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BACKGROUND AND OBJECTIVES: The HUC-HEART Trial (ClinicalTrials.gov Identifier: NCT02323477) was a controlled, prospective, phase I/II, multicenter, single-blind, three-arm randomized study of intramyocardial delivery of human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) combined with coronary artery bypass-grafting (CABG) in patients with chronic ischemic cardiomyopathy (CIC). The trial aimed to assess (i) the safety and the efficacy of cell transplantation during one-year follow-up, (ii) to compare the efficacy of HUC-MSCs with autologous bone-marrow- derived mononuclear cells (BM-MNCs) in the same clinical settings. METHODS AND RESULTS: Fifty-four patients who were randomized to receive HUC-MSCs (23×106) (n=26) or BM-MNCs (70×107) (n=12) in combination with CABG surgery. The control patients (n=16) received no cells/vehicles but CABG intervention. All patients were screened at baseline and 1, 3, 6, 12 months after transplantation. Forty-six (85%) patients completed 12 months follow-up. No short/mid-term adverse events were encountered. Decline in NT-proBNP (baselineâ¼ 6 months) in both cell-treated groups; an increase in left ventricular ejection fraction (LVEF) (5.4%) and stroke volume (19.7%) were noted (baselineâ¼6 or 12 months) only in the HUC-MSC group. Decreases were also detected in necrotic myocardium as 2.3% in the control, 4.5% in BM-MNC, and 7.7% in the HUC-MSC groups. The 6-min walking test revealed an increase in the control (14.4%) and HUC-MSC (23.1%) groups. CONCLUSIONS: Significant findings directly related to the intramyocardial delivery of HUC-MSCs justified their efficacy in CIC. Stricter patient selection criteria with precisely aligned cell dose and delivery intervals, rigorous follow-up by detailed diagnostic approaches would further help to clarify the responsiveness to the therapy.
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OBJECTIVE: Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) gained importance in acute/chronic ischemic cardiomyopathy because of their outstanding regenerative potential in various pathologic conditions. The present study was designed to determine to what extent hUC-MSCs contribute to myocardial regeneration in acute experimental myocardial infarction (MI) in rats. METHODS: Animals were assigned into two groups; the control group received intramyocardial PBS injections, while the hUC-MSC group received calcein-AM-labeled 8.8 × 106/kg hUC-MSCs. Three weeks following the acute MI induction, rats were sacrificed after assessing the left ventricular (LV) function using echocardiography. For the assessment of infarct size, the triphenyl tetrazolium chloride (TTC) test was used in isolated hearts. Collagen-rich scar tissue was demonstrated using Masson's trichrome staining, followed by the detection of cardiac troponin I (cTnI), α-sarcomeric actin (α-SA), von Willebrand factor (vWF), CD68 and CD206 expressions in control and cell-injected sections. RESULTS: Echocardiography revealed a significant difference (P = 0.037) in the LV ejection fraction between groups. TTC assays demonstrated a significant difference (P = 0.006) between the groups regarding the ratio of the infarcted LV area. Calcein-AM-loaded cells were identified mostly in ischemic myocardium. Transplanted cells also expressed human-specific cTnI, providing concrete proof of transdifferentiation into cardiomyocytes, and α-SA. vWF+ cells verified the neovascularization in the ischemic myocardium. Finally, a slight shift from pro-inflammatory to anti-inflammatory macrophages (CD68+/CD206+) was noted in both groups. CONCLUSIONS: We found that the intramyocardial transplanted hUC-MSCs engrafted and partially transdifferentiated into cardiomyocytes, reduced scar formation, and induced angiogenesis through the association of pro/anti-inflammatory macrophages.
