RESUMO
BACKGROUND: Peripheral intravenous analysis (PIVA) has been shown to be more sensitive than central venous pressure (CVP) for detecting hemorrhage and volume overload. We hypothesized that PIVA is superior to CVP for detecting right ventricular (RV) failure in a rat model of respiratory arrest. METHODS: Eight Wistar rats were studied in accordance with the ARRIVE guidelines. CVP, mean arterial pressure (MAP), and PIVA were recorded. Respiratory arrest was achieved with IV Rocuronium. PIVA utilizes Fourier transform to quantify the amplitude of the peripheral venous waveform, expressed as the "f1 amplitude". RV diameter was measured with transthoracic echocardiography. RESULTS: RV diameter increased from 0.34 to 0.54 cm during arrest, p = 0.001, and returned to 0.33 cm post arrest, p = 0.97. There was an increase in f1 amplitude from 0.07 to 0.38 mmHg, p = 0.01 and returned to 0.08 mmHg, p = 1.0. MAP decreased from 119 to 67 mmHg, p = 0.004 and returned to 136 mmHg, p = 0.50. There was no significant increase in CVP from 9.3 mmHg at baseline to 10.5 mmHg during respiratory arrest, p = 0.91, and recovery to 8.6 mmHg, p = 0.81. CONCLUSIONS: This study highlights the utility of PIVA to detect RV failure in small-caliber vessels, comparable to peripheral veins in the human pediatric population. IMPACT: Right ventricular failure remains a diagnostic challenge, particularly in pediatric patients with small vessel sizes limiting invasive intravascular monitor use. Intravenous analysis has shown promise in detecting hypovolemia and volume overload. Intravenous analysis successfully detects right ventricular failure in a rat respiratory arrest model. Intravenous analysis showed utility despite utilizing small peripheral venous access and therefore may be applicable to a pediatric population. Intravenous analysis may be helpful in differentiating various types of shock.
Assuntos
Insuficiência Cardíaca , Insuficiência Respiratória , Humanos , Criança , Animais , Ratos , Ratos Wistar , Pressão Venosa Central , Ecocardiografia , Infusões IntravenosasRESUMO
BACKGROUND: Early detection and quantification of perioperative hemorrhage remains challenging. Peripheral intravenous waveform analysis (PIVA) is a novel method that uses a standard intravenous catheter to detect interval hemorrhage. We hypothesize that subclinical blood loss of 2% of the estimated blood volume (EBV) in a rat model of hemorrhage is associated with significant changes in PIVA. Secondarily, we will compare PIVA association with volume loss to other static, invasive, and dynamic markers. METHODS: Eleven male Sprague Dawley rats were anesthetized and mechanically ventilated. A total of 20% of the EBV was removed over ten 5 minute-intervals. The peripheral intravenous pressure waveform was continuously transduced via a 22-G angiocatheter in the saphenous vein and analyzed using MATLAB. Mean arterial pressure (MAP) and central venous pressure (CVP) were continuously monitored. Cardiac output (CO), right ventricular diameter (RVd), and left ventricular end-diastolic area (LVEDA) were evaluated via transthoracic echocardiogram using the short axis left ventricular view. Dynamic markers such as pulse pressure variation (PPV) were calculated from the arterial waveform. The primary outcome was change in the first fundamental frequency (F1) of the venous waveform, which was assessed using analysis of variance (ANOVA). Mean F1 at each blood loss interval was compared to the mean at the subsequent interval. Additionally, the strength of the association between blood loss and F1 and each other marker was quantified using the marginal R2 in a linear mixed-effects model. RESULTS: PIVA derived mean F1 decreased significantly after hemorrhage of only 2% of the EBV, from 0.17 to 0.11 mm Hg, P = .001, 95% confidence interval (CI) of difference in means 0.02 to 0.10, and decreased significantly from the prior hemorrhage interval at 4%, 6%, 8%, 10%, and 12%. Log F1 demonstrated a marginal R2 value of 0.57 (95% CI 0.40-0.73), followed by PPV 0.41 (0.28-0.56) and CO 0.39 (0.26-0.58). MAP, LVEDA, and systolic pressure variation displayed R2 values of 0.31, and the remaining predictors had R2 values ≤0.2. The difference in log F1 R2 was not significant when compared to PPV 0.16 (95% CI -0.07 to 0.38), CO 0.18 (-0.06 to 0.04), or MAP 0.25 (-0.01 to 0.49) but was significant for the remaining markers. CONCLUSIONS: The mean F1 amplitude of PIVA was significantly associated with subclinical blood loss and most strongly associated with blood volume among the markers considered. This study demonstrates feasibility of a minimally invasive, low-cost method for monitoring perioperative blood loss.
