title: Increased tolerance of the chronically hypoxic immature heart to ischemia. Contribution of the KATP channel.
abstract: BACKGROUND
  Hypoxia from birth in immature rabbits increases the tolerance of isolated hearts to ischemia compared with age-matched normoxic rabbits. We determined whether this increased tolerance to ischemia was due to an alteration in the ATP-sensitive potassium (KATP) channel and whether increased KATP channel activation was associated with increases in intracellular lactate.
  
  
  RESULTS
  Isolated immature rabbit hearts (7 to 10 days old) were perfused with bicarbonate buffer at 39 degrees C in the Langendorff mode at a constant pressure. Saline-filled latex balloons were placed in the left and right ventricles for measurement of developed pressure. A KATP channel agonist (bimakalim) or a KATP channel antagonist (glibenclamide) was added 15 minutes before a global ischemic period of 18 minutes, followed by 35 minutes of reperfusion. Rabbits raised from birth in hypoxic conditions (FIO2 = 0.12) displayed significantly enhanced recovery of developed pressure. The right ventricle was more tolerant of ischemia than the left ventricle in normoxic and hypoxic hearts. Bimakalim (1 mumol/L) increased the recovery of left ventricular developed pressure in normoxic hearts to values not different from those of hypoxic controls (43 +/- 3% to 67 +/- 5%) and slightly increased developed pressure in hypoxic hearts (67 +/- 5% to 72 +/- 5%). Glibenclamide (3 mumol/L) abolished the cardioprotective effect of hypoxia (67 +/- 5% to 43 +/- 5%). Constant-flow studies indicated that the effects of bimakalim and glibenclamide were independent of their actions on coronary flow. Ventricular lactate and lactate dehydrogenase concentrations were elevated in hypoxic hearts compared with normoxic control hearts.
  
  
  CONCLUSIONS
  Increased tolerance to ischemia exhibited by chronically hypoxic rabbit hearts is associated with increased activation of the KATP channel. This increased KATP activity may be the result of increased intracellular concentrations of lactate.
authors.affiliation: Department of Pharmacology, Medical College of Wisconsin, Milwaukee 53226, USA. jbaker@post.its.mcw.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Baker
authors.forename: B D
authors.initials: BD
authors.lastname: Curry
authors.forename: G N
authors.initials: GN
authors.lastname: Olinger
authors.forename: G J
authors.initials: GJ
authors.lastname: Gross
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001578:Benzopyrans / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D007773:Lactates / Q000032:analysis; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D011817:Rabbits; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects
chemical_list: D001578:Benzopyrans; D004095:Dihydropyridines; D007773:Lactates; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C061050:bimakalim; D007770:L-Lactate Dehydrogenase; D005905:Glyburide