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Células Madre Mesenquimatosas/citología , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patología , Miocitos Cardíacos/citología , Cordón Umbilical/citología , Animales , Células Cultivadas , Ecocardiografía , Femenino , Humanos , Inmunohistoquímica , Masculino , Células Madre Mesenquimatosas/metabolismo , Miocitos Cardíacos/metabolismo , Neovascularización Fisiológica/fisiología , Embarazo , Ratas , Ratas WistarRESUMEN
BACKGROUND: The HUC-HEART Trial is a clinical study of intramyocardial delivery of current Good Manufacturing Practice (cGMP)-grade human umbilical cord multipotent stromal cells (HUC-MSCs) in ischemic cardiomyopathy where 2â¯×â¯107 cells are administered to peri-infarcted myocardium. Prior to the onset of the trial, we aimed to optimize the transport/storage conditions for obtaining the highest cell viability and proliferation rate of cells to be transplanted. METHODS: Cells were tested after being transported in phosphate-buffered saline (PBS) or Ringer's lactate-based (RL) transport media supplemented with human serum albumin (HSA) and/or hydroxyethyl starch (HES) at two temperatures (2-10°C or 22-24°C). RESULTS: The effects of transport conditions on cell viability following 6 h were found highest (93.4 ± 1.5) in RL-based media at 2-10°C. Karyotypes were found normal upon transportation in any of the formulations and temperatures. However, the highest proliferation rate was noted (3.1-fold increase) in RL (1% HSA) media at 2-10°C over 6 days in culture. From that point, RL (1% HSA) media at 2-10°C was used for further experiments. The maximum cell storage time was detected around 24 h at 2-10°C. Extended storage periods resulted in a decrease in cell viability but not in MSC marker expression. An increase in actin quantity was detected in hypoxia (5% O2) groups in early culture days; no difference was noted between hypoxic versus normoxic (21% O2) conditions in later days. DISCUSSION: The overall results suggest that non-commercial, simple media formulations with extended storage intervals at 2-10°C temperatures are capable of retaining the characteristics of clinical-grade HUC-MSCs. The above findings led us to use RL (1% HSA) media at 2-10°C for transport and storage in the HUC-HEART Trial; 23 patients received HUC-MSCs by August 2018; no adverse effects were noted related to cell processing and transplantation.
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Técnicas de Cultivo de Célula/métodos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/fisiología , Isquemia Miocárdica/terapia , Manejo de Especímenes/métodos , Cordón Umbilical/citología , Actinas/análisis , Hipoxia de la Célula/fisiología , Proliferación Celular , Supervivencia Celular , Femenino , Humanos , Recién Nacido , Cariotipo , TemperaturaRESUMEN
OBJECTIVE: This study was designed to test the effects of different types of preconditioning and postconditioning methods on spinal cord protection following aortic clamping. METHODS: The animals (rabbits) were divided into sham-operated, ischemic preconditioning, remote ischemic preconditioning, simultaneous aortic and ischemic remote preconditioning, and ischemic postconditioning groups. After neurological evaluations, ultrastructural analysis and immunohistochemical staining for caspase-3 were evaluated after 24 h following ischemia. RESULTS: The neurological outcomes of the remote ischemic preconditioning (4.2 ± 0.4) and ischemic postconditioning (4.6 ± 0.8) groups were significantly improved when compared with the ischemia group (2.2 ± 04). The immunohistochemical analysis revealed that the lowest percentage of apoptosis was in-group ischemic preconditioning at 12.5 ± 30.6%. In the comparison of intracellular edema in an ultrastructural analysis, the ischemic preconditioning and ischemic postconditioning groups had significantly lower values than the ischemia group. CONCLUSION: The conditioning methods attenuate ischemia-reperfusion injury for spinal cord injury. Ischemic and remote preconditioning and also postconditioning methods are simple to perform and inexpensive.
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Aorta Abdominal/cirugía , Arteria Axilar/cirugía , Poscondicionamiento Isquémico/métodos , Precondicionamiento Isquémico/métodos , Daño por Reperfusión/prevención & control , Isquemia de la Médula Espinal/prevención & control , Médula Espinal/irrigación sanguínea , Animales , Aorta Abdominal/fisiopatología , Apoptosis , Arteria Axilar/fisiopatología , Caspasa 3/metabolismo , Constricción , Modelos Animales de Enfermedad , Actividad Motora , Conejos , Flujo Sanguíneo Regional , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Médula Espinal/metabolismo , Médula Espinal/ultraestructura , Isquemia de la Médula Espinal/metabolismo , Isquemia de la Médula Espinal/patología , Isquemia de la Médula Espinal/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: Aortic aneurysms are vascular diseases that are associated with high mortality and morbidity. Cytochrome P450 CYP1A1 and glutathione S-transferase (GSTP1) isozymes were searched and compared with the patients who had experienced aortic surgery due to aortic aneurysm and atherosclerotic patients without aneurysm to find the relation of the oxidative stress with the aneurysms. MATERIALS AND METHODS: Study group consisted of the patients with the diagnosis of aortic aneurysm (group I, n: 12) and control group who were operated for coronary bypass surgery: preoperatively drug users (group II, n: 21) and nonusers (group III, n: 15). Paraffin sections (4 µm thick) of aortic biopsy materials were stained with hematoxylin and eosine, CYP1A1 and GSTP1 immunohistochemical markers. The specimens were evaluated using light microscopy at 40- to 400-fold magnification. RESULTS: The expressions of CYP1A1 and GSTP1 isozymes were found statistically significantly higher in the patients who have an aortic aneurysm than both the control groups (p < 0.05). There was no significant association between protein expressions, drugs and duration of usage, patient's demographic variables, and smoking (p > 0.05). CONCLUSIONS: In this pioneering study, CYP1A1 and GSTP1 isozymes are related with the aneurysms. The strategy that prevents the oxidative stress for the patients who had aortic aneurysms could be a valuable choice of searching to effect the aneurysmal progression.
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Aorta/enzimología , Aneurisma de la Aorta/enzimología , Citocromo P-450 CYP1A1/análisis , Gutatión-S-Transferasa pi/análisis , Anciano , Aorta/patología , Aorta/cirugía , Aneurisma de la Aorta/diagnóstico , Aneurisma de la Aorta/cirugía , Biopsia , Estudios de Casos y Controles , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Regulación hacia ArribaRESUMEN
BACKGROUND: The mortality and morbidity rates of even extensive thoracoabdominal replacement have improved markedly in recent years. We investigated the effects of a temporary occlusion of the aorta as a direct precondition and temporary occlusion of the axillary artery for remote preconditioning to determine any effects that preconditioning may have on indirect (nonischemic) injuries to visceral organs (indirect effects of remote ischemia/reperfusion injury). METHODS: Thirty-seven New Zealand white rabbits were divided into five groups: controls (sham-operated; group 1); direct ischemia to the infrarenal aorta without preconditioning (group 2); direct ischemic preconditioning to the infrarenal aorta (group 3); remote ischemic preconditioning before clamping the infrarenal aorta (group 4); and simultaneous direct aortic and remote ischemic preconditioning before the clamping and during clamping of the infrarenal aorta (group 5). We used a 30-minute ischemia period for aortic occlusion for spinal cord ischemia/reperfusion. The axillary artery was used for remote preconditioning. After 24 hours, tissue specimens of the internal organs were obtained. RESULTS: Myocardial congestion was the main pathology detected in all groups. Histopathologic evaluation of tissue samples taken from the hearts showed no significant differences in terms of the degree of polymorphonuclear leukocyte (PMNL) infiltration and edema between the groups. Lung congestion and pneumonic cell infiltration were detected in all the groups. Pneumonic cell infiltration was significantly high in groups 2 and 3. Cell infiltration was lowest in group 4 at 71.4% of normal values, which differed from the normal values of 25-33.3% in the other groups (P < 0.05). Although there is a difference between the groups in case of renal congestion, there is not any difference as tubular damage and PMN. There was a significant difference with regard to renal congestion between groups 2 and 3. Renal congestion was normal in 80% of the kidneys in group 3. This differed from the normal values observed in the other groups (14.3-57.1%, P < 0.05). Liver congestion was detected in all groups. CONCLUSIONS: Different preconditioning methods may play an important role in distinct organ injuries during aortic cross-clamping. The visceral organs that exhibited positive and constructive results with direct and remote preconditioning included the lungs and kidneys during indirect ischemia/reperfusion injury. Remote ischemic conditioning was determined to be especially advantageous as a protection method, due to the fact that it is easy to use and effective for indirect ischemia/reperfusion injury.
