Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prenalterol is a new beta-adrenergic agonist which stimulates mainly beta 1-receptors, in contrast to isoprenaline which stimulates both beta 1- and beta 2-receptors. We studied the hemodynamic effects of prenalterol and isoprenaline in seven patients with complete heart block and idioventricular escape rhythm due to ischemic heart disease. Isoprenaline was given as a continuous infusion at two increasing doses (1.7 micrograms/min and 3.4 micrograms/min each given for 30 min). After the second dose of isoprenaline the cardiac index was increased from 2.27 +/- 0.06 to 3.61 +/- 0.60 1/min/m2, heart rate was increased from 34.1 +/- 1.2 to 50.4 +/- 3.1 beats/min and mean blood pressure was decreased by 12.4 mm Hg. Mean pulmonary artery pressure was increased by 2 mm Hg. Prenalterol was given as two i.v. bolus injections of 3.5 mg and 7.0 mg at 15-min intervals. The first dose of prenalterol increased the cardiac index from 2.22 +/- 0.10 to 2.42 +/- 0.12 and heart rate from 37.0 +/- 1.8 to 40.1 +/- 1.7. Mean blood pressure and mean pulmonary artery pressure were unchanged. The second dose of prenalterol did not change the hemodynamic variables significantly compared to the changes after the first dose. We conclude that isoprenaline is preferable to prenalterol for treatment of complete heart block.
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PMID:A comparison of the hemodynamic effects of prenalterol and isoprenaline in patients with complete heart block. 620 27

Sympathomimetic amines are useful in the treatment of patients with ischemic heart disease complicated by heart failure and shock. These agents influence the cardiovascular system by action on alpha-adrenergic, beta-adrenergic, and dopamine receptors. Recent evidence has demonstrated the existence of subtypes of the classic adrenergic and dopamine receptors that mediate distinct physiologic effects. The relative actions of sympathomimetic amines on these receptors differ substantially, resulting in considerable variation in their cardiac and peripheral vascular effects. Two classes of sympathomimetic amines are being intensively investigated at present: (1) compounds acting predominantly on beta 1-adrenergic receptors (i.e., they increase cardiac contractile force with little or no peripheral vascular effects) and (2) compounds acting on both beta 1-adrenergic and dopamine receptors. Orally active compounds of these two classes have been synthesized recently and are now under study for the treatment of patients with heart failure. Results of preliminary studies with such components are briefly reviewed.
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PMID:Sympathomimetic amines: potential clinical applications in ischemic heart disease. 627 12

The cardiovascular risk of hypertension depends not only on blood pressure under resting conditions, but particularly on blood pressure increases induced by daily physical and emotional activity. Therefore, the ability of the beta 1-receptor antagonist acebutolol (400 mg/day) and of the alpha 1-receptor antagonist prazosin (4 mg/day) to reduce exercise-induced increases in blood pressure and pressure-rate product during and after standardized ergometric work (50-100 W) was compared in an intrapatient study including 20 outpatients with arterial hypertension (WHO stage 1-2) aged 29-55 years. Both drugs resulted in a significant reduction of systolic (p less than 0.01) and diastolic (p less than 0.001) blood pressure at rest. However, systolic blood pressure (p less than 0.001) and pressure-rate product (p less than 0.001) during exercise were only significantly reduced by acebutolol. The strongest blood pressure lowering effect under all conditions could be achieved by the combination of prazosin and acebutolol. From these findings it is concluded that: (1) beta-adrenoreceptor-blocking agents are the drugs of first choice in the baseline therapy of mild to moderate arterial hypertension, and (2) prazosin potentiates the antihypertensive effect of beta-blocking agents. This therapeutic regimen is recommended especially for hypertensives with ischemic heart disease, because prazosin fails to reduce pressure-rate product as a measure of myocardial O2-consumption.
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PMID:[Effect of the alpha 1-receptor blocker prazosin and the beta 1-receptor blocker acebutolol and their combination on blood pressure and pressure rate product. Ergometric studies of hypertensive patients]. 636 45

