Improved recovery of cardiac function after hypothermic ischemic storage with ouabain.
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.
Lagerstrom
C F
CF
Division of Thoracic and Cardiovascular Surgery, University of Texas Medical School, Houston.
McElroy
D D
DD
Taegtmeyer
H
H
Walker
W E
WE
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006003:Glycogen / Q000378:metabolism; D006321:Heart; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods*; D010042:Ouabain; D010725:Phosphocreatine / Q000378:metabolism; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014700:Verapamil
D000227:Adenine Nucleotides; D010725:Phosphocreatine; D010042:Ouabain; D000255:Adenosine Triphosphate; D006003:Glycogen; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase