Insulin-like growth factor 1 improves the relationship between systemic oxygen consumption and delivery in piglets after cardiopulmonary bypass

OBJECTIVE: We sought to assess the effects of insulin-like growth factor 1 on the balance between systemic oxygen consumption and oxygen delivery after cardiopulmonary bypass in piglets. METHODS: Twelve piglets weighing 4.5 to 8.3 kg undergoing hypothermic (28 degrees C) cardiopulmonary bypass for 70 to 120 minutes with 40 minutes of aortic crossclamping were studied before and during the first 6 hours after cardiopulmonary bypass. Oxygen consumption was continuously measured by an indirect calorimeter, Deltatrac II MBM-200 Metabolic Monitor (Datex Division Instrumentarium, Helsinki, Finland). Oxygen delivery and cardiac output were calculated from oxygen consumption and the arterial and mixed venous oxygen contents sampled before and every 30 minutes after cardiopulmonary bypass. Oxygen extraction ratio was derived by the ratio of oxygen consumption to oxygen delivery. Arterial blood lactate was measured before and every 30 minutes after cardiopulmonary bypass. Six animals were randomly assigned to receive an intravenous infusion of insulinlike growth factor 1 at 1.2 mg/h from 1 to 6 hours after cardiopulmonary bypass; the remaining 6 served as a control group. RESULTS: Relative to the control group, intravenous infusion of insulin-like growth factor 1 significantly reduced oxygen consumption (P =.02) and increased cardiac output (P =.016) and oxygen delivery (P =.049) during the first 6 hours after surgery with hypothermic cardiopulmonary bypass. As a result, oxygen extraction was significantly decreased (P =.012). CONCLUSIONS: Intravenous infusion of insulin-like growth factor 1 improved oxygen transport by reducing oxygen consumption as well as increasing cardiac output and oxygen delivery during the first 6 hours after cardiopulmonary bypass in piglets. This may have important clinical implications for the care of critically ill children after surgery with cardiopulmonary bypass.     

Cerebral effects of anaesthesia and hypothermia

Cerebral blood flow, cerebral oxygen and glucose consumption, and cerebral lactate and pyruvate release were measured; spectral analysis of the EEG was recorded in 10 male patients who had coronary artery bypass surgery. The measurements were taken to evaluate the effects of fentanyl-midazolam anaesthesia during normothermia and during hypothermic nonpulsatile cardiopulmonary bypass at 26 degrees C venous blood temperature, when a temperature-corrected PaCO2-value of 5.3 kPa was maintained. Anaesthesia with fentanyl 7 micrograms/kg and midazolam 200 micrograms/kg as induction doses, followed by infusions of fentanyl 0.15 micrograms/kg/minute and midazolam 3 micrograms/kg/minute, was characterised by a decrease in fast-wave activity and an increase in high-amplitude, slow-wave activity in the EEG. There was also a decrease in cerebral blood flow (38%), oxygen consumption (22%) and glucose consumption (25%), while lactate and pyruvate production remained unchanged. Hypothermia of 26 degrees C venous blood temperature suppressed EEG almost completely and decreased oxygen and glucose consumption by a further 61% and 54%, respectively, with no changes in lactate and pyruvate production while cerebral blood flow increased by 145%. These results show that the effects of fentanyl-midazolam anaesthesia on cerebral metabolism are enhanced during hypothermic cardiopulmonary bypass while the influence of anaesthesia on cerebral blood flow is overshadowed by the practice of a temperature-corrected acid-base management.     

Superior hepatic mitochondrial oxidation-reduction state in normothermic cardiopulmonary bypass

