L-thyroxine increases susceptibility of adult rats to low K+-induced ventricular fibrillation, and sinus rhythm restoration in old rats.

Hypokalaemia increases the risk for life-threatening arrhythmias; however, data about interaction with thyroid status are lacking. The aim of this study was to investigate vulnerability of l-thyroxine (T(4))-treated adult and old rats to low K(+)-induced ventricular fibrillation (VF) as well as the ability of the heart to recover sinus rhythm. The experiments were performed on isolated heart preparations using the heart of 4- and 20-month-old female Wistar rats without and with feeding with T(4) 50 microg (100 g day)(-1) over a period of 2 weeks. Perfusion of the isolated heart with oxygenated Krebs-Henseleit solution at constant pressure was followed by perfusion with K(+)-deficient solution until occurrence of VF (< 10 min). After 2 min of sustained VF, the heart was perfused with normal solution for 10 min, during which sinus rhythm was restored. ECG, left ventricular pressure (LVP) and coronary flow were continuously monitored. The results showed that compared with untreated rats, the onset of low K(+)-induced ventricular premature beats was delayed and their number was significantly decreased in both T(4)-treated groups. Nevertheless, VF occurred earlier in T(4)-treated than in non-treated adult rats (6.78 +/- 0.28 vs. 9.59 +/- 0.55 min, P < 0.05), whereas the difference was not significant in aged animals. Furthermore, sinus rhythm appeared earlier in old T(4)-treated rats compared with non-treated rats (7.18 +/- 0.57 vs. 8.94 +/- 0.64 min, P < 0.05), whereas in adult hearts it set in at practically the same time regardless of treatment. In conclusion, our results indicate that administration of a pharmacological dose of T(4) can increase the risk of low K(+)-induced VF in adult but not in old animals; in the latter it even facilitated restoration of sinus rhythm. Moreover, enhanced mechanical function was observed in both adult and old T(4)-treated hearts.

Remodelling of the sarcolemma in diabetic rat hearts: the role of membrane fluidity.

The hyperglycaemia and oxidative stress, that occur in diabetes mellitus, cause impairment of membrane functions in cardiomyocytes. Also reduced sensitivity to Ca-overload was reported in diabetic hearts (D). This enhanced calcium resistance is based on remodelling of the sarcolemmal membranes (SL) with down-regulated, but from the point of view of kinetics relatively well preserved Na,K-ATPase and abnormal Mg- and Ca-ATPase (Mg/Ca-ATPase) activities. It was hypothesised that in these changes may also participate the non-enzymatic glycation of proteins (NEG) and the related free radical formation (FRF), that decrease the membrane fluidity (SLMF), which is in reversal relationship to the fluorescence anisotropy (D 0.235 +/- 0.022; controls (C) 0.185 +/- 0.009; p < 0.001). In order to check the true role of SLMF in hearts of the diabetic rats (streptozotocin, single dose, 45 mg/kg i.v.) animals were treated in a special regimen with resorcylidene aminoguanidine (RAG 4 mg/kg i.m.). The treatment with RAG eliminated completely the diabetes-induced decrease in the SLMF (C 0.185 +/- 0.009; D + RAG 0.167 +/- 0.013; p < 0.001) as well as in NEG (fructosamine microg x mg(-1) of protein: C 2.68 +/- 0.14; D 4.48 +/- 0.85; D + RAG 2.57 +/- 0.14; p < 0.001), and FRF in the SL (malondialdehyde: C 5.3 +/- 0.3; D 8.63 +/- 0.2; D + RAG 5.61 +/- 0.53 micromol x g(-1); p < 0.05). Nevertheless, the SL ATPase activity in diabetic animals was not considerably influenced by RAG (increase in D + RAG vs. D 3.3%, p > 0.05). On the other hand, RAG increased considerably the vulnerability of the diabetic heart to overload with external Ca2+ (C 100% of hearts failed, D 83.3%, D + RAG 46.7% of hearts survived). So we may conclude, that: (i) The NEG and FRF caused alterations in SLMF, that accompanied the diabetes-induced remodelling of SL, also seem to participate in the protection of diabetic heart against Ca2+-overload; (ii) Although, the changes in SLMF were shown to influence considerably the ATPase activities in cells of diverse tissues, they seem to be little responsible for changes in ATPases-mediated processes in the SL of chronic diabetic hearts.