Cerebral physiology in paediatric cardiopulmonary bypass

PURPOSE: To analyze studies of neurological injury after open-heart surgery in infants and children and to discuss the effects of cardiopulmonary bypass, hypothermia and deep hypothermic circulatory arrest on cerebral blood flow, cerebral metabolism and brain temperature. SOURCE: Articles were obtained from the databases, Current Science and Medline, from 1966 to present. Search terms include cardiopulmonary bypass (CPB), hypothermia, cerebral blood flow (CBF), cerebral metabolism and brain temperature. Information and abstracts obtained from meetings on the topic of brain and cardiac surgery helped complete the collection of information. PRINCIPAL FINDINGS: In adults the incidence of neurological morbidity is between 7 to 87% with stroke in about 2-5%, whereas the incidence of neurological morbidity increases to 30% in infants and children undergoing cardiopulmonary bypass. Besides the medical condition of the patient, postoperative cerebral dysfunction and neuronal ischaemia associated with cardiac surgery in infants and small children are a combination of intraoperative factors. Deep hypothermic circulatory arrest impairs CBF and cerebral metabolism even after termination of CPB. Inadequate and/or non-homogenous cooling of the brain before circulatory arrest, as well as excessive rewarming of the brain during reperfusion are also major contributory factors. CONCLUSION: Newer strategies, including the use of low-flow CPB, pulsatile CPB, pH-stat acid-base management and a cold reperfusion, are being explored to ensure better cerebral protection. Advances in monitoring technology and better understanding of the relationship of cerebral blood flow and metabolism during the different modalities of cardiopulmonary bypass management will help in the medical and anaesthetic development of strategies to improve neurological and developmental outcomes.     

A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery. I. Mortality and cardiovascular morbidity

The impact of perfusion technique and mode of pH management during cardiopulmonary bypass has not been well characterized with respect to postoperative cardiovascular outcome. METHODS: This double-blind, randomized study comparing outcomes after alpha-stat or pH-stat management and pulsatile or nonpulsatile perfusion during moderate hypothermic cardiopulmonary bypass was undertaken in 316 patients undergoing coronary artery bypass operations. RESULTS: Cardiovascular morbidity and mortality were not affected by pH management, and the incidence of stroke (2.5%) did not differ between groups. Overall in-hospital mortality was 2.8%, eight of the nine deaths occurring in the nonpulsatile group (5.1% versus 0.6%; p = 0.018). The incidence of myocardial infarction was 5.7% in the nonpulsatile group and 0.6% in the pulsatile group (p = 0.010), and use of intraaortic balloon pulsation was significantly more common in the nonpulsatile group (7.0% versus 1.9%; p = 0.029). The overall percentage of patients having major complications was also significantly higher in the nonpulsatile group (15.2% versus 5.7%; p = 0.006). Duration of cardiopulmonary bypass, age, and use of nonpulsatile perfusion all correlated significantly with adverse outcome. CONCLUSIONS: Use of pulsatile perfusion during cardiopulmonary bypass was associated with decreased incidences of myocardial infarction, death, and major complications.     

Influences of cardiopulmonary bypass and fentanyl anesthesia on hepatic circulation and oxygen metabolism in beagles

Decreases in hepatic blood flow (HBF) have been reported in patients and in animal experiments during cardiopulmonary bypass (CPB). We examined changes in HBF and hepatic oxygen metabolism during CPB in 16 beagles anesthetized with fentanyl. Hepatic arterial blood flow (HABF) and portal venous blood flow (PVBF) were measured by using an electromagnetic flowmeter before and during normothermic and hypothermic CPB with 10 microg x kg(-1) x h(-1) (F-10 group; n = 8) or 50 microg x kg(-1) x h(-1) (F-50 group; n = 8) of fentanyl anesthesia. CPB was conducted with membrane oxygenation and a nonpulsatile pump flow of 2.4 L x m(-2) x min(-1). Hepatic oxygen delivery (HDO2) and consumption (HVO2) were calculated from HBF and oxygen content in arterial, portal venous, and hepatic venous blood. HABF did not change during normothermic CPB in the F-10 group, but it decreased significantly during hypothermic CPB in both groups, especially the F-50 group. During CPB, PVBF and total HBF decreased significantly in both groups-more so with the larger dose of fentanyl--whereas HDO2 decreased significantly because the arterial and portal venous blood oxygen levels decreased. The HVO2 was stable in the F-10 group but was significantly depressed during CPB in the F-50 group. Our results indicate that during hypothermic nonpulsatile CPB larger doses of fentanyl are associated with reduced HBF and impaired HDO2 and HVO2. Implications: Hepatic dysfunction after cardiopulmonary bypass (CPB) has been frequently reported and could be partly attributed to hepatic circulatory disturbance during CPB. We found that, in beagles, large doses of fentanyl were associated with greater decreases in hepatic blood flow and hepatic oxygen metabolism during hypothermic CPB than smaller doses of fentanyl.     

