Neurochemical approaches to the prevention of ventricular fibrillation

Current evidence indicates that susceptibility to ventricular fibrillation (VF) can be reduced by decreasing cardiac sympathetic activity and by increasing vagal tone. Pharmacological agents that favor such a pattern of autonomic outflow protect the heart against fibrillation. These include morphine sulfate, clonidine, digitalis drugs, and bromocriptine. An intriguing new approach involves changing the serum concentration of amino acid precursors of the central neurotransmitters that modulate autonomic traffic. Considerable evidence indicates that accumulation of serotonin in the brain reduces sympathetic neural activity. When L-tryptophan or 5-hydroxytryptophan is administered with phenelzine (a monoamine oxidase inhibitor) and carbidopa (a selective peripheral L-amino acid decarboxylase inhibitor) to raise brain serotonin, a significant increase in myocardial electrical stability is observed. This effect results from a decrease in cardiac sympathetic tone as indicated by selective denervation and nerve recording studies. Enhancing serotoninergic neurotransmission can also significantly reduce vulnerability to VF during acute coronary artery occlusion. The effect of augmenting serotoninergic activity without the use of enzyme inhibitors has been investigated by administering agents such as melatonin, 5-methoxytryptophol, and 6-chloro-2-(1-piperazinyl) pyrazine (MK-212). Each of these substances increases cardiac electrical stability. The protective influence is unaffected by bilateral vagotomy but is blocked by the specific serotonin antagonist methergoline. Diminution of cardiac sympathetic drive appears to be the main mechanism of action. Thus, neurochemical interventions can exert a profound effect on cardiac electrical stability. Recent advances in neurochemistry and psychopharmacology promise new insights into the problem of sudden death and suggest a fresh approach for the management of life-threatening arrhythmias.     

Selective Acylation of Plasma Membrane Proteins of Mycoplasma mycoides subsp. mycoides SC,the Contagious Bovine Pleuropneumonia Agent

The plasma membrane of Mycoplasma mycoides subsp. mycoides SC (strain KH₃J) contains over 160 polypeptides with apparent molecular masses ranging from 14 to 125 kDa and isoelectric point values (pIs) from 5 to 9. In vivo labeling with [¹⁴C]-fatty acids revealed about 35 acylated polypeptides including the two major components p42 and p65 and displaying pIs between 5.5 and 9.0, with a majority between 6.5 and 8. The amphiphilic nature of most of these acyl proteins was confirmed by Triton X-114 phase partitioning. Gas-liquid chromatography analyses showed that the order of preference for protein acylation was 16:0 > 18:2c > 18:1c > 18:0 > 14:0, with 16:0 being the major O-ester-bound fatty acyl chain and 18:2c the major N-linked chain. The presence of S-glycerylcysteine and a ratio of [O-ester-bound acyl chains + N-linked chains]/O-ester bound chains of ≈ 1.2 in M. mycoides subsp. mycoides SC membrane proteins are consistent with a lipid modification similar to that occurring in lipoproteins of Gram-negative eubacteria that contain an N-terminal acyl S-glycerylcysteine.