Assuntos
Pressão Arterial , Volume Sanguíneo , Masculino , Animais , Ratos , Ratos Sprague-Dawley , Pressão Sanguínea , Hemorragia/diagnóstico , HemodinâmicaRESUMO
Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Varied mechanisms of injury contribute to the heterogeneity of this patient population as demonstrated by the multiple published grading scales and diverse required criteria leading to diagnoses from mild to severe. TBI pathophysiology is classically separated into a primary injury that is characterized by local tissue destruction as a result of the initial blow, followed by a secondary phase of injury constituted by a score of incompletely understood cellular processes including reperfusion injury, disruption to the blood-brain barrier, excitotoxicity, and metabolic dysregulation. There are currently no effective pharmacological treatments in the wide-spread use for TBI, in large part due to challenges associated with the development of clinically representative in vitro and in vivo models. Poloxamer 188 (P188), a Food and Drug Administration-approved amphiphilic triblock copolymer embeds itself into the plasma membrane of damaged cells. P188 has been shown to have neuroprotective properties on various cell types. The objective of this review is to provide a summary of the current literature on in vitro models of TBI treated with P188.
Assuntos
Lesões Encefálicas Traumáticas , Poloxâmero , Humanos , Poloxâmero/farmacologia , Lesões Encefálicas Traumáticas/metabolismo , Membrana Celular/metabolismo , Barreira Hematoencefálica/metabolismo , Neurônios/metabolismoRESUMO
Liver and biliary disease complicates pregnancy in varying degrees of severity to the mother and fetus, and anesthesiologists may be asked to assist in caring for these patients before, during, and after birth of the fetus. Therefore, it is important to be familiar with how different liver diseases impact the pregnancy state. In addition, knowing symptoms, signs, and laboratory markers in the context of a pregnant patient will lead to faster diagnosis and treatment of such patients. This review article discusses changes in physiology of parturients, patients with liver disease, and parturients with liver disease. Next, general treatment of parturients with acute and chronic liver dysfunction is presented. The article progresses to specific liver diseases with treatments as they relate to pregnancy. And finally, important aspects to consider when anesthetizing parturients with liver disease are discussed.
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Anestesia Obstétrica/métodos , Doenças dos Ductos Biliares/terapia , Hepatopatias/terapia , Complicações na Gravidez/terapia , Cuidado Pré-Natal/métodos , Anestesia Obstétrica/normas , Doenças dos Ductos Biliares/epidemiologia , Feminino , Humanos , Hepatopatias/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Cuidado Pré-Natal/normasRESUMO
Myocardial infarction is a leading cause for morbidity and mortality worldwide. The only viable treatment for the ischemic insult is timely reperfusion, which further exacerbates myocardial injury. Maintaining mitochondrial function is crucial in preserving cardiomyocyte function in ischemia reperfusion (IR) injury. Poloxamer (P) 188 has been shown to improve cardiac IR injury by improving cellular and mitochondrial function. The aim of this study was to show if P188 postconditioning has direct protective effects on mitochondrial function in the heart. Langendorff prepared rat hearts were subjected to IR injury ex-vivo and reperfused for 10 min with 1 mM P188 vs. vehicle. Cardiac mitochondria were isolated with 1 mM P188 vs. 1 mM polyethylene glycol (PEG) vs. vehicle by differential centrifugation. Mitochondrial function was assessed by adenosine triphosphate synthesis, oxygen consumption, and calcium retention capacity. Mitochondrial function decreased significantly after ischemia and showed mild improvement with reperfusion. P188 did not improve mitochondrial function in the ex-vivo heart, and neither further P188 nor PEG induced direct mitochondrial protection after IR injury in this model.
