Response of cerebral blood flow to phenylephrine infusion during hypothermic cardiopulmonary bypass: influence of PaCO2 management

Twenty-eight adult patients anesthetized with fentanyl, then subjected to hypothermic cardiopulmonary bypass (CPB), were studied to determine the effect of phenylephrine-induced changes in mean arterial pressure (MAP) on cerebral blood flow (CBF). During CPB patients managed at 28 degrees C with either alpha-stat (temperature-uncorrected PaCO2 = 41 +/- 4 mmHg) or pH-stat (temperature-uncorrected PaCO2 = 54 +/- 8 mmHg) PaCO2 for blood gas maintenance received phenylephrine to increase MAP greater than or equal to 25% (group A, n = 10; group B, n = 6). To correct for a spontaneous, time-related decline in CBF observed during CPB, two additional groups of patients undergoing CPB were either managed with the alpha-stat or pH-stat approach, but neither group received phenylephrine and MAP remained unchanged in both groups (group C, n = 6; group D, n = 6). For all patients controlled variables (nasopharyngeal temperature, PaCO2, pump flow, and hematocrit) remained unchanged between measurements. Phenylephrine data were corrected based on the data from groups C and D for the effect of diminishing CBF over time during CPB. In patients in group A CBF was unchanged as MAP rose from 56 +/- 7 to 84 +/- 8 mmHg. In patients in group B CBF increased 41% as MAP rose from 53 +/- 8 to 77 +/- 9 mmHg (P less than 0.001). During hypothermic CPB normocarbia maintained via the alpha-stat approach at a temperature-uncorrected PaCO2 of approximately equal to 40 mmHg preserves cerebral autoregulation; pH-stat management (PaCO2 approximately equal to 57 mmHg uncorrected for temperature, or 40 mmHg when corrected to 28 degrees C) causes cerebrovascular changes (i.e., impaired autoregulation) similar to those changes produced by hypercarbia in awake, normothermic patients.     

Increasing mean arterial pressure improves jugular venous oxygen saturation in patients with and without preexisting stroke during normothermic cardiopulmonary bypass

STUDY OBJECTIVE: To examine whether increasing mean arterial pressure (MAP) with the administration of phenylephrine would improve internal jugular venous oxygen saturation (SjvO2) during normothermic cardiopulmonary bypass (CPB) in patients with preexisting stroke. DESIGN: Prospective, controlled study. SETTING: Cardiovascular center and university hospital. PATIENTS: 17 patients with preexisting stroke who were scheduled for elective coronary artery bypass graft (CABG) surgery, and a control group of 17 age-matched patients without preexisting stroke. INTERVENTIONS: After the induction of anesthesia, a fiberoptic oximetry catheter was inserted into the right jugular bulb to monitor SjvO2. After measuring the baseline partial pressure of the arterial and jugular venous blood gases and cardiovascular hemodynamic values immediately before the start of the study protocol, MAP was increased by the repeated administration of a 10 microg bolus of phenylephrine, until it reached 200% of baseline values. MEASUREMENTS: Partial pressure of the arterial and jugular venous blood gases and cardiovascular hemodynamic values before and after the treatment were recorded. MAIN RESULTS: There was no significant difference between the groups in SjvO2 values at baseline (Mann-Whitney U test: p = 0.22). SjvO2 values in both groups were increased after the administration of phenylephrine (SjvO2 values in the control group: 60 +/- 5%, SjvO2 values in the stroke group: 57 +/- 5%). There was no significant difference between the stroke and control groups in SjvO2 values after the administration of phenylephrine (Mann-Whitney U test: p = 0.08). CONCLUSIONS: Increasing MAP improves SjvO2 in patients with or without preexisting stroke during normothermic CPB.     

Support of mean arterial pressure during tepid cardiopulmonary bypass: effects of phenylephrine and pump flow on systemic oxygen supply and demand.

