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Therapeutic efficacy of a combination of a beta1-adrenoreceptor (AR) blocker and beta2-AR agonist in a rat model of postmyocardial infarction dilated heart failure exceeds that of a beta1-AR blocker plus angiotensin-converting enzyme inhibitor.

ABSTRACT: We had proposed previously a novel combination of beta2-adrenoreceptor (AR) agonist and beta1-AR blocker that in the rat model of postmyocardial infarction (MI) dilated cardiomyopathy exceeds the therapeutic effectiveness of either monotherapy. In the present study, we compared that treatment with a combination of beta1-AR blocker and angiotensin-converting enzyme inhibitor (ACEi), a current standard chronic heart failure (CHF) therapy. Two weeks after coronary artery ligation, rats were divided into groups of similar average MI size, measured by echocardiography, and the following 12-month treatments were initiated: fenoterol (250 microg/kg/day), a beta2-AR agonist, plus metoprolol (100 mg/kg/day), a beta1-AR blocker (beta1-beta2+); metoprolol plus enalapril (20 mg/kg/day), an ACEi (beta1-ACEi); and a combination of all three drugs (beta1-beta2+ACEi). These treatment groups were compared with each other and with nontreated (nT) and sham groups. The 12-month mortality was significantly reduced in all treatment groups (44% in beta1-beta2+, 56% in beta1-beta2+ACEi, 59% in beta1-ACEi versus 81% in nT). Bimonthly echocardiography revealed significant attenuation of the left ventricular (LV) chamber remodeling, LV functional deterioration, and MI expansion in all three treatment groups, but effects were significantly more pronounced when treatment included a beta2-AR agonist. The results indicated that a combination of beta1-AR blocker and beta2-AR agonist is equipotent to a combination of beta1-AR blocker and ACEi in the treatment of CHF in rats, with the respect to mortality, and exceeds the latter with respect to cardiac remodeling and MI expansion. Thus, this novel therapeutic regimen for CHF warrants detailed clinical investigation.

SUBMITTER: Ahmet I

PROVIDER: S-EPMC2766223 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Therapeutic efficacy of a combination of a beta1-adrenoreceptor (AR) blocker and beta2-AR agonist in a rat model of postmyocardial infarction dilated heart failure exceeds that of a beta1-AR blocker plus angiotensin-converting enzyme inhibitor.

Ahmet Ismail I Morrell Chris C Lakatta Edward G EG Talan Mark I MI

The Journal of pharmacology and experimental therapeutics 20090708 1

We had proposed previously a novel combination of beta2-adrenoreceptor (AR) agonist and beta1-AR blocker that in the rat model of postmyocardial infarction (MI) dilated cardiomyopathy exceeds the therapeutic effectiveness of either monotherapy. In the present study, we compared that treatment with a combination of beta1-AR blocker and angiotensin-converting enzyme inhibitor (ACEi), a current standard chronic heart failure (CHF) therapy. Two weeks after coronary artery ligation, rats were divided ...[more]

PMID: 19587314

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Project description:ImportancePatients with acute kidney injury (AKI) are at an increased long-term risk of death. Effective strategies that improve long-term outcomes in patients with AKI are unknown.ObjectiveTo evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) after hospital discharge is associated with better outcomes in patients with AKI.Design, setting, and participantsThis retrospective cohort study used data from the Alberta Kidney Disease Network population database to evaluate 46 253 adults 18 years or older with an episode of AKI during a hospitalization between July 1, 2008, and March 31, 2015, in Alberta, Canada. All patients who survived to hospital discharge were followed up for a minimum of 2 years.ExposuresUse of an ACEI or ARB within 6 months after hospital discharge.Main outcomes and measuresThe primary outcome was mortality; secondary outcomes included hospitalization for a renal cause, end-stage renal disease (ESRD), and a composite outcome of ESRD or sustained doubling of serum creatinine concentration. An AKI was defined as a 50% increase between prehospital and peak in-hospital serum creatinine concentrations. Propensity scores were used to construct a matched-pairs cohort of patients who did and did not have a prescription for an ACEI or ARB within 6 months after hospital discharge.ResultsThe study evaluated 46 253 adults (mean [SD] age, 68.6 [16.4] years; 24 436 [52.8%] male). Within 6 months of discharge, 22 193 (48.0%) of the participants were prescribed an ACEI or ARB. After adjustment for comorbidities, ACEI or ARB use before admission, demographics, baseline kidney function, other factors related to index hospitalization, and prior health care services, ACEI or ARB use was associated with lower mortality in patients with AKI after 2 years (adjusted hazard ratio, 0.85; 95% CI, 0.81-0.89). However, patients who received an ACEI or ARB had a higher risk of hospitalization for a renal cause (adjusted hazard ratio, 1.28; 95% CI, 1.12-1.46). No association was found between ACEI or ARB use and progression to ESRD.Conclusions and relevanceAmong patients with AKI, ACEI or ARB therapy appeared to be associated with lower mortality but a higher risk of hospitalization for a renal cause. These results suggest a potential benefit of ACEI or ARB use after AKI, but cautious monitoring for renal-specific complications may be warranted.

Dataset Information

Therapeutic efficacy of a combination of a beta1-adrenoreceptor (AR) blocker and beta2-AR agonist in a rat model of postmyocardial infarction dilated heart failure exceeds that of a beta1-AR blocker plus angiotensin-converting enzyme inhibitor.

Publications

Therapeutic efficacy of a combination of a beta1-adrenoreceptor (AR) blocker and beta2-AR agonist in a rat model of postmyocardial infarction dilated heart failure exceeds that of a beta1-AR blocker plus angiotensin-converting enzyme inhibitor.

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