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Aorta/fisiopatología , Arteria Axilar/fisiopatología , Precondicionamiento Isquémico/métodos , Riñón/irrigación sanguínea , Hígado/irrigación sanguínea , Pulmón/irrigación sanguínea , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión/prevención & control , Animales , Constricción , Modelos Animales de Enfermedad , Riñón/patología , Hígado/patología , Pulmón/patología , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Conejos , Flujo Sanguíneo Regional , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Factores de TiempoRESUMEN
PURPOSE: Although deep vein thrombosis and thromboembolic diseases differ among various races, they are still important in our day. The difficulties in treatment and following-up of these diseases are caused by secret genetic mutations rather than predisposing factors. METHODS: Between January 2011 and May 2013, patients who were traced for deep vein thrombosis and/or pulmonary embolism were evaluated retrospectively. 84 patients (53.6% males and 46.4% females) were included in the study. Their family histories, predisposing factors and treatments were researched. Factor V Leiden (G 1691A), Factor II G20210A, Plasminogen Activator Inhibitor-Type 1 (4G/5G), and Methylene Tetrahydrofolate Reductase (C677T, A1298C) mutations were investigated from peripheral venous blood. RESULTS: Among the genetic mutations we searched, the incidence of single mutation rate was observed at 11.9%, double mutation collocation at 44%, triple mutation collocation at 29.8%, quadruple mutation collocation at 13.1%, and finally, quintuplet mutation collocation at 1.2%. Our approximate mutation number was found as 2.47 ± 0.91. CONCLUSION: We observed that multiple mutations were high in number compared to single genetic mutations. The patients who have multiple mutations should be more in the front line considering their diagnosis, treatment and following up, and also in terms of decreasing mortality, morbidity and recurrence.
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Epistasis Genética/genética , Embolia Pulmonar/genética , Trombosis de la Vena/genética , Adulto , Estudios de Casos y Controles , Factor V/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Persona de Mediana Edad , Mutación , Inhibidor 1 de Activador Plasminogénico/genética , Protrombina/genética , Embolia Pulmonar/epidemiología , Estudios Retrospectivos , Trombosis de la Vena/epidemiologíaRESUMEN
OBJECTIVE: Impaired wound healing could be a disaster especially in diabetes and amputation is the major risk. The aim of this study was to evaluate the benefit of BMMCs and CBS on wound healing. METHODS: Diabetic rats were underwent bilateral limb ischemia and wounding of skin defects on both extremities. The groups were formed as BMMCs (group A), BMMCs and CBS (group B), only CBS (group C), and phosphate buffer solution (group D) that were injected into wounds on right legs. RESULTS: The complete recovery of right legs was established as a mean of 21.4 ± 1.1 days, 12.9 ± 1.5 days, 30.0 ± 0.0 days and 38.1 ± 1.5 days according to Groups A, B, C, and D (p < 0.05). The recovery of left legs were calculated as a mean of 27.0 ± 0.0 days, 24.0 ± 0.0 days, 35.6 ± 1.1 days and 37.3 ± 1.6 days according to Groups A, B, C and D (p < 0.05). At the end of the recovery, the HE staining showed that vascularity was increased in groups A and B. CONCLUSION: Transplantation of BMMCs and CBS to the ischemic wounds of the diabetic rats accelerate the repair. The recovery was also superior in the same group although the treatment was not applied to the left extremity directly.