OBJECTIVE: To examine the effects of phenylephrine infusion and increases in pump flow on systemic oxygen supply and demand when they are used to support mean arterial pressure (MAP) during cardiopulmonary bypass (CPB). DESIGN: Prospective, unblinded study. SETTING: The animal cardiopulmonary laboratory at the Mayo Foundation (Rochester, MN). PARTICIPANTS: Twelve pigs. INTERVENTIONS: Twelve pigs had systemic oxygen delivery (DO2) and consumption (VO2) measured before CPB and then underwent CPB at 35 degrees C. During CPB, measurements of DO2 and VO2 were obtained at an MAP of approximately 50 mmHg and a pump flow of 2.2 L/min/m2. Thereafter, MAP was elevated to 70 mmHg either by increases in pump flow or by a phenylephrine infusion, and the balance between systemic oxygen supply and demand was reassessed. MEASUREMENTS AND MAIN RESULTS: Before CPB, DO2 was 375 +/- 83 mL/min/m2 and decreased with the onset of CPB mainly because of the effects of hemodilution. During CPB, with a pump flow of 2.2 L/min/m2 and an MAP of 53 mmHg, DO2 was 218 +/- 40 mL/min/m2. Increasing perfusion pressure to an MAP of 72 mmHg with phenylephrine and maintaining pump flow constant (2.2 L/min/m2) did not change DO2 (222 +/- 37 mL/min/m2), and the oxygen extraction ratio (OER) was increased relative to pre-CPB levels. In contrast, increasing MAP to 71 mmHg by increasing pump flow to 3.2 L/min/m2 resulted in a significantly greater DO2, and the OER normalized to the pre-CPB value. CONCLUSIONS: During CPB with conventional flow rates, DO2 is decreased. Supporting MAP with increases in pump flow better maintains DO2 than the administration of an alpha-agonist.     

Increasing mean arterial blood pressure has no effect on jugular venous oxygen saturation in insulin-dependent patients during tepid cardiopulmonary bypass

Preexisting diabetes mellitus is one of the major factors related to adverse postoperative neurological disorders after cardiac surgery. In previous reports, we found that diabetic patients more often experienced cerebral desaturation than nondiabetic patients during normothermic cardiopulmonary bypass (CPB). The purpose of this study was to examine the effects of increasing mean arterial blood pressure (MAP) by the administration of phenylephrine on internal jugular venous oxygen hemoglobin saturation (SjvO2) during tepid CPB in diabetic patients. We studied 20 diabetic patients scheduled for elective coronary artery bypass graft surgery and, as a control, 20 age-matched nondiabetic patients. After the induction of anesthesia, a fiberoptic oximetry catheter was inserted into the right jugular bulb to monitor SjvO2. After measuring the baseline partial pressure of the arterial and jugular venous blood gases and cardiovascular hemodynamic values, MAP was increased by the repeated administration of a 10-microg bolus of phenylephrine until it reached 100% of baseline values. There was a significant difference in SjvO2 value between the Diabetic and Control groups after the administration of phenylephrine (Diabetic group, 56% +/- 6%; Control group: 60% +/- 4%) (P < 0.05). There was a significant difference in the arterial-jugular oxygen content difference value between the Diabetic and Control groups after the administration of phenylephrine (diabetic group, 4.9% +/- 0.6%; Control group, 4.5% +/- 0.4%) (P < 0.05). We subdivided the Diabetic group into three groups (Diet Therapy group [n = 4], Glibenclamide group [n = 10], and Insulin-Dependent group [n = 6]). There was a significant difference in the mean slopes of SjvO2 versus cerebral perfusion pressure for increasing cerebral perfusion pressure between the Insulin-Dependent group and the other groups (Dunnett test: P = 0.04). Increasing MAP had no effects on the SjvO2 value in insulin-dependent patients during tepid CPB. IMPLICATIONS: We examined the effects of increasing mean arterial blood pressure (MAP) by the administration of phenylephrine on internal jugular venous oxygen saturation (SjvO2) during tepid cardiopulmonary bypass in diabetic patients and found that increasing MAP had no effect on the SjvO2 value in insulin-dependent patients.     

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.     

Phenylephrine increases regional cerebral blood flow following hemorrhage during isoflurane-oxygen anesthesia

Using the radioactive microsphere technique regional cerebral blood flow (rCBF) and total CBF (tCBF) were examined in rats at three time periods: baseline (CBF1) during 1.5 MAC inspired isoflurane-oxygen anesthesia, CBF2; during 1.5 MAC inspired isoflurane anesthesia combined with hypotension induced by hemorrhage and CBF3; during isoflurane and hemorrhage plus phenylephrine infused to restore mean arterial pressure (MAP) to baseline. For CBF1 MAP was 89 +/- 3 mmHg (mean +/- SEM, n = 9) with PaCO2 44 +/- 1 mmHg. For CBF2 following graded hemorrhage MAP was 48 +/- 2 mmHg and PaCO2 43 +/- 1 mmHg. For CBF3 MAP was 93 +/- 2 and PaCO2 45 +/- 1 mmHg, following infusion of phenylephrine (PE) at 13.9 +/- 4.0 micrograms.kg-1.min-1. Total CBF1 was 1.84 +/- 0.18 ml.g-1.min-1, tCBF2 1.32 +/- 0.09 ml.g-1.min-1 (P less than 0.05 vs. tCBF1) and tCBF3 2.60 +/- 0.18 (P less than 0.05 vs. tCBF1 and 2). For tCBF3 hemoglobin concentration had decreased 23% from 14.2 +/- 0.2 g.100 ml-1 to 11.0 +/- 0.5 g.100 ml-1 (P less than 0.05). Regional CBF decreased significantly in seven of 12 regions examined from CBF1 to CBF2 and was significantly higher in all regions for CBF3. For CBF1-3 infratentorial blood flows (cerebellar and brain stem) were significantly higher than flows to the supratentorial structures (cerebral cortical and basal ganglia). During isoflurane anesthesia, phenylephrine infused to support MAP following hemorrhagic hypotension effectively maintains rCBF and tCBF. There is no indication that phenylephrine infused to increase MAP following hemorrhage results in cerebral vasoconstriction in rats anesthetized with isoflurane.     

Phenylephrine Increases Cerebral Blood Flow during Low-flow Hypothermic Cardiopulmonary Bypass in Baboons

Background: Although low-flow cardiopulmonary bypass (CPB) has become a preferred technique for the surgical repair of complex cardiac lesions in children, the relative hypotension and decrease in cerebral blood flow (CBF) associated with low flow may contribute to the occurrence of postoperative neurologic injury. Therefore, it was determined whether phenylephrine administered to increase arterial blood pressure during low-flow CPB increases CBF.

Methods: Cardiopulmonary bypass was initiated in seven baboons during fentanyl, midazolam, and isoflurane anesthesia. Animals were cooled at a pump flow rate of 2.5 l *symbol* min-1 *symbol* m-2 until esophageal temperature decreased to 20 degrees C. Cardiopulmonary bypass flow was then reduced to 0.5 l *symbol* min-1 *symbol* m-2 (low flow). During low-flow CPB, arterial partial pressure of carbon dioxide (PCO2) and blood pressure were varied in random sequence to three conditions: (1) PCO2 30-39 mmHg (uncorrected for temperature), control blood pressure; (2) PCO2 50-60 mmHg, control blood pressure; and (3) PCO2 30-39 mmHg, blood pressure raised to twice control by phenylephrine infusion. Thereafter, CPB flow was increased to 2.5 l *symbol* min-1 *symbol* m-2, and baboons were rewarmed to normal temperature. Cerebral blood flow was measured by washout of intraarterial133 Xenon before and during CPB.

Results: Phenylephrine administered to increase mean blood pressure from 23+/-3 to 46+/-3 mmHg during low-flow CPB increased CBF from 14+/-3 to 31+/-9 ml *symbol* min-1 *symbol* 100 g-1, P < 0.05. Changes in arterial PCO2 alone during low flow bypass produced no changes in CBF.     

The effect of hemodilution on blood flow regulation in normal and postischemic intestine

We investigated the effect of hemodilution on intestinal blood flow and oxygen consumption (VO2) in denervated rat small intestinal preparations. In one series of experiments, intestinal blood flow (IBF) and intestinal oxygen extraction (A-VO2) were measured during graded decreases in perfusion pressure. Control animals underwent consecutive studies without hemodilution; experimental animals were studied before and after isovolemic hemodilution. In a second series of experiments, normovolemic hemodilution was performed in experimental animals NH while hematocrit was maintained in controls, C. Preparations were then subjected to 30 min of complete ischemia followed by 30 min of reperfusion. Hemodilution (40.5 +/- 0.8% to 17.2 +/- 2.5%) decreased A-VO2 (3.9 +/- 0.5 to 2.1 +/- 0.4 ml/dl; P less than 0.05) but increased IBF (77.5 +/- 9.8 to 132.1 +/- 15.0 ml/min/100 gm; P less than 0.01). IBF was maintained to the limit of pressure:flow autoregulation (69 mmHg). Below this point, decreases in IBF were accompanied by increases in A-VO2 thus maintaining VO2. At a much lower "critical pressure" (42 mmHg) maximal oxygen extraction was reached and VO2 decreased with IBF. In the second series of experiments, hemodiluted animals (hematocrit 25 +/- 1%) studied during the reperfusion period maintained higher O2 consumption [30 min values (ml/min/100 gm): 4.8 +/- 0.9 NH vs 1.6 +/- 0.2 C, P less than 0.01] and A-VO2 difference [30 min values (vol%): 3.9 +/- 0.4 NH vs 2.1 +/- 0.4 C, P less than 0.005] than control animals (hct 33 +/- 2%). Hemodilution does not impair the intestine's ability to maintain O2 consumption during hypotension and hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sodium nitroprusside infusion does not dilate cerebral resistance vessels during hypothermic cardiopulmonary bypass

