ischemia miocardica e cardiopatia ischemica cronica - unich.it ischemica.pdf · ischemia miocardica...

Ischemia Miocardica e

Cardiopatia Ischemica Cronica

Raffaele De Caterina

12-12-00

Cattedra di Cardiologia

Università G. D’Annunzio Chieti

Domande preliminari -

test di autovalutazione

• Ipossia vs ischemia

• Perché nel miocardio sono quasi equivalenti

• Origine dell’ischemia miocardica (e di

organo in generale)



The Supply/Demand Balance



Determinants of Myocardial

Oxygen Consumption

TABLE 36-2 DETERMINANTS OF MYOCARDIAL OXYGEN

CONSUMPTION

1. Tension development

2. Contractile state

3. Heart rate

4. Shortening against a load (Fenn effect)

5. Maintenance of cell viability in basal state

6. Depolarization

7. Activation

8. Maintenance of active state

9. Direct metabolic effect of catecholamines

10. Fatty acid uptake Cattedra di Cardiologia


Determinants of Myocardial

Oxygen Consumption

TOTAL: 6-8 cc/min/100 gm

DISTRIBUTION

Basal 20% Volume work 15%

Electrical 1% Pressure work 64%

EFFECTS ON MVO2 of 50% INCREASES IN

Wall stress 25% Heart rate 50%

Contractility 45% Volume work 4%

Pressure work 50%

The table demonstrates the dominant contribution to MVO2

made by pressure work and prominent effects of increasing

pressure work and heart rate on MVO2.

From Gould, K. L.: Coronary Artery Stenosis, New York, Elsevier, 1991, p. 8.



The Myocardium-Vascular

Resistance Coupling



Coronary Blood Flow Regulation



Epicardial/Endocardial

Inhomogeneity



Epicardial/Endocardial

Differences in Coronary Reserve



Stenosis vs Flow

Relation between pressure reduction

across a stenosis (DP) and flow through

the stenosis (Q). Relations are shown for

concentric stenoses of 30, 50, 70, 80, and

90 per cent internal diameter. The

numbers in parentheses below each per

cent diameter stenosis represent residual

luminal cross-sectional area, calculated on

the basis of a normal internal diameter of

3 mm and cross-sectional area of 7.1

mm2. The level of flow corresponding to

basal metabolic needs is represented by

the vertical dotted line; stenosis

resistances for this level of flow are shown

as the dashed tangent lines to the

individual pressure-flow relations. In the

inset on the right, stenosis resistance (R) is

plotted as a function of degree of stenosis.

(From Klocke, F. J.: Measurements of

coronary blood flow and degree of

stenosis: Current clinical implications and

continuing uncertainties. Newsletter of the

Council on Clinical Cardiology of the

American Heart Association. Vol 7, No. 3,

July 1982.)Cattedra di Cardiologia


Epicardial vs. Myocardial Resistances



Lesion Diameter vs Flow



Reactive Hyperemia



Myocardial Consequences of

Ischemia



The Proposed Mechanisms of

Myocardial Stunning1. Insufficient energy production by mitochondria

2. Impaired energy use by myofibrils

3. Impaired sympathetic neuronal responsiveness

4. Impaired myocardial perfusion

5. Damage to the extracellular collagen matrix

6. Decreased sensitivity of myofilaments to calcium

7. Calcium overload

8. Excitation-contraction uncoupling due to dysfunction of sar-

coplasmic reticulum

9. Generation of damaging oxygen free radicals

Modified from Bolli, R.: Postischemic myocardial stunning. In Yellon, D. M., and

Jennings, R. B. (eds.): Myocardial Protection: The Pathophysiology of Reperfusion

and Reperfusion Injury. New York, Raven Press, Ltd., 1992.



The wavefront of myocardial

necrosis



Ischemia and

Necrosis



Potential Causes of

Irreversibility

High-energy phosphate depletion/cessation of anaerobic glycolysis

Catabolism without resynthesis of macromolecules

Reduced transsarcolemmal gradients of Na+ and K+

Cell Swelling

Calcium overload

Activation of phospholipases/proteases

Impaired mitochondrial function

Activation of ATPases

Catabolite accumulation (lactate, H+ (acidosis), fatty acid derivatives, free

radicals, ammonia, inorganic phosphate, etc.)

Enzyme denaturation

Membrane damage

Increased intracellular osmolarity

Cell swelling



The

spectrum of

myocardial

ischemia



Variable supply-demand ratios



L’informazione con test

diagnostici

• Test da sforzo: presenza d’ischemia miocardica - non

localizzazione

• ECO basale: presenza di anomalie di contrazione (necrosi-

stunning-ibernazione)

• stress ECO: presenza d’ischemia - localizzazione - vitalità

• scintigrafia da stress (Tl201-99mTc-sestamibi):

ipoperfusioni/vitalità

• angiografia: anatomia delle coronarie

• riserva coronarica: significato funzionale di una stenosi



Stress ECG test



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