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Tratamiento Basado en Trasplante de Células y Tejidos , Diabetes Mellitus Experimental/terapia , Sangre Fetal/trasplante , Isquemia/terapia , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/trasplante , Cicatrización de Heridas , Animales , Células de la Médula Ósea/citología , Diabetes Mellitus Experimental/inducido químicamente , Masculino , Ratas , Ratas Wistar , Estreptozocina , Cicatrización de Heridas/efectos de los fármacosRESUMEN
OBJECTIVE: Pulmonary hypertension (PHT) exacerbates the functions of both ventricles. This prospective, randomised study was planned to investigate the effects of PHT on kinetics of both ventricles and the septum. METHODS: Twenty-five patients were randomly selected among the patients who had been planned to undergo mitral valve replacement (MVR) because of isolated mitral stenosis and divided into two groups according to their preoperative pulmonary artery pressure (PAP) values. Blood pool gated single photon emission tomography (BPGS) and transthoracic echocardiography were performed. Ventricles' regional, global and functional parameters were also assessed by using pulsed wave Doppler tissue imaging (DTI). RESULTS: Preoperative and postoperative PAP of the group 1 (PAP < 50 mmHg) were 40.0 ± 2.8 and 30.0 ± 2.6 mmHg (p = 0.03), group 2 (PAP ≥ 50 mmHg) were 71.9 ± 4.7 and 50.6 ± 3.5 mmHg (p < 0.05). The global right and left ventricle scores were decreased after the operation. The decrement was only significant in group 2. Considering the septal kinetics, right ventricle septal score was decreased from 7.6 to 3.3 (p < 0.05) in group 1, from 3.8 to 1.6 (p < 0.05) in group 2 postoperatively. CONCLUSION: Following MVR, a decrement in PAP values, and an improvement in ventricular function, especially in the right ventricular and septal kinetics were achieved. Furthermore, it was found that both DTI and BPGS techniques are beneficial to investigate the functional changes postoperatively and in the follow-up period of the patients who undergo mitral valve surgery.
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Imagen de Acumulación Sanguínea de Compuerta , Tabiques Cardíacos , Hipertensión Pulmonar , Estenosis de la Válvula Mitral , Función Ventricular Derecha , Adulto , Femenino , Tabiques Cardíacos/diagnóstico por imagen , Tabiques Cardíacos/fisiopatología , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/cirugía , Masculino , Estenosis de la Válvula Mitral/diagnóstico por imagen , Estenosis de la Válvula Mitral/fisiopatología , Estenosis de la Válvula Mitral/cirugía , Estudios ProspectivosRESUMEN
OBJECTIVE: We aimed to investigate the effects of bone marrow derived mesenchymal stem cells (MSCs), minocycline, and these two therapies combined on functional and histological improvement in cerebral ischemic injury created rats. MATERIALS AND METHODS: Twenty-eight Sprague Dawley female rats, weighing 250-300 g, were included in the study. Two male rats with similar properties were sacrificed for bone marrow derived MSC production. Group 1 was established as the control group. Group 2 was the group of only minocycline administered rats. Group 3 was the one of only MSCs administered rats. Group 4 was composed of the rats given the combination of MSCs and minocycline. Hematoxylin and eosin staining was done to assess the degeneration of the cells. Immunohistochemical staining was performed to evaluate the regeneration. Motor functions were examined by using Bederson's score. RESULTS: Cell degeneration was the least in group 4. The cells stained with GFAP were observed mostly in group 4. The cells stained with Neu N in group 1 were statistically lower than in other groups. When the groups were ordered in terms of functional improvement at the end of the second week, group 4 had the most and group 1 had the least. CONCLUSIONS: Bone marrow derived MSCs can lead to more histological and functional improvement when administered with minocycline, which is a neuroprotective agent as early as 24 h following the ischemic injury in a rat model. Minocycline therapy alone can be as effective as bone marrow derived MSCs therapy alone in ischemic cerebral rat model.
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Antibacterianos/farmacología , Lesiones Encefálicas/terapia , Isquemia Encefálica/terapia , Trasplante de Células Madre Mesenquimatosas , Minociclina/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Biomarcadores/análisis , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Terapia Combinada , Femenino , Proteína Ácida Fibrilar de la Glía/análisis , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Ratas , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
OBJECTIVE: Coagulation tests are influenced by pre-analytic conditions such as blood collection systems. Change of glass collection tubes with plastic ones will cause alteration of the test results. The aim of this study was to compare three plastic blood collection tubes with a standard glass blood collection tube and each plastic collection tube with the other two for possible additional tube-to- tube differences. MATERIAL AND METHODS: A total of 284 blood samples were obtained from 42 patients receiving warfarin during their routine controls, besides 29 healthy volunteers. Subgroup analyses were done according to health status. RESULTS: Our study demonstrated that different blood collection tubes have a statistically significant influence on coagulation tests. The magnitude of the effect depends on the tube used. However most of the tests performed on samples obtained from any tube correlated significantly with results obtained from other tube samples. CONCLUSION: Although blood collection tubes with different brands or properties will have distinct effects on coagulation tests, the influence of these blood collection tubes may be relatively small to interfere with decision-making on dose prescription, therefore lack clinical importance. Correlations between the results showed that, one of these plastic blood collection tubes tested in our study, can be used interchangably for a wide variety of coagulation assays. CONFLICT OF INTEREST: None declared.
