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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. This study was undertaken to find out if early postoperative high-dose infusion of the selective beta 1-blocking agent metoprolol tartrate has additional effects on metabolic variables related to myocardial energy supply/demand balance compared with those obtained with a late preoperative oral dose. The study included 21 male patients undergoing coronary bypass grafting. All patients received an oral dose of metoprolol before the operation. After the operation, patients were randomized to a control group or a group receiving intravenous infusion of metoprolol. Myocardial uptake of oxygen and substrates was determined before and during atrial pacing. Metoprolol reduced arterial concentrations of free fatty acids, reduced myocardial uptake of free fatty acids, and enhanced myocardial uptake of lactate. During paced tachycardia, the metoprolol concentration correlated negatively with myocardial uptake of free fatty acids (r = -0.80; p < 0.001) and positively with myocardial uptake of lactate (r = 0.53; p < 0.05). It is concluded that postoperative infusion of metoprolol induces myocardial metabolic changes compatible with an improved energy supply/demand balance.
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PMID:Influence of beta 1-blockade on myocardial substrates early after a coronary operation. 144 2

To explore the effect of beta-adrenergic blockade on low heart rate-related (mental stress) ischemia, 19 patients with coronary artery disease were randomized into a double-blind crossover trial of metoprolol, 100 mg twice daily, and underwent serial mental stress/bicycle exercise studies. Mental stress-induced wall motion abnormalities occurred at a lower heart rate than exercise-induced wall motion abnormalities during placebo administration (81 +/- 16 vs. 123 +/- 20 beats/min, p less than 0.05). Metoprolol reduced the mean magnitude of exercise-induced wall motion abnormalities (2.8 +/- 2.0 vs. 1.6 +/- 2.4, p = 0.003); improvement was related to the magnitude of hemodynamic beta-blockade effect. Metoprolol did not significantly reduce the mean magnitude of mental stress-induced wall motion abnormalities (3.0 +/- 2.2 vs. 2.6 +/- 2.2), although individual responses predominantly either improved (50%) or worsened (29%). Unlike exercise, the magnitude of hemodynamic beta-blockade did not predict mental stress response and metoprolol did not block mental stress-induced blood pressure elevations. Patients with abolition of exercise-induced ischemia were more likely to have reduction of mental stress-induced ischemia. Patients whose ischemia worsened with metoprolol during mental stress had more easily inducible ischemia, as assessed by exercise-induced placebo wall motion abnormality, chest pain and prior myocardial infarction. Beta-blockade was associated with a lowering of ischemia-related hemodynamic thresholds compared with placebo. These results suggest that beta-blockade has a variable effect on low heart rate-related ischemia that may be due to a lack of effect on mental stress-induced blood pressure elevation in patients with easily induced ischemia or to effects on coronary vasomotor tone, or both.
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PMID:Effect of beta-blockade on low heart rate-related ischemia during mental stress. 167 34

Although the benefit of beta-adrenergic blocking agents in acute coronary ischemia has been well documented, it is unclear whether the responsible mechanisms include the modification of platelet function. In recent studies, metoprolol appeared to reduce the total number and duration of episodes of silent ischemia in patients with stable coronary artery disease throughout the day. This effect was not associated with a change in baseline or circadian variability of the platelet aggregability. Since the treatment caused significant decreases in heart rate and blood pressure, the drug effect is more likely to be based on reduction of myocardial oxygen demand. Metoprolol, however, prevented a platelet aggregability increase and intracellular cAMP decrease during exercise stress testing in patients with stable angina pectoris. We speculate that this effect of beta 1-adrenergic blockade may be due to hemodynamic and neurohormonal changes, or possibly also to an increase in synthesis or release of platelet inhibiting substances.
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PMID:Beta 1-blockade and acute coronary ischemia. Possible role of platelets. 195 17

