Fluid filtration and vascular compliance during cardiopulmonary bypass: effects of two volatile anesthetics.

BACKGROUND: As intraoperative fluid accumulation may negatively impact post-operative organ function, strategies minimizing edema generation should be sought for. During general anesthesia, isoflurane in contrast to sevoflurane has been associated with increased fluid extravasation and edema generation. In this study, we tested sevoflurane against isoflurane with focus on vascular compliance and fluid shifts in an experimental cardiopulmonary bypass (CPB) model. METHODS: Sixteen pigs underwent 120 min of cardiopulmonary bypass with isoflurane or sevoflurane anesthesia. Net fluid balance, plasma volume, serum-electrolytes, serum-albumin, serum-protein, colloid osmotic pressures in plasma and interstitial fluid, hematocrit levels, and total tissue water content were recorded. Intra-abdominal and intracranial pressures were measured directly, and fluid extravasation rates were calculated. RESULTS: Fluid extravasation rate increased dramatically in both groups during initiation of cardiopulmonary bypass, with no group differences. The animals of the sevoflurane group needed significantly more fluid supplementation to maintain a constant reservoir volume in the CPB circuit during bypass. Plasma volumes prior to bypass were 56.5 ± 7.9 ml/kg (mean ± SD) and 58.7 ± 3.8 ml/kg in the isoflurane group and sevoflurane group, respectively. During bypass, plasma volumes in the isoflurane group decreased about 25%, and remained significantly lowered when compared to the sevoflurane group, where the values remained stable. CONCLUSIONS: No differences in fluid extravasation rates were observed between sevoflurane and isoflurane. The increased net fluid balance in the sevoflurane group during cardiopulmonary bypass was not associated with edema generation. Plasma volume was retained in the sevoflurane group, in contrast to the isoflurane group.

Portal cytokine response and metabolic markers in the early stages of abdominal sepsis in pigs.

BACKGROUND: The portal vein could play a major role in disseminating the local inflammation of acute bacterial peritonitis since it is responsible for the venous drainage of the gastrointestinal tract. We hypothesized that after peritoneal exposure to Escherichia coli, a gradient between the portal and systemic levels of cytokines would be expected. METHODS: Acute peritonitis was induced by depositing 200 ml of broth with live E. coli in the peritoneal cavity of the animals in the B-group (n = 7). They were then observed for 4 h and compared with a control group (C-group, n = 7). Tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-10 and vascular endothelial growth factor were measured repeatedly in the portal vein and the femoral artery. Portal vein metabolic markers (microdialysis), haemodynamics, biochemistry, plasma volume (PV), fluid shifts and total tissue water content were recorded or calculated. RESULTS: The intervention led to PV contraction, increased fluid extravasation, increased pulmonary vascular resistance and reduced urinary output in the B-group as compared with the C-group. The levels of glucose in the portal vein were reduced in both study groups with no between-group differences. The levels of TNF-α and IL-6 increased markedly in the portal vein as well as in the systemic circulation of the B-group, but no gradient was seen between them. The corresponding levels of TNF-α and IL-6 remained low and stable in the C-group. CONCLUSION: The portal vein appears to play a minor role in supplying TNF-α and IL-6 to the systemic circulation after peritoneal exposure to a substantial dose of E. coli.

Accelerometry May be Superior to EMG for Early Evaluation of Vocal Cord Function After Nerve Injury in a Pig Model.

