The inotropic and chronotropic effects of catecholamines on the dog heart

1. The chronotropic and inotropic responses of the denervated dog heart to intravenous infusions of noradrenaline, adrenaline and isoprenaline were studied.

2. The maximum rate of rise of pressure in the left ventricle of the heart, (dP/dt max) measured at a constant heart rate and mean systemic arterial pressure during each series of infusions, was used as an index of inotropic changes (Furnival, Linden & Snow, 1970).

3. The order of potency of the catecholamines in producing both chronotropic and inotropic effects was isoprenaline > adrenaline > noradrenaline.

4. For the same increase in heart rate produced by an infusion of a catecholamine, noradrenaline caused a greater inotropic effect than adrenaline, which in turn caused a greater increase than isoprenaline.

5. The chronotropic and inotropic effects of noradrenaline were potentiated by an intravenous injection of cocaine HCl (5 mg/kg), whereas those of isoprenaline were unchanged.

6. The relative difference between the responses to noradrenaline and isoprenaline was abolished by an intravenous injection of cocaine HCl.

7. It is concluded that the different relative chronotropic and inotropic effects of isoprenaline and noradrenaline are due to the greater uptake of noradrenaline by sympathetic nerve endings in the sinu-atrial node than in the muscle of the left ventricle.

     

The inotropic effect on the heart of stimulating the vagus in the dog, duck and toad

1. The chronotropic and inotropic effects of stimulating the vagus on the hearts of the dog, duck and toad were studied.2. The maximum rate of rise of pressure in the left ventricle (dP/dt max) measured at a constant heart rate and mean aortic pressure was used as an index of the inotropic changes.3. The sensitivity of dP/dt max as an index of inotropic changes brought about by stimulating the vagus was established in the toad where a 49% reduction in heart rate was associated with a 30% reduction in dP/dt max.4. In the dog stimulation of the vagus resulted in a reduction in heart rate of 38% and only a small reduction in dP/dt max of 6%.5. Results similar to those found in the dog were obtained in the duck where the reduction in heart rate of 44% was associated with reduction in dP/dt max of only 3%.6. It is concluded that the vagus has only a small and negligible negative inotropic effect on the ventricles of the dog and duck.     

Origin of sympathetic efferent axons in the renal nerves of the cat

The origin of efferent axons in the renal nerves of the cat was examined using retrograde transport of horseradish peroxidase (HRP). Nerves on the surface of the left renal blood vessels were dissected 5-7 horseradish mm proximal to the medial margin of the kidney, transected and the central cut ends exposed to HRP. Labeled neurons were typically identified in three locations: (1) centrally along the renal nerve, (2) in the superior mesenteric ganglion, and (3) in the ipsilateral sympathetic chain ganglia (T12-L3). HRP was not detected in preganglionic neurons in the thoracolumbar spinal cord. Labeled cells ranged in size from 15 to 50 micrometers, with those in the renal nerve at the smaller end of the spectrum and those in the superior mesenteric ganglion at the larger end. In the superior mesenteric ganglion labeled cells were typically localized to a small region in the caudal pole of the ganglion around the origin of the renal nerve. The results show that the sympathetic efferent innervation of the kidney is derived from both paravertebral and prevertebral ganglia. In the latter (superior mesenteric ganglion), renal efferent neurons exhibited a topographic distribution.     

Ultrastructural identification of afferent fibers of cardiac origin in thoracic sympathetic nerves in the dog

While cardiac afferent nerve activity has been recorded from the ventrolateral (VLCN) and ventromedial (VMCN) cardiac nerves, left dorsal and ventral ansae subclaviae, and left upper thoracic white rami communicantes, little anatomical evidence for the existence of afferent fibers in these nerves has been reported. This study was designed to characterize the normal ultrastructure of the above nerves and to identify afferent fibers in them through Wallerian degeneration produced by dorsal root ganglionectomy. Laminectomies followed by dorsal root ganglionectomies were performed on left thoracic roots T₁-T₄ in six mongrel dogs. The nerves to be examined were removed from two animals at 1, 2, and 3 weeks following ganglionectomy and prepared for electron microscopy. Control nerves were obtained from two normal dogs. Degenerating nonmyelinated fibers were characterized by watery axoplasm containing clumps of electron-dense material. Degenerating myelinated fibers were distinguished by the separation of their myelin lamellae, producing characteristic whorls. After three weeks, afferent nonmyelinated axons had degenerated in all nerves, leaving only layered processes of Schwann cells in these areas. Approximately 5–15% of the fibers in each nerve degenerated, indicating their afferent nature. Of these fibers, 85–90% were nonmyelinated C fibers and the remainder myelinated Aδ fibers. These results indicate participation of both Aδ fibers and a large population of C fibers in transmission of cardiac afferent activity.     

