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)

The effect of molsidomine-induced venodilation on cardiac preload was studied in conscious resting dogs, instrumented to analyze left ventricular function and myocardial perfusion. Direct effects on veins were studied during chloralose anesthesia by measuring regional venous capacitance changes with an induction angiometer. Kinetics of molsidomine-induced effects were compared to those induced by nitroglycerin and isosorbide dinitrate. This comparison was restricted to low i.v. dosages, causing only transient threshold effects on peripheral resistance and heart rate. During molsidomine-induced venous pooling, neither any direct effect on the coronary circulation nor any direct cardiac depressant activity of the drug was detected. 100 microgram/kg molsidomine caused a reduction of left ventricular preload by 5 mm Hg, lasting at least 4 hours. This effect was significantly more pronounced than that induced by 1 microgram/kg nitroglycerin or by 25 microgram/kg isosorbide dinitrate, lasting 2 min or 20 min, respectively. However, in raising regional venous capacitance, these nitrate dosages were equi-effective to 100 microgram/kg molsidomine, the effect of which was persistent and with a greater delay in onset. These results indicate that the lasting persistance of venodilation is a decisive factor for the amount of volume pooled in the capacitance system and, consequently, for the extent of preload reduction obtained. It is concluded, that lasting vasodilation, restricted to the veins, is beneficial for ventricular performance in ischemic heart disease.
 ...
PMID:Hemodynamic and myocardial effects of long-lasting venodilation in the conscious dog: analysis of molsidomine in comparison with nitrates. 10 34

Nitrate monotherapy was assessed by treadmill exercise stress testing in 18 patients with significant but relatively asymptomatic myocardial ischemia who were receiving no other antianginal therapy. In addition, prolonged ambulatory electrocardiographic monitoring was performed in 7 patients with demonstrable ischemia during baseline monitoring. After baseline assessment, 5 treatment periods were used in a random order (each of 1 week duration), incorporating 2 dose levels of transdermal nitrate (10 and 20 mg/24 hours) and isosorbide dinitrate (ISDN) (30 and 60 mg/day in divided doses) with a 10-hour nitrate-free interval every 24 hours, as well as a placebo period using a double-blind technique. All treatment periods (including placebo) showed a significant (p < 0.01) 45 to 69% prolongation in the time to 1 mm ST depression during exercise. Paired baseline times of 231 +/- 28 and 233 +/- 30 seconds increased to 367 +/- 37 seconds with 30 mg/day of ISDN, 393 +/- 37 seconds with 60 mg/day of ISDN, 381 +/- 31 seconds with 10 mg/day of transdermal nitrate, and 372 +/- 33 seconds with 20 mg/day of transdermal nitrate. The value for placebo was 342 +/- 29 seconds, which was not significantly different from active treatment (p > 0.1). Some patients appeared to individually respond to > or = 1 nitrate preparation significantly more than to placebo, but this appeared to be unpredictable and largely independent of dosage level and route of administration. There was a qualitatively similar but statistically insignificant reduction in total ischemic time during ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Placebo effect of nitrate monotherapy for myocardial ischemia. 144 72

Prolonged exposure to organic nitrates has been shown to lead to the rapid development of tolerance to the peripheral and coronary vasodilatory effects of these drugs. As a result of this phenomenon, the hemodynamic and anti-ischemic effects of nitrates may be rapidly attenuated in patients with ischemic heart disease, congestive heart failure, or both. This nitrate tolerance appears to be both dose- and time-dependent. Likely mechanisms proposed for its development are multifactorial and include depletion of sulfhydryl groups, a nitrate-mediated increase in blood volume, and neurohormonal stimulation with activation of vasoconstrictive mechanisms.
 ...
PMID:Possible mechanisms of nitrate tolerance. 144

The organic nitrates have remarkably diverse actions that are or should be beneficial in patients with ischemic heart disease. These drugs are effective in all the important ischemic syndromes. Preliminary data in patients with acute infarction suggest that the drugs may be truly cardioprotective, resulting in improved mortality. This review has not discussed the role of nitrates in congestive heart failure or LV dysfunction, a subject of great importance. The nitrates are useful adjunctive agents in these syndromes, and the two VeHfT trials support the concept that long-term nitrate administration, in conjunction with hydralazine, may favorably alter the natural history of heart failure. This cardioprotective effect is similar to that suggested for the post-MI patient. The data are not strong enough for definitive conclusions at this time. The clinical benefits of nitrates in decreasing subjective (angina) and objective indices of ischemia in stable and unstable angina, as well as limited data in asymptomatic myocardial ischemia, are unequivocal and are as favorable as those for beta blockers or calcium antagonists. Tolerance is an important problem that unfavorably influences the potential benefits of nitrate therapy. I believe that this problem can be avoided with well-designed dosing regimens. Current research into endothelial biology in health and disease has further supported a physiologic role for the organic nitrates in patients with ischemic heart disease. The nitrate-platelet story, while controversial, is promising and offers another positive rationale for nitrate administration. The concept of nitrates replenishing disordered EDRF release or action is an exciting one. Physicians should feel fortunate to have such a remarkable group of drugs available for their patients.
 ...
PMID:Use of nitrates in ischemic heart disease. 151 14

