Human Integrative Physiology

Leader: Han van Lieshout


Our research interest lies in the integrated in-vivo cardiovascular regulation in humans. The primary focus in our laboratory is the study of systemic and regional circulatory control in relation to physical stress (gravity, exercise) in health and disease. Results of last three years concern a) brain perfusion and metabolism and b ) cerebrovascular autoregulatory capacity in small vessel disease. We showed that the CO2 responsiveness of the brain does not account for the postural reduction in cerebral perfusion whereas brain perfusion depends on cardiac performance beyond arterial pressure. Gravity dominates the choice for venous outflow pathway of the human brain and we characterized the effects of body position on CO2 transfer from blood to alveolar gas and on the cerebral CO2 responsiveness. When addressing the mechanism of the increase in regional cerebral blood flow activated by dynamic exercise the arterial lactate-to-pyruvate ratio appears to modulate cerebral blood flow during cerebral activation independently. Loss of dynamic cerebral autoregulatory capacity was established in malignant hypertension, and unilaterally in large cerebral artery territory stroke but bilaterally in unilateral lacunar ischemic stroke. We found that cerebral autoregulatory dysfunction in type 2 diabetes appears prior to the clinical expression of diabetic vasculopathy independently from plasma glucose level supporting our premise that vascular disease endangers cerebral control functions early.

Future Studies

We pursue improvement of the traditional volume treatment paradigm by developing a practical goal-directed fluid treatment models against the background that no single variable responds exclusively to a reduced central blood volume and the usual clinical and hemodynamic parameters are not reliable indices of preload to the heart. We expect that moving from the traditional fixed volume to goal-directed fluid treatment contributes to securing tissue oxygenation.

Team members

Han van LieshoutGroup Leader (PI)
John KaremakerScientist
Wim StokScientist
Bjorn van der SterGuest

Key publications