OBJECTIVE: This study is the first comparative investigation of hepatic blood flow and oxygen metabolism during normothermic and hypothermic cardiopulmonary bypass. METHODS: Twenty-four patients undergoing coronary bypass operations were randomly divided into 2 groups according to their perfusion temperatures, either normothermia (36 degrees C) or hypothermia (30 degrees C). The clearance of indocyanine green was measured at 3 points. Arterial and hepatic venous ketone body ratios (an index of mitochondrial redox potential) and hepatic venous saturation were measured. RESULTS: Hepatic blood flow in both groups was identical before, during, and after cardiopulmonary bypass (normothermia, 499 +/- 111, 479 +/- 139, and 563 +/- 182 mL/min, respectively; hypothermia, 476 +/- 156, 491 +/- 147, and 560 +/- 202 mL/min, respectively). The hepatic venous saturation levels were significantly lower during cardiopulmonary bypass in the normothermic group (normothermia, 41% +/- 13%; hypothermia, 61% +/- 18%; P <.01), indicating a higher level of oxygen extraction use. The arterial ketone body ratio in the hypothermic group decreased severely after the onset of cardiopulmonary bypass (P <.01) and did not return to its subnormal value (>0.7) until the second postoperative day. However, the reduction in arterial ketone body ratio was less severe in the normothermic group. The difference in hepatic venous ketone body ratios was more obvious, and the hepatic venous ketone body ratios in the normothermic group were statistically superior to those of the hypothermic group throughout the course (P <.05-.01). CONCLUSIONS: Normothermic cardiopulmonary bypass provides adequate liver perfusion and results in a better hepatic mitochondrial redox potential than hypothermic cardiopulmonary bypass. Because arterial ketone body ratios reflect hepatic energy potential, normothermia was considered to be physiologically more advantageous for hepatic function.     

Optimal perfusion flow rate for the brain during deep hypothermic cardiopulmonary bypass at 20 degrees C. An experimental study

The relationship between the perfusion flow rate and cerebral oxygen consumption during deep hypothermic cardiopulmonary bypass at 20 degrees C was investigated in dogs. In 10 dogs the perfusion flow rate was decreased in steps from 100 to 60, 30, and 15 ml/kg/min every 30 minutes. Although cerebral blood flow decreased as perfusion flow rate decreased, the ratio of cerebral blood flow to the perfusion flow rate increased significantly (p less than 0.05) at a perfusion flow rate of 15 ml/kg/min compared to that at a perfusion flow rate of 100 or 60 ml/kg/min. The arterial-sagittal sinus blood oxygen content difference increased as perfusion flow rate decreased. Consequently, cerebral oxygen consumption did not vary significantly at perfusion flow rates of 100 (0.48 +/- 0.10), 60 (0.43 +/- 0.14), and 30 ml/kg/min (0.44 +/- 0.12 ml/100 gm/min), and it decreased significantly to 0.31 +/- 0.22 ml/100 gm/min at a perfusion flow rate of 15 ml/kg/min. In five dogs the perfusion flow rate was decreased in one step from 100 to 15 ml/kg/min, and after 60 minutes' perfusion at a perfusion flow rate of 15 ml/kg/min, the perfusion flow rate was returned to 100 ml/kg/min. Cerebral oxygen consumption decreased significantly during 60 minutes' perfusion at a perfusion flow rate of 15 ml/kg/min and did not return to its initial value after the perfusion flow rate was returned to 100 ml/kg/min. These data indicate that the optimal perfusion flow rate for the brain during deep hypothermic cardiopulmonary bypass at 20 degrees C appears to be 30 ml/kg/min, with a possible oxygen debt in the brain resulting in anaerobic metabolism if the perfusion flow rate is kept at 15 ml/kg/min or less.     

Neuromuscular blockade significantly decreases systemic oxygen consumption during hypothermic cardiopulmonary bypass.

The design limits of cardiopulmonary bypass (CPB) equipment and the performance characteristics of membrane oxygenators may place the patient with a very large body surface area at risk for incurring an oxygen debt during CPB. The influence of resting muscle tone on systemic oxygen consumption (VO2) during hypothermic (25 to 28 degrees C) nonpulsatile CPB was calculated using the Fick equation prior to, and following, neuromuscular blockade (pancuronium, 0.15 mg/kg, n = 10; or succinylcholine, 1.5 mg/kg, n = 7). During hypothermic CPB, initial VO2 was 70 +/- 30 mL/min/m2, which was significantly reduced (by 30%) to 49 +/- 13 mL/min/m2 after onset of neuromuscular blockade, with a concomitant increase in mixed venous O2 saturation from 73% +/- 18% to 83% +/- 14%. Choice of muscle relaxant did not influence the change in VO2. With succinylcholine there was a return of VO2 to control values with recovery of neuromuscular function. This study demonstrates that in the unconscious and unmoving patient during hypothermic CPB, administration of muscle relaxants to achieve complete neuromuscular blockade can significantly reduce systemic oxygen consumption.     