Laterality in direct and indirect inotropic effects of sympathetic stimulation in isolated canine heart

Although sympathetic nerve stimulation is known to increase ventricular contractility, concomitant increases in heart rate (HR) make it difficult to separate its direct inotropic effect from indirect inotropic effect through a force-frequency mechanism. We stimulated the stellate ganglia in 8 isolated canine hearts with functional sympathetic nerves. Right sympathetic stimulation at 10 Hz increased ventricular end-systolic elastance (E(es)) by 95.7 +/- 7.5% (p < 0.001) and HR by 32.5 +/- 4.2% (p < 0.05). In contrast, left sympathetic stimulation at 10 Hz increased E(es) by 70.7 +/- 6.5% (p < 0.001) without significant changes in HR. Preventing the chronotropic response by fixed-rate pacing attenuated the E(es) response to right sympathetic stimulation at 5 Hz (52.0 +/- 5.1 vs. 22.8 +/- 2.8%, p < 0.001), but not to left sympathetic stimulation at 5 Hz (54.5 +/- 3.4 vs. 53.3 +/- 2.2%, NS). In the isolated canine heart, the right sympathetic nerve affected E(es) by both the direct inotropic effect and the indirect HR-dependent inotropic effect. In contrast, the left sympathetic nerve regulated E(es) primarily by its direct inotropic effect.     

The effect of 2-deoxy-D-glucose and D-glucose on the efferent discharge rate of sympathetic nerves.

Efferent discharges were recorded from nerve filaments dissected from the adrenal and renal nerves in the rabbit. 2. An increase in discharge rate was observed in the adrenal nerve filaments following I.V. administration of 2-deoxy-D-glucose (2-DG). No change in discharge rate after 2-DG infusion was observed in the renal nerve filaments. 3. A decrease in discharge rate of the adrenal nerve filaments was observed after I.V. injection of glucose, but there was no change in the activity of renal nerve filaments. 4. Transection of the spinal cord abolished the adrenal nerve response to the systemic administration of 2-DG and glucose. 5. It is suggested that there might be a pathway from the hypothalmic area to the adrenal nerve cells of the spinal cord, but not to the renal nerve cells, through which activity of the adrenal nerve might be changed in response to 2-DG and glucose infusion.     

去心交感神经对QT离散度的影响

目的：采用动物实验方法，观察去心交感神经对QT离散度（QTd）的影响，并观察QT离散度的昼夜节律变化，以探讨QT离散度变化的电生理基础。 方法： 以新西兰兔作为实验对象，实验组手术去除心交感神经支配，对照组手术保留心交感神经支配。观察两组手术前后QTd变化及24 h内QTd的昼夜变化。 结果： 实验组在手术后QTd显著减小(P＜0.05)，对照组在手术前后QTd无显著变化（P＞0.05）；实验组在手术后24 h内QTd始终低于对应的对照组，且无明显节律变化，对照组在24 h内QTd呈现出显著的昼夜节律变化。 结论： 心交感神经活动可能是产生QTd的机制之一。     

Reflex inhibition of heart rate and efferent cardiac sympathetic outflow induced by colorectal distension in anesthetized rats

Colorectal distensions of 60 and 80 mmHg significantly reduced heart rate (HR) and cardiac sympathetic nerve activity in anesthetized rats. This bradycardiac response was not influenced by the intravenous administration of atropine, but was abolished by propranolol, suggesting that it was elicited by sympathetic but not vagal efferent nerves.     

Chronotropic effects of nitric oxide in the denervated human heart

Nitric oxide synthase is expressed in the sino-atrial node and animal data suggests a direct role for nitric oxide on pacemaker activity. Study of this mechanism in intact humans is complicated by both reflex and direct effects of nitric oxide on cardiac autonomic control. Thus, we have studied the direct effects of nitric oxide on heart rate in human cardiac transplant recipients who possess a denervated donor heart. In nine patients, the chronotropic effects of systemic injection of the nitric oxide synthase inhibitor N ^G-monomethyl- l -arginine ( l -NMMA) (3 mg kg⁻¹) or increasing bolus doses of the nitric oxide donor, sodium nitroprusside (SNP), were studied. Injection of l -NMMA increased mean arterial pressure by 17 ± 2 mmHg (mean ± s.e.m. ;   P < 0.001  ) and also had a significant negative chronotropic effect, lengthening the R-R interval by 54 ± 8 ms ( P < 0.001). This bradycardia was not reflex in origin since injection of the non-NO-dependent vasoconstrictor, phenylephrine (100 μg) achieved a similar rise in mean arterial pressure (18 ± 3 mmHg;   P < 0.001  ) but failed to change R-R interval duration (ΔR-R =−3 ± 4 ms). Furthermore, no change in levels of circulating adrenaline was observed with l -NMMA. Conversely, injection of sodium nitroprusside resulted in a positive chronotropic effect with a dose-dependent shortening of R-R interval duration, peak ΔR-R =−25 ± 8 ms with 130 μg ( P < 0.01). These findings indicate that nitric oxide exerts a tonic, direct, positive chronotropic influence on the denervated human heart. This is consistent with the results of animal experiments showing that nitric oxide exerts a facilitatory influence on pacemaking currents in the sino-atrial node.     

Tone of sympathetic nerves and regulation of heart activity

Tone of sympathetic nerves to the heart was studied in rats and guinea pigs. Experiments with pharmacological blockade of the sympathetic nervous system and vagotomy confirmed the general notion on the absence of tonic effects of sympathetic nerves on the heart. Reduction of the heart rate reported previously probably attests to various experimental designs (type and depth of anesthesia, possible hypothermia, duration of observations, and pharmacological preparations). As differentiated from the vascular tone, the heart rate under rest conditions depends on the vagal tone and circulating humoral substances. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 10, pp. 370–373, October, 2000