Pulsatile versus nonpulsatile flow. No difference in cerebral blood flow or metabolism during normothermic cardiopulmonary bypass in rabbits

BACKGROUND: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees C. METHODS: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees C for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees C. At 30 and 60 min of CPB, physiologic measurements were made as before. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 +/- 6 vs. 77 +/- 9 ml.100 g-1.min-1, respectively (median +/- quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 +/- 0.5 vs. 4.1 +/- 0.6 ml O2.100 g-1.min-1, respectively) and decreased slightly (0.4 +/- 0.4 ml O2.100 g-1.min-1) between measurements. CONCLUSIONS: During CPB in rabbits at 37 degrees C, neither CBF nor CMRO2 is affected by arterial pulsation. The absence of pulsation per se is not responsible for the small decreases in CMRO2 observed during CPB.     

Pulsatile versus nonpulsatile cardiopulmonary bypass. No difference in brain blood flow or metabolism at 27 degrees C

BACKGROUND: It is unclear whether nonpulsatile perfusion adversely affects the brain. This study compared cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) betwen pulsatile and nonpulsatile cardiopulmonary bypass (CPB) in rabbits at 27 degrees C. METHODS: In experiment A, 24 anesthetized New Zealand white rabbits underwent pulsatile CPB at 27 degrees C, using alpha-stat acid-base management. Animals were randomized to three groups based upon the duration of the period of systolic ejection (100, 120, 140 ms) and were perfused for 20 min at each of three pulse rates (150, 200, 250 pulse/min), generating nine arterial pressure waveforms. Arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (radiolabeled microspheres), and CMRO2 (Fick) were measured at the end of each 20-min period. In experiment B, 16 anesthetized rabbits were randomized to pulsatile (120-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 27 degrees C. AFter 1 h, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF and CMRO2 were measured. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all nine waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile bypass, 30 +/- 4 versus 32 +/- 5 ml.100 g-1.min-1, respectively. CMRO2 did not differ between pulsatile and nonpulsatile bypass, 1.7 +/- 0.2 versus 1.6 +/- 0.2 ml.100 g-1.min-1, respectively. CONCLUSIONS: During CPB in rabbits at 27 degrees C, neither CBF nor CMRO2 is affected by flow character.     

A mechanistic study of beta-adrenoceptor antagonists on ethanol-induced gastric damage

BACKGROUND: In the first weeks of life there are important maturational changes in the central nervous system in many species in energy metabolism, synapse number, and concentration of neuronal excitatory receptors. METHODS: Four groups of 10 piglets (aged 1, 2, 4, and 10 weeks) underwent 1 hour of deep hypothermic circulatory arrest at 15 degrees C, with cooling and rewarming on cardiopulmonary bypass. Cerebral blood flow and metabolic rate measurements and electroencephalographic recordings were obtained from 5 animals per group. The remaining animals underwent cerebral magnetic resonance spectroscopy. RESULTS: Preoperative cerebral blood flow and glucose consumption were higher at 4 and 10 weeks than at 1 and 2 weeks. Cerebral adenosine triphosphate content decreased more rapidly during deep hypothermic circulatory arrest at 4 and 10 weeks. Phosphocreatine recovery was greater at 30 minutes of reperfusion at 10 weeks compared with 1 week. Recovery of cerebral phosphocreatine/ adenosine triphosphate ratio and intracellular pH was remarkably uniform at all ages. Latency to recovery of electroencephalographic activity decreased with increasing age (p = 0.04). CONCLUSIONS: Differences in acute recovery of brain energy metabolism and electroencephalogram after cardiopulmonary bypass and 1 hour of deep hypothermic circulatory arrest in piglets between 1 and 10 weeks of age are small. Further studies are required to correlate these acute findings with subsequent neurologic outcome.     