This study determined whether sodium nitroprusside (SNP) changes cerebral vascular resistance during stable, hypothermic cardiopulmonary bypass (CPB). Cerebral blood flow (CBF) was measured using Xenon clearance in 39 patients anesthetized with fentanyl. In 25 patients (group 1), CBF was measured before and during infusion of SNP at a rate sufficient to reduce mean arterial pressure (MAP) approximately 20%. In 14 other patients (group 2), CBF was measured before and during simultaneous infusion of SNP and phenylephrine; SNP was continued at a rate that had reduced MAP approximately 20% while phenylephrine was added in a dose sufficient to restore MAP to preinfusion levels. Patients within each group were randomized to maintenance of PaCO2 approximately 40 mmHg (groups 1a and 2a), uncorrected for body temperature, or to maintenance of PaCO2 approximately 50 mmHg (groups 1b and 2b). The following variables were maintained within a narrow range: nasopharyngeal temperature (26-29 degrees C), pump oxygenator flow (1.7-2.5 l.min-1.m-2), PaO2 (150-300 mmHg), and Hct (22-28 vol%). In each patient, controlled variables varied no more than +/- 5% between measurements. In group 1a (PaCO2 approximately 40 mmHg), MAP was 86 +/- 9 mmHg (mean +/- SD) before and 65 +/- 8 mmHg during SNP infusion (P less than 0.0001). CBF was 12 +/- 3 ml.100g-1.min-1 before and 10 +/- 2 ml.100(-1).min-1 during SNP infusion (P less than 0.01). In group 1b (PaCO2 approximately 55 mmHg), MAP was 86 +/- 11 mmHg before and 66 +/- 13 mmHg during SNP infusion (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of hypervolemic hemodilution with and without hypertension on cerebral blood flow following middle cerebral artery occlusion in rats anesthetized with isoflurane

The effect of hypervolemic hemodilution or hypervolemic hemodilution with dopamine-induced hypertension on cerebral blood flow (CBF) was investigated during 1.2 MAC isoflurane anesthesia in rats (n = 24) subjected to middle cerebral artery occlusion (MCAO). Prior to MCAO each animal was randomized to one of the following groups: 1) control, mean arterial pressure (89 +/- 10 mmHg [mean +/- SD]), blood volume, and hematocrit (46 +/- 1) were not manipulated; 2) hypervolemic hemodilution (HH), 30 min before MCAO, 5% albumin was administered to reduce the hematocrit to 29-32%; or 3) hypervolemic hemodilution/dopamine hypertension (HH/Dop), hemodilution was accomplished and dopamine (10 micrograms.kg-1.min-1) was infused during the ischemic period to achieve a mean arterial pressure of 111 +/- 10 mmHg (mean +/- SD). Ten minutes after occlusion of the left middle cerebral artery, CBF was determined using 14C-iodoantipyrine. Five coronal brain sections were analyzed to determine the area within each brain section with CBF ranges of 0-15 ml.100 g-1.min-1 and 15-23 ml.100 g-1.min-1. The area of 0-15 ml.100 g-1.min-1 CBF was less in both the HH and HH/Dop groups compared with control (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral response to hemodilution during hypothermic cardiopulmonary bypass in adults.