Isoflurane and hypothermic cardiopulmonary bypass: vasodilation without metabolic effects

During cardiopulmonary bypass, isoflurane may have beneficial effects on systemic oxygen uptake and vascular resistance. For this reason, the effects of isoflurane during low-flow (1.6 L/min/m2), hypothermic (27 degrees to 29 degrees C) cardiopulmonary bypass on systemic hemodynamics and oxygen uptake were studied in 20 patients in a cross-over experiment. Mean arterial and central venous pressures were measured during two consecutive periods of 10 minutes' duration. Blood samples were aspirated at the end of each period from the arterial and venous lines and analyzed for oxygen content. The concentration of isoflurane in the arterial samples was also determined. Systemic oxygen uptake and vascular resistance were calculated. Isoflurane had no significant effect on systemic oxygen uptake. Significant inverse relationships between blood isoflurane concentration and both mean arterial pressure and systemic vascular resistance were found. It is concluded that isoflurane is a vasodilator under the abnormal conditions of hypothermic cardiopulmonary bypass, but has no effect on systemic oxygen uptake.     

Oxygen consumption after cardiopulmonary bypass surgery in children: determinants and implications

OBJECTIVE: We sought to assess oxygen consumption and its determinants in children shortly after undergoing cardiopulmonary bypass operations. METHODS: Twenty children, aged 2 months to 15 years (median, 3.75 years), undergoing hypothermic cardiopulmonary bypass operations were studied during the first 4 hours after arrival in the intensive care unit. Central and peripheral temperatures were monitored. Oxygen consumption was continuously measured by using respiratory mass spectrometry. Oxygen delivery was calculated from oxygen consumption and arterial and mixed venous oxygen contents, which were sampled every 30 minutes. Oxygen extraction was derived by the ratio of oxygen consumption and oxygen delivery. Arterial blood lactate levels were measured every 30 minutes. RESULTS: There was a correlation between oxygen consumption and age in patients older than 3 months (r = -0.76). Mean oxygen consumption increased by 14.7% during the study. The increase in oxygen consumption was correlated with the increase in central temperature (r = 0.73). Nine patients had an arterial lactate level above 2 mmol/L on arrival. There were no significant differences in oxygen consumption, oxygen delivery, and oxygen extraction between the group with lactate levels between 2 and 3 mmol/L and the groups with normal lactate levels both on arrival and at 2 hours. One patient with a peak lactate level of 6.8 mmol/L had initially low oxygen delivery (241.3 mL. min(-1). m(-2)). CONCLUSIONS: During the early hours after a pediatric cardiac operation, the increase in oxygen consumption is mainly attributed to the increase in central temperature. Oxygen consumption is negatively related to age. Mild lactatemia is common and does not appear to reflect oxygen delivery or oxygen consumption or a more complicated recovery.     

Lamotrigine attenuates cortical glutamate release during global cerebral ischemia in pigs on cardiopulmonary bypass

BACKGROUND: The dose-response effects of pretreatment with lamotrigine (a phenyltriazine derivative that inhibits neuronal glutamate release) in a porcine cerebral ischemia model during cardiopulmonary bypass were studied. METHODS: Sagittal sinus catheters and cortical microdialysis catheters were inserted into anesthetized pigs. Animals undergoing normothermic cardiopulmonary bypass were pretreated with lamotrigine 0, 10, 25, or 50 mg/kg (n = 10 per group). Fifteen minutes of global cerebral ischemia was produced, followed by 40 min of reperfusion and discontinuation of cardiopulmonary bypass. Cerebral oxygen metabolism was calculated using cerebral blood flow (radioactive microspheres) and arterial-venous oxygen content gradients. Concentrations of microdialysate glutamate and aspartate were quantified; electroencephalographic signals were recorded. After cardiopulmonary bypass, blood and cerebrospinal fluid were sampled for S-100B protein, and a biopsy was performed on the cerebral cortex for metabolic profile. RESULTS: Lamotrigine caused dose-dependent reductions in systemic vascular resistance so that additional fluid was required to maintain venous return. Concentrations of glutamate and aspartate did not change during reperfusion after 50 mg/kg lamotrigine in contrast to fivefold and twofold increases, respectively, with lower doses. There were no intergroup differences in cerebral metabolism, electroencephalographic scores, cortical metabolites, brain lactate, or S-100B protein concentrations in the cerebrospinal fluid and blood. CONCLUSIONS: Lamotrigine 50 mg/kg significantly attenuated excitatory neurotransmitter release during normothermic cerebral ischemia during cardiopulmonary bypass without improving other neurologic parameters. Lamotrigine caused arterial and venous dilation, which limits its clinical usefulness.     