The effects of hemodilution on cerebral hemodynamics and oxygen consumption during nonpulsatile hypothermic cardiopulmonary bypass

The effects of hemodilution on cerebral hemodynamics and oxygen consumption during nonpulsatile hypothermic cardiopulmonary bypass (CPB) were investigated in 16 patients undergoing elective open heart surgery under CPB. They were divided into 2 groups; high (25%) (H) and low hematocrit (15%) (L) groups according to the hematocrit values during CPB. Simultaneous measurements of blood flow velocity in the middle cerebral artery (VMCA) and oxygen tension in the jugular venous bulb (PjvbO2) were performed at prebypass, bypass, and post bypass periods. There were no significant differences in nasopharyngeal temperature (NPT), cerebral perfusion pressure, pump flow rate, and PaCO2 between the two groups at any period. VMCA changed in correlation with NPT in both groups, and VMCA in the L group was faster than that in the H group at any period. PjvbO2 increased during aortic cross clamp, and decreased on rewarming in both groups. However, there were no significant differences in VMCA and PjvbO2 between the two groups at any period. These findings suggest that increased cerebral blood flow may compensate the decreased oxygen content due to the hemodilution during CPB. Therefore, the profound hemodilution up to 15% of hematocrit is considered to be a safe technique during CPB.     

Granular cell tumor of the pituitary stalk

Erythropoietin is a hormone responsible for regulation of red blood cell production. Circulating erythropoietin values are regulated by renal oxygen supply, which is determined by hemoglobin concentration, hemoglobin oxygen saturation, and renal blood flow. Previous animal and human studies regarding erythropoietin regulation have assumed pulsatile renal blood flow. During cardiopulmonary bypass, non-pulsatile renal perfusion has been shown to result in decreased glomerular filtration rate and decreased renal blood flow in comparison to pulsatile perfusion. Repair of congenital heart disease during cardiopulmonary bypass is an attractive circumstance in which to study the effect of non-pulsatile blood flow on erythropoietin production. The hypothesis in this study was that non-pulsatile perfusion would result in increased erythropoietin production because of decreased renal oxygen supply. Fourteen children with congenital heart disease and without preoperative renal insufficiency or anemia were enrolled in the study. All patients underwent cardiopulmonary bypass with non-pulsatile flow. In addition, 10 control patients without congenital heart disease were enrolled. Six cardiopulmonary bypass patients had 1.5- to 6-fold increases in plasma erythropoietin concentrations from baseline. These patients had longer cardiopulmonary bypass times, more commonly performed under low flow deep hypothermic conditions. The remaining 8 patients with congenital heart disease, and all control patients, did not develop increased postoperative erythropoietin concentrations. The conditions under which cardiopulmonary bypass are performed appear to influence postoperative circulating erythropoietin concentrations.     

Impact of systemic depulsation on tissue perfusion and sympathetic nerve activity

BACKGROUND: We postulated that pathophysiologic processes under nonpulsatile circulation are related to the behavior of the sympathetic nerve activity that regulates tissue perfusion. METHODS: Pulsatile and nonpulsatile pumps were installed in parallel in the left heart bypass circuit of anesthetized goats (n = 9) so that pulsatile circulation could be converted to nonpulsatile circulation instantly. At 5 minutes before and after systemic depulsation, we measured hemodynamic indices, renal nerve activity, and regional blood flow of the brain, heart, and renal cortex. RESULTS: Renal nerve activity was significantly elevated after systemic depulsation (15.6 +/- 9.3 versus 19.4 +/- 9.8 microV), when mean aortic pressure remained almost constant. The renal cortical flow was significantly reduced after depulsation (3.61 +/- 1.23 versus 2.93 +/- 1.19 mL.min-1.g-1), whereas no significant difference was found in the regional blood flow of the brain or the heart. CONCLUSIONS: The significant reduction of renal cortical blood flow after systemic depulsation is associated with a significant increase in renal nerve activity. Our results suggest that increased renal nerve activity plays an important role in the reduction of renal function after systemic depulsation.     

