Lack of autoregulatory blood flow escape in the skin after infusion of therapeutic levels of noradrenaline through a microdialysis system in healthy volunteers

Introduction

In burn-injured patients we have previously shown that skin has a decreased autoregulatory blood flow adjustment. Lack of such a function in skin would make uncontrolled use of vasoconstrictors detrimental to this organ. If ischemia-like conditions are produced in the skin, use could enhance the inflammatory response and increase the risk of organ dysfunction. We exposed local areas of the skin in healthy volunteers to therapeutic levels of noradrenaline (NA) by infusion through microdialysis (MD) intradermally, to investigate whether autoregulatory escape is present in the skin during strong α₁-adrenergic stimulation.

Methods

Five subjects received three MD catheters (CMA 70) intradermally in the lower arm. Catheters were perfused for a 90-minute stabilizing period, Ringer solution with 20 mmol/l urea, for skin blood flow determinations (urea clearance). Thereafter NA 0.5 or 5 μg/ml was perfused (2 μl/min) for 60 minutes followed by a buffer washout period. After this 0.5 mg/ml nitroglycerine was perfused (2 μl/min) for 60 minutes. Samples were collected every 10 minutes and analysed for urea, lactate, pyruvate and glucose.

Results

During perfusion with NA 5 and 0.5 μg/ml, skin blood flow decreased significantly as indicated by changes in urea clearance; increased lactate pyruvate quotients and corresponding rapid decreases in tissue glucose levels. These changes further increased during the perfusion of pure buffer. Normalization was first noted during infusion of nitroglycerine.

Conclusion

Both doses of NA, previously claimed to be physiological, induce a reproducible and severe vasoconstriction as indicated by effects on urea clearance, increases in lactate pyruvate quotients and decreases in tissue glucose. These data suggest that skin lacks an autoregulatory escape function and ischemia was induced in the skin of healthy volunteers by the NA infusion. The ischemia situation further deteriorated until an active vasodilatation was started. In this skin vascular model, in healthy volunteers, NA shows negative effects that may also be important for the critical care setting. Further studies are needed to validate these findings.