Nitroglycerin and the long-acting nitrates are widely used in all of the anginal syndromes and have proven effectiveness in relieving or preventing myocardial ischemia. Recent developments into nitrate mechanisms of action provide new insights as to the many anti-ischemic effects of these agents. Important concepts relating to coronary arterial endothelial function are germane to nitrate therapy. Endothelial-derived relaxing factor (EDRF) is presently believed to be nitric oxide (NO), which exerts vasodilatory and/or antiplatelet actions by increasing intracellular cyclic guanosine monophosphate as a result of activation of the enzyme guanylate cyclase. In the setting of coronary atherosclerosis, or even hyperlipidemia without histologic vascular disease, endothelial dysfunction may be present, promoting a vasoconstrictor/proplatelet aggregatory milieu. Nitroglycerin and the organic nitrates are NO donors; NO is the final product of nitrate metabolism, and in the vascular smooth muscle NO induces relaxation, resulting in vasodilation of arteries and veins. In the presence of inadequate EDRF production and/or release, it appears that nitroglycerin may partially replenish EDRF-like activity. Nitrates have long been known to have major peripheral circulatory actions resulting in a marked decrease in cardiac work. Venodilation and arterial relaxation result in a decrease in intracardiac chamber size and pressures, with a resultant decrease in myocardial oxygen consumption. In addition, a variety of direct coronary circulatory actions of the nitrates have been documented. These include not only epicardial coronary artery dilation, but the prevention of coronary vasoconstriction, enhanced collateral flow, and coronary stenosis enlargement. Recent work suggests that the nitrates may also act by preventing distal coronary artery or collateral vasoconstriction, which can reduce blood flow downstream from a total coronary obstruction. Thus, there are many anti-ischemic mechanisms of action by which nitroglycerin and the organic nitrates may be beneficial in both acute and chronic ischemic heart disease syndromes. The unique salutory effects of the nitrates in subjects with left ventricular dysfunction or congestive heart failure make these drugs particularly attractive for patients with abnormal systolic function and intermittent myocardial ischemia. Finally, the emergent role of intravenous nitroglycerin in acute myocardial infarction offers new prospects that nitrate therapy may prove to be beneficial in acute myocardial infarction as well as postmyocardial infarction for the reduction of left ventricular remodeling.
 ...
PMID:Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia. 152 24

Apart from their ability to relieve myocardial ischemia, nitrates have an important role to play on preservation of left ventricular (LV) geometry and function after acute myocardial infarction (MI). In the first 48 hours after acute MI, intravenous nitroglycerin infusion titrated to a low-dose regimen produces multiple benefits, including smaller infarct size, better regional and global LV function, less remodeling, fewer in-hospital complications, and fewer deaths in-hospital and up to 1 year. This regimen might be an effective adjunct during reperfusion therapy for salvaging ischemic myocardium, LV geometry, and function. Recent studies indicate that prolonged therapy with nitrates during the healing phase after acute MI can effectively further limit progressive LV remodeling (less LV dilation, expansion, thinning, and aneurysm formation) and preserve LV function. Tolerance with chronic therapy is avoided by an eccentric dose regimen to provide a nitrate-free interval.
 ...
PMID:Role of nitrates after acute myocardial infarction. 152 30

The hemodynamics influencing effect of Nitromint sublingual tablet and aerosol (EGIS Pharmaceuticals) has been examined in 22 ischaemic heart disease patients during heart catheterisation. The patients were hospitalized and took also the earlier prescribed drugs. On the basis of the results of examinations it may be concluded that Nitromint aerosol has a therapeutic action comparable to other short-acting nitrate preparations such as sublingual nitroglycerin tablet. According to the observations of the patients the drug action develops within a significantly shorter period. Considering the type of side-effects there was no difference between the two drug forms. Primarily, Nitromint tablet caused systemic effects (headache, dizziness, throbbing head) while aerosol caused predominantly local symptoms (burning of the tongue, disagreeable taste). These effects were only temporary and ceased within 10 minutes. According to the above described observations Nitromint aerosol may successfully be used as a new nitroglycerin containing drug form in all forms of angina pectoris: in rest angina, effort angina, as a prophylaxis, in mixed type angina pectoris, as a first-aid in emergency cases in acute left heart failure, preceding the application of infusion.
 ...
PMID:Comparative haemodynamic examination of Nitromint (sublingual tablet and aerosol). 158 77

