Protection against cellular damage in the rat heart by hyperosmotic solutions.
In this comparative study, rat hearts were perfused at 37 degrees C with three clearly defined protocols: the Ca2+ paradox, the O(2) paradox, and with 20 mM caffeine. Each protocol involved an initial priming (Ca(2+)(0) depletion or anoxia; stage 1) and subsequent full activation (Ca(2+)(0) repletion, caffeine or reoxygenation; stage 2) of the damage system of the sarcolemma. Creatine kinase release in stage 2 was completely inhibited (P < 0.001) in all three protocols when 420 mOsm was added to the perfusion medium throughout the experiments, or only during stage 1, or only during stage 2. Increasing the perfusion pressure in the Ca2+ paradox significantly (P < 0.001) exacerbated creatine kinase release, although this was still completely inhibited at 28 degrees C. Amiloride (1 mM) inhibited creatine kinase release completely at 40 cm of water pressure but only some 50% at 80 cm of water pressure. It is suggested that the transmembrane damage system needs to be uncoupled or deactivated by modifying its relationship with the cytosol or with the underlying cytoskeleton by hyperosmotic cell shrinkage for only one of the stages in all three protocols to block the damage pathway. Increased perfusion pressure has the opposite effect and exacerbates damage.
Harding
R J
RJ
School of Biological Sciences, University of Liverpool, Derby Building, Liverpool, L69 3BX, United Kingdom.
Duncan
C J
CJ
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006335:Heart Injuries / Q000503:physiopathology / Q000517:prevention & control*; D006982:Hypertonic Solutions; D000860:Hypoxia / Q000503:physiopathology; D009997:Osmotic Pressure; D010100:Oxygen; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
D006982:Hypertonic Solutions; D002110:Caffeine; D003402:Creatine Kinase; D010100:Oxygen; D002118:Calcium