Atenolol depresses post-ischaemic recovery in the isolated rat heart

Sonia Allibardi, Giampiero Merati, Sergio Chierchia, Michele Samaja

Research output: Contribution to journalArticlepeer-review

Abstract

Metabolic events during ischaemia are probably important in determining post-ischaemic myocardial recovery. The aim of this study was to assess the effects of the β-blocker atenolol and the high energy demand in an ischaemia-reperfusion model free of neurohormonal and vascular factors. We exposed Langendorff-perfused isolated rat hearts to low-flow ischaemia (30 min) and reflow (20 min). Three groups of hearts were used: control hearts (n = 11), hearts that were perfused with 2.5 μg l-1 atenolol (n = 9), and hearts electrically paced during ischaemia to distinguish the effect of heart rate from that of the drug (n = 9). The hearts were freeze-clamped at the end of reflow to determine high-energy phosphates and their metabolites. During ischaemia, the pressure-rate product was 2.3 ± 0.2, 5.2 ± 1.1, and 3.3 ± 0.3 mmHg 103 min in the control, atenolol and paced hearts, respectively. In addition, the ATP turnover rate, calculated from venous (lactate), oxygen uptake and flow, was higher in atenolol (11.2 ± 1.7 μmol min-1) and paced (8.1 ± 0.8 μmol min-1) hearts than in control (6.2 ± 0.8 μmol min-1). At the end of reflow, the pressure x rate product recovered 75.1 ± 6.4% of baseline in control vs 54.1 ± 9.1 and 48.8 ± 4.4% in atenolol and paced hearts (P <0.05). In addition, the tissue content of ATP was higher in the control hearts (15.8 ± 1.0 μmol g(dw)-1) than in atenolol (10.5 ± 2.6 μmol g(dw)-1) and paced (10.9 ± 1.3 μmol g(dw)-1) hearts. Thus, by suppressing the protective effects of down-regulation both atenolol and pacing apparently depress myocardial recovery in this model.

Original languageEnglish
Pages (from-to)431-435
Number of pages5
JournalPharmacological Research
Volume39
Issue number6
DOIs
Publication statusPublished - Jun 1999

Keywords

  • β-blocker
  • Bioenergetics
  • High-energy phosphates
  • Low-flow ischaemia

ASJC Scopus subject areas

  • Pharmacology

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