Calcium delivery and time: factors affecting the progression of cellular damage during the calcium paradox in the rat heart.
Using an isolated rat heart preparation we have investigated the influence of calcium delivery and time upon the induction of cellular injury during the calcium paradox. Hearts were subjected to 10 min of calcium depletion. This was followed by calcium repletion for up to 20 min during which time the calcium concentration in the perfusate was varied between 0.025 and 1.00 mmol X litre-1. For the lowest calcium repletion concentration, cumulative leakage of creatine kinase activity was small and linear with time over the 20 min repletion period, and relatively few damaged cells were observed, these being situated around coronary vessels. For calcium concentrations of 0.05 mmol X litre-1 and above the progression of structural injury was dependent on both increasing calcium concentration and time. After 1 min of repletion with 0.10 mmol calcium X litre-1 the percentage damaged cells was 2%, this sharply increased to 95% after 10 min of repletion but without a parallel increase in the profile for creatine kinase leakage. For calcium repletion at 0.05 mmol X litre-1 morphological injury was shown to be highly heterogeneous both within and between hearts. Uniform cellular damage (ie greater than 95%) in the concentration range 0.25 to 1.00 mmol calcium X litre-1 was only seen after 10 min of calcium readmission. Maximal cumulative creatine kinase activity only occurred after 15 to 20 min of repletion with 0.50 and 1.00 mmol calcium X litre-1. Our results show calcium delivery and time can both modulate the progression of cellular injury and allow a dissociation between indices of tissue damage.
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003402:Creatine Kinase / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007473:Ion Channels; D003402:Creatine Kinase; D002118:Calcium