Soluble complement receptor-1 protects heart, lung, and cardiac myofilament function from cardiopulmonary bypass damage.

BACKGROUND: Host defense system activation occurs with cardiopulmonary bypass (CPB) and is thought to contribute to the pathophysiological consequences of CPB. Complement inhibition effects on the post-CPB syndrome were tested with soluble complement receptor-1 (sCR1). METHODS AND RESULTS: Twenty neonatal pigs (weight 1.8 to 2.8 kg) were randomized to control and sCR1-treated groups. LV pressure and volume, left atrial pressure, pulmonary artery pressure and flow, and respiratory system compliance and resistance were measured. Preload recruitable stroke work, isovolumic diastolic relaxation time constant (tau), and pulmonary vascular resistance were determined. Pre-CPB measures were not statistically significantly different between the 2 groups. After CPB, preload recruitable stroke work was significantly higher in the sCR1 group (n=5, 46.8+/-3.2x10(3) vs n=6, 34.3+/-3.7x10(3) erg/cm(3), P=0.042); tau was significantly lower in the sCR1 group (26.4+/-1.5, 42.4+/-6. 6 ms, P=0.003); pulmonary vascular resistance was significantly lower in the sCR1 group (5860+/-1360 vs 12 170+/-1200 dyn. s/cm(5), P=0.009); arterial PO(2) in 100% FIO(2) was significantly higher in the sCR1 group (406+/-63 vs 148+/-33 mm Hg, P=0.01); lung compliance and airway resistance did not differ significantly. The post-CPB Hill coefficient of atrial myocardium was higher in the sCR1 group (2.88+/-0.29 vs 1.88+/-0.16, P=0.023). CONCLUSIONS: sCR1 meaningfully moderates the post-CPB syndrome, supporting the hypothesis that complement activation contributes to this syndrome.

The free radical spin trap alpha-phenyl-tert-butyl nitrone attenuates the cerebral response to deep hypothermic ischemia.

OBJECTIVE: The aim of this study was to assess the role of reactive oxygen species in the impairment of cerebral recovery that follows deep hypothermic circulatory arrest. METHODS: Twelve 1-week-old piglets were randomized to placebo (control group; n = 6) or 100 mg x kg(-1) intravenous alpha-phenyl-tert -butyl nitrone, a free radical spin trap (PBN group; n = 6). All piglets underwent cardiopulmonary bypass, cooling to 18 degrees C, 60 minutes of circulatory arrest followed by 60 minutes of reperfusion, and rewarming. Cerebral blood flow and metabolism were determined at baseline before deep hypothermic circulatory arrest and after 60 minutes of reperfusion. RESULTS: In control animals, mean global cerebral blood flow (+/- 1 standard error) before circulatory arrest was 48.4 +/- 3.6 mL x 100 g(-1) x min(-1) and fell to 25.1 +/- 3.6 mL x 100 g(-1) x min(-1) after circulatory arrest (P =.001). Global cerebral metabolism fell from 3.5 +/- 0.2 mL x 100 g(-1) x min(-1) before arrest to 2.2 +/- 0.2 mL x 100 g(-1) x min(-1) after circulatory arrest (P =.0002). In the PBN group after circulatory arrest, the mean global cerebral blood flow and metabolism of 37.2 +/- 4.9 and 3.6 +/- 0.5 mL. 100 g(-1). min(-1), respectively, were significantly higher than in the control group (P <.05). Recovery of cerebral blood flow in the PBN group was 78% of pre-arrest level compared with 52% in the control group (P =.002). Global cerebral metabolism after circulatory arrest was 100% of the pre-arrest value compared with 61% in the control group (P =.01). Regional recovery of cerebral metabolism in the cerebellum, brain stem, and basal ganglia was 131%, 130%, and 115%, respectively, of pre-arrest values in the PBN group compared with 85%, 78%, and 70% in the control group (P <.04). CONCLUSIONS: Reactive oxygen species contribute to the impairment of cerebral recovery that follows deep hypothermic circulatory arrest. The use of alpha-phenyl-tert -butyl nitrone before the arrest period attenuates the normal response to ischemia and improves recovery by affording protection from free radical-mediated damage.

Blood gas management and degree of cooling: effects on cerebral metabolism before and after circulatory arrest.

