Preconditioning in isolated superfused human muscle.
Studies in isolated superfused rabbit papillary muscles indicate that preconditioning (PC) is not confined to arterially perfused myocardium. In the present study PC of isolated human right atrial trabeculae was investigated avoiding the problems of invasive experimentation in patients. Atrial trabeculae were suspended in an organ bath, superfused with Tyrode's solution and field stimulated at 1 Hz. After stabilization, muscles were randomly allocated to five groups (n = 8 per group). Control (C) muscles had no additional treatment. PC was induced by 3 min rapid pacing at 3 Hz with hypoxic substrate-free buffer, followed by reoxygenation with substrate for 12 min. In two additional groups 8-p-sulfophenyltheophylline (SPT) was added to the superfusate either during stabilization in controls (C+SPT) or during preconditioning (PC+SPT). In the final group, R-phenyl-isopropyl adenosine (R-PIA) was added to the superfusate for 5 min to see whether or not this could substitute for preconditioning. All muscles were then exposed to 90 min hypoxia with no substrate and pacing at 3 Hz, followed by 120 min reoxygenation at 1 Hz. Recovery of developed tension was significantly improved by PC 46.5 +/- 2.4% v 24.6 +/- 2.3% in controls) and this protective effect was blocked by the addition of SPT without adversely affecting controls (recovery in PC+SPT, 25.8 +/- 4.1% and C+SPT, 22.7 +/- 2.9%). R-PIA protected the muscles to a similar extent as PC (43.8 +/- 1.9%). These data provide evidence for the involvement of adenosine in preconditioning in human myocardium.
Hatter Institute for Cardiovascular Studies, Division of Cardiology, University College Hospital, London, UK.
D M
DM
Walker
J M
JM
Walker
W B
WB
Pugsley
C W
CW
Pattison
D M
DM
Yellon
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D016275:Atrial Function; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010477:Perfusion; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000502:physiology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D018047:Receptors, Purinergic P1; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000241:Adenosine