Differential regulation of vitamin D receptors in clonal populations of a chronic myelogenous leukemia cell line

BACKGROUND: Both crystalloid and blood cardioplegia result in cardiac dysfunction associated with myocardial edema. This edema is partially due to the lack of myocardial contraction during cardioplegia, which stops myocardial lymph flow. As an alternative, acceptable surgical conditions have been created in patients undergoing coronary artery bypass operations with esmolol-induced minimal myocardial contraction. We hypothesized that minimal myocardial contraction during circulatory support using either standard cardiopulmonary bypass (CPB) or a biventricular assist device would prevent myocardial edema by maintaining cardiac lymphatic function and thus prevent cardiac dysfunction. METHODS: We placed 6 dogs on CPB and 6 dogs on a biventricular assist device and serially measured myocardial lymph flow rate and myocardial water content in both groups and preload recruitable stroke work only in the CPB dogs. In all dogs we minimized heart rate with esmolol for 1 hour during total circulatory support. RESULTS: Although myocardial lymph flow remained at baseline level during CPB and increased during biventricular assistance, myocardial water accumulation still occurred during circulatory support. However, as edema resolved rapidly after separation from circulatory support, myocardial water content was only slightly increased after CPB and biventricular assistance, and preload recruitable stroke work was normal. CONCLUSIONS: Our data suggest that minimal myocardial contraction during both CPB and biventricular assistance supports myocardial lymphatic function, resulting in minimal myocardial edema formation associated with normal left ventricular performance after circulatory support. The concept of minimal myocardial contraction may be a useful alternative for myocardial protection, especially in high-risk patients with compromised left ventricular function.     

Pulsatile and nonpulsatile perfusion: the continuing controversy

This report discusses pulsatile and nonpulsatile perfusion with regard to hemodynamics, cell metabolism, and the visceral consequences of these forms of cardiopulmonary bypass. It argues that differences between the two modes and a benefit for pulsatile perfusion, are most clearly manifested in identifiable high-risk patient groups.     

Effects of cardiopulmonary bypass and circulatory arrest on endothelium-dependent vasodilation in the lung

Endothelial injury with failure of pulmonary endothelium-dependent vasodilatation has been proposed as a possible cause for the increased pulmonary vascular resistance observed after cardiopulmonary bypass, but the mechanisms underlying this response are not understood. An in vivo piglet model was used to investigate the role of endothelium-dependent vasodilatation in postbypass pulmonary hypertension. The pulmonary vascular responses to acetylcholine, a receptor-mediated endothelium-dependent vasodilator, and nitric oxide, an endothelium-independent vasodilator, were studied in one group of animals after preconstriction with the thromboxane A2 analog U46619 (n = 6); a second group was studied after bypass with 30 minutes of deep hypothermic circulatory arrest (n = 6). After preconstriction with U46619, both acetylcholine and nitric oxide caused significant decreases in pulmonary vascular resistance (34% +/- 6% decrease, p = 0.007, and 39% +/- 4% decrease, p = 0.001). After cardiopulmonary bypass with circulatory arrest, acetylcholine did not significantly change pulmonary vascular resistance (0% +/- 8% decrease, p = 1.0), whereas nitric oxide produced a 32% +/- 4% decrease in pulmonary vascular resistance (p = 0.007). These results demonstrate a loss of receptor-mediated endothelium-dependent vasodilatation with normal vascular smooth muscle function after circulatory arrest. Administration of the nitric oxide synthase blocker Ngamma-nitro-L-arginine-methyl-ester after circulatory arrest significantly increased pulmonary vascular resistance; thus, although endothelial cell production of nitric oxide may be diminished, it continues to be a major contributor to pulmonary vasomotor tone after cardiopulmonary bypass with deep hypothermic circulatory arrest. In summary, cardiopulmonary bypass with deep hypothermic circulatory arrest results in selective pulmonary endothelial cell dysfunction with loss of receptor-mediated endothelium-dependent vasodilatation despite preserved ability of the endothelium to produce nitric oxide and intact vascular smooth muscle function.     

A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery

BACKGROUND: Hypothermic circulatory arrest is a widely used support technique during heart surgery in infants, but its effects on neurologic outcome have been controversial. An alternative method, low-flow cardiopulmonary bypass, maintains continuous cerebral circulation but may increase exposure to known pump-related sources of brain injury, such as embolism or inadequate cerebral perfusion. METHODS: We compared the incidence of perioperative brain injury after deep hypothermia and support consisting predominantly of total circulatory arrest with the incidence after deep hypothermia and support consisting predominantly of low-flow cardiopulmonary bypass in a randomized, single-center trial. The criteria for eligibility included a diagnosis of transposition of the great arteries with an intact ventricular septum or a ventricular septal defect and a planned arterial-switch operation before the age of three months. RESULTS: Of 171 patients with D-transposition of the great arteries, 129 (66 of whom were assigned to circulatory arrest and 63 to low-flow bypass) had an intact ventricular septum, and 42 (21 assigned to circulatory arrest and 21 to low-flow bypass) had a ventricular septal defect. After adjustment for diagnosis, assignment to circulatory arrest as compared with low-flow bypass was associated with a higher risk of clinical seizures (odds ratio, 11.4; 95 percent confidence interval, 1.4 to 93.0), a tendency to a higher risk of ictal activity on continuous electroencephalographic (EEG) monitoring during the first 48 hours after surgery (odds ratio, 2.5; 95 percent confidence interval, 1.0 to 6.4), a longer recovery time to the first reappearance of EEG activity (only in the group with an intact ventricular septum, P < 0.001), and greater release of the brain isoenzyme of creatine kinase in the first 6 hours after surgery (P = 0.046). Analyses comparing durations of circulatory arrest produced results similar to those of analyses comparing treatments. CONCLUSIONS: In heart surgery in infants, a strategy consisting predominantly of circulatory arrest is associated with greater central nervous system perturbation in the early postoperative period than a strategy consisting predominantly of low-flow cardiopulmonary bypass. Assessment of the effect of these findings on later outcomes awaits follow-up of this cohort.     

Cerebral oxygenation during cardiopulmonary bypass in children

OBJECTIVE: Previous work has found cerebral oxygen extraction to decrease during hypothermic cardiopulmonary bypass in children. To elucidate cardiopulmonary bypass factors controlling cerebral oxygen extraction, we examined the effect of perfusate temperature, pump flow rate, and hematocrit value on cerebral hemoglobin-oxygen saturation as measured by near infrared spectroscopy. METHODS: Forty children less than 7 years of age scheduled for cardiac operations with continuous cardiopulmonary bypass were randomly assigned to warm bypass, hypothermic bypass, hypothermic low-flow bypass, or hypothermic low-hematocrit bypass. For warm bypass, arterial perfusate was 37 degrees C, hematocrit value 23%, and pump flow 150 ml/kg per minute. Hypothermic bypass differed from warm bypass only in initial perfusate temperature (22 degrees C); hypothermic low-flow bypass and low-hematocrit bypass differed from hypothermic bypass only in pump flow (75 ml/kg per minute) and hematocrit value (16%), respectively. Cerebral oxygen saturation was recorded before bypass (baseline), during bypass, and for 15 minutes after bypass had been discontinued. RESULTS: In the warm bypass group, cerebral oxygen saturation remained at baseline levels during and after bypass. In the hypothermic bypass group, cerebral oxygen saturation increased 20% +/- 2% during bypass cooling (p < 0.001), returned to baseline during bypass rewarming, and remained at baseline after bypass. In the hypothermic low-flow and hypothermic low-hematocrit bypass groups, cerebral oxygen saturation remained at baseline levels during bypass but increased 6% +/- 2% (p = 0.05) and 10% +/- 2% (p < 0.03), respectively, after bypass was discontinued. CONCLUSIONS: In children, cortical oxygen extraction is maintained during warm cardiopulmonary bypass at full flow and moderate hemodilution. Bypass cooling can decrease cortical oxygen extraction but requires a certain pump flow and hematocrit value to do so. Low-hematocrit hypothermic bypass and low-flow hypothermic bypass can also alter cortical oxygen extraction after discontinuation of cardiopulmonary bypass.     

Platelet hyporeactivity in young infants during cardiopulmonary bypass

Platelet dysfunction is one of the most important factors contributing to a postoperative hemorrhagic diathesis in children with congenital heart disease undergoing operations requiring cardiopulmonary bypass (CPB). However, very little is known about the influence of CPB on platelets in neonates and young infants. We studied 16 patients--8 young infants (<2 mo old) and 8 children (>12 mo old)--with congenital heart disease undergoing CPB. Surface density of an important platelet adhesive receptor, glycoprotein Ib, and degree of platelet activation, indicated by p-selectin positivity, were measured by whole blood flow cytometry in samples obtained at seven time points during the operations. We found that the percentage of p-selectin-positive platelets increased significantly in children, but not in young infants, during CPB. The young infant group exhibited a significantly smaller reduction of glycoprotein Ib than the child group during CPB (21.0% +/- 12.0% vs 32.7% +/- 18.1%; P < 0.05). Lack of CPB-induced increase of p-selectin and a smaller decrease of glycoprotein Ib in young infants in the current study suggest reduced platelet reactivity in young infants and neonates during CPB. The clinical significance of the reduced platelet reactivity in young infants and neonates remains to be determined. Implications: Platelets of young infants are less reactive than those of children during cardiopulmonary bypass, as determined by the cardiopulmonary bypass-induced alterations in platelet membrane adhesive receptors.     