To the extent that they have deficient glucagon secretory responses to plasma glucose decrements, as they commonly do, patients with insulin-dependent diabetes mellitus (IDDM) are dependent on epinephrine-mediated beta-adrenergic mechanisms to promote recovery from hypoglycemia. Thus, they are at increased risk for prolonged hypoglycemia if treated with a nonselective beta-adrenergic antagonist such as propranolol. If the hyperglycemic actions of epinephrine are mediated through beta 2-adrenergic mechanisms, therapeutic efficacy (e.g., for hypertension or ischemic heart disease) could be accomplished without increased risk of hypoglycemia by selective beta 1-adrenergic blockade in such patients. However, oral administration of the relatively selective beta 1-adrenergic antagonist metoprolol (100 mg) and of the nonselective beta-adrenergic antagonist propranolol (80 mg) both impaired recovery from insulin-induced hypoglycemia in patients with IDDM. Thus, at a dose of 100 mg, oral metoprolol is not safer than oral propranolol with respect to recovery from hypoglycemia in patients with IDDM.
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PMID:Oral propranolol and metoprolol both impair glucose recovery from insulin-induced hypoglycemia in insulin-dependent diabetes mellitus. 637 17

The genetic determination of pre-beta 1-lipoprotein and its relation to insulin response was studied in 18 male monozygotic and 13 male dizygotic twin pairs, aged 51-74. They had been selected from the Swedish Twin Registry by means of an angina pectoris questionnaire. Results revealed a heritability index for the pre-beta 1-lipoprotein, determined quantitatively, to be as high as 0.94. The subjects in whom pre-beta 1-lipoprotein was present exhibited a significantly delayed early insulin response compared to subjects without this lipoprotein fraction. Our data seem to justify the use of pre-beta 1-lipoprotein as a genetic marker. Data also indicate that important metabolic differences may exist between pre-beta 1+ and pre-beta 1- individuals, and it is possible that such differences may explain in part an increased susceptibility to ischemic heart disease for those possessing the pre-beta 1 fraction.
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PMID:Pre-beta 1-lipoprotein in patients with ischemic heart disease. Genetic determination and relation to early insulin response. 701 Sep 28

A randomized study was performed on 70 patients undergoing elective coronary bypass grafting to examine whether the combined infusion of the calcium channel blocker nifedipine (10 micrograms/kg per hour) and the beta 1-blocker metopropol (12 micrograms/kg per hour, n = 34) reduces the prevalence of perioperative myocardial ischemia and arrhythmias. The control group received nifedipine alone (n = 36). In both groups the infusion was started from the onset of extracorporal circulation and maintained over a period of 24 hours. Repeated 12-lead electrocardiographic and 3-channel Holter monitor recordings for 48 hours were used to define perioperative myocardial ischemia (transient ischemic event, myocardial infarction) and arrhythmias (sinus tachycardia, supraventricular tachycardia, atrial flutter/fibrillation, ventricular tachycardia). Hemodynamic parameters were repeatedly assessed for 24 hours and serum enzyme levels (creatine kinase, MB isoenzyme of creatine kinase) for up to 36 hours after the operation. The two groups did not differ significantly with respect to preoperative anamnestic and surgical data. No signs of perioperative myocardial infarction were detected in either group. However, a significantly lower incidence of transient ischemic episodes was observed in the nifedipine-metoprolol group than in the nifedipine group (3% vs 11%; p < 0.05). In addition, there was a tendency toward lower creatine kinase MB levels and peak values of creatine kinase and creatine kinase MB in the nifedipine-metoprolol group. With regard to perioperative arrhythmias, there was a significantly lower incidence of sinus tachycardia and atrial flutter/fibrillation in the nifedipine-metoprolol group (9% and 6%) than in the nifedipine group (33% and 27%, p < 0.05). In addition, postoperative heart rate was lower in the nifedipine-metoprolol group starting from the sixth hour after release of the aortic crossclamp (p < 0.05 and p < 0.01, respectively). No other hemodynamic parameters showed significant differences between the two groups and all returned to preoperative levels within 24 hours. In conclusion, perioperative application of nifedipine and metoprolol in patients undergoing elective coronary bypass grafting reduces the prevalence of perioperative myocardial ischemia and arrhythmias without significant negative inotropic effects. The combined infusion of the two drugs appears superior to nifedipine alone in preventing perioperative myocardial ischemia and reducing reperfusion-induced arrhythmias.
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PMID:Comparison of perioperative myocardial protection with nifedipine versus nifedipine and metoprolol in patients undergoing elective coronary artery bypass grafting. 747 98

