Cardio and Renovascular Effects of Isometric Exercise in the Healthy Human Measured by PET/CT and MRI

Cardio and Renovascular Effects of Static Muscle Work in the Healthy Human - Measured With Finapres® and Positron Emission Tomography (PET) Using 15-oxygen Labeled Water as Tracer Compared to Magnetic Resonance (MR)

This randomized crossover study aims to validate measurements of renal perfusion in healthy males with PET/CT, using 15-oxygen labeled water as tracer, against the validated multiparametric MRI technique.

The study will determine:

• Total renal blood flow and regional renal perfusion at baseline (rest) and during isometric muscle exercise of the upper arm, using PET/CT (with 15-oxygen labeled water as a tracer) and MRI.
• The coefficient of variation of renal blood flow and regional renal perfusion measurements at baseline and during isometric muscle exercise of the upper arm, using PET/CT (with 15-oxygen labeled water as a tracer) and MRI.
• Regional renal oxygenation and oxygen extraction at baseline and during isometric muscle exercise of the upper arm using MRI.
• The coefficient of variation on regional renal oxygenation and oxygen extraction measurements at baseline and during isometric muscle exercise of the upper arm using MRI.

Measuring tissue perfusion with PET/CT using 15-oxygen labeled water is routinely used as a non-invasive tool to examine cerebral and myocardial perfusion. With a 100% tissue extraction, 15-oxygen labeled water is gold standard.

The aim of the present study is to validate renal perfusion measurements with PET/CT using 15-oxygen labeled water as tracer against the validated multiparametric MRI technique.

Once validated the imaging technique will be beneficial in examining vascular damage in the kidneys caused by different renal diseases.

This is a randomized, crossover study where each participant will participate in 1 study day.

Ten healthy male participants in the age group 20-60 years are screened and randomized, and expected to complete the present study. Informed consent is obtained before the screening meeting.

All participants consume a controlled diet with fixed salt intake corresponding to a daily intake of 50-70 mmol + 2 mmol/kg sodium for 4 days before the experiment. On the fourth day, 24-hour urine collection will be performed. Throughout the 4 day period, water intake will be ad libitum and physical activity will not be allowed.

Each participant will undergo both PET/CT and MRI separated by around 1.5 hour.

Total renal blood flow and regional renal perfusion are measured repeatedly altogether 5 times with both PET/CT and MRI. Renal oxygenation and oxygen extraction are measured repeatedly 5 times as well, using MRI. The 5 measurements consist of 2 at baseline (rest), 2 during isometric exercise (handgrip) and 1 during recovery (rest).

Isometric muscle exercise is conducted by squeezing a handgrip coupled to a dynamometer. This increases sympathetic nervous activity, leading to preglomerular vasoconstriction.

Inclusion Criteria:

• Normal health stated through medical questionnaire, examination and blood samples.

Exclusion Criteria:

• Immunosuppressive treatment
• Alcohol abuse
• Treatment with glucocorticoids, Glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase 4 (DPP-4)-inhibitors
• Medical treatment affecting insulin secretion or cardiovascular endpoints
• Liver disease
• Decreased kidney function
• Severe claustrophobia
• Elements incompatible with MR.