Consequences of static and pulsatile pressure on transmembrane exchanges during in vitro microdialysis: implication for studies in cardiac physiology

Microdialysis is an established technique for measuring the kinetics of var ious neurotransmitters within the extracellular space in the field of neuro chemistry. Recently, its use has been extended to sampling in other tissues , including liver, kidney and the heart. A persistent problem in cardiac mi crodialysis concerns two parameters related to myocardial function: pressur e and frequency (heart rate). The aim of the study is to evaluate the conse quences of pressure and frequency on transmembrane exchanges. Linear flexib le microdialysis probes (membrane length: 12 mm, outside diameter: 390 mu m , MWCO 50,000 Daltons) were designed in our laboratory. The probes, perfuse d at 2 mu L/min with sterile water, were placed in a system filled with a g lucose solution (2 g/L) and able to generate either static: 0 to 400 mmHg ( 0 to 53.31 kPa) or pulsatile pressure: 0-100; 0-200; 0-300 mmHg (0-13.32; 0 -26.65; 0-39.98 kPa) at different frequencies: 1, 2 and 3 Hz. At 2 mu litre min(-1) perfusion rate, the pressure inside the probe is estimated to be 8 0 mmHg (10.66 kPa). Under static pressure conditions, the glucose recovery rate can be expressed as an exponential function, and the outflow rate can be expressed as a linear function of the external pressure level. Under dyn amic conditions, the external mean pressure must be accounted for. When ext ernal mean pressure exceeds 80 mmHg (10.66 kPa) (pressure generated by the flow rate of perfusion inside the probe), the recovery rate increases with frequency. Conversely, if the outer mean pressure is lower than 80 mmHg (10 .66 kPa), the recovery rate decreases with frequency. Theoretical and exper imental modelling results in a nomogram that can be used to estimate in viv o recovery. In conclusion, mass transfer across a microdialysis membrane is dependent on the direction of the transmembrane pressure gradient and incr eases with heart rate. These findings must be taken into account when in vi vo recovery rates during cardiac microdialysis are determined.