We examined the cerebral response to changing hematocrit during hypothermic cardiopulmonary bypass (CPB) in 18 adults. Cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and cerebral oxygen delivery (CDO2) were determined using the nitrous oxide saturation technique. Measurements were obtained before CPB at 36 degrees C, and twice during 27 degrees C CPB: first with a hemoglobin (Hgb) of 6.2 +/- 1.2 g/dL and then with a Hgb of 8.5 +/- 1.2 g/dL. During hypothermia, appropriate reductions in CMRO2 were demonstrated, but hemodilution-associated increases in CBF offset the reduction in CBF seen with hypothermia. At 27 degrees C CPB, as the Hgb concentration was increased from 6.2 to 8.5 g/ dL, CBF decreased. CDO2 and CMRO2 were no different whether the Hgb was 6.2 or 8.5 g/dL. In eight patients in whom the Hgb was less than 6 g/dL, CDO2 remained more than twice CMRO2. IMPLICATIONS: This study suggests that cerebral oxygen balance during cardiopulmonary bypass is well maintained at more pronounced levels of hemodilution than are typically practiced, because changes in cerebral blood flow compensate for changes in hemoglobin concentration.     

Electrical correlates of brain injury resulting from severe hypotension and hemodilution in monkeys

The effects of hypotension, hemodilution, and their combination on the relationship between concurrent brain electrical activity and resulting brain injury were studied in anesthetized monkeys. The authors compared changes in the electroencephalogram and somatosensory and auditory evoked potentials with eventual neuropathologic outcome. Our goals were: 1) to define the margin of safety for the monkey brain during hemodilution and hypotension under several simulated clinical conditions; and 2) to determine whether noninvasive measurements of brain electrical activity can predict ischemic brain cell damage. Forty-one monkeys were anesthetized with halothane (0.8 vol % inspired) and ventilated mechanically. Arterial hypotension was induced with trimethaphan (25 +/- 8 mmHg mean arterial blood pressure [MABP] for 30 min). Hemodilution was induced by replacing blood with lactated Ringer's solution (14 +/- 2% hematocrit for 1 h). Combined hemodilution and hypotension consisted of 30 min of hemodilution alone followed by superimposing hypotension for 30 min (16 +/- 3% hematocrit and 29 +/- 5 mmHg MABP). Ten monkeys died following severe hypotension alone or combined hemodilution and hypertension as a consequence of cardiac arrest or undetermined (possibly neurologic) causes. No histologic evidence of ischemic brain cell injury was found in surviving monkeys subjected to hemodilution or hypotension alone. Neuropathologic alterations in the cerebral cortex, cerebellum, hippocampus and globus pallidus as well as neurologic and behavioral deficits were found in seven of 16 surviving monkeys subjected to both hemodilution and hypotension. These findings resulted from combinations of hematocrit less than 20% and MABP below 40 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Critical Hematocrit in Intestinal Tissue Oxygenation during Severe Normovolemic Hemodilution

Background: A critical point in oxygen supply for microvascular oxygenation during normovolemic hemodilution has not been identified. The relation between organ microvascular oxygen partial pressure ([mu]Po2) and organ oxygen consumption ( o2) during a decreasing oxygen delivery (Do2) is not well understood. The present study was designed to determine the systemic hematocrit and organ Do2 values below which organ [mu]Po2 and o2 cannot be preserved by regulatory mechanisms during normovolemic hemodilution.

Methods: Eighteen male Wistar rats were randomized between an experimental group (n = 12), in which normovolemic hemodilution was performed with pasteurized protein solution (PPS), and a control group (n = 6). Systemic hemodynamic and intestinal oxygenation parameters were monitored. Intestinal [mu]Po2 was measured using the oxygen-dependent quenching of palladium-porphyrin phosphorescence.

Results: Baseline values in hemodilution and control group were similar. Hemodilution decreased hematocrit to 6.2 +/- 0.8% (mean +/- SD). Constant central venous pressure measurements suggested maintenance of isovolemia. Despite an increasing mesenteric blood flow, intestinal Do2 decreased immediately. Initially, [mu]Po2 was preserved, whereas mesenteric venous Po2 (Pmvo2) decreased; below a hematocrit of 15%, [mu]Po2 decreased significantly below Pmvo2. Critical Do2 was 1.5 +/- 0.5 ml[middle dot]kg-1[middle dot]min-1 for o2, and 1.6 +/- 0.5 ml[middle dot]kg-1[middle dot]min-1 for [mu]Po2. Critical hematocrit values for o2 and [mu]Po2 were 15.8 +/- 4.6% and 16.0 +/- 3.5%, respectively.     

