The Journal of Thoracic and Cardiovascular Surgery, Vol 96, 782-788, Copyright © 1988 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
Improved recovery of cardiac function after hypothermic ischemic storage with ouabain
CF Lagerstrom, DD McElroy, H Taegtmeyer and WE Walker
Division of Thoracic and Cardiovascular Surgery, University of Texas Medical School, Houston.
We investigated the hypothesis that ouabain would reduce energy expenditure
in the hypothermic, ischemic heart by inhibiting membrane- bound
sodium/potassium-activated adenosine triphosphatase and lead to improved
function on reperfusion. Additionally, we compared ouabain with another
potential adjunct, the calcium channel blocker verapamil. The isolated
rabbit heart was used as a model, and three experimental groups were
studied after 1, 6, 12, and 24 hours of 4 degrees C ischemia. Hearts in
group I were stored in a standard high potassium solution; hearts in groups
II and III were stored in the same solution supplemented with verapamil (2
mg/L) and ouabain (3 mg/L), respectively. After ischemia, all hearts were
reperfused for 45 minutes on a modified Langendorff apparatus, and left
ventricular function was measured before freeze-clamping the heart for
metabolite determination. At 1 and 6 hours, hearts in all groups functioned
well, but the group III hearts had higher levels of adenosine triphosphate,
phosphocreatine, total adenine nucleotides, and glycogen. After 12 hours of
ischemia, function was significantly better in group III hearts (p less
than 0.01) compared with that of hearts in groups I and II. Group III
hearts also exhibited higher levels of high energy phosphates and glycogen.
After 24 hours of storage, all hearts functioned poorly, and there was a
marked decline in measured metabolites. Although we could show no
improvement with the addition of verapamil, ventricular function was
improved after storage in a high potassium hypothermic solution containing
ouabain. Because ouabain inhibits the hydrolysis of adenosine triphosphate
by sodium/potassium- activated adenosine triphosphatase, this result
suggests that the glycoside maintains energy-rich phosphates necessary for
optimal resumption of cardiac function.