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BACKGROUND: Bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with coronary heart disease are impaired with respect to number and mobilization. However, it is unknown whether the mobilization of BM-CPCs depends on the number of diseased coronary arteries. Therefore, in our study, we analysed the correlation between the diseased coronary arteries and the frequency of CD34/45+ BM-CPCs in peripheral blood (PB) in patients with ischemic heart disease (IHD). METHODS: The frequency of CD34/45+ BM-CPCs was measured by flow cytometry in 120 patients with coronary 1 vessel (IHD1, n = 40), coronary 2 vessel (IHD2, n = 40), coronary 3 vessel disease (IHD3, n = 40) and in a control group of healthy subjects (n = 40). There was no significant difference of the total number of cardiovascular risk factors between IHD groups, beside diabetes mellitus (DM), which was significantly higher in IHD3 group compared to IHD2 and IHD1 groups. RESULTS: The frequency of CD34/45+ BM-CPCs was significantly reduced in patients with IHD compared to the control group (CD34/45+; p < 0.001). The frequency of BM-CPCs was impaired in patients with IHD3 compared to IHD1 (CD34/45+; p < 0.001) and to IHD2 (CD34/45+; p = 0.001). But there was no significant difference in frequency of BM-CPCs between the patients with IHD2 and IHD1 (CD34/45+; p = 0.28). In a subgroup we observed a significant negative correlation between levels of hemoglobin AIc (HbAIc) and the frequency of BM-CPCs (CD34/45+; p < 0.001, r = -0.8). CONCLUSIONS: The frequency of CD34/45+ BM-CPCs in PB is impaired in patients with IHD. This impairment may augment with an increased number of diseased coronary arteries. Moreover, the frequency of CD34/45+ BM-CPCs in ischemic tissue is further impaired by diabetes in patients with IHD.
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Antígenos CD34/sangre , Células de la Médula Ósea/patología , Movimiento Celular , Enfermedad de la Arteria Coronaria/patología , Diabetes Mellitus/patología , Isquemia Miocárdica/patología , Células Madre/patología , Anciano , Biomarcadores/sangre , Células de la Médula Ósea/inmunología , Estudios de Casos y Controles , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/inmunología , Diabetes Mellitus/sangre , Diabetes Mellitus/inmunología , Femenino , Citometría de Flujo , Alemania , Hemoglobina Glucada/análisis , Humanos , Antígenos Comunes de Leucocito/sangre , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/sangre , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/inmunología , Índice de Severidad de la Enfermedad , Células Madre/inmunologíaAsunto(s)
Rastreo Celular/métodos , Colorantes Fluorescentes/farmacología , Células Madre Mesenquimatosas/citología , Absorción Cutánea/efectos de los fármacos , Piel/efectos de los fármacos , Animales , Colorantes Fluorescentes/administración & dosificación , Masculino , Modelos Animales , Ratas , Ratas WistarRESUMEN
PURPOSE: Resveratrol has been shown to have vasoprotective effects by upregulating oxidative defense mechanisms in a variety of pathophysiological conditions. However, the effect of resveratrol on diabetic oxidative stress and vascular and metabolic abnormalities is not completely understood. Therefore, this study was designed to evaluate whether long-term resveratrol supplementation has a protective effect on vascular function and integrity in association with metabolic parameters and oxidative stress in insulin-dependent diabetes. METHODS: Diabetes was induced in rabbits with alloxan and maintained for 8 weeks. We used a resveratrol dose of 5 mg/L (10 weeks, starting 14 days before alloxan injection) and 50 mg/L (8 or 10 