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)

Asymmetric dosage regimens are used to circumvent development of nitrate tolerance and are believed to restore totally the hemodynamic responsiveness to an acute dosage of nitrates. This study assessed invasively the hemodynamics during supine rest before and for 50 min after peroral 30 mg isosorbide dinitrate (ISDN) in 16 patients with stable ischemic heart disease; 8 previously untreated patients (NT group) and 8 patients treated asymmetrically b.i.d. with 30 mg ISDN for 14 days prior to the invasive investigation (T group). Before initiation of treatment, both groups had identical mean arterial pressure (MAP) and heart rate (HR). On the day of invasive investigation, before intake of ISDN, MAP was higher in the T group but unchanged in the NT group. After the intake of ISDN, right atrial pressure (RAP), mean pulmonary arterial pressure, and pulmonary arterial wedge pressure declined markedly within 10 to 15 min in both groups, while MAP showed a more protracted decline, reaching a new level only after 25 to 30 min. In the NT group, HR accelerated markedly and remained elevated throughout the observation period, whereas in the T group HR showed no significant alteration after ISDN intake. At the end of the observation period, the cardiac index (CI) was definitely reduced in the NT group, but remained unchanged in the T group, while the systemic vascular resistance index was unchanged in the former and was clearly reduced in the latter. It is concluded that the fall in MAP in the NT group was solely due to a fall in CI, and that the decline in RAP and venous return in the NT group induced neurohumoral reflexes leading to a rise in HR and prevention of arterial dilation, whereas in the T group, already influenced by chronic treatment, such acute counterregulatory responses were markedly attenuated or absent.
 ...
PMID:Early hemodynamic effects at rest with acute and chronic isosorbide dinitrate treatment in patients with ischemic heart disease. 758 63

Coronary arteriovenous difference in stable end-products of nitric oxide metabolism, nitrate and nitrite, was increased in ischemic canine hearts. In accordance with the reduction of coronary blood flow by 40, 67, 80 and 100%, the plasma nitrate+nitrite concentration increased from 3.2 +/- 0.6 to 8.7 +/- 1.3, 12.5 +/- 1.8, 15.9 +/- 2.7, and 20.2 +/- 2.3 microM, respectively. The plasma nitrate+nitrite concentrations were further elevated during reperfusion. Administration of NG-nitro-L-arginine methyl ester decreased the production of both nitrate+nitrite and coronary blood flow; the former was restored by the concomitant administration of L-arginine. These findings suggest that the increases in the nitric oxide production result from the action of nitric oxide synthase during myocardial ischemia and reperfusion, decreasing coronary vascular resistance and attenuating myocardial ischemia.
 ...
PMID:Plasma nitric oxide end products are increased in the ischemic canine heart. 779 46

This study was undertaken to test the hypothesis that percutaneous transluminal coronary angioplasty (PTCA) is a reasonable alternative to coronary artery bypass grafting (CABG) for some high-risk patients with medically refractory rest angina. Over a 5-year period, 1 operator at a tertiary Veterans Affairs Medical Center performed angioplasty on 624 patients, of whom 441 had unstable angina. Of these 441 patients, 288 had rest angina and 225 had medically refractory rest angina. Medically refractory unstable angina was defined as reversible myocardial ischemia occurring at rest in an intensive care unit setting with low flow oxygen despite the following medications: (1) oral aspirin, intravenous heparin, or both; (2) some combination of beta blocker, calcium blocker, and/or nitrate so that resting heart rate is < 70 beats/min or resting blood pressure < 140 mm Hg, or both. There were 207 patients with medically refractory rest angina who had > or = 1 of the following characteristics predictive of a more than twofold increased risk of operative death at CABG: age > 70 years, prior CABG, recent myocardial infarct, need for intravenous nitroglycerin, need for intraaortic balloon pump, and left ventricular ejection fraction < 0.35. Of these 207 patients, 11 died (5%) during index hospitalization, 196 (95%) were discharged, and 186 (90%) went home angina free. There were 2 emergency CABGs and 9 acute myocardial infarctions. At follow-up (3 to 60 months, average 24), there were 27 late deaths (for a total of 38 [18%]), 8 (4%) late CABGs, and 44 (21%) late PTCAs (with 17 [8%] late myocardial infarctions). The 2-year mortality of 18% for this cohort is comparable to a 21% 2-year mortality observed in a group of 1,073 "high-risk" patients who underwent CABG in the Veterans Affairs Medical Center from 1987 to 1988. These data support the hypothesis that PTCA provides an alternative to CABG in some high-risk patients with medically refractory rest angina.
 ...
PMID:Effectiveness of percutaneous transluminal coronary angioplasty for patients with medically refractory rest angina pectoris and high risk of adverse outcomes with coronary artery bypass grafting. 783 30