The effect of acid-base management on the oxygen uptake of the human body during hypothermic extracorporeal circulation]

The effects of two different systems of acid-base management on whole-body oxygen consumption during and following hypothermic cardiopulmonary bypass were investigated in 42 patients undergoing coronary artery bypass grafting or valve replacement surgery. In group I (22 patients) pH-stat management and in group II (20 patients) alpha-stat management was used. METHODS. Anesthesia was performed with fentanyl, midazolam, and pancuronium bromide. Halothane was added whenever MAP exceeded 100 mmHg. Cardiopulmonary bypass was conducted with a membrane oxygenator and a roller pump. Pump flow varied between 2 and 2.5 l/min per m2 body surface area. Once patients had been initially cooled down to a venous blood temperature of 27 degrees C they were kept stable between 28 degrees C and 30 degrees C during the ischemic phase. Measurements were performed after sternotomy during normothermia (control values) and every 15 min from the start until termination of bypass. RESULTS AND DISCUSSION. Neither hemodynamic parameters (MAP, CI, SVR) nor rectal or skin temperatures differed significantly between the two groups during the entire study period. Although at 27 degrees C oxygen availability fell by 43% and 35% in groups I and II, respectively, mixed venous oxygen saturation was significantly elevated compared with the control value, because of a decrease of 60% and 51%, respectively, in the arterio-venous oxygen content difference and of 62% and 55%, respectively, in oxygen consumption. Rewarming led to normalization of the metabolic parameters except for oxygen availability, which was still decreased as a result of low hemoglobin content. After termination of the bypass oxygen consumption increased steadily, which may have been due either to the beginning of shivering or to repayment of an oxygen debt caused by hypothermic bypass. As statistically significant differences were detected between the two groups in metabolic parameters during the course of the investigation, the hypothesis of Rahn and Reeves [2, 3], according to which oxygen consumption must be expected to be higher with alpha-stat than with pH-stat management, could not be verified by this study.     

Warming during cardiopulmonary bypass is associated with jugular bulb desaturation.

The objective of this study was to characterize cerebral venous effluent during normothermic nonpulsatile cardiopulmonary bypass. Thirty-one (23%) of 133 patients met desaturation criteria (defined as jugular bulb venous oxygen saturation less than or equal to 50% or jugular bulb venous oxygen tension less than or equal to 25 mm Hg) during normothermic cardiopulmonary bypass (after hypothermic cardiopulmonary bypass at 27 degrees to 28 degrees C). Cerebral blood flow, calculated using xenon 133 clearance methodology, was significantly (p less than 0.005) higher in the saturated group (33.7 +/- 10.3 mL.100 g-1.min-1) than in the desaturated group (26.2 +/- 6.9 mL.100 g-1.min-1), whereas the cerebral metabolic rate for oxygen was significantly lower (p less than 0.005) in the saturated group (1.28 +/- 0.39 mL.100 g-.min-1) than in the desaturated group (1.52 +/- 0.36 mL.100 g-1.min-1) at normothermia. The arteriovenous oxygen difference at normothermia was lower in the saturated group (3.92 +/- 1.12 mL/dL) than in the desaturated group (5.97 +/- 1.05 mL/dL). Neuropsychological testing was performed in 74 of the 133 patients preoperatively and on day 7 postoperatively. There was a general decline in mean scores of all tests postoperatively in both groups with no significant difference between the groups. We conclude that cerebral venous desaturation represents a global imbalance in cerebral oxygen supply-demand that occurs during normothermic cardiopulmonary bypass and may represent transient cerebral ischemia. These episodes, however, are not associated with impared neuropsychological test performance as compared with the performance of patients with no evidence of desaturation.     

