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OBJECTIVES: To describe the incidence of postoperative hypotension in patients undergoing cardiac surgery during the first 12 hours in the intensive care unit (ICU) and any relationship between hypotension and the development of acute kidney injury (AKI). DESIGN: This was a retrospective, observational cohort study. SETTING: The study took place in a single-center tertiary teaching hospital in London, UK. PARTICIPANTS: Adult patients (n = 100) who underwent elective cardiac surgery requiring intraoperative cardiopulmonary bypass between May and November 2021 were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A hypotensive event was defined as mean arterial pressure <65 mmHg lasting at least 1 minute. Invasive blood pressure data was analyzed for the first 12 hours after surgery, and any association between postoperative hypotension and AKI was assessed. A total of 91% of patients experienced hypotension in the first 12 hours postprocedure. On average, patients experienced 9 hypotensive events, with events lasting an average of 5 minutes. A total of 16 patients (16%) developed at least stage 1 AKI. The average duration of hypotension was significantly higher in the AKI group (4.6 min [IQR 3.3, 8.0] v 8.1 min [IQR 5.2, 14.2], p = 0.029). Those suffering AKI had longer ICU and hospital stays. CONCLUSIONS: This study demonstrated that hypotension in the first 12 hours following cardiac surgery is common and prolonged hypotensive events are associated with developing AKI. This emphasizes the importance of treating hypotension aggressively and highlights a target for further research and intervention.
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Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Hipotensão , Complicações Pós-Operatórias , Humanos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Masculino , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Feminino , Hipotensão/epidemiologia , Hipotensão/etiologia , Hipotensão/diagnóstico , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Idoso , Incidência , Estudos de Coortes , Unidades de Terapia IntensivaRESUMO
Introduction and aims: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized therapeutic choice in patients with cardiogenic shock, however, high complication rate often counteracts with its beneficial cardiopulmonary effects. The assessment of left ventricular (LV) function in key in the management of this population, however, the most commonly used measures of LV performance are substantially load-dependent. Non-invasive myocardial work is a novel LV functional measure which may overcome this limitation and estimate LV function independent of the significantly altered loading conditions of VA-ECMO therapy. The Usefulness of Myocardial Work IndeX in ExtraCorporeal Membrane Oxygenation Patients (MIX-ECMO) study aims to examine the prognostic role of non-invasive myocardial work in VA-ECMO-supported patients. Methods: The MIX-ECMO is a multicentric, prospective, observational study. We aim to enroll 110 patients 48-72â h after the initiation of VA-ECMO support. The patients will undergo a detailed echocardiographic examination and a central echocardiography core laboratory will quantify conventional LV functional measures and non-invasive myocardial work parameters. The primary endpoint will be failure to wean at 30 days as a composite of cardiovascular mortality, need for long-term mechanical circulatory support or heart transplantation at 30 days, and besides that other secondary objectives will also be investigated. Detailed clinical data will also be collected to compare LV functional measures to parameters with established prognostic role and also to the Survival After Veno-arterial-ECMO (SAVE) score. Conclusions: The MIX-ECMO study will be the first to determine if non-invasive myocardial work has added prognostic value in patients receiving VA-ECMO support.
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Purpose: In diabetic subjects, early visual functional alterations such as color vision deficiencies (CVDs) are known to precede clinically apparent diabetic retinopathy. Prominent photoreceptor outer segment degeneration and an increase in the number of retinal dual cones (co-expressing S- and M-opsins simultaneously) have been described in diabetic rat models, suggesting a connection with the development of CVDs. As cone opsin expression is controlled by thyroid hormones, we investigated the diabetic retina in association with thyroid hormone alterations. Methods: In rat models of type 1 and 2 diabetes, dual cones were labeled by immunohistochemistry, and their numbers were analyzed in relation to free triiodothyronine (fT3) and free thyroxine (fT4) levels. Quantification of dual cones was also performed in human postmortem retinas. Additionally, a cross-sectional case-control study was performed where thyroid hormone levels were measured and color vision was assessed with Lanthony desaturated D15 discs. Results: A higher number of dual cones was detectable in diabetic rats, correlating with fT4 levels. Dual cones were also present in postmortem human retinas, with higher numbers in the three diabetic retinas. As expected, age was strongly associated with CVDs in human patients, and the presence of diabetes also increased the risk. However, the current study failed to detect any effect of thyroid hormones on the development of CVDs. Conclusions: Our results point toward the involvement of thyroid homeostasis in the opsin expression changes in diabetic rats and human samples. The evaluation of the possible clinical consequences warrants further research.