This study investigated the effects of different cooling strategies on cerebral metabolic response to circulatory arrest. In particular, it examined the impact of blood gas management and degree of cooling on cerebral metabolism before and after deep hypothermic circulatory arrest. Sixty-nine 1-week-old piglets (2 to 3 kg) were placed on cardiopulmonary bypass (37 degrees C) at 100 ml/kg per minute. Animals were cooled to 18 degrees or 14 degrees C as follows: alpha-stat strategy to 18 degrees C (n = 9) or 14 degrees C (n = 6), pH-stat strategy to 18 degrees C (n = 12) or 14 degrees C (n = 10). Animals underwent 60 minutes of circulator arrest followed by rewarming with alpha-stat strategy to 36 degrees C. Control animals were cooled with alpha-stat strategy to 18 degrees C (n = 10) or 14 degrees C (n = 3) and then maintained on cold cardiopulmonary bypass (100 ml/kg per minute) for 60 minutes. Three animals were excluded (see text). With the use of xenon 133 clearance methods, cerebral blood flow was measured at the following points: point I, cardiopulmonary bypass (37 degrees C); point II, cardiopulmonary bypass before circulatory arrest or control flow (18 degrees or 14 degrees C); and point III, cardiopulmonary bypass after rewarming (36 degrees C). Cerebral metabolic rate of oxygen consumption was calculated for each point. At point II, cerebral metabolism was more suppressed at 14 degrees C compared with that at 18 degrees C. At any given temperature (18 degrees or 14 degrees C), pH-stat strategy provided the greatest suppression of of cerebral metabolism. In control animals, cerebral metabolic oxygen consumption of point III returned to baseline values after 60 minutes of cold bypass. Sixty minutes of circulatory arrest resulted in a significant reduction in cerebral metabolic oxygen consumption at point III compared with that at point I regardless of cooling temperature or blood gas strategy. The amount of cerebral metabolic recovery was significantly reduced in the pH-stat 14 degrees C group compared with that in the pH-stat 18 degrees C group at point III. The use of pH-stat strategy followed by a switch to alpha-stat at 14 degrees C provided better cerebral metabolic recovery compared with either strategy used alone. The use of pH-stat strategy during initial cooling may provide the animal with maximal cerebral metabolic suppression. The cerebral acidosis produced with pH-stat cooling may worsen cerebral metabolic injury from circulatory arrest, but this affect is eliminated with the use of alpha-stat just before the period of circulatory arrest.

The effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest.

OBJECTIVE: The purpose of this study was to determine the effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest. METHODS: Sixteen 1-week-old piglets underwent cardiopulmonary bypass, were cooled to 18 degrees C, and underwent 60 minutes of circulatory arrest, followed by 60 minutes of reperfusion and rewarming. Global and regional cerebral blood flow, cerebral oxygen metabolism, and renal blood flow were determined before cardiopulmonary bypass, after the institution of cardiopulmonary bypass, and at 1 hour of deep hypothermic circulatory arrest. In the study group (n = 8 piglets), a leukocyte-depleting arterial blood filter was placed in the arterial side of the cardiopulmonary bypass circuit. RESULTS: With cardiopulmonary bypass, no detectable change occurred in the cerebral blood flow, cerebral oxygen metabolism, and renal blood flow in either group, compared with before cardiopulmonary bypass. In control animals, after deep hypothermic circulatory arrest, blood flow was reduced to all regions of the brain (P <.004) and the kidneys (P =.02), compared with before deep hypothermic circulatory arrest. Cerebral oxygen metabolism was also significantly reduced to 60.1% +/- 11.3% of the value before deep hypothermic circulatory arrest (P =.001). In the leukocyte-depleting filter group, the regional cerebral blood flow after deep hypothermic circulatory arrest was reduced, compared with the value before deep hypothermic circulatory arrest (P <.01). Percentage recovery of cerebral blood flow was higher in the leukocyte filter group than in the control animals in all regions but not significantly so (P >.1). The cerebral oxygen metabolism fell to 66.0% +/- 22.3% of the level before deep hypothermic circulatory arrest, which was greater than the recovery in the control animals but not significantly so (P =.5). After deep hypothermic circulatory arrest, the renal blood flow fell to 81.0% +/- 29.5% of the value before deep hypothermic circulatory arrest (P =.06). Improvement in renal blood flow in the leukocyte filter group was not significantly greater than the recovery to 70.2% +/- 26.3% in control animals (P =.47). CONCLUSIONS: After a period of deep hypothermic circulatory arrest, there is a significant reduction in cerebral blood flow, cerebral oxygen metabolism, and renal blood flow. Leukocyte depletion with an in-line arterial filter does not appear to significantly improve these findings in the neonatal piglet.

Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets: timing of dose is important.

INTRODUCTION: Cardiopulmonary bypass produces an inflammatory response that can cause significant postoperative pulmonary dysfunction and total body edema. This study evaluates the efficacy of preoperative methylprednisolone administration in limiting this injury in neonates and compares the effect of giving methylprednisolone 8 hours before an operation to the common practice of adding methylprednisolone to the cardiopulmonary bypass circuit prime. METHODS: A control group of neonatal pigs (control; n = 6) received no preoperative medication. One experimental group (n = 6) received methylprednisolone sodium succinate (30 mg/kg) both 8 and 1.5 hours before the operation. A second experimental group received no preoperative treatment, but methylprednisolone (30 mg/kg) was added to the cardiopulmonary bypass circuit prime. All animals underwent cardiopulmonary bypass and 45 minutes of deep hypothermic circulatory arrest. Hemodynamic and pulmonary function data were acquired before cardiopulmonary bypass and at 30 and 60 minutes after bypass. RESULTS: In the control group, pulmonary compliance, alveolar-arterial gradient, and pulmonary vascular resistance were significantly impaired after bypass (P <.01 for each by analysis of variance). In the group that received methylprednisolone, compliance (P =.02), alveolar-arterial gradient (P =.0003), pulmonary vascular resistance (P =.007), and extracellular fluid accumulation (P =.003) were significantly better after bypass when compared with the control group. Results for the group that received no preoperative treatment fell between the control group and the group that received methylprednisolone. CONCLUSIONS: When given 8 hours and immediately before the operation, methylprednisolone improves pulmonary compliance after bypass, alveolar-arterial gradient, and pulmonary vascular resistance compared with no treatment. The addition of methylprednisolone to the cardiopulmonary bypass circuit prime is beneficial but inferior to preoperative administration.

Modified ultrafiltration versus conventional ultrafiltration: a randomized prospective study in neonatal piglets.

UNLABELLED: Cardiopulmonary bypass in neonates generates large increases in inflammatory mediators, causing edema formation that may lead to multiple organ dysfunction. Clinical strategies aimed at removing inflammatory mediators, reducing edema formation, and improving organ function include conventional and modified ultrafiltration. OBJECTIVE: This study examines the effectiveness of conventional and modified ultrafiltration in preventing weight gain, myocardial edema formation, and left ventricular dysfunction in neonatal piglets undergoing cardiopulmonary bypass. METHODS: In this randomized prospective study, 18 1-week-old piglets were supported with cardiopulmonary bypass at 100 ml kg(-1) x min(-1), cooled to 25 degrees C, exposed to 75 minutes of cardioplegic arrest, rewarmed to 37 degrees C, and weaned from bypass. Left ventricular myocardial contractility was assessed by the preload-recruitable stroke work method, with the use of a sonomicrometric two-dimensional cylindrical model, before bypass and at 10, 60, and 120 minutes after separation from bypass. RESULTS: Total body weight gain was significantly less in the modified ultrafiltration group than in either the conventional ultrafiltration group or the control group (no filtration). Myocardial wet/dry ratios were also improved with modified ultrafiltration, but not with conventional ultrafiltration, when compared with no filtration (control group). Hemodynamically, modified ultrafiltration was superior to conventional ultrafiltration and no filtration (control) in raising the mean arterial pressure and increasing the left ventricular preload-recruitable stroke work after bypass. CONCLUSION: Modified ultrafiltration is superior to conventional ultrafiltration and no filtration in reducing the total body weight gain, lessening myocardial edema, raising mean arterial pressure, and improving left ventricular contractility in neonatal piglets undergoing cardiopulmonary bypass and cardioplegic arrest.

The role of endothelial nitric oxide synthase expression in the development of pulmonary hypertension in chronically hypoxic infant swine.

OBJECTIVE: Our goal was to determine the role of pulmonary endothelial nitric oxide synthase expression in the development of pulmonary hypertension in infants with congenital cyanotic heart disease. METHODS: Two groups of 4-week-old piglets were studied. In one group, the piglets were raised in an environment of 10% oxygen from 2 days of age (cyanotic, n = 6), and in the other group the piglets were raised at room air (control, n = 5). Pulmonary hemodynamics were measured in vivo for each animal, and peripheral lung biopsy specimens were obtained for Western blot analysis with the use of antiendothelial nitric oxide synthase antibody and for activity analysis with the use of the tritiated L-arginine assay. RESULTS: The piglets in the chronically hypoxic group had significant increases in mean pulmonary arterial pressure (44.0 +/- 3.8 mm Hg vs 14.8 +/- 1.2 mm Hg in controls, p = 0.0007) and pulmonary vascular resistance (7272.0 +/- 871.1 dyne x cm x sec(-5) vs 1844.5 +/- 271.2 dyne x cm x sec(-5) in controls, p = 0.002). These changes in the pulmonary hemodynamics of the hypoxic piglets were accompanied by a twofold increase in the expression of pulmonary endothelial nitric oxide synthase (p = 0.0043) but no corresponding increase in nitric oxide synthase activity. CONCLUSIONS: Raising infant piglets in an environment of 10% oxygen for 4 weeks results in significant pulmonary arterial hypertension accompanied by increased expression of nitric oxide synthase within the lung endothelium. Furthermore, the increased levels of nitric oxide synthase within the lungs of the hypoxic swine were not accompanied by a proportional increase in enzyme activity. These findings suggest that the development of pulmonary hypertension in infants with congenital cyanotic disease is not due to decreased expression of endothelial nitric oxide synthase, but instead may be related to a decreased ability of the enzyme to produce sufficient nitric oxide.

Platelet-activating factor receptor antagonism improves cerebral recovery after circulatory arrest.

BACKGROUND: The aim of this study was to determine the effects of antagonism of platelet-activating factor receptors on cerebral recovery after deep hypothermic circulatory arrest (DHCA). METHODS: Fourteen 1-week-old piglets were randomly assigned to either placebo (n = 7), or 10 mg/kg intravenous ginkgolide B (BN52021), a naturally occurring platelet-activating factor receptor antagonist. All piglets had cardiopulmonary bypass, cooling to 18 degrees C, 60 minutes of circulatory arrest followed by 60 minutes of reperfusion and rewarming. Global and regional cerebral blood flow, cerebral oxygen metabolism and renal blood flow were determined at baseline before DHCA and after 60 minutes of reperfusion. RESULTS: Blood flow was significantly reduced in all regions of the brain (p < 0.001) and the kidneys (p = 0.02) after DHCA in control animals. Cerebral oxygen metabolism was also significantly reduced after DHCA to 59.2% +/- 3.2% of the pre-DHCA value (p = 0.0003). In the ginkgolide B group, recovery of global cerebral blood flow to 60.4% +/- 2.8% of pre-DHCA level and of global cerebral oxygen metabolism to 77.1% +/- 5.8% of pre-DHCA value were significantly higher than the recovery in the control group (p < 0.02). Regional recovery of cerebral blood flow and oxygen metabolism in the gingkolide B group was greatest in the cerebellum and brainstem. Renal blood flow did not decrease significantly after DHCA in the gingkolide B group (p = 0.23). CONCLUSIONS: These results suggest that production of platelet-activating factor is increased in the brain after DHCA. Platelet-activating factor receptor antagonism with ginkgolide B before the circulatory arrest period can significantly improve recovery of cerebral blood flow and oxygen metabolism and renal blood flow after DHCA.

Intermittent perfusion protects the brain during deep hypothermic circulatory arrest.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) has been shown to cause impairment in recovery of cerebral blood flow (CBF) and cerebral metabolism (CMRO2) proportional to the duration of the DHCA period. This effect on CMRO2 may be a marker for brain injury, because CMRO2 recovers normally after cardiopulmonary bypass (CPB) when DHCA is not used. The aim of this study was to investigate the effects of intermittent perfusion during DHCA on the recovery of CMRO2 after CPB and to correlate these findings with electron microscopy (EM) of the cerebral microcirculatory bed. METHODS: Fifteen neonatal piglets were placed on CPB and cooled to 18 degrees C. Each animal then underwent either: (1) 60 minute continuous CPB (control), (2) 60 minute uninterrupted DHCA (UI-DHCA), or (3) 60 minute DHCA with intermittent perfusion (1 minute every 15 minutes) (I-DHCA). All animals were then rewarmed and weaned from CPB. Measurements of CBF and CMRO2 were taken before and after CPB. A further 9 animals underwent CPB without DHCA (2 animals) or with DHCA (7 animals), under various conditions of arterial blood gas management, intermittent perfusion, and reperfusion time. RESULTS: UI-DHCA resulted in significant impairment to recovery of CMRO2 after CPB (p < 0.05). Regardless of the blood gas strategy used, the EM after UI-DHCA revealed extensive damage characterized by perivascular intracellular and organelle edema, and vascular collapse. I-DHCA, on the other hand, produced a pattern of normal CMRO2 recovery identical to controls, and the EM was normal for both these groups. CONCLUSIONS: Intermittent perfusion during DHCA is clinically practical and results in normal cerebral metabolic and ultrastructural recovery. Furthermore, the correlation between brain structure and CMRO2 suggests that monitoring CMRO2 during the operation may be an outstanding way to investigate new strategies for neuroprotection designed to reduce cerebral damage in children undergoing correction of congenital cardiac defects.

Effects of ischemia on pulmonary dysfunction after cardiopulmonary bypass.

BACKGROUND: Pulmonary hypertension and lung injury secondary to cardiopulmonary bypass (CPB) are probably caused by a combination of ischemia and inflammation. This study was undertaken to investigate the potential ischemic effects of cessation of pulmonary arterial flow during CPB on pulmonary injury. METHODS: Twenty neonatal piglets (2.5 to 3.1 kg) were randomly assigned to two groups. Group A (n = 10) underwent 90 minutes of CPB at full flow (100 mL x kg(-1) x min(-1)) and clamping of the main pulmonary artery (PA). Group B (n = 10) underwent 90 minutes of partial CPB (66 mL x kg(-1) x min(-1)) with continued mechanical ventilation and without clamping of the PA. All hearts were instrumented with micromanometers and a PA ultrasonic flow probe. Endothelial function was assessed by measuring endothelial-dependent relaxation (measured by change in pulmonary vascular resistance after PA infusion of acetylcholine) and endothelial-independent relaxation (measured by change in pulmonary vascular resistance after ventilator infusion of nitric oxide and PA infusion of sodium nitroprusside). RESULTS: All groups exhibited signs of pulmonary injury after CPB as evidenced by significantly increased pulmonary vascular resistance, increased alveolar-arterial O2 gradients, and decreased pulmonary compliance (p<0.05); however, pulmonary injury was significantly worse in group A (p<0.05). CONCLUSIONS: This study suggests that although exposure to CPB alone is enough to cause pulmonary injury, cessation of PA flow during CPB contributes significantly to this pulmonary dysfunction.

Preoperative high dose methylprednisolone attenuates the cerebral response to deep hypothermic circulatory arrest.

OBJECTIVE: The aim of this study was to assess the effects of preoperative high dose methylprednisolone on cerebral recovery following a period of deep hypothermic circulatory arrest (DHCA). METHODS: Sixteen 1-week-old piglets were randomized to placebo (n=8), or 30 mg/kg intramuscular methylprednisolone sodium succinate (MPRED) given at 8 and 2 h before induction of anaesthesia. All piglets underwent cardiopulmonary bypass, cooling to 18 degrees C, 60 min of circulatory arrest followed by 60 min of reperfusion and rewarming. The radiolabelled microsphere method was used to determine the global and regional cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) at baseline before DHCA and after 60 min of reperfusion. RESULTS: In controls, mean global CBF (+/-1 standard error) before DHCA was 53.7+/-2.4 ml/100 g per min and fell to 23.8+/-1.2 ml/100 g per min following DHCA (P<0.0001). This represents a post-DHCA recovery to 45.1+/-3.3% of the pre-DHCA value. In the MPRED group recovery of global CBF post-DHCA was significantly higher at 63.6+/-5.2% of the pre-DHCA value (P=0.009). The regional recovery of CBF in the cerebellum, brainstem and basal ganglia was 80, 75 and 69% of pre-DHCA values in the MPRED group respectively compared to 66, 60 and 55% in controls (P<0.05). Global CMRO(2) in controls fell from 3.9+/-0.2 ml/100 g per min before to 2. 3+/-0.2 ml/100 g per min after DHCA (P=0.0001). This represents a post-DHCA recovery to 58.6+/-4.4% of the pre-DHCA value. In the MPRED group, however, recovery of global CMRO(2) post-DHCA was significantly higher at 77.9+/-7.1% of the pre-DHCA value (P=0.04). CONCLUSIONS: Treatment with high dose methylprednisolone at 8 and 2 h preoperatively attenuates the normal cerebral response to a period of deep hypothermic ischaemia. This technique may therefore offer a safe and inexpensive strategy for cerebral protection during repair of congenital heart defects with the use of DHCA.

