoacidosis and glucose control are necessary and can be achieved through a variety of approaches, depending on whether the patient suffers from Type 1 or Type 2 diabetes. The threshold for transfusion has increased in recent years, as has the use of erythropoietin and autologous blood donation. There is no longer an absolute hemoglobin that requires transfusion, although most require transfusion for hemoglobins less than 8 mg/dL, especially in the setting of cardiac disease and bloody surgery. The elderly require surgery at an increased rate and often do not do as well as younger patients. The primary issues are, however, not their age but their increased frequency of underlying disease and diminished reserve. The latter makes them prone to postoperative delirium, sensitivity to medications, and cardiac and pulmonary problems. Despite the many diseases that patients often have and the stresses of surgery itself, modern anesthetic and surgical techniques allow almost all patients to undergo necessary procedures at acceptable risk. The internist plays a critical role in minimizing this risk even further.
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PMID:Recognition and management of preoperative risk. 1046 30

AMP-activated protein kinase (AMPK) is a metabolic stress-sensing protein kinase responsible for coordinating metabolism and energy demand. In rodents, exercise accelerates fatty acid metabolism, enhances glucose uptake, and stimulates nitric oxide (NO) production in skeletal muscle. AMPK phosphorylates and inhibits acetyl-coenzyme A (CoA) carboxylase (ACC) and enhances GLUT-4 translocation. It has been reported that human skeletal muscle malonyl-CoA levels do not change in response to exercise, suggesting that other mechanisms besides inhibition of ACC may be operating to accelerate fatty acid oxidation. Here, we show that a 30-s bicycle sprint exercise increases the activity of the human skeletal muscle AMPK-alpha1 and -alpha2 isoforms approximately two- to threefold and the phosphorylation of ACC at Ser(79) (AMPK phosphorylation site) approximately 8.5-fold. Under these conditions, there is also an approximately 5.5-fold increase in phosphorylation of neuronal NO synthase-mu (nNOSmu;) at Ser(1451). These observations support the concept that inhibition of ACC is an important component in stimulating fatty acid oxidation in response to exercise and that there is coordinated regulation of nNOSmu to protect the muscle from ischemia/metabolic stress.
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PMID:AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. 1105 78

A hypothesis is presented that explains one of the mechanisms by which a heart starts to fail. The hypothesis is that myocardial function of an overloaded or otherwise stressed heart may become impaired by cellular troponin degradation in vital cardiomyocytes. The troponins (I, T and C) regulate actin-myosin interaction, thereby controlling contraction and relaxation. Troponins have been shown to be targets of activated calpain I. This enzyme, that is activated by elevated intracellular Ca2+ concentrations, such as occurs during ischemia, degrades troponins, leading to impaired interaction between actin and myosin and, thereby, less contractile force. Several reports about troponin degradation in viable myocardium support this hypothesis. Also, results are discussed that demonstrate the presence of immunoreactive troponin fragments in plasma under conditions in which myocardial necrosis can be excluded or is unlikely. The hypothesis implicates that release of troponin and/or troponin degradation products is not specific for necrotic myocardium but may occur from viable myocardium as well. To test this hypothesis, several lines of research are suggested. If the hypothesis is not rejected in the near future, the concept that a positive troponin test reflects 'even microscopic zones of myocardial necrosis' as used by the Joint ESC/ACC Committee for the Redefinition of Myocardial Infarction [The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Myocardial infarction redefined-A consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513], should be withdrawn.
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PMID:Hypothesis: troponin degradation is one of the factors responsible for deterioration of left ventricular function in heart failure. 1223 61

