Letter to the Editor Postcardiac arrest syndrome: second thoughts regarding therapeutic hypothermia To the Editor: We have read with great interest the excellent article by Wold et al. (2012) which has been published in the latest issue of Acta Physiologica. The authors concluded that the cardiac contractile dys- function after rewarming is explained not only by the aggravation of calcium overload during deep hypo- thermia (15 °C), but also by the decreased recovery of calcium homoeostasis during rewarming. Although there is evidence that calcium ion concentration increases considerably after deep hypothermia and rewarming in animals with intact heart in a nonarrest- ed state (Fedorov et al. 2005, Wold et al. 2012), mild therapeutic postresuscitation hypothermia (32–34 °C) shares similar characteristics that may be of particular importance. It is known that during cardiac arrest, the increased membrane permeability together with changes in sarcolemma and sarcoplasmic reticulum increases the intracellular calcium concentration, which in turn activates various proteases, resulting in sustained impairment of contractility and mitochon- drial swelling (Chalkias & Xanthos 2012a). Consid- ering that the abrupt loss of effective blood flow results in decrease in tissue temperature and meta- bolic rate, it would be of major interest to determine whether this ischaemia-induced onset of cellular hypothermia is one of the initial events that eventu- ally lead to calcium overload (Goetzenich et al. 2009, Tisherman 2012). Interestingly, human myocardium not only shows a negative inotropic effect when exposed to hypothermia, but also calcium-dependent inotropy is suppressed at temperatures below 34 °C (Goetzenich et al. 2009). In addition, with the onset of blood flow due to chest compressions (compression-induced cellular rewarming), the low concentrations of oxygen that are transferred to myocardium enhance the produc- tion of adenosine triphosphate, which together with calcium overload lead to uncontrolled activation of contractile machinery, thus partly explaining the dif- ficulties in recovering calcium homoeostasis reported by Wold et al. (2012). Moreover, the oxidation products of catecholamines increase intracellular cal- cium overload (Dhalla et al. 2010), while comple- ment activation during rewarming may result in polymorphonuclear leucocytes chemotaxis and adherence, release of reactive oxygen species, aggra- vation of calcium overload and cell death (Kopil et al. 2011, Bisschops et al. 2012, Chalkias & Xan- thos 2012a,b). Therefore, as hypothermia and rew- arming may exacerbate postresuscitation myocardial stunning, further research is needed to determine optimal duration of therapeutic hypothermia, opti- mum target temperature and rates of cooling and rewarming. Conflicts of interest There are none. A. Chalkias and T. Xanthos Department of Anatomy, Medical School, National and Kapodistrian University of Athens, Athens, Greece E-mail: thanoschalkias@yahoo.gr References Bisschops, L.L., Hoedemaekers, C.W., Mollnes, T.E. & van der Hoeven, J.G. 2012. Rewarming after hypothermia after cardiac arrest shifts the inflammatory balance. Crit Care Med 40, 1136–1142. Chalkias, A. & Xanthos, T. 2012a. Pathophysiology and pathogenesis of post-resuscitation myocardial stunning. Heart Fail Rev 17, 117–128. Chalkias, A. & Xanthos, T. 2012b. Redox-mediated programed death of myocardial cells after cardiac arrest and cardiopulmonary resuscitation. Redox Rep 17, 80–83. Dhalla, N.S., Adameova, A. & Kaur, M. 2010. Role of cate- cholamine oxidation in sudden cardiac death. Fundam Clin Pharmacol 24, 539–546. Fedorov, G.S., Potekhina, I.L. & Ivanov, K.P. 2005. About a correlation between calcium ion concentration (Ca2+) in the blood and the state of physiological functions in ani- mals in deep cooling. Ross Fiziol Zh Im I M Sechenova 91, 1205–1212. Goetzenich, A., Schroth, S.C., Emmig, U., Autschbach, R., Pieske, B., Rossaint, R. & Christiansen, S. 2009. Hypo- thermia exerts negative inotropy in human atrial prepara- tions: in vitro-comparison to rabbit myocardium. J Cardiovasc Surg (Torino) 50, 239–245. Kopil, C.M., Vais, H., Cheung, K.H., Siebert, A.P., Mak, D.O., Foskett, J.K. & Neumar, R.W. 2011. Calpain- cleaved type 1 inositol 1,4,5-trisphosphate receptor (InsP (3)R1) has InsP(3)-independent gating and disrupts © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society, doi: 10.1111/apha.12029 324 Acta Physiol 2013, 207, 324–325