Effects of nucleoside transport inhibition on long-term ex vivo preservation of canine hearts.
The effect of nucleoside transport inhibition on 24-hour preservation of canine hearts was studied in 36 hearts arrested either with a cold hyperkalemic cardioplegic solution without (group I) or with supplementation of a specific nucleoside transport inhibitor (R75231, 1 mg/L) (groups II and III). The hearts were excised and stored for 24 hours at 0.5 degrees C. Then they were reperfused for 3 hours with use of a closed perfusion system primed with normal blood (groups I and II) or with blood supplemented with the same nucleoside transport inhibitor (0.32 mg/L) (group III). Serial biopsy specimens for determination of myocardial purines were taken. Creatine kinase and heat-stable lactate dehydrogenase release from the myocardium were examined during reperfusion. Recovery of function was studied during reperfusion by measurement of isometric contraction in a fluid-filled intraventricular balloon. After 24 hours of preservation, without the use of the drug, myocardial inosine and hypoxanthine accumulated to, respectively, 4.05 +/- 1.18 and 0.28 +/- 0.08 mumol/gm dry weight. In the drug-treated groups (II and III pooled), significantly less inosine and hypoxanthine accumulated (1.68 +/- 0.33 and 0.05 +/- 0.02 mumol/gm dry weight, respectively) (p < 0.05 versus group I). Upon reperfusion, intramyocardial adenosine was lost in the control hearts and maintained in the drug-treated hearts. Hypoxanthine accumulated significantly (p < 0.05) during reperfusion in group I (1.08 +/- 0.43 versus 0.16 +/- 0.13 in group II and 0.03 +/- 0.03 mumol/gm dry weight in group III). The rate of creatine kinase and heat-stable lactate dehydrogenase release was significantly lower (p < 0.05) in group III (that is, pretreatment and posttreatment with the drug) than in the control group. Functional recovery of hearts in group III was superior to that in group II (p < 0.05), while hearts in group I showed no recovery at all. We conclude that nucleoside transport inhibition improves long-term preservation of the heart and that the mechanism of this protection may be related to an increase in endogenous adenosine and reduction of myocardial hypoxanthine content.
Masuda
M
M
Laboratory of Experimental Cardiac Surgery, Katholieke Universiteit Leuven, Belgium.
Chang-Chun
C
C
Möllhoff
T
T
Van Belle
H
H
Flameng
W
W
D000227:Adenine Nucleotides / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000241:Adenosine / Q000032:analysis; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000737:chemistry; D003402:Creatine Kinase / Q000378:metabolism; D004285:Dogs; D007042:Hypoxanthines / Q000032:analysis*; D066298:In Vitro Techniques; D007288:Inosine / Q000032:analysis; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D009926:Organ Preservation / Q000379:methods; D010879:Piperazines / Q000494:pharmacology*; D011684:Purine Nucleosides / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D016277:Ventricular Function, Left
D000227:Adenine Nucleotides; D002314:Cardioplegic Solutions; D007042:Hypoxanthines; D010879:Piperazines; D011684:Purine Nucleosides; C072040:draflazine; D007288:Inosine; D003402:Creatine Kinase; D000241:Adenosine