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Pós-Condicionamento Isquêmico , Mitocôndrias Cardíacas/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Poloxâmero/farmacologia , Trifosfato de Adenosina/biossíntese , Animais , Cálcio/metabolismo , Respiração Celular/efeitos dos fármacos , Complexo II de Transporte de Elétrons/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Ratos Sprague-DawleyRESUMO
Endotracheal intubation is a vital component of many rat in vivo experiments to secure the airway and allow controlled ventilation. Even in the hands of experienced researchers, however, the procedure remains technically challenging. The safest and most reliable way for human intubation is by video laryngoscopy. Previous attempts to apply this technique in rodents have been complicated and expensive. We, hereby, describe a novel, noninvasive method to safely intubate rats orally by video laryngoscopy, thus avoiding the need for a surgical tracheostomy. By repurposing a commercially available ear wax removal device, visualization of the rat larynx can be significantly enhanced. Because of its small diameter, integrated illumination, and a powerful camera with adequate focal length, the device has all of the necessary properties for exploring the upper airway of a rat. After identifying the vocal cords by video laryngoscopy, the insertion of an endotracheal tube (a 14G intravenous catheter) into the trachea under constant visual control is facilitated by using PE50 polyethylene tubing as a stylet (Seldinger technique). The procedure has been performed more than 60 times in our laboratory; all intubations were successful on the first attempt, and no adverse events were observed. We conclude that the described procedure is a simple and effective way to intubate a rat noninvasively, using inexpensive and commercially available equipment.
Assuntos
Intubação Intratraqueal/instrumentação , Laringoscopia/instrumentação , Laringe/diagnóstico por imagem , Traqueia/diagnóstico por imagem , Cirurgia Vídeoassistida/instrumentação , Animais , Humanos , Intubação Intratraqueal/métodos , Laringoscopia/métodos , Masculino , Otoscópios , Ratos , Ratos Sprague-Dawley , Respiração Artificial/instrumentação , Respiração Artificial/métodos , Cirurgia Vídeoassistida/métodosRESUMO
PURPOSE: Visualization of the surgical field is essential for patient safety during endoscopic transsphenoidal tumor surgery. In this retrospective chart review and data analysis of patients undergoing endoscopic transsphenoidal resection of pituitary tumors under general anesthesia we sought to determine if total intravenous anesthesia with propofol and remifentanil leads to decreased bleeding, surgical duration, time to extubation and/or length of stay in the recovery room compared to inhaled anesthesia with sevoflurane or desflurane. METHODS: After IRB approval, chart reviews of 193 American Society of Anesthesiologists class 1 to 3 patients were conducted who had undergone transsphenoidal, endonasal resections of pituitary tumors under total intravenous or inhaled anesthesia at an academic teaching hospital in the United States over a seven-year time period. One hundred four patients fulfilled the inclusion criteria and were further reviewed. Primary outcome was intraoperative blood loss; secondary outcomes were surgical duration, time to extubation and length of stay in the recovery room. RESULTS: Gender, age, and Lund-Mackay-Scores were equally distributed between the two anesthetic groups. We found no significant effect of the anesthetic technique, age, gender, or Lund Mackay score on any of the primary or secondary outcomes. The only significant predictor for recovery room length of stay was intraoperative blood loss. CONCLUSION: Our study shows no evidence that total intravenous anesthesia is superior to inhaled anesthesia or vice versa during endoscopic transsphenoidal sinus surgery with regard to relevant clinical outcome parameters.
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Anestesia Geral , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Endoscopia , Neoplasias Hipofisárias/cirurgia , Propofol/administração & dosagem , Extubação , Analgésicos Opioides/administração & dosagem , Perda Sanguínea Cirúrgica , Desflurano/administração & dosagem , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Remifentanil/administração & dosagem , Estudos Retrospectivos , Sevoflurano/administração & dosagemRESUMO
OBJECTIVE: This study compared noninvasively measured hemoglobin and arterial hemoglobin before and after cardiopulmonary bypass in patients undergoing coronary artery or valve surgery. DESIGN: Observational study with retrospective data analysis. SETTING: Veterans Affairs hospital. PARTICIPANTS: Thirty-five men. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hemoglobin values were measured noninvasively by co-oximetry to corresponding arterial hemoglobin concentrations taken at clinically relevant time points chosen at the discretion of the cardiac anesthesiologist. Thirty-five and 27 pooled pairs of data were obtained before and after cardiopulmonary bypass, respectively. Arterial hemoglobin concentration was analyzed using i-STAT CG8+test cartridges routinely used in the authors' operating rooms and those of other institutions. Linear regression and Bland-Altman analysis revealed a significant positive bias, wide limits of agreement, and low correlation coefficients between the noninvasive and arterial hemoglobin measurements. These findings were especially notable after compared with before cardiopulmonary bypass. CONCLUSIONS: The results suggested that noninvasive measurement of hemoglobin overestimates arterial hemoglobin by almost 1 g/dL when compared to iSTAT. A lack of precision also was observed with noninvasive measurement of hemoglobin, especially after cardiopulmonary bypass. These findings supported the contention that sole reliance on noninvasive measurement of hemoglobin for transfusion decisions in cardiac surgery patients may be inappropriate.
