Validation in the canine model of a new non-invasive method of measuring coronary blood flow reserve: split dose thallium-201 rest/stress imaging.

Diffusely impaired coronary blood flow reserve is difficult to measure non-invasively. We developed and tested a quantitative non-invasive method of measuring coronary blood flow reserve using thallium-201 perfusion imaging. Ten anesthetized dogs were injected simultaneously at rest with thallium-201 and either Ru-103 or Sn-113 microspheres. SPECT images were obtained followed by varying doses of intravenous adenosine, and a second thallium-201 dose was injected simultaneously with either Nb-95 or Sc-46 microspheres. SPECT images were then repeated. The heart was removed, sectioned and counted, along with arterial blood samples. Blood flow was calculated at rest and stress. Peak resting counts in four regions in each of three SPECT slices were subtracted from stress values and stress/rest thallium-201 count ratios (coronary flow reserve (CFR)) were calculated and correlated with the corresponding microsphere flow ratios. Overall correlation of the imaging and microsphere flow ratios was 0.77 (p = 0.0001). Regional correlation coefficients ranged from 0.65-0.86 (p = 0.0001). Coronary blood flow reserve ratios by the microsphere method ranged from 0.7 to 5.3, and by thallium-201 imaging from 0.33-2.45. The non-invasively measured coronary blood flow reserve with thallium-201 imaging and adenosine stress correlates well with microsphere-measured coronary blood flow reserve over a wide range of coronary flows, and should be useful in clinical studies of CFR impairment.

Can retrograde perfusion mitigate cerebral injury after particulate embolization? A study in a chronic porcine model.

OBJECTIVE: We assessed the impact on histologic and behavioral outcome of an interval of retrograde cerebral perfusion after arterial embolization, comparing retrograde cerebral perfusion with and without inferior vena caval occlusion with continued antegrade perfusion. METHODS: Sixty Yorkshire pigs (27 to 30 kg) were randomly assigned to the following groups: antegrade cerebral perfusion control; antegrade cerebral perfusion after embolization; retrograde cerebral perfusion control; retrograde cerebral perfusion after embolization; retrograde cerebral perfusion with inferior vena cava occlusion, retrograde cerebral perfusion with inferior vena cava occlusion control, and retrograde cerebral perfusion with inferior vena cava occlusion after embolization. After cooling to 20 degrees C, a bolus of 200 mg of polystyrene microspheres 250 to 750 (microm diameter (or saline solution) was injected into the isolated aortic arch. After 5 minutes of antegrade cerebral perfusion, 25 minutes of antegrade cerebral perfusion, retrograde cerebral perfusion, or retrograde cerebral perfusion with inferior vena cava occlusion was instituted. After the operation, all animals underwent daily assessment of neurologic status until the time of death on day 7. RESULTS: Aortic arch return, cerebral vascular resistance, and oxygen extraction data during retrograde cerebral perfusion showed differences, suggesting that more effective flow occurs during retrograde cerebral perfusion with inferior vena cava occlusion, which also resulted in more pronounced fluid sequestration. Microsphere recovery from the brain revealed significantly fewer emboli after retrograde cerebral perfusion with inferior vena cava occlusion. Behavioral scores showed full recovery in all but one control animal (after retrograde cerebral perfusion with inferior vena cava occlusion) by day 7 but were considerably lower after embolization, with no significant differences between groups. The extent of histopathologic injury was not significantly different among embolized groups. Although no histopathologic lesions were present in either the antegrade cerebral perfusion control group or the retrograde cerebral perfusion control group, mild significant ischemic damage occurred after retrograde cerebral perfusion with inferior vena cava occlusion even in control animals. CONCLUSIONS: Although effective washout of particulate emboli from the brain can be achieved with retrograde cerebral perfusion with inferior vena cava occlusion, no advantage of retrograde cerebral perfusion with inferior vena cava occlusion after embolization is seen from behavioral scores, electroencephalographic recovery, or histopathologic examination; retrograde cerebral perfusion with inferior vena cava occlusion results in greater fluid sequestration and mild histopathologic injury even in control animals. Retrograde cerebral perfusion with inferior vena cava occlusion shows clear promise in the management of embolization, but further refinements must be sought to address its still worrisome potential for harm.

