Recovery of myocardial function after ischaemia: the effects of AMP and inhibition of endocytosis.

Recovery from ischaemia in heart tissue can be accelerated by addition of precursors of ATP such as AMP to the coronary circulation. Endocytosis in capillary endothelia is also stimulated by AMP; therefore endocytosis may be important in the transport of AMP from the circulation into myocytes. Alternatively, the increase in endocytotic transport itself could be responsible for accelerated recovery, irrespective of the stimulating agent. The effects of sham, AMP, cytochalasin-D (an inhibitor of endocytosis), and cytochalasin-D + AMP infusates given prior to, during, and following a 15 min ischaemic episode, were examined. AMP accelerated biochemical and functional recovery after episodes of ischaemia and stimulated endocytosis in coronary capillaries. Cytochalasin-D strongly inhibited contractility before, during, and after ischaemia, and similarly depressed ATP and creatine phosphate levels. Cytochalasin-D also strongly inhibited endocytosis and caused swelling of the capillary endothelium. When cytochalasin-D and AMP were provided together, the beneficial effects of AMP were only partially inhibited by cytochalasin-D. In fact, AMP was able to reverse most of the effects of cytochalasin-D including the inhibition of endocytosis. This suggests accelerated recovery of ischaemic myocytes requires precursors of ATP such as AMP, and the stimulation of endocytosis may abet transport of these precursors, or may be a spurious phenomenon.