The purpose of this study was to compare the efficacy of three standard antianginal agents, nitrate, Ca antagonist, and beta blocker on myocardial ischemia in patients with effort angina (EA) using ambulatory electrocardiographic monitoring (AEM). Forty-three patients, mean age 57 +/- 11 years, with positive exercise tests were studied. AEM was performed for 24-hours, initially with the patients off all antianginal medication and then after 1-2 weeks treatment with each agent. Antianginal drugs used were long-acting isosorbide dinitrate 40-80 mg/day for nitrate (17 patients), diltiazem 90-180 mg/day for Ca antagonist (13 patients), and propranolol 30-60 mg/day or metoprolol 60-120 mg/day for beta blocker (13 patients). The following results were obtained: 1) The severity of ischemia (total magnitude and duration of ST depression) was improved with each three agent. 2) Although the number of total ischemic episodes was reduced significantly with each three agent, the number of asymptomatic episodes was reduced significantly only with beta blocker. 3) Circadian variation of ischemic episodes displayed a pattern with a peak frequency in daytime. In addition, nitrate and Ca antagonist did not reduce ischemic episodes in daytime (especially asymptomatic episodes), while beta blocker reduced both symptomatic and asymptomatic episodes in daytime resulting in change in the pattern of circadian variation of ischemia. Thus, it was concluded that beta blocker was the most effective means of reducing myocardial ischemia, including silent ischemia, in patients with EA.
 ...
PMID:[Comparative effect of anti-anginal drugs on myocardial ischemia in patient with effort angina: evaluation by ambulatory electrocardiographic monitoring]. 168 Jul 82

10 patients (6 females and 4 males with an average age of 75 years) with stable angina pectoris were treated transdermally with mepindolol in a balanced, randomized, controlled, crossover study to compare the anti-ischemic effects of 12-hour overnight, and 24-hour applications. The number of angina pectoris attacks, the oral nitrate consumption and the ischemic parameters in 24-hour ECG, i.e. episodes of manifest (MMI) and silent (SMI) myocardial ischemia, the total duration of ischemia and 24-hour heart rate profiles were investigated. Both application schemes showed typical systemic beta blocker effects in all patients and significant clinical efficacy. A dose/effect relationship and a time/effect relationship between the two different application schemes were demonstrated across all the parameters investigated. Systemic and local tolerance of the therapy was good. 2 patients showed transient, mild skin irritation, but only during one phase of the study. Premature discontinuation was not necessary in any cases. There were no relevant changes in the clinical-chemistry. The new therapeutic concept of 24-hour treatment for a. pectoris with 12-hour overnight transdermal applications showed both good clinical efficacy and a good safety profile.
 ...
PMID:Transdermal monotherapy with mepindolol BIO TSD in patients with stable angina pectoris. Placebo-controlled, crossover investigation of a new therapeutic concept with 12-hours overnight application. 180 Mar 88

Intravenous nitroglycerin therapy during acute myocardial infarction has beneficial effects on infarct size, infarct complications, and mortality. Numerous dosage formulas for the continuous administration of nitrates are currently used, although several studies have demonstrated the rapid development of tolerance during long-term treatment in patients with ischemic heart disease. The dose and dosage of a continuous nitrate application in the clinical setting of acute myocardial infarction has thus yet to be resolved. This study investigated the hemodynamic effects of a 60-h, low- (33 micrograms/min) vs high- (133 micrograms/min) dose intravenous nitroglycerin (NTG) infusion in 16 patients with uncomplicated acute myocardial infarction. In group I (33 micrograms/min NTG; n = 8) the initial nitrate effect on the pulmonary capillary pressure (PCP-control: 14 +/- 1.5; 4 h: 7 +/- 0.9; 60 h: 7 +/- 0.8; mean +/- SEM; all values in mm Hg) and mean pulmonary artery pressure (PAPM-control: 23 +/- 2.3; 4 h: 15 +/- 1.3; 60 h: 14 +/- 1.3) remained unchanged for 60 h. In group II (133 micrograms/min NTG; n = 8) an almost complete loss of the initial effect on PCP (control: 15 +/- 1.6; 4 h: 5 +/- 1.4; 60 h: 12 +/- 1.3) and PAPM (control: 25 +/- 2.0; 4 h: 14 +/- 1.8; 60 h: 20 +/- 1.3) was observed. In contrast to high-dose application the low-dose NTG-infusion induced comparable acute hemodynamic effects that were not attenuated by tolerance development.
 ...
PMID:[Dose and time dependence of hemodynamic tolerance development during intravenous nitrate therapy in acute myocardial infarct]. 190 22


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