1. Nervous Regulation of the Heart Qiang XIA (夏强), PhD Department of Physiology Room C518, Block C, Research Building, School of Medicine Tel: 88208252 Email: xiaqiang@zju.edu.cn

2. Innervation of the heart Cardiac sympathetic nerve Cardiac vagus nerve 1. 起源 origin 2. 节前纤维 preganglionic fiber 3. 外周神经节 ganglion 4. 节后纤维 postganglionic fiber 5. 支配 distribution 6. 递质 neurotransmitter

7. Cardiac sympathetic actions Positive chronotropic effect 正性变时作用 Positive dromotropic effect 正性变传导作用 Positive inotropic effect 正性变力作用

8. Cardiac mechanisms of norepinephrine

9. Mechanisms of norepinephrine —increase Na + & Ca 2+ permeability I f  & I Ca,T , phase 4 spontaneous depolarization , autorhythmicity  Ca 2+ influx (I Ca,L ) , phase 0 amplitude & velocity , conductivity  Ca 2+ influx (I Ca,L ) , Ca 2+ release , [Ca 2+ ] i , contractility  (CICR)

11. Asymmetrical innervation of sympathetic nerve

12. Cardiac parasympathetic actions Negative chronotropic effect 负性变时作用 Negative dromotropic effect 负性变传导作用 Negative inotropic effect 负性变力作用

13. Cardiac mechanisms of acetylcholine

14. Mechanisms of acetylcholine —increase K + & decrease Ca 2+ permeability K + outward (GIRK) , If  & I Ca,T , |MRP| , phase 4 spontaneous depolarization , autorhythmicity  Inhibition of Ca 2+ channel, phase 0 amplitude & velocity , conductivity  G protein→PLC → NOS → NO → GC → cGMP  ， Ca 2+ influx  (I Ca,L ), [Ca 2+ ] i , contractility 

15. Cardiac effect of parasympathetic stimulation

16. Vagal Maneuvers Valsalva maneuver –A maneuver in which a person tries to exhale forcibly with a closed glottis (the windpipe) so that no air exits through the mouth or nose as, for example, in strenuous coughing, straining during a bowel movement, or lifting a heavy weight. The Valsalva maneuver impedes the return of venous blood to the heart. –Named for Antonio Maria Valsalva, a renowned Italian anatomist, pathologist, physician, and surgeon (1666-1723) who first described the maneuver.

18. Physiological response in Valsalva maneuver The normal physiological response consists of 4 phases

19. Physiological response in Valsalva maneuver The normal physiological response consists of 4 phases –Initial pressure rise : On application of expiratory force, pressure rises inside the chest forcing blood out of the pulmonary circulation into the left atrium. This causes a mild rise in stroke volume. –Reduced venous return and compensation : Return of systemic blood to the heart is impeded by the pressure inside the chest. The output of the heart is reduced and stroke volume falls. This occurs from 5 to about 14 seconds in the illustration. The fall in stroke volume reflexively causes blood vessels to constrict with some rise in pressure (15 to 20 seconds). This compensation can be quite marked with pressure returning to near or even above normal, but the cardiac output and blood flow to the body remains low. During this time the pulse rate increases. –Pressure release : The pressure on the chest is released, allowing the pulmonary vessels and the aorta to re-expand causing a further initial slight fall in stroke volume (20 to 23 seconds) due to decreased left ventricular return and increased aortic volume, respectively. Venous blood can once more enter the chest and the heart, cardiac output begins to increase. –Return of cardiac output : Blood return to the heart is enhanced by the effect of entry of blood which had been dammed back, causing a rapid increase in cardiac output (24 seconds on). The stroke volume usually rises above normal before returning to a normal level. With return of blood pressure, the pulse rate returns towards normal.

20. Interaction of sympathetic and parasympathetic nerves

21. Predominance of autonomic nerves

22. Tonus 紧张 Cardiac vagal tone 心迷走紧张 Cardiac sympathetic tone 心交感紧张

23. Innervation of the blood vessels Vasoconstrictor nerve 缩血管神经 –Sympathetic vasoconstrictor nerve 交感缩血管神 经 Vasodilator nerve 舒血管神经 –Sympathetic vasodilator nerve 交感舒血管神经 –Parasympathetic vasodilator nerve 副交感舒血管 神经 –Dorsal root vasodilator nerve 脊髓背根舒血管神 经

26. Cardiovascular Center A collection of functionally similar neurons that help to regulate HR, SV, and blood vessel tone

27. Vasomotor center Located bilaterally mainly in the reticular substance of the medulla and of the lower third of the pons –Vasoconstrictor area –Vasodilator area –Cardioinhibitor area – dorsal nuclei of the vagus nerves and ambiguous nucleus –Sensory area – tractus solitarius

28. Vasomotor center

32. –Reticular substance of the pons –Mesencephalon –Diencephalon –Hypothalamus –Cerebral cortex –Cerebellum Higher cardiovascular centers

33. Baroreceptor Reflexes 压力感受性反射 Arterial baroreceptors 动脉压力感受器 –Carotid sinus receptor –Aortic arch receptor Afferent nerves (Buffer nerves ，缓冲神经 ) Cardiovascular center: medulla Efferent nerves: cardiac sympathetic nerve, sympathetic constrictor nerve, vagus nerve Effector: heart & blood vessels

34. Baroreceptor neurons function as sensors in the homeostatic maintenance of MAP by constantly monitoring pressure in the aortic arch and carotid sinuses.