Renal hypoxanthine balance in cardiac surgery: effects of felodipine

OBJECTIVE: To test the hypothesis that felodipine, a renal vasodilator, can prevent a release of hypoxanthine during rewarming after moderate hypothermic cardiopulmonary bypass and that this is related to improved renal oxygen supply. DESIGN: A prospective, randomized, and controlled study. SETTING: Operating room in the cardiothoracic surgery department of a university hospital. PARTICIPANTS: Twenty-two patients submitted to elective first-time coronary bypass surgery. INTERVENTIONS: A catheter was placed in the left renal vein for thermodilution renal blood flow (RBF) measurement and blood sampling. In 11 patients, felodipine was infused during the hypothermic period of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Renal uptake (renal arteriovenous concentration difference x RBF) of hypoxanthine was maintained during rewarming in felodipine-treated patients but not in control patients (55+/-28 v. -39+/-1 nmol/min, p<0.05). Oxygen consumption was higher after felodipine infusion despite unchanged total RBF. A positive correlation between renal oxygen consumption and hypoxanthine uptake and release (r = 0.74, p<0.01) was observed. CONCLUSIONS: Felodipine maintained renal uptake of hypoxanthine during rewarming after hypothermic cardiopulmonary bypass. This maintenance is the effect of improved renal oxygen supply secondary to improved nutritive blood flow at the expense of nonnutritive renal blood flow.     

Impairment of hepatosplanchnic oxygenation and increase of serum hyaluronate during normothermic and mild hypothermic cardiopulmonary bypass

Hepatic sinusoidal endothelial cells (SECs) are more vulnerable to hypoxia or hypothermia than hepatocytes. To test the hypothesis that hepatic venous desaturation during cardiopulmonary bypass (CPB) leads to impairment of SEC function, we studied the plasma kinetics of endogenous hyaluronate (HA), a sensitive indicator of SEC function, and hepatosplanchnic oxygenation during and after CPB. Twenty-five consecutive patients scheduled for elective coronary artery bypass graft surgery, who underwent normothermic (>35 degrees C; n = 15) or mild hypothermic (32 degrees C; n = 10) CPB participated in this study. A hepatic venous catheter was inserted into each patient to monitor hepatosplanchnic oxygenation and serum levels of HA concentration. Hepatic venous oxygen saturation decreased essentially to a similar degree during normothermic and mild hypothermic CPB. Hepatosplanchnic oxygen consumption and extraction increased during normothermic (P < 0.05), but not mild hypothermic, CPB. Both arterial and hepatic venous HA concentrations showed threefold increases during and after CPB in both groups. A positive correlation was found between hepatosplanchnic oxygen consumption and arterial HA concentrations during CPB, suggesting a role of changes in hepatosplanchnic oxygen metabolism in the mechanisms of increases in serum HA concentrations. The failure of the liver to increase HA extraction to a great degree suggests that a functional impairment of the SEC may contribute to the observed increase of serum HA. IMPLICATIONS: Hepatic sinusoidal endothelial cells (SECs) are pivotal in the regulation of sinusoidal blood flow. This study showed that SEC function might be impaired during and after cardiopulmonary bypass, irrespective of the temperature management.     

Reduced jugular venous oxygen saturation during rewarming from deep hypothermic circulatory arrest: cerebral overextraction?

Deep hypothermic circulatory arrest may impair cerebral cellular functions, and physiological parameters following circulatory arrest may deviate from the normal. The intention of this study was to monitor jugular venous oxygen saturation during cardiopulmonary bypass before and after deep hypothermic circulatory arrest. Jugular venous oxygen saturation were obtained on 18 patients by using a retrograde jugular vein catheter during replacement of the ascending aorta. Indications for operations were ascending aortic dilatation (n=15) and acute aortic dissection (n=3). Hypothermic cardiopulmonary bypass (233+/-60 min), cardioplegic arrest (105+/-37 min) and circulatory arrest (22+/-7 min) were utilized during the operations. Jugular venous oxygen saturation increased during hypothermia and decreased during rewarming. Compared with cooling, jugular venous oxygen saturation during the initial part of rewarming were significantly lower (87+/-5% vs. 97+/-1%, 89+/-4% vs. 95+/-2%, 81+/-4% vs. 87+/-5% at 16, 20 and 24 degrees C respectively, p<0.05). One patient required re-exploration because of bleeding. All patients were found neurologically normal before being discharged from the hospital (mean 14+/-7 days). In conclusion, jugular venous oxygen saturation is inversely related to the body temperature in patients undergoing hypothermic cardiopulmonary bypass. Significantly decreased jugular venous oxygen saturation during the initial part of rewarming may signify an increased cerebral extraction of oxygen.     