Improved understanding of the pathogenesis of symptomatic and silent myocardial ischemia has led to important advances in the prevention and treatment of these syndromes. For example, recognition of the role of platelets in the atherogenic process and of thrombosis in acute myocardial ischemia has led to extensive use of aspirin and thrombolytic therapy, with resultant decreases in mortality. Both nitrates and beta-adrenergic blockers effectively alleviate myocardial ischemia. However, long-term nitrate use is limited by the occurrence of tolerance. beta blockers have been shown to decrease subsequent cardiovascular events in patients with acute myocardial infarction; however, adverse effects are often associated with their use. Calcium antagonists have been shown to be effective in the treatment of stable and vasospastic angina. In patients with coronary artery disease and symptoms resulting from either fixed obstruction or vasospasm, these agents decrease the frequency of angina episodes. The 3 types of calcium antagonists currently available--phenylalkylamine, benzothiazepine, and dihydropyridine derivatives--while chemically a heterogeneous group, share the common property of decreasing depolarization of smooth muscle, albeit to varying degrees. Nonetheless, other characteristics, including varying electrophysiologic effects, distinguish these groups. The novel calcium antagonist amlodipine is effective and well tolerated as an antianginal agent, and offers the advantage of once-daily dosing. Calcium antagonists appear to be well tolerated in patients with concomitant conditions such as diabetes and are effective in commonly coexistent cardiovascular disorders such as hypertension.
 ...
PMID:Emerging options in the management of myocardial ischemia. 790 91

As a result of recent advances in our understanding of the role of nitric oxide and endothelial-derived relaxing factor (EDRF) in vascular control, physicians now have the potential to overcome the loss of EDRF effect by administering nitrates. Nitrates are converted to nitric oxide, resulting in vasodilator effects that improve the myocardial oxygen supply-demand imbalance responsible for myocardial ischemia. This discovery has resulted in a renewed interest in the nitrates for the treatment of ischemic syndromes, particularly chronic stable angina pectoris. Over the past 2 years, an important new formulation of nitrate has become available--isosorbide-5-mononitrate. Three different mononitrate formulations are available in the United States: Ismo tablets in December 1992; followed over a year later by Monoket tablets, available since June 1993; and Imdur extended-release tablets, available since August 1993. Although the mononitrates share the same generic name, they are not similar in regard to their formulations, which suggests the need for future studies designed to explore any clinical differences.
 ...
PMID:Mononitrates: defining the ideal long-acting nitrate. 791 30

1. The pharmacological properties of KRN2391 in animal experiments are reviewed. 2. The vasodilating mechanism of KRN2391 is based on both a nitrate action and a K channel opening action, and whether KRN2391 acts as a nitrate and/or a K channel opener depends on the type and the segment of blood vessels. 3. KRN2391 causes a preferential increase in coronary blood flow in anesthetized dogs. 4. KRN2391 produces an increase in oxygen supply to the heart and a decrease in myocardial oxygen consumption in anesthetized dogs. 5. KRN2391 shows antiangial effects in various anginal models of rats and cardioprotective effects in perfused rat hearts. 6. KRN2391 does not develop self-tolerance or cross-tolerance between KRN2391 and other nitrates in coronary dilating and vasodepressor effects. 7. The pharmacological properties of KRN2391 are thought to be beneficial for the treatment of patients with ischemic heart disease.
 ...
PMID:Pharmacological properties of KRN2391, a novel vasodilator of the nitrate-potassium channel opener hybrid type. 795 18