The effect of retrograde cerebral perfusion after particulate embolization to the brain.

Neurologic injury as a consequence of cerebral embolism of either air or atherosclerotic debris during cardiac or aortic surgery is still a major cause of postoperative morbidity and mortality. While exploring various means of improving cerebral protection during complex cardiothoracic procedures, we have developed a chronic porcine model to study retrograde cerebral perfusion. We have previously demonstrated that retrograde perfusion results in a small amount of nutritive flow and provides cerebral protection that appears to be superior to simple prolonged hypothermic circulatory arrest. The current study was designed to evaluate the efficacy of retrograde cerebral perfusion in mitigating the effects of particulate cerebral embolism occurring during cardiac surgery. Four groups of pigs (19 to 28 kg) underwent cardiopulmonary bypass with deep hypothermia at an esophageal temperature of 20 degrees C: an antegrade control group (AC, n = 5), an antegrade embolism group (AE, n = 10), a retrograde control group (RC, n = 5), and a retrograde embolism group (RE, n = 10). In addition, because of extreme heterogeneity in outcome in the initial RE group, an additional group of 10 animals underwent embolism and retrograde perfusion at a later time. Embolization was accomplished by injection of 200 mg of polystyrene microspheres (250 to 750 micrograms in diameter) via the aortic cannula into an isolated aortic arch preparation in the AE and RE groups; the control groups received injections of 10 ml of saline solution. After infusion of the microspheres or saline solution, conventional perfusion, with the aortic arch pressure maintained at 50 mm Hg, was continued for a total of 30 minutes in the antegrade groups; in the retrograde groups, retrograde flow was initiated via a cannula positioned in the superior vena cava, and was continued for 25 minutes. Superior vena caval flow was regulated to maintain a sagittal sinus pressure of approximately 30 mm Hg in the retrograde groups, and blood returning to the isolated aortic arch was collected and measured. All animals were allowed to recover and were evaluated daily according to a quantitative behavioral score in which 9 indicates apparently complete normalcy, with lower numbers indicating various degrees of cerebral injury. At the time of planned death on day 6, half of the brain was used for recovery of embolized microspheres after digestion with 10N sodium hydroxide. The other half was submitted for histologic study. Neurologic recovery in both the antegrade and retrograde control groups appeared to be complete, although mild evidence of histologic damage was present in some animals in the retrograde control group.(ABSTRACT TRUNCATED AT 400 WORDS)

Quantitative electroencephalography: a method to assess cerebral injury after hypothermic circulatory arrest.

Although hypothermic circulatory arrest and low-flow cardiopulmonary bypass are routinely used for surgical correction of congenital cardiac anomalies, use of long durations of arrest, often required for more complex repairs, raises serious concerns about cerebral safety. Searching for an intraoperative assessment that can reliably predict cerebral injury, we have found an excellent correlation between changes in quantitative electroencephalography intraoperatively and immediately postoperatively after prolonged hypothermic arrest, and neurologic and behavioral evidence of cerebral injury. After epidural placement of four recording electroencephalographic electrodes and baseline neurologic/behavioral and electroencephalographic assessment, 32 puppies were randomly assigned to one of four groups: hypothermic controls in which cooling to 18 degrees C was followed immediately by rewarming, 30 minutes of hypothermic circulatory arrest at 18 degrees C, 90 minutes of arrest at 18 degrees C, and 90 minutes of low-flow cardiopulmonary bypass at 25 ml/kg per minute at 18 degrees C. An electroencephalogram was recorded at baseline, after cooling, during rewarming, and at 2, 4, and 8 hours after the start of rewarming, as well as before the operation and 1 week after the operation. Postoperative neurologic and behavioral outcome was assessed 24 hours after cardiopulmonary bypass and daily for 1 week by means of a graded scale in which 0 is normal and 12 and 13 indicate severe neurologic injury (coma and death). Thirty animals survived the experimental protocol: two animals in the 90-minute hypothermic arrest group died before neurologic evaluation could be completed, and the remainder exhibited various degrees of neurologic and behavioral impairment, more severe on day 1 than on day 6. No animal in the remaining groups had a significant neurologic deficit. Quantitative electroencephalographic analysis shows marked differences between the 90-minute arrest group and the controls in the percent electroencephalographic silence during rewarming and at 2 hours, and in the percent recovery of baseline power at 2, 4, and 8 hours. At 2 hours after the start of rewarming, a correlation between electroencephalographic amplitude and neurologic/behavioral score on day 1 was carried out, which predicts with great certainty (p < 0.00001) that if electroencephalographic power at this time is less than 500 microV2, overt neurologic injury will subsequently become apparent. In addition, a significant shift from higher to lower frequency in the day 6 postoperative electroencephalogram compared with baseline occurs only in the 90-minute arrest group.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolic correlates of neurologic and behavioral injury after prolonged hypothermic circulatory arrest.

