1. Cardiac Physiology (III) A. Rüçhan Akar Ankara University School of Medicine December- 2003 A. Rüçhan Akar Ankara University School of Medicine December- 2003

2. Coronary Circulation

3. Coronary Blood Flow coronary blood flow: 250 ml/min 5% of resting cardiac output 60-80 ml blood/100g tissue/min entirely during diastole ~ aortic diastolic pressure minus LVDP ~ duration of diastole pressure < 150 mmHg oxygenated by superb membrane oxygenator-”the lungs” coronary blood flow: 250 ml/min 5% of resting cardiac output 60-80 ml blood/100g tissue/min entirely during diastole ~ aortic diastolic pressure minus LVDP ~ duration of diastole pressure < 150 mmHg oxygenated by superb membrane oxygenator-”the lungs”

4. Cerebral Blood Flow Cerebral blood flow: 750 ml/min 15% of resting cardiac output 50-55 ml blood/100g tissue/min Cerebral blood flow: 750 ml/min 15% of resting cardiac output 50-55 ml blood/100g tissue/min

5. Right coronary blood flow Left coronary blood flow * The peak left coronary flow occurs at the end of isovolumetric relaxation *

6. Cessation of Myocardial Blood Flow mitochondria cellular pO 2 < 5mmHg within seconds oxidative phosporilation stops mitochondria cellular pO 2 < 5mmHg within seconds oxidative phosporilation stops cytosol anaerobic glycolysis glycogen glucose-6-phosphate pyruvate lactate cellular acidosis depletion of ATP

7. Depletion of ATP < 50% of Normal Level- irreversible lethal cell injury glycolysis is blocked increasing cellular acidity protein denaturation structural, enzymatic, nuclear changes irreversible lethal cell injury glycolysis is blocked increasing cellular acidity protein denaturation structural, enzymatic, nuclear changes

8. Blood Vessel

9. Measurement of Cardiac Output Fick Principle

10. The Fick Principle Q = VO 2 C aO 2 – C vO 2. – Q: cardiac output VO 2 : O 2 consumption C aO 2 :arterial O 2 content C vO 2 : mixed venous O 2 content

11. Blood Vessel Intima primarily the endothelial lining Media vascular smooth muscle, collagen, elastin Adventitia connective tissue Intima primarily the endothelial lining Media vascular smooth muscle, collagen, elastin Adventitia connective tissue

12. Vascular Endothelium Vasodilators Vasoconstrictors Nitric Oxide Prostacyclin Endothelium-derived hyperpolarizing factor Bradykinin Endothelin-1 Angiotensin II Wilson SH, Lerman A. Heart Physiology and Pathophysiology, Academic Press (edited by Sperelakis N.) 473-480

13. L-Arginine is converted to NO by the enzyme nitric oxide synthase (NOS)

14. Nitric Oxide (NO) Function Vasodilator Inhibitor of vascular smooth muscle cell proliferation Inhibitor of platelet adherence/aggregation Inhibitor of leukocyte/endothelial interactions Vasodilator Inhibitor of vascular smooth muscle cell proliferation Inhibitor of platelet adherence/aggregation Inhibitor of leukocyte/endothelial interactions

15. Endothelin-1 (ET-1) Peptide first sequenced in 1988 Most potent vasoconstrictor in humans Maintenance of basal arterial vasomotor tone Strong chemoattractant for circulating monocytes and macrophage activation “proatherogenic” Peptide first sequenced in 1988 Most potent vasoconstrictor in humans Maintenance of basal arterial vasomotor tone Strong chemoattractant for circulating monocytes and macrophage activation “proatherogenic”

16. Endothelial Dysfunction Imbalance of endothelium-derived relaxing and contracting factors Atherosclerotic risk factors Decreased NO bioavailability Increased levels of ET-1

17. Functional Classification of Vessel Wall elastic arteries muscular arteries resistance vessels capillaries (exchange vessels) venules (capacitance vessels ) elastic arteries muscular arteries resistance vessels capillaries (exchange vessels) venules (capacitance vessels ) JR Levick, 1995 An Introduction to Cardiovascular Physiology Butterworth-Heinemann

18. Elastic Arteries aorta, pulmonary artery and major branches diameter = 1-2 cm tunica media is rich in elastin (extensible) collagen (prevents overdistension) aorta, pulmonary artery and major branches diameter = 1-2 cm tunica media is rich in elastin (extensible) collagen (prevents overdistension)

19. intima media Elastic fibers Smoot h muscle adventitia AORTA Bergman RA, Afifi AK, Heidger PM Atlas of Microscopic Anatomy, 1989 W.B. Saunders Company

20. Conduit (Muscular) Arteries diameter = 1mm-1cm popliteal, radial, cerebral, coronary arteries tunica media is thicker, contains more smooth muscle rich autonomic nerve supply (contraction and relaxation) diameter = 1mm-1cm popliteal, radial, cerebral, coronary arteries tunica media is thicker, contains more smooth muscle rich autonomic nerve supply (contraction and relaxation)

21. Resistance Vessels main resistance to blood flow resides in the; –smallest, terminal arteries (diameter = 100-500  m) –arterioles (< 100  m) “single layer of muscle in the media” richly innervated by vasoconstrictor nerve fibres actively regulate local blood flow to match local demand main resistance to blood flow resides in the; –smallest, terminal arteries (diameter = 100-500  m) –arterioles (< 100  m) “single layer of muscle in the media” richly innervated by vasoconstrictor nerve fibres actively regulate local blood flow to match local demand

22. Capillaries (Exchange vessels) diameter: 4-7  m wall: single layer of endothelial cells wall thickness = 0.5  m large cross-sectional area slow blood velocity red cell transit time = 1-2 sec diameter: 4-7  m wall: single layer of endothelial cells wall thickness = 0.5  m large cross-sectional area slow blood velocity red cell transit time = 1-2 sec

23. Arteriovenous Anastomosis shunt vessels ( diameter = 20-135  m) connect arterioles to venules, bypassing the capillaries skin, nasal mucosa temperature regulation shunt vessels ( diameter = 20-135  m) connect arterioles to venules, bypassing the capillaries skin, nasal mucosa temperature regulation

24. The Veins “Capacitance Vessels” diameter 50-200  m thin wall in limb veins, intima possesses pairs of valves low resistance to flow storing large volumes of blood under low pressure ~ 60-70% of the circulating blood volume diameter 50-200  m thin wall in limb veins, intima possesses pairs of valves low resistance to flow storing large volumes of blood under low pressure ~ 60-70% of the circulating blood volume

25. Distribution of blood volume in a resting man ( 5.5 litres) Folkow B, Neil E. 1971, Oxford University Press, London