title: Metabolic adaptation during a sequence of no-flow and low-flow ischemia. A possible trigger for hibernation.
abstract: BACKGROUND
  Myocardial hibernation is an adaptive phenomenon occurring in patients with a history of acute ischemia followed by prolonged hypoperfusion.
  
  
  RESULTS
  We investigated, in isolated rabbit heart, whether a brief episode of global ischemia followed by hypoperfusion maintains viability. Four groups were studied; group 1,300 minutes of aerobia; group 2,240 minutes of total ischemia and 60 minutes of reperfusion; group 3, 10 minutes of total ischemia, 230 minutes of hypoperfusion (90% coronary flow reduction), and 60 minutes of reperfusion; and group 4, 240 minutes of hypoperfusion followed by reperfusion. In group 3, viability was maintained. Ten minutes of ischemia caused quiescence, a fall in interstitial pH (from 7.2 +/- 0.01 to 6.1 +/- 0.8), creatine phosphate (CP), and ATP (from 54.5 +/- 5.0 and 25.0 +/- 1.9 to 5.0 +/- 1.1 and 15.3 +/- 2.5 mumol/g dry wt, P < .01). Subsequent hypoperfusion failed to restore contraction and pH but improved CP (from 5.0 +/- 1.1 to 20.1 +/- 3.4, P < .01). Reperfusion restored pH, developed pressure (to 92.3%), and NAD/NADH and caused a washout of lactate and creatine phosphokinase with no alterations of mitochondrial function or oxidative stress. In group 4, hypoperfusion resulted in progressive damage. pH fell to 6.2 +/- 0.7, diastolic pressure increased to 34 +/- 5.6 mm Hg, CP and ATP became depressed, and oxidative stress occurred. Reperfusion partially restored cardiac metabolism and function (47%).
  
  
  CONCLUSIONS
  A brief episode of total ischemia without intermittent reperfusion maintains viability despite prolonged hypoperfusion. This could be mediated by metabolic adaptation, preconditioning, or both.
authors.affiliation: Chair of Cardiology, University of Brescia, Italy. ferrari@master.cci.unibs.it
authors.forename: R
authors.initials: R
authors.lastname: Ferrari
authors.forename: A
authors.initials: A
authors.lastname: Cargnoni
authors.forename: P
authors.initials: P
authors.lastname: Bernocchi
authors.forename: E
authors.initials: E
authors.lastname: Pasini
authors.forename: S
authors.initials: S
authors.lastname: Curello
authors.forename: C
authors.initials: C
authors.lastname: Ceconi
authors.forename: T J
authors.initials: TJ
authors.lastname: Ruigrok
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism; D006321:Heart / Q000503:physiopathology; D006706:Homeostasis; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology; D017202:Myocardial Ischemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000209:etiology*; D009206:Myocardium / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D011817:Rabbits
chemical_list: D010710:Phosphates; D011687:Purines; D009243:NAD; D019344:Lactic Acid; D003402:Creatine Kinase; D002118:Calcium