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Diabetes Mellitus Experimental/sangue , Retinopatia Diabética/sangue , Células Fotorreceptoras Retinianas Cones/patologia , Hormônios Tireóideos/sangue , Adulto , Idoso , Animais , Glicemia/metabolismo , Estudos de Casos e Controles , Visão de Cores/fisiologia , Opsinas dos Cones/metabolismo , Estudos Transversais , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Retinopatia Diabética/patologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley , Ratos Zucker , Células Fotorreceptoras Retinianas Cones/metabolismo , Adulto JovemRESUMO
AIMS AND OBJECTIVES: Acute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia-reperfusion injury and the corollary renal dysfunction. METHODS: Male Wistar rats underwent 180 min bilateral lower limb ischemia followed by 4 or 24 hours of reperfusion. Intravenous Levosimendan was administered continuously (0.2µg/bwkg/min) throughout the whole course of ischemia and the first 3h of reperfusion. Results were compared with sham-operated and ischemia-reperfusion groups. Hemodynamic monitoring was performed by invasive arterial blood pressure measurement. Kidney and lower limb muscle microcirculation was registered by a laser Doppler flowmeter. After 4h and 24h of reperfusion, serum, urine and histological samples were collected. RESULTS: Systemic hemodynamic parameters and microcirculation of kidney and the lower limb significantly improved in the Levosimendan treated group. Muscle viability was significantly preserved 4 and 24 hours after reperfusion. At the same time, renal functional laboratory tests and kidney histology demonstrated significantly less expressive kidney injury in Levosimendan groups. TNF-α levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion. CONCLUSION: The results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications.
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BACKGROUND: Major lower limb vascular surgeries may result in severe, remote injury of the gastrointestinal system, which has high mortality rates. Postconditioning is a technique with potential capability of reducing remote gastrointestinal complications. Our aim was to assess the remote macro- and micro-hemodynamic changes of the small intestine following an infrarenal aortic occlusion and to evaluate the effects of postconditioning on these alterations. METHODS: Rats underwent 3h of infrarenal aortic occlusion followed by 4h of reperfusion. In one group, postconditioning was applied. Blood pressure, superior mesenteric artery flow and mucosal microcirculation of the duodenum, jejunum and ileum were assessed. Samples were taken from each intestinal segment for histological examinations. RESULTS: Superior mesenteric artery flow, as well as microcirculation of the duodenum, jejunum and ileum showed significant impairment in the IR group, while histological damage was significantly worsened. Postconditioning was able to limit flow reduction in all three small bowel segments and in the superior mesenteric artery, and was able to significantly reduce histological damage. Strong negative correlation was found between microcirculatory values and histological damage. CONCLUSIONS: Microcirculatory impairment might be responsible for remote intestinal injury following infrarenal aortic occlusion. Postconditioning was able to reduce this remote intestinal damage.
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Aorta/patologia , Arteriopatias Oclusivas/patologia , Intestino Delgado/patologia , Isquemia/patologia , Pós-Condicionamento Isquêmico , Microcirculação , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Hemodinâmica , Mucosa Intestinal/irrigação sanguínea , Masculino , Artéria Mesentérica Superior/patologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologiaRESUMO
BACKGROUND: Postconditioning is a novel reperfusion technique to reduce ischemia-reperfusion injuries. The aim of the study was to investigate this method in an animal model of lower limb revascularization for purpose of preventing postoperative renal failure. METHODS: Bilateral lower limb ischemia was induced in male Wistar rats for 3 hours by infrarenal aorta clamping under narcosis. Revascularization was allowed by declamping the aorta. Postconditioning (additional 10 sec reocclusion, 10 sec reperfusion in 6 cycles) was induced at the onset of revascularization. Myocyte injury and renal function changes were assessed 4, 24 and 72 hours postoperatively. Hemodynamic monitoring was performed by invasive arterial blood pressure registering and a kidney surface laser Doppler flowmeter. RESULTS: Muscle viability studies showed no significant improvement with the use of postconditioning in terms of ischemic rhabdomyolysis (4 h: ischemia-reperfusion (IR) group: 42.93 ± 19.20% vs. postconditioned (PostC) group: 43.27 ± 27.13%). At the same time, renal functional laboratory tests and kidney myoglobin immunohistochemistry demonstrated significantly less expressed kidney injury in postconditioned animals (renal failure index: 4 h: IR: 2.37 ± 1.43 mM vs. PostC: 0.92 ± 0.32 mM; 24 h: IR: 1.53 ± 0.45 mM vs. PostC: 0.77 ± 0.34 mM; 72 h: IR: 1.51 ± 0.36 mM vs. PostC: 0.43 ± 0.28 mM), while systemic hemodynamics and kidney microcirculation significantly improved (calculated reperfusion area: IR: 82.31 ± 12.23% vs. PostC: 99.01 ± 2.76%), and arterial blood gas analysis showed a lesser extent systemic acidic load after revascularization (a defined relative base excess parameter: 1(st) s: IR: 2.25 ± 1.14 vs. PostC: 1.80 ± 0.66; 2(nd) s: IR: 2.14 ± 1.44 vs. PostC: 2.44 ± 1.14, 3(rd) s: IR: 3.99 ± 3.09 vs. PostC: 2.07 ± 0.82; 4(th) s: IR: 3.28 ± 0.32 vs. PostC: 2.05 ± 0.56). CONCLUSIONS: The results suggest a protective role for postconditioning in major vascular surgeries against renal complications through a possible alternative release of nephrotoxic agents and exerting a positive effect on hemodynamic stability.
