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The Vicious Cycle of Chronic Congestive Heart Failure.

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Presentation on theme: "The Vicious Cycle of Chronic Congestive Heart Failure."— Presentation transcript:

1 The Vicious Cycle of Chronic Congestive Heart Failure

2 Spironolactone

3 Overflow and Underfilling Hypotheses of Sodium and Water Retention in Cirrhosis

4 PERIPHERAL ARTERIAL VASODILATION HYPOTHESIS Peripheral Arterial Vasodilation Plasma Hormones (AVP, Renin, Aldosterone, NE) Plasma Volume COMPENSATED CIRRHOSIS (No Ascites) DECOMPENSATED CIRRHOSIS (Ascites) Hepatorenal Syndrome Normal

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10 Hypothalamic AVP-mRNA of Control and Cirrhotic Rats

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12 “I have ascites and have desire for water, Although I know this water will kill me.” Rami (1226-1294 A.D.)

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14 Effects of Non-Peptide AVP Antagonist in Liver Cirrhosis

15 Effect of V1-Vasopressin Antagonist on Arterial Blood Pressure in Experimental Cirrhosis in Rats

16 ALDOSTERONE ANTAGONISM PROMOTES WEIGHT LOSS AND DISAPPEARANCE OF ASCITES IN DECOMPENSATED CIRRHOSIS PARAMETER Death Weight loss (lb) Disappearance of ascites CONTROL (n-22) 7 6 + 2 4 SPIRONOLACTONE (n=21) 5 24 + 4 16 CIRRHOTIC PATIENTS Gregory et al., 1977

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19 Increased Distal Tubular Sodium Delivery with Mannitol Resulted in a Marked Natriuresis During ANP Infusion

20 Urinary cGMP Increased Significantly During ANP and ANP + Mannitol

21 Distal Sodium Delivery During Mannitol and ANP + Mannitol in Cirrhotic Patients

22 Mean Arterial Pressure is Increased by Immersion Plus Norepinephrine but not by Immersion Alone

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24 Effect of Increased Arterial Circulatory Integrity to Normalize Renal Water Excretion in Decompensated Cirrhotic Patients

25 Correlation Between Increase in Systemic Vascular Resistance and an Increase in Water Excretion in Cirrhotic Patients

26 Effects of Terlipressin and Albumin on Renal Function in Hepatrorenal Syndrome

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28 Cirrhosis – Arterial Underfilling – Ascites

29 Effect of Chronic NOS Inhibition on Systemic Vascular Resistance in Cirrhotic Rats with Ascites

30 Effect of NOS Inhibition for 7 Days on eNOS Protein Expression in Aortas and Mesenteric Arteries in Cirrhotic Rats with Ascites

31 Effect of Chronic NO Synthesis Inhibition on Aortic cGMP in Cirrhotic Rats with Ascites

32 Effect of NOS Inhibition for 7 Days on Plasma Arginine Vasopressin and Atrial Natriuretic Peptide in Cirrhotic Rats with Ascites

33 Effect of NOS Inhibition for 7 Days on Water Excretion in Cirrhotic Rats with Ascites

34 Effect of NOS Inhibition for 7 Days on Plasma Renin Activity and Aldosterone in Cirrhotic Rats with Ascites

35 Sodium Excretion is Increased by Chronic L-Name Treatment in Cirrhotic Rats

36 Changes in Systemic Hemodynamic s and Plasma Volume During Pregnancy

37 Chronic L-NAME Treatment in Day 14 Pregnant Rats Returns Cardiac Output and SVR to Nonpregnant Levels

38 Chronic L-NAME Treatment in Day 14 Pregnant Rats Returns GFR and RPF to Nonpregnant Levels

39 Protein Expression of AQP 2 in Pregnancy

40 Effect of Vehicle and V2 Antagonist on Water Balance in Pregnant Rats

41 PATHOPHYSIOLOGY OF WATER METABOLISM IN EDEMATOUS DISORDERS NON-OSMOTIC VASOPRESSIN RELEASE VASOPRESSIN V2 RECEPTOR AQUAPORIN-2 INCREASED WATER PERMEABILITY OF COLLECTING DUCT WATER RETENTION CONGESTIVE CARDIAC FAILURE  CARDIAC OUTPUT CIRRHOSIS PERIPHERAL VASODILATION PREGNANCY V2 RECEPTOR ANTAGONIST Nitric Oxide


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