Abolition of reperfusion-induced arrhythmias in hearts from thiamine-deficient rats

Abstract

tensive work has been done regarding the impact of thiamine deprivation on the nervous system. In cardiac tissue, chronic thiamine deficiency is described to cause changes in the myocardium that can be associated with arrhythmias. However, compared with the brain, very little is known about the effects of thiamine deficiency on the heart. Thus this study was undertaken to explore whether thiamine deprivation has a role in cardiac arrhythmogenesis. We examined hearts isolated from thiamine-deprived and control rats. We measured heart rate, diastolic and systolic tension, and contraction and relaxation rates. Whole cell voltage clamp was performed in rat isolated cardiac myocytes to measure L-type Ca 2ϩ current. In addition, we investigated the global intracellular calcium transients by using confocal microscopy in the line-scan mode. The hearts from thiaminedeficient rats did not degenerate into ventricular fibrillation during 30 min of reperfusion after 15 min of coronary occlusion. The antiarrhythmogenic effects were characterized by the arrhythmia severity index. Our results suggest that hearts from thiamine-deficient rats did not experience irreversible arrhythmias. There was no change in L-type Ca 2ϩ current density. Inactivation kinetics of this current in Ca 2ϩ -buffered cells was retarded in thiamine-deficient cardiac myocytes. The global Ca 2ϩ release was significantly reduced in thiaminedeficient cardiac myocytes. The amplitude of caffeine-releasable Ca 2ϩ was lower in thiamine-deficient myocytes. In summary, we have found that thiamine deprivation attenuates the incidence and severity of postischemic arrhythmias, possibly through a mechanism involving a decrease in global Ca 2ϩ release.arrhythmia; calcium current; confocal microscopy THIAMINE DEFICIENCY CAUSES cardiovascular and neurological damage that presents clinically as beriberi. Thiamine pyrophosphate is an important cofactor in several vital enzymatic reactions involved in metabolism and energy production (34, 39). Following its uptake by the cell, thiamine rapidly undergoes pyrophosphorylation, yielding thiamine pyrophosphate, which is the active substance. Extensive work has been done regarding the impact of thiamine deprivation on the nervous system. However, very little is known about the effects of thiamine deficiency on the myocardium (5). Cappelli et al. (5) have shown evidence that supports the view that cardiac contractility is deeply affected in the rat by thiamine deficiency. Thiamine is also considered a clinically important factor in heart function, and its deficiency has been reported to cause heart failure (28, 33, 35). The general view that reperfusion of the ischemic myocardium exerts a beneficial effect by preventing the ischemiainduced changes in cardiac performance has been supported by a number of studies; however, reperfusion after a certain critical time has been shown to be deleterious to cardiac function (16). Intracellular Ca 2ϩ has an important role in heart function, and studies have been conducted to investigate pos...

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“…The confocal line-scan imaging was performed with a Zeiss LSM 510META confocal microscope. The amplitude of the Ca 2ϩ transient evoked by the application of a Ca 2ϩ -and Na ϩ -free solution containing 10 mM caffeine was used as an indicator of the SR Ca 2ϩ load (36). Cells were subjected to a series of preconditioning pulses (1 Hz) before caffeine was applied.…”

“…An EPC-9.2 instrument (HEKA Electronics) was used to patch clamp single ventricular cardiomyocytes in whole-cell voltage and current clamp configurations, using specific protocols according to the ionic conductance evaluated (8,36,42). Measurements started 5 min after breaking into the cell in order to attain equilibrium between the pipette solution and the cell cytoplasm.…”

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