The effect of ethanol and acetaldehyde on the perfused nonworking rat and guinea pig hearts was studied. Ethanol (100 mM) initially increased the coronary vascular resistance, but had no appreciable effect on oxygen consumption, glucose-U-14C oxidation, or anaerobic glycolysis. Acetaldehyde (1 mM) increased the heart rate and oxygen consumption, and decreased the coronary vascular resistance. The decrease in coronary resistance was not affected by propranolol but the increase in heart rate was partially blocked. The loss of amino acids or aspartate transminase activity from the heart was not affected by the presence of ethanol. Ethanol-1-14C, either at 10 or 100 mM, was not oxidized by the perfused rat heart.

In a genetic mouse model of human phenylketonuria we have examined the offspring of hyperphenylalaninemic mothers for the presence of cardiovascular defects, an important feature of the pathology of the human maternal phenylketonuria syndrome. Beginning at 14.5 d after conception (75% through gestation), a variety of cardiovascular defects became apparent among the progeny of the hyperphenylalaninemic females. These defects ranged from mild to serious and correlated with the maternal but not the fetal Pah genotype. Nearly all of the defects were vascular, however, whereas the most reported in humans so far have been cardiac. The predisposing biochemical condition in this mouse disease model seems to be the same as in the human disease; elevated maternal blood phenylalanine levels concentrated across the placental barrier to produce a teratogenic developmental environment. This model for congenital cardiovascular defects should enhance two related areas of research. 1) It should allow a more thorough investigation of the relationship between maternal diet and maternal phenylketonuria birth defects, and 2) it should provide an experimental tool to gain insight into the normal process of cardiovascular development.

Increased lysophosphatidylcholine (LPC) production by the ischemic heart is associated with tissue damage. In vitro, LPC produces an increase in cytosolic [Ca2+], usually followed by cell contracture and lysis. Since ethanol reportedly protect cells during ischemia-reperfusion, we wished to determine whether ethanol could protect heart cells against LPC-induced Ca2+ overload. Newborn rat heart cells in culture were loaded with Fura-2 and [Ca2+]i recorded in individual cells. The presence of 22 or 44 mM ethanol increased the time required for 10 microM x L-palmitoyl-LPC to produce maximal Ca2+ accumulation from 8.4+/-0.4 min (n=47) to 21.1+/-2.1 x min (n=32; P<0.01) and 23.8+/-1.8 min (n=10; P<0.01) respectively. The onset of the [Ca2+]i increase could be reversed partially by the addition of ethanol (44 or 88 mM). After the addition of 22 mM ethanol, the cells retained the Fura-2 three times longer than under control conditions. Ethanol (88 mM) decreased the critical micelle concentration of LPC, thus decreasing the LPC monomer concentration in this solution. La3+ also protected the cells against LPC but no further protection was afforded by the addition of ethanol. Our results suggest that ethanol concentrations commonly found in the blood of social drinkers protect heart cells against the deleterious effect of LPC.

No abstract

The isolated, nonworking guinea-pig heart was perfused with 14C-labelled glucose, pyruvate, and acetate. Labelled and total alanine, glutamate, aspartate, and glutamine were measured. The alanine content of the heart varied directly with the medium pyruvate concentration. The sum of the concentrations of glutamate and aspartate varied inversely with the alanine concentration. The sum of alanine, glutamate, aspartate, and glutamine in the heart was constant under most perfusion conditions, but loss into the medium increased in the presence of ouabain, low Ca2+ concentration, or malonate. The sum of the total amino acids from the heart and medium remained constant under all conditions except in the presence of malonate, when it was decreased.Labelling of amino acids from 14C-labelled substrates indicated that alanine, glutamate, and aspartate exchanged readily with their α-oxo acids. However, only 30% of the glutamine exchanged with glutamate during 1 h; this proportion varied little with perfusion conditions or the metabolic flux. The results indicate that in a closed system, most of the changes in the concentrations of amino acids are brought about by transamination.