Control of Myocardial Blood Flow

Transcription

1 Control of Myocardial Blood Flow Blood goes where it is needed John Hunter, 1794 Cited by Dunker DJ and Bache RJ Physiol Rev, 2008 Bernard De Bruyne, MD, PhD Cardiovascular Center Aalst OLV-Clinic Aalst, Belgium

2 The Control of Resting Myocardial Blood Flow Neuro-humoral factors α 1 α 2 Metabolic factors Noradrenaline Adrenaline β 1 β 2 NO PGI 2 EDHF A 2 Adenosine Acethylcholine M M α 2 PO 2 Arterial Pressure Coronary pressure RAP, LVDP and Pf=0 TXA 2 5-HT TXA 2 NO PGI 2 EDHF P 2 Endothelium 5-HT P 2 H 1 B 2 NO PGI 2 EDHF H 1 ET ET B H 2 AT 1 ET A ET B Histamine PCO 2, H +, K + Angiotensine II Systolic compression Diastolic compression Physical factors Bradykinine Endo- and paracrine factors Adapted from D.J.G.M. Duncker

3 The Control of Resting Myocardial Blood Flow Neuro-humoral factors Noradrenaline Adrenaline Acethylcholine Arterial Pressure Coronary pressure RAP, LVDP and Pf=0 Systolic compression Diastolic compression Physical factors M TXA 2 5-HT α 1 α 2 β 1 β 2 M α 2 NO PGI 2 EDHF H 1 A 2 TXA 2 NOEndothelium ET ET A PGI 2 5-HT ET B EDHF ET P B 2 AT B 1 2 H 1 NO PGI 2 EDHF H 2 P 2 Bradykinine Adenosine PO 2 Histamine Metabolic factors PCO 2, H +, K + Angiotensine II Endo- and paracrine factors The balance between supply and demand depends on mechanisms which are multiple, interacting, cumulative, nonlinear Adapted from D.J.G.M. Duncker

4 ...Myocardial blood flow during resting conditions... in normal human subjects is generally reported in the range of ml/min/g of myocardium. The wide range of resting values of left ventricular blood flow in awake animals appears to be related to the state of alertness. Animals conditioned to rest quietly in the laboratory have the lowest reported values, whereas animals standing on a treadmill ready to run have higher heart rates and higher coronary flow rates... (Dunker DJ and Bache RJ Physiol Review 2008)

5 ABC of Coronary Physiology For the Interventionalist 1. About Pressure, flow, mass, resistance, etc, Epicardial vs microvascular compartments 3. Flow-function relationship 4. Coronary autoregulation

6 The Control of Resting Myocardial Blood Flow Neuro-humoral factors α 1 α 2 Metabolic factors Noradrenaline Adrenaline β 1 β 2 NO PGI 2 EDHF A 2 Adenosine Acethylcholine M M α 2 PO 2 Arterial Pressure Coronary pressure RAP, LVDP and Pf=0 TXA 2 5-HT TXA 2 NO PGI 2 EDHF P 2 Endothelium 5-HT P 2 H 1 B 2 NO PGI 2 EDHF H 1 ET ET B H 2 AT 1 ET A ET B Histamine PCO 2, H +, K + Angiotensine II Systolic compression Diastolic compression Physical factors Bradykinine Endo- and paracrine factors Adapted from D.J.G.M. Duncker

7 Extravascular Compressive Forces Pressure Aorta LV

8 Extravascular Compressive Forces Pressure Aorta LV LAD FLOW

9 Extravascular Compressive Forces Pressure Aorta Coronary LV LAD FLOW

10 Extravascular Compressive Forces Pressure Aorta RV LAD FLOW RCA FLOW

11 Extravascular Compressive Forces Pressure Aorta RV LAD FLOW RCA FLOW

12 Extravascular Compressive Forces Pressure Aorta RV LAD FLOW RCA FLOW

13 Extravascular Compressive Forces Pressure Aorta RV LAD FLOW RCA FLOW

14 Cross-Sectional Lumenal Area (cm²) Relation between Vessel Size and Myocardial Mass Normals 0.2 CAD Regional Myocardial Mass (g) C. Seiler et al Circulation 1992

15 Pressure, Flow, Resistance, and Vessel Size BASE APEX 100 % of value at the ostium Diameter Mass Pressure Flow Distance from the ostium