Bisoprolol is a selective beta 1-adrenoceptor antagonist devoid of partial agonist activity that can be used for treatment of chronic and acute myocardial ischemia. In this condition, it is important to demonstrate that a stable beta-blocking effect at steady state can be predicted by a mathematical model determined by plasma concentration-effect relationship after an acute intravenous (i.v.) dose. This relation was studied in 10 healthy volunteers in a double-blind, randomized, cross-over, placebo-controlled study after a 5-min i.v. infusion of bisoprolol (5 mg) or placebo. Standardized exercise tests were recorded at different times for 48 h after infusion with simultaneous bisoprolol assay (high-performance liquid chromatography, HPLC) in plasma. After a 1-week interval, subjects received oral bisoprolol (10 mg once daily) for 5 days and exercise tests were repeated on day 5 before and 2, 3, and 4 h after dosing, with bisoprolol plasma level determined simultaneously. In the acute period, bisoprolol significantly decreased exercise heart rate (HR: peak effect -20.5 +/- 4%) as compared with placebo. There was a direct relationship (no hysteresis) between beta-blockade and plasma concentrations with a sigmoid (7 subjects) or a linear (3 subjects) best-fit model. After repeated bisoprolol administration, steady-state plasma levels were achieved and 88% of the observed decreases in exercise HR were within the 95% confidence interval (CI) for individual prediction. These data suggest that bisoprolol-induced beta-blockade after repeated oral dosing can be predicted by single-test i.v. dose administration.
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PMID:Relationships between acute and chronic beta-blocking effects of bisoprolol in healthy volunteers: a practical approach to predict intensity of beta-blockade. 751 19

The beneficial effect of chronic beta-blockade in patients with congestive heart failure has been repeatedly shown since its introduction into treatment for this condition in 1975. Still this kind of therapy remains controversial, it is sometimes regarded as a therapeutic paradox, and its use is mainly limited to specialist centers. Various favorable effects of beta-blockers in patients with heart failure due to idiopathic dilated cardiomyopathy and ischemic heart disease have been demonstrated, the principal among them being reduction in energy requirements and ischemia, antiarrhythmogenic effect, improvement of diastolic function, protection of myocytes against catecholamine overload, centrally mediated increase in vagal tone, upregulation of beta-adrenergic receptors, and possible blockade of autoantibodies against beta 1-receptors. Although most of the studies used metoprolol, these effects may be relevant to certain other beta-blockers. Despite very solid pathophysiological and pharmacological rationales for the use of beta-blockade, a major obstacle for a general acceptance of this therapeutic concept is the striking contrast between hemodynamic changes during the acute effect and long-term treatment. When titrated carefully from very low doses and used with a true commitment to long-term treatment, beta-blockers have been shown to prevent further deterioration of heart failure and to improve hemodynamics, exercise tolerance, quality of life, and prognosis.
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PMID:Use of beta-adrenoceptor blockers in patients with congestive heart failure. 766 94

