In vivo molecular imaging of apoptosis and necrosis in atherosclerotic plaques using microSPECT-CT and microPET-CT imaging.

PURPOSE: The purpose of this paper is to study molecular imaging of apoptosis and necrosis, two key players in atherosclerosis instability, using a multimodal imaging approach combining single photon emission computed tomography (SPECT), positron emission tomography (PET), and computed tomography (CT). PROCEDURES: Collar-induced carotid atherosclerosis ApoE knockout mice were imaged with (99m)Tc-AnxAF568 SPECT-CT to study apoptosis and sequentially with PET-CT following (124)I-Hypericin ((124)I-Hyp) injection to visualize necrosis. RESULTS: SPECT depicted increased (99m)Tc-AnxAF568 uptake in both atherosclerotic carotid arteries, whereas our data suggest that this uptake is not merely apoptosis related. Although PET of (124)I-Hyp was hampered by the slow blood clearance in atherosclerotic mice, (124)I-Hyp was able to target necrosis in the atherosclerotic plaque. CONCLUSION: Both (99m)Tc-AnxAF568 and (124)I-Hyp uptake are increased in atherosclerotic carotid vasculature compared to control arteries. While apoptosis imaging remains challenging, necrosis imaging can be feasible after improving the biodistribution characteristics of the probe.

Selective internal radiation therapy (SIRT) in primary or secondary liver cancer.

Most patients with a history of common solid tumors will in the end develop liver metastases. Next to that, primary liver cancer, is a frequent cancer with fatal liver failure in the majority of patients. Selective internal radiation therapy (SIRT), has gradually been introduced over the recent years and is a promising, innovative albeit palliative treatment modality. The specific clinical background with regard to the indication and methodology of SIRT is presented and discussed in this paper.

Therapy of hepatocellular carcinoma with 131I-lipiodol: patient dosimetry.

AIM: Dosimetry in (131)I-lipiodol therapy for hepatocellular carcinoma (HCC) in the hitherto largest existing patient cohort. PATIENTS, METHODS: 38 courses of intra-arterial (131)I-lipiodol therapy with a total activity up to 6.7 GBq were performed in 18 patients with HCC. Liver and tumour volume were measured by computed tomography (CT) and (131)I-activity by scintigraphy on day 3, 6, 14, 28 and 42 after injection. Lipiodol deposition in tumour nodules as shown by CT rendered definite attachment to scintigraphic data possible. The radiation dose in tumour nodules, liver and lungs was calculated according to the MIRD concept and the tumour dose related to pre-therapeutic tumour volume, response and survival. RESULTS: Mean tumour dose was 23.6 +/- 3.6 Gy (14.2 +/- 2.1 mGy/MBq) with maximal 162 Gy (90.1 mGy/MBq) after one and 274 Gy after three courses. The dose to nontumourous liver was 1.9 +/- 0.2 Gy (1.2 +/- 0.1 mGy/MBq) and the mean dose ratio of tumour / nontumourous liver 11.1 +/- 1.7 (max. 82). The pulmonary dose was 25.9 +/- 1.8 mGy (16.3 +/- 1.2 microGy/MBq) and therefore much lower. There was a reciprocal relation between tumour dose and pretherapeutic tumour volume. Tumour dose had no effect on response or survival. CONCLUSION: High radiation doses are particularly in small tumour nodes achievable but not necessarily related to tumour response. The dose of non-tumourous liver and lungs is much lower.

Impact of thyroid metabolism on the course of INR levels in a patient with systemic anticoagulation suffering from amiodarone-induced thyrotoxicosis.

We report the case of a 60 year old female patient on continuous systemic anticoagulation therapy with coumarin due to mechanical aortic valve replacement and a more than 3 years lasting amiodarone therapy due to severe ventricular extrasystoles suffering from amiodarone induced thyrotoxicosis (AIT). During the course of AIT, showing different thyroid metabolic conditions, INR levels revealed a course closely related to the thyroid conditions indicating a significant and clear-cut effect of both hyper- and hypothyroidism on systemic anticoagulation therapy with coumarin. This continuous interaction of different thyroid metabolic conditions and the anticoagulation state could be well documented in the presented case over a time period of approximately five months.

[Graves' disease and papillary thyroid cancer--coincidence or association?]. / Basedow-Struma mit papillärem Schilddrüsenkarzinom--Zufall oder Zusammenhang?

