Beneficial effects of timolol on infarct size and late ventricular tachycardia in patients with acute myocardial infarction.

Roqué, Fernando; Amuchastegui, Luis M.; Morillos, M A Lopez; Mon, G A; Girotti, Arnoldo Luis; Drajer, Saúl; Fortunato, Martino; Moreyra, Eduardo; Tuero, P; Solchaga, J C

doi:10.1161/01.cir.76.3.610

Cited by 21 publications

(3 citation statements)

References 47 publications

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“…The proportion of patients included with heart failure varied substantially between trials. For example, three trials contained no patients with heart failure [,,]. By contrast, two trials contained only patients with heart failure or major ventricular dysfunction [,] although one of these included only ‘diastolic’ heart failure [].…”

Section: Resultsmentioning

confidence: 99%

Are beta‐blockers effective in patients who develop heart failure soon after myocardial infarction? A meta‐regression analysis of randomised trials

Houghton

Freemantle

Cleland

2000

European J of Heart Fail

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Background: The great majority of post-infarction studies of beta-blockers were conducted in an era when these agents were widely held to be contra-indicated for the management of heart failure. We now know that beta-blockers are highly effective for the management of patients with chronic stable heart failure. However, there remains uncertainty about their role in the setting of post-infarction heart failure and ventricular dysfunction. Aim: the primary objective in this paper, was to investigate the extent to which heart failure or evidence of major cardiac dysfuntion influenced outcome in previous trials of beta-blockers in heart failure after myocardial infarction. Methods: We assessed the extent to which the inclusion of patients with heart failure or major cardiac dysfunction influenced outcome in randomised trials of long-term use of beta-blockade after myocardial infarction. The primary analysis was to assess the extent to which the proportion of patients included in each trial with heart failure influenced the relative odds of all-cause mortality in the trials. All randomised trials without crossover with treatment lasting more than one month and with 50 or more patients were considered. All those that provided information on the proportion of patients with heart failure or major cardiac dysfunction in the original or subsequent articles were included in the analysis. Results: Overall treatment with a beta-blocker was associated with a 22.6% reduction in the Ž . odds of death 95% C1 11᎐32.3% . There were very few data on the effects of beta-blockers after myocardial infarction in patients with documented left ventricular systolic dysfuntion. In the analysis that included heart failure as a factor, treatment with a beta-blocker was associated with a non-significant interaction with the presence of heart failure. However, because the group including heart failure patients were at higher risk, the absolute benefit of treatment with beta-blockers appeared greater in this group. Conclusions: This analysis suggests that the relative benefit of beta-blockers on mortality after a myocardial infarction is similar in the presence or absence of heart failure but that the absolute benefit may be greater in the former. However, as current clinical practice has changed radically from the time when the majority of these trials were conducted, further trial evidence would be desirable.ᮊ

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Section: Resultsmentioning

confidence: 99%

Are beta‐blockers effective in patients who develop heart failure soon after myocardial infarction? A meta‐regression analysis of randomised trials

Houghton

Freemantle

Cleland

2000

European J of Heart Fail

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“…In contrast, a multicenter, randomized, double-blind study including 73 patients with AMI receiving timolol and 71 patients receiving placebo demonstrated a significant reduction of CK release in the timolol group [105]. In a placebo-controlled study, a decrease in the cumulative total CK and CK-MB release was detected in patients with AMI without thrombolysis treated with timolol [94]. The incidence of ventricular tachycardia was lower in the timolol group.…”

Section: Historical Data the Cardioprotective Effect Of β-Ar Antagoni...mentioning

confidence: 99%

The role of β‐adrenergic receptors in the regulation of cardiac tolerance to ischemia/reperfusion. Why do β‐adrenergic receptor agonists and antagonists protect the heart?

Maslov,

Naryzhnaya,

Voronkov

et al. 2024

Fundamemntal Clinical Pharma

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BackgroundCatecholamines and β‐adrenergic receptors (β‐ARs) play an important role in the regulation of cardiac tolerance to the impact of ischemia and reperfusion. This systematic review analyzed the molecular mechanisms of the cardioprotective activity of β‐AR ligands.MethodsWe performed an electronic search of topical articles using PubMed databases from 1966 to 2023. We cited original in vitro and in vivo studies and review articles that documented the cardioprotective properties of β‐AR agonists and antagonists.ResultsThe infarct‐reducing effect of β‐AR antagonists did not depend on a decrease in the heart rate. The target for β‐blockers is not only cardiomyocytes but also neutrophils. β1‐blockers (metoprolol, propranolol, timolol) and the selective β2‐AR agonist arformoterol have an infarct‐reducing effect in coronary artery occlusion (CAO) in animals. Antagonists of β1‐ and β2‐АR (metoprolol, propranolol, nadolol, carvedilol, bisoprolol, esmolol) are able to prevent reperfusion cardiac injury. All β‐AR ligands that reduced infarct size are the selective or nonselective β1‐blockers. It was hypothesized that β1‐AR blocking promotes an increase in cardiac tolerance to I/R. The activation of β1‐AR, β2‐AR, and β3‐AR can increase cardiac tolerance to I/R. The cardioprotective effect of β‐AR agonists is mediated via the activation of kinases and reactive oxygen species production.ConclusionsIt is unclear why β‐blockers with the similar receptor selectivity have the infarct‐sparing effect while other β‐blockers with the same selectivity do not affect infarct size. What is the molecular mechanism of the infarct‐reducing effect of β‐blockers in reperfusion? Why did in early studies β‐blockers decrease the mortality rate in patients with acute myocardial infarction (AMI) and without reperfusion and in more recent studies β‐blockers had no effect on the mortality rate in patients with AMI and reperfusion? The creation of more effective β‐AR ligands depends on the answers to these questions.

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“…Several studies in Europe and in the United States of America demonstrated that β-blockade therapy in acute myocardial infarction may decrease infarct size, incidence of ventricular arrhythmias and mortality [17][18][19][20][21][22][23]; however, a more recent study in the Chinese population indicated that metoprolol administration in acute myocardial infarction may not be as beneficial due to an increase in cardiogenic shock [24]. The discrepancy in these results may be at least partially related to the various responses to β-blockade therapy in different ethnic groups [25].…”

Section: Pharmacogenetics and β-Adrenergic Receptorsmentioning

confidence: 99%

Beta-adrenergic receptor polymorphisms: A basis for pharmacogenetics

Theofilogiannakos¹,

Boudoulas²,

Gawronski³

et al. 2013

WJCD

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Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of Caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 C/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%); this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg

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Beneficial effects of timolol on infarct size and late ventricular tachycardia in patients with acute myocardial infarction.

Cited by 21 publications

References 47 publications

Are beta‐blockers effective in patients who develop heart failure soon after myocardial infarction? A meta‐regression analysis of randomised trials

Are beta‐blockers effective in patients who develop heart failure soon after myocardial infarction? A meta‐regression analysis of randomised trials

The role of β‐adrenergic receptors in the regulation of cardiac tolerance to ischemia/reperfusion. Why do β‐adrenergic receptor agonists and antagonists protect the heart?

Beta-adrenergic receptor polymorphisms: A basis for pharmacogenetics

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