OBJECTIVE: Vocal cord (VC) movement has been demonstrated by the use of accelerometry (ACC) to decrease in parallel with the electromyographic amplitude (EMG) during ongoing traction injury to the recurrent laryngeal nerve (RLN). When RLN function recovers, discrepancies between EMG and VC movement have been reported in clinical and experimental studies. The present study was conducted to clarify the actual relationship between EMG and VC movement measured by ACC during nerve recovery. METHODS: EMG obtained by continuous nerve monitoring (C-IONM) was compared with ACC during traction injury to the RLN, and throughout 40-min nerve recovery. A three-axis linear accelerometer probe was attached to the VC, and ACC data were registered as described. Traction damage was applied to the RLN until there was a 70% amplitude decrease from baseline EMG, or until loss of signal (LOS), that is, EMG values ≤100 µV. RESULTS: Thirty-two RLN from 16 immature pigs were studied. Correlation between EMG and ACC were calculated during nerve injury and nerve recovery. The mean correlations were for the 70% and LOS group from start to end of traction: 0.82 (±0.17) and 0.87 (±0.17), respectively. Corresponding correlation coefficients during 40-min recovery was 0.50 (±0.48) in the 70% group and 0.53 (±0.33) in the LOS group. CONCLUSION: There is a high correlation between EMG and VC movement during nerve injury, and a moderate correlation during early nerve recovery. EMG recovery after RLN injury ensures sufficient VC function as assessed by ACC. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:1485-1491, 2024.

Does ß2-adrenergic stimulation attenuate fluid extravasation during hypothermic cardiopulmonary bypass? An experimental study in pigs.

OBJECTIVES: Hypothermic cardiopulmonary bypass (CPB) is associated with increased fluid filtration, edema formation and, occasionally, organ dysfunction. Cold-induced reduction in endothelial barrier function may play a role. ß(2)-adrenergic activation elevates cellular cyclic adenosine monophosphate (cAMP) which maintains endothelial barrier properties. In this study, we tested whether ß-adrenergic stimulation could influence the increase in fluid extravasation observed during hypothermic CPB. MATERIALS AND METHODS: Fourteen pigs randomly received terbutaline infusion (T-group) (n=7) or a control infusion (C-group) (n=7). All animals were given 60 min of normothermic CPB, followed by 90 min of hypothermic CPB. Fluid input and losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum proteins and total tissue water content were measured and the fluid extravasation rates (FER) calculated. STATISTICS: by SPSS. Values presented as mean ± SD. Repeated measure analysis of variance was performed and a t-test used when appropriate. RESULTS: The commencement of normothermic CPB resulted in a 20% hemodilution, with an abrupt increase in fluid requirements during the first 10 min. FER increased from 0.18 (0.06) pre-bypass to 0.78 (0.27) ml/kg/min (T-group) (p=0.002) and from 0.16 (0.05) to 0.93 (0.26) ml/kg/min (C-group) (p<0.001) with no between-group differences. Thereafter, FER stabilized at a level of 0.32 (0.13) and 0.27 (0.14) ml/kg/min in the T-group and C-group, respectively. After the start of cooling, FER increased in the T-group to 0.55 (0.12) ml/kg/min (P=0.046) and in the C-group to 0.54 (0.13) ml/kg/min (P=0.006), with no between-group differences (P=0.738). CONCLUSION: In the present experimental study, we were unable to demonstrate any clinically relevant modulating effect of terbutaline on fluid extravasation during hypothermic cardiopulmonary bypass.

Isolation of interstitial fluid in skin during volume expansion: evaluation of a method in pigs.

The ability to isolate interstitial fluid (IF) from skin would make it possible to study the microcirculation and proteins in this environment both during normal and pathophysiological conditions. Traditional IF sampling using implanted wicks suffer from low volumes with risk of contamination by local inflammatory, intracellular, and vascular proteins. To sample larger volumes of true IF, a recently described tissue centrifugation method was compared with dry and wet wicks from porcine skin under normal conditions and following volume expansion. With all three methods, volume expansion caused a significant lowering of interstitial colloid osmotic pressure as expected, and the fluid was similar to plasma when compared using size-exclusion HPLC. The centrifugation method was superior with respect to isolating larger amounts of true IF for further studies. Mass spectrometry of IF sampled with centrifugation showed that most of the proteins reflected the major plasma proteins with some tissue-specific proteins like decorin, gelsolin, and orosomucoid-1. Lumican, pigment epithelium-derived factor, and fatty acid-binding protein 4 were only identified in IF after volume expansion, possibly reflecting a local response to increased fluid filtration. Tissue centrifugation to collect IF from skin should be applicable to both clinical and experimental studies on IF balance during different pathophysiological conditions and interventions.

