Disruption of vagal efferent axon and nerve terminal function in the postischemic myocardium

Abstract

Despite the importance of vagal control over the ventricle, little is known regarding vagal efferent conduction and nerve terminal function in the postischemic myocardium. To elucidate postischemic changes in the cardiac vagal efferent neuronal function, we measured myocardial interstitial acetylcholine (ACh) levels by using in vivo cardiac microdialysis and examined the ACh responses to electrical stimulation of the vagi or local administration of ouabain in anesthetized cats. Sixty-minute occlusions of the left anterior descending coronary artery (LAD) followed by 60-min reperfusion abolished electrical stimulation-induced ACh release (20.4 Ϯ 3.9 vs. 0.9 Ϯ 0.4 nmol/l; means Ϯ SE, P Ͻ 0.01). In different groups of animals, 60-min LAD occlusion followed by 60-min reperfusion decreased but did not completely abolish ouabain-induced release of ACh (9.2 Ϯ 1.8 vs. 3.9 Ϯ 0.7 nmol/l; P Ͻ 0.05). These results indicate that function of the vagal efferent axon was completely interrupted, whereas the local ACh release was partially suppressed in the postischemic myocardium. The postischemic disruption of vagal efferent neuronal function might exert deleterious effects on cardiac regulation. cardiac microdialysis; vagal stimulation; ouabain; cats; acetylcholine AUTONOMIC DERANGEMENT ASSOCIATED with acute myocardial ischemia or infarction has deleterious effects on the heart (3, 6). The autonomic derangement occurs during postischemic as well as ischemic periods. Elucidating the underlying mechanisms of autonomic disturbance during the postischemic period is important to understand the pathophysiology of postischemic events such as those occurring after thrombolytic therapies. In the sympathetic nervous system, nerve terminal function as assessed by tyramine-induced norepinephrine release recovers 60-120 min after reperfusion of the coronary artery (1, 14). On the other hand, the myocardial response to electrical stimulation of sympathetic efferent neurons remains impaired up to 2 h after reperfusion, despite a preserved myocardial response to exogenous norepinephrine (5). Therefore, injury to sympathetic efferent axons (4, 8) is considered to be responsible for sympathetic denervation in the postischemic myocardium. However, conduction of the postganglionic axons in response to electrical stimulation of the epicardial sites was unaffected by regional ventricular ischemia (9), suggesting that the intrinsic cardiac fibers in the epicardial region were resistant to myocardial ischemia. We speculate that changes in the environment surrounding the postganglionic axons traveling through the midcardium affected the axonal conduction (15) even if the axon itself was not injured.In contrast to the sympathetic efferent nervous system, little is known regarding vagal efferent neuronal function in the postischemic myocardium in vivo. We have measured myocardial interstitial acetylcholine (ACh) levels by using a cardiac microdialysis technique in anesthetized cats (2, 10-13). The ACh levels measured by the cardiac microdialysis were ab...

Vagal nerve modulation: A promising new therapeutic approach for cardiovascular diseases

“…Autonomic derangement occurs in the ischaemic myocardium. Disruption of vagal function also causes a deterioration of cardiac function 4,5 . Moreover, the reduction of vagal activity associated with ischaemic heart disease is independent of impaired coronary flow, immune system effects and hormonal effects.…”

“…Disruption of vagal function also causes a deterioration of cardiac function. 4,5 Moreover, the reduction of vagal activity associated with ischaemic heart disease is independent of impaired coronary flow, immune system effects and hormonal effects. A study in 68 patients has shown a sustained decrease in HRV 1 h ischaemic events, with HRV reaching a minimum at the onset of ischaemia, showing the extent of reduced vagal activity.…”

The action of high K+ and aglycaemia on the electrical properties and synaptic transmission in rat intracardiac ganglion neurones in vitro

“…While the effects of ischaemia and reperfusion on cardiac cell function have been the subject of many studies (Toda, 1969; Kourie, 1998; Carmeliet, 1999; Rodriguez et al 2006), there are few reports of their action on the intrinsic cardiac nervous system. The negative chronotropic action of vagal activation was blunted in a rat model of myocardial infarction (Du et al 1998), and the release of acetylcholine during vagal stimulation was abrogated by ischaemia in the anaesthetized dog (Kawada et al 2002). Accordingly, conditions simulating ischaemia, for example high K + , also attenuated the negative chronotropic action of vagal activation in the rat (Sears et al 1999).…”

Reflex Cardiac Activity in Ischemia and Reperfusion

“…A disruption of vagal efferent neuronal function itself has also been shown in postischemic myocardium. 15 Recent experimental data suggest that baroreceptor depression is also mediated by a change in cardiac volume and/or compliance rather than simply by infarct size. 16 Consistent with that report, we observed a trend toward higher values for left ventricular end-diastolic filling pressure and lower values for left ventricular ejection fraction in TIMI 2 patients and moderate correlations of these hemodynamic parameters with HRT.…”