(D-L) Nebivolol is a new beta 1-selective adrenoceptor blocker which in normal individuals preserves rest and exercise hemodynamics. We assessed the effects of the enantiomers (L- and D-nebivolol) on left ventricular (LV) systolic and diastolic function and compared their effects with those of the racemic mixture. LV angiography (+Millar) was performed before and after intravenous (i.v.) infusion of either D- or L-nebivolol (1.25-2.5 mg, n = 22) in patients with ischemic heart disease and previous myocardial infarction. Neither L- nor D-nebivolol produced significant changes in heart rate (HR), peak (+) dP/dt, (dP/dt) DP40, cardiac index (CI) or ejection fraction (EF). Diastolic distensibility, evaluated from the shift of the pressure-volume data at the time of mitral valve opening, did not improve after D- or L-enantiomers administration. In contrast, both D-L-nebivolol 2.5 mg (n = 9) and atenolol 15 mg (n = 9) significantly reduced HR and peak (+) dP/dt, but in comparison to atenolol D-L nebivolol improved EF (+4% after D-L nebivolol vs. -4% after atenolol; p < 0.05 D-L nebivolol vs. atenolol) and maintained cardiac output CO, (+2% vs. -21%; p < 0.05 between groups). Moreover, unlike any of the other drugs in the study, the racemate shifted the diastolic pressure-volume data downward, suggesting improved LV distensibility. The beneficial effects of nebivolol on LV systolic and diastolic function appears to require the presence of both D- and L-enantiomers.
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PMID:Effects of D-nebivolol and L-nebivolol on left ventricular systolic and diastolic function: comparison with D-L-nebivolol and atenolol. 769 55

Acute myocardial ischemia leads to a rapid increase of cardiac beta-adrenergic receptors in plasma membranes despite the release of large and desensitizing amounts of endogenous catecholamines. Part of this increase has been shown to occur at the expense of intracellular receptors. To investigate whether an additional expressional regulation of beta-adrenergic receptors due to an increase of mRNA levels is involved, the mRNA levels specific for beta 1- and beta 2-adrenergic receptors were determined after various periods of global ischemia in isolated perfused rat hearts. The subtype-specific quantification of mRNA for beta 1- and beta 2-adrenergic receptors was determined using reverse-transcription followed by PCR (RT-PCR) and RNA protection assays. RT-PCR resulted in single amplification products of the expected sizes (159 bp for beta 1-adrenergic receptors and 240 bp for beta 2-adrenergic receptors). The specificity of these amplification products was confirmed by specific restriction digests. Southern blot hybridizations with internal oligonucleotides and sequencing using the dideoxy chain termination method. For quantification purposes, the mRNAs of housekeeping gene GAPDH and of cardiac alpha-actin were determined as internal standards. Additionally, cRNAs specific for beta 1- and beta 2-adrenergic receptors were used as external standards. Brief periods of global ischemia induced a rapid increase in the steady state level of mRNA for beta 1-adrenergic receptors. There was a statistically significant rise already after 15 min by 57% compared to controls. After 30 min of ischemia the mRNA levels had almost doubled. After 60 min of ischemia, the mRNA levels specific for beta 1-adrenergic receptors tended to decrease, but remained significantly above normoxic controls. In contrast, the mRNA levels specific for beta 2-adrenergic receptors remained constant up to 60 min of global myocardial ischemia. To investigate, whether agonist occupancy of the receptors may contribute to this regulation, the effect of preperfusion with the beta-blocker alprenolol was determined. Contrary to expectation, beta-blockade did not influence the ischemia-induced increase of mRNA levels specific for beta 1-adrenergic receptors. These data demonstrate for the first time, that acute myocardial ischemia induces a rapid, and subtype-selective regulation of mRNA levels for beta 1-adrenergic receptors. However, occupation or activation of beta-adrenergic receptors by an agonist is not involved in this newly characterized regulation of mRNA for beta 1-adrenergic receptors in acute myocardial ischemia.
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PMID:Regulation of beta-adrenergic receptors in acute myocardial ischemia: subtype-selective increase of mRNA specific for beta 1-adrenergic receptors. 776 Mar 63


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