CHANGED SYSTEMIC AND CEREBRAL HEMODYNAMICS AND OXYGEN-SUPPLY DUE TO GRADUAL HEMORRHAGIC HYPOTENSION INDUCED BY AN EXTERNAL PID-CONTROLLER IN NEWBORN SWINE

An experimental design including an external closed-loop ID-(proportio nal-integral-differential-)controller is presented which enables the i nduction of gradual hemorrhagic hypotension at different stages of blo od flow reduction up to stages of critically disturbed systemic and re gional hemodynamics and oxygen supply. For this purpose nine newborn p iglets (12-26 hours old, body weight 1626 +/- 160 g) were anesthetized and artificially ventilated. Gradual hemorrhagic hypotension was indu ced at four different steady state stages (stage 1 = 60 mmHg; stage 2 = 50 mmHg; stage 3 = 40 mmHg; stage 4 = 35 mmHg) every 30 minutes by g radual blood withdrawal using external PID controller equipment. Cardi ac output and brain regional blood flows were measured by the colored microsphere technique. Systemic and brain regional hemodynamics and O- 2 supply, metabolic parameters and blood catecholamine concentrations were obtained under baseline conditions and at every 25(th) minute of the four different steady state stages. About 35 percent of the calcul ated total blood volume (cTBV) was withdrawn in order to reach the fir st stage of hemorrhagic hypotension. Further blood withdrawal of about 10 percent of the cTBV, about 5 percent of the cTBV, and about 3 perc ent of the cTBV were necessary to reach the other respective hypotensi ve stages. Gradual hemorrhagic hypotension led to an increasing reduct ion of the cardiac output at every hypotensive stage up to about 20 pe rcent of the baseline value (p < 0.05). This was accompanied by a conc omitant increase of the total peripheral resistance to about 2.5 fold (p < 0.05) and a huge increase in the blood catecholamine concentratio ns (epinephrine: about 64 fold; norepinephrine: about 35 fold). The in duced redistribution of the circulating blood volume was shunted to th e vital organs. Therefore, brain cortical blood flow was slightly incr eased at stage 1 and stage 2. A significant reduction of rCBF did not occur until stage 4 (p < 0.05). Regional cerebrovascular resistance wa s concomitantly reduced at stage 1 and stage 2 (p < 0.05) and thereaft er again slightly elevated. Brain cortical oxygen consumption was main tained up to stage 2, reduced by about 20 % at the next stage of hemor rhagic hypotension (p < 0.05) and reached the lowest level of about 50 % from baseline at stage 4 (p < 0.05). Exellent accuracy and stabilit y was shown at each stage for the external PLD controller equipment, s o that each given setpoint of the instantaneous mean arterial blood pr essure was reached and stabilized even at the lowest hypotensive stage (stage 1: 59.53 +/- 0.23; stage 2: 50.03 +/- 0.56; stage 3: 39.18 +/- 1.75; stage 4: 35.28 +/- 0.45 mmHg (mean +/- SD)). We conclude that t he experimental design presented, with an external PID controller to i nduce gradual hemorrhagic hypotension in newborn piglets is sufficient for producing functional states with changed systemic and cerebral fe atures with high stability and accuracy, enabling a systematic study o f disturbed regional hemodynamics and energy metabolism under steady s tate conditions even under critically changed states of the systemic c ardiovascular regulation.