Assuntos
Ponte Cardiopulmonar , Vasos Coronários/cirurgia , Valvas Cardíacas/cirurgia , Hemoglobinas/análise , Oximetria/estatística & dados numéricos , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The role of microRNA-21 in isoflurane-induced cardioprotection is unknown. The authors addressed this issue by using microRNA-21 knockout mice and explored the underlying mechanisms. METHODS: C57BL/6 and microRNA-21 knockout mice were echocardiographically examined. Mouse hearts underwent 30 min of ischemia followed by 2 h of reperfusion in vivo or ex vivo in the presence or absence of 1.0 minimum alveolar concentration of isoflurane administered before ischemia. Cardiac Akt, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) proteins were determined by Western blot analysis. Opening of the mitochondrial permeability transition pore (mPTP) in cardiomyocytes was induced by photoexcitation-generated oxidative stress and detected by rapid dissipation of tetramethylrhodamine ethyl ester fluorescence using a confocal microscope. RESULTS: Genetic disruption of miR-21 gene did not alter phenotype of the left ventricle, baseline cardiac function, area at risk, and the ratios of phosphorylated-Akt/Akt, phosphorylated-eNOS/eNOS, and phosphorylated-nNOS/nNOS. Isoflurane decreased infarct size from 54 ± 10% in control to 36 ± 10% (P < 0.05, n = 8 mice per group), improved cardiac function after reperfusion, and increased the ratios of phosphorylated-Akt/AKT, phosphorylated-eNOS/eNOS, and phosphorylated-nNOS/nNOS in C57BL/6 mice subjected to ischemia-reperfusion injury. These beneficial effects of isoflurane were lost in microRNA-21 knockout mice. There were no significant differences in time of the mPTP opening induced by photoexcitation-generated oxidative stress in cardiomyocytes isolated between C57BL/6 and microRNA-21 knockout mice. Isoflurane significantly delayed mPTP opening in cardiomyocytes from C57BL/6 but not from microRNA-21 knockout mice. CONCLUSIONS: Isoflurane protects mouse hearts from ischemia-reperfusion injury by a microRNA-21-dependent mechanism. The Akt/NOS/mPTP pathway is involved in the microRNA-21-mediated protective effect of isoflurane.
Assuntos
Isoflurano/administração & dosagem , MicroRNAs/fisiologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Óxido Nítrico Sintase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Cardiotônicos/administração & dosagem , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Poro de Transição de Permeabilidade Mitocondrial , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Técnicas de Cultura de Órgãos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
Cardioprotection may be genome dependent. One example is the increased tolerance to cardiac ischemia-reperfusion (IR) in Brown Norway (BN) compared with Dahl salt-sensitive (SS) rats. By narrowing the genetic difference to chromosome 6 only, we found the consomic SS(6BN) to be similarly IR tolerant as BN. We hypothesized that better preserved mitochondrial structure and function are genetically determined and therefore critically linked to myocardial IR tolerance associated with BN chromosome 6. Langendorff-prepared BN, SS, and SS(6BN) rat hearts were subjected to IR, while corresponding controls were continuously perfused. Though largely equal in nonischemic controls, assessment of functional data and ventricular infarct size in IR experiments confirmed that BN and SS(6BN) have an equally higher tolerance to IR than SS hearts. This was complemented by equally better preserved mitochondrial structure, oxidative phosphorylation, and calcium retention capacity in BN and SS(6BN) vs. SS hearts. For the first time, our data indicate that SS(6BN) are as resistant to IR injury as BN hearts in mitochondrial and myocardial function and viability compared with SS hearts. These findings not only link myocardial and mitochondrial protection in a genetic model but also suggest that genetic information on rat chromosome 6 is critical for mitochondrial preservation and IR tolerance.
