Effects of hypothermic ischemia on purine catabolism in canine, primate, and human myocardium.
After hypothermic cardiac arrest, creatine phosphate (CrP) and adenine nucleotide catabolism was compared in myocardium from dogs (n = 7), baboons (n = 5), and man (n = 7; patients undergoing cardiac transplantation) during cold (0.5 degree C) storage for up to 24 hours. Although hypothermia delayed the catabolism in dog myocardium it still remained very extensive. CrP dropped to virtually nil and ATP fell to below 15% of the total purines within 6 hours. The majority of the adenine nucleotides was broken down to adenosine (ADO; 32% of total purines) and inosine (INO; 21%). Apart from the delay (7 to 9-fold), hypothermia also reversed the ratio between ADO and INO when compared to normothermia, suggesting a profound effect of temperature on the nucleoside transporter. In human myocardium even after 12 hours of hypothermia ATP still contributed more than 60% to the total purines. Concomitantly, nucleoside formation proceeded slowly with almost no intermediate ADO. Under similar conditions, the catabolism of ATP in baboon myocardium occurred at a higher rate than in man but still far below canine metabolism. Irrespective of the relatively higher fall in ATP, ADP and AMP accumulated more in baboon myocardium indicating a limited dephosphorylation of the nucleotides. Only in the baboon myocardium did inosine monophosphate increase above the detection limits. In none of the species did purine catabolism proceed beyond hypoxanthine and even this could hardly be detected in the primates. It is concluded that considerable species differences do exist in the rate as well as in the pattern of nucleotide catabolism even during storage of the myocardium at low temperature.
Möllhoff
T
T
Laboratory of Experimental Cardiac Surgery, Katholieke Universiteit, Leuven, Belgium.
Sukehiro
S
S
Hendrickx
M
M
Van Belle
H
H
Flameng
W
W
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004285:Dogs; D006324:Heart Arrest, Induced; D016027:Heart Transplantation; D006801:Humans; D007036:Hypothermia, Induced; D007288:Inosine / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010215:Papio; D010725:Phosphocreatine / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D013045:Species Specificity; D014970:Xanthines / Q000378:metabolism
D000227:Adenine Nucleotides; D011687:Purines; D014970:Xanthines; D010725:Phosphocreatine; D000249:Adenosine Monophosphate; D007288:Inosine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine