RESUMO
BACKGROUND: Rewarming on cardiopulmonary bypass (CPB) is associated with increased metabolic demands; however, it remains unclear whether cerebral autoregulation is affected during this phase. This RCT aims to describe the effects of 20% supranormal, compared to normal CPB flow, on monitoring signs of inadequate perfusion, oxygenation, and disturbed cerebral autoregulation, during the rewarming phase of CPB. METHOD: Thirty two patients scheduled for coronary artery bypass grafting were allocated to a Control group (n = 16) receiving a CPB pump flow corresponding to preoperatively measured cardiac output, and an Intervention group (n = 16) receiving the corresponding CPB pump flow increased by 20% during rewarming. Cerebral Oximetry Index (COx) was calculated with the aid of Near Infrared Spectroscopy. RESULTS: Twenty five patients were included in the data. Results show a median COx value of 0.0 (IQR -0.33-0.5) (Control) and 0.0 (IQR -0.15-0.25) (Intervention), respectively; p = .85 with individual variations within groups. The median cerebral perfusion pressure (CPP) was 55 (52-58) (Control) and 61 (54-66) mmHg (Intervention); p = .08. No significant difference in rSO2 values was observed between the groups (58.5% (50-61) versus 64% (58-68); p = .06). CONCLUSION: The present study showed no difference between increased and normal CPB pump flow with respect to cerebral autoregulation during rewarming. Large variations in cerebral autoregulation were seen at individual level.
Assuntos
Ponte Cardiopulmonar , Reaquecimento , Humanos , Oximetria/métodos , Circulação Cerebrovascular/fisiologia , Homeostase/fisiologia , Oxigênio/metabolismo , Encéfalo/metabolismoRESUMO
BACKGROUND: One-lung ventilation (OLV) with induced capnothorax carries the risk of severely impaired ventilation and circulation. Optimal PEEP may mitigate the physiological perturbations during these conditions. METHODS: Right-sided OLV with capnothorax (16 cm H2 O) on the left side was initiated in eight anesthetized, muscle-relaxed piglets. A recruitment maneuver and a decremental PEEP titration from PEEP 20 cm H2 O to zero end-expiratory pressure (ZEEP) was performed. Regional ventilation and perfusion were studied with electrical impedance tomography and computer tomography of the chest was used. End-expiratory lung volume and hemodynamics were recorded and. RESULTS: PaO2 peaked at PEEP 12 cm H2 O (49 ± 14 kPa) and decreased to 11 ± 5 kPa at ZEEP (P < 0.001). PaCO2 was 9.5 ± 1.3 kPa at 20 cm H2 O PEEP and did not change when PEEP step-wise was reduced to 12 cm H2 O PaCO2. At lower PEEP, PaCO2 increased markedly. The ventilatory driving pressure was lowest at PEEP 14 cm H2 O (19.6 ± 5.8 cm H2 O) and increased to 38.3 ± 6.1 cm H2 O at ZEEP (P < 0.001). When reducing PEEP below 12-14 cm H2 O ventilation shifted from the dependent to the nondependent regions of the ventilated lung (P = 0.003), and perfusion shifted from the ventilated to the nonventilated lung (P = 0.02). CONCLUSION: Optimal PEEP was 12-18 cm H2 O and probably relates to capnothorax insufflation pressure. With suboptimal PEEP, ventilation/perfusion mismatch in the ventilated lung and redistribution of blood flow to the nonventilated lung occurred.
Assuntos
Insuflação/métodos , Ventilação Monopulmonar/métodos , Pico do Fluxo Expiratório , Anestesia , Animais , Procedimentos Cirúrgicos Cardíacos , Impedância Elétrica , Insuflação/efeitos adversos , Ventilação Monopulmonar/efeitos adversos , Consumo de Oxigênio , Músculos Respiratórios/fisiologia , Suínos , Tórax/diagnóstico por imagem , Tórax/fisiologia , Volume de Ventilação Pulmonar , TomografiaRESUMO
BACKGROUND: Survivors of cardiac arrest often experience neurologic deficits. To date, treatment options are limited. Associated hyperglycemia is believed to further worsen the neurologic outcome. The aim with this study was to characterize expression pathways induced by hyperglycemia in conjunction with global brain ischemia. METHODS: Pigs were randomized to high or normal glucose levels, as regulated by glucose and insulin infusions with target levels of 8.5-10 mM and 4-5.5 mM, respectively. The animals were subjected to 5-minute cardiac arrest followed by 8 minutes of cardiopulmonary resuscitation and direct-current shock to restore spontaneous circulation. Global expression profiling of the cortex using microarrays was performed in both groups. RESULTS: A total of 102 genes differed in expression at P < .001 between the hyperglycemic and the normoglycemic pigs. Several of the most strongly differentially regulated genes were involved in transport and metabolism of glucose. Functional clustering using bioinformatics tools revealed enrichment of multiple biological processes, including membrane processes, ion transport, and glycoproteins. CONCLUSIONS: Hyperglycemia during cardiac arrest leads to differential early gene expression compared with normoglycemia. The functional relevance of these expressional changes cannot be deduced from the current study; however, the identified candidates have been linked to neuroprotective mechanisms and constitute interesting targets for further studies.
Assuntos
Córtex Cerebral/metabolismo , Metabolismo Energético/genética , Parada Cardíaca/genética , Hiperglicemia/genética , Animais , Biologia Computacional , Bases de Dados Genéticas , Modelos Animais de Doenças , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Parada Cardíaca/etiologia , Parada Cardíaca/metabolismo , Hiperglicemia/induzido quimicamente , Hiperglicemia/metabolismo , Insulina , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Sus scrofa , Fatores de TempoRESUMO
PURPOSE: Perfusion assessment by monitoring the transport of a tracer bolus depends critically on conversion of signal intensity into tracer concentration. Two main assumptions are generally applied for this conversion; (1) contrast agent relaxivity is identical in blood and tissue, (2) change in signal intensity depends only on the primary relaxation effect. The purpose of the study was to assess the validity and influence of these assumptions. MATERIALS AND METHODS: Blood and cerebral tissue relaxivities r1, r2, and r2* for gadodiamide were measured in four pigs at 1.5 T. Gadolinium concentration was determined by inductively coupled plasma atomic emission spectroscopy. Influence of the relaxivities, secondary relaxation effects and choice of singular value decomposition (SVD) regularization threshold was studied by simulations. RESULTS: In vivo relaxivities relative to blood concentration [in s(-1) mM(-1) for blood, gray matter (GM), white matter (WM)] were for r1 (2.614 ± 1.061, 0.010 ± 0.001, 0.004 ± 0.002), r2 (5.088 ± 0.952, 0.091 ± 0.008, 0.059 ± 0.014), and r2* (13.292 ± 3.928, 1.696 ± 0.157, 0.910 ± 0.139). Although substantial, by a nonparametric test for paired samples, the differences were not statistically significant. The GM to WM blood volume ratio was estimated to 2.6 ± 0.9 by r1, 1.6 ± 0.3 by r2, and 1.9 ± 0.2 by r2*. Secondary relaxation was found to reduce the tissue blood flow, as did the SVD regularization threshold. CONCLUSION: Contrast agent relaxivity is not identical in blood and tissue leading to substantial errors. Further errors are introduced by secondary relaxation effects and the SVD regularization.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Encéfalo/fisiologia , Circulação Cerebrovascular/fisiologia , Gadolínio DTPA/farmacocinética , Angiografia por Ressonância Magnética/métodos , Modelos Cardiovasculares , Animais , Encéfalo/anatomia & histologia , Simulação por Computador , Meios de Contraste/farmacocinética , Substância Cinzenta/anatomia & histologia , Substância Cinzenta/fisiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suínos , Substância Branca/anatomia & histologia , Substância Branca/fisiologiaRESUMO
OBJECTIVE: To investigate the effects of cardiac arrest on cerebral perfusion and oxidative stress during hyperglycemia and normoglycemia. DESIGN: Experimental animal model. SETTING: University laboratory. SUBJECTS: Triple-breed pigs (weight, 22-27 kg). INTERVENTIONS: Thirty-three pigs were randomized and clamped at blood glucose levels of 8.5-10 mM (high) or 4-5.5 mM (normal) and thereafter subjected to alternating current-induced 12-min cardiac arrest followed by 8 mins of cardiopulmonary resuscitation and direct-current shock to restore spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, regional near-infrared light spectroscopy, regional venous Hbo2, and biochemical markers (Protein S100beta, troponin I, F2-isoprostanes reflecting oxidative stress and inflammation) were monitored and/or sampled throughout an observation period of 4 hrs. No significant differences were seen in hemodynamics or biochemical profile. The cerebral oxygenation by means of regional near-infrared light spectroscopy was higher in the hyperglycemic (H) than in the normal (N) group after restoration of spontaneous circulation (p < .05). However, tendencies toward increased protein S100beta and 15-keto-dihydro-prostaglandin F2alpha were observed in the H group but were not statistically significant. CONCLUSIONS: The responses to 12-min cardiac arrest and cardiopulmonary resuscitation share large similarities during hyperglycemia and normoglycemia. The higher cerebral tissue oxygenation observed in the hyperglycemia needs to be confirmed and the phenomenon needs to be addressed in future studies.
Assuntos
Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Parada Cardíaca/complicações , Hiperglicemia/complicações , Consumo de Oxigênio , Animais , Biomarcadores/sangue , Glicemia/análise , Isquemia Encefálica/etiologia , Reanimação Cardiopulmonar/métodos , Intervalos de Confiança , Modelos Animais de Doenças , Parada Cardíaca/terapia , Hemodinâmica/fisiologia , Insulina/sangue , Insulina/farmacologia , Estresse Oxidativo , Distribuição Aleatória , SuínosRESUMO
BACKGROUND: Previously, we have been able to demonstrate the possibility of coating the inner surface of the renal arteries in porcine kidneys with a heparin conjugate during hypothermic machine perfusion (HMP). The purpose of this study was to assess the efficacy of this treatment in reducing early ischemia-reperfusion injury. METHOD: Brain death was induced in male landrace pigs by stepwise volume expansion of an epidural balloon catheter until negative cerebral perfusion pressure (CPP) was obtained. Both kidneys (matched pairs; n = 6 + 6) were preserved for 20 hours by HMP during which 50 mg heparin conjugate was added to one of the HMP systems (treated group). A customized ex vivo normothermic oxygenated perfusion (NP) system with added exogenous creatinine was used to evaluate early kidney function. Blood, urine and histological samples were collected during the subsequent 3 hours of NP. RESULTS: Kidney weight was lower at the end of NP (P = 0.017) in the treated group compared with control kidneys. The rate of decline in creatinine level was faster (P = 0.024), total urinary volume was higher (P = 0.031), and the level of urine neutrophil gelatinase-associated lipocalin (NGAL) was lower (P = 0.031) in the treated group. Histologically, less tubular changes were seen (P = 0.046). During NP intrarenal resistance remained lower (P < 0.0001) in the treated group. CONCLUSIONS: Perfusion of porcine kidneys with heparin conjugate during HMP reduces preservation injury and improves organ function shortly after reperfusion. No increased risk of bleeding was seen in this setup. This protective strategy may potentially improve the quality of transplanted kidneys in the clinical setting.
Assuntos
Heparina/farmacologia , Transplante de Rim/métodos , Perfusão/métodos , Traumatismo por Reperfusão/prevenção & controle , Animais , Lipocalina-2/urina , Masculino , Suínos , TromboelastografiaRESUMO
BACKGROUND: Perfusion strategies during aortic surgery usually comprise hypothermic circulatory arrest (HCA), often combined with selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion. Cerebral blood flow (CBF) is a fundamental parameter for which the optimal level has not been clearly defined. We sought to determine the CBF at a pump flow level of 6 mL/kg/min, previously shown likely to provide adequate SACP at 20°C in pigs. METHODS: Repeated positron emission tomography (PET) scans were used to quantify the CBF and glucose metabolism throughout HCA and SACP including cooling and rewarming. Eight pigs on cardiopulmonary bypass were assigned to either HCA alone (n = 4) or HCA+SACP (n = 4). The CBF was measured by repeated [15O]water PET scans from baseline to rewarming. The cerebral glucose metabolism was examined by [18F]fluorodeoxyglucose PET scans after rewarming to 37°C. RESULTS: Cooling to 20°C decreased the cortical CBF from 0.31 ± 0.06 at baseline to 0.10 ± 0.02 mL/cm3/min (p = 0.008). The CBF was maintained stable by SACP of 6 mL/kg/min during 45 minutes. After rewarming to 37°C, the mean CBF increased to 0.24 ± 0.07 mL/cm3/min, without significant differences between the groups at any time-point exclusive of the HCA period. The net cortical uptake (Ki) of [18F]fluorodeoxyglucose after rewarming showed no significant difference between the groups. CONCLUSIONS: Cooling autoregulated the CBF to 0.10 mL/cm3/min, and 45 minutes of SACP at 6 mL/kg/min maintained the CBF in the present model. Cerebral glucose metabolism after rewarming was similar in the study groups.
Assuntos
Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Parada Circulatória Induzida por Hipotermia Profunda/métodos , Perfusão/métodos , Tomografia por Emissão de Pósitrons/métodos , Complicações Pós-Operatórias/prevenção & controle , Fluxo Sanguíneo Regional , Animais , Aorta Torácica/cirurgia , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Modelos Animais de Doenças , Glucose/metabolismo , Complicações Pós-Operatórias/diagnóstico , Reprodutibilidade dos Testes , Suínos , Procedimentos Cirúrgicos Vasculares/efeitos adversosRESUMO
OBJECTIVES: Superior venous outflow obstruction affects cerebral perfusion negatively by reducing cerebral perfusion pressure (CPP). We present a randomized study designed to compare two alternative strategies to preserve the CPP during superior vena cava (SVC) congestion and cardiopulmonary bypass (CPB). METHODS: Fourteen pigs on bi-caval CPB were subjected to 75% occlusion of the SVC flow. CPP was restored either by vasopressor treatment (VP, n = 7) or by partial relief (PR) of the congestion (n = 7). The cerebral effects of the interventions were studied for 60 min with intracranial pressure (ICP) monitoring, cerebral blood flow measurement, the near-infrared light spectroscopy tissue oxygen saturation index (StO2), arterial and venous blood gas analyses and serial measurements of the glial cell damage marker protein S100ß. RESULTS: Both strategies restored the CPP to baseline levels and no signs of severe ischaemia were observed. In the PR group, the venous and ICPs were normalized in response to the intervention, while in the VP group those parameters remained elevated throughout the experiment. The haemoglobin oxygen saturation in the sagittal sinus (SsagO2) was increased by both VP and PR, while significant improvement in the StO2 was observed only in the PR group. The S100ß concentrations were similar in the two groups. CONCLUSIONS: Experimental SVC obstruction during CPB may reduce the CPP, resulting in impaired cerebral perfusion. Both vasopressor treatment and improved venous drainage can, in the short term, individually restore the CPP during these circumstances.
Assuntos
Ponte Cardiopulmonar/métodos , Síndrome da Veia Cava Superior/tratamento farmacológico , Vasoconstritores/farmacologia , Animais , Pressão Venosa Central/efeitos dos fármacos , Pressão Venosa Central/fisiologia , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Pressão Intracraniana/efeitos dos fármacos , Pressão Intracraniana/fisiologia , Norepinefrina/farmacologia , Oxigênio/sangue , Distribuição Aleatória , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Espectroscopia de Luz Próxima ao Infravermelho , Síndrome da Veia Cava Superior/fisiopatologia , SuínosRESUMO
BACKGROUND: Selective antegrade cerebral perfusion (SACP) enables surgery on the aortic arch, where cerebral ischemia may cause neurologic sequels. This study aims to identify the minimum arterial flow level to maintain adequate cerebral perfusion during SACP in deep hypothermia in the pig. METHODS: Two groups of pigs were subjected to SACP at 20(°)C α-stat. In group 1 (n = 6), flow was stepwise adjusted from 8-6-4-2-8 mL · kg(-1) · min(-1) and in group 2 (n = 5), flow was kept constant at 6 mL · kg(-1) · min(-1). Magnetic resonance imaging and spectroscopy were performed at each flow level together with hemodynamic monitoring and blood gas analysis. The biochemical marker of cerebral damage protein S100ß was measured in peripheral blood. RESULTS: Decreased mixed venous oxygen saturation and increased lactate in magnetic resonance spectroscopy was seen as a sign of anaerobic metabolism below 6 mL · kg(-1) · min(-1). No ischemic damage was seen on diffusion-weighted imaging, but the concentrations of S100ß were significantly elevated in group 1 compared with group 2 at the end of the experiment (p < 0.05). Perfusion-weighted imaging showed coherence between flow setting and cerebral perfusion, increase of blood volume across time, and regional differences in perfusion during SACP. CONCLUSIONS: The findings suggest an ischemic threshold close to 6 mL · kg(-1) · min(-1) in the present model. Regional differences in perfusion during SACP may be of pathogenic importance to focal cerebral ischemia.
