Plasma-soluble marker for intraorgan regional flows

Area of Science:

• Physiology
• Pharmacology
• Biomedical Engineering

Background:

• Accurate measurement of regional plasma flow is crucial for understanding substrate and drug delivery to cells.
• An ideal deposition marker for estimating plasma flow should be fully extracted and retained within tissues.
• Desmethylimipramine (DMI), a norepinephrine reuptake inhibitor, exhibits properties suitable for such a marker.

Purpose of the Study:

• To evaluate Desmethylimipramine (DMI) as a tracer for measuring regional plasma flow.
• To assess the extraction and retention characteristics of DMI in biological systems.

Main Methods:

• Simultaneous injection of [3H]DMI and 131I-albumin into the coronary artery inflow of isolated rabbit hearts.
• Measurement of DMI extraction and retention at various plasma flow rates (Fs).
• Validation in ex vivo dog hearts.

Main Results:

• DMI extraction exceeded 99% at plasma flows up to 2.3 ml x g-1 x min-1 and 94% up to 5.1 ml x g-1 x min-1.
• Tissue retention of DMI averaged over 96% at 3 minutes for flows less than 2.3 ml x g-1 x min-1.
• Fractional escape rates were low (approx. 1%/min) after 2 minutes, indicating stable deposition.

Conclusions:

• Desmethylimipramine (DMI) functions as a near-ideal tracer for regional plasma flow measurement.
• DMI's high extraction and retention properties allow for accurate quantification of tissue substrate and drug delivery.
• DMI can be effectively utilized as a 'molecular microsphere' in physiological studies.