Stanley, Peter Graham; (1994) Guanine nucleotides in ischaemic heart. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

In isolated perfused rat hearts the concentration of guanine nucleotides following periods of global no-flow ischaemia and reperfusion were found to parallel those of adenine nucleotides under all conditions tested. Short periods of ischaemia (up to 20 minutes) resulted in decreases of about 50% in both ATP and GTP concentration, with full recovery usually occurring after 10 minutes of reperfusion, while longer periods of ischaemia resulted in greater decreases in ATP and GTP and a lower rate of recovery on reperfusion. Similar results were observed in isolated rat myocytes subjected to periods of anoxia. Discrepancies were noted in total guanine compounds following ischaemia; the changes to guanine nucleotides were apparently not balanced by corresponding changes to breakdown products (eg guanosine), in either perfused hearts or isolated myocytes. The post-ischaemic/anoxic recovery of guanine nucleotides was unaffected by IMP-dehydrogenase inhibitors, suggesting that neither de novo synthesis nor the existing adenine nucleotide pool contributed significantly to the recovery. No correlation was found between the GTP concentration or the GTP/GDP ratio and the post-ischaemic response of hearts to either adrenaline or carbachol, suggesting that neither GTP availability nor a depressed GTP/GDP ratio was acting as the rate-limiting factor in the signal transmission process.

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