Infusion of hypertonic saline/starch during cardiopulmonary bypass reduces fluid overload and may impact cardiac function.

OBJECTIVE: Peri-operative fluid accumulation resulting in myocardial and pulmonary tissue edema is one possible mechanism behind post-operative cardiopulmonary dysfunction. This study aimed to confirm an improvement of cardiopulmonary function by reducing fluid loading during an open-heart surgery. MATERIALS AND METHODS: Forty-nine elective CABG patients were randomized to an intraoperative infusion of hypertonic saline/hydroxyethyl starch (HSH group) or Ringer's solution (CT group). Both groups received 1 ml/kg/h of the study solution for 4 h after baseline values were obtained (PICCO transpulmonary thermodilution technique). Net fluid balance (NFB), hemodynamic and laboratory parameters were measured. RESULTS: NFB was four times higher in the CT group compared with the HSH group during the first 6 h post-operatively. The total fluid gain until the next morning was lower in the HSH group, 2993.9 (938.6) ml, compared with the CT group, 4298.7 (1059.3) ml (P<0.001). Normalized values (i.e., %-changes from the baseline) of the cardiac index and the global end diastolic volume index increased post-operatively in both groups. Both parameters were significantly higher at 6 h in the HSH group compared with CT group (P=0.002 and 0.005, respectively). Normalized values of the intrathoracic blood volume index were lower in the HSH group at 6 h post-operatively when compared with the CT group. The PaO(2)/FiO(2) ratio decreased similarly in both groups early post-operatively, but recovery tended to be more rapid in the HSH group. Although serum-sodium and serum-chloride levels were significantly higher in the HSH group, the acid-base parameters remained similar and within the normal range. CONCLUSIONS: An intraoperative infusion of HSH during cardiac surgery contributes to reduced fluid loading and an improvement in the post-operative cardiac performance. No adverse effects of the HSH infusion were observed.

Can the use of methylprednisolone, vitamin C, or alpha-trinositol prevent cold-induced fluid extravasation during cardiopulmonary bypass in piglets?

OBJECTIVE: Hypothermic cardiopulmonary bypass is associated with capillary fluid leakage, resulting in edema and occasionally organ dysfunction. Systemic inflammatory activation is considered responsible. In some studies methylprednisolone has reduced the weight gain during cardiopulmonary bypass. Vitamin C and alpha-trinositol have been demonstrated to reduce the microvascular fluid and protein leakage in thermal injuries. We therefore tested these three agents for the reduction of cold-induced fluid extravasation during cardiopulmonary bypass. METHODS: A total of 28 piglets were randomly assigned to four groups of 7 each: control group, high-dose vitamin C group, methylprednisolone group, and alpha-trinositol-group. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass was initiated in all animals and continued to 90 minutes. The fluid level in the extracorporeal circuit reservoir was kept constant at the 400-mL level and used as a fluid gauge. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit, and total water contents in different tissues were recorded, and the protein masses and the fluid extravasation rate were calculated. RESULTS: Hemodilution was about 25% after start of normothermic cardiopulmonary bypass. Cooling did not cause any further changes in hemodilution. During steady-state normothermic cardiopulmonary bypass, the fluid need in all groups was about 0.10 mL/(kg.min), with a 9-fold increase during the first 30 minutes of cooling (P <.001). This increased fluid need was due mainly to increased fluid extravasation from the intravascular to the interstitial space at a mean rate of 0.6 mL/(kg.min) (range 0.5-0.7 mL/[kg.min]; P <.01) and was reflected by increased total water content in most tissues in all groups. The albumin and protein masses remained constant in all groups throughout the study. CONCLUSION: Pretreatment with methylprednisolone, vitamin C, or alpha-trinositol was unable to prevent the increased fluid extravasation rate during hypothermic cardiopulmonary bypass. These findings, together with the stability of the protein masses throughout the study, support the presence of a noninflammatory mechanism behind the cold-induced fluid leakage seen during cardiopulmonary bypass.