Assuntos
Mitocôndrias Cardíacas/genética , Traumatismo por Reperfusão Miocárdica/genética , Animais , Cálcio/metabolismo , Modelos Animais de Doenças , Coração/fisiologia , Masculino , Mitocôndrias Cardíacas/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Fosforilação Oxidativa , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos DahlRESUMO
BACKGROUND: Ischemic post-conditioning (IPoC) has been shown to improve outcomes in limited pre-clinical models. As down-time is often unknown, this technique needs to be investigated over a range of scenarios. As this tool limits reperfusion injury, there may be limited benefit or even harm after short arrest and limited ischemia-reperfusion injury. METHODS: Eighteen male Wistar rats underwent 7 min of asphyxial arrest. Animals randomized to IPoC received a 20 s pause followed by 20 s of compressions, repeated four times, initiated 40 s into cardiopulmonary resuscitation. If return of spontaneous circulation (ROSC) was achieved, epinephrine was titrated to mean arterial pressure (MAP) of 70 mmHg. Data were analyzed using t-test or Mann-Whitney test. Significance set at p ≤ 0.05. RESULTS: The rate of ROSC was equivalent in both groups, 88%. There was no statistically significant difference in time to ROSC, epinephrine required post ROSC, carotid flow, or peak lactate at any timepoint. There was a significantly elevated MAP with IPoC, 90.7 mmHg (SD 13.9), as compared to standard CPR, 76.7 mmHg (8.5), 2 h after ROSC, p = 0.03. CONCLUSIONS: IPoC demonstrated no harm in a model of short arrest using a new arrest etiology for CPR based IPoC intervention in a rat model.
Assuntos
Asfixia , Modelos Animais de Doenças , Parada Cardíaca , Pós-Condicionamento Isquêmico , Ratos Wistar , Animais , Parada Cardíaca/terapia , Parada Cardíaca/complicações , Parada Cardíaca/fisiopatologia , Masculino , Pós-Condicionamento Isquêmico/métodos , Ratos , Asfixia/complicações , Reanimação Cardiopulmonar/métodos , EpinefrinaRESUMO
Ischemia/reperfusion (I/R) injury significantly contributes to the morbidity and mortality associated with cardiac events. Poloxamer 188 (P188), a nonionic triblock copolymer, has been proposed to mitigate I/R injury by stabilizing cell membranes. However, the underlying mechanisms remain incompletely understood, particularly concerning endothelial cell function and nitric oxide (NO) production. We employed human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) and endothelial cells (ECs) to elucidate the effects of P188 on cellular survival, function, and NO secretion under simulated I/R conditions. iPSC-CMs contractility and iPSC-ECs' NO production were assessed following exposure to P188. Further, an isolated heart model using Brown Norway rats subjected to I/R injury was utilized to evaluate the ex-vivo cardioprotective effects of P188, examining cardiac function and NO production, with and without the administration of a NO inhibitor. In iPSC-derived models, P188 significantly preserved CM contractile function and enhanced cell viability after hypoxia/reoxygenation. Remarkably, P188 treatment led to a pronounced increase in NO secretion in iPSC-ECs, a novel finding demonstrating endothelial protective effects beyond membrane stabilization. In the rat isolated heart model, administration of P188 during reperfusion notably improved cardiac function and reduced I/R injury markers. This cardioprotective effect was abrogated by NO inhibition, underscoring the pivotal role of NO. Additionally, a dose-dependent increase in NO production was observed in non-ischemic rat hearts treated with P188, further establishing the critical function of NO in P188 induced cardioprotection. In conclusion, our comprehensive study unveils a novel role of NO in mediating the protective effects of P188 against I/R injury. This mechanism is evident in both cellular models and intact rat hearts, highlighting the potential of P188 as a therapeutic agent against I/R injury. Our findings pave the way for further investigation into P188's therapeutic mechanisms and its potential application in clinical settings to mitigate I/R-related cardiac dysfunction.
RESUMO
Alpha Gal Syndrome (AGS) is an emerging immune response to mammalian products (MP) containing the oligosaccharide galactose-α-1,3 galactose (α-Gal) which includes meats and inactive ingredients in certain medications. This becomes clinically important in the perioperative realm as MPs are commonly found in the operating room, and pre- and post-operative settings, and can trigger responses as severe as anaphylaxis. In this review, authors discuss the epidemiology, diagnosis and treatment of AGS reactions. Additionally, strategies are explored in order to screen and prevent exposure to MP with a multidisciplinary approach. While this emerging allergy is still not fully understood, it is of paramount importance that all anesthesia providers recognize the implications of MP exposure in AGS patients and ultimately prevent harm in this highly vulnerable population.
Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Animais , Humanos , Galactose , Hipersensibilidade Alimentar/epidemiologia , Anafilaxia/diagnóstico , Anafilaxia/epidemiologia , Anafilaxia/etiologia , Carne/efeitos adversos , MamíferosRESUMO
AIM: Increasing venous return during cardiopulmonary resuscitation (CPR) has been shown to improve hemodynamics during CPR and outcomes following cardiac arrest (CA). We hypothesized that a high central venous pressure amplitude (CVP-A), the difference between the maximum and minimum central venous pressure during chest compressions, could serve as a robust predictor of return of spontaneous circulation (ROSC) in addition to traditional measurements of coronary perfusion pressure (CPP) and end-tidal CO2 (etCO2) in a porcine model of CA. METHODS: After 10 min of ventricular fibrillation, 9 anesthetized and intubated female pigs received mechanical chest compressions with active compression/decompression (ACD) and an impedance threshold device (ITD). CPP, CVP-A and etCO2 were measured continuously. All groups received biphasic defibrillation (200 J) at minute 4 of CPR and were classified into two groups (ROSC, NO ROSC). Mean values were analyzed over 3 min before defibrillation by repeated-measures Analysis of Variance and receiver operating characteristic (ROC). RESULTS: Five animals out of 9 experienced ROSC. CVP-A showed a statistically significant difference (p = 0.003) between the two groups during 3 min of CPR before defibrillation compared to CPP (p = 0.056) and etCO2 (p = 0.064). Areas-under-the-curve in ROC analysis for CVP-A, CPP and etCO2 were 0.94 (95% Confidence Interval 0.86, 1.00), 0.74 (0.54, 0.95) and 0.78 (0.50, 1.00), respectively. CONCLUSION: In our study, CVP-A was a potentially useful predictor of successful defibrillation and return of spontaneous circulation. Overall, CVP-A could serve as a marker for prediction of ROSC with increased venous return and thereby monitoring the beneficial effects of ACD and ITD.
Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Feminino , Animais , Suínos , Pressão Venosa Central , Parada Cardíaca/terapia , Fibrilação Ventricular/terapia , Hemodinâmica , Modelos Animais de DoençasRESUMO
Ex vivo lung preparations are a useful model that can be translated to many different fields of research, complementing corresponding in vivo and in vitro models. Laboratories wishing to use isolated lungs need to be aware of important steps and inherent challenges to establish a setup that is affordable, reliable, and that can be easily adapted to fit the topic of interest. This paper describes a DIY (do it yourself) model for ex vivo rat lung ventilation and perfusion to study drug and gas effects on pulmonary vascular tone, independent of changes in cardiac output. Creating this model includes a) the design and construction of the apparatus, and b) the lung isolation procedure. This model results in a setup that is more cost-effective than commercial alternatives and yet modular enough to adapt to changes in specific research questions. Various obstacles had to be resolved to ensure a consistent model that is capable of being used for a variety of different research topics. Once established, this model has proven to be highly adaptable to different questions and can easily be altered for different fields of study.
Assuntos
Circulação Extracorpórea , Respiração , Animais , Ratos , Perfusão , PulmãoRESUMO
Reperfusion after ischemia causes additional cellular damage, known as reperfusion injury, for which there is still no effective remedy. Poloxamer (P)188, a tri-block copolymer-based cell membrane stabilizer (CCMS), has been shown to provide protection against hypoxia/reoxygenation (HR) injury in various models by reducing membrane leakage and apoptosis and improving mitochondrial function. Interestingly, substituting one of its hydrophilic poly-ethylene oxide (PEO) blocks with a (t)ert-butyl terminus added to the hydrophobic poly-propylene oxide (PPO) block yields a di-block compound (PEO-PPOt) that interacts better with the cell membrane lipid bi-layer and exhibits greater cellular protection than the gold standard tri-block P188 (PEO75-PPO30-PEO75). For this study, we custom-made three different new di-blocks (PEO113-PPO10t, PEO226-PPO18t and PEO113-PPO20t) to systemically examine the effects of the length of each polymer block on cellular protection in comparison to P188. Cellular protection was assessed by cell viability, lactate dehydrogenase release, and uptake of FM1-43 in mouse artery endothelial cells (ECs) following HR injury. We found that di-block CCMS were able to provide the same or better EC protection than P188. Our study provides the first direct evidence that custom-made di-block CCMS can be superior to P188 in improving EC membrane protection, raising their potential in treating cardiac reperfusion injury.
