Relation between energy metabolism, glycolysis, noradrenaline release and duration of ischemia.
We studied the effect of 12-36 min of global ischemia followed by 36 min of reperfusion in Langendorff perfused rabbit hearts (n = 26). Metabolism was determined in terms of peak and total release of purines (adenosine, inosine, hypoxanthine), lactate and noradrenaline during reperfusion; and myocardial content of nucleotides (ATP, ADP, AMP), glycogen and noradrenaline at the end of reperfusion. An inverse relationship (r = -0.79) existed between duration of ischemia and developed pressure post-ischemia. Early during reperfusion, after 12 min of ischemia, the purine concentration (peak release) increased 100x (p < 0.01), that of lactate and noradrenaline 10x (p < 0.05). Total purine release rose with progression of the ischemic period (30x after 36 min of ischemia; p < 0.01), concomitant with a reduction in nucleotide content. Lactate release was independent from the duration of ischemia, although glycogen had declined by 30% (p < 0.01) after 36 min of ischemia. The acid insoluble glycogen fraction, which presumably contains proglycogen, increased substantially during short-term ischemia. Peak noradrenaline increased 100x, and 200x, (p < 0.05) after 24 and 36 min of ischemia, respectively. Total noradrenaline release due to various periods of ischemia mirrored its peak release. Function recovery was inversely related to total purine and noradrenaline efflux (both r = -0.81); it correlated with tissue nucleotide content (r = 0.84). In conclusion, larger amounts of noradrenaline are released only after a substantial drop in myocardial ATP. During severe ischemia ATP consumption more than limited ATP production by anaerobic glycolysis, is a key factor affecting recovery on subsequent reperfusion. In contrast to lactate efflux, purine and noradrenaline release are useful markers of ischemic and reperfusion damage.
Fondazione Clinica del Lavoro, Centro di Fisiopatologia Cardiovascolare Salvatore Maugeri, Brescia, Italy.
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Cargnoni
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Ceconi
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Curello
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Benigno
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de Jong
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Ferrari
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D019271:Hypoxanthine / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011687:Purines / Q000378:metabolism; D011817:Rabbits
D011687:Purines; D019271:Hypoxanthine; D019344:Lactic Acid; D007288:Inosine; D006003:Glycogen; D000241:Adenosine; C030985:purine; D009638:Norepinephrine