The present study was performed in compliance with the Declaration of Helsinki and the Good Clinical Practice (GCP) guidelines. After approval of the study protocol by the ethics committee of the Vienna University School of Medicine and after written informed consent was obtained, 12 healthy nonsmoking male subjects were studied (age: 28 ± 4 years, mean ± SD). All subjects were drug free for at least 3 weeks before inclusion and passed a prestudy screening during the 4 weeks before the first study day that included medical history and physical examination, 12-lead electrocardiogram, complete blood count, activated partial thromboplastin time, thrombin time, clinical chemistry (sodium, potassium, creatinine, uric acid, glucose, cholesterol, triglycerides, alanine aminotransferase, aspartate transcarbamylase, γ-glutamyltransferase, alkaline phosphatase, total bilirubin, and total protein), hepatitis-A, -B, and -C and HIV serology, urinanalysis and an ophthalmic examination. Subjects were excluded if any abnormality was found as part of the pretreatment screening, unless the investigators considered an abnormality to be clinically irrelevant. In addition, subjects with ametropia of more than 3 D, anisometropia more than 1 D, or any evidence of eye disease that might have interfered with the purpose of the present trial were excluded. During the last week after completion of the study, a follow-up safety investigation was scheduled for all participating subjects. This follow-up investigation included complete blood count, activated partial thromboplastin time, thrombin time, clinical chemistry (sodium, potassium, creatinine, uric acid, glucose, cholesterol, triglycerides, alanine aminotransferase, aspartate transcarbamylase, γ-glutamyltransferase, alkaline phosphatase, total bilirubin, and total protein), and urinanalysis. All subjects had several training sessions with the laser Doppler flowmetry (LDF) system before inclusion in the study. In addition, all subjects participated in periods of squatting, during which LDF measurements were performed. Only subjects with excellent target fixation and highly reproducible blood flow results during isometric exercise were considered for inclusion in the study.