HISTORY AND ADMISSION FINDINGS: A 41-year-old woman presented with hyperhydrosis, tremor, restlessness, sleeplessness and diarrhea. She had a tachycardia and later she developed soreness of her conjunctives. A tender goitre could be palpated. INVESTIGATIONS: Laboratory results showed thryeotoxicosis and later elevated TRAK. Ultrasound revealed a thyroid nodule. Scintigraphic uptake was generally elevated. Graves disease was diagnosed. TREATMENT AND COURSE: After 12 months of thyreostatic medication recurrence occurred and a thyroidectomy was performed. Histologically a papillary cancer was found and postoperative radioiodinetherapy was added. CONCLUSION: Due to leading symptoms of thyreotoxicosis the thyroid nodule has preoperatively not been paid enough attention to. A pathophysiologic association of Graves disease and differentiated thyroid cancer is controversely discussed but seems possible considering present literature data. Scintigraphically "cold" nodules in graves disease, as in simple nodular goitre, have a higher probability of malignancy.

Incidental diagnosis of a PSA-negative prostate cancer by 18FDG PET/CT in a patient with hypopharyngeal cancer.

Diagnosis of prostate cancer (PC) still remains critical as non-invasive screening with prostate specific-antigen (PSA) lacks to indicate malignancy of the prostate in some cases. Recent research has shown that clinically meaningful PC can develop in patients with a PSA value <4 ng/ml, frequently defined as upper limit of normal serum PSA levels. Furthermore, both morphological (computed tomography (CT), magnetic resonance imaging, transrectal ultrasound) and functional imaging with (18)fluorodeoxyglucose positron emission tomography (FDG-PET) are associated with several limitations for primary diagnosis of PC. We report a case of an incidentally diagnosed PSA-negative PC by (18)FDG PET/CT in a patient with a previous diagnosis of a hypopharyngeal cancer.

(18)F-FDG PET and conventional imaging for assessment of Hodgkin's disease and non Hodgkin's lymphoma. An analysis of 193 patient studies.

UNLABELLED: The AIM of this study was to assess the diagnostic value of FDG-PET and conventional imaging (CI) in a large series of patient with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) at three time points during their course of disease. PATIENTS, METHODS: 169 consecutive lymphoma patients (69 HD; 100 NHL) were included. 193 FDG-PET studies were performed for staging at baseline in 42 cases, for post-therapeutic monitoring in 103, and for diagnosis of recurrence in 48 cases. Performance indices of sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and accuracy of metabolic FDG-PET and morphological CI were calculated. Differences in staging and diagnosis of residual or recurrent lymphoma were compared. RESULTS: FDG-PET changed staging in 36% of cases for staging at baseline, in 52% of cases for monitoring response to treatment, and in 29% for diagnosis of recurrence. FDG-PET staging results were confirmed in 80% for staging at baseline, in 74% for monitoring response to treatment, and in 50% for diagnosis of recurrence. FDGPET and CI differed significantly at monitoring response to treatment for sensitivity (0.91 versus 0.69; p < 0.02), specificity (0.90 versus 0.38; p < 0.00001), PPV (0.77 versus 0.42; p < 0.001), and accuracy (0.83 versus 0.55; p < 0.02). CONCLUSION: FDG-PET should be considered as the diagnostic modality of choice for post-therapeutic assessment of lymphoma patients and may be a reliable alternative to CI for staging at baseline and diagnosis of recurrence.

FDG-PET in immunocompetent patients with primary central nervous system lymphoma: correlation with MRI and clinical follow-up.

PURPOSE: The role of FDG-PET in primary central nervous system lymphoma (PCNSL) is unclear. It was the aim of this study to investigate the role of FDG-PET in detecting PCNSL and in predicting response to chemotherapy. METHODS: An FDG-PET scan of the brain was performed in 15 patients with histologically proven PCNSL (16 PET examinations, Siemens ECAT EXACT). PET was planned to investigate patients at the time of primary diagnosis, after chemotherapy and at the time of suspected relapse in seven, five and three cases, respectively. All except two patients simultaneously underwent MRI of the brain. FDG-PET results were correlated with histological results after stereotactic biopsy (primary diagnosis group) and with clinical data and MRI during follow-up. RESULTS: Six of the seven patients in the primary diagnosis group demonstrated a true positive finding (86%). In one of the true positive PET patients, there were two tumour lesions, one of which was only detectable on the FLAIR MRI sequence. In five patients, FDG-PET showed no sign of PCNSL during ongoing chemotherapy. These results were confirmed by the clinical follow-up (mean 26.6 months). MRI demonstrated minimal residual disease which had disappeared on further follow-up MRI in three of these five patients at the time of PET scanning. Recurrence of disease was confirmed concordantly by FDG-PET and MRI in three different patients. The standardised uptake value of all tumours was 10.2 (4.3-13.7). CONCLUSION: PCNSLs demonstrate high FDG uptake and can be diagnosed by FDG-PET with high sensitivity. It seems that FDG-PET is suitable for early therapeutic monitoring after chemotherapy.

Diabetes in patients undergoing coronary artery bypass grafting. Impact on perioperative outcome.

Diabetes mellitus is an established risk factor related to significant morbidity and mortality after coronary artery bypass grafting. Data on 9682 patients undergoing coronary artery bypass grafting either with (n=8917) or without cardiopulmonary bypass (off-pump coronary artery bypass grafting; n=765) were subjected to an univariate analysis to identify potential associations between diabetes mellitus and 26 a priori selected perioperative outcome variables. Those having a significant association with diabetes were then subjected to a stepwise logistic regression model to identify the impact of diabetes as compared to additional 22 different a priori chosen patient related risk factors and treatment variables. Prevalence of outcome variables independently associated with diabetes has been determined in the subgroup of diabetics undergoing coronary artery bypass grafting with cardiopulmonary bypass or off-pump coronary artery bypass grafting surgery to evaluate the effect of avoiding cardiopulmonary bypass on perioperative patient outcome. Diabetes mellitus was defined as glucose intolerance either treated dietary, with oral hypoglycemics or with insulin. According to this definition of diabetes mellitus we found an overall prevalence of 37.1% (coronary artery bypass grafting with cardiopulmonary bypass: 37.5%; off-pump coronary artery bypass grafting: 32.5%). Eleven outcome variables having a significant association with diabetes were identified. Diabetes could be identified as an independent predictor of postoperative delirium, renal dysfunction and respiratory insufficiency. Prevalence of these three variables was lower in diabetics undergoing off-pump coronary artery bypass grafting as in those undergoing coronary artery bypass grafting with cardiopulmonary bypass surgery reaching statistical significance with regard to postoperative delirium and respiratory insufficiency. In conclusion, diabetes mellitus is a significant independent predictor for three postoperative outcome variables in coronary artery bypass surgery. Avoiding cardiopulmonary bypass in diabetics seems to have a beneficial effect.

[Combined FDG PET/CT imaging for restaging of colorectal cancer patients: impact of image fusion on staging accuracy]. / PET-CT in der Nachsorge des kolorektalen Karzinoms: Einfluss der Bildfusion auf die Staginggenauigkeit.

PURPOSE: To evaluate the diagnostic impact of positron emission tomography (PET) with fluorine-18-labeled deoxy-D-glucose (FDG) combined with non-contrast computed tomography (CT) as PET-CT modality in restaging colorectal cancer patients. MATERIAL AND METHODS: In this retrospective study, 29 consecutive patients with histologically proven colorectal cancer (17 female, 12 male, aged 51-76 years) underwent whole body scans in one session on a dual modality PET-CT system (Siemens Biograph) 90 min. after i.v. administration of 370 MBq 18F-FDG. The CT imaging was performed with 40 mAs, 130 kV, slice-thickness 5 mm and without i.v. contrast administration. PET and CT images were reconstructed with a slice-thickness of 5 mm in coronal, sagittal and transverse planes. During a first step of analysis, PET and CT images were scored blinded and independently by a group of two nuclear medicine physicians and a group of two radiologists, respectively. For this purpose, a five-point-scale was used. The second step of data-analysis consisted of a consensus reading by both groups. During the consensus reading, first a virtual (meaning mental) fusion of PET and CT images and afterwards the "real" fusion (meaning coregistered) PET-CT images were also scored with the same scale. The imaging results were compared with histopathology findings and the course of disease during further follow-up. RESULTS: The total number of malignant lesions detected with the combined PET/CT were 86. For FDG-PET alone it was n = 68, and for CT alone n = 65. Comparing PET-CT and PET, concordance was found in 81 of 104 lesions. Discrepancies predominantly occurred in the lung, where PET alone often showed true positive results in lymph nodes and soft tissue masses, where CT often was false negative. Comparing mental fusion and "real" co-registered images, concordance was found in 94 of 104 lesions. In 13 lesions or, respectively, in 7 of 29 patients, a relevant information was gathered using fused images. CONCLUSION: Combined PET/CT leads to greater accuracy in the interpretation of data and is a valuable tool for diagnosis and anatomic localization of metastases in colorectal cancer patients.

A simple and fast method for the preparation of n.c.a. 2-[18F]F-A85380 for human use.

2-[18F]F-A85380 is the first subtype selective PET-radiotracer to visualize the distribution of alpha4beta2 nicotinic acetylcholine receptors in human brain in vivo. We investigated a fast and safe automated production of 2-[18F]F-A85380 by purification of the BOC-protected intermediate product with a combination of solid phase extraction cartridges. After deprotection, adjustment of the pH and sterile filtration n.c.a. 2-[18F]F-A85380 was applicable for the use in human studies with a high specific activity and an overall radiochemical yield of 55% in 35 minutes.

Requirement for renal replacement therapy in patients undergoing cardiac surgery.

BACKGROUND: Despite refinements in perioperative patient management renal insufficiency requiring renal replacement therapy (RRT) is still a common complication after cardiac surgical procedures associated with impaired patient outcome and increased costs. METHODS: Prospective data on 16,184 patients undergoing different cardiac surgical procedures (CABG, n = 8917; beating heart CABG, n = 1842 [OPCAB, n = 765; MIDCAB, n = 1077]; aortic valve surgery, n = 1830; mitral valve surgery, n = 708; double valve surgery, n = 381; CABG and valve surgery, n = 2506) between April 1996 and August 2001 were subjected to univariate and multivariate logistic regression analysis. Postoperative RRT was defined as any postoperative renal insufficiency requiring first time hemofiltration or dialysis during the postoperative stay. Patients with preoperative dialysis dependent renal insufficiency were excluded from further analysis. RESULTS: The overall prevalence of postoperative RRT was 4.7% which varied according to different surgical procedures. 45 out of 49 selected pre- and intraoperative patient- and treatment-related variables had a significant association with postoperative RRT. 10 of these (renal disease, myocardial infarction, diabetes, cardiogenic shock, urgent operation, NYHA > or = 3, intraoperative hemofiltration, perfusion time > or = 2 hours, intraoperative low cardiac output, perioperative high transfusion requirement) were independent predictors. OPCAB surgery and younger patient age were identified as having a significantly lower predictive value for postoperative RRT. Patients with postoperative RRT were found to have a significantly longer ICU- and total postoperative hospital stay as well as a higher 30-day mortality. CONCLUSION: Identifying perioperative risk factors associated with postoperative RRT will help to reduce the incidence of this complication. Avoiding cardiopulmonary bypass seem to be beneficial with regard to the prevalence of postoperative RRT.

Impact of diabetes mellitus on cardiac surgery outcome.

BACKGROUND: Diabetes mellitus is an established independent risk factor related to significant morbidity and mortality after cardiac surgical procedures. METHODS: Data on 16,184 patients undergoing cardiac surgery with and without cardiopulmonary bypass between April 1996 and August 2001 were prospectively evaluated. Diabetes mellitus as a patient related risk factor was subjected to univariate analysis to identify potential associations to 28 intra- and postoperative outcome variables. Outcome variables having a significant association with diabetes mellitus (p < 0.05) were then subjected to a stepwise logistic regression model to identify the influence of diabetes mellitus as compared to additional 30 different patient related risk factors and treatment variables. Diabetes mellitus was defined as glucose intolerance treated either dietary, with oral hypoglycemics or with insulin. RESULTS: Overall prevalence of diabetes mellitus was 33.3 %. Compared to non-diabetic patients the group with diabetes mellitus was older (p < 0.0001) and had a significantly lower ejection fraction (p < 0.0001). 15 outcome variables having a significant association with diabetes mellitus were identified. Furthermore, diabetes mellitus could be identified as an independent predictor for 7 postoperative outcome variables (prolonged ICU-stay, sternal instability and/or infection, sternal revision and refixation respiratory insufficiency, postoperative delirium, perioperative stroke, renal dysfunction, postoperative reintubation). CONCLUSION: Diabetes mellitus is a significant independent predictor for several postoperative outcome variables after cardiac surgery associated with higher postoperative morbidity and prolonged hospital stay.

Computer-enhanced "robotic" cardiac surgery: experience in 148 patients.