In an epidemiological and follow-up survey on 712 patients, 52 subjects with proven ischaemic heart disease were matched with and compared to 52 coronary-prone subjects with similar major cardiovascular risk factors (high-risk controls, HR) as well as to 52 patients at low cardiovascular risk (low-risk controls, LR). HR and LR patients were all free of overt ischaemic heart disease. Both the average daily dietary magnesium intake and the 24 h renal magnesium output were slightly higher in HR as compared to LR and ischaemic heart disease patients. No difference could be observed between the three groups with respect to serum magnesium levels, whereas erythrocyte magnesium levels were lower in ischaemic heart disease patients than in LR (P = 0.089) and to HR (P = 0.042). Ischaemic heart disease patients below 60 years had significantly lower erythrocyte magnesium levels than older (> 60 years) ischaemic heart disease patients. Lower erythrocyte magnesium levels in ischaemic heart disease patients were also associated with an increased incidence of cardiac events in the follow-up period and with a more unfavourable outcome. A pilot phase 6 month open trial of oral magnesium supplementation in nine ischaemic heart disease patients with low erythrocyte magnesium levels led to significant increases of erythrocyte magnesium in these patients, and to an impressive decrease of anginal attacks and nitrate consumption, as well as to a lesser degree of ST segment depression on surface ECG obtained at exercise testing in seven patients.
 ...
PMID:Should magnesium therapy be considered for the treatment of coronary heart disease? II. Epidemiological evidence in outpatients with and without coronary heart disease. 799 29

Recently, a new class of drugs has been developed with unique properties with regard to cardiovascular pharmacology: K(+)-channel openers. The increased K+ efflux from smooth muscle cells induced by these drugs is accompanied by a reduced intracellular availability of free Ca++, which in turn induces vascular relaxation. This property is currently being exploited to achieve peripheral and coronary artery dilatation in patients with ischemic heart disease. Cromakalim, pinacidil, and nicorandil, are the most extensively investigated agents in this class. Nicorandil, in addition to its K(+)-channel opener property, also shows a nitrate-like activity on guanylate cyclase of vascular smooth muscle cells. Clinical trials demonstrate that chronic administration of nicorandil can significantly increase exercise tolerance in patients with coronary artery disease. In experimental studies, this drug has also shown protective effects against myocardial injury induced by ischemia and reperfusion, by mechanisms partly independent of its vasodilating properties. These results suggest that K(+)-channel openers may have a relevant place in the pharmacological treatment of patients with ischemic heart disease.
 ...
PMID:[Anti-angina activity of potassium-channel activators]. 802 48

Nitroglycerin and other organic nitrates are beneficial in ischaemic heart disease and myocardial infarction and as adjunctive therapy in congestive heart failure. The nitrates are inactive prodrugs, and their vascular effects depend on metabolic conversion to vasoactive intermediates like nitric oxide and/or nitrosothiols with subsequent stimulation of guanylate cyclase causing increased formation of cyclic GMP. The compounds relax vascular smooth muscle producing venous dilatation at low concentrations and at higher concentrations dilation of coronary arteries and collaterals and systemic arterial vessels. Nitrate tolerance is, however, a problem with continuous nitrate therapy. Tolerance is most likely to occur with frequent dosing or with the use of long-acting nitrates or transdermal applications resulting in constant plasma concentrations. Therapeutic strategies should be designed to provide a daily low-nitrate period or nitrate-free period to obviate the development of tolerance and thus maintain the antianginal effects.
 ...
PMID:[Nitroglycerin preparations. Effect and tolerance]. 806 82

Nitrates are the most widely prescribed drug category in ischemic heart disease, being able to prevent and to interrupt episodes of myocardial ischemia, alleviate anginal symptoms, exert favorable effects in acute myocardial infarction. Their vascular actions, on peripheral arteries and veins, as well as on coronary arteries, can explain most of these effects. However, nitrates also exhibit platelet-inhibiting properties, mediated by the same cellular mechanisms operating on smooth muscle cells, i.e., via stimulation of guanylate cyclase and subsequent increase in cytosolic levels of cyclic GMP. When added to platelet suspensions, nitrates inhibit platelet aggregation induced by most stimuli. These in vitro effects usually require high drug concentrations; there is evidence, however, that nitrates may inhibit platelet function also in vivo. Such evidence derives from a) ex vivo studies with platelet aggregometry; b) the appreciation of a synergism between nitrates and prostacyclin; c) the appreciation of a need, for nitrate actions in vivo, of sulfhydryl group donors, such as N-acetylcysteine, and d) from studies on bleeding time. Antiplatelet effects of nitrates may be an explanation for the protection from cardiac death and reinfarction inferred on the basis of a meta-analysis of many studies of nitrates in acute myocardial infarction.
 ...
PMID:[Nitro derivatives as antiplatelet agents]. 808 22


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