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

To study the anti-ischemic effect of slow-release nifedipine ten patients with stable angina pectoris and a positive effort test were selected. Nifedipinemia was measured by a gas chromatographic method. At the peak level of effort intensity slow-release nifedipine significantly decreased the mean ST-segment depression (p < 0.05) and the ischemic score (p < 0.01) when compared to the control effort test, without decreasing the double product. Nifedipine induced no more tachycardia additional to that produced by effort. At the beginning of the effort test the level of nifedipine (15.9 +/- 2.51 ng/ml) was superior to the value considered as minimal effective and was positively correlated with the ischemic score (r = 0.67; p < 0.05). A worsening of ischemia was noted in 2 patients probably due to a steal phenomenon.
 ...
PMID:The effect of slow-release nifedipine on ST-segment depression induced by effort test. Correlations with serum levels. 864 88

This was a double-blind, within-patient, crossover study to evaluate the effects of a new formulation of metoprolol on blood pressure (BP) and myocardial ischemia. Twenty outpatients with mild to moderate essential arterial hypertension, chronic stable angina pectoris and positive exercise test, after a 2-week baseline placebo period, were randomized to receive long-acting metoprolol (OROS) 14/190 mg o.d., nifedipine SR 20 mg b.i.d. or their combination in a sequence of a 3 x 3 Latin square design. Two patients withdrew from the study (1 for adverse event during metoprolol and 1 for rise of BP during nifedipine). Nifedipine, metoprolol and their combination significantly reduced the weekly number of angina attacks and nitroglycerin consumption with respect to baseline. The total number of ischemic events (at 24-hour ECG monitoring) significantly decreased after each treatment with respect to baseline. Twenty-four hours mean systolic and diastolic BP were reduced by both nifedipine alone and metoprolol alone; the combination of the two drugs led to a further decrease in both systolic and diastolic BP. The duration of silent ischemic episodes was significantly reduced by nifedipine and combination but not by metoprolol. On the other hand 24 hours symptomatic attacks/patient were significantly reduced by beta-blocker and combination, but not by nifedipine. Metoprolol alone and administered with nifedipine caused a decrease, with respect to placebo baseline, in 24-hour mean heart rate (HR) and reduced the increase of HR and systolic BP at the onset of ST depression during symptomatic ischemic episodes. The effort time and time to ST = -1 mm at treadmill were significantly increased by treatment with nifedipine alone, with metoprolol alone and with their combination, but the combination was more effective than the individual therapies. ST depression at peak exercise was significantly reduced by each treatment. The slopes of correlations between the ST-segment variation and systolic BP, HR and rate-pressure product during exercise, significantly decreased after all treatments with respect to placebo baseline, more with the combination therapy than with nifedipine alone and metoprolol alone. In conclusion, based on our results the favourable interaction of metoprolol OROS and nifedipine given concomitantly, is likely to be due to a better control, respect to each individual therapy, of the pathogenetic mechanism of myocardia ischemia: BP and HR increases during exercise and during symptomatic ischemic episodes are controlled by the beta-blocker and coronary vasoconstriction during silent ischemia is prevented by the calcium-antagonist.
 ...
PMID:Treatment of hypertension associated with stable angina pectoris: favourable interaction between new metoprolol formulation (OROS) and nifedipine. 883 Nov 81

