Effector mechanism of adenosine in acute ischemic preconditioning of skeletal muscle against infarction

被引:70
作者
Pang, CY
Neligan, P
Zhong, AG
He, W
Xu, H
Forrest, CR
机构
[1] UNIV TORONTO, DEPT SURG, TORONTO, ON M5G 1X8, CANADA
[2] UNIV TORONTO, DEPT PHYSIOL, TORONTO, ON M5G 1X8, CANADA
关键词
pig skeletal muscle; ischemic tolerance; energy metabolism; myeloperoxidase activity;
D O I
10.1152/ajpregu.1997.273.3.R887
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
We used adenosine A(1) receptor agonist N-6-1-(phenyl-2R-isopropyl)adenosine (PIA), A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and ATP-sensitive K+ (K-ATP) channel blockers sodium 5-hydroxydecanoate (5-HD) and glibenclamide (Glib), as probes to investigate the role and mechanism of adenosine in ischemic preconditioning (IPC) of noncontractile skeletal muscle against infarction, using the pig latissimus dorsi muscle flap model. Except for Glib, all drugs were delivered to each muscle flap by 10-min local intra-arterial infusion to avoid systemic effects. Muscle flaps that were subjected to 4 h of global ischemia and 48 h of reperfusion sustained 40 +/- 2% infarction. IPC with three cycles of 10 min ischemia and reperfusion, preischemic adenosine, or PIA treatment reduced (P < 0.05) muscle infarction to 24 +/- 2, 18 +/- 2, and 24 +/- 2%, respectively. The anti-infarction effect of IPC and adenosine was blocked by DPCPX, 5-HD, and Glib (P < 0.05). Preischemic adenosine treatment also maintained higher muscle contents of phosphocreatine, ATP, and energy charge potential and lower muscle contents of dephosphorylated metabolites and lactate during ischemia and a lower muscle myeloperoxidase (MPO) activity during reperfusion compared with the control (P < 0.05). Preischemic adenosine treatment did not increase muscle content of adenosine during ischemia or reperfusion. Furthermore, adenosine given at the onset of reperfusion was not effective in attenuating muscle MPO activity or infarction. Taken together, these observations indicate that adenosine, through A(1) receptors, initiates the mechanism of IPC with postreceptor involvement of K-ATP channels in skeletal muscle. However, adenosine is unlikely to play a key role in the effector mechanism. Presently, the cause and role of energy sparing and neutrophil inhibitory effects associated with the anti-infarction effect of preischemic adenosine treatment are unknown.
引用
收藏
页码:R887 / R895
页数:9
相关论文
共 39 条
  • [1] FRUCTOSE-1,6-DIPHOSPHATE OR ADENOSINE ATTENUATE LEUKOCYTE ADHERENCE IN POSTISCHEMIC SKELETAL-MUSCLE
    AKIMITSU, T
    WHITE, JA
    CARDEN, DL
    GUTE, DC
    KORTHUIS, RJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1995, 269 (05): : H1743 - H1751
  • [2] Ischemic preconditioning attenuates postischemic leukocyte adhesion and emigration
    Akimitsu, T
    Gute, DC
    Korthuis, RJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1996, 271 (05): : H2052 - H2059
  • [3] NA-H EXCHANGE IN MYOCARDIUM - EFFECTS OF HYPOXIA AND ACIDIFICATION ON NA AND CA
    ANDERSON, SE
    MURPHY, E
    STEENBERGEN, C
    LONDON, RE
    CALA, PM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 259 (06): : C940 - C948
  • [4] ADENOSINE-A(1) RECEPTORS, K(ATP) CHANNELS, AND ISCHEMIC PRECONDITIONING IN DOGS
    AUCHAMPACH, JA
    GROSS, GJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 264 (05): : H1327 - H1336
  • [5] THE ADENOSINE NEUTROPHIL PARADOX RESOLVED - HUMAN NEUTROPHILS POSSESS BOTH A1 AND A2 RECEPTORS THAT PROMOTE CHEMOTAXIS AND INHIBIT O-2- GENERATION, RESPECTIVELY
    CRONSTEIN, BN
    DAGUMA, L
    NICHOLS, D
    HUTCHISON, AJ
    WILLIAMS, M
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (04) : 1150 - 1157
  • [6] ROLE OF XANTHINE-OXIDASE IN REPERFUSION INJURY OF ISCHEMIC SKELETAL-MUSCLES IN THE PIG AND HUMAN
    DORION, D
    ZHONG, AG
    CHIU, C
    FORREST, CR
    BOYD, B
    PANG, CY
    [J]. JOURNAL OF APPLIED PHYSIOLOGY, 1993, 75 (01) : 246 - 255
  • [7] Acute adenosine treatment is effective in augmentation of ischemic tolerance in muscle flaps in the pig
    Forrest, CR
    Neligan, P
    Zhong, AG
    He, W
    Yang, RZ
    Pang, CY
    [J]. PLASTIC AND RECONSTRUCTIVE SURGERY, 1997, 99 (01) : 172 - 182
  • [8] HAIMOVICI H, 1979, J CARDIOVASC SURG, V20, P349
  • [9] HAIMOVICI H, 1979, SURGERY, V85, P461
  • [10] PURINE METABOLISM AFTER INVIVO ISCHEMIA AND REPERFUSION IN RAT SKELETAL-MUSCLE
    IDSTROM, JP
    SOUSSI, B
    ELANDER, A
    BYLUNDFELLENIUS, AC
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 258 (06): : H1668 - H1673