Evaluation of cerebral oxygen balance during normothermic cardiopulmonary bypass using jugular oxygen saturation

BACKGROUND: Previous studies suggest that normothermic cardiopulmonary bypass(CPB) impairs cerebral oxygen balance. We studied the effect of normothermic CPB on cerebral oxygen balance evaluated by continuous measurement of oxygen saturation in the jugular vein (SjO2). METHODS: Eleven patients undergoing coronary artery bypass grafting with normothermic CPB were studied. A 4 Fr oxymetry catheter was inserted into the internal jugular bulb for SjO2 monitoring. We measured mean arterial pressure (MAP), SjO2 and hemoglobin (Hgb) concentration at five time points-1) pre CPB, 2) 3) 4) 5, 30, 60 min after the onset of CPB, respectively, 5) 5 min after the end of CPB. RESULTS: MAP decreased significantly 30 min (47 +/- 9 mmHg) and 60 min (48 +/- 9 mmHg) after the onset of CPB compared with the pre CPB (80 +/- 14 mmHg) value. Hgb also decreased significantly 5 min (7.8 +/- 1.1 g x dl(-1)) and 30 min (7.1 +/- 1.0 g x dl(-1)) and 60 min (7.1 +/- 0.8 g x dl(-1)) after the onset of CPB compared with the pre CPB (11 +/- 1.0 g x dl(-1)) value. However, SjO2 showed no significant change throughout the study period. No significant correlation was observed between MAP and SjO2. CONCLUSIONS: Cerebral oxygen balance assessed by SjO2 was not impaired during normothermic CPB, and was unaffected by hypotension and hemodilution.     

Cerebral blood flow does not change following sodium nitroprusside infusion during hypothermic cardiopulmonary bypass

Changes in cerebral blood flow (CBF) associated with decreases in mean arterial pressure (MAP) produced by sodium nitroprusside (SNP) infusion were measured by intra-aortic injection of 133Xe in 17 patients during hypothermic cardiopulmonary bypass (CPB). In each patient, CBF was determined at baseline and then again following SNP-induced reduction of MAP. Two groups were studied. In Group I (n = 9), PaCO2 was maintained near 42 mm Hg uncorrected for nasopharyngeal temperature (NPT). In Group II (n = 8), PaCO2 was maintained near 60 mm Hg, uncorrected for NPT. Nasopharyngeal temperature, MAP, pump oxygenator flow, PaO2, and hematocrit were maintained within a narrow range in each patient during both studies. Since the baseline CBF determinations were conducted at the higher MAP in all subjects, we corrected post-SNP CBF data for the spontaneous decline that occurs over time during CPB. In Group I, a reduction in MAP from 76 +/- 9 mm Hg (mean +/- SD) to 50 +/- 6 mm Hg was associated with a reduction in CBF from 17 +/- 5 to 13 +/- 3 ml.100 g.min-1 (P less than 0.01), a decrease that became statistically insignificant once the time correction factor had been applied (16 +/- 4 ml.100 g-1.min-1). In Group II, MAP declined from 75 +/- 5 mm Hg to 54 +/- 5 mm Hg, and CBF declined from 25 +/- 10 to 17 +/- 7 ml.100 g.min-1 (P less than 0.01), but, again, after time correction, the CBF decline was statistically insignificant (22 +/- 8 ml.100 g-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Intracarotid Infusion of the Nitric Oxide Synthase Inhibitor, l-NMMA, Modestly Decreases Cerebral Blood Flow in Human Subjects

Background: The authors hypothesized that if nitric oxide (NO) was a determinant of background cerebrovascular tone, intracarotid infusion of NG-monomethyl-l-arginine (l-NMMA), a NO synthase (NOS) inhibitor, would decrease cerebral blood flow (CBF) and intracarotid l-arginine would reverse its effect.

Methods: In angiographically normal cerebral hemispheres, after the initial dose-escalation studies (protocol 1), the authors determined the effect of intracarotid l-NMMA (50 mg/min for 5 min) on CBF and mean arterial pressure (MAP) over time (protocol 2). Changes in CBF and MAP were then determined at baseline, during l-NMMA infusion, and after l-NMMA during l-arginine infusion (protocol 3). To investigate effects of higher arterial blood concentrations of l-NMMA, changes in CBF and MAP were assessed at baseline and after a bolus dose of l-NMMA (250 mg/1 min), and vascular reactivity was tested by intracarotid verapamil (1 mg/min, protocol 4). CBF changes were also assessed during induced hypertension with intravenous phenylephrine (protocol 5).