OBJECTIVE: A computer-enhanced instrumentation system was used in 148 patients to minimize access in cardiac surgical procedures. METHODS: The da Vinci telemanipulation system (Intuitive Surgical, Mountain View, Calif) provides a high-resolution 3-dimensional videoscopic image and allows remote, tremor-free, and scaled control of endoscopic surgical instruments with 6 degrees of freedom. By April 2000, the system had been used in 131 patients for coronary artery bypass grafting and 17 patients for mitral valve repair. In the coronary bypass group, the system was used in one of three ways: (1) to take down the internal thoracic artery followed by a minimally invasive direct coronary bypass procedure (n = 81); (2) to perform the anastomosis between the internal thoracic artery and the left anterior descending coronary artery in standard-sternotomy coronary bypass (n = 15); or (3) for total endoscopic coronary artery bypass grafting to anastomose the left internal thoracic artery to the left anterior descending on the arrested heart (n = 27) or the beating heart (n = 8). In 17 patients with nonischemic mitral valve insufficiency the mitral valve was repaired. Closed-chest cardiopulmonary bypass with cardioplegic arrest (Port-Access technique; Heartport, Inc, Redwood City, Calif) was used for arrested-heart total endoscopic coronary bypass and mitral valve repair. RESULTS: The da Vinci system allows for precise tissue handling and enables the endoscopic performance of cardiac surgical tasks that require a high degree of dexterity (coronary anastomosis, mitral valve repair). No technical mishaps have occurred. The internal thoracic artery was successfully taken down in 79 of 81 patients in the group undergoing minimally invasive coronary bypass and, after a steep learning curve, is currently performed in less than 40 minutes. The postoperative patency rate is 96.3%. Total endoscopic coronary bypass was completed in 22 of 27 cases with 95.4% patency as demonstrated by angiography at 3 months' follow-up. Closed-chest endoscopic beating-heart bypass grafting was successfully performed in 2 out of 8 patients with the use of a new endoscopic stabilizer. In the group having mitral valve repair, primary endoscopic computer-enhanced repair was successfully completed in 14 of 17 patients; three others had to be changed to a standard endoscopic technique, including 1 who required valve replacement. At 3 months' follow-up, 1 additional patient underwent early reoperation for recurrent mitral insufficiency. Overall early and late mortality in this cohort of 148 patients was 2.0% and was not related to the use of the system. CONCLUSION: In conclusion, computer-enhanced endoscopic cardiac surgery can be performed safely in selected patients. Internal thoracic artery takedown is now routinely performed with good results. Total endoscopic coronary bypass is feasible on the arrested heart but does not offer a major benefit over the minimally invasive direct approach because cardiopulmonary bypass is still required. The early clinical experience with closed-chest beating-heart bypass grafting outlines the limitations of this approach despite some procedural success.

Pain is significantly reduced by cryoablation therapy in patients with lateral minithoracotomy.

BACKGROUND: In minimally invasive cardiac surgery use of a lateral minithoracotomy is associated with early postoperative rehabilitation but also relatively high pain levels during the first 3 postoperative days. Cryoablation therapy was evaluated prospectively. METHODS: From April 1999 until September 1999, 57 patients underwent lateral minithoracotomy for mitral valve operation (n = 18) or minimally invasive direct coronary artery bypass grafting (n = 39). Intraoperatively, patients were randomly assigned to cryoablation or intercostal application of local anesthetic agents. A standardized questionnaire was used for prospective pain assessment on postoperative days 1 to 7. RESULTS: From postoperative day 1 to 7 pain levels declined in all groups. Overall pain levels were significantly lower in the cryo group than in the control group (p < 0.0001, GLM). According to diagnoses, pain levels were significantly lower after MIDCABG and cryo versus control; after mitral valve operation they were lower in the cryo group and almost reached significance. CONCLUSIONS: Cryoablation is easy to perform and leads to a significant reduction in pain and lower request for additional pain medication after lateral minithoracotomy in minimally invasive cardiac operation.

Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. I. Gaseous microemboli.

OBJECTIVES: Recent studies suggest that myocardial reperfusion injury is exacerbated by free radicals when pure oxygen is used during cardiopulmonary bypass. Partial replacement of the oxygenator gas mixture with nitrogen, however, such as has already been adopted clinically in many centers, could increase the risk of gaseous nitrogen microembolus formation and therefore of brain damage because of the low solubility of nitrogen, particularly under conditions of hypothermia. METHODS: Ten 7- to 10-kg piglets were cooled for 30 minutes to 15 degrees C on cardiopulmonary bypass and then rewarmed for 40 minutes to 37 degrees C. In 5 piglets cardiopulmonary bypass was normoxic and in 5 it was hyperoxic. In each group 3 bubble oxygenators without arterial filters and 2 membrane oxygenators with filters were used. Cerebral microemboli were monitored continuously by carotid Doppler ultrasonography (8 MHz) and intermittently by fluorescence retinography. RESULTS: Embolus count was greater with lower rectal temperature (P <.001), use of a bubble oxygenator (P <.001), and lower oxygen concentration (P =.021) but was not affected by the temperature gradient between blood and body during cooling or rewarming. CONCLUSIONS: Gaseous microemboli are increased with normoxic perfusion, but this is only important if a bubble oxygenator without a filter is used.

Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. II. hypoxic versus free radical injury.

OBJECTIVES: Laboratory studies suggest that myocardial reperfusion injury is exacerbated by free radicals when pure oxygen is used during cardiopulmonary bypass. In phase I of this study we demonstrated that normoxic perfusion during cardiopulmonary bypass does not increase the risk of microembolic brain injury so long as a membrane oxygenator with an arterial filter is used. In phase II of this study we studied the hypothesis that normoxic perfusion increases the risk of hypoxic brain injury after deep hypothermia with circulatory arrest. METHODS: With membrane oxygenators with arterial filters, 10 piglets (8-10 kg) underwent 120 minutes of deep hypothermia and circulatory arrest at 15 degrees C, were rewarmed to 37 degrees C, and were weaned from bypass. In 5 piglets normoxia (PaO2 64-181 mm Hg) was used during cardiopulmonary bypass and in 5 hyperoxia (PaO2 400-900 mm Hg) was used. After 6 hours of reperfusion the brain was fixed for histologic evaluation. Near-infrared spectroscopy was used to monitor cerebral oxyhemoglobin and oxidized cytochrome a,a3 concentrations. RESULTS: Histologic examination revealed a significant increase in brain damage in the normoxia group (score 12.4 versus 8.6, P =.01), especially in the neocortex and hippocampal regions. Cytochrome a,a 3 and oxyhemoglobin concentrations tended to be lower during deep hypothermia and circulatory arrest in the normoxia group (P =.16). CONCLUSIONS: In the setting of prolonged deep hypothermia and circulatory arrest with membrane oxygenators, normoxic cardiopulmonary bypass significantly increases histologically graded brain damage with respect to hyperoxic cardiopulmonary bypass. Near-infrared spectroscopy suggests that the mechanism is hypoxic injury, which presumably overwhelms any injury caused by increased oxygen free radicals.

Postischemic hyperthermia exacerbates neurologic injury after deep hypothermic circulatory arrest.

BACKGROUND: Aggressive surface warming is a common practice in the pediatric intensive care unit. However, recent rodent data emphasize the protective effect of mild (2 degrees - 3 degrees C) hypothermia after cerebral ischemia. This study evaluates different temperature regulation strategies after deep hypothermic circulatory arrest with a survival piglet model. METHODS: Fifteen piglets were randomly assigned to 3 groups. All groups underwent 100 minutes of deep hypothermic circulatory arrest at 15 degrees C. Brain temperature was maintained at 34 degrees C for 24 hours after cardiopulmonary bypass in group I, 37 degrees C in group II, and 40 degrees C in group III. Neurobehavioral recovery was evaluated daily for 3 days after extubation by neurologic deficit score (0, normal; 500, brain death) and overall performance category (1, normal; 5, brain death). Histologic examination was assessed for hypoxic-ischemic injury (0, normal; 5, necrosis) in a blinded fashion. RESULTS: All results are expressed as mean +/- standard deviation. Recovery of neurologic deficit score (12.0 +/- 17.8, 47.0 +/- 49.95, 191.0 +/- 179.83; P = .05 for group I vs III), overall performance category (1.0 +/- 0.0, 1.4 +/- 0.6, 2.8 +/- 1.3; P < .05 for group I vs III), and histologic scores (0.0 +/- 0.0, 1.0 +/- 1.2, 2.8 +/- 1.8; P < .05 for group I vs III cortex) were significantly worse in hyperthermic group III. These findings were associated with a significantly lower cytochrome aa3 recovery determined by near-infrared spectroscopy in group III animals (P = .0041 for group I vs III). No animal recovered to baseline electroencephalographic value by 48 hours after deep hypothermic circulatory arrest. Recovery was significantly delayed in the hyperthermic group III animals, with a lower amplitude 14 hours after the operation, which gradually increased with time (P < .05 for group III vs groups I and II). CONCLUSIONS: Mild postischemic hyperthermia significantly exacerbates functional and structural neurologic injury after deep hypothermic circulatory arrest and should therefore be avoided.