The recent document of the ESC/ACC Committee for the redefinition of myocardial infarction (MI) has introduced the measurement of cardiac troponin as the biochemical standard for the diagnosis of MI. This change has been mainly driven by the demonstration that any amount of myocardial damage, as detected by cardiac troponins, implies a worse long-term outcome of the patient. The results of several studies consistently show that there is a continuous relationship between the degree of troponin elevation and the patient's prognosis. The new definition has important consequences on the diagnostic and therapeutic approaches to patients with acute coronary syndromes; in fact, patients with increased troponins, i.e. patients with MI, necessitate more aggressive treatment than those without troponin elevations, i.e. patients with unstable angina. The application of the new definition is expected to increase the number of cases of MI by about 30% and to decrease mortality. We believe that several aspects of the new definition need to be discussed before the new criteria for MI are used in clinical practice in Italy. The most relevant issues are the following: 1) the definition of troponin elevation should meet the analytical performance of the available assays, the diagnostic cutoff of which is frequently too imprecise. We propose that troponin elevations be defined as values exceeding the concentration corresponding to a total analytical imprecision of 10%. We disclose such a concentration for the currently available assays and suggest its use in clinical practice to mitigate the possibility of false-positive values; 2) the number of samples required for the diagnosis should be sufficient for the assessment of the changes in concentration over time. When only one sample is available, or when the temporal pattern of the changes in marker concentration is not consistent with the time elapsed from the onset of symptoms, we suggest that objective evidence that myocardial ischemia is the likely cause of myocardial damage should be obtained; 3) the diagnosis of MI after a percutaneous coronary intervention represents a unique situation. In contrast with myocardial damage occurring during spontaneous ischemia, available data do not support the concept that any troponin elevation is associated with an adverse prognosis. In the absence of conclusive studies, we suggest that the diagnosis of MI after a percutaneous coronary intervention be based on conventional criteria. Finally, we propose this summary with the aim of overcoming some of the more controversial aspects of the ESC/ACC redefinition of MI: Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) elevation of biochemical markers of myocardial necrosis (preferably troponin) with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); d) coronary artery intervention (e.g., coronary angioplasty). Marker elevations should be accompanied by objective evidence that myocardial ischemia is the likely cause of myocardial damage when: a) only one blood sample is available; b) marker changes over time are not consistent with the onset of symptoms; 2) pathologic findings of an acute MI. Criteria for established MI. Anyone of the following criteria satisfies the diagnosis for established MI: 1) development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed; 2) pathologic findings of a healed or healing MI.
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PMID:The new definition of myocardial infarction: analysis of the ESC/ACC Consensus Document and reflections on its applicability to the Italian Health System. 1240 56

The recent document of the ESC/ACC Committee for the redefinition of myocardial infarction (MI) has introduced the measurement of cardiac troponin as the biochemical standard for the diagnosis of MI. This change has been mainly driven by the demonstration that any amount of myocardial damage, as detected by cardiac troponins, implies a worse long-term outcome of the patient. The results of several studies consistently show that there is a continuous relationship between the degree of troponin elevation and the patient's prognosis. The new definition has important consequences on the diagnostic and therapeutic approaches to patients with acute coronary syndromes; in fact, patients with increased troponins, i.e. patients with MI, necessitate more aggressive treatment than those without troponin elevations, i.e. patients with unstable angina. The application of the new definition is expected to increase the number of cases of MI by about 30% and to decrease mortality. We believe that several aspects of the new definition need to be discussed before the new criteria for MI are used in clinical practice in Italy. The most relevant issues are the following: 1) the definition of troponin elevation should meet the analytical performance of the available assays, the diagnostic cut-off of which is frequently too imprecise. We propose that troponin elevations be defined as values exceeding the concentration corresponding to a total analytical imprecision of 10%. We disclose such a concentration for the currently available assays and suggest its use in clinical practice to mitigate the possibility of false-positive values; 2) the number of samples required for the diagnosis should be sufficient for the assessment of the changes in concentration over time. When only one sample is available, or when the temporal pattern of the changes in marker concentration is not consistent with the time elapsed from the onset of symptoms, we suggest that objective evidence that myocardial ischemia is the likely cause of myocardial damage should be obtained; 3) the diagnosis of MI after a percutaneous coronary intervention represents a unique situation. In contrast with myocardial damage occurring during spontaneous ischemia, available data do not support the concept that any troponin elevation is associated with an adverse prognosis. In the absence of conclusive studies, we suggest that the diagnosis of MI after a percutaneous coronary intervention be based on conventional criteria. Finally, we propose this summary with the aim of overcoming some of the more controversial aspects of the ESC/ACC redefinition of MI: Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) elevation of biochemical markers of myocardial necrosis (preferably troponin) with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); d) coronary artery intervention (e.g., coronary angioplasty). Marker elevations should be accompanied by objective evidence that myocardial ischemia is the likely cause of myocardial damage when: a) only one blood sample is available; b) marker changes over time are not consistent with the onset of symptoms; 2) pathologic findings of an acute MI. Criteria for established MI. Anyone of the following criteria satisfies the diagnosis for established MI: 1) development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed; 2) pathologic findings of a healed or healing MI.
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PMID:[New definition of myocardial infarction: analysis of the consensus document ESC/ACC and thoughts about applicability to the Italian health situation]. 1240 66


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