calcimycin and acadesine

Crystalloid cardioplegia may cause coronary microvascular endothelial dysfunction during cardiopulmonary bypass. The perioperative administration of either adenosine or AICA-riboside (acadesine, 5-aminoimidazole-4-carboxamide-1-ribofuranoside) has been associated with improved myocardial functional preservation and improved coronary blood flow after ischemic arrest. To examine if this enhanced recovery of myocardial function and perfusion may be related to improved endothelial preservation, pigs were placed on cardiopulmonary bypass and the hearts were arrested with plain cold, hyperkalemic (K+ = 25 mmol/L) crystalloid cardioplegia, or cardioplegic solution containing either 0.1 mmol/L adenosine or 50 mumol/L AICA-riboside, which causes the release of endogenous adenosine. AICA-riboside (375 mg) also was infused over 30 minutes before cardioplegia in the later group. After 1 hour of ischemic cardioplegia, hearts were reperfused for 1 hour while the pigs were weaned from cardiopulmonary bypass. Coronary arterioles (90 to 190 microns in diameter) from both subepicardial and subendocardial regions of the left ventricle were studied in vitro in a pressurized, no-flow state with videomicroscopy. After contraction of vessels by 25% to 40% of the baseline diameter, drugs were applied extraluminally. Relaxation of control arterioles to serotonin was slightly greater in vessels from the subendocardial region compared with vessels from the subepicardial region, and subendocardial arterioles were more affected by cardioplegia than were subepicardial vessels. In contrast, relaxations of control microvessels to bradykinin and the calcium ionophore A23187 were similar in the two transmural myocardial regions. Responses to bradykinin and A23187 were significantly and similarly reduced after ischemic arrest with plain crystalloid cardioplegia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine; Aminoimidazole Carboxamide; Animals; Blood; Bradykinin; Calcimycin; Cardioplegic Solutions; Cardiopulmonary Bypass; Coronary Vessels; Endothelium, Vascular; Female; Heart Arrest, Induced; Male; Muscle, Smooth, Vascular; Myocardial Reperfusion Injury; Nitroprusside; Ribonucleosides; Swine

Stimulated mast cells produce and release adenosine, and the release of mast cell mediators is potentiated by adenosine, yet very little is known regarding mast cell purine metabolism. Because 5-amino-4-imidazolecarboxamide riboside (AICA riboside) has been shown to alter adenosine metabolism and accelerate the repletion of ATP pools in other tissues, its effects on mast cell function were examined. Neither simultaneous addition of A23187 and AICA riboside nor a 1-hr preincubation with AICA riboside altered mast cell beta-hexosaminidase release to an appreciable degree. However, mouse bone marrow-derived mast cells cultured for 2 or more days in the presence of 1-100 microM AICA riboside exhibited a markedly attenuated mediator release response to A23187 compared to control cells with or without the additional presence of adenosine. IgE-mediated leukotriene C4 generation from AICA riboside-exposed mast cells was even more profoundly inhibited without affecting cell viability or resting mediator content. An unusual ribonucleotide triphosphate previously identified in folate-depleted cells, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl 5'-triphosphate (ZTP), has been identified in AICA riboside-treated mast cells as well. Although the mechanism of this global inhibition of mast cell mediator release by chronic AICA riboside treatment is not clear, alterations in mast cell purine metabolism may prove to be important in the treatment of allergic diseases.

Topics: Adenosine Triphosphate; Aminoimidazole Carboxamide; Animals; beta-N-Acetylhexosaminidases; Bone Marrow Cells; Calcimycin; Cells, Cultured; Imidazoles; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ribonucleosides; SRS-A