Jugular ligation does not increase intracranial pressure but does increase bihemispheric cerebral blood flow and metabolism.

OBJECTIVES: To answer the following questions: a) Does jugular venous ligation (simulating venovenous extracorporeal life support) alter proximal jugular venous pressure, intracranial pressure, hemispheric cerebral blood flow, or cerebral metabolism? b) Does release of ligation reverse these effects? and c) What are the comparative effects of venous ligation alone vs. venous ligation in combination with arterial ligation? DESIGN: Prospective, randomized, laboratory investigation. SETTING: Multidisciplinary laboratory setting. SUBJECTS: Sixteen swine, weighing 8.1 to 12.1 kg, 3 to 4 wks of age. INTERVENTIONS: Sixteen swine were randomly assigned to two groups, utilizing a random sequence of vessel ligation. Nine swine underwent occlusion of the right internal and external jugular veins alone (venovenous ligation) followed by release of the occlusion and then occlusion of the right common carotid artery and the right internal and external jugular veins together (venoarterial ligation). The remaining seven swine underwent venoarterial ligation, followed by release of the occlusion and then venovenous ligation. In the experimental group in which venovenous ligation was performed first, the 5, and 30-min release periods after ligation were taken to represent the effects of draining the right jugular vein during venovenous extracorporeal life support. MEASUREMENTS AND MAIN RESULTS: Data were obtained at baseline, 5, and 30 mins after each ligation/release period. Intracranial pressure, right and left internal jugular pressures/flow rates, and cerebral sinus lactate concentrations were measured. Cerebral blood flow was determined using 133Xe clearance methodology, and the cerebral metabolic rate was calculated. There were no significant differences between the ipsilateral internal jugular pressure or extracorporeal life support at 5 or 30 mins after venovenous or venoarterial ligation compared with baseline values or compared with the release of the ligation at 5 or 30 mins. There was a significant increase in right-side (44.7 +/- 2.0 vs. 38.8 +/- 2.4 mL/kg/min; p < .05) and left-side (42.9 +/- 2.3 vs. 38.7 +/- 1.9 mL/kg/min; p < .05) cerebral blood flow 5 mins after venovenous ligation when compared with baseline values. Similarly, after venoarterial ligation, there was a significant increase in right-side (44.6 +/- 2.2 vs. 38.8 +/- 2.4 mL/kg/min; p < .05) and left-side (43.9 +/- 1.5 vs. 38.7 +/- 1.9 mL/kg/min; p < .05) and cerebral blood flow. Cerebral oxygen consumption was significantly increased after venovenous (2.7 +/- 0.2 to 3.2 +/- 0.2 mL/kg/min; p < .05) and venoarterial (2.7 +/- 0.2 to 3.1 +/- 0.2 mL/kg/min; p < .05) ligation at 5 mins after ligation. This increase persisted at the 30-min period and after release of ligation. CONCLUSIONS: Ligation of the right jugular veins alone (venovenous ligation) or jugular veins and right carotid artery (venoarterial ligation) does not increase jugular venous pressures or intracranial pressure. However, this procedure does increase cerebral blood flow and cerebral oxygen consumption. These findings demonstrate that there is adequate decompression of the venous system by the cerebrovascular system and retrograde decompression during extracorporeal life support appears unwarranted.