Effect of cytidine diphosphate choline on anoxia tolerance of cultured myocardial cells.

Three series of cultured Wistar rat heart cells (10 treated and 10 controls x 3) were examined with a laser contraction-meter in a special chamber for anoxia to determine whether cytidine diphosphate choline (CDPC), a membrane phospholipid precursor, can protect against total oxygen deprivation. Heart rate and force of contraction (inotropism) were monitored during a 40-minute period of hypoxia. CDPC in a concentration of 142 micrograms/ml-1 was added to the culture medium only during the anoxia period in series I, during the 3 days of culture in series II, and during the 3 days of culture and the 40-minute hypoxia period in series III. In series I, inotropism decreased by 21% versus 55% in control group (P less than 0.05). In series II, inotropism decreased by 25% versus 43% in control group (P less than 0.05). In series III, inotropism decreased by 22% versus 44% in control group (P less than 0.05). Compared with control cells, cells treated with CDPC during anoxia maintained a significantly greater inotropic state. The effect is greatest if the cells are weak, as in series I. CDPC may be a useful component of the cardioplegic mixture during cardiopulmonary bypass and in the treatment of myocardial ischemia.

Increased iron content in rat myocardium after 5-fluorouracil chronic administration.

The isovolumic perfused rat heart model according to Langendorff has been used in order to characterize the changes occurring in the heart following 5-Fluorouracil (5-FU) administration. Preliminary published data pointed out that perfusion of isolated heart with 1 mg/l 5-FU failed to show any differences in contractility and oxygen consumption in comparison with the control group. However, when Wistar rats received 5-FU once a day (50 mg/kg, I.P.) for five consecutive days a consistent increase in oxygen consumption throughout the 80 min of perfusion associated with a decrease in the fractional extraction of oxygen and a lowered + dP/dt max were observed, without any drug added during the in vitro perfusion. Further investigation has been performed for a better understanding of the results observed after 5-FU pretreatment. Magnesium, potassium, calcium, copper and iron contents in the myocardium (at 0 min of perfusion) were measured by flame atomic absorption spectrophotometry. Iron levels were 20% higher in the 5-FU pretreated group than in the control group, whereas as no differences were observed for the other elemental concentrations. Both initial glycogen and ATP contents were respectively 42% and 29% higher in the pretreated than in the control group and alpha-hydroxybutyrate dehydrogenase release was lower after 40 min of perfusion in the pretreated group. However, 5-FU pretreatment increased net tissue water gain after 80 min of perfusion. Increases in mean oxygen partial pressure in the myocardium and in oxygen consumption associated with increased iron level might be candidates responsible for 5-FU induced cardiotoxicity through an increased in oxygen derived free radicals. Sympathetic over-stimulation or calcium overload do not appear to be involved in 5-FU induced cardiotoxicity.

[Cardiovascular pathology and magnesium]. / Pathologie cardiovasculaire et magnésium.

There is no univocal clinical cardiovascular pattern associated with magnesium deficiency. Only an acute hypomagnesaemia gives the evidence of a real magnesium deficiency. Arrhythmias corrected by magnesium are associated with potassium deficiency. Magnesium deficiency appears to be one risk factor of arrhythmias and coronary spasms. The influence of intravenous magnesium salts was clearly evaluated on cardiovascular electrophysiology allowing protocols infusion. The major beneficial effect of magnesium on total incidence of arrhythmias appears to have been due to a reduction in supraventricular tachyarrhythmias and especially in "torsade de pointes". Antiarrhythmic mechanisms still remain to be clarified. It is likely that magnesium influences cardiac conduction and refractoriness by affecting calcium dependent processes as if acting as an indirect inactivator of slow inward calcium current, probably secondary to an inward shift of the background potassium mediated current. Recent studies demonstrated beneficial effect of intravenous magnesium treatment in acute myocardial infraction, both as to mortality and to early cardiac insufficiency. Beside antiarrhythmic and vasodilatator effects, magnesium seems to show cardiac cells protective action against ischaemia.