Accidental hypothermia with cardiac arrest: complete recovery after prolonged resuscitation and rewarming by extracorporeal circulation.

A 51-year-old male remained immersed in sea water (6 degrees C) for 40 min. Brought ashore, the ECG showed asystole. Advanced life support was immediately commenced. On arrival in hospital his rectal temperature was 27 degrees C, but continued to fall to 24 degrees C. The ECG remained isoelectric. Cardiopulmonary resuscitation was continued until extracorporeal circulation was established 190 min after rescue. Upon rewarming ventricular fibrillation occurred which was converted to sinus rhythm with a bolus of lignocaine followed by D.C. conversion at 31.5 degrees C. When rewarming was complete after 60 min, signs of severe heart failure became evident. Sternotomy and pericardiotomy were performed to exclude cardiac tamponade. After 60 min of re-perfusion the patient was be weaned from bypass supported by a high-dose vasopressor infusion and nitroglycerine. He was discharged after 13 days with no evidence of any permanent organ damage. Given the advantage of providing circulatory support, extracorporeal circulation may be useful when rewarming hypothermic victims with cardiac arrest.

Rewarming from accidental hypothermia by extracorporeal circulation. A retrospective study.

OBJECTIVE: Twenty-six patients with accidental hypothermia combined with circulatory arrest or severe circulatory failure were rewarmed to normothermia by use of extracorporeal circulation (ECC). The aim of the present study was to evaluate our results. PATIENTS AND METHODS: The treatment of six female and 20 male patients (median age: 26.7 years; range 1.9--76.3 years) rewarmed in the period 1987--2000 was evaluated retrospectively. Hypothermia was related to immersion/submersion in cold water (n=17), avalanche (n=1) or prolonged exposure to cold surroundings (n=8). Prior to admission, the trachea was intubated and cardiopulmonary resuscitation (CPR) initiated in all patients with cardiorespiratory arrest (n=22), whereas in those with respiration/circulation (n=4) only oxygen therapy via a face mask was given. RESULTS: Nineteen of the 26 patients were weaned off ECC whereas seven died because of refractory respiratory and/or cardiac failure. Eight of the 19 successfully weaned patients were discharged from hospital after a median of 10 days. One patient died 3 days after circulatory arrest (complete atrioventricular block) resulting in severe cerebral injury. The remaining ten patients died following 1--2 days due to severe hypoxic brain injury (n=5), cerebral bleeding (n=1) or irreversible cardiopulmonary insufficiency (n=4). Based on the reports from the site of accident, two groups of patients were identified: the asphyxia group (n=15) (submersions (n=14); avalanche accident (n=1)) and the non-asphyxia group (n=11) (patients immersed or exposed to cold environment). Seven intact survivors discharged from hospital belonged to the non-asphyxia group whereas one with a severe neurological deficit was identified within the asphyxia group. CONCLUSION: Patients with non-asphyxiated deep accidental hypothermia have a reasonable prognosis and should be rewarmed before further therapeutic decisions are made. In contrast, drowned patients with secondary hypothermia have a very poor prognosis. The treatment protocol under such conditions should be the subject for further discussion.

Effects of velocity distribution, diameter measurement and velocity tracing on the accuracy of cardiac output measurement by pulsed Doppler echocardiography in the aortic annulus of pigs.

