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Increased tolerance of the chronically hypoxic immature heart to ischemia. Contribution of the KATP channel. Circulation 1997 Mar 04;95(5):1278-85

Date

03/04/1997

Pubmed ID

9054860

DOI

10.1161/01.cir.95.5.1278

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.

METHODS AND 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.

Author List

Baker JE, Curry BD, Olinger GN, Gross GJ

Author

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analysis of Variance
Animals
Animals, Newborn
Benzopyrans
Coronary Circulation
Dihydropyridines
Glyburide
Heart
Heart Rate
Hemodynamics
Hypoxia
In Vitro Techniques
L-Lactate Dehydrogenase
Lactates
Myocardial Ischemia
Myocardial Reperfusion
Myocardium
Potassium Channel Blockers
Potassium Channels
Rabbits
Ventricular Function, Left
Ventricular Function, Right
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a