TY - JOUR
T1 - Glibenclamide does not abolish the protective effect of preconditioning on stunning in the isolated perfused rat heart
AU - Fralix, Teresa A.
AU - Steenbergen, Charles
AU - London, Robert E.
AU - Murphy, Elizabeth
N1 - Funding Information:
CS is supported by NIH grant HL 39752.
PY - 1993
Y1 - 1993
N2 - Objective: The aim was to determine if the beneficial effects of preconditioning would be affected by inhibiting ATP sensitive potassium (KATP) channels in the isolated, perfused rat heart. Methods: The effects of inhibiting KATP channels with glibenclamide (10 μM) were evaluated on ionic alterations and recovery of function after 30 min ischaemia in non-preconditioned hearts and in hearts that had been preconditioned with four intermittent periods of 5 min ischaemia each separated by 5 min of reflow. [Ca2+]i, pHi, and high energy phosphate levels were measured using 19F and 31P nuclear magnetic resonance during the preconditioning periods of ischaemia, during 30 min of ischaemia, and during reflow, in the presence and absence of 10 μM glibenclamide. Results: High energy phosphate contents were decreased during the preconditioning period to a greater extent in glibenclamide treated hearts and the onset of contracture was hastened during the subsequent 30 min period of sustained ischaemia. However, glibenclamide (10 μM) did not abolish the protective effects of preconditioning on ion accumulation during ischaemia or on postischaemic recovery of contractile function. Recovery of left ventricular developed pressure (as % of initial value) following 30 min of ischaemia was 74(SEM 5)% in the preconditioned hearts without drug and 62(4)% in the preconditioned hearts with glibenclamide, while recovery was 25(5)% in the non-preconditioned hearts without drug and 19(2)% in the non-preconditioned hearts with drug. The alterations in [Ca2+]i and pHi during ischaemia were similar in the glibenclamide treated and untreated preconditioned hearts and in both cases were less marked than in the non-preconditioned untreated hearts. Conclusions: Thus, although inhibition of KATP channels accelerates high energy phosphate depletion during the preconditioning period, this does not result in accentuation of the ionic derangements during a subsequent sustained period of ischaemia and does not abolish the protective effect of preconditioning on stunning in the isolated rat heart.
AB - Objective: The aim was to determine if the beneficial effects of preconditioning would be affected by inhibiting ATP sensitive potassium (KATP) channels in the isolated, perfused rat heart. Methods: The effects of inhibiting KATP channels with glibenclamide (10 μM) were evaluated on ionic alterations and recovery of function after 30 min ischaemia in non-preconditioned hearts and in hearts that had been preconditioned with four intermittent periods of 5 min ischaemia each separated by 5 min of reflow. [Ca2+]i, pHi, and high energy phosphate levels were measured using 19F and 31P nuclear magnetic resonance during the preconditioning periods of ischaemia, during 30 min of ischaemia, and during reflow, in the presence and absence of 10 μM glibenclamide. Results: High energy phosphate contents were decreased during the preconditioning period to a greater extent in glibenclamide treated hearts and the onset of contracture was hastened during the subsequent 30 min period of sustained ischaemia. However, glibenclamide (10 μM) did not abolish the protective effects of preconditioning on ion accumulation during ischaemia or on postischaemic recovery of contractile function. Recovery of left ventricular developed pressure (as % of initial value) following 30 min of ischaemia was 74(SEM 5)% in the preconditioned hearts without drug and 62(4)% in the preconditioned hearts with glibenclamide, while recovery was 25(5)% in the non-preconditioned hearts without drug and 19(2)% in the non-preconditioned hearts with drug. The alterations in [Ca2+]i and pHi during ischaemia were similar in the glibenclamide treated and untreated preconditioned hearts and in both cases were less marked than in the non-preconditioned untreated hearts. Conclusions: Thus, although inhibition of KATP channels accelerates high energy phosphate depletion during the preconditioning period, this does not result in accentuation of the ionic derangements during a subsequent sustained period of ischaemia and does not abolish the protective effect of preconditioning on stunning in the isolated rat heart.
KW - ATP sensitive K channel
KW - Glibenclamide
KW - Perfused heart
KW - Preconditioning
UR - http://www.scopus.com/inward/record.url?scp=0027192137&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027192137&partnerID=8YFLogxK
M3 - Article
C2 - 8324797
AN - SCOPUS:0027192137
SN - 0008-6363
VL - 27
SP - 630
EP - 637
JO - Cardiovascular research
JF - Cardiovascular research
IS - 4
ER -