16 Pressure, Flow, Resistance, and Vessel Size 100 % of value at the ostium Diameter Mass Pressure Flow BMII

17 Pressure, Flow, Resistance, and Vessel Size

18 Pressure, Flow, Resistance, and Vessel Size 5 Ref Diam (mm) < 4 mm² = significant stenosis? % Stenosis for an Cross Sectional Area of 4 mm² 0

19 Pressure, Flow, Resistance, and Vessel Size Relationship between CSA by IVUS and FFR FFR to MLD FFR to MLA r = P < Waksman R et al JACC 2013

20 Angiographic Definition of CAD Diagnostic Accuracy 70% 60% 50% 66% N = 4089 Stenoses Toth G, Hamilos M et al Submitted 2013

21 Coronary Physiology Function trumps anatomy Aalst-Eindhoven Course, June 2012

22 ABC of Coronary Physiology For the Interventionalist 1. About Pressure, flow, resistance, etc, Epicardial vs microvascular compartments 3. Flow-function relationship 4. Coronary autoregulation

23 Two-Compartment Model of the Coronary Circulation The coronary angiogram detects only 5% of the total coronary tree

24 Two-Compartment Model of the Coronary Circulation Epicardial Artery Microvasculature FFR IMR CFR

25 Two-Compartment Model of the Coronary Circulation Conductance Arteries Resistance Arteries >500 µ <500 µ Microvasculature P a 100 MACRO MICRO

26 Two-Compartment Model of the Coronary Circulation Adenosine FFR = 0.98 CFR = 4.15

27 Conductance Arteries Focal Stenosis >500 µ Resistance Arteries <500 µ Microvasculature P a 100 MACRO MICRO

28 Conductance Arteries >500 µ Resistance Arteries <500 µ Microvasculature Stent P a 100 MACRO MICRO

29 Conductance Arteries Focal Stenosis >500 µ Resistance Arteries <500 µ Microvasculature P a 100 Diffuse Atherosclerosis MACRO MICRO

30 Conductance Arteries >500 µ Resistance Arteries <500 µ Microvasculature Stent P a 100 Diffuse Atherosclerosis MACRO MICRO

31 Conductance Arteries >500 µ Resistance Arteries <500 µ Microvasculature P a 100 Diffuse Atherosclerosis MACRO MICRO

32 Endothelial Control of Coronary Blood Flow Blood Flow ACh Shear Stress Bradykinine Endotheline Normal Endothelium L-Arginine enos NO PGI 2 EDHF Vascular Smooth Muscle Cell Guanyl Cyclase cgmp Dilatation

33 Endothelial Control of Coronary Blood Flow Blood Flow ACh Shear Stress Bradykinine Endotheline Abnormal Endothelium L-Arginine enos NO Vascular Smooth Muscle Cell Guanyl Cyclase cgmp Constriction

34 Importance of Maximal Vasodilation Epicardial = Conductance Arteries > 550 µ Microvasculature = Resistance Arteries < 550 µ Nitrates Vasospasm Adenosine Autoregulation

35 ABC of Coronary Physiology For the Interventionalist 1. About Pressure, flow, resistance, etc, Epicardial vs microvascular compartments 3. Flow-function relationship 4. Coronary autoregulation

36 ABC of Coronary Physiology For the Interventionalist 1. About Pressure, flow, resistance, etc, Epicardial vs microvascular compartments 3. Flow-function relationship 4. Coronary autoregulation

37 The Control of Resting Myocardial Blood Flow Neuro-humoral factors α 1 α 2 Metabolic factors Noradrenaline Adrenaline β 1 β 2 NO PGI 2 EDHF A 2 Adenosine Acethylcholine M M α 2 PO 2 Arterial Pressure Coronary pressure RAP, LVDP and Pf=0 TXA 2 5-HT TXA 2 NO PGI 2 EDHF P 2 Endothelium 5-HT P 2 H 1 B 2 NO PGI 2 EDHF H 1 ET ET B H 2 AT 1 ET A ET B Histamine PCO 2, H +, K + Angiotensine II Systolic compression Diastolic compression Physical factors Bradykinine Endo- and paracrine factors Adapted from D.J.G.M. Duncker

38 Coronary Physiology The Control of Myocardial Blood Flow Endothelium Metabolic factors Physical factors Neuro-humoral factors Endo- and paracrine factors Multiple, interacting, cumulative, nonlinear mechanisms Coronary Autoregulation Aalst-Eindhoven Course, June 2012 Adapted from D.J.G.M. Duncker

