|dc.identifier.isbn||978-82-308-0492-6 (print version)||eng
|dc.description.abstract||Global and regional organ perfusion during cardiopulmonary bypass (CPB) depends
on hemodynamic parameters as mean arterial pressure (MAP) and perfusion flow rate. These
parameters may also exert influence on the load of micro-emboli delivered to the central
nervous system (Sungurtekin et al., 1999), to the operating conditions (Cartwright &
Mangano, 1998) and to the degree of extravascular fluid accumulation during CPB (Paper
The present thesis focus on some specific consequences of different MAP and
perfusion flow rate values during CPB. Two particular endpoints have been addressed:
A. Net fluid balance and fluid extravasation rate during CPB (Paper I - III)
B. Cerebral biochemical changes associated with energy metabolism and ultrastructural
integrity (Paper IV – V)
Paper I compares a group of animals with lowered MAP (LP-group, n=7) by use of
nitroprusside and a historical control group (C-group, n=7)) with respect to fluid shifts.
Paper II compares groups with elevated MAP by norepinephrine (HP-group, n=8)) and
lowered MAP by phentolamine (LP-group, n=8)), also with respect to fluid shifts.
Paper III determines fluid shifts in groups with two different CPB perfusion flow rates (LFgroup,
n=8 and HF-group, n=8).
Paper IV assesses cerebral biochemical markers in groups with elevated MAP by
norepinephrine (HP-group, n=6) and lowered MAP by nitroprusside (LP-group, n=6).
Paper V assesses the same cerebral markers as well as mitochondrial ultrastructure by electron
microscopy in animals with elevated MAP by norepinephrine (HP-group, n=8) and lowered
MAP by phentolamine (LP-group, n=8). Methods:
Young pigs aged 10-12 weeks were given general anesthesia and underwent 60
minutes of normothermic CPB (38°C) followed by 90 minutes of hypothermic CPB (28°C).
Acetated Ringer’s solution was given with 5 ml/kg/h i.v. and as CPB prime. Extra acetated
Ringer’s solution was added to the CPB venous reservoir whenever necessary, to maintain a
constant level. In paper I, II, IV and V infusions of vasoactive agents were given during the whole
CPB period. MAP was kept between 60 – 80 mmHg in the animals with elevated arterial
pressure and at 40 – 45 mmHg in the animals with reduced arterial pressure. The two groups
of animals in paper III had CPB perfusion flow rate set to 80 ml/kg/min and 110 ml/kg/min,
Colloid osmotic pressure in plasma and interstitial fluid (wick method) was measured
in addition to acid base parameters and blood chemistry. Plasma volume was determined by
the carbon-monoxide method and subsequent changes were calculated based on new values of
hematocrit and the measured amount of bleeding. Fluid extravasation rate was calculated as
net fluid balance minus the change in plasma volume over a defined period of time.
Intracranial pressure was monitored. Cerebral glucose, lactate, pyruvate and glycerol
were measured by microdialysis. After each experiment, total tissue water content was
determined in relevant organs. In paper V, cerebral tissue from cortex and thalamus in two
animals from each group, were examined by electron microscopy.
Net fluid balance was higher in the LP-group as compared with the C-group after 30 min of
CPB. Fluid extravasation rate tended to be higher in the LP-group. The animals of the LPgroup
did have higher tissue water content in the myocardium, skin and gastrointestinal tract
as compared with the control group.
Plasma volume was higher in the LP-group as compared with the HP-group after 60 minutes
of CPB. Net fluid balance and fluid extravasation rate did not differ between the two study
groups. Left myocardial tissue water content was slightly higher in the LP-group compared
with the HP-group.
Plasma volume was higher in the HF-group compared with the LF-group after 60 minutes of
CPB. During the initial phase of CPB, fluid extravasation rate was significantly higher in the
HF-group. The average net fluid balance during CPB was higher and the average fluid
extravasation rate tended strongly to be higher in the HF-group as compared with the LF group (P=0.07). Total tissue water content of the kidneys were higher in the HF-group and
tended to be higher in most other organs as compared with the LF-group.
Intracranial pressure increased in both groups during CPB. Intracerebral glucose decreased
while lactate-pyruvate ratio and cerebral glycerol increased significantly during CPB in the
LP-group as compared with pre-bypass values. The values remained stable and within normal
range in the HP-group.
Cerebral lactate was higher in LP-group as compared with HP-group during normothermic
CPB. Compared to baseline, cerebral glucose decreased and cerebral lactate, lactate-pyruvate
ratio and glycerol increased in the LP-group during normothermic CPB. The values remained
unchanged in the HP-group. Electron microscopy of cortical and thalamic tissue, showed a
higher frequency of altered mitochondria in the LP-group as compared with the HP-group.