Biocompatibility in cardiopulmonary bypass

Recent advances in surgical techniques and perfusion technology allow cardiac operations to be performed routinely with low mortality rates. However, patients undergoing cardiac operations with cardiopulmonary bypass (CPB) are still associated with bleeding disorders, thrombotic complications, massive fluid shifts, and the activation of blood components that are collectively known as the whole body inflammatory response. In this review, the effect of cardiopulmonary bypass on various humoral and cellular components of blood is examined. Blood activation caused by interaction with artificial materials of extracorporeal circuit and by material-independent stimuli is discussed. Methods to control blood activation during and after cardiopulmonary bypass are described. These include surface modification of extracorporeal circuit, control of flow dynamics in the circuit, pharmacological intervention, and the use of extracorporeal devices to remove inflammatory mediators. Recent findings on the effects of heparin-coated circuits on inflammatory response and clinical outcome are reviewed. It appears that the causes of inflammatory response to cardiopulmonary bypass are multifactorial and that an integrated strategy is needed to control and eliminate the negative effects of CPB.     

Gut mucosal ischemia during normothermic cardiopulmonary bypass results from blood flow redistribution and increased oxygen demand

Impaired gut mucosal perfusion has been reported during cardiopulmonary bypass. To better define the adequacy of gut blood flow and oxygenation during cardiopulmonary bypass, we measured overall gut blood flow and ileal mucosal flow and their relationship to mucosal pH, mesenteric oxygen delivery and oxygen consumption in immature pigs (n = 8). Normothermic, noncross-clamped, right atrium-to-aorta cardiopulmonary bypass was maintained at 100 ml/kg per minute for 120 minutes. Animals were instrumented with an ultrasonic Doppler flow probe on the superior mesenteric artery, a mucosal laser Doppler flow probe in the ileum, and pH tonometers in the stomach, ileum, and rectum. Radioactive microspheres were injected before and at 5, 60, and 120 minutes of cardiopulmonary bypass for tissue blood flow measurements. Overall gut blood flow significantly increased during cardiopulmonary bypass as evidenced by increases in superior mesenteric arterial flow to 134.1% +/- 8.0%, 137.1% +/- 7.5%, 130.3% +/- 11.2%, and 130.2% +/- 12.7% of baseline values at 30, 60, 90, and 120 minutes of bypass, respectively. Conversely, ileal mucosal blood flow significantly decreased to 53.6% +/- 6.4%, 49.5% +/- 6.8%, 58.9% +/- 11.6%, and 47.8% +/- 10.0% of baseline values, respectively. Blood flow measured with microspheres was significantly increased to proximal portions of the gut, duodenum and jejunum, during cardiopulmonary bypass, whereas blood flow to distal portions, ileum and colon, was unchanged. Gut mucosal pH decreased progressively during cardiopulmonary bypass and paralleled the decrease in ileal mucosal blood flow. Mesenteric oxygen delivery decreased significantly from 67.0 +/- 10.0 ml/min per square meter at baseline to 42.4 +/- 4.6, 44.9 +/- 3.5, 46.0 +/- 3.6, and 42.9 +/- 3.9 ml/min per square meter at 30, 60, 90, and 120 minutes of bypass. Despite the decrease in mesenteric oxygen delivery, mesenteric oxygen consumption increased progressively from 10.8 +/- 1.4 ml/min per square meter at baseline to 13.4 +/- 1.2, 15.9 +/- 1.2, 16.7 +/- 1.4, and 16.6 +/- 1.54 ml/min per square meter, respectively. We conclude that gut mucosal ischemia during normothermic cardiopulmonary bypass results from a combination of redistribution of blood flow away from mucosa and an increased oxygen demand.     

Comparative study of artificial circulation for the liver after cardiogenic shock: pulsatile or nonpulsatile?

