Purine metabolism and release during cardioprotection with hyperkalemia and hypothermia.
This work investigates whether purine metabolism and release is related to cardioprotection with hyperkalemia and hypothermia. Langendorff guinea-pig hearts were used to either monitor metabolism during ischemia or to measure functional recovery, myocardial injury and release of purine during reperfusion. Hearts underwent 30 min ischemia using one of the following protocols: control (normothermic buffer), hyperkalaemia (high-potassium buffer), hypothermia (20 degrees C) and hyperkalemia + hypothermia. At the end of 30 min ischemia, hyperkalemia was associated with similar metabolic changes (rise in purine and lactate and fall in adenine nucleotides) to control group. Accumulation of purine was due to a rise in inosine, xanthine and hypoxanthine and was largely prevented by hypothermia and hyperkalemia + hypothermia. Upon reperfusion, there was a time-dependent release of all purine, lactate and AMP. A fast (peak in less than 20 sec) release of inosine, xanthine, hypoxanthine and lactate was highest in control followed by hyperkalemia then hypothermia and little release in hyperkalemia + hypothermia. Adenosine and AMP release was slow (peak at 3 min), only significant in control and was likely to be due to sarcolemmal disruption as the profile followed lactate dehydrogenase release. Recovery (left ventricular developed pressure) was 63% control, 82% hyperkalemia, 77% hypothermia and 98% for hyperkalemia + hypothermia. The loss of purine during reperfusion but not their production during ischemia is related to cardioprotection with hyperkalemia. The possibility that the consequences of hyperkalemia modulate a sodium-dependent purine efflux, is discussed. The reduced loss of purine in hypothermia or in hyperkalemia + hypothermia is likely to be due to a lower metabolic activity during ischemia.
Imura
Hajime
H
Bristol Heart Institute, Bristol University, UK.
Ayres
Ben E
BE
Suleiman
M Saadeh
MS
D000225:Adenine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006947:Hyperkalemia / Q000378:metabolism*; D007035:Hypothermia / Q000378:metabolism*; D019271:Hypoxanthine / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011687:Purines / Q000378:metabolism*; D015427:Reperfusion Injury; D013696:Temperature; D013997:Time Factors; D019820:Xanthine / Q000378:metabolism
D007773:Lactates; D011687:Purines; D019820:Xanthine; D019271:Hypoxanthine; D000249:Adenosine Monophosphate; D007288:Inosine; D007770:L-Lactate Dehydrogenase; D000225:Adenine; D000241:Adenosine