Morphological changes of heart muscle caused by successive perfusion with calcium-free and calcium-containing solutions (calcium paradox)

The phenomenon ‘calcium paradox’ has been found by increase of motional freedom of phospholipids and leakage Zimmerman and myself in 1966 [1]. At that time I was upon recalcification, resulting in loss of soluble cell interested in the effects of fatty acids and ketone bodies as constituents [4]. This paper mentions that cooling or energy sources for the beating heart, after studies on addition of amphipathic (membranophilic) compounds, isolated heart mitochondria. Fortunately, I heard from such as local anaesthetics, tranquilizers (or other positively Zimmerman of his work on isolated rat hearts, perfused charged amphipathic compounds such as acylcarnitines) 21 according to the Langendorff technique. I prepared an may protect against imminent Ca overload and cell isotonic, neutral, solution of sodium acetylacetate to be damage [5]. Conclusion: the ‘calcium paradox’ has been a 21 added to the glucose-containing Ringer salt-solution used. warning clinical use of Ca -free perfusion in cardiac 21 Due to a misunderstanding, the mixing of the two solutions surgery, as return to Ca -containing media causes tissue did not take place. Instead, after perfusion of the heart with destruction. the Ringer solution, brief perfusion with the aqueous sodium acetylacetate took place. The result was unexpected as the heart stopped beating immediately while its electrical activity continued, known as electro-mechanical References dissociation [2]. Prolonged preperfusion with the 0.15 M aqueous acetylacetate, however, led to irreversible arrest of ̈ [1] Zimmerman ANE, Hulsmann WC. Paradoxal influence of calcium ions on the permeability of the cell membranes of the isolated rat the heart in systole after resuming perfusion with the heart. Nature 1966;211(49):646–647. Ringer solution, while the reddish color of the heart ̈ [2] Zimmerman ANE, Meyler FL, Hulsmann WC. The inhibitory effect disappeared and the effluent became brownish–red, due to of acetoacetate on myocardial contraction. Lancet 1962;757–758. the loss of myoglobin from the heart. Morphological ̈ [3] Zimmerman ANE, Daems W, Hulsmann WC et al. Morphological studies of the heart showed hypercontracted carchanges of heart muscle caused by successive perfusion with diomyocytes alternated with ‘empty’ cardiomyocyten calcium-free and calcium-containing solutions (calcium paradox). Cardiovasc Res 1967;1:201–209. along the sarcomeres [3]. ̈ [4] Hulsmann WC. On the mechanism of the calcium paradox ‘the In summary, the ‘calcium paradox phenomenon’ is the 21 release of hydrolytic enzymes’. Eur Heart J 1983;4:57–61. result of a technical error as Ca -free perfusion, after a ̈ [5] Hulsmann WC, Dubelaar ML, Lamers JM, Maccari F. Protection by 21 few minutes, followed by Ca -containing perfusion, acylcarnitines and phenylmethylsulfonyl–fluoride of rat hearts sub21 results in Ca overload of cells and therefore to hyjected to ischemia and reperfusion. Biochim Biophys Acta percontraction. Decalcification of plasmalemma results in 1985;847:62–66.