weeks, starting concomitantly or 14 days before alloxan injection) in the drinking water of rabbits. RESULTS: Relaxation to acetylcholine was impaired (control 75.6 ± 3.59%, versus diabetic 42.23 ± 2.53%) and contractions to phenylephrine increased (control 136.89 ± 2.27%, versus diabetic 159.37 ± 6.27%) in aortas from diabetic animals. These changes were associated with increased basal or NAD(P)H-induced superoxide production, as well as lipid peroxide and superoxide dismutase (SOD) levels in the aortic samples. The maximal relaxation to acetylcholine improved by 75.74 ± 9.04% in diabetic rabbits treated with resveratrol. The increased contractions to phenylephrine were not restored to control values after resveratrol treatments, but sensitivity to the contractions tended to decrease. Resveratrol increased nitrite/nitrate levels and suppressed basal or NAD(P)H-induced superoxide production and lipid peroxide levels in the aortas. Importantly, resveratrol increased serum insulin levels without affecting blood glucose and the lipid profile in diabetic rabbits. Using electron microscopic examinations, resveratrol was found to markedly protect the endothelial integrity from diabetes. CONCLUSION: Overall, there was no noticeable difference between resveratrol treatment groups on the recovery from diabetes. Our results indicate that resveratrol alleviates type 1 diabetes-induced vasculopathy by decreasing vascular oxidative stress and thereby increasing the bioavailability of nitric oxide without changing metabolic abnormalities.
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Antioxidantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Estilbenos/farmacología , Enfermedades Vasculares/tratamiento farmacológico , Acetilcolina/sangre , Acetilcolina/metabolismo , Animales , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Catalasa/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Estrógenos/sangre , Insulina/sangre , Peróxidos Lipídicos/análisis , Peróxidos Lipídicos/fisiología , Lípidos/sangre , Lípidos/fisiología , Masculino , NADP/metabolismo , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/fisiología , Conejos , Resveratrol , Estilbenos/metabolismo , Estilbenos/uso terapéutico , Superóxido Dismutasa/metabolismo , Testosterona/sangre , Factores de Tiempo , Enfermedades Vasculares/prevención & controlRESUMEN
To analyze the effect of central venous pressure on cerebrospinal fluid oxygen tension and intrathecal pressure, multiparameter sensors were introduced into the intrathecal space for continuous monitoring of cerebrospinal fluid Po(2), Pco(2), and intrathecal pressure in 15 pigs. After 20 min of aortic clamping, hypervolemia was established for 20 min, followed by normovolemia. The animals were divided into 3 groups: in group 1, cerebrospinal fluid Po(2) = 0% at some time during crossclamping; in group 2, cerebrospinal fluid Po(2) was <50%; and in group 3, cerebrospinal fluid Po(2) remained > or = 50%. Mean decreases in cerebrospinal fluid Po(2) during the initial 20 min of crossclamping were 82%, 57%, and 15% in groups 1, 2, and 3, respectively. Following induction of hypervolemia, central venous and cerebrospinal fluid pressures increased simultaneously; this caused a significant decrease in cerebrospinal fluid Po(2) in group 2 only. In this model, aortic clamping did not increase cerebrospinal fluid pressure if central venous pressure was not elevated. The detrimental effect of elevated intrathecal pressure on cerebrospinal fluid oxygenation was seen only in animals with an intermediate degree of spinal cord ischemia. This might have important implications for the prevention of paraplegia during thoracoabdominal aortic replacement.