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

The acute hemodynamic responses to beta-adrenoceptor blockade with the beta 1-selective antagonist metoprolol, and to combined alpha/beta-receptor blockade with labetalol, were compared intraindividually in a randomized single-blind, cross-over study. Fourteen patients with proved ischemic heart disease, aged 52-64 years, were studied at rest (supine) and during ischemia-inducing exercise (in the seated posture) using invasive percutaneous techniques. Metoprolol reduced heart rates and cardiac output greatly (p less than 0.001) and systemic arterial pressures slightly (p less than 0.001) under all conditions. Left ventricular filling pressures increased. Labetalol induced a slight decrease in heart rates during exercise, while cardiac output was unchanged. Systemic arterial pressures and vascular resistances, pressures and resistances in the pulmonary circulation, and left ventricular filling pressures were distinctly lower. During ischemia-inducing exercise, the differences between the effects of labetalol and metoprolol on heart rate, cardiac output, systemic vascular resistance, and left ventricular filling pressures were highly significant. The effects on the rate X pressure product and on angina were similar. It is concluded that combined alpha/beta-blockade with labetalol offsets or attenuates the potential adverse hemodynamic effects of beta-receptor blockade alone without loss of symptomatic efficacy.
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PMID:Hemodynamic effects at rest and during exercise of combined alpha/beta-receptor blockade and of beta-receptor blockade alone in patients with ischemic heart disease. 244 2

To determine the effect of metoprolol on silent ischemia and platelet aggregability, 10 patients with coronary artery disease were studied with a randomized, double-blind, placebo-controlled, crossover trial. Patients were treated with metoprolol (200 mg b.i.d.) or placebo for 1 week and then received the alternate therapy. Two days before the end of each treatment period, platelet aggregability was studied for 24 hours, and a 48-hour ambulatory electrocardiogram was obtained. Compared with placebo, metoprolol significantly decreased the total number (from 26 to 4, p less than 0.1) and duration (from 735 to 84 minutes, p less than 0.01) of silent ischemic episodes. This decrease was accompanied by a decrease in the mean blood pressure (from 127/81 to 118/71 mm Hg, p less than 0.01) and the mean heart rate (from 70 to 54 beats/min, p less than 0.01). The incidence of silent ischemic episodes in the morning was significantly higher in untreated patients than in treated patients. The few episodes observed during metoprolol treatment occurred at the same time as the peak incidence observed during placebo treatment. During placebo treatment, platelet aggregability increased from 6:00 to 9:00 AM as reflected by a decrease in the threshold concentrations of ADP and epinephrine required to induce biphasic platelet aggregation (from 4.8 +/- 0.8 to 2.6 +/- 0.4 microM, p less than 0.02; and from 7.3 +/- 2.3 to 1.8 +/- 0.9 microM, respectively, p less than 0.02). Metoprolol did not alter the basal level nor blunt the morning increase of platelet aggregability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppression of silent ischemia by metoprolol without alteration of morning increase of platelet aggregability in patients with stable coronary artery disease. 264 63

The hemodynamic responses to 3 different therapeutical regimens: beta-adrenoceptor blockade, calcium inflow inhibition and combined alpha-beta-blockade were evaluated in 3 matched randomized groups of patients with ischemic heart disease and typical exercise-induced angina. The groups consisted of 22, 16 and 15 men, mean age 55-59 years. They were studied at rest and during ischemia-inducing exercise, before and after single oral doses of 100 mg metoprolol, 10 mg nifedipine and 200 mg labetalol. Pressures in the brachial artery and the pulmonary circulation were recorded by means of percutaneously introduced catheters. Cardiac output was determined according to the Fick principle. Metoprolol reduced mean arterial pressures, heart rate and cardiac output. Systemic vascular resistance and left ventricular filling pressure increased. Nifedipine resulted under all conditions in a distinct reduction of systemic vascular resistance and arterial pressures and a slight increase in heart rate and cardiac output. Left ventricular filling pressure was significantly lowered, the more the higher the initial level. The effect of labetalol was similar to that of nifedipine; however, cardiac output was unchanged and heart rate was slightly reduced. Left ventricular filling pressure was significantly lower. It is apparent that suppression of adrenergic stimulation by beta-receptor blockade alone may have adverse hemodynamic effects in ischemic heart disease and prompt further functional deterioration. Conversely, both calcium and combined alpha-beta-receptor blockade tend to improve left ventricular function by lowering both left ventricular preload and total systemic vascular resistance. The results strongly suggest that in patients in whom beta-receptor blockers appear indicated, their adverse hemodynamic effects can be offset by concomitant alpha1-receptor blockade or vasodilation without losing symptomatic efficacy. Combined alpha-beta-receptor blockade has the advantage over calcium antagonists alone to prevent any increase in adrenergic activity and related hyperkinetic response.
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PMID:Differential hemodynamic effects of beta-adrenoceptor blockers, Ca antagonists and combined alpha-beta-receptor blockade in ischemic heart disease. 286 48