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Pós-Condicionamento Isquêmico , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Animais , Proteínas de Choque Térmico HSP72/metabolismo , Hemodinâmica , Imuno-Histoquímica , Córtex Renal/irrigação sanguínea , Córtex Renal/patologia , Córtex Renal/fisiopatologia , Testes de Função Renal , Fluxometria por Laser-Doppler , Peroxidação de Lipídeos , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/fisiopatologia , Masculino , Microcirculação , Músculos/patologia , Mioglobina/metabolismo , Ratos Wistar , Insuficiência Renal/fisiopatologia , Traumatismo por Reperfusão/prevenção & controleRESUMO
BACKGROUND: The ability of remote ischemic perconditioning (RIPER) to protect the liver from ischemic-reperfusion (IR) injury has been reported before; however, the mechanism behind the positive effects of RIPER remains unrevealed. Therefore, we aimed to investigate the potential role of neural elements to transfer protective signals evoked by perconditioning. MATERIALS AND METHODS: Male Wistar rats were randomly allocated into six groups (sham, IR, RIPER ± denervation; n = 7 per group). Half of the animals underwent left femoral and sciatic nerve resection. In IR and RIPER groups, normothermic, partial (70%) liver ischemia lasting for 60 min was induced; parallel animals in the RIPER groups received perconditioning treatment (4 × 5 - 5 min IR, left femoral artery clamping). Hepatic microcirculation and systemic blood pressure were monitored during the first postischemic hour. After 24 h of reperfusion, liver samples were taken for histology and redox-state analysis. Automated image analysis software was used for necrosis quantification. Serum alanine aminotransferase, aspartate aminotransferase, and bilirubin levels were measured. RESULTS: Microcirculation and blood pressure showed significant improvement during reperfusion after perconditioning. This phenomenon was completely abolished by nerve resection (P < 0.05; RIPER versus IR, IR + denervation, and RIPER + denervation). Results of necrosis quantification showed similar pattern. Besides noncharacteristic changes in aspartate aminotransferase levels, alanine aminotransferase values were significantly lower (P < 0.05) in the RIPER group compared with the other IR groups. Mild but significant alterations were observed in liver function assessed by total bilirubin levels. Further supporting results were obtained from analysis of redox homeostasis. CONCLUSIONS: Perconditioning was able to reduce liver IR injury in our model via a mechanism most probably involving interorgan neural pathways.
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Artéria Femoral , Precondicionamento Isquêmico , Hepatopatias/prevenção & controle , Extremidade Inferior/inervação , Traumatismo por Reperfusão/prevenção & controle , Animais , Nervo Femoral/fisiologia , Nervo Femoral/cirurgia , Fígado/irrigação sanguínea , Extremidade Inferior/irrigação sanguínea , Masculino , Microcirculação , Oxirredução , Distribuição Aleatória , Ratos Wistar , Nervo Isquiático/fisiologia , Nervo Isquiático/cirurgiaRESUMO
INTRODUCTION: Operation on the infrarenal aorta and large arteries of the lower extremities may cause rhabdomyolysis of the skeletal muscle, which in turn may induce remote kidney injury. NIM-811 (N-metyl-4-isoleucine-cyclosporine) is a mitochondria specific drug, which can prevent ischemic-reperfusion (IR) injury, by inhibiting mitochondrial permeability transition pores (mPTP). OBJECTIVES: Our aim was to reduce damages in the skeletal muscle and the kidney after IR of the lower limb with NIM-811. MATERIALS AND METHODS: Wistar rats underwent 180 minutes of bilateral lower limb ischemia and 240 minutes of reperfusion. Four animal groups were formed called Sham (receiving vehicle and sham surgery), NIM-Sham (receiving NIM-811 and sham surgery), IR (receiving vehicle and surgery), and NIM-IR (receiving NIM-811 and surgery). Serum, urine and histological samples were taken at the end of reperfusion. NADH-tetrazolium staining, muscle Wet/Dry (W/D) ratio calculations, laser Doppler-flowmetry (LDF) and mean arterial pressure (MAP) monitoring were performed. Renal peroxynitrite concentration, serum TNF-α and IL-6 levels were measured. RESULTS: Less significant histopathological changes were observable in the NIM-IR group as compared with the IR group. Serum K+ and necroenzyme levels were significantly lower in the NIM-IR group than in the IR group (LDH: p<0.001; CK: p<0.001; K+: pâ=â0.017). Muscle mitochondrial viability proved to be significantly higher (pâ=â0.001) and renal function parameters were significantly better (creatinine: pâ=â0.016; FENa: p<0.001) in the NIM-IR group in comparison to the IR group. Serum TNF-α and IL-6 levels were significantly lower (TNF-α: pâ=â0.003, IL-6: pâ=â0.040) as well as W/D ratio and peroxynitrite concentration were significantly lower (pâ=â0.014; p<0.001) in the NIM-IR group than in the IR group. CONCLUSION: NIM-811 could have the potential of reducing rhabdomyolysis and impairment of the kidney after lower limb IR injury.