UNLABELLED: The accuracy of cardiac output measurement by pulsed Doppler echocardiography can be affected by several factors, such as the velocity distribution, the measurement of diameter and the method of tracing the pulsed Doppler flow spectrum. This experimental study was designed to find the most accurate way of measuring cardiac output in consideration of all these factors. In 10 open-chest normal piglets (24 +/- 1 kg), the velocity distribution in the aortic annulus was evaluated using Doppler colour flow mapping. Cardiac output was measured by pulsed Doppler echocardiography in the aortic annulus by a number of different ways and compared to the simultaneous result of the thermodilution method. All measurements were made at baseline, after intravenous injection of esmolol and during infusion of dobutamine. RESULTS: (1) the velocity distribution in the aortic annulus in the piglets was just slightly skewed during all three haemodynamic situations; (2) The in vivo measurements of the diameter of the aortic annulus varied throughout the ejection period, but the average of the three largest diameter measurements was almost identical with the diameter measured in vitro (18.5 +/- 0.3 mm vs. 18.6 +/- 0.2 mm; p = NS); (3) Tracing the maximal velocity of the pulsed Doppler flow spectrum produced a cardiac output that was 18%-21% higher than that measured by the thermodilution method, while tracing the brightest part (modal velocity) of the pulsed Doppler flow spectrum yielded a cardiac output very close to the thermodilution measurement. CONCLUSION: The velocity distribution in the aortic annulus in the piglet has little effect on cardiac output measurement by pulsed Doppler. Using the maximal measurable diameter of the aortic annulus and tracing the brightest part of the pulsed Doppler flow spectrum yielded the cardiac output closest to that measured by the thermodilution method.

Sampling of interstitial fluid and measurement of colloid osmotic pressure (COPi) in pigs: evaluation of the wick method.

The wick method for sampling of interstitial fluid from subcutis was applied in fluid balance studies in young pigs. Colloid osmotic pressure was measured in serum (COPs) and interstitial fluid (COPi) using a membrane colloid osmometer. Our aims were to determine the 'true' COPi, and to find the optimal duration of wick implantation. In series I (n = 6) a 'crossover' experiment was performed using wicks soaked in different priming solutions (non-diluted and diluted serum protein solutions or isotonic salt solution). Circulatory arrest was induced just before wick insertion in order to eliminate the vascular part of the acute inflammation. In series II (n = 6) wicks were removed in sequence after 60, 90, 120 and 180 min sampling time in anaesthetized pigs in vivo. COPs, COPi and haematocrit (HCT) together with haemoglobin (Hgb), serum albumin and total protein concentrations were determined in the same animals. In series I average COPs and COPi were 13.7 (1.4) and 7.2 (1.4) mmHg respectively (SD). In series II the optimal wick implantation times were estimated to be 60-90 min for wicks soaked in diluted protein solution, and 90-120 min for dry and saline-soaked wicks. COPs averaged 13.0 (0.7) mmHg, HCT 30.0 (1.6)%, Hgb 8.3 (0.9) g/dl, s-albumin 22.7 (0.6) g/l and s-protein 47.3 (2.3) g/l. Compared to commonly reported reference values, we found surprisingly low values for most of the measured variables. This may be related to the fact that we used immature pigs. An analysis of the validity of the wick method based on our own results and published reports is presented. We conclude that sampling of interstitial fluid with subcutaneous wicks is easy to perform in young pigs. However, the COP-values measured in wick fluid have to be carefully evaluated especially when sampling is performed in vivo.

Midazolam-fentanyl-isoflurane anaesthesia is suitable for haemodynamic and fluid balance studies in pigs.

The domestic pig is a useful model in certain areas of biomedical research. Effective use of this species is often encumbered by lack of reference values in conscious as well as anaesthetized animals. Anaesthesia itself influences physiological and biological variables; the anaesthetic technique often affects experimental results. The relationship between anaesthesia and haemodynamics is well characterized in man, but less established in pigs. We studied the effect of midazolam-fentanyl-isoflurane anaesthesia in six immature, male, domestic pigs (Norwegian landrace). Haemodynamic variables (heart rate, arterial systolic, mean, diastolic pressures, pulmonary systolic, mean, diastolic pressures, pulmonary capillary wedge pressure), tissue perfusion, lymph flow (thoracic duct) were recorded for 3 h in animals with open chest through midline sternotomy. Variables relevant to fluid balance, e.g. interstitial hydrostatic pressure (Pi), serum-colloid osmotic pressure (s-COP) and serum-albumin (s-albumin) and -protein (s-protein) concentrations were measured. With the chosen anaesthetic technique haemodynamic variables, including lymph flow, and laboratory variables remained constant during the study period. Most variables were similar to conditions in humans. In contrast to adult humans exposed to the same anaesthetic technique, these pigs had lower haemoglobin-, s-albumin- and s-protein concentrations. A finding which may reflect immaturity. Liver and lung perfusion decreased significantly during the study period whereas perfusion of the other organs studied remained constant. Lack of responses to defined noxious stimuli during the study period suggest adequate analgesia. We conclude that midazolam, fentanyl and isoflurane provide cardiovascular stability including normal microvascular fluid exchange, which are essential elements for securing the quality of results obtained during cardiovascular research in anaesthetized pigs.

