Department of Physiology Special Circulation XIA Qiang (夏强), PhD Department of Physiology School of Medicine Tel: 88206417, 88208252 Email: xiaqiang@zju.edu.cn

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

System Overview Neural, myogenic, metabolic, and endothelial mechanisms control regional blood flow Neural mechanism: Autonomic nervous system (sympathetic division) Myogenic mechanism: Metabolic mechanism: PO2, pH, etc. Endothelial mechanism: NO, EDHF, PGI2, ET, EDCF, etc. Blood pressure Cardiac output Local blood flow Autoregulation in the vessels of heart, brain, skeletal muscle, and kidneys Local control in the vessels of heart, brain, skeletal muscle during exercise Relaxing or contracting VSMCs

Sophisticated feedback, System Overview Sophisticated feedback, Mechanical forces, etc. Neural mechanism: Autonomic nervous system (sympathetic division) Myogenic mechanism: Metabolic mechanism: PO2, pH, etc. Endothelial mechanism: NO, EDHF, PGI2, ET, EDCF, etc. Local circulation Resting vasomotor tone Vasomotor control Electrical and chemical signalling VSMCs ECs Gap junction

Coronary circulation 冠脉循环

Coronary circulation Heart: view from front

Coronary circulation Heart: view from diaphragm

Coronary circulation Coronary circulation receives 5%of the resting cardiac output from the left heart, and mostly returns it to the right heart Heart muscle consumes as much O2 as does equal mass of SM during vigorous exercise Heart tissue extracts maximal amount of O2 at rest The only way to increase of energy is by increasing blood flow Autoregulation: relative stable flow between 70 and more than 150mmHg

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

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

Myocardial blood flow parallels myocardial metabolism Metabolic signals are the principal determinants of O2 delivery to myocardium Resting: 60-80 ml/100g/min Exercise: 300-400 ml/100g/min O2 consumption 7-9 ml/100g/min is about 65-70% of O2 extraction Adenosine activates purinoceptors to induce vasodilation by lowing [Ca2+]i

Local metabolic changes that cause vasodilation in the systemic circulation MECHANISM ↓ PO2 ↓ [ATP]i, adenosine release ↑ PCO2 ↓ pHo ↓ pH ↑ [K+]o Depolarization → opens voltage-gated Ca2+ channels ↑ [lactic acid]o Probably ↓ pHo ↓ [ATP]i Opens KATP channels ↑ [ATP]o Activates purinergic receptors ↑ [ADP]o ↑ [Adenosine]o

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”

Collateral vessel

Coronary steal

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

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

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

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

Cerebral Blood Flow Neural control: Sympathetic nerve Parasympathetic nerve Sensory nerve: “axon reflex” Metabolic control: PO2 PCO2 pH Myogenic control

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

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.

The End.