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Injúria Renal Aguda/etiologia , Ciclosporina/farmacologia , Extremidade Inferior/cirurgia , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Traumatismo por Reperfusão/complicações , Rabdomiólise/complicações , Rabdomiólise/etiologia , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Sobrevivência Celular , Ciclosporina/administração & dosagem , Modelos Animais de Doenças , Hemodinâmica , Interleucina-6/sangue , Interleucina-6/metabolismo , Testes de Função Renal , Masculino , Microcirculação , Poro de Transição de Permeabilidade Mitocondrial , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Ratos , Traumatismo por Reperfusão/metabolismo , Rabdomiólise/tratamento farmacológico , Rabdomiólise/patologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
UNLABELLED: Mesenteric ischemia-reperfusion (IR) is associated with impairment of the gut barrier function and the initiation of a proinflammatory cascade with life-threatening results. Therefore methods directed to ameliorate IR injury are of great importance. We aimed at describing the effects of postconditioning (PC) on the alterations of the intestinal mucosal function and the inflammatory response upon mesenteric IR. METHODS: Male Wistar rats were gavaged with green fluorescent protein-expressing E. coli suspensions. Animals were randomized into three groups (n = 15), sham-operated, IR-, and PC-groups, and underwent 60 minutes of superior mesenteric artery occlusion, followed by 6 hours of reperfusion. Postconditioning was performed at the onset of reperfusion. Blood and tissue samples were taken at the end of reperfusion, for histological, bacteriological, and plasma examinations. RESULTS: The PC-group presented a more favorable claudin-2, claudin-3, claudin-4, and zonula occludens-1 membrane expression profile, and significantly lower rates of bacterial translocation to distant organs and plasma D-lactate levels compared to the IR-group. Histopathological lesions, plasma I-FABP, IL-6, and TNF- α levels were significantly lower in the PC-group compared to the IR-group. CONCLUSION: The use of postconditioning improved the integrity of the intestinal mucosal barrier upon mesenteric IR, and thus reduced the incidence of bacterial translocation and development of a systemic inflammatory response.
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Mucosa Intestinal/metabolismo , Pós-Condicionamento Isquêmico , Isquemia Mesentérica/sangue , Traumatismo por Reperfusão/metabolismo , Animais , Escherichia coli/patogenicidade , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Isquemia Mesentérica/microbiologia , Isquemia Mesentérica/patologia , Oclusão Vascular Mesentérica , Ratos , Traumatismo por Reperfusão/microbiologia , Traumatismo por Reperfusão/patologiaRESUMO
PURPOSE/AIM OF THE STUDY: Long-lasting lower limb arterial occlusion is a condition with high incidence and complication rates. With the absence of appropriate treatment to cure advanced complications, mortality rates are high. Postconditioning (PC) might be capable of limiting the degree of ischemic-reperfusion (IR) injuries, thus reducing complications and mortality rates. The aim of this study was to evaluate the impact of postconditioning during the first postoperative day on skeletal muscle after a long-lasting arterial occlusion. MATERIALS AND METHODS: Male Wistar rats (n = 72) underwent 8 hr of infrarenal aortic occlusion followed by 2, 6, 12, or 24 hr of reperfusion. In one group of each reperfusion period, postconditioning was applied. Muscle samples were collected for histological examinations. Furthermore, muscle fiber viability and muscle wet-to-dry ratio were assessed. Blood samples were taken for creatine-kinase measurements. RESULTS: Postconditioning strongly reduced morphological injury compared to the corresponding ischemic-reperfusion group (p < .001). Serum creatine-kinase levels showed a peak at 6 hr post-ischemia (IR: 6702.2 ± 797.5; PC: 5523.3 ± 769.3 IU/l) and decreased to normal level by the end of the experiment (Sham: 171.5 ± 71.6; IR: 186.2 ± 82.7; PC: 174.2 ± 72.4 IU/l). Creatine-kinase levels were significantly reduced by postconditioning (p2hr = .028; p6hr = .06; p12hr = .042). A marked decrease in viability was observed in the ischemic-reperfusion groups (2 hr: 11.0 ± 4.1; 6 hr: 10.3 ± 3.6; 12 hr: 9.4 ± 3.3; 24 hr: 8.6 ± 2.8%), whereas with postconditioning, viability was preserved (2 hr: 26.4 ± 5.5; 6 hr: 24.6 ± 4.5; 12 hr: 24.5 ± 6.8; 24 hr: 26.2 ± 6.1%; p < .001); moreover, a significant decrease in the wet-to-dry ratio was achieved (p < .001). CONCLUSION: Postconditioning was able to reduce local complications after a long-lasting lower limb vascular occlusion.
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Pós-Condicionamento Isquêmico/métodos , Músculo Esquelético/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Arteriopatias Oclusivas/enzimologia , Arteriopatias Oclusivas/patologia , Arteriopatias Oclusivas/prevenção & controle , Creatina Quinase/sangue , Extremidades , Masculino , Músculo Esquelético/enzimologia , Músculo Esquelético/lesões , Ratos , Ratos Wistar , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Fatores de TempoRESUMO
Acute lower extremity ischemia is a limb- and life-threatening clinical problem. Rapid detection of the degree of injury is crucial, however at present there are no exact diagnostic tests available to achieve this purpose. Our goal was to examine a novel technique - which has the potential to accurately assess the degree of ischemic muscle injury within a short period of time - in a clinically relevant rodent model. Male Wistar rats were exposed to 4, 6, 8 and 9 hours of bilateral lower limb ischemia induced by the occlusion of the infrarenal aorta. Additional animals underwent 8 and 9 hours of ischemia followed by 2 hours of reperfusion to examine the effects of revascularization. Muscle samples were collected from the left anterior tibial muscle for viability assessment. The degree of muscle damage (muscle fiber viability) was assessed by morphometric evaluation of NADH-tetrazolium reductase reaction on frozen sections. Right hind limbs were perfusion-fixed with paraformaldehyde and glutaraldehyde for light and electron microscopic examinations. Muscle fiber viability decreased progressively over the time of ischemia, with significant differences found between the consecutive times. High correlation was detected between the length of ischemia and the values of muscle fiber viability. After reperfusion, viability showed significant reduction in the 8-hour-ischemia and 2-hour-reperfusion group compared to the 8-hour-ischemia-only group, and decreased further after 9 hours of ischemia and 2 hours of reperfusion. Light- and electron microscopic findings correlated strongly with the values of muscle fiber viability: lesser viability values represented higher degree of ultrastructural injury while similar viability results corresponded to similar morphological injury. Muscle fiber viability was capable of accurately determining the degree of muscle injury in our rat model. Our method might therefore be useful in clinical settings in the diagnostics of acute ischemic muscle injury.
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Isquemia/patologia , Fibras Musculares Esqueléticas/patologia , Animais , Isquemia/fisiopatologia , Masculino , Microcirculação , Fibras Musculares Esqueléticas/ultraestrutura , NADH Tetrazólio Redutase/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Sobrevivência de TecidosRESUMO
PURPOSE: Rats are the most commonly used animal model for studies of acute lower limb ischemia-reperfusion. The ischemia induced by arterial clamping may cause milder damage than the application of a tourniquet if the presence of a possible collateral system is considered. METHODS: Male Wistar rats were randomized into three groups: in group A, the muscle weight affected by ischemia was measured; in group B, the severity of muscle damage caused by the application of a tourniquet and by infrarenal aortic occlusion was examined. Blood and muscle samples were taken from group B to assess the serum necroenzyme, potassium and TNF-α levels, as well as the muscle fiber viability and for histological examinations. In group C, the identification of the lower limb collateral system was performed using corrosion casting. RESULTS: Tourniquet application affected the lower muscle mass and resulted in significantly more severe injury compared to infrarenal aortic occlusion. This difference was reflected in the serum necroenzyme, potassium and TNF-α levels. The histological examination and viability assay confirmed these findings. The corrosion casts showed several anastomoses capable of supplying the lower limb. CONCLUSION: Tourniquet application proved to be capable of inducing absolute lower limb ischemia, in contrast to infrarenal aortic ligation, where a rich collateral system is considered to help mitigate the injury.
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Aorta , Circulação Colateral/fisiologia , Isquemia/fisiopatologia , Extremidade Inferior/irrigação sanguínea , Traumatismo por Reperfusão/fisiopatologia , Reperfusão , Animais , Arteriopatias Oclusivas/patologia , Arteriopatias Oclusivas/fisiopatologia , Modelos Animais de Doenças , Isquemia/patologia , Rim/irrigação sanguínea , Ligadura , Masculino , Ratos Wistar , Traumatismo por Reperfusão/patologia , TorniquetesRESUMO
BACKGROUND: Mesenteric ischemia is a serious clinical condition requiring immediate surgical intervention. The unavoidable ischemic-reperfusion (IR) injury may be ameliorated using the appropriate postconditioning protocol. The aim of the present study was to investigate the optimal postconditioning algorithm in a rat model of intestinal ischemic-reperfusion injury. MATERIALS AND METHODS: Male Wistar rats were randomized into five groups (n = 10), one sham-operated, one IR, and three postconditioned groups, each with different protocols. The animals were subjected to 60 min of mesenteric ischemia, followed by 60 min of reperfusion. Postconditioning was applied at the onset of reperfusion using three different algorithms. Arterial pressure and mucosal microcirculation were monitored throughout the experiment. Mesenteric pH was determined at the early phase of reperfusion. Blood and tissue samples were taken at the end of reperfusion for histologic evaluation, serum lactate dehydrogenase, serum creatine kinase, serum tumor necrosis factor-α, serum interleukin-6, detailed mucosal antioxidant, and scavenger capacity assays. RESULTS: The shorter and intermediate length cycles of postconditioning enhanced mucosal microcirculation and redox state and significantly delayed the normalization of mesenteric pH. Furthermore, milder histopathologic lesions and lower concentrations of serum necroenzymes and proinflammatory cytokines were detected compared with the IR group. The protective effect of postconditioning using longer cycles could only be seen in a tendentious manner. CONCLUSIONS: In a rat model of intestinal ischemia-reperfusion, the shorter and intermediate length cycles of postconditioning proved to be more effective than the use of longer cycles.
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Intestino Delgado/irrigação sanguínea , Pós-Condicionamento Isquêmico/métodos , Traumatismo por Reperfusão/cirurgia , Traumatismo por Reperfusão/terapia , Algoritmos , Animais , Creatina Quinase/sangue , Modelos Animais de Doenças , Hemodinâmica/fisiologia , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestino Delgado/metabolismo , Intestino Delgado/patologia , L-Lactato Desidrogenase/sangue , Masculino , Microcirculação/fisiologia , Distribuição Aleatória , Ratos , Ratos Endogâmicos WF , Traumatismo por Reperfusão/metabolismo , Fatores de TempoRESUMO
INTRODUCTION: Temporary occlusion of the hepatoduodenal ligament leads to an ischemic-reperfusion (IR) injury in the liver. Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels. The aim of this study was to examine possible protective effects of levosimendan in a rat model of hepatic IR injury. MATERIAL AND METHODS: Levosimendan was administered to male Wistar rats 1 hour (early pretreatment) or 24 hours (late pretreatment) before induction of 60-minute segmental liver ischemia. Microcirculation of the liver was monitored by laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH-TR) as well as for laboratory tests. Furthermore, liver antioxidant status was assessed and HSP72 expression was measured. RESULTS: In both groups pretreated with levosimendan, significantly better hepatic microcirculation was observed compared to respective IR control groups. Similarly, histological damage was also reduced after levosimendan administration. This observation was supported by significantly lower activities of serum ALT (p early = 0.02; p late = 0.005), AST (p early = 0.02; p late = 0.004) and less DNA damage by TUNEL test (p early = 0.05; p late = 0.034) and PAR positivity (p early = 0.02; p late = 0.04). Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis. Further, significantly better mitochondrial function was detected in animals receiving late pretreatment. Finally, HSP72 expression was increased by IR injury, but it was not affected by levosimendan pretreatment. CONCLUSION: Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection.
