Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008031 (chest pain)
 17,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glyceryl trinitrate (GTN) has found widespread use for the treatment of angina pectoris, a pathological condition manifested by chest pain resulting from insufficient blood supply to the heart. Metabolic conversion of GTN, a nitric oxide (NO) pro-drug, into NO induces vasodilation and improves blood flow. Patients develop tolerance to GTN after several weeks of continuous use, limiting the potential for long-term therapy. The mechanistic cause of nitrate tolerance is relatively unknown. We developed a cell culture model of nitrate tolerance that utilizes stable isotopes to measure metabolism of 15N3-GTN into 15N-nitrite. We performed global metabolomics to identify the mechanism of GTN-induced nitrate tolerance and to elucidate the protective role of vitamin C (ascorbic acid). Metabolomics analyses revealed that GTN impaired purine metabolism and depleted intracellular ATP and GTP. GTN inactivated xanthine oxidase (XO), an enzyme that is critical for the metabolic bioactivation of GTN into NO. Ascorbic acid prevented inactivation of XO, resulting in increased NO production from GTN. Our studies suggest that ascorbic acid has the ability to prevent nitrate tolerance by protecting XO, but not aldehyde dehydrogenase (another GTN bioactivating enzyme), from GTN-induced inactivation. Our findings provide a mechanistic explanation for the previously observed beneficial effects of ascorbic acid in nitrate therapy.
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PMID:Metabolomics-Driven Elucidation of Cellular Nitrate Tolerance Reveals Ascorbic Acid Prevents Nitroglycerin-Induced Inactivation of Xanthine Oxidase. 3031 19

A 61-year-old man was admitted to our hospital due to chest pain on both rest and effort. After the computed tomography coronary angiography, coronary stenosis was recognized at segment 3. Because inferior ischemia on stress myocardial perfusion scintigraphy with 201 thallium chloride induced by adenosine was found, we planned to perform the coronary intervention. After control coronary angiography, no significant stenosis was found in the right coronary artery. Intracoronary acetylcholine testing disclosed diffuse spasm at segment 4, whereas intracoronary ergonovine administration documented the total spasm at segment 3. After the intracoronary administration of nitrate, we diagnosed him with coronary spastic angina without organic stenosis. <Learning objective: We describe a case of coronary spastic angina whose spontaneous coronary spasm was detected by computed tomography coronary angiography incidentally.>.
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PMID:Spontaneous coronary artery spasm detected by computed tomography coronary angiography: Provoked spasm site similar to intracoronary injection of ergonovine but not acetylcholine. 3176 35

We report the case of a 33-year-old woman with no history of coronary risk factors or chest pain who experienced intermittent chest pain at rest for several minutes from 2 PM. At 8 AM the next day, chest pain recurred and persisted for about 1 hour. She was transported to our hospital by ambulance, where electrocardiogram showed ST-elevation in the precordial leads, and blood tests showed elevation of cardiac markers. She was diagnosed with ST-elevation myocardial infarction. Because she was a young woman without any risk factors, coronary spastic angina was suspected. Coronary angiography without intracoronary nitrate administration revealed diffuse 75% stenosis in the proximal right coronary artery (RCA) and diffuse 90% stenosis in the left anterior descending artery (LAD). A coronary spasm provocation test elicited chest pain; coronary angiography showed 99% diffuse stenosis of LAD; and electrocardiogram showed precordial ST-segment elevation. Although intracoronary nitroglycerin injection attenuated the coronary spasm in the RCA and proximal LAD, 90% stenosis and coronary dissection were observed in the midportion of the LAD. When the imaging test that was carried out before the provocation test was reexamined, the dissection was recognized, and there was no clear dissection progress after the test. Intravascular ultrasound showed dissection of the LAD, as did angiography. We treated the patient using medical therapy instead of percutaneous coronary intervention.The patient did not suffer any anginal attack and improved sufficiently to be discharged. She remained free of attacks for about 10 years to the present time, and follow-up is continuing.
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PMID:Acute Myocardial Infarction Caused by Coronary Spasm and Dissection Treated with Medical Therapy. 3195 46


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