The Effects of Post-Conditioning and Administration of Vitamin C on Intramuscular High Energy Phosphate Levels (IRI in MRI)

Ischemic injury to muscular tissue is common in cardiovascular medicine. The most effective treatment to avoid ischemic damage is the rapid re-establishment of reperfusion. However, reperfusion itself can result in additional damage to ischemic tissue. This phenomenon is called ischemia - reperfusion (IR) injury and is caused by different pathologic mechanisms.

Therapies are required which can be administered after the onset of an ischemic event to protect the tissue against IR injury. Therefore, a promising strategy to reduce IR injury is post-conditioning.

Likewise, pharmacological therapies administered after the onset of reperfusion might prevent tissue injury. We have recently shown that high concentrations of exogenous vitamin C abrogate experimental IR injury of the forearm vasculature in patients with peripheral artery disease and in healthy subjects.

Study hypothesis

We hypothesize that the administration of mechanical post-conditioning or of high-dose vitamin C may protect skeletal muscle against IR injury. This shall be studied employing MR spectroscopy of the leg, which is an established model to assess muscle aerobic energy metabolism.

Design

Three periods, three way cross over study in 10 volunteers. One screening visit, three one-day study days with two washout periods of >3 days in between are scheduled for each participant. The order of experimental days will be randomized. After the last treatment a final follow-up examination will be performed within one week.

• Drug: Vit C
• Procedure: Postconditioning
• Other: no intervention

• Placebo Comparator: 1
  No intervention after IR injury
  Intervention: Other: no intervention
• Experimental: 2
  Postconditioning
  Intervention: Procedure: Postconditioning
• Experimental: 3
  Vit. C
  Intervention: Drug: Vit C

Inclusion Criteria:

• Men aged between 18 and 45 years
• Nonsmoker for more than 3 months
• Body mass index between 18 and 25 kg/m2
• Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant

Exclusion Criteria:

Any of the following will exclude a subject from the study:

• Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
• Evidence of hypertension, pathologic hyperglycemia, hyperlipidemia
• Treatment in the previous 3 weeks with any drug including over-the-counter drugs.
• Symptoms of a clinically relevant illness in the 2 weeks before the first study day
• History or presence of gastrointestinal, liver of kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of the study drug
• Blood donation during the previous 3 weeks
• History of hypersensitivity to parenteral vitamin C.
• Glucose-6-phosphate dehydrogenase deficiency
• Thalassemia, haemochromatosis
• History of urolithiasis
• Any metallic or paramagnetic device not removable
• Claustrophobia
• Regular use of supplementary oral Vitamin C or Vitamin C containing substances