Asunto(s)
Aorta/cirugía , Presión Venosa Central/fisiología , Isquemia/prevención & control , Isquemia/fisiopatología , Médula Espinal/irrigación sanguínea , Animales , Aorta/fisiología , Volumen Sanguíneo/fisiología , Dióxido de Carbono/sangre , Líquido Cefalorraquídeo/metabolismo , Hemodilución , Oxígeno/sangre , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/prevención & control , Médula Espinal/fisiología , Instrumentos Quirúrgicos , PorcinosRESUMEN
In a model of aortic cross-clamping, we studied the use of a multiparameter sensor for measurement of cerebrospinal fluid (CSF) PO(2), PCO(2), and pH during and after aortic cross-clamping. The present study addressed the above-mentioned alterations and their relation according to time intervals. In 31 pigs, a sensor was introduced into the intrathecal space and epidural laser Doppler was used to measure spinal cord blood flow (SCF). By placing the aortic clamp at different levels, three different spinal cord ischemia groups were obtained (mild, moderate, and severe). CSF variables with SCF were studied for 25%, 50%, and 100% changes according to baseline level. In the clamping period, SCF decreased 71.5%, 40.0%, and 33.3% in groups 1, 2, and 3, respectively. CSF O(2) tension reached 0 in group 1, decreased 74.8% in group 2, and was 12.7% in group 3. CSF CO(2) tension increased 247.2% and 202.0% in groups 1 and 2, respectively, but slightly increased in group 3. The maximum reaction time of CSF O(2) tension was about 16.7-26.9min, although this range was 34.5-49.8min in CSF CO(2) tension. We recognized that O(2) tension reacts faster than PCO(2) and pH. It is possible for O(2) tension to be used faster than produced CO(2) in the ischemic medium, although it is known that the diffusion rate of CO(2) is much higher. Spinal cord O(2) tension monitoring is an important method to detect ischemic changes.
Asunto(s)
Dióxido de Carbono/líquido cefalorraquídeo , Monitoreo Fisiológico , Oxígeno/líquido cefalorraquídeo , Isquemia de la Médula Espinal/líquido cefalorraquídeo , Médula Espinal/irrigación sanguínea , Animales , Aorta Torácica/cirugía , Constricción , Modelos Animales de Enfermedad , Electrodos , Femenino , Tecnología de Fibra Óptica , Concentración de Iones de Hidrógeno , Flujometría por Láser-Doppler , Masculino , Monitoreo Fisiológico/instrumentación , Flujo Sanguíneo Regional , Isquemia de la Médula Espinal/diagnóstico por imagen , Isquemia de la Médula Espinal/fisiopatología , Porcinos , Factores de Tiempo , UltrasonografíaRESUMEN
BACKGROUND AND AIM: Postoperative neurologic deficit is the most devastating complication after surgical thoracic aorta repair. Cerebrospinal fluid drainage and some medications are used for spinal cord protection during and after the operation. METHODS: A 25-year-old patient applied to our clinic with a traumatic descending aortic aneurysm. We performed a surgical repair for the aneurysm but could not achieve to place a lumbar catheter to provide cerebrospinal fluid drainage. Levosimendan was chosen for spinal cord ischemic preconditioning because of its vasodilatory effects. RESULTS: Postoperative course was uneventful. Hemodynamic and neurologic complication was not observed, and the patient was discharged from the hospital in the postoperative 5th day. CONCLUSIONS: Levosimendan can be used for preconditioning and spinal cord protection from ischemic injury during descending aorta repair. We clearly benefit from the vasodilator peculiarity of the drug for improving spinal cord perfusion.
Asunto(s)
Aneurisma de la Aorta Torácica/cirugía , Hidrazonas/uso terapéutico , Precondicionamiento Isquémico/métodos , Piridazinas/uso terapéutico , Médula Espinal/irrigación sanguínea , Vasodilatadores/uso terapéutico , Adulto , Humanos , Masculino , Simendán , Isquemia de la Médula Espinal/prevención & controlRESUMEN
The internal thoracic artery (ITA) is the gold-standard conduit for coronary artery bypass surgery. It stays patent well in the long-term period, and this evidence is directly related to the superior later outcome in terms of longevity. Coronary artery bypass grafting with multiarterial grafts can be performed safely, and better long-term result can be expected with the use of arterial conduits, especially ITA. We describe a simple and practical technique for the left ITA grafting by dividing the ITA graft and using its proximal and distal parts in situ for the distal left anterior descending (LAD) artery and the obtuse marginal artery grafting.