title: Optimizing ischemia/reperfusion in the failing rat heart--improved myocardial protection with acute ACE inhibition.
abstract: BACKGROUND
  Whereas the number of patients with reduced left ventricular function after myocardial infarction who need revascularization is increasing, the operative outcome is still inadequate. Consequently, drugs that increase myocardial perfusion and decrease oxygen consumption of the remodeled myocardium are of particular interest to cardiac surgeons. Angiotensin-converting enzyme inhibitors (ACE-I) provide this pharmacologic profile. This study tests the hypothesis whether acute ACE inhibition during cardioplegic arrest improves outcome in failing rat hearts.
  
  
  RESULTS
  Male Wistar rats (260+/-15 g) underwent coronary ligation. Ten weeks later the rats had developed heart failure (HF). Hearts were harvested and studied on a red cell-perfused working heart: 60 minutes of ischemia, protected by cold blood cardioplegia (CP) every 20 minutes, and 45 minutes of reperfusion. Rats were randomly assigned to 2 groups, 1 group receiving the ACE-I quinaprilat with CP (QuinaMI, n=11), and 1 group receiving CP only (MI, n=8). Hemodynamic recovery, high-energy phosphates (HEP), and morphometry were analyzed. Groups showed similar degrees of myocardial infarction (44+/-5 versus 39+/-4% of LVmass), LVEDP (5.0+/-1 versus 4+/-1 mm Hg) and no differences in baseline values such as external heart work (EHW) and coronary flow (CF). At the end of reperfusion, EHW and CF were significantly higher in QuinaMI than MI (P<0.05 and 0.01), LVEDP had returned to baseline in QuinaMI (P<0.01). HEP were significantly higher preserved in QuinaMI than MI (P<0.05).
  
  
  CONCLUSIONS
  Acute ACE inhibition during CP improves postischemic systolic and diastolic function, coronary perfusion as well as HEP-levels in a rat model of HF. These results may have clinical impact on patients with HF undergoing cardiac surgery.
mesh_terms: D000227:Adenine Nucleotides / Q000032:analysis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000503:physiopathology; D006324:Heart Arrest, Induced; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D007546:Isoquinolines / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry; D009924:Organ Culture Techniques; D010725:Phosphocreatine / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines
chemical_list: D000227:Adenine Nucleotides; D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D010725:Phosphocreatine; C054501:quinaprilat