Membrane effects of the n-3 fish oil fatty acids, which prevent fatal ventricular arrhythmias.

Fish oil fatty acids are known to exert beneficial effects on the heart and vascular systems. We have studied the membrane effects on ion channel conductance by the n-3 fish oil fatty acids that account for these beneficial effects. We have confirmed that these fatty acids prevent fatal cardiac arrhythmias in a reliable dog model of sudden cardiac death. This finding was followed by experiments indicating that the n-3 fatty acids electrically stabilize heart cells and do so largely through modulation of the fast voltage-dependent Na(+) currents and the L-type Ca(2+) channels in a manner, which makes the heart cells resistant to arrhythmias. Others and we have demonstrated that these membrane effects on the heart can prevent fatal cardiac arrhythmias in humans.

The antiarrhythmic effect of n-3 polyunsaturated fatty acids: modulation of cardiac ion channels as a potential mechanism.

Sudden cardiac death remains one of the most serious medical challenges in Western countries. Increasing evidence in recent years has demonstrated that the n-3 polyunsaturated fatty acids (PUFAs) can prevent fatal ventricular arrhythmias in experimental animals and probably in humans. Dietary supplement of fish oils or intravenous infusion of the n-3 PUFAs prevents ventricular fibrillation caused by ischemia/reperfusion. Similar antiarrhythmic effects of these fatty acids are also observed in cultured mammalian cardiomyocytes. Based on clinical observations and experimental studies in vitro and in vivo, several mechanisms have been postulated for the antiarrhythmic effect of the n-3 PUFAs. The data from our laboratory and others have shown that the n-3 PUFAs are able to affect the activities of cardiac ion channels. The modulation of channel activities, especially voltage-gated Na(+) and L-type Ca(2+) channels, by the n-3 fatty acids may explain, at least partially, the antiarrhythmic action. It is not clear, however, whether one or more than one mechanism involves the beneficial effect of the n-3 PUFAs on the heart. This article summarizes our recent studies on the specific effects of the n-3 PUFAs on cardiac ion channels. In addition, the effect of the n-3 PUFAs on the human hyperpolarization-activated cyclic-nucleotide-modulated channel is presented.

The antiarrhythmic and anticonvulsant effects of dietary N-3 fatty acids.

It has been shown in animals and probably in humans, that n-3 polyunsaturated fatty acids (PUFAs) are antiarrhythmic. We report recent studies on the antiarrhythmic actions of PUFAs. The PUFAs stabilize the electrical activity of isolated cardiac myocytes by modulating sarcolemmal ion channels, so that a stronger electrical stimulus is required to elicit an action potential and the refractory period is markedly prolonged. Inhibition of voltage-dependent sodium currents, which initiate action potentials in excitable tissues, and of the L-type calcium currents, which initiate release of sarcoplasmic calcium stores that increase cytosolic free calcium concentrations and activate the contractile proteins in myocytes, appear at present to be the probable major antiarrhythmic mechanism of the PUFAs.

n-3 fatty acids in the prevention of cardiac arrhythmias.

In animals and probably in humans n-3 polyunsaturated fatty acids (PUFA) are antiarrhythmic. A report follows on the recent studies of the antiarrhythmic actions of PUFA. The PUFA stabilize the electrical activity of isolated cardiac myocytes by inhibiting sarcolemmal ion channels, so that a stronger electrical stimulus is required to elicit an action potential and the relative refractory period is markedly prolonged. This appears at present to be the probable major antiarrhythmic mechanism of PUFA.

Dietary n-3 fatty acids in the prevention of cardiac arrhythmias.

It has been shown that in animals, and probably in humans, n-3 polyunsaturated fatty acids (PUFAs) are antiarrhythmic. We discuss recent studies on the antiarrhythmic actions of polyunsaturated fatty acids. Polyunsaturated fatty acids stabilize the electrical activity of isolated cardiac myocytes by inhibiting sarcolemmal ion channels so that a stronger electrical stimulus is required to elicit an action potential and the relative refractory period is markedly prolonged. This appears at present to be the probable major antiarrhythmic mechanism of polyunsaturated fatty acids.

Acetylcholine in the posterior hypothalamic nucleus is involved in the elevated blood pressure in the spontaneously hypertensive rat.

Intravenous injection of physostigmine, 40 and 80 ug/kg, in unanesthetized normotensive rats increased systolic blood pressure (SBP) by 21 +/- 3 and 42 +/- 7 mmHg. This pressor response was 80% inhibited by intracerebroventricular (icv) injection of hemicholinium-3 (HC-3), 20 ug. Simultaneous icv injection of HC-3 and choline (365 ug) prevented the inhibition of the pressor response by HC-3. In spontaneously hypertensive rats, injection of HC-3 either icv (20 ug) or bilaterally into the posterior hypothalamic nuclei (1 ug) decreased SBP by about 40 mmHg. The effect of intrahypothalamic HC-3 was completely blocked by simultaneous injection of choline (24.3 ug) into the same site. The hypotensive effect of icv HC-3 was completely blocked by icv choline (243 ug) and was inhibited up to 60% by injections of choline (24.3 ug) into the posterior hypothalamic nuclei.

The role of M2 muscarinic receptors in the posterior hypothalamus in the pressor response to intracerebroventricularly-injected neostigmine.

Injection of neostigmine into the lateral cerebral ventricle of urethane-anesthetized rats increases arterial blood pressure. Prior injection of atropine or the muscarinic M2 antagonist 4-DAMP into the posterior hypothalamic nuclei inhibited the pressor response to neostigmine by up to approximately 56%. The same maximum degree of inhibition was elicited by bilateral electrical lesions of the posterior hypothalamic nuclei. The response was not modified by intrahypothalamic injection of pirenzepine or intraventricular injection of hexamethonium, but was prevented by intraventricular injection of 4-DAMP. The results indicate that about half of the pressor response to intraventricular injection of neostigmine was mediated through M2 muscarinic receptors in the posterior hypothalamic nuclei, and the remainder through M2 muscarinic receptors in other regions of the brain.