Thirty-two inbred weanling puppies were divided into four groups to study the effect on cerebral blood flow and metabolism of different hypothermic strategies for cerebral protection similar to those used during cardiac operations in infancy. All animals were cooled to 18 degrees C. The animals in the hypothermic control group were immediately rewarmed. One group underwent 30 minutes of hypothermic circulatory arrest at 18 degrees C; another group had 90 minutes of hypothermic circulatory arrest at 18 degrees C, and the final group had low-flow cardiopulmonary bypass (25 ml/kg per minute) at 18 degrees C for 90 minutes. All animals had preoperative and postoperative neurologic and behavioral evaluation and extensive intraoperative monitoring of cerebral blood flow, cerebral vascular resistance, and oxygen and glucose uptake and metabolism: quantitative electroencephalography was also monitored before, during and after operation, but those results are reported separately. Two animals in the 90-minute arrest group died, and all the survivors showed evidence of clinical, neurologic, and behavioral impairment on postoperative day 1, with residual abnormalities in all but one animal on day 6. In contrast, the survivors in all the other groups showed no significant clinical or behavioral sequelae. Cerebral metabolism was reduced only to 32% to 40% of baseline values at 18 degrees C in all groups, although systemic metabolism was only 16% of normal. Cerebral metabolism returned promptly to baseline in all groups during rewarming and remained at baseline levels throughout the 8 hours of follow-up. Cerebral blood flow showed marked hyperemia in the hypothermic arrest groups during rewarming but then significant reductions below baseline values in all groups except the controls at 2 and 4 hours after the operation, lasting as late as 8 hours after the operation in the 90-minute arrest group. Cerebral vascular resistance showed increases in all groups at 2 and 4 hours after the operation, which persisted in the 90-minute arrest group at 8 hours. Cerebral metabolism was maintained at baseline levels despite postoperative decreases in cerebral blood flow and increases in cerebral vascular resistance by increases in oxygen and glucose extraction. The result was very low sagittal sinus oxygen saturations in all groups, most marked in the 90-minute arrest groups, which had a saturation of only 24% 8 hours after the operation. Our data show a severe, prolonged disturbance in cerebral blood flow and cerebral vascular resistance after 90 minutes of hypothermic circulatory arrest at 18 degrees C, which correlates with clinical evidence of cerebral injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of retrograde cerebral perfusion to antegrade cerebral perfusion and hypothermic circulatory arrest in a chronic porcine model.