37. Characteristics of baroreceptors:  Sensitive to stretching of the vessel walls  Proportional firing rate to increased stretching  Responding to pressures ranging from 60- 180 mmHg  Receptors within the aortic arch are less sensitive than the carotid sinus receptors

38. The action potential frequency in baroreceptor neurons is represented here as being directly proportional to MAP.

39. Baroreceptor neurons deliver MAP information to the medulla oblongata’s cardiovascular control center (CVCC); the CVCC determines autonomic output to the heart. i.e., MAP is above homeostatic set point i.e., reduce cardiac output

40. Reflex pathway

41. Click here to play the Baroreceptor Reflex Control of Blood Pressure Flash Animation

42. Typical carotid sinus reflex

43. Maintaining relatively constant arterial pressure, reducing the variation in arterial pressure Physiological Significance

44. Cardiovascular Responses to Exercise When exercise begins, mechanosensory input from working limbs combines with descending pathways from the motor cortex to activate the cardiovascular control center in the medulla oblongata. The center responds with sympathetic discharge that increases cardiac output and causes vasoconstriction in many peripheral arterioles.

45. Cardiac output increases during exercise

47. Peripheral blood flow redistributes to muscle during exercise

48. Blood pressure rises slightly during exercise VO 2 max (also maximal oxygen consumption, maximal oxygen uptake or aerobic capacity) is the maximum capacity of an individual's body to transport and utilize oxygen during incremental exercise, which reflects the physical fitness of the individual.

49. Baroreceptor reflex adjusts to exercise During exercise, blood pressure increases without activating homeostatic compensation of baroreceptor reflex Why? –Signal from the motor cortex during exercise reset the arterial baroreceptor threshold to a higher pressure

51. Case A 48-year-old man, who engaged in regular physical exercise, went to see his physician because of recurrent headaches. Physical examination revealed that the patient had a mean heart rate of 55 beats/min. His physician noted that the patient's cardiac rhythm varied substantially with the phases of respiration; the heart rate increased during inspiration and decreased during expiration. 1. What changes in cardiac sympathetic and parasympathetic activity take place during the respiratory cycle? 2. Are the respiratory fluctuations in heart rate produced by the rhythmic changes in sympathetic activity, in parasympathetic activity, or both?

52. The physician diagnosed this patient's headaches as migraine. He advised the patient to take propranolol, a β-adrenergic receptor antagonist, to relieve the headaches. The physician noted that after the patient had taken the propranolol, the mean heart rate diminished very slightly, and the respiratory fluctuations in heart rate were not appreciably different from those observed before the propranolol was taken. 3. Does the failure of propranolol to induce a substantial change in mean heart rate or in the respiratory fluctuations in heart rate necessarily signify that the patient's cardiac sympathetic neural activity was negligible at the time he was being examined?

53. Three years later, the patient began to experience frequent episodes of chest pain on exertion. The patient's cardiologist recommended a diagnostic cardiac catheterization. His aortic pressure (Pa) and his electrocardiogram (ECG) were recorded during the procedure; one segment of the record is shown in Fig. 1. As the cardiac catheter was being manipulated, it initiated several premature ventricular depolarizations, one of which (designated R') is shown in this figure. 4. Why did the premature ventricular depolarization (Fig. 1) not affect the aortic pressure tracing? 5. Why did the ventricular contraction after the premature beat produce such a large aortic pulse pressure (difference between maximum and minimum aortic pressures)?

54. About 1 year later, the patient developed 2:1 atrioventricular (AV) block (i.e., only alternate cardiac impulses were propagated from atria to ventricles). The patient's ECG is shown in Fig. 2. Note that before the patient was given atropine (top tracing), those P-P intervals that include an R wave are shorter (0.7 s) than those that do not include an R wave (0.8 s). The cardiologist gave the patient test injections of propranolol and of atropine to determine the role of both divisions of the autonomic nervous system in the production of the AV block and of the alternating P-P interval durations. The cardiologist found that propranolol had little effect either on the 2:1 AV block or on the alternation of the P-P intervals. He also observed that atropine had little effect on the AV block, but it did cause the mean P-P interval to diminish (to 0.6 s), and the alternations of the P-P intervals were no longer evident (bottom tracing).

55. 6. What is the most likely explanation for the alternating durations of the P-P intervals (Fig. 2)? 7. How do you explain the abolition of the alternations by atropine (Fig. 2), but the absence of any appreciable effect by propranolol?

56. The End.