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1、ACEI 19 (Heart J. 1998; 19 (Suppl Suppl F): F62-F71.F): F62-F71.Myocardial ischemiaRAS activationSystemic VasoconstrictionVasoconstriction of coronary arteries (both large and small)SNS activation Adrenergic tone MVO2Renin-Angiotensin Aldosterone System circulating hormonal system local endogenous t
2、issue hormonal system with autocrine and paracrine effects neurotransmitter and neuromodulator Action of Angiotensin IITISSUE AFFECTEDACTION ArteryStimulates contraction, growth AdrenalStimulates secretion of aldosterone KidneyInhibits release of renin Increases tubular reabsorption of sodium Stimul
3、ates vasoconstriction Release prostaglandins BrainStimulates thirst and the release of vaospressin SympatheticIncreases central sympathetic outflow nervousFacilitates peripheral sympathetic transmission systemIncreases adrenal release of epinephrine Heart Increases contractility and ventricular hype
4、rtrophyGoodfriend et al. NEJM 1996; 334: 1649-1654.Cardioprotective Effects of ACEI Restoring the balance between myocardial oxygen supply and demand Reduction in LV preload and afterload Reduction in LV mass Reduction in sympathetic stimulation Beneficial effect on reperfusion injury * Eva Eva Lonn
5、Lonn, et al. Circulation 1994; 90(4):2056-69., et al. Circulation 1994; 90(4):2056-69.* Not demonstrated conclusively in humans* Not demonstrated conclusively in humansAngiotensin IAngiotensin II1. vasoconstriction (systemic and coronary) 2. sympathetic nervous system (central and peripheral)ACEIVas
6、culoprotective Effects of ACEI Direct antiatherogenic effect * Antiproliferative and antimigratory effects on smooth muscle cells, neutrophils and mononuclear cells Improvement and/or restoration of endothelial function Protection from plaque rupture * Antiplatelet effects Enhancement of endogenous
7、fibrinolysis * Antihypertensive effects Improvement in arterial compliance and toneEva Eva LonnLonn, et al. Circulation 1994; 90(4):2056-69., et al. Circulation 1994; 90(4):2056-69.* Not demonstrated conclusively in humans* Not demonstrated conclusively in humansUse of ACEI in the Management of Card
8、iovascular Disease Hypertension Severe CHF Moderate LV dysfunction with or without MI High-risk patients for major cardiovascular events-receptor antagonists 5:357-382.-Heart Failure Society of America (1999)“The single most significant addition to the pharmacological management of heart failure sin
9、ce the publication of previous guidelines ACC/AHA involves the use of beta-receptor antagonists.”Pathogenesis and Sequelae of Heart FailureAdapted from Cohn J. N Engl J Med. 1996;335:490-498.Coronary artery diseaseHypertensionCardiomyopathyValvular diseaseLeft ventricular dysfunctionNon- cardiac fac
10、torsRemodelingLow ejection fractionArrhythmiaDeathPump failureSymptoms: Dyspnea Fatigue EdemaChronic heart failure Neurohormonal stimulation Endothelial dysfunction Vasoconstriction Renal sodium retentionEichhorn EJ, JCF. 2000;6(suppl 1):40-46. LVEFTime (months)Biologic EffectPharmacologic Effectb-B
11、locker Initiatedb-Blocker Discontinued0 01 13 36 68 8b-Blocker Effects On Ejection Fraction in Heart FailureThe RESOLVD Investigators. Circulation. 2000;101:378-384. Time (wk)024P =.02225215205195185175Time (wk)300290280270260250 024P =.001Time (wk)323130292827 024P 25 mm hg at rest or 30 mm hg with
12、 exercise, in absence of demonstrable cause.PULMONARY HYPERTENSION Secondary Pulmonary Hypertension: It refers to an increase in pulmonary artery impedance due to either intrinsic parenchymal lung disease or disease extrinsic to lung. Pulm. Hypertension is considered when PAS and PAM is 30 mm hg and
13、 20 mm hg respectivelyCauses of Secondary PH HYPOXIC VASOCONSTRICTION DECREASED AREA OF PULMONARY VASCULAR BED VOLUME/PRESSURE OVERLOADVasodilatorslCalcium Channel BlockerslACEIlPGE1lInhaled vasodilatorsInhaled Vasodilators Ann Int Med 1996; 4 pt. With PPH compared the short term administration of n
14、itric oxide, aerosolized epoprostenol, and an aerosolized preparation of the prostaglandin analog iloprost to IV Flolan in pt with severe PPH. in PAP and PVR were observed with all medications, but IV therapy was less effective in PAP and produced some systemic hypotension. Inhaled nitric oxide was less effective pulmonary vasodilators than epoprostenol. These finding were confirmed later in series of 7 pt. Eu Heart J 1997.四、血流动力学监测下合 理应用血管活性药血流动力学类型和治疗