Retrograde cerebral perfusion (RCP) is a new method of cerebral protection that has been touted as an improvement over hypothermic circulatory arrest (HCA). However, RCP has been used clinically for durations and at temperatures that are "safe" for HCA alone. This study was designed to compare RCP to HCA and antegrade cerebral perfusion (ACP) deliberately exceeding "safe" limits, in order to determine unequivocally whether RCP provides better cerebral protection than HCA. Four groups of six Yorkshire pigs (20 to 30 kg) were randomly assigned to undergo 90 minutes of RCP, ACP, HCA, or HCA with heads packed in ice (HCA-HP) at an esophageal temperature of 20 degrees C. Arterial, mixed venous and cerebral venous oxygen, glucose and lactate contents; quantitative EEG; were monitored at baseline (37 degrees C); at the end of cooling cardiopulmonary bypass (20 degrees C); during rewarming (30 degrees C); and at two and four hours post intervention. Animals were recovered and were evaluated daily using a quantitative behavioral score (0 to 9). Mean behavioral score was lower in the HCA group than in the other three groups at seven days (HCA 5.8 +/- 1.1; RCP 8.5 +/- 0.2; ACP 9.0 +/- 0.0; HCA-HP 8.5 +/- 0.2, p < 0.05). Recovery of QEEG was better in the ACP group than in all others, but the RCP group had faster EEG recovery than HCA alone, although not better than HCA-HP (HCA 15 +/- 4; RCP 27 +/- 3; ACP 78 +/- 5; HCA-HP 19 +/- 3, p < 0.001). However, histopathological evidence of ischemic injury was present in 5 of 6 HCA animals and also in 4 of 6 of the HCP-HP group, but only in 1 of 6 RCP animals and in none of the ACP group. This study demonstrates that ACP affords the best cerebral protection by all outcome measures, but RCP provides clear improvement compared to HCA.

Pathogenesis of spinal cord injury during simulated aneurysm repair in a chronic animal model.

The pathogenesis of paraplegia after repair of thoracic aortic aneurysms is controversial. Using direct spinal cord evoked potential monitoring, critical intercostal arteries (CICA) were identified to evaluate the impact of backbleeding and ligation versus that of preservation during simulated aneurysm repair. Thirty pigs (40 kg) were randomly assigned to one of five groups. In groups 1 through 4, a thoracic segment containing CICA was cross-clamped for 60 minutes and distal aortic perfusion was provided by a centrifugal pump. In groups 1 and 2, the thoracic segment was vented, maintaining segment pressure at 0 mm Hg; CICA were ligated in group 1 and preserved in group 2. Thoracic segment was perfused at 70 mm Hg in groups 3 and 4; CICA were ligated in group 3 and preserved in group 4. Critical intercostal artery ligations were performed at the end of the cross-clamp period. In group 5 simple cross-clamping at the left subclavian artery was performed as a control. The combination of venting and ligation of CICA correlated with impaired neurologic outcome according to Tarlov's score (median, 1.5 in group 1 versus 3 in group 2; p = 0.015), indicated by a significant difference in median values of direct spinal cord evoked potential amplitude (expressed as a fraction of baseline values) at 120 minutes after cross-clamping (0.76 in group 1 versus 0.98 in group 2; p = 0.0082).(ABSTRACT TRUNCATED AT 250 WORDS)

The natural history of thoracic aortic aneurysms.

Because improved understanding of the natural history of thoracic aneurysms would enhance our ability to determine in which cases the risk of surgical treatment is justified, the rate of enlargement of thoracic aneurysms and thoracoabdominal aneurysms was studied in 67 patients by means of serial computer-generated three-dimensional reconstructions of computed tomographic scans. Patients were followed for a mean of 1.5 +/- 0.15 years (0.2 to 5.35 years) with an average interval between examinations of 0.9 +/- 0.1 year (0.2 to 5.0 years). Thirty-nine patients continue to be followed; 7 were lost to follow-up; 14 died during follow-up (4 after aneurysm rupture), and 10 underwent an operation. Indications for operation included the presence of pain, an absolute aortic diameter larger than 8 cm, an increase in aortic diameter of more than 1 cm per year, or marked irregularity of aneurysm contour. Aortic diameter and volume data were generated from the aortic silhouette obtained by tracing each computed tomographic slice with a translucent digitizing tablet. Estimated change in aortic diameter after 1 year was 0.43 cm; estimated change in aortic volume was 88.1 ml. The impact of possible risk factors on the enlargement of aneurysms was examined by analysis of variance (p < 0.05). A significantly higher rate of aneurysm expansion was found in patients with a larger aortic diameter (> 5 cm) at diagnosis (change in diameter = 0.17 cm versus 0.79 cm; change in volume = 40 ml versus 141.8 ml), and in smokers (change in diameter = 0.35 cm versus 0.70 cm; change in volume = 78.3 ml versus 120.8 ml). Changes in diameter and volume for aneurysms of different initial diameters and volumes was predicted by exponential regression by the equations: change in diameter = 0.0167 (initial aortic diameter)2.1; change in volume = 0.0356 (initial aortic volume)1.322. No correlation was noted between the rate of enlargement and age, sex, or the presence of dissection. A history of hypertension correlated with a greater aortic diameter at diagnosis but did not significantly affect the rate of enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of cerebral metabolism and quantitative electroencephalography after hypothermic circulatory arrest and low-flow cardiopulmonary bypass at different temperatures.

Although widely used for repair of complex cardiovascular pathologic conditions, long intervals of hypothermic circulatory arrest and low flow cardiopulmonary bypass may both result in cerebral injury. This study examines cerebral hemodynamics, metabolism, and electrical activity to evaluate the risks of cerebral injury after 60 minutes of hypothermic circulatory arrest at 8 degrees C, 13 degrees C, and 18 degrees C, compared with 60 minutes of low flow cardiopulmonary bypass at 18 degrees C. Thirty-two puppies were randomly assigned to one of four experimental groups and centrally cooled to the appropriate temperature. Serial evaluations of quantitative electroencephalography, radioactive microsphere determinations of cerebral blood flow, calculations of cerebral oxygen consumption, cerebral glucose consumption, cerebral vascular resistance, cerebral oxygen extraction, systemic oxygen metabolism, and systemic vascular resistance were done. Measurements were obtained at baseline (37 degrees C), at the end of cooling, at 30 degrees C during rewarming, and at 2, 4, and 8 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass. At the end of cooling, cerebral vascular resistance remained at baseline levels in all groups, but systemic vascular resistance was increased in all groups. Cerebral oxygen consumption became progressively lower as temperature was reduced: it was only 5% of baseline at 8 degrees C; 20% at 13 degrees C; and 34% and 39% at 18 degrees C. Quantitative electroencephalography was silent in the 8 degrees C and 13 degrees C groups, but significant slow wave activity was present at 18 degrees C. Systemic vascular resistance and cerebral oxygen consumption returned to baseline values in all groups by 2 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass, but cerebral vascular resistance remained elevated at 2 and 4 hours, not returning to baseline until 8 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass. All but two of the long-term survivors (27 of 32) appeared neurologically normal; after hypothermic circulatory arrest at 8 degrees and 18 degrees C two animals had an unsteady gait. Comparison of quantitative electroencephalography before operation and 6 days after operation showed a significant increase in slow wave activity (delta activity) after hypothermic circulatory arrest and low flow cardiopulmonary bypass at 18 degrees C, a change that suggests possible cerebral injury. Although undetected after operation by simple behavioral and neurologic assessment, significant differences in cerebral metabolism, vasomotor responses, and quantitative electroencephalography do exist during and after hypothermic circulatory arrest and low flow cardiopulmonary bypass at various temperatures and may be implicated in the occurrence of cerebral injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebral effects of low-flow cardiopulmonary bypass and hypothermic circulatory arrest.

Although both hypothermic circulatory arrest (HCA) and low-flow cardiopulmonary bypass (CPB) are accepted techniques for the operative management of complex cardiovascular pathology, the potential for neurologic sequelae is still a concern. To assess the relative safety of these techniques, we compared cerebral hemodynamics and clinical outcome in two groups of puppies. Sixteen puppies underwent 45 minutes of either HCA or low-flow CPB (25 mL.kg-1.min-1) after cooling to 13 degrees C. Methodology included radioactive microsphere determination of cerebral blood flow; calculation of cerebral oxygen extraction (arteriovenous oxygen content difference) and consumption; measurement of glucose consumption, and determination of cerebrovascular resistance. Measurements were obtained at baseline (37 degrees C), 13 degrees C, and 30 degrees C and at 2, 4, and 8 hours after HCA or low-flow CPB. No neurologic deficits were observed in any of the survivors (15/16). In both groups, cerebral metabolic rate of oxygen was maintained at baseline or greater levels postoperatively. Cerebrovascular resistance rose slightly in the low-flow CPB group postoperatively in contrast to a marked elevation in the HCA group. During the period of high cerebrovascular resistance after HCA, cerebral metabolic rate of oxygen was maintained by increased oxygen extraction. After low-flow CPB, oxygen extraction was not significantly different from baseline, presumably because of less severe changes in cerebrovascular resistance. Glucose metabolism followed the same trends as oxygen metabolism in both groups. These data suggest that after HCA there is a vulnerable interval, lasting as late as 8 hours postoperatively, in which cerebrovascular resistance remains high and cerebral metabolism is maintained primarily by high oxygen and glucose extraction. Any additional stress during this interval (a decrease in arterial oxygen content or perfusion pressure) could result in cerebral injury.

