Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The purpose of this study was to examine the protective activity of a low concentration of nifedipine (3 x 10(-8) M) against global myocardial ischemic injury in isolated perfused hearts from streptozotocin (STZ) diabetic rats (DR) as compared with control rats (CR). Hearts were subjected to 45-min global ischemia followed by 45-min reperfusion. During ischemia, the period of time until onset of the ischemic contracture was significantly longer in hearts from DR than in hearts from CR (20.3 +/- 1.0 and 15.5 +/- 0.5 min, p less than 0.05). The degree of the ischemic contracture was similar in both types of hearts. During reperfusion, a significantly smaller recovery of left ventricular pressure (LVP) was observed as was a tendency for postischemic coronary flow (CF) to be lower in hearts from DR than in those from CR. After pretreatment with nifedipine, the time of onset of the ischemic contracture was significantly more delayed in hearts from DR than in those from CR: from 20.3 +/- 1.0 to 28.1 +/- 1.2 min (p less than 0.05) and from 15.5 +/- 0.6 to 18.1 +/- 0.9 min (p less than 0.05), respectively. In addition, the degree of the ischemic contracture was reduced (45.3%) in hearts from DR but not in those from CR. During reperfusion, the CF was increased only in hearts from DR. No beneficial effects on functional recovery of LVP were observed in either type of hearts, although recovery tended to be better in diabetic hearts. Nifedipine in a low concentration appears to be more effective against myocardial ischemic injury in diabetes, resulting in an improvement in postischemic CF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of nifedipine on global myocardial ischemic injury in hearts from diabetic and age-matched control rats. 172 31

Seventy-four patients with chronic stable mild angina, mild coronary artery disease (83% had one- or two-vessel disease) and normal left ventricular function were studied to measure the response of treadmill exercise performance and painful and silent ischemia in the ambulatory setting to randomly assigned treatment with nifedipine or propranolol and their combination; titration to maximal tolerated dosages was performed in double-blind manner. At 3 months both nifedipine and propranolol reduced the weekly angina rate (p less than 0.05); during treadmill exercise testing, increases (p less than 0.05) were noted in time to angina and total exercise time and decreases in maximal ST depression at the end of exercise. There were no differences between the responses to nifedipine and propranolol and no significant additional changes were seen after another 3 months of therapy. The combination of nifedipine and propranolol reduced the number of patients with angina on exercise treadmill testing from 64% to 38% (p less than 0.05). During ambulatory electrocardiographic monitoring before treatment, there were 1.4 +/- 2.4 (mean +/- SD) episodes/24 h of painful ischemia and a very low silent ischemia frequency: mean 1.1 +/- 2.7 episodes/24 h, mean duration 16 +/- 25 min/24 h. Treatment with propranolol and nifedipine resulted in reduction of episodes and duration of painful and painless ischemia; approximately 77% of patients were free of all ischemic episodes. It is concluded that patients with chronic stable mild angina have a low incidence of silent ischemia. Nifedipine or propranolol alone, titrated to individualized maximally tolerated dosages, are equally effective in long-term control of painful and painless ischemia, anginal episodes and exercise-induced ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response of angina and ischemia to long-term treatment in patients with chronic stable angina: a double-blind randomized individualized dosing trial of nifedipine, propranolol and their combination. 173 70

Because of the absence of a generally accepted definition of unstable angina, the clinical context of drug trials for this condition has varied from trial to trial. Early- versus late-entry trials must be distinguished, and the possibility of a modification of effect caused by the nature of drug therapy already given when the patient became unstable or by concomitant treatment in addition to experimental treatment must be taken into account. These factors cannot be overlooked when the results from a limited number of reported trials are pooled together. The largest early-entry trial with a beta-blocker and a calcium antagonist was the Holland Interuniversity Nifedipine/metoprolol Trial (HINT), which enrolled patients with suspected unstable angina diagnosed at coronary care unit admission. HINT results showed that unstable angina cannot be reliably differentiated from evolving myocardial infarction (MI) in this particular context and that there are few early MIs that could have been prevented. In patients who were not already taking a beta-blocker, metoprolol reduced the incidence of acute MI or recurrent ischemia, and there was no benefit of nifedipine. On the other hand, the addition of nifedipine was effective in patients whose conditions became unstable despite maintenance treatment with a beta-blocker. Thus, previous beta-blockade modified the effect of the calcium antagonist studied. Based on evidence from HINT and other trials, it is concluded that beta-blockers should be used as the first-line treatment in patients with unstable angina and that a calcium antagonist should be added when patients remain unstable despite beta-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Medical management of unstable angina. What have we learned from the randomized trials? 197 26

