• a. Test the hypothesis that angiotensin II induces oxidation and inflammation in humans through endogenous aldosterone
• b. Test the hypothesis that exogenous aldosterone induces oxidation and inflammation in humans through a mineralocorticoid receptor-dependent mechanism
• c. Test the hypothesis that exogenous aldosterone induces oxidation and inflammation in humans through an AT1 receptor-dependent mechanism

• Intra-operative MAP [ Time Frame: Measured during surgery ] [ Designated as safety issue: Yes ]
• Intra-operative and post-operative requirements for pressors. [ Time Frame: Measured until the time of hospital discharge ] [ Designated as safety issue: Yes ]
• Death [ Time Frame: Measured until the time of hospital discharge ] [ Designated as safety issue: Yes ]
• Length of hospital stay [ Time Frame: Measured until the time of hospital discharge ] [ Designated as safety issue: No ]
• Post-operative IL-6, PAI-1, t-PA and CRP concentrations and other biomarkers [ Time Frame: Measured until the time of hospital discharge ] [ Designated as safety issue: No ]
• Serum potassium concentrations [ Time Frame: Measured until the time of hospital discharge ] [ Designated as safety issue: Yes ]
• Creatinine concentrations(measured throughout the patient's hospital stay) [ Time Frame: Measured until the time of hospital discharge ] [ Designated as safety issue: Yes ]
• Stroke [ Time Frame: Measured until the time of hospital discharge ] [ Designated as safety issue: Yes ]

AF is the most prevalent, sustained type of irregular heartbeat and affects over 2 million Americans. Post-operative AF, which leads to significant morbidity and a prolonged hospital stay, complicates 20% to 40% of CPB surgical procedures. While recent studies indicate that interruption of the renin-angiotensin-aldosterone system by either ACE inhibition or AT1 receptor antagonism decreases the incidence of AF following a heart attack or cardioversion (electric shock to the heart), its effect on the incidence of post-operative AF has not been throughly studied. Studies in both animals and humans suggest that inflammation-induced atrial remodeling plays an important role in the cause of AF. Recent studies also provide evidence that activation of the renin-angiotensin-aldosterone system induces inflammation, myocyte injury, proarrhythmic electrical remodeling, and fibrosis through aldosterone.

AF is the most prevalent, sustained type of irregular heartbeat and affects over 2 million Americans. Post-operative AF, which leads to significant morbidity and a prolonged hospital stay, complicates 20% to 40% of CPB surgical procedures. While recent studies indicate that interruption of the renin-angiotensin-aldosterone system by either ACE inhibition or AT1 receptor antagonism decreases the incidence of AF following a heart attack or cardioversion (electric shock to the heart), its effect on the incidence of post-operative AF has not been throughly studied. Studies in both animals and humans suggest that inflammation-induced atrial remodeling plays an important role in the cause of AF. Recent studies also provide evidence that activation of the renin-angiotensin-aldosterone system induces inflammation, myocyte injury, proarrhythmic electrical remodeling, and fibrosis through aldosterone.

This study will evaluate the effectiveness of ACE inhibition and aldosterone receptor antagonism at decreasing inflammation and AF following CPB surgery.

• Drug: Placebo
• Drug: Ramipril
• Drug: Spironolactone

• Experimental: ACE inhibitor
• Experimental: MR antagonist

Inclusion Criteria:

1. Undergoing elective valvular heart surgery, coronary artery bypass grafting
2. If female, must be postmenopausal for at least 1 year, status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and willing to undergo urine beta-hcg testing prior to drug treatment and throughout the study

Exclusion Criteria

1. History of AF other than remote paroxysmal AF
2. Ejection fraction less than 30%
3. Evidence of coagulopathy (INR greater than 1.7 without warfarin therapy)
4. Emergency surgery
5. History of ACE inhibitor-induced angioedema
6. Low blood pressure (systolic blood pressure less than 100 mmHg and evidence of hypoperfusion)
7. Hyperkalemia (potassium level greater than 5.0 mEq/L at study entry)
8. Impaired kidney function (serum creatinine level greater than 1.6 mg/dl)
9. Any underlying or acute disease requiring regular medication that could possibly cause complications or make implementation of the study or interpretation of the study results difficult
10. Inability to discontinue current ACE inhibitor, AT1 receptor antagonist, or aldosterone receptor antagonist therapy
11. History of alcohol or drug abuse
12. Treatment with any investigational drug in the month prior to study entry
13. Mental condition that makes it impossible to understand the nature, scope and possible consequences of the study
14. Inability to comply with the study procedures (e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study)
15. Pregnant or breastfeeding