39 The Control of Resting Myocardial Blood Flow Neuro-humoral factors α 1 α 2 Metabolic factors Noradrenaline Adrenaline β 1 β 2 NO PGI 2 EDHF A 2 Adenosine Acethylcholine M M α 2 PO 2 Arterial Pressure Coronary pressure RAP, LVDP and Pf=0 TXA 2 5-HT TXA 2 NO PGI 2 EDHF P 2 Endothelium 5-HT P 2 H 1 B 2 NO PGI 2 EDHF H 1 ET ET B H 2 AT 1 ET A ET B Histamine PCO 2, H +, K + Angiotensine II Systolic compression Diastolic compression Physical factors Bradykinine Endo- and paracrine factors Adapted from D.J.G.M. Duncker

40 Maximal hyperemia is easier to get than true resting conditions

41 Autoregulation The ability of the heart of maintaining flow constant in case of change of perfusion pressure without the intervention of any other external mechanism

42 Coronary Blood Flow (ml/min) Coronary Autoregulation Coronary Perfusion Pressure (mm Hg) Rubio and Berne, Prog CV Disease 1975

43 Coronary Blood Flow (ml/min) Autoregulatory Range Initial Pressure Coronary Perfusion Pressure (mm Hg) Rubio and Berne, Prog CV Disease 1975

44 Coronary Blood Flow (ml/min) Autoregulatory Range Coronary Perfusion Pressure (mm Hg) Rubio and Berne, Prog CV Disease 1975

45 De Bruyne et al, 1996 unpublished data Autoregulation Proximal LAD stenosis (n = 26) Normal LV systolic function PET fow measurements ( 15 O-labeled water) at rest Distal Coronary Pressure (mm Hg)

46 % Control Flow Flow, Pressure, and Resistance R myo P a F R epi P v F = P 25 R epi + R myo % Area Stenosis K. Lance Gould, 1974

47 % Control Flow Flow, Pressure, and Resistance R myo P a F R epi P v F = P 25 R epi + R myo % Area Stenosis K. Lance Gould, 1974

48 % Control Flow Flow, Pressure, and Resistance R myo P a F R epi P v F = P 25 R epi + R myo % Area Stenosis K. Lance Gould, 1974

49 % Control Flow Flow, Pressure, and Resistance R myo P a F R epi P v F = P 25 R epi + R myo % Area Stenosis K. Lance Gould, 1974

50 % Control Flow Flow, Pressure, and Resistance R myo P a F R epi P v F = P 25 R epi + R myo % Area Stenosis K. Lance Gould, 1974

51 De Bruyne et al, 1996 unpublished data Autoregulation Proximal LAD stenosis (n = 26) Normal LV systolic function PET fow measurements ( 15 O-labeled water) at rest Distal Coronary Pressure (mm Hg)

52 Fractional Flow Reserve FFR = ratio of hypermic flow in the stenotic vessel to hyperemic flow in the same vessel but in the absence of the stenosis FFR = extent to which (%) maximal myocardial flow is limited by the epicardial stenosis P a S Q max FFR = = N Q max P d P a P d During maximal hyperemia (i.e. during maximal transstenotic flow, when the relationship between pressure flow is linear)

53 Hyperemic Coronary Blood Flow ( % of Normal ) Pressure-Flow Relationship During Maximal Vasodilation P a 100 P d 100 P v Q N max P a 100 P d 70 P v Q s max Hyperemic Coronary Perfusion Pressure ( % of normal )

54 Spaan, J. A.E. et al. Circulation 2006 Non-Linearity of the Pressure-Resistance Relationship?

55 Diameter Normalized to the Passive Diameter at 100 mm Hg Adapted from Spaan, J. A.E. et al. Circulation 2006 Non-Linearity of the Pressure-Resistance Relationship? Pressure (mm Hg)

56 Diameter Normalized to the Passive Diameter at 100 mm Hg Non-Linearity of the Pressure-Resistance Relationship? Pressure (mm Hg) Adapted from Spaan, J. A.E. et al. Circulation 2006

57 Hyperemic Coronary Blood Flow ( % of Normal ) Pressure-Flow Relationship During Maximal Vasodilation Hyperemic Coronary Perfusion Pressure ( % of normal )

58 Conclusions The control of myocardial blood flow is amazingly complicated This complexity is due to the importance of constantly matching oxygen demand When performing coronary physiology in the cath lab a thorough understanding of the basic mechanisms is mandatory

59 Conclusions