Effects of right and left vagal stimulation on left ventricular acetylcholine levels in the cat

To test the effectiveness of, and the interactions between, right and left vagal stimulation on left ventricular acetylcholine (ACh) levels, we applied the dialysis technique to the heart of anaesthetized cats. Dialysis probes were implanted in the left ventricular myocardium and perfused with Krebs–Henseleit buffer containing eserine. Dialysate ACh content was measured as an index of ACh release from post‐ganglionic vagal nerve terminals in the left ventricular myocardium. We electrically stimulated the right and left cervical vagal nerves separately or together and investigated the dialysate ACh response. In two different regions of the left ventricle, substantial dialysate ACh responses were observed by the stimulation (20 Hz) of both right and left cervical vagal nerves. At stimulation frequencies of both 10 and 20 Hz, the dialysate ACh response to the bilateral vagal stimulation was almost algebraically the calculated sum of the individual dialysate ACh responses to unilateral vagal stimulation. In conclusion, ACh levels in the left ventricle are affected by both right and left vagal nerves and show little evidence of interactions between right and left vagal nerves at the level of the cardiac ganglia.     

Release of gastrin on vagal stimulation in the cat.

Gastrin released by electrical vagal stimulation was measured in the portal blood of eviscerated cats. Blood flow was recorded by a drop chamber technique and the total gastrin output calculated. Basal peripheral gastrin levels averaged 65 pg/ml and basal portal levels 225 pg/ml. On unilateral vagal stimulation with frequencies above 3-4 Hz gastrin release rapidly increased, reaching a peak within 5-10 min. In spite of continued stimulation and independent of frequency, the gastrin levels declined and returned to basal values after a total of 2-3 000 stimuli. A new maximal response could be induced first after a recovery period of 15-30 min. In the same cat stimulation of either the left or the right vagus released equal maximal amounts of gastrin (average 32 000 pg). The maximal gastrin output on vagal stimulation corresponds to less than 1% of the total content of antral gastrin determined with radioimmunoassay.     

Plasma `cortisol'' levels in right and left ventricular failure

Plasma ;cortisol' values are reported in 36 patients during or following right ventricular failure, and 12 during or following left ventricular failure. In patients with right ventricular failure the normal circadian rhythm was abolished with elevation of midnight values. Disturbance of rhythm was less marked in left ventricular failure, although midnight values were usually raised. Dexamethasone suppression of plasma ;cortisol' levels was abolished or reduced in right ventricular failure. These results confirm our earlier findings and further support our contention that the disturbance of circadian rhythm is not due to a simple stress mechanism. The results are of importance in the differential diagnosis of Cushing's syndrome based on plasma ;cortisol' values, if there is concomitant right ventricular failure.     

大鼠实验性左室心肌梗塞对右室收缩性能的影响

对左室心肌梗塞(MI)是否会直接影响右室功能,至今尚有争议。本实验观察大鼠左室MI时右室dp/dt max的改变及其与左室dp/dt max和梗塞范围(IS)间的关系。结果发现冠脉结扎后1天,在左室dp/dt max显著降低的同时,右室dp/dt max也显著降低,且与左室dp/dt max呈显著的直线正相关,而与IS呈显著的直线负相关。在冠脉结扎后3天时,左室dp/dt max有显著恢复,但仍低于对照水平,而右室dp/dt max已恢复正常,且与左室的dp/dt max和IS间不再具有显著的直线相关关系。由此证明;在大鼠左室MI早期,右室收缩性能可受到直接影响,影响的程度与IS及左室收缩性能降低的程度相关;但当左室收缩性能恢复到一定程度时,这种影响消失。     

Origins of the vagal drive controlling left ventricular contractility

AbstractThe strength, functional significance and origins of direct parasympathetic innervation of the left ventricle (LV) remain controversial. In the present study we used an anaesthetized rat model to first confirm the presence of tonic inhibitory vagal influence on LV inotropy. Using genetic neuronal targeting and functional neuroanatomical mapping we tested the hypothesis that parasympathetic control of LV contractility is provided by vagal preganglionic neurones located in the dorsal motor nucleus (DVMN). It was found that under systemic β‐adrenoceptor blockade (atenolol) combined with spinal cord (C1) transection (to remove sympathetic influences), intravenous administration of atropine increases LV contractility in rats anaesthetized with urethane, but not in animals anaesthetized with pentobarbital. Increased LV contractility in rats anaesthetized with urethane was also observed when DVMN neurones targeted bilaterally to express an inhibitory Drosophila allatostatin receptor were silenced by application of an insect peptide allatostatin. Microinjections of glutamate and muscimol to activate or inhibit neuronal cell bodies in distinct locations along the rostro‐caudal extent of the left and right DVMN revealed that vagal preganglionic neurones, which have an impact on LV contractility, are located in the caudal region of the left DVMN. Changes in LV contractility were only observed when this subpopulation of DVMN neurones was activated or inhibited. These data confirm the existence of a tonic inhibitory muscarinic influence on LV contractility. Activity of a subpopulation of DVMN neurones provides functionally significant parasympathetic control of LV contractile function.

Abbreviations

ABP

arterial blood pressure

ACh

acetylcholine

AlstR

allatostatin receptor

DVMN

dorsal vagal motor nucleus

Ees

end‐systolic elastance

eGFP

enhanced green fluorescent protein

LV

left ventricle

LVdP/dt_max

maximum of the first differential of LVP

LVEDP

left ventricular end diastolic pressure

LVESP

left ventricular end systolic pressure

LVP

left ventricular pressure

LVV

lentiviral vector

MAP

mean arterial pressure

     

Effects of leptin on cat intestinal vagal mechanoreceptors

Vagal afferent nerve fibres are involved in the transmission to the central nervous system of information relating to food intake and immune reactions. Leptin is involved in the control of food intake and has specific receptors in afferent vagal neurones. To investigate the role of these receptors, we studied the effects of leptin on single vagal afferent activities from intestinal mechanoreceptors in anaesthetized cats. The activity of 35 intestinal vagal mechanoreceptors was recorded by means of glass microelectrodes implanted in the nodose ganglion. Leptin (10 μg), administered into the artery irrigating the upper part of the intestine, induced activation in 17 units ( P < 0.001), inhibition in 8 units ( P < 0.05), and had no effect on 10 units. The excitatory effects of leptin were blocked by the endogenous interleukine-1β receptor antagonist, (Il-1ra, 250 μg, i.a .). Cholecystokinin (CCK, 10 μg, i.a .) induced an activatory response only in the two types of units which were responsive to leptin alone. When leptin was administered after CCK, its excitatory effects were enhanced and its inhibitory effects were blocked, whereas it had no effect on the units which were not affected by leptin alone. The interactions between leptin and CCK are specific ones, since other substances (phenylbiguanide, a serotoninergic agonist; substance P) known to activate the mechanoreceptors did not modify the effects of leptin. These results indicate that leptin appears to play a role in the control of immune responses and food intake via intestinal vagal afferent nerve fibres and that there is a functional link between leptin and Il-1β.