Preconditioning ischemia (PI) increases the speed of the initial vasodilatation (vascular preconditioning) of a subsequent coronary reactive hyperemia (CRH) and reduces total hyperemic flow (THF). We investigated whether changes in CRH similar to those induced by PI are obtained with diazoxide, a mitochondrial ATP-sensitive K+ channel opener, and whether diazoxide influences the effects of a subsequent PI on CRH. In anesthetized goats, flow was recorded from the left circumflex coronary artery (LCCA). CRH and PI were obtained with 15-s and 5-min LCCA occlusions, respectively. CRH was studied before and after PI, before and after diazoxide (2.5 mg/kg i.v.) as well as before and after PI was induced after diazoxide pre-treatment. After PI, the time to peak (ttp) of CRH and THF decreased by 51+/-13% and 23+/-8%, respectively. Diazoxide did not change CRH. After diazoxide and PI, when basal flow had returned to the control level, the ttp of CRH was reduced as after PI alone (-45+/-12%), whereas THF was reduced to a greater extent (-41+/-9% versus -23+/-8%; P<0.01). In conclusion, PI alters CRH by decreasing THF and reducing the ttp of CRH. Whilst diazoxide does not reproduce the effects of PI on CRH, pre-treatment with diazoxide potentiates the effects of PI on THF.

Mitochondrial ATP-sensitive channel opener does not induce vascular preconditioning, but potentiates the effect of a preconditioning ischemia on coronary reactive hyperemia in the anesthetized goat.

PAGLIARO, Pasquale;RASTALDO, Raffaella;LOSANO, Giovanni;MACERAUDI, Donatella
2001

Abstract

Preconditioning ischemia (PI) increases the speed of the initial vasodilatation (vascular preconditioning) of a subsequent coronary reactive hyperemia (CRH) and reduces total hyperemic flow (THF). We investigated whether changes in CRH similar to those induced by PI are obtained with diazoxide, a mitochondrial ATP-sensitive K+ channel opener, and whether diazoxide influences the effects of a subsequent PI on CRH. In anesthetized goats, flow was recorded from the left circumflex coronary artery (LCCA). CRH and PI were obtained with 15-s and 5-min LCCA occlusions, respectively. CRH was studied before and after PI, before and after diazoxide (2.5 mg/kg i.v.) as well as before and after PI was induced after diazoxide pre-treatment. After PI, the time to peak (ttp) of CRH and THF decreased by 51+/-13% and 23+/-8%, respectively. Diazoxide did not change CRH. After diazoxide and PI, when basal flow had returned to the control level, the ttp of CRH was reduced as after PI alone (-45+/-12%), whereas THF was reduced to a greater extent (-41+/-9% versus -23+/-8%; P<0.01). In conclusion, PI alters CRH by decreasing THF and reducing the ttp of CRH. Whilst diazoxide does not reproduce the effects of PI on CRH, pre-treatment with diazoxide potentiates the effects of PI on THF.
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P. PAGLIARO; R. RASTALDO; G. LOSANO; D. MACERAUDI GATTULLO
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/37067
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