In a randomized double-blind study, treatment with either metoprolol, nifedipine, or their combination was compared for effects on ischemic variables and heart rate obtained during ambulatory monitoring in 42 patients with chronic stable angina. All patients had severe chronic stable angina of at least 6 months' duration despite medical treatment, and exhibited coronary artery stenosis of 75% in one or more coronary arteries. Metoprolol reduced the frequency of total (p less than 0.01) and asymptomatic ischemic episodes (p less than 0.05), the duration of ischemia (p less than 0.05), and the ischemic burden (p less than 0.05), which contrasted to the lack of any similar significant effect during nifedipine monotherapy. During combination therapy, there was a tendency to further improvement, which did not reach statistical significance compared with metoprolol monotherapy. Heart rate at the onset of ischemia was reduced by metoprolol therapy (p less than 0.01), indicating that metoprolol acts by reducing myocardial oxygen demand even during ischemic episodes observed in daily life, where impairments of myocardial oxygen supply are suspected. No change in heart rate at the onset of ischemia could be detected during nifedipine monotherapy. It is concluded that metoprolol monotherapy, as well as its combination with nifedipine, effectively reduces total ischemic activity compared with placebo and nifedipine monotherapy. Control of ischemic activity in chronic stable angina may have prognostic implications.
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PMID:Randomized double-blind comparison of metoprolol, nifedipine, and their combination in chronic stable angina: effects on total ischemic activity and heart rate at onset of ischemia. 317 96

This study investigates effects of beta-adrenergic blockade on total silent ischemic time assessed by ambulatory electrocardiographic monitoring and its relation to heart rate and time of day in ambulatory men with coronary artery disease. Metoprolol, when titrated to optimal dose in a controlled trial in 9 patients, reduced both total silent ischemic time (from 156 +/- 65 to 20 +/- 15 minutes, p = 0.04) and frequency of silent ischemic episodes (from 8 +/- 2 to 2 +/- 2 episodes, p = 0.03) compared with placebo. Mean daily heart rate was reduced, from 82 +/- 2 beats/min during placebo to 58 +/- 1 beats/min, as was heart rate at onset of 1 mm of ST-segment depression (106 +/- 2 to 74 +/- 4 beats/min, both p less than 0.001). Heart rate increased 10 +/- 1 beats/min during silent ischemia with placebo therapy, but increased only 4 +/- 1 beats/min during metoprolol treatment (p less than 0.03). During placebo administration the largest proportion of silent ischemic time occurred between 0600 and 1200 hours. Metoprolol attenuated this circadian variation in silent ischemia while reducing (p less than 0.05) total silent ischemic time in all periods. Thus, beta-adrenergic blockade reduces the frequency of silent myocardial ischemic episodes and total silent ischemic time, while mean daily heart rate and heart rate at onset of ischemia and maximal ischemia decrease. Metoprolol treatment also attenuates circadian variation of silent ischemia. These data may be interpreted to suggest that beta-adrenergic activation operates in the pathogenesis of silent myocardial ischemia and its circadian variation.
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PMID:Effects of titrated beta blockade (metoprolol) on silent myocardial ischemia in ambulatory patients with coronary artery disease. 363 Sep 34

The effects of pretreatment with metoprolol (2 mg/kg, i.v.), UK 38,485 (5 mg/kg, i.v.), and a combination of the two drugs were examined on early (0-0.5/hr) and late (0.5-4 hr) ischemic arrhythmias resulting from coronary artery ligation in the anesthetized rat. Metoprolol was administered at different times after the onset of ischemia to determine any relationship between antiarrhythmic effects and the time of administration. Studies with two other thromboxane synthetase inhibitors, dazoxiben and carboxyheptylimizadole, and a thromboxane analogue, U 46,619, were performed on the early arrhythmias to investigate a possible role of thromboxane A2 in the genesis of ischemic arrhythmias. Pretreatment and very early intervention with metoprolol caused a significant reduction in the incidence of ventricular fibrillation (VF) in the 0-0.5 hr period. The number of ventricular ectopic beats (VEBs) and the incidence of ventricular tachycardia (VT) during the 0.5-4 hr period were markedly reduced by both pretreatment and late intervention with metoprolol. VEBs and VT in the 0-0.5 hr phase were reduced by UK 38,485 and carboxyheptylimidazole and increased by U 46,619. Administration of a combination of the drugs produced a significant reduction in early VF and late VEBs.
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PMID:The effect of beta-adrenoceptor blockade and of thromboxane synthetase inhibition, alone and in combination, on arrhythmias resulting from myocardial ischemia. 403 60


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