Preconditioning with brief ischemia before a sustained period of ischemia reduces infarct size in the perfused heart. A cultured chick ventricular myocyte model was developed to investigate the role of adenosine receptor subtypes in cardiac preconditioning. Brief hypoxic exposure, termed preconditioning hypoxia, prior to prolonged hypoxia, protected myocytes against injury induced by the prolonged hypoxia. Activation of the adenosine A1 receptor with CCPA or the A3 receptor with C1-IB-MECA can replace preconditioning hypoxia and simulate preconditioning, with a maximal effect at 100 nM. While activation of the A2a receptor by 1 microM CGS21680 could not mimic preconditioning, its stimulation during preconditioning hypoxia, however, attenuated the protection against hypoxia-induced injury. Blockade of A2a receptors with the selective antagonist CSC (1 microM) during preconditioning hypoxia enhanced the protective effect of preconditioning. Nifedipine, which blocked the A2a receptor-mediated calcium entry, abolished the A2a agonist-induced attenuation of preconditioning. Isoproterenol, forskolin, and BayK 8644, which stimulated calcium entry, also attenuated preconditioning. Nifedipine blocked the increase in calcium uptake by these agents as well as their attenuating effect on preconditioning. The present study provides the first evidence that the adenosine A3 receptor is present on ventricular myocytes and can mediate simulation of preconditioning. The data demonstrate, for the first time, that activation of the A2a receptor antagonizes the preconditioning effect of adenosine, with increased calcium entry during the preconditioning stimuli as a novel mechanism.
 ...
PMID:Direct preconditioning of cultured chick ventricular myocytes. Novel functions of cardiac adenosine A2a and A3 receptors. 887 27

In hypertension, several factors disturb coronary circulation and the metabolic reserve of the heart. This study was undertaken to test whether in hypertensive patients global and regional left ventricular (LV) function is related during exercise to the presence of significant coronary stenosis and whether lowering of coronary perfusion pressure through rapid normalization of the diastolic pressure may modify the dynamics of the left ventricle. Thirty-five patients with mild to moderate hypertension undergoing coronary angiography for the evaluation of chest pain were included in the study; upright bicycle exercise echocardiography tests were performed without therapy and 1 day later 1 h after sublingual administration of nifedipine. LV ejection fraction and regional wall motion scores were evaluated and compared at baseline, peak exercise, immediate postexercise, and recovery phases in each test through digital on-line storing of echocardiographic images. Twenty-one patients had normal coronary arteries (group 1) and 14 significant coronary stenoses (group 2); age, gender, heart rate, blood pressure, left ventricular diameter and mass index, and ejection fraction were similar in the two groups. At peak exercise LV ejection fraction slightly increased in group 1, whereas it slightly decreased in group 2 (both during the test without therapy and after nifedipine administration). All patients in group 1 had normal left ventricular wall motion during exercise; 13 of 14 patients in group 2 had LV wall motion abnormalities at peak exercise. Nifedipine did not produce any effect on LV regional wall motion in group 1, but it induced significant changes in LV regional wall motion in seven patients in group 2. Changes in LV wall motion between the two test groups were related to the number of the stenotic coronary vessels: the normal exercise test before and after therapy and the two normalized tests after nifedipine administration were in fact observed in patients with one-vessel disease, whereas worsening or changes in the site of ischemia were observed only in patients with multivessel disease. Regional and global left ventricular dynamics during exercise is mainly dependent on the existence of significant coronary artery disease. Rapid decrease of blood pressure does not alter the regional dynamics of the left ventricle during exercise in patients without coronary artery disease, but it may induce normalization, worsening, or changes in the site of wall motion abnormalities in hypertensives with significant coronary stenoses.
 ...
PMID:Relation between exercise-induced left ventricular wall motion abnormalities and coronary artery disease in hypertensive patients: effects of blood pressure normalization. 905 87

Efonidipine is a dihydropyridine derivative having a vasodilating action, which is slower in onset and longer in duration than that of nifedipine. In the present study, we compared the effects of efonidipine with those of nifedipine on the ischemic myocardial metabolism in anesthetized dogs. The heart was made ischemic by ligating the left anterior descending coronary artery (LAD) completely for 3 or 30 min. Efonidipine or nifedipine was injected intravenously, 10 or 3 min, respectively, before the start of LAD occlusion. Efonidipine (0.01 or 0.03 mg/kg) decreased both blood pressure and heart rate, whereas nifedipine (0.003 mg/kg) decreased blood pressure and increased heart rate. The magnitude of decrease in mean blood pressure induced by 0.03 mg/kg efonidipine was similar to that induced by 0.003 mg/kg nifedipine. Although efonidipine did not modify the changes in myocardial carbohydrate metabolism induced by ischemia, it attenuated the ischemia-induced decrease in the myocardial level of adenosine triphosphate and energy charge potential. Nifedipine, however, did not modify the changes in both myocardial energy and carbohydrate metabolism induced by ischemia. The results suggest that efonidipine has a cardioprotective effect in the dog, probably because of its negative chronotropic effect.
 ...
PMID:Effect of efonidipine, a novel dihydropyridine derivative, on myocardial metabolic changes induced by coronary artery ligation in dogs: comparison with nifedipine. 924 56