Assuntos
Aorta Torácica/cirurgia , Isquemia Encefálica/prevenção & controle , Circulação Cerebrovascular , Parada Circulatória Induzida por Hipotermia Profunda , Perfusão/métodos , Complicações Pós-Operatórias/prevenção & controle , Animais , Fluxo Sanguíneo Regional , SuínosRESUMO
BACKGROUND: Hyperglycemia exacerbates focal ischemic brain damage supposedly through various mechanisms. One such mechanism is oxidative stress involving reactive oxygen and nitrogen species (RONS) production. Nitrones attenuate oxidative stress in various models of brain injury. Sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) can be administered experimentally and has been shown to be neuroprotective in experimental brain trauma. AIMS OF THE STUDY: We hypothesized that S-PBN might be neuroprotective in hyperglycemic focal cerebral ischemia. MATERIAL AND METHODS: Rats were made hyperglycemic by an intraperitoneal bolus injection of glucose (2 g/kg) and then subjected to 90 min transient middle cerebral artery occlusion (MCAO). They were randomized to a therapeutic regime of S-PBN (156 mg/kg) or saline given intravenously. Neurological testing according to Bederson and tetrazolium red staining were performed after 1 day. RESULTS: S-PBN improved the neurological performance at day 1 both in Bederson score (1.3+/-0.8 versus 2.7+/-0.48) and on the inclined plane (74.5%+/-4.6 (S-PBN) versus 66%+/-8.3 (control), P<0.05) but did not reduce the infarct size. Physiological data did not differ between groups. CONCLUSION: S-PBN may improve neurological performance at short-term survival (1 day) in the present model of hyperglycemic-ischemic brain injury in rats. This effect appeared not to be primarily related to reduced infarct size.
Assuntos
Benzenossulfonatos/uso terapêutico , Isquemia Encefálica/prevenção & controle , Hiperglicemia/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Animais , Benzenossulfonatos/farmacologia , Isquemia Encefálica/patologia , Hiperglicemia/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
To investigate the effects on cerebral perfusion by experimental venous congestion of the superior vena cava (SVC) during bicaval cardiopulmonary bypass (CPB) at 34 °C, pigs were subjected to SVC obstruction at levels of 75%, 50%, 25% and 0% of baseline SVC flow at two arterial flow levels (low, LQ, high, HQ). The cerebral perfusion was examined with near-infrared spectroscopy (NIRS), cerebral microdialysis and blood gas analysis. SVC obstruction caused significant decreases in the NIRS tissue oxygenation index (TOI) and in SVC oxygen saturations (P<0.05, both groups), while the mixed venous saturation was decreased only in the LQ group. Sagittal sinus venous saturations were measured in the HQ group and found significantly reduced in response to venous congestion (P<0.05). No microdialysis changes were seen at the group level, however, individual ischemic patterns in terms of concomitant venous desaturation, decreased TOI and increased lactate/pyruvate occurred in both groups. The total venous drainage remained stabile throughout the experiment, indicating increased flow in the inferior vena cava cannula. The results indicate that SVC congestion may impair cerebral perfusion especially in the case of compromised arterial flow during CPB. Reduced SVC cannula flow may pass undetected during bicaval CPB, if SVC flow is not specifically monitored.
Assuntos
Isquemia Encefálica/etiologia , Ponte Cardiopulmonar/efeitos adversos , Circulação Cerebrovascular , Monitorização Intraoperatória , Síndrome da Veia Cava Superior/complicações , Animais , Biomarcadores/sangue , Gasometria , Glicemia/metabolismo , Isquemia Encefálica/sangue , Isquemia Encefálica/fisiopatologia , Pressão Venosa Central , Modelos Animais de Doenças , Glicerol/sangue , Hipotermia Induzida , Ácido Láctico/sangue , Microdiálise , Monitorização Intraoperatória/métodos , Oxigênio/sangue , Ácido Pirúvico/sangue , Fluxo Sanguíneo Regional , Espectroscopia de Luz Próxima ao Infravermelho , Síndrome da Veia Cava Superior/sangue , Síndrome da Veia Cava Superior/fisiopatologia , Suínos , Veia Cava Inferior/fisiopatologiaRESUMO
Hyperglycemia aggravates ischemic brain injury, possibly due to the activation of signaling pathways involving reactive oxygen species, Src and mitogen-activated protein kinases. The aim of this study was to investigate the effects of the spin trap agent alpha-phenyl-N-tert-butyl nitrone (PBN), the Src family kinase inhibitor PP2 and the MEK1-inhibitor U0126 on focal hyperglycemic ischemic brain injury. Temporary middle cerebral artery occlusion (90 min) was induced in four groups of rats (PBN, PP2, and U0126 vs. control). Neurological testing and tetrazolium red staining were performed after 1 day. PBN decreased the infarct volume by 70% compared with the control (P<0.05) and a tendency towards reduced infarcts was seen in the PP2 or U0126 groups. Furthermore, neurological testing was consistent with the volumetric analysis. In conclusion, PBN appears to be a potential neuroprotective agent in hyperglycemic, focal ischemic brain injury, while the efficacy of PP2 and U0126 could not be confirmed by the present data.