Determination of plasma volume in anaesthetized piglets using the carbon monoxide (CO) method.

Based on measurements of the circulating red blood cell volume (V(RBC)) in seven anaesthetized piglets using carbon monoxide (CO) as a label, plasma volume (PV) was calculated for each animal. The increase in carboxyhaemoglobin (COHb) concentration following administration of a known amount of CO into a closed circuit re-breathing system was determined by diode-array spectrophotometry. Simultaneously measured haematocrit (HCT) and haemoglobin (Hb) values were used for PV calculation. The PV values were compared with simultaneously measured PVs determined using the Evans blue technique. Mean values (SD) for PV were 1708.6 (287.3)ml and 1738.7 (412.4)ml with the CO method and the Evans blue technique, respectively. Comparison of PVs determined with the two techniques demonstrated good correlation (r = 0.995). The mean difference between PV measurements was -29.9 ml and the limits of agreement (mean difference +/-2SD) were -289.1 ml and 229.3 ml. In conclusion, the CO method can be applied easily under general anaesthesia and controlled ventilation with a simple administration system. The agreement between the compared methods was satisfactory. Plasma volume determined with the CO method is safe, accurate and has no signs of major side effects.

Percutaneous left ventricular assist device can prevent acute cerebral ischaemia during ventricular fibrillation.

AIMS: A percutaneous left ventricular assist device has been shown to be able to perfuse cardiac and cerebral tissues during cardiac arrest and may be a useful supplement to current methods in resuscitation. We wished to assess device-assisted circulation during cardiac arrest with microspheres injections and continuous end-tidal CO(2) monitoring, and used cerebral microdialysis to detect ischaemia in the brain. METHODS: 12 anaesthetised pigs had microdialysis and pressure catheters implanted via craniotomy. The percutaneous assist device was deployed transfemorally. Ventricular fibrillation was induced by angioplasty-balloon occlusion of the left coronary artery. Cerebral microdialysis samples representing 0-20 and 20-40 min of cardiac arrest with assisted circulation were analysed for markers of cerebral injury (glucose, pyruvate, lactate, and glycerol). RESULTS: Microdialysis showed no ischaemic changes after 20 min of cardiac arrest (P=NS to Baseline for glucose, glycerol, lactate, pyruvate and lactate/pyruvate ratio) in subjects with maintained end-tidal CO(2) values above 1.3 kPa (10 mmHg). After 40 min only lactate showed a significant change compared to Baseline (P<0.05). Microspheres flow to the brain was 57% and myocardial flow was 72% compared to Baseline after 15 min (P<0.05). After 45 min flow declined to 22% and 40% of Baseline, respectively (P=NS vs. 15 min). CONCLUSIONS: A percutaneous left ventricular assist device may prevent ischaemic cerebral injury during cardiac arrest for a limited time. Cerebral injury and tissue perfusion were indicated by end-tidal CO(2).

A hyperosmolar-colloidal additive to the CPB-priming solution reduces fluid load and fluid extravasation during tepid CPB.

