Cardiac myocyte transplantation does not increase global epicardial repolarization heterogeneity in a rat infarct model.

BACKGROUND: Using a rat in vivo infarct model we tested the hypothesis that fetal cardiomyocyte (FCM) implantation would increase repolarization heterogeneity. METHODS: Four groups of rats were studied: two groups served as controls and underwent injection with FCM or culture medium in a region of the left ventricle (LV) supplied by the left anterior descending artery (LAD), and two groups underwent LAD ligation followed 3 weeks later by the injection of either FCM or culture medium. Epicardial monophasic action potential (MAP) recordings were obtained 4 to 5 weeks after cell injection from the right ventricle (RV), LV infarction region and LV region remote from the LAD. The maximum difference in action potential duration (MAPD90) between the three sites was defined as repolarization heterogeneity. RESULTS: LAD ligation (in the control media injection group) resulted in an increase in repolarization heterogeneity from 6.9 +/- 0.9 to 13.8 +/- 1.2 ms (p < 0.005). Similarly, injection of FCM without coronary ligation resulted in an increase in heterogeneity from 6.9 +/- 3.9 to 20.7 +/- 1.3 ms (p = 0.001). However, injection of FCM into regions of infarction did not result in an increase in heterogeneity when compared with the control media group (13.8 +/- 1.9 vs 13.0 +/- 2.6 ms, respectively, p = 0.752). CONCLUSIONS: Both fetal cardiomyocyte engraftment in the normal myocardium and coronary ligation increased repolarization heterogeneity. However, fetal cardiomyocyte engraftment in an infarcted region did not further increase repolarization heterogeneity.

Decreased activity of brain phospholipid metabolic enzymes in human users of cocaine and methamphetamine.

Phospholipids are essential components of cell membranes which may also function to mediate some of the behavioural effects of dopamine receptor stimulation caused by psychostimulant drugs. Neuroimaging and pharmacological data suggest that abnormal brain metabolism of phospholipids might explain some of the consequences of chronic exposure to drugs of abuse including drug craving. We previously reported decreased activity of calcium-stimulated phospholipase A(2) (Ca-PLA(2)) in autopsied putamen of human cocaine users. To establish the specificity of this change in phospholipid metabolism and whether decreased Ca-PLA(2) might be a general feature of all abused drugs which enhance dopaminergic neurotransmission, we measured activity of 11 major phospholipid metabolic enzymes in dopamine-rich (putamen) and poor brain areas of chronic users of cocaine and of methamphetamine. Enzyme changes were restricted to the putamen which showed decreased (-21%, as compared with the control subjects) Ca-PLA(2) activity in users of methamphetamine and reduced (-31%) activity of phosphocholine cytidylyltransferase (PCCT), the rate-limiting enzyme of phosphatidylcholine synthesis, in the cocaine users. We suggest that chronic exposure to psychostimulant drugs might cause a compensatory downregulation of Ca-PLA(2) in dopamine-rich brain areas due to excessive dopamine-related stimulation of the enzyme. Decreased striatal Ca-PLA(2) and/or PCCT activity in cocaine users might also help to explain why CDP choline, which enhances phospholipid synthesis, reduces craving in some users of the drug cocaine.

Terikalant and barium decrease the area of vulnerability to ventricular fibrillation induction by T-wave shocks.

The area of vulnerability (AOV) to ventricular fibrillation (VF) induction by high-voltage shocks has been proposed as a measure of vulnerability to VF. Biphasic shocks spanning the T wave and ranging between 50 V and the upper limit of vulnerability (ULV) to VF were delivered before and after terikalant (1 mg/kg) and barium (1.1 mg/kg load followed by 0.05-0.10 mg/kg/min maintenance) or vehicle in dogs. The AOV decreased by 34% and 28% (p < 0.01) after terikalant and barium (n = 8 dogs each), respectively. Mean ULV, defibrillation threshold (DFT), and ventricular vulnerability period (VVP) decreased by 16%, 23%, and 31% (p < 0.01), respectively, after terikalant, and by 25%, 17% (p < 0.01), and 13% (p = 0.08), respectively, after barium. Vehicle (n = 14) did not significantly alter any of these variables. The ULV was correlated with the DFT before and after terikalant (r = 0.78, p < 0.01) and barium (r = 0.83, p < 0.01). Potassium channel blockers of the current reduce the ability to induce VF; this effect may be related to the anti-fibrillatory action of class III anti-arrhythmic drugs and their ability to decrease DFT.