A randomized, double-blind, crossover study was conducted in 10 patients to assess the effect of nifedipine versus placebo on total ischemic activity and circadian distribution of ischemic episodes. After baseline exercise treadmill testing and 48-hour ambulatory electrocardiographic ST-segment monitoring, patients received either nifedipine (mean dose, 80 mg/day) or placebo administered 4 times per day, with the initial dose taken immediately upon arising in the morning. Patients were maintained on a stable dose of each study drug for 7 days, after which they underwent repeat exercise treadmill testing and 48-hour ambulatory electrocardiography. During exercise treadmill testing, greater exercise duration was achieved by patients receiving nifedipine than by those receiving placebo (421 +/- 121 vs 353 +/- 155 seconds, respectively; p less than 0.05). Time to greater than or equal to 1 mm ST depression was significantly greater with nifedipine (282 +/- 146 seconds) than at baseline (130 +/- 72 seconds, p less than 0.003) and with placebo (150 +/- 98 seconds, p less than 0.0005). During ambulatory electrocardiographic monitoring, nifedipine reduced both the total number of ischemic episodes (18 vs 54 at baseline and 63 with placebo; p less than 0.02 for both) and the total duration of ischemia (260 vs 874 at baseline and 927 minutes with placebo; p less than 0.02 for both). The surge of ischemia between 06:00 and 12:00 noted at baseline and during placebo therapy was nearly abolished during nifedipine treatment. Nifedipine at this dosage, administered in this manner, is effective in reducing total ischemic activity and may prevent morning surges of ischemic episodes.
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PMID:Effect of nifedipine on total ischemic activity and circadian distribution of myocardial ischemic episodes in angina pectoris. 272 45

The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week treatment with a beta blocker (metoprolol CR, 200 mg once daily) or a dihydropyridine calcium antagonist (nifedipine retard 20 mg twice daily) were then compared according to a double-blind, parallel group design. Metoprolol significantly reduced the number and duration of the ischemic episodes during daily life (p less than 0.05) irrespective of the patients' clinical characteristics. Nifedipine was ineffective, particularly in patients with angina predominantly on effort and with a moderate to severe reduction in exercise tolerance. It is concluded that in patients with mixed angina, ischemic episodes during daily life are more likely to occur in patients with a clinical presentation suggesting poor coronary reserve.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine. 201 12

To assess whether pretreatment with intracoronary nifedipine protects the myocardium against acute ischemia induced by coronary occlusion, 18 patients were studied during coronary angioplasty of the left anterior coronary artery. After a control occlusion of 60 seconds, 0.1 mg nifedipine was injected and occlusion was repeated for 60 seconds. Before and during the occlusion period, pulmonary capillary pressure was measured and the intracoronary epicardial ECG was recorded. After intracoronary administration of nifedipine, the onset of the rise in diastolic filling pressure was delayed from 23 to 38 seconds (p less than 0.01) and the changes at 60 seconds of occlusion were reduced from 14 to 11 mmHg (p less than 0.05). Nifedipine delayed the appearance of ischemic ST-segment elevation in the intracoronary ECG from 11 to 21 seconds (p less than 0.01) and diminished the changes at 60 seconds of occlusion from 1.8 to 1.2 mV (p less than 0.05). These findings suggest that pretreatment with intracoronary nifedipine protects the myocardium against some of the mechanical and electrocardiographic consequences of regional ischemia during acute coronary occlusion.
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PMID:Protective effects of pretreatment with intracoronary nifedipine on myocardial ischemia and dysfunction. 207 95

