Ability of Metoprolol to Alter the Exercise Induced Elevation of Catecholamines (MEXICHO)

• Change in stress-triggered blood pressure response. [ Time Frame: 2 weeks and 3 days ] [ Designated as safety issue: No ]
• Change in stress-triggered pulse response. [ Time Frame: 2 weeks and 3 days ] [ Designated as safety issue: No ]

Heart failure is a frequent disease in Denmark, and it is associated with very high mortality. Around 60,000 people in Denmark have heart failure, and there is about 11,000 hospitalizations every year due to this disease. From the time of diagnosis, patients survive an average of 4-5 years.

A critical illness mechanism in heart failure is that these patients have high blood levels of catecholamines; epinephrine and norepinephrine, which is stress hormones from the sympathetic nervous system. Standard treatment of heart failure is with the two medical preparations betablockers and ACE-inhibitors.

It is not known what effect betablocker-treatment have on blood concentration of epinephrine and norepinephrine.

It is the purpose of this study, to investigate the effect of Selo-Zok ® (metoprolol) on the blood concentration of epinephrine and norepinephrine. This is done by creating a stress condition for the body, in this case with the bicycle test, while doing blood samples to determine the concentration of catecholamines. This will be done by 1-week treatment of tablet Selo-Zok ® followed by 1-week treatment of placebo (a substance with no medical effect). Blood samples will be taken to determine small changes in inheritance material (DNA) in the form of point mutations also called single nucleotide polymorphisms, since these changes can affect how we respond to metoprolol treatment.

• Drug: Metoprolole (Selo-Zok ®)
  Tablets, 200 mg, once a day, 10 days
• Drug: Placebo

• Experimental: 1
  Metoprolol for 10 days followed by placebo for 7 days.
  Interventions:

  • Drug: Metoprolole (Selo-Zok ®)
  • Drug: Placebo
• Placebo Comparator: 2
  Placebo for 7 days followed by Metoprolol for 10 days
  Interventions:

  • Drug: Metoprolole (Selo-Zok ®)
  • Drug: Placebo

Inclusion Criteria:

• Kaukaser
• Healthy men
• 18 years < age < 30 years
• Non-smoker
• 18 < BMI < 25
• No chronic diseases
• Motor-disability that disables completement of cardio-pulmonary exercise-test.

Exclusion Criteria:

• Alcohol abuse or any other abuse
• Intake of any narcotic drugs (example: cannabinoids, narcotics, stimulants of central nervous system, hypnotics, hallucinogenes)

• Any of following medication:

  • astmamedication
  • heartmedication
  • antihistamines
  • antipsycotics
  • NSAIDs
  • rifampicine
  • chinidine
  • glucocorticoids
• Abnormal ECG, particularly 2. or 3. degree AV-block, sinusbradycardia, sick sinusnode-syndrome, sign of heart failure or ischemia.
• Allergy or intolerance of metoprolole
• Lactoseallergy
• 110 mmHg < Systolic blood pressure < 140 mmHg
• 60 mmHg < Diastolic blood pressure < 90 mmHg
• Bloodsucker > 11,1 mmol/L, or fasting, venous bloodsucker >= 7,0 (measured if: 7,8 < BS < 11,1)