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Cardiotônicos/farmacologia , Hidrazonas/farmacologia , Fígado/irrigação sanguínea , Piridazinas/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Western Blotting , Dano ao DNA/efeitos dos fármacos , Proteínas de Choque Térmico HSP72/metabolismo , Imuno-Histoquímica , Fígado/metabolismo , Masculino , Microcirculação/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Oxirredução/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/fisiopatologia , Simendana , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Ischemia-reperfusion (IR)-induced injury is a frequent sequel of major liver resections. IR injury after prolonged surgical interventions could be the source of increased risk of postoperative morbidity and mortality. Hepatoprotective effects of this new feasible method called remote ischemic perconditioning (RIPER) were investigated in our rat model of IR injury. MATERIALS AND METHODS: Male Wistar rats underwent ischemia for 60 min on two-thirds of their livers, followed by 1, 6, and 24 h of reperfusion (n = 72, 8 per group). During liver ischemia, but before reperfusion, rats in the treated groups received four cycles of brief infrarenal aortic clamping as perconditioning. Liver microcirculation was monitored by laser Doppler flowmeter parallel with mean arterial pressure measurements. Liver tissue injury and redox homeostasis were investigated. Furthermore, serum tumor necrosis factor alpha (TNF-α) levels were measured. RESULTS: In the RIPER group, compared with the IR group, serum transaminase levels were significantly lower after each reperfusion period (alanine aminotransferase: 1 h, P < 0.001; 6 h, P < 0.05; 24 h, P < 0.01 and aspartate aminotransferase: 1 h, P < 0.001; 6 h, P < 0.05; 24 h, P < 0.05). Reperfusion microcirculatory parameters significantly improved in the perconditioned group compared with those in the IR group (reperfusion area: P = 0.005; maximal plateau: P = 0.0002). Regarding TNF-α levels, significant differences were detected between the two IR injured groups (RIPER versus IR: 1 h, 34.3 ± 12.8 pg/mL versus 205.7 ± 60.9 pg/mL, P < 0.001; 6 h, 60.6 ± 11.7 pg/mL versus 110.4 ± 21.6 pg/mL, P < 0.05). Results of the histologic assessment and redox state measurements also showed favorable changes. CONCLUSIONS: Our team firstly reported the protective effects of RIPER on liver morphology, redox homeostasis, and microcirculation and proposed the changes of TNF-α expression.
Assuntos
Precondicionamento Isquêmico/métodos , Hepatopatias/diagnóstico por imagem , Hepatopatias/prevenção & controle , Fígado/diagnóstico por imagem , Traumatismo por Reperfusão/diagnóstico por imagem , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Radicais Livres/metabolismo , Fluxometria por Laser-Doppler , Fígado/irrigação sanguínea , Fígado/metabolismo , Circulação Hepática/fisiologia , Hepatopatias/metabolismo , Masculino , Microcirculação/fisiologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Fator de Necrose Tumoral alfa/sangue , UltrassonografiaRESUMO
The most severe complication of ischemia-reperfusion injury following lower limb arterial surgery is reperfusion syndrome. Therefore, our aim was to describe the extent of muscle damage and the reperfusion syndrome-related remote organ lesions in detail, through a well-documented case of long-lasting infrarenal aorta thrombosis. After urgent revascularization, several clinical signs of multiple organ dysfunction were detectable, including the circulatory, urinary, respiratory, gastrointestinal, and hemostatic systems. Upon histological examination, intraoperative muscle biopsy showed severe muscle damage. Muscle fiber viability was assessed with a special nitroblue tetrazolium staining-based viability test developed by our team; the obtained results indicated significant degree of muscle damage before this was confirmed by conventional histological methods. Thorough postmortem examination confirmed the presence of remote organ damage. The pathological findings included acute tubular necrosis, myocardial and jejunal infarctions, ischemic pancreatitis, and diffuse alveolar damage with hyaline membrane formation in the lungs and focal centrilobular liver necrosis. By using special staining techniques, the presence of myoglobin and lipofuscin deposits was confirmed in the kidney samples. In this paper, we present a patient who developed all major complications following long-lasting arterial occlusion. We also introduce a novel method to assess the degree of ischemic injury, which may be suitable in the near future for the rapid detection of irreversible muscle injury. Therefore, the mortality of the disease might be reduced.
Assuntos
Doenças da Aorta/etiologia , Implante de Prótese Vascular/efeitos adversos , Síndromes Compartimentais/etiologia , Oclusão de Enxerto Vascular/etiologia , Músculo Esquelético/irrigação sanguínea , Traumatismo por Reperfusão/etiologia , Trombose/etiologia , Doença Aguda , Doenças da Aorta/diagnóstico , Doenças da Aorta/fisiopatologia , Doenças da Aorta/cirurgia , Autopsia , Síndromes Compartimentais/diagnóstico , Síndromes Compartimentais/fisiopatologia , Estado Terminal , Progressão da Doença , Evolução Fatal , Oclusão de Enxerto Vascular/diagnóstico , Oclusão de Enxerto Vascular/fisiopatologia , Oclusão de Enxerto Vascular/cirurgia , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Músculo Esquelético/patologia , Necrose , Reoperação , Traumatismo por Reperfusão/diagnóstico , Traumatismo por Reperfusão/fisiopatologia , Traumatismo por Reperfusão/cirurgia , Trombose/diagnóstico , Trombose/fisiopatologia , Trombose/cirurgia , Fatores de TempoRESUMO
BACKGROUND: Operations on the infrarenal aorta can cause ischemic-reperfusion (IR) injury in local tissues, which could result in remote organ (e.g., lung) damage. Treatment of such injuries remains an unresolved problem. OBJECTIVES: Our aim was to reduce remote lung damage after lower limb IR by means of postconditioning. MATERIALS AND METHODS: Male Wistar rats were divided into three groups: Sham-operated, IR, and Postconditioned (PostC). In the latter two groups rats underwent 180 min of exclusion of the infrarenal aorta. The reperfusion time was 4 h. Serum-free radical levels, tumor necrosis factor-α and interleukin-6 concentrations, histologic changes in the lung, wet/dry-ratio, myeloperoxidase activity, heat shock protein 72 level and blood gas changes were investigated. RESULTS: Postconditioning reduced histological damage in the lung (P < 0.05). Free radical levels and tumor necrosis factor-α concentrations were significantly lower in the PostC group than in the IR group (P < 0.05 and P < 0.01, respectively). Interleukin-6 concentrations did not significantly differ in the PostC group. Compared with the IR group, lung myeloperoxidase activity was lower in the PostC group. Decreased pulmonary heat shock protein 72 level was observed in the PostC group compared with the IR group and the wet/dry-ratio was also significantly lower in the PostC group (P < 0.05). A noticeably higher arterial pO2 level was manifest in the PostC group after 2 and 4 h of reperfusion (P < 0.05). CONCLUSIONS: Postconditioning reduced lung damage under experimental conditions, in the early period of reperfusion after lower limb IR injury.
