The Metformin-FMD Trial

Radboud University Medical Center26 enrolled

Overview

In acute myocardial infarction early restoration of coronary blood flow is the most effective strategy to limit infarct-size. Paradoxically, reperfusion itself also aggravates myocardial injury and contributes to final infarct size, a process termed 'reperfusion injury'. Ischemia and reperfusion (IR)-induced endothelial dysfunction seems to play a pivotal role in this process, resulting in vasoconstriction and reduced blood flow to the already ischemic tissue. Recently, it has been shown that the glucose-lowering drug metformin is able to limit IR-injury in murine models of myocardial infarction, probably by increased formation of the endogenous nucleoside adenosine. In the current research proposal, the investigators aim to translate this finding to the human in vivo situation, using flow-mediated dilation (FMD) of the brachial artery as a well-validated model of (endothelial) IR-injury.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Ischemia Reperfusion Injury Endothelial Function

Interventions

Eligibility

Sex: ALLMin age: 30 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age 30-50 years * Written informed consent Exclusion Criteria: * Smoking * Hypertension (in supine position: systolic BP \> 140 mmHg, diastolic BP \> 90 mmHg) * Hyperlipidaemia (fasting total cholesterol \> 5.5 mmol/L or random \> 6.5 mmol/L) * Diabetes Mellitus (fasting glucose \> 7.0 mmol/L or random glucose \> 11.0 mmol/L) * History of any cardiovascular disease * Concomitant use of medication * Renal dysfunction (MDRD \< 60 ml/min) * Professional athletes

Outcomes

Primary Outcomes

Metformin-FMD trial: The effect of pretreatment with metformin on FMD of the brachial artery after forearm ischemia and reperfusion.

Metformin-FMD trial: To study the effect of oral pretreatment with metformin (500 mg three times ad ay for 3 days) on flow mediated dilation of the brachial artery after 20 minutes of forearm ischemia and 20 minutes of reperfusion in healthy volunteers.

Time frame: approx. 6 months

Control trial: the effect of caffeine on the protective effect of metformin on FMD after ischemia and reperfusion.

Control trial: when metformin displays a protective effect on endothelial function, we will conduct a second experiment to study whether caffeine, an adenosine receptor antagonist, attenuates the protective effect of metformin on flow mediated dilation after 20 minutes of ischemia and 20 minutes of reperfusion in healthy volunteers.