Atenolol depresses post-ischaemic recovery in the isolated rat heart.
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 beta-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 micrograms l-1atenolol (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 10(3)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 micromol min-1) and paced (8.1+/-0.8 micromol min-1) hearts than in control (6.2+/-0.8 micromol min-1). At the end of reflow, the pressurexrate 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 micromol g(dw)(-1)) than in atenolol (10.5+/-2.6 micromol g(dw)(-1)) and paced (10.9+/-1.3 micromol g(dw)(-1)) hearts. Thus, by suppressing the protective effects of down-regulation, both atenolol and pacing apparently depress myocardial recovery in this model.
Allibardi
S
S
Dipartimento di Scienze e Tecnologie Biomediche, Universitá di Milano, via Cervi 93, Milano, I-20090, Italy.
Merati
G
G
Chierchia
S
S
Samaja
M
M
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D003401:Creatine / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects; D010725:Phosphocreatine / Q000187:drug effects / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D051381:Rats
D000227:Adenine Nucleotides; D000319:Adrenergic beta-Antagonists; D011687:Purines; D010725:Phosphocreatine; D019344:Lactic Acid; D001262:Atenolol; D000255:Adenosine Triphosphate; D003401:Creatine