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2.
J Cardiothorac Surg ; 16(1): 94, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865409

RESUMO

BACKGROUND: Congenital heart disease is a leading cause of death in newborns and infants. The feasibility of fetal cardiac surgery is linked to extracorporeal circulation (ECC); therefore, cardioplegic solutions need to be effective and long-lasting. METHODS: Eighteen pregnant sheep were divided into an ECC-only group, St. Thomas' Hospital cardioplegic solution (STH1) group (STH group), and HTK preservation solution (Custodiol®) group (HTK group). Markers of myocardial injury including troponin I (cTnI), troponin T (cTnT) and creatine kinase myocardial band (CKMB) were measured at specific time points (T1: pre-ECC, T2: 30 min of ECC, T3: 60 min of ECC, T4: 60 min post-ECC, T5: 120 min post-ECC). Myocardial tissue was removed from the fetal sheep at T5, and apoptosis was detected by TUNEL staining. RESULTS: Changes in the serum cTnI, cTnT and CKMB concentrations were not significantly different among the three groups before and during the ECC(T1,T2,T3). At 60 min after ECC shutdown(T4), cTnI and cTnT concentrations were significantly higher in the STH group than before the start of ECC. The concentration of cTnI was higher