Assuntos
Vasos Coronários , Traumatismo por Reperfusão , Camundongos , Animais , Células Endoteliais , Membrana Celular , Polietilenoglicóis/farmacologia , Polietilenoglicóis/química , Polímeros/farmacologiaRESUMO
Oxidative damage and impaired cytosolic Ca(2+) concentration ([Ca(2+)](cyto)) handling are associated with mitochondrial [Ca(2+)] ([Ca(2+)](mito)) overload and depressed functional recovery after cardiac ischemia-reperfusion (I/R) injury. We hypothesized that hearts from old guinea pigs would demonstrate impaired [Ca(2+)](mito) handling, poor functional recovery, and a more oxidized state after I/R injury compared with hearts from young guinea pigs. Hearts from young (â¼4 wk) and old (>52 wk) guinea pigs were isolated and perfused with Krebs-Ringer solution (2.1 mM Ca(2+) concentration at 37°C). Left ventricular pressure (LVP, mmHg) was measured with a balloon, and NADH, [Ca(2+)](mito) (nM), and [Ca(2+)](cyto) (nM) were measured by fluorescence with a fiber optic probe placed against the left ventricular free wall. After baseline (BL) measurements, hearts were subjected to 30 min global ischemia and 120 min reperfusion (REP). In old vs. young hearts we found: 1) percent infarct size was lower (27 ± 9 vs. 57 ± 2); 2) developed LVP (systolic-diastolic) was higher at 10 min (57 ± 11 vs. 29 ± 2) and 60 min (55 ± 10 vs. 32 ± 2) REP; 3) diastolic LVP was lower at 10 and 60 min REP (6 ± 3 vs. 29 ± 4 and 3 ± 3 vs. 21 ± 4 mmHg); 4) mean [Ca(2+)](cyto) was higher during ischemia (837 ± 39 vs. 541 ± 39), but [Ca(2+)](mito) was lower (545 ± 62 vs. 975 ± 38); 5) [Ca(2+)](mito) was lower at 10 and 60 min REP (129 ± 2 vs. 293 ± 23 and 122 ± 2 vs. 234 ± 15); 6) reduced inotropic responses to dopamine and digoxin; and 7) NADH was elevated during ischemia in both groups and lower than BL during REP. Contrary to our stated hypotheses, old hearts showed reduced [Ca(2+)](mito), decreased infarction, and improved basal mechanical function after I/R injury compared with young hearts; no differences were noted in redox state due to age. In this model, aging-associated protection may be linked to limited [Ca(2+)](mito) loading after I/R injury despite higher [Ca(2+)](cyto) load during ischemia in old vs. young hearts.
Assuntos
Envelhecimento/metabolismo , Cálcio/metabolismo , Mitocôndrias/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Animais , Cardiotônicos/farmacologia , Circulação Coronária/fisiologia , Citosol/metabolismo , Digoxina/farmacologia , Dopamina/farmacologia , Cobaias , Contração Miocárdica/fisiologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , NAD/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologiaRESUMO
Traumatic brain injury can lead to fatal outcomes such as disability and death. Every year, it affects many patients all over the world. Not only the primary ischemic event, but also the subsequent reperfusion can cause severe brain injury. This so-called ischemia/reperfusion injury combined with mechanical forces lead to cellular disruption. Hence, this paper describes a special in-vitro model, mimicking traumatic brain injury by combining both hypoxia/reoxygenation and compression to simulate ischemia/reperfusion injury as well as the mechanical effects that occur concurrently when suffering traumatic brain injury. Through this approach, stroke, concussion, and traumatic brain injury can be studied on different cell lines in a simplified way. We used two primary mouse brain cell cultures, namely neurons and endothelial cells. Our results show that for the different cell types, different timelines of hypoxia and compression need to be explored to achieve the optimal amount of cellular damage in order to effectively mimic traumatic brain injury. Thus, this model will be useful to test potential treatments of brain injury in future in-vitro studies.