Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC148

Poster Communications

Acute caloric restriction reduces free radical damage in heart, reperfusion arrhythmias and myocardial infarction size in rats

M. Snorek1,4, J. Neckar3, A. Skoumalova2, D. Hodyc1, V. Sedivy1, J. Durisova1, J. Wilhelm2, F. Kolar3, J. Herget1

1. Department of Physiology, Charles University in Prague - Second Medical School, Prague, Czech Republic. 2. Department of the Medical Chemistry and Biochemistry, Charles University in Prague - Second Medical School, Prague, Czech Republic. 3. Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. 4. Heart Center, Ceske Budejovice Hospital, Ceske Budejovice, Czech Republic.


Reduced coronary perfusion in acute coronary syndrome causes myocardial ischemia. However, therapeutical process of restoring blood flow to the ischemic myocardium, i.e. reperfusion therapy, can induce injury. In the post-ischemic heart reactive oxygen species (ROS) formation is increased and could serve as a mechanism of this myocardial reperfusion injury (1). ROS formation and subsequent oxidative damage is reduced by, long-term (months) and short-term (weeks), caloric restriction (2,3) and is probably modulated by the cell redox state (4). The effect of acute caloric restriction (couple days immediately before the ischemic episode) has not yet been properly examined. We investigated whether the 3-day fasting affects production of ROS, incidence of ventricular arrhythmias during ischemia/reperfusion, myocardial infarction size and redox state of mitochondria. Adult male Wistar rats, anesthetized by sodium pentobarbitone (60 mg/kg body weight, intraperitoneally) were used. We analyzed production of the lipid peroxidation end products (lipofuscin-like pigments, LFP) in the heart tissue according to Goldstein & McDonagh (5). LFP concentration was expressed in relative fluorescence units (RFU) per mg of the tissue weight. Open-chest rats were intubated through the tracheotomy with a cannula connected to a rodent ventilator (Ugo Basile, Italy) and ventilated with room air at 65-70 breaths/min (tidal volume of 1.2 ml/100 g body weight). Then, the animals were subjected to 20-min left anterior descending coronary artery occlusion followed by reperfusion. A single lead ECG was recorded and arrhythmias were assessed. The infarction size in excised hearts was determined by triphenyltetrazolium chloride staining and it was normalized to area at risk (IS/AR). To assess redox state of the mitochondrial compartment we analyzed, in the excised hearts, acetoacetate/β-hydroxybutyrate ratio (AA/BHB) correlating with NADH/NAD+ ratio. All results are expressed as means ± S.E.M. The statistical significance of differences was determined by one-way ANOVA and subsequent Fisher’s PLSD test and the Games/Howell post hoc test, as appropriate. Three day fasting reduced LFP production in heart tissue: 1.9±0.1 RFU in fasting rats (n=9) vs. 3.1±0.3 RFU in controls (n=7), p<0.005. It did not affect ischemic arrhythmias. During early reperfusion the number of premature ventricular complexes was reduced in fasting rats (n=12, 12.5±5.8) compared to controls (n=11, 194.9±21.9), p<0.005, as well as ventricular tachycardia duration (0.6±0.4 sec vs. 18.8±2.5 sec), p<0.005. In fasting rats (n=6) the IS/AR reached 48.5±3.3 % while in controls (n=5) it was 74.3±2.2 %, p<0.005. AA/BHB ratio in fasting rats (n=11) was 0.03±0,01, while in controls (n=10) it was 0,17±0,04, p<0.05. Acute caloric restriction limits free radical damage in heart, reperfusion ventricular arrhythmias and myocardial infarction size in rats. This protective effect could be induced by changes of mitochondrial redox state.

Where applicable, experiments conform with Society ethical requirements