Cardiopulmonary bypass(CPB) is associated with fluid overload. We hypothesized that fluid gain during CPB could be reduced by substituting parts of a crystalloid prime with 7.2% hypertonic saline and 6% poly (O-2-hydroxyethyl) starch solution (HyperHaes). 14 animals were randomized to a control group (Group C) or to Group H. CPB-prime in Group C was Ringer's solution. In group H, 4 ml/kg of Ringer's solution was replaced by the hypertonic saline/hydroxyethyl starch solution. After 60 min stabilization, CPB was initiated and continued for 120 min. All animals were allowed drifting of normal temperature (39.0 degrees C) to about 35.0 degrees C. Fluid was added to the CPB circuit as needed to maintain a 300-ml level in the venous reservoir. Blood chemistry, hemodynamic parameters, fluid balance, plasma volume, fluid extravasation rate (FER), tissue water content and acid-base parameters were measured/calculated. Total fluid need during 120 min CPB was reduced by 60% when hypertonic saline/hydroxyethyl starch solution was added to the CPB prime (p < 0.01). The reduction was related to a lowered FER. The effect was most pronounced during the first 30 min on CPB, with 0.6 (0.43) (Group H) compared with 1.5 (0.40) ml/kg/min (Group C) (p < 0.01). Hemodynamics and laboratory parameters were similar in both groups. Serum concentrations of sodium and chloride increased to maximum levels of 148 (1.5) and 112 (1.6) mmol/l in Group H. To conclude: addition of 7.2% hypertonic saline and 6% poly (O-2-hydroxyethyl) starch solution to crystalloid CPB prime reduces fluid needs and FER during tepid CPB.

Reduced fluid gain during cardiopulmonary bypass in piglets using a continuous infusion of a hyperosmolar/hyperoncotic solution.

BACKGROUND: The aim of this study was to evaluate how a continuous infusion of a hyperosmolar/hyperoncotic solution influences fluid shifts and intracranial pressure during cardiopulmonary bypass in piglets. METHODS: Fourteen animals, randomized to the control (CT) group or the hypertonic saline/hydroxyethyl starch (HyperHaes) (HSH) group, received acetated Ringer's solution as prime and supplemental fluid. The HSH group received, in addition, HyperHaes 1 ml/kg/h. After 1 h of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (28 degrees C) was initiated and continued for 90 min. Fluid balance, plasma volume, tissue water content, acid-base parameters and intracranial pressure were recorded, and protein masses and fluid extravasation rates were calculated. RESULTS: At the start of normothermic cardiopulmonary bypass, the fluid extravasation rates (ml/kg/min) increased from 0.19 (0.06) to 1.57 (0.71) and 0.19 (0.09) to 0.82 (0.14) in the CT and HSH groups, respectively, with no between-group differences (P = 0.081) During hypothermic cardiopulmonary bypass, the fluid extravasation rates (ml/kg/min) increased from 0.19 (0.14) to 0.51 (0.10) (P < 0.01) and 0.15 (0.08) to 0.33 (0.08) (P < 0.05), respectively, with significantly lower extravasation rates in the HSH group (P < 0.01). In the HSH group, the total fluid gain during cardiopulmonary bypass decreased by about 50% (P < 0.05) and the tissue water content was significantly lower in the left and right heart as well as in the lungs. The intracranial pressure remained stable in the HSH group, but increased in the CT group. CONCLUSIONS: A continuous infusion of HSH (HyperHaes) during cardiopulmonary bypass reduced the fluid extravasation rate and the total fluid gain during bypass. No electrolyte or acid-base disturbances were present. The intracranial pressure remained stable in the HSH group.

