1. Special Circulation 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. System Overview  The blood flow to organs depends on ⒈ The difference between aortic pressure and central venous pressure ⒉ The diastolic and systolic state of blood vessel in this organ  The blood flow to individual organs must vary to meet the needs of the particular organ, as well as of the whole body

3. Neural, myogenic, metabolic, and endothelial mechanisms control regional blood flow  Neural mechanism: Autonomic nervous system (sympathetic division)  Myogenic mechanism:  Metabolic mechanism: PO 2, pH, etc.  Endothelial mechanism: NO, EDHF, PGI 2, ET, EDCF, etc. System Overview Autoregulation in the vessels of heart, brain, skeletal muscle, and kidneys Blood pressure Cardiac output Local blood flow Local control in the vessels of heart, brain, skeletal muscle during exercise Relaxing or contracting VSMCs

4.  Neural mechanism: Autonomic nervous system (sympathetic division)  Myogenic mechanism:  Metabolic mechanism: PO 2, pH, etc.  Endothelial mechanism: NO, EDHF, PGI 2, ET, EDCF, etc. System Overview Resting vasomotor tone ECs VSMCs Gap junction Electrical and chemical signalling Vasomotor control Sophisticated feedback, Mechanical forces, etc. Local circulation

5. Coronary circulation 冠脉循环

6. Coronary circulation Heart: view from front

7. Coronary circulation Heart: view from diaphragm

8. Coronary circulation Coronary circulation receives 5%of the resting cardiac output form the left heart, and mostly returns it to the right heart Heart muscle consumes as much O 2 as does equal mass of SM during vigorous exercise Heart tissue extracts maximal amount of O 2 at rest The only way to increase of energy is by increasing blood flow Autoregulation: relative stable flow between 70 and more than 150mmHg

9. Diagram of the epicardial, intramuscular, and subendocardial coronary vasculature The branches of left and right coronary artery often penetrate myocardium in direction perpendicular to cardiac surface Myocardial capillary distribution is extremely abundance Collateral coincidence between coronary is less

10. Extravascular compression impairs coronary blood flow during systole Isovolumic contraction phase ↓↓→ rapid ejection phase ↑→reduced ejection phase ↓→ diastolic phase ↑ (isovolumic relaxation phase↑↑)

11. Myocardial blood flow parallels myocardial metabolism Metabolic signals are the principal determinants of O 2 delivery to myocardium –Resting: 60-80 ml/100g/min –Exercise: 300-400 ml/100g/min –O 2 consumption 7-9 ml/100g/min is about 65-70% of O 2 extraction Adenosine activates purinoceptors to induce vasodilation by lowing [Ca2+] i

12. Local metabolic changes that cause vasodilation in the systemic circulation CHANGEMECHANISM ↓ PO2↓ [ATP]i, adenosine release ↑ PCO2↓ pHo ↓ pH↓ pHo ↑ [K+]oDepolarization → opens voltage-gated Ca2+ channels ↑ [lactic acid]oProbably ↓ pHo ↓ [ATP]iOpens K ATP channels ↑ [ATP]oActivates purinergic receptors ↑ [ADP]oActivates purinergic receptors ↑ [Adenosine]oActivates purinergic receptors

13. Notes Although sympathetic stimulation directly constricts coronary vessels, accompanying metabolic effects predominate, producing an overall vasodilation Collateral vessel growth can provide blood flow to ischemic regions Vasodilator drugs may comprise myocardial flow through “coronary steal”

14. Collateral vessel

15. Coronary steal

16. Cerebral circulation The major arteries of the brain. (A) Ventral view, Lateral (B) and (C) midsagittal views, (D) Idealized frontal section circle of Willis

17. Cerebral circulation Blood supply of the three subdivisions of the brainstem. (A) Diagram of major supply. (B) Sections through different levels of the brainstem indicating the territory supplied by each of the major brainstem arteries

18. Cerebral circulation Brain weight: 2% of body weight Blood flow: 15% of cardiac output at rest Brain is the least tolerant of ischemia Arteries: internal carotid arteries, vertebral arteries Brain lacks lymphatic vessels

19. 1. 脑循环特点  SENS 1: Low- intensity electrical stimulation of hand  SENS 2:High- intensity electrical stimulation of hand Changes in regional blood flow

20. Cerebral Blood Flow Neural control: –Sympathetic nerve –Parasympathetic nerve –Sensory nerve: “axon reflex” Metabolic control: –PO 2 –PCO 2 –pH Myogenic control

21. Autoregulation Nearly constant blood flow: perfusion pressure from 70 to 150 mmHg

22. Cushing Reflex Cushing reflex is a physiological nervous system response to increased intracranial pressure (ICP) Cushing's triad: –Hypertension –Bradycardia –irregular respiration It was first described in detail by American neurosurgeon Harvey Cushing in 1902.

23. The End.