Relationship between hemodynamics and cardiac metabolism in the reperfusion period following hypothermic global ischemia

Ten mongrel dogs were subjected to hypothermic ischemic cardioplegia for two hours followed by 30 minutes of reperfusion to characterize the relationship between hemodynamic parameters during reperfusion and the recovery of high energy store of the post-ischemic left ventricular myocardium. Dogs were anesthetized with intravenous pentobarbital 30 mg/kg, and standard cardiopulmonary bypass was instituted with the flow rate of 80 ml/min/kg and perfusion pressure around 80 mmHg. Ischemic cardioplegia was obtained by cross-clamping of the aorta for 2 hours under 20°C of myocardial temperature. After termination of cardioplegia, the heart was rewarmed by the support of cardiopulmonary bypass with the flow rate of 80 ml/min/kg until the myocardial temperature reached 36 °C. Hemodynamic parameters were measured throughout the experiment and myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) were measured at the end of experiment. Correlation was significant between myocardial ATP and coronary blood flow and myocardial oxygen consumption. However, myocardial creatine phosphate correlated poorly to coronary blood flow, myocardial oxygen consumption and other hemodynamic parameters. These results indicate that the recovery of myocardial high energy store is partly related to coronary blood flow and myocardial oxygen consumption, but other parameters are probably involved in the process of early recovery of the myocardium from ischemic cardioplegia. This study was supported in part by a Grant from the Japan Heart Foundation for 1979.     

Postischemic [Ca2+] repletion improves cardiac performance without altering oxygen demands

The positive inotropism expected with correction of postischemic hypocalcemia might be counterbalanced by potential aggravation of reperfusion injury, in particular by calcium overload. We evaluated the effect of normalizing blood calcium concentration ([Ca2+]) on postischemic left ventricular systolic and diastolic mechanics using oxygen consumption and indices derived from pressure-diameter relations. In 10 open-chest dogs on cardiopulmonary bypass, the hearts underwent 30 minutes of normothermic global ischemia followed by one hour of multidose hypothermic (4 degrees C), hypocalcemic (0.3 mmol/L) blood cardioplegia. After reperfusion, systemic [Ca2+] had decreased to 70% of control (p = 0.017). The left ventricular inotropic state was significantly depressed from baseline (control) values, but was restored to baseline levels by resumption of normocalcemia after one hour of reperfusion. Chamber stiffness increased by 308% (p = 0.006) after hypocalcemic reperfusion but decreased significantly after [Ca2+] correction. Recovery of left ventricular performance with [Ca2+] correction did not augment myocardial oxygen consumption from the postischemic uncorrected state (5.0 +/- 0.3 mL O2/min/100 g versus 5.3 +/- 0.3 mL O2/min/100 g). We conclude that normalizing [Ca2+] after blood cardioplegia improves postischemic left ventricular performance without adversely affecting compliance or oxygen consumption.     

Optimal blood flow for cooled brain at 20 degrees C.