Low arterial pressure during cardiopulmonary bypass in piglets does not decrease fluid leakage.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with increased fluid filtration occasionally leading to post-operative organ dysfunction. One of the factors determining fluid filtration is the capillary hydrostatic pressure which depends on arterial pressure, venous pressure and pre- to post-capillary resistance ratio. The purpose of this study was to assess whether lowering of the mean arterial pressure and/or the central venous pressure could reduce fluid extravasation during normothermic and hypothermic CPB. METHODS: Seven piglets were given nitroprusside to a mean arterial pressure of 35-40 mmHg during 60 min of normothermic and 90 min of hypothermic CPB (LP group). They were compared with a control group (C group, n = 7) without blood pressure interventions. Blood chemistry, net fluid balance, plasma volume, colloid osmotic pressure in plasma and interstitial fluid, intravascular protein masses, fluid extravasation rate and total tissue water content were measured or calculated. RESULTS: Mean arterial pressure was significantly lower in the LP group than in the C group during CPB. Plasma volume tended to increase in the LP group (P > 0.05), but remained essentially unchanged in the C group. Net fluid balance in the LP group was more positive than in the C group 30 min after CPB start [1.02 (0.15) vs. 0.56 (0.13) ml/kg/min (Mean (SEM) P < 0.05)]. Fluid extravasation rate tended to be higher in the LP group and total tissue water content of the gastrointestinal tract, left myocardium and skin was significantly elevated compared with the C group. CONCLUSION: During CPB, lowering of the mean arterial pressure using nitroprusside did not reduce fluid extravasation. On the contrary, the data may implicate an increase in edema formation during low pressure CPB.

Fluid shift is moderate and short-lived during acute crystalloid hemodilution and normothermic cardiopulmonary bypass in piglets.

BACKGROUND: Crystalloids are commonly used as priming solutions during cardiopulmonary bypass (CPB). Consequently, hemodilution is a regular occurrence at the start of a CPB. This study describes the time-course variations of hemodynamic parameters, plasma volume (PV) and fluid exchange following crystalloid hemodilution at start of normothermic CPB. METHODS: Forty-five anesthetized piglets were given 60-min normothermic CPB. Ringer's solution was used as priming solution and maintenance fluid. Fluid input/losses, PV, colloid osmotic pressures (plasma/interstitium), hematocrit, and s-proteins were measured, and fluid extravasation rates (FER) and intravascular protein-masses calculated. RESULTS: Start of CPB resulted in a 25-30% hemodilution. To keep the fluid level of the CPB-reservoir constant after start of bypass, fluid addition [2.08 +/- 0.36 (mean +/- SEM) ml kg(-1) min(-1)] was necessary during the first 5 min. Thereafter the fluid needs to be leveled off [0.17 +/- 0.03 ml kg(-1) min(-1) (10-60 min), P < 0.001]. Fluid extravasation rate increased immediately following hemodilution from a baseline value of 0.08 +/- 0.01 to 1.75 +/- 0.34 ml kg(-1) min(-1) with a delayed decrease compared to fluid additions, to reach a 'steady-state' level of 0.22 +/- 0.03 ml kg(-1) min(-1) after 30 min (P < 0.001). Differences in time-course variations between fluid added and fluid extravasated were accompanied by changes in PV and mean arterial pressure. The colloid osmotic gradient decreased about 50% throughout the study and could partly explain the increased FER. CONCLUSION: Acute crystalloid hemodilution contributes to fluid overload during normothermic CPB. The resulting increase in fluid extravasation is, however, moderate, short-lived and levels off to baseline values within 30 min.

Studies on the efflux of metalloporphyrin from isolated rat liver mitochondria. Effect of respiratory substrates and metabolic inhibitors.

Intramitochondrially synthesized Co-deuteroporphyrin is released to the incubation medium at a rate inversely correlated to the energy state of the mitochondria; i.e. the rate of efflux increases when substrate is depleted, respiration inhibited or the mitochondria are uncoupled. The efflux of Co-deuteroporphyrin from mitochondria remains low as long as the residual membrane potential is above one-third that of maximally energized mitochondria. Globin enhances the efflux of Co-deuteroporphyrin not only from mitochondria depleted of substrates [Husby & Romslo (1980) Biochem. J. 188, 459-465], but also from maximally energized mitochondria. The results provide further evidence for a co-operative mechanism between the mitochondria and their surroundings for the mobilization of metalloporphyrin from mitochondria.