Cerebral blood flow and metabolism in hypothermic circulatory arrest.

Although hypothermic circulatory arrest has been accepted for use in cardiovascular operations, the potential for cerebral injury exists. The mechanism of the cerebral injury remains unclear. To address these questions we studied cerebral blood flow and metabolism. Sixteen puppies were randomly assigned to undergo either 45 or 90 minutes of hypothermic circulatory arrest after perfusion/surface cooling to 13 degrees C. Cerebral blood flow, cerebral oxygen and glucose metabolism, and cerebral vascular resistance measurements were obtained at 37 degrees C, 13 degrees C, 10 minutes after reperfusion, 30 degrees C and 2 and 4 hours after hypothermic circulatory arrest. No neurologic or behavioral changes were observed in any of the long-term survivors (11/16). Metabolic and cerebral blood flow data did not differ between groups. Cerebral blood flow was significantly lower in the late postarrest measurements, whereas oxygen and glucose consumption had returned to baseline values. In the presence of low cerebral blood flow and high cerebral vascular resistance it is notable that control levels of oxygen consumption were attained by abnormally high oxygen extraction. These data strongly suggest a vulnerable interval after hypothermic circulatory arrest in which cerebral metabolism is limited by cerebral blood flow.

Poloxamer 188 improves neurologic outcome after hypothermic circulatory arrest.

Poloxamer 188, an amphipathic copolymer with cytoprotective properties, was investigated as a means of improving neurologic outcome after a prolonged period (150 minutes) of deep hypothermic circulatory arrest. Dogs were perfusion cooled and surface cooled to 10 degrees C, the heart was arrested for 150 minutes, and then the dogs were rewarmed and weaned from bypass. Seven dogs were treated with poloxamer 188 before and after deep hypothermic circulatory arrest. Six control dogs were treated with saline. Surviving dogs were evaluated for 1 week after deep hypothermic circulatory arrest for neurologic deficits or behavioral changes. Neurologic outcome was graded by the following system: grade 1, death within the observation period; grade 2, comatose; grade 3, holds head up; grade 4, sits up; grade 5, stands; grade 6, normal in both behavior and gait. There were no deaths in the seven poloxamer 188-treated animals versus three deaths in the six control dogs. Poloxamer 188-treated dogs also manifested significantly less neurologic dysfunction after deep hypothermic circulatory arrest than did the control group (p less than 0.003). This study shows that poloxamer 188 has a significant impact in improving neurologic outcome after exceptionally long periods of deep hypothermic circulatory arrest.

Postoperative infections following autologous and homologous blood transfusions.

Perioperative homologous blood transfusion has been linked to immune suppression and increased risk of postoperative infection. Autologous blood transfusion may not be associated with increased risk of infection because it presumably is not immunosuppressive. Fifty recipients of preoperatively donated autologous blood were matched to 50 recipients of homologous blood who underwent the same procedure, and the hospital course was reviewed for evidence of postoperative infection in both groups. Postoperative leukocytosis and febrile episodes were more common in homologous blood recipients (17 and 6 vs. 12 and 4, respectively). Sixteen percent of the 50 homologous blood recipients had positive cultures, as compared to 4 percent of the 50 autologous blood recipients (p less than 0.05). This study suggests that the association of blood transfusion with infection may be partially abrogated by the use of autologous blood.