Results: Infusion of l-NMMA (50 mg/min for 5 min, n = 7, protocol 2) increased MAP by 17% (86 +/- 8 to 100 +/- 11 mmHg;P < 0.0001) and decreased CBF by 20% (45 +/- 8 to 36 +/- 6 ml [middle dot] 100 g-1 [middle dot] min-1;P < 0.005) for 10 min. Intracarotid l-arginine infusion after l-NMMA (protocol 3) reversed the effect of l-NMMA. Bolus l-NMMA (protocol 4) increased MAP by 20% (80 +/- 11 to 96+/-13 mmHg;P < 0.005), but there was no significant decrease in CBF. Intracarotid verapamil increased CBF by 41% (44+/- 8 to 62 +/- 9 ml [middle dot] 100 g-1 [middle dot] min-1;P < 0.005). Phenylephrine-induced hypertension increased MAP by 20% (79 +/- 9 to 95 +/- 6 mmHg;P = 0.001) but did not affect CBF.     

Critical hematocrit in intestinal tissue oxygenation during severe normovolemic hemodilution

BACKGROUND: A critical point in oxygen supply for microvascular oxygenation during normovolemic hemodilution has not been identified. The relation between organ microvascular oxygen partial pressure (microPO2) and organ oxygen consumption (VO2) during a decreasing oxygen delivery (DO2) is not well understood. The present study was designed to determine the systemic hematocrit and organ DO2 values below which organ microPO2 and VO2 cannot be preserved by regulatory mechanisms during normovolemic hemodilution. METHODS: Eighteen male Wistar rats were randomized between an experimental group (n = 12), in which normovolemic hemodilution was performed with pasteurized protein solution (PPS), and a control group (n = 6). Systemic hemodynamic and intestinal oxygenation parameters were monitored. Intestinal microPO2 was measured using the oxygen-dependent quenching of palladium-porphyrin phosphorescence. RESULTS: Baseline values in hemodilution and control group were similar. Hemodilution decreased hematocrit to 6.2 +/- 0.8% (mean +/- SD). Constant central venous pressure measurements suggested maintenance of isovolemia. Despite an increasing mesenteric blood flow, intestinal DO2 decreased immediately. Initially, microPO2 was preserved, whereas mesenteric venous PO2 (P(mv)O2) decreased; below a hematocrit of 15%, microPO2 decreased significantly below P(mv)O2. Critical DO2 was 1.5 +/- 0.5 ml x kg(-1) x min(-1) for VO2, and 1.6 +/- 0.5 ml x kg(-1) x min(-1) for microPO2. Critical hematocrit values for VO2 and microPO2 were 15.8 +/- 4.6% and 16.0 +/- 3.5%, respectively. CONCLUSIONS: Intestinal microPO2 and VO2 were limited by a critical decrease in DO2 and hematocrit at the same time. Beyond these critical points not only shunting of oxygen from the microcirculation could be demonstrated, but also a significant correlation between intestinal microPO2 and VO2.     

Hemodilution during Venous Gas Embolization Improves Gas Exchange, without Altering V̇A/Q̇ or Pulmonary Blood Flow Distributions

Background: Isovolemic anemia results in improved gas exchange in rabbits with normal lungs but in relatively poorer gas exchange in rabbits with whole-lung atelectasis. In the current study, the authors characterized the effects of hemodilution on gas exchange in a distinct model of diffuse lung injury: venous gas embolization.

Methods: Twelve anesthetized rabbits were mechanically ventilated at a fixed rate and volume. Gas embolization was induced by continuous infusion of nitrogen via an internal jugular venous catheter. Serial hemodilution was performed in six rabbits by simultaneous withdrawal of blood and infusion of an equal volume of 6% hetastarch; six rabbits were followed as controls over time. Measurements included hemodynamic parameters and blood gases, ventilation-perfusion ( A/ ) distribution (multiple inert gas elimination technique), pulmonary blood flow distribution (fluorescent microspheres), and expired nitric oxide (NO; chemoluminescence).