BACKGROUND: Optimal conditions for deep hypothermic perfusion and protective brain blood flow remain unclear. METHODS: Dogs (n = 52) underwent 120 minutes of cardiopulmonary bypass at 20 degrees C with perfusion flow rates of 2.5, 5, 10, 20, 40, and 100 mL x kg(-1) x min(-1). We examined the effect of the various flow rates and different perfusion pressures on brain blood flow, metabolism, and intracellular pH. RESULTS: The brain was ischemic and acidotic when the perfusion flow rate was less than 5 mL kg(-1) x min(-1) and pressure was less than 10 mm Hg. When perfusion pressure was higher than 10 mm Hg, cerebral cortex blood flow was more than 9 mL x 100 g(-1) x min(-1) and intracellular pH, higher than 6.95. The cerebral metabolic rate for oxygen decreased at a flow rate of 2.5 mL x kg(-1) min(-1). The cerebral metabolic ratio of glucose to oxygen and the cerebral vascular resistance were lowest when perfusion pressure was 10 to 30 mm Hg. Full-flow (100 mL x kg(-1) x min(-1)) perfusion caused paradoxical brain acidosis; a flow of 40 mL x kg(-1) x min(-1) provided the best results. CONCLUSIONS: Both extremely low-flow perfusion and excessive perfusion cause brain acidosis. Low-flow perfusion at a pressure of 20 mm Hg provides cerebral vasorelaxation and aerobic metabolism during operations at 20 degrees C.     

Hemodilution elevates cerebral blood flow and oxygen metabolism during cardiopulmonary bypass in piglets

BACKGROUND: Hemodilution continues to be widely used during cardiopulmonary bypass (CPB) for both adults and children. Previous studies with nonbypass models have suggested that an increase in cerebral blood flow (CBF) compensates for the reduced oxygen-carrying capacity; however, this increased CBF is achieved by an increase in cardiac output. We hypothesized that even with the fixed-flow perfusion of CPB, CBF would be increased during hemodilution. METHODS: Two experiments were conducted and analyzed separately. In each experiment, 10 piglets were randomized to two different groups, one with a total blood prime yielding a high hematocrit (25% or 30%), and the other with a crystalloid prime resulting in a low hematocrit (10% or 15%). Animals were cooled with pH-stat strategy at full flow (100 or 150 mL.kg(-1).min(-1)) to a nasopharyngeal temperature of 15 degrees C, a period of low flow (50 mL.kg(-1).min(-1)) preceding deep hypothermic circulatory arrest (45 or 60 minutes), and a period of rewarming at full flow. Cerebral blood flow was measured at the beginning of CPB, at the end of cooling, at the end of low flow, 5 minutes after the start of rewarming, and at the end of rewarming by injection of radioactive microspheres. RESULTS: Mean arterial pressure was significantly greater with higher hematocrit at each time point (p< 0.05). Cerebral blood flow and the cerebral metabolic rate of oxygen decreased during cooling and further during low flow bypass but were significantly greater with lower hematocrit during mild hypothermia and at the end of rewarming (p< 0.05). CONCLUSIONS: Hemodilution is associated with decreased perfusion pressure, increased CBF and increased the cerebral metabolic rate of oxygen during hypothermic CPB.     

Direct visualization of minimal cerebral capillary flow during retrograde cerebral perfusion: an intravital fluorescence microscopy study in pigs

BACKGROUND: Retrograde cerebral perfusion (RCP) is used in some centers during aortic arch surgery for brain protection during hypothermic circulatory arrest. It is still unclear however whether RCP provides adequate microcirculatory blood flow at a capillary level. We used intravital microscopy to directly visualize the cerebral capillary blood flow in a piglet model of RCP. METHODS: Twelve pigs (weight 9.7 +/- 0.9 kg) were divided into two groups (n = 6 each): deep hypothermic circulatory arrest (DHCA) and RCP. After the creation of a window over the parietal cerebral cortex, pigs underwent 10 minutes of normothermic bypass and 40 minutes of cooling to 15 degrees C on cardiopulmonary bypass ([CPB] pH-stat, hemocrit 30%, pump flow 100 mL x kg(-1) x min(-1)). This was followed by 45 minutes of DHCA and rewarming on CPB to 37 degrees C. In the RCP group the brain was retrogradely perfused (pump flow 30 mL x kg(-1) x min(-1)) during DHCA through the superior vena cava after inferior vena cava occlusion. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessing microvascular diameter and functional capillary density (FCD), defined as total length of erythrocyte-perfused capillaries per observation area. Cerebral tissue oxygenation was determined by nicotinamide adenine dinucleotide hydrogen (NADH) autofluorescence, which increases during tissue ischemia. RESULTS: During normothermic and hypothermic antegrade cerebral perfusion the FCD did not significantly change from base line (97% +/- 14% and 96% +/- 12%, respectively). During retrograde cerebral perfusion the FCD decreased highly significantly to 2% +/- 2% of base line values (p < 0.001). Thus there was no evidence of significant capillary blood flow during retrograde cerebral perfusion. The microvascular diameter of cerebral arterioles that were slowly perfused significantly decreased to 27% +/- 6% of base line levels during RCP. NADH fluorescence progressively and significantly increased during RCP, indicating poorer tissue oxygenation. At the end of retrograde cerebral perfusion there was macroscopic evidence of significant brain edema. CONCLUSIONS: RCP does not provide adequate cerebral capillary blood flow and does not prevent cerebral ischemia. Prolonged RCP induces brain edema. However, there might be a role for a short period of RCP to remove air and debris from the cerebral circulation after DHCA because retrograde flow could be detected in cerebral arterioles.     

