Involvement of microtubules in the tolerance of cardiomyocytes to cold ischemia-reperfusion.

Before transplantation, the heart graft is preserved by the use of cold storage in order to limit ischemia-reperfusion stress. However, sustained exposure to low temperature may induce myocardial ultrastructural damage, particularly microtubules (MT) disruption. Previous data suggested that tubulin-binding agents are able to attenuate cold-induced cytoskeleton alterations.

Tubulin ligands suggest a microtubule-NADPH oxidase relationship in postischemic cardiomyocytes.

Alterations of the microtubule network, which is involved in many vital processes, occur in several pathological conditions, such as cardiac ischemia. However, the connection between the microtubule assembly state and the factors affecting myocardial reperfusion injury, especially oxidative stress, is unknown. We aimed thus to study the effects of different tubulin ligands on the changes in the microtubule network and in several markers of cell injury and oxidative activity in cardiac muscle cells submitted to a reversible substrate-free, hypoxia-reoxygenation model of ischemia-reperfusion.

Dependence on the phospholipid polyunsaturated fatty acids of the oxidative injury of isolated cardiomyocytes.

We investigated the influence of PUFA in phospholipids (PL) on the functional characteristics of cultured cardiomyocytes (CM) in basal conditions and during free radical (FR) stress provoked either by the xanthine/xanthine oxidase (X/XO) system or by a (9Z, 11E, 13 (S), 15Z)-13-hydroperoxyoctadecatrienoic acid (13-HpOTrE). CM were grown in media containing either n - 3 (eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA) or n - 6 (arachidonic acid, AA). These two groups of CM displayed different PUFA n - 6/n - 3 ratio in PL.

Substrate dependence of the postischemic cardiomyocyte recovery: dissociation between functional, metabolic and injury markers.

Defining the substrate that influences the most favourably the myocardial post-ischemic recovery is subject of debates, due to dissociation between functional and biochemical benefits. Hence, we studied the effects of either glucose or different fatty acids on the functional and metabolic recovery of post-ischemic cardiomyocytes in a substrate-free hypoxia model of simulated ischemia-reperfusion. Rat cardiomyocytes were submitted to a 2.

Direct, pleiotropic protective effect of cyclosporin A against simulated ischemia-induced injury in isolated cardiomyocytes.

Cyclosporin A is an immunosuppressor that prolongs graft survival but its use is limited by cardiotoxicity. The effects of cyclosporin A on several functional and biological characteristics were thus evaluated in rat cardiomyocytes in normal conditions and in a substrate-free, hypoxia-reoxygenation model of ischemia-reperfusion. Cyclosporin A (100 and 1000 ng/ml) did not induce cardiocytotoxicity in basal conditions.

Physiological and metabolic actions of mycophenolate mofetil on cultured newborn rat cardiomyocytes in normoxia and in simulated ischemia.

Mycophenolate mofetil (MMF) is a new immunosuppressive drug used to reduce acute rejection after heart transplantation. As with other immunosuppressive drugs, MMF therapy is associated with several adverse effects. However, the direct effects of MMF on myocardial tissue has not been yet evaluated.

Deep hypothermia during ischemia improves functional recovery and reduces free-radical generation in isolated reperfused rat heart.

Background: We investigated the influence of deep hypothermia (4 degrees C) during ischemia-reperfusion in the isolated rat heart model.

Methods: Isolated, perfused rat hearts underwent either 30 minutes of normothermic ischemia (control group) or 30 minutes of hypothermic ischemia (hypothermia-treated group), followed by 30 minutes of reperfusion in both groups. We recorded functional parameters and used electron spin resonance (ESR) spectroscopy to detect ascorbyl radicals, as markers of free-radical production, in samples of coronary effluents.

Microtubule alteration is an early cellular reaction to the metabolic challenge in ischemic cardiomyocytes.

Cytoskeleton damage, particularly microtubule (MT) alterations, may play an important role in the pathogenesis of ischemia-induced myocardial injury. However, this disorganization has been scarcely confirmed in the cellular context. We evaluated MT network disassembly in myoblast cell line H9c2 and in neonatal rat cardiomyocytes in an in vitro substrate-free hypoxia model of simulated ischemia (SI).

Specific electromechanical responses of cardiomyocytes to individual and combined components of ischemia.

The main factors of myocardial ischemia are hypoxia, substrate deprivation, acidosis, and high extracellular potassium concentration ([K+]e), but the influence of each of these factors has not yet been evaluated in a cardiomyocyte (CM) culture system. Electromechanical responses to the individual and combined components of ischemia were studied in CM cultured from newborn rat ventricles. Action potentials (APs) were recorded using glass microelectrodes and contractions were monitored photometrically.

Assessment of the cytoprotective role of adenosine in an in vitro cellular model of myocardial ischemia.

This work aimed to detect functional adenosine receptors in isolated rat cardiomyocytes and to study the influence of stimulation of these receptors in an in vitro model of ischemia. Cultures of cardiomyocytes were prepared from newborn rat ventricles. The contractions were photometrically monitored.