Compensatory mechanisms

1. Compensatory mechanisms 刘赛 高莉 王峻瑶 周越 艾富强

2. Case study 1971 1992 2002 心悸 劳力性心衰 易疲劳 晚上，争吵 端坐，呼困 发绀，劳累 颈静脉无怒张 心呈靴型 MI三项阳性 Drink and smoke MUCH MORE Drink and smoke 1988 1994 Hyperlipemia, obesity, Hepatic steatosis, Drink and smoke 憋气，心慌，极易疲劳 垫2-3个枕头 高血压 心肌缺血 肺水肿 AS Angina? hight HR 左下壁MI 高血压 平卧位 戒烟酒 2005 2006

3. 病程简要分析 SNS 和RAS激活 血液粘滞，血栓形成，循环血量不足，心肌缺氧 烟酒，高血脂，肥胖，高血压 急性心肌梗死伴窦性心动过速 心脏代偿，不断重塑肥大 心肌代偿障碍，劳力性心衰 陈旧梗死伴炎症发生 呼吸困难， 端坐 肺淤血水肿，高血压加重 肺动脉压增高 左心衰 MI辅查 双下肢无凹陷性水肿，颈静脉无怒张 无右心衰 CK-MB,cTnT,Myo阳性

4. Howcan he survive for so long?

5. Compensatory mechanisms • Neurohormonal mechanisms • Ventricular remodeling

6. Compensatory mechanisms • Neurohormonal mechanisms • activation of SNS • activation of RAS • neurohormonal alterations of renal function • neurohormonal alteratons in the periheral vasculature • nitric oxide

7. Compensatory mechanisms • Ventricular remodeling • alterations in myocyte biology • myocardial changes • alterations in ventricular chamber geometry

8. SNS Damage and remodeling PSNS↓ Ach↓ heart β1-R↑ HR、contractility ↑ Too long and too much BP↑ RAS↑ CO↑ kidney NE↑ SNS↑ α-R↑ Peripheral vascular resistance↑ β-R↑ CNS↑ Redistribution of blood flow input↑ β2-R↑ release↑ hypersensitization

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10. RAS AVP↑ SNS↑ angiotensinogen kidney↑ RAS↑ renin↑ CNS cardioregulatory centers↑ Angiotensin I Adrenal gland ACE heart Baroceptors unload Angiotensin II Peripheral vasoconstriction Adrenal gland ↑ Reabsorption of water and sodium, ↑secretion of potassium and hydrogen ions Aldosterone↑ ↑cardiac myocytes remodeling Retention of water and sodium

12. Nitric oxide NO synthase(NOS):--NOS1:neuronal; --NOS2:inducible; --NOS3:endothelial-constitutive NO activates GC cGMP PKG signaling events vasodilation;modulates the activity of several key Ca channels involved in excitation contraction coupling, mitochondrial respiratory complexs(normal) HF:vasodilation blunted; myocardium—complex(short-term alterations in function and energetics long-term on structure) subcellular location of NO becomes disrupted

13. Ventricular remodeling Alterations in Myocyte Biology --hypertrophy;β-R desenditization; fetal gene expression Myocardial Changes --myocyte loss(necrosis,apoptosis,autophagy) --alterations in extracellular matrix(degradation,fibrosis) Alterations in Left Ventricular Chamber Geometry --dilation(sphericity);wall thinning;mitral valve incompetence

14. Pressure(hypertension or aortic stensis)↑ Systolic wall stress↑ ↑ Sarcomeres parallel myocyte widening Concentric cardiac hypertrophy Ventricular volume↑ Diastolic wall stress↑ ↑Sarcomeres series myocyte lengthing eccentric cardiac hypertrophy preload↑ Ventricular remodeling hypertrophy Hemodynamic overloading↑ MMPs↑ hypoxemia afterload↑ ECM degradation↑ Growth factor↑ Energy utilization↑ Energy starvation Progressive dilation↑ apoptosis↑ necrosis↑

15. Myocyte hypertrophy

16. Cardiac hypertrophy

18. Summary HF is a progressive disease, which has many compensatory mechanisms. Something new is needed to be found.

19. Thanks a lot Thanks a lot !!!