Pharmacologic cerebral capillary blood flow improvement after deep hypothermic circulatory arrest: an intravital fluorescence microscopy study in pigs

BACKGROUND: Despite meticulous investigation of bypass techniques for deep hypothermic circulatory arrest, unfavorable long-term neurologic deficits have been well documented. Our aim was to improve brain perfusion by reducing platelet plugging with a glycoprotein IIb/IIIa inhibitor (eptifibatide) in an experimental model of deep hypothermic circulatory arrest-reperfusion in pigs. METHODS: Two groups of 12 piglets each (eptifibatide group [eptifibatide + unfractionated heparin] vs UFH group [only unfractionated heparin]) underwent 10 minutes of normothermic bypass, 40 minutes of cooling during cardiopulmonary bypass (hematocrit, 30%; cardiopulmonary bypass flow, 100 mL x kg(-1) x min(-1)), 60 minutes of circulatory arrest at 15 degrees C, and a 40-minute rewarming period. Intravital fluorescence microscopy of pial vessels at set intervals was performed. RESULTS: During the cooling period, there was a tendency toward reduced functional capillary density values without statistical significance in both groups. During reperfusion, the eptifibatide group demonstrated a significantly decreased platelet adhesion and aggregation (at 30 minutes of reperfusion: functional capillary density, 104% +/- 3% vs 77% +/- 4% relative to baseline, P = .02; red blood cell velocity, 0.65 vs 0.30 mm/s, P < .004). A more rapid recovery of tissue oxygenation (P < .001) was documented. Furthermore, a significant microvascular permeability reduction was achieved compared with that seen in the UFH group (P < .02). The use of eptifibatide resulted in fewer ultrastructural changes in hippocampal tissue, which is demonstrated by histologic examination. CONCLUSIONS: Platelet plugging reduction with the glycoprotein IIb/IIIa inhibitor eptifibatide improves cerebral capillary blood flow and reduces cerebral ischemia in the setting of deep hypothermic circulatory arrest. Furthermore, significant endothelial cell injury and perivascular edema reduction can be achieved.     

Hepatosplanchnic oxygenation is better preserved during mild hypothermic than during normothermic cardiopulmonary bypass

PURPOSE: To assess and compare the effects of normothermic and mild hypothermic cardiopulmonary bypass (CPB) on hepatosplanchnic oxygenation. METHODS: We studied 14 patients scheduled for elective coronary artery bypass graft surgery who underwent normothermic (>35 degrees C; group I, n=7) or mild hypothermic (32 degrees C; group II, n=7) CPB. After induction of anesthesia, a hepatic venous catheter was inserted into the right hepatic vein to monitor hepatic venous oxygen saturation (ShvO(2)) and hepatosplanchnic blood flow by a constant infusion technique that uses indocyanine green. RESULTS: The ShvO(2) decreased from a baseline value in both groups during CPB and was significantly lower at ten minutes and 60 min after the onset of CPB in group I (39.5 +/- 16.2% and 40.1 +/- 9.8%, respectively) than in group II (61.1 +/- 16.2% and 61.0 +/- 17.9%, respectively; P <0.05). During CPB, the hepatosplanchnic oxygen extraction ratio was significantly higher in group I than in group II (44.0 +/- 7.2% vs 28.7 +/- 13.1%; P <0.05). CONCLUSION: Hepatosplanchnic oxygenation was better preserved during mild hypothermic CPB than during normothermic CPB.