The effects of bisoprolol on transient myocardial ischemia have been compared with those of nifedipine in patients with coronary artery disease in end-stage renal failure maintained on haemodialysis. We also evaluated the tolerability of both drugs. Sixty patients (42 males, 18 females, mean age 52 +/- 4 years) in renal failure maintained on haemodialysis, with coronary artery disease and more than four significant episodes of transient myocardial ischemia (> or = 1 min) during 48-hour Holter monitoring, were included in the study. All cardiovascular drugs were discontinued > or = 6 days before this 48-hour ambulatory ECG monitoring, with the exception of sublingual nitrates allowed for relief of anginal attacks. Patients were then randomized to receive either bisoprolol or nifedipine for 2 weeks. After a 15-day wash-out period, they were crossed over to receive either bisoprolol or nifedipine for other 2 weeks. Statistical analysis was carried out using the Student's t test. A p value < 0.01 was considered significant. Both bisoprolol and nifedipine reduced number and duration of transient ischemic episodes as well as the total ischemic burden. Reductions were statistically significant for both antianginal drugs. Only bisoprolol was effective in silent ischemia (p < 0.001). It also reduced heart rate (p < 0.001), while nifedipine raised it (p < 0.001). Both drugs reduced systolic and diastolic blood pressure. The circadian variations of transient ischemic episodes showed two peaks in the 24 hours. Both peaks were reduced with bisoprolol. Nifedipine brought a clear overall reduction in the number of episodes but the circadian pattern was unchanged. During the study, 10 patients taking bisoprolol and 12 patients taking nifedipine had drug adverse effects. No one of them had to be withdrawn from treatment. In conclusion, bisoprolol seems to be more useful than nifedipine because its effects, in transient ischemic episodes, are greatly superior to those of nifedipine, and because it is effective also in silent ischemia. Both drugs showed a good tolerability in these patients. Bisoprolol, reducing the two daily peaks of ischemic episodes frequency, has a protective role towards mortality due to coronary artery disease.
 ...
PMID:[Effectiveness and tolerability of bisoprolol vs. nifedipine in uremic patients with ischemic cardiopathy in dialysis treatment]. 924 44

Halothane has been shown to be a powerful myocardial protectant during normothermic cardioplegic arrest and subsequent reperfusion. In view of its multiple effects on cellular Ca2+ movements and the role of this ion in ischemia-reperfusion injury, the questions of whether halothane is capable of maximally protecting the heart or whether combination therapy of halothane with other Ca2+ blocking agents may be more effective arose. Therefore, the effects of combination therapy with halothane and a calcium antagonist (nifedipine), or a Na+/H+ inhibitor (HOE 694), or a Na+/Ca2+ inhibitor (quinacrine) on postcardioplegic functional recovery were evaluated. The isolated perfused rat heart subjected to 45 minutes normothermic cardiac arrest was used as an experimental model. Dose-response curves were performed for each drug. Using the optimal dosage for each drug, the following results were obtained: (1) Nifedipine (10(-7) M; administered retrogradely 10 minutes before and after cardioplegia) and halothane (1.5% administered during cardioplegia), when administered separately, improved functional recovery. Combination therapy did not further improve protection. (2) HOE 694 (10(-7) M) or quinacrine (10(-9) M) improved post-cardioplegic functional recovery when added for 2 minutes at the onset of reperfusion. Simultaneous administration of HOE 694 and 1.5% halothane was the only combination that yielded additive protection. (3) Quinacrine, a phospholipase and Na+/Ca2+ exchanger inhibitor, appeared to be the most powerful drug used. In summary, the results obtained indicate that interventions aimed at preventing intracellular Ca2+ overload improve recovery after cardioplegic arrest. The beneficial effects of halothane could be further improved by HOE 694.
 ...
PMID:Postcardioplegic myocardial recovery: effects of halothane, nifedipine, HOE 694, and quinacrine. 978 6