Assuntos
Lesão Pulmonar Aguda/terapia , Pós-Condicionamento Isquêmico/métodos , Complicações Pós-Operatórias/terapia , Traumatismo por Reperfusão/complicações , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Animais , Aorta Abdominal/cirurgia , Modelos Animais de Doenças , Radicais Livres/metabolismo , Membro Posterior/irrigação sanguínea , Membro Posterior/cirurgia , Interleucina-6/metabolismo , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Instrumentos Cirúrgicos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
INTRODUCTION: Operation on the infrarenal aorta could cause ischemic-reperfusion (IR) injury in local tissues and remote organs (e.g. the lung). OBJECTIVES: Our aim was to reduce long-term lung damage, after lower limb IR with postconditioning. MATERIALS AND METHODS: Male Wistar rats underwent 180 minutes of bilateral lower limb ischemia. Animals were divided into three groups: Sham-operated, IR, Postconditioned (PostC) and further to two subgroups according to reperfusion time: 24 h and 72 h. Serum free radical and IL-6 levels, histological changes, Wet/Dry (W/D) ratio, tissue myeloperoxidase (MPO) activity and Hsp72 levels were investigated. RESULTS: Postconditioning can reduce histological changes in the lung. Free radical levels are significantly lower in PostC groups than in IR groups (42.9 ± 8.0 vs. 6.4 ± 3.4; 27.3 ± 4.4 vs. 8.3 ± 4.0 RLU%; p < 0.05). IL-6 level (238.4 ± 31.1 vs. 209.1 ± 18.8; 190.0 ± 8.8 vs. 187.0 ± 14.9 pg/ml) and Hsp72 expression did not show any significant difference. Compared to the IR group, lung MPO activity did not change in the PostC groups. W/D ratio in PostC groups is significantly lower at all measured time-points (68% vs. 65%; 72% vs. 68%; p < 0.05). CONCLUSION: Postconditioning may reduce long-term damages of the lung after lower limb ischemic-reperfusion injury.
Assuntos
Pós-Condicionamento Isquêmico , Extremidade Inferior/irrigação sanguínea , Lesão Pulmonar/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Animais , Biomarcadores/sangue , Radicais Livres/metabolismo , Proteínas de Choque Térmico HSP72/sangue , Interleucina-6/sangue , Lesão Pulmonar/etiologia , Lesão Pulmonar/patologia , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
INTRODUCTION: Several techniques have been developed to reduce ischemic-reperfusion injury. A novel method is the remote ischemic perconditioning, applied parallel with target organ ischemia. AIM: The aim of the study was to determine the extent of liver ischemic-reperfusion injury via the application of this novel method. METHODS: Male Wistar rats (n = 30, 10/group) were subjected to 60-minute partial liver ischemia and 60-minute reperfusion. Rats in the perconditioned group received conditioning treatment during the last 40 minutes of liver ischemia by infrarenal aortic clamping. Hepatic and lower limb microcirculation was monitored by laser Doppler flowmeter during reperfusion. After reperfusion, liver samples were taken for routine histological examination and redox-state assessment. Serum transaminase activities and liver tissue heat-shock protein-72 expression were measured. RESULTS: Parameters of microcirculation showed significant (p<0.05) improvement in the perconditioned group in comparison with the control. Besides the significant improvement observed in the serum alanine amino-transferase activities, significantly milder tissue injury was detected histologically in the liver sections of the perconditioned group. Moreover, significant improvement was found in the redox-state parameters. CONCLUSION: Perconditioning may be a reasonable possibility to reduce liver ischemic-reperfusion injury.