Results: Venous gas embolization resulted in a decrease in partial pressure of arterial oxygen (PaO2) and an increase in partial pressure of arterial carbon dioxide (PaCO2), with markedly abnormal overall A/ distribution and a predominance of high A/ areas. Pulmonary blood flow distribution was markedly left-skewed, with low-flow areas predominating. Hematocrit decreased from 30 +/- 1% to 11 +/- 1% (mean +/- SE) with hemodilution. The alveolar-arterial PO2 (A-aPO2) difference decreased from 375 +/- 61 mmHg at 30% hematocrit to 218 +/- 12.8 mmHg at 15% hematocrit, but increased again (301 +/- 33 mmHg) at 11% hematocrit. In contrast, the A-aPO2 difference increased over time in the control group (P< 0.05 between groups over time). Changes in PaO2 in both groups could be explained in large part by variations in intrapulmonary shunt and mixed venous oxygen saturation (SvO2); however, the improvement in gas exchange with hemodilution was not fully explained by significant changes in A/ or pulmonary blood flow distributions, as quantitated by the coefficient of variation (CV), fractal dimension, and spatial correlation of blood flow. Expired NO increased with with gas embolization but did not change significantly with time or hemodilution.     

Effects of perfusion pressure on cerebral blood flow and oxygenation during normothermic cardiopulmonary bypass

BACKGROUND: Central nervous system dysfunction after cardiopulmonary bypass (CPB) is an important cause of morbidity and mortality after cardiac surgery. Perfusion pressure (PP) during CPB could be one of the important determinants of cerebral blood flow (CBF). The objective of the present study was to determine the effect of PP on CBF and cerebral oxgenation during normothermic CPB. METHODS: Twelve adult patients undergoing coronary artery bypass graft surgery were randomly assigned to one of two groups based on PP (High and Low group). Patients in High group received phenylephrine immediately after the onset of CPB to maintain PP between 60 and 80 mmHg. Oxyhemoglobin (O2Hb), deoxyhemoglobin (HHb), tissue oxygenation index (TOI), and oxidized cytochrome aa3 (CtOx) were measured by near-infrared spectroscopy, and internal jugular venous bulb blood oxygen saturation (SjvO2) was measured simultaneously. S-100 beta protein concentrations were also measured before and after CPB. RESULTS: SjvO2 in High group increased significantly during CPB. CtOx in Low group decreased significantly during CPB, whereas TOI was unchanged. Although S-100 beta increased significantly at the end of CPB, there was no difference between the groups. CONCLUSIONS: These results suggest that maintaining high PP is benefical for CBF during normothermic CPB.     

A comparison of the cerebral pressure-flow relationship for halothane and isoflurane at haemodynamically equivalent end-tidal concentrations in the rabbit

The cerebral pressure-flow relationship for halothane and isoflurance was studied at end-tidal concentrations which resulted in similar baseline mean arterial pressure (MAP). Two groups of New Zealand white rabbits (n = 8; each group) were studied with five regional blood flow determinations in each animal. Blood flow was determined by injecting radioactive microspheres during the following conditions: injection 1: after stable 2.05 per cent end-tidal isoflurane (1.0 MAC) Group I; or after stable 0.74 +/- 0.04 per cent end-tidal halothane (0.53 MAC) Group H. Injections 2-5: after MAP was increased 20, 40, 60, and 80 per cent respectively above baseline MAP by phenylephrine infusion. Baseline MAP was the same for both groups (64.3 +/- 3.1 vs 67.2 +/- 2.0 mmHg; mean +/- SEM; Group I and H respectively). Baseline total CBF (tCBF; 0.68 +/- 0.03 vs 0.86 +/- 0.05) and hemispheric CBF (hCBF; 0.64 +/- 0.03 vs 0.96 +/- 0.06) were significantly greater in Group H; no significant difference between groups was seen for baseline posterior fossa CBF (pCBF; 0.79 +/- 0.06 vs 0.75 +/- 0.04). For each experiment a pressure-flow curve was generated by curvilinear regression analysis. Significantly greater phenylephrine concentrations were required for injections 2-5 in Group H. Mean slopes and intercepts were derived for each group. Within each group comparison of the pressure-flow curves for hCBF vs MAP and pCBF vs MAP showed autoregulation was less impaired in posterior fossa structures (cerebellum and brain stem) for both anaesthetic agents (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)