Paper I-II suggest that different levels of MAP by use of nitroprusside, phentolamine
or norepinephrine have essentially no influence on fluid extravasation rate. An impact on net
fluid balance was found in paper I.
Paper III demonstrate that elevation of CPB flow rate to 110 ml/kg/min, may lead to
higher positive net fluid balance and probably higher fluid extravasation rate as compared
with a CPB flow rate of 80 ml/kg/min.
Plasma volume was affected by the use of these vasoactive agents and was
significantly higher in the study groups receiving phentolamine as compared with
norepinephrine. Indeed, plasma volume was also affected by CPB flow rate, resulting in
higher values in the experimental group with higher CPB flow rate.
In paper IV and V we found that a reduction of MAP to about 40 mmHg during CPB
by nitroprusside or phentolamine was associated with changes in cerebral markers of
metabolism and membrane integrity compatible with cerebral ischemia and membrane
degradation. Electron microscopic examination of cortical and thalamic tissue demonstrated a
high frequency of mitochondrial alterations in two animals with reduced MAP by
phentolamine in paper V.||en
|dc.publisher||The University of Bergen||eng
|dc.relation.haspart||Paper I: Acta Anaesthesiologica Scandinavica 49(9), Haugen, O.; Farstad, M.; Kvalheim, V.; Rynning, S. E.; Mongstad, A.; Husby, P., Low arterial pressure during cardiopulmonary bypass in piglets does not decrease fluid leakage, pp. 1255-1262. Copyright 2005 Acta Anaesthesiologica Scandinavica. Full text not available in BORA due to publisher restrictions. The published version is available at: <a href="http://dx.doi.org/10.1111/j.1399-6576.2005.00808.x" target="blank">http://dx.doi.org/10.1111/j.1399-6576.2005.00808.x</a>||eng
|dc.relation.haspart||Paper II: Perfusion 22(4), Haugen, O.; Farstad, M.; Kvalheim, V.; Hammersborg, S.; Husby, P., Intraoperative fluid balance during cardiopulmonary bypass: effects of different mean arterial pressures, pp. 273-278. Copyright 2007 SAGE Publications. Full text not available in BORA due to publisher restrictions. The published version is available at: <a href="http://dx.doi.org/10.1177/0267659107084148" target="blank">http://dx.doi.org/10.1177/0267659107084148</a>||eng
|dc.relation.haspart||Paper III: The Journal of Thoracic and Cardiovascular Surgery 134(3), Haugen, O.; Farstad, M.; Kvalheim, V.; Bøe, O.; Husby, P., Elevated flow rate during cardiopulmonary bypass is associated with fluid accumulation, pp. 587-593. Copyright 2007 The American Association for Thoracic Surgery. Full text not available in BORA due to publisher restrictions. The published version is available at: <a href="http://dx.doi.org/10.1016/j.jtcvs.2007.04.040" target="blank">http://dx.doi.org/10.1016/j.jtcvs.2007.04.040</a>||eng
|dc.relation.haspart||Paper IV: Scandinavian Cardiovascular Journal 40(1), Haugen, O.; Farstad, M.; Kvalheim, V. L.; Rynning, S. E.; Hammersborg, S.; Mongstad, A.; Husby, P., Mean arterial pressure about 40 mmHg during CPB is associated with cerebral ischemia in piglets, pp. 54-61. Copyright 2006 Taylor & Francis. Full text not available in BORA due to publisher restrictions. The published version is available at: <a href="http://dx.doi.org/10.1080/14017430500365185" target="blank"> http://dx.doi.org/10.1080/14017430500365185</a>||eng
|dc.relation.haspart||Paper V: Scandinavian Cardiovascular Journal 41(5), Haugen, O.; Farstad, M.; Myklebust, R.; Kvalheim, V.; Hammersborg, S.; Husby, P., Low perfusion pressure during CPB may induce cerebral metabolic and ultrastructural changes, pp. 331-338. Copyright 2007 Taylor & Francis. Full text not available in BORA due to publisher restrictions. The published version is available at: <a href="http://dx.doi.org/10.1080/14017430701393218" target="blank"> http://dx.doi.org/10.1080/14017430701393218</a>||eng
|dc.title||Interventions on arterial pressure and perfusion flow rate during cardiopulmonary bypass : effects on global fluid shifts, cerebral metabolic and structural markers in a porcine model||eng
|dc.subject.nsi||VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Generell kirurgi: 780||nob