A large body of evidence suggests that persistently high heart rate may be associated with a significant increase in sudden death, myocardial infarction and total mortality. Such deleterious effects may be mediated via neurohumoral activation. Conversely, interventions, such as beta-blockers, that consistently reduce heart rate may reduce sudden death and prolong survival, especially in patients who survive myocardial infarction. Thus, the deleterious effect of antianginal compounds, which may increase heart rate, is especially important in chronic myocardial syndromes as well as in chronic stable angina. In this setting, the evidence is consistent with the belief that antianginal agents that increase heart rate significantly, irrespective of their other properties, may also increase the incidence of myocardial infarction or death, in contrast to agents that induce little or no tachycardic effect or those that produce frankly bradycardic responses. Data discussed in this paper indicate that long acting calcium channel blockers of the dihydropyridine type do not increase heart rate significantly. Their slower onset and offset of action may reflect a lack of neurohumoral activation, recently confirmed in the case of nifedipine gastrointestinal therapeutic system (GITS). Data from the Nifedipine gastrointestinal therapeutic system Circadian Antiischemic Program (N-CAP) study, summarized herein, confirmed that the GITS formulation produces a minimal increase in heart rate over a period of 24 h. When the compound was given alone or with a beta-blocker, it was highly effective in suppressing symptomatic and asymptomatic episodes of myocardial ischemia in patients with chronic stable angina. These findings have important implications for the treatment of ischemia in patients with chronic stable angina.
 ...
PMID:The relevance of sympathetic activity in the pharmacological treatment of chronic stable angina. 1020 52

When both common carotid arteries of Mongolian gerbils were occluded for 5 min to produce ischemic insult, locomotor activity was increased the following day. The effect of calcium channel blockers on this ischemia-induced hyperactivity was investigated. Nimodipine, at doses of 5, 10, and 20 mg/kg, dose dependently and significantly decreased ischemia-induced hyperactivity. Nicardipine significantly decreased ischemia-induced hyperactivity and doses of 10 and 20 mg/kg. Nifedipine and flunaridine also significantly decreased ischemia-induced hyperactivity at doses of 20 mg/kg. Verapamil had no effect on ischemia-induced hyperactivity at a dose of 20 mg/kg. These findings suggest that ischemia-induced hyperactivity is related to calcium channels. These relationship between calcium channels and dopaminergic function is discussed.
 ...
PMID:Effect of calcium channel blockers on cerebral ischemia-induced hyperactivity in Mongolian gerbils. 1054 96

Diltiazem has cardioprotective properties following myocardial ischemic injury. However, there are controversial results regarding the beneficial effects of diltiazem on regional myocardial flow after ischemia. Therefore, we investigated the effect of diltiazem on changes in regional myocardial flow due to ischemia for different periods. Non-radioactive colored microspheres were used for this measurement in isolated rat heart. After 20 or 40 min of global ischemia and 40 min of reperfusion, regional myocardial flow was decreased, especially in the endocardial layer. The endocardial/epicardial ratio was also decreased. The decreases in endocardial flow and the endocardial/epicardial ratio were more remarkable after 40 min of ischemia than after 20 min of ischemia. Diltiazem (10(-6) M), which was administered 15 min before ischemia, prevented only the decrease in endocardial flow and endocardial/epicardial ratio after 20 min of ischemia, whereas it did not prevent that after 40 min of ischemia. Nifedipine (2x10(-6) M) did not exert a cardioprotective effect. These findings suggested that the effect of ischemia is marked in the endocardium and, also, that the protective effect of diltiazem is seen only during a decrease in endocardial flow following short-term and reversible ischemia.
 ...
PMID:Protective effect of diltiazem against ischemia-induced decreases in regional myocardial flow in rat heart. 1085 51


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