Exercise treadmill tests and ambulatory monitoring were used in a double-blind, placebo-controlled, double-dummy crossover comparison of nifedipine (10 mg, 3 times daily) and transdermal nitroglycerin (15 mg). All patients (n = 20) had chronic stable angina with symptomatic and silent events. All patients had 3 episodes of angina/week and 3 episodes of ischemia/24 hr. The protocol was made up of 2 weeks of placebo followed by 2 weeks of active drug, then crossed over for 2 weeks of placebo followed by the other active drug. At the end of each 2-week period, patients had ambulatory monitoring and exercise treadmill testing. All ambulatory monitoring reports were read blind and entered into an independent data base. The results were the following: on transdermal nitroglycerin, the duration of ischemia decreased by 57% from 140 min/24 hr to 60 min/24 hr (p = 0.0054). The exercise time increased by 5.5% from 4.8 to 5.0 minutes (p = 0.16). With nifedipine, the duration of ischemia decreased by 22% from 175 min/24 hr to 137 min/24 hr (p = 0.16). The exercise tolerance time increased by 13% from 4.5 to 5.0 minutes (p = 0.0264). Nifedipine increased exercise time without altering total ischemic time, while transdermal nitroglycerin decreased total ischemic time without increasing exercise time. Thus, changes in exercise time do not necessarily predict changes in total ischemic time.
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PMID:Dissociation of exercise tolerance and total myocardial ischemic burden in chronic stable angina pectoris. 211 64

Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Differential effects on ambulatory ischemia, exercise performance, and anginal symptoms. The ASIS Study Group. 224 50

Prognostic data on the importance of silent ischemia is lacking. Preliminary reports suggest that ambulatory electrocardiographic monitoring provides additional information not contained in the exercise test, but it is still unclear whether silent ischemia is a marker of subsequent events or is responsible for their development. Recent investigations also suggest that intermittent episodes of ischemia may cause myocardial necrosis. Drugs that are effective in the treatment of angina are also effective in the treatment of silent ischemia, but their value in terms of long-term morbidity and mortality is unclear. Recently, the circadian distribution of silent ischemia has been reported in 150 patients off therapy, in 33 receiving nifedipine, and in 41 receiving atenolol. Most ischemic episodes off therapy occurred between 7:30 AM and 7:30 PM with a peak in the morning and a lesser peak in the evening. Nifedipine did not alter the circadian pattern of ischemic episodes; atenolol abolished the morning peak, the peak incidence of ischemia then occurring in the evening. This circadian distribution of ischemic episodes and the observed changes with treatment resemble the reported circadian variations of acute myocardial infarction and sudden death. Large multicenter studies are now being performed to determine the effects of treatment on silent ischemia and how this treatment may influence outcome. Until such studies have been completed, it is not possible to clearly define the indication for drug therapy in the management of silent ischemia.
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PMID:Therapeutic rationale for the management of silent ischemia. 220 62

Retrogradely perfused, isovolumically beating, paced rat hearts were subjected to 30 min of global ischemia in the absence and presence of nifedipine, verapamil, bepridil and quaternary bepridil at a concentration ranging from 3 to 10,000 nmol/l. Under constant pressure conditions, the arrest of coronary flow and the reduction of ventricular contraction during global ischemia were readily reversible and quickly returned at reperfusion. During ischemia, however, a diastolic contracture developed, which was slowly reversible upon reperfusion. The calcium antagonists studied appeared to delay and diminish in a concentration-dependent way the diastolic contracture during ischemia. Furthermore, they accelerated the reduction of this contracture at reperfusion. Nifedipine, bepridil and quaternary bepridil showed a 100 to 1000 times higher potency in accelerating the recovery of the diastolic contracture during the reperfusion phase than in reducing the development of diastolic tension during the ischemic period itself, whereas verapamil hardly discriminated these two phases. When the hearts were reperfused with nifedipine under constant flow conditions, reduction of the diastolic contracture during ischemia could still be observed, but the accelerated reduction of end-diastolic pressure during reperfusion was no longer present. The results are discussed in relation to the energy saving, negative inotropic activity of the drugs before the ischemic period and the strong coronary vasodilation, which seems to be involved in the protective activity of the drugs, especially during reperfusion.
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PMID:Calcium antagonists show two modes of protection in ischemic heart failure. 232 11


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