title: Preconditioning: myocardial function and energetics during coronary hypoperfusion and reperfusion.
abstract: BACKGROUND
  Ischemic preconditioning (IP) is gaining more acceptance as a protective method in beating heart surgery. Yet it remains controversial whether preconditioning can attenuate myocardial dysfunction during reperfusion after severe coronary hypoperfusion. We examined this issue and also the issue of whether this protection is mediated by adenosine A1 receptors.
  
  
  METHODS
  In isolated, blood-perfused rabbit hearts, the effects of IP (3 minutes of no flow ischemia and 8 minutes of reperfusion) during 30 minutes of coronary hypoperfusion and 60 minutes of reperfusion were investigated. In two groups (n = 8 each) with and without (control group) preconditioning, ventricular function was assessed by load-insensitive measures: slope of the end-systolic pressure-volume relation (Emax), slope of the stroke work/end-diastolic volume relation (Mw), and end-diastolic pressure-volume relation. External efficiency was calculated, and contractile efficiency was assessed using the reciprocal of the myocardial oxygen consumption-pressure-volume area relationship. To investigate the possible role of adenosine, the adenosine A1 receptor antagonist DPCPX (2.5 micromol/L) was administered before preconditioning in a third group (n = 7).
  
  
  RESULTS
  The effects of hypoperfusion on systolic function, diastolic function (dP/dtmin, end-diastolic pressure-volume relation), external efficiency, and contractile efficiency were similar in both the IP and control groups. Lactate efflux was significantly reduced after preconditioning (p = 0.02). During reperfusion, recovery of systolic function and coronary flow were significantly improved in the IP group compared with controls: aortic flow, 85% versus 63% (p = 0.01); dP/dtmax, 91% versus 67% (p = 0.001); pressure-volume area, 97% versus 68% (p = 0.01); Emax, 74% versus 62% (p = 0.03); and Mw, 94% versus 84% (p = 0.04). Release of creatine kinase was reduced in the IP group, 9.6 +/- 1.3 U x 5 min(-1) x 100 g(-1) wet weight, versus controls, 12.7 +/- 2.7 U x 5 min(-1) x 100 g(-1) wet weight (p = 0.04). During reperfusion, contractile efficiency (p = 0.03) and external efficiency (p = 0.02) recovered better in preconditioned than in untreated hearts. Recovery was less pronounced in the DPCPX group compared with the IP group (p, not significant).
  
  
  CONCLUSIONS
  The results, derived from load-insensitive measures, confirm that IP provides protection after episodes of severe hypoperfusion by attenuating systolic dysfunction without improving diastolic dysfunction and reduces the severity of anaerobic metabolism as well as ischemic injury. Contractile efficiency and external efficiency both indicate improved energetics after IP (oxygen utilization by the contractile apparatus). The protective effect, at least in part, is mediated by adenosine A1 receptors.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Heinrich-Heine-University, Duesseldorf, Germany. usunderdiek@aol.com
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sunderdiek
authors.forename: Simone
authors.initials: S
authors.lastname: Schmitz-Spanke
authors.forename: Bernhard
authors.initials: B
authors.lastname: Korbmacher
authors.forename: Emmeran
authors.initials: E
authors.lastname: Gams
authors.forename: Jochen D
authors.initials: JD
authors.lastname: Schipke
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D003971:Diastole / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D016277:Ventricular Function, Left / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; D019344:Lactic Acid; C051360:1,3-dipropyl-8-cyclopentylxanthine; D003402:Creatine Kinase