Because of multiple organ failure (MOF), the survival rate of patients with mechanical circulatory support has not been satisfactory, The purpose of this study is to estimate the effects of pulsatile and nonpulsatile artificial circulation on hepatic microcirculation and function. Cardiogenic shock was induced experimentally by ligating of left anterior descending branch in pigs. For the right ventricular assist device, a nonpulsatile pump (Nikkiso HPM-15) was employed. The left ventricular function was supported by either a nonpulsatile pump (Nikkiso HPM-15: NP group) or a pulsatile pump (Zeon Medical: P group). NP group was further divided into 80% support (NP-1 group) and 100% support (NP-2 group) of the control cardiac output. All groups were maintained at an equivalent mean aortic pressure of 3 hours. We measured the hepatic artery blood flow, portal vein flow and hepatic regional blood flow. For the metabolic and hepatic oxygen metabolic data, GOT, GPT, arterial blood ketone body ratio (AKBR), lactate/pirubic acid (L/P), and hyaluronic acid were evaluated. The mean aortic pressure was higher in the NP-2 group than in the other groups. The hepatic arterial blood flow was significantly higher in the P group than in the others. The AKBR and hepatic oxygen metabolism showed significant improvement in the P group in comparison with others. The regional blood flow in the liver showed improvements in the P and NP-2 groups. These findings suggested that pulsatile circulation may be beneficial for microcirculation of the liver; and the augmented nonpulsatile flow had effects similar to those of pulsatile flow in hepatic circulation.     

Increased portal endothelin-1 level is associated with the liver function after cardiopulmonary bypass in rabbits: influence of hypothermia on the damage

The purpose of this study was to prove the hypothesis that ET-1 production is increased in the splanchnic-hepato circulation during cardiopulmonary bypass (CPB) with or without hypothermia and this greatly affects hepatocellular function after surgery. Twelve Japanese white rabbits were used. In group I (n = 6), the rectal temperature was kept at 37.0 degrees C during CPB (90 min). In group II (n = 6), the rectal temperature was lowered to 26 degrees C during the first 30 minutes and then increased to 37 degrees C for the following 60 minutes. In group I, surface liver tissue blood flow (LBF) remained stable during CPB. While, in group II, LBF was significantly reduced to 66.9% of baseline values during hypothermic CPB, but it increased during the rewarming phase to 84.3% of the baseline value (p = 0.0070). At the end of CPB, portal ET-1 levels were increased in both groups, but they were significantly higher in group II (7.32 +/- 0.50 pg/ml and 9.29 +/- 0.61 pg/ml, respectively). Serum GOT, GPT, LDH and arterial ammonia levels were also higher in group II. Portal ET-1 levels had a significant positive correlation with those liver enzymes. Histopathological examination after CPB showed severe damage of the hepatic parenchyma in zone 3 associated with microvesicular fatty infiltration in group II.     

Consequences of electroencephalographic-suppressive doses of propofol in conjunction with deep hypothermic circulatory arrest

BACKGROUND: Some patients who undergo cerebral aneurysm surgery require cardiopulmonary bypass and deep hypothermic circulatory arrest. During bypass, these patients often are given large doses of a supplemental anesthetic agent in the hope that additional cerebral protection will be provided. Pharmacologic brain protection, however, has been associated with undesirable side effects. These side effects were evaluated in patients who received large doses of propofol. METHODS: Thirteen neurosurgical patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest to facilitate clip application to a giant or otherwise high-risk cerebral aneurysm. Electroencephalographic burst suppression was established before bypass with an infusion of propofol, and the infusion was continued until the end of surgery. Hemodynamic and echocardiographic measurements were made before and during the prebypass propofol infusion and again after bypass. Emergence time also was determined. RESULTS: Prebypass propofol at 243 +/- 57 micrograms.kg-1.min-1 decreased vascular resistance from 34 +/- 8 to 27 +/- 8 units without changing heart rate, arterial or filling pressures, cardiac index, stroke volume, or ejection fraction. Propofol blood concentration was 8 +/- 2 micrograms/ml. Myocardial wall motion appeared hyperdynamic at the end of cardiopulmonary bypass, and all patients were weaned therefrom without inotropic support. After bypass, vascular resistance decreased further, and cardiovascular performance was improved compared to baseline values. Nine of the 13 patients emerged from anesthesia and were able to follow commands at 3.1 +/- 1.4 h. Three others had strokes and a fourth had cerebral swelling. CONCLUSIONS: Propofol infused at a rate sufficient to suppress the electroencephalogram does not depress the heart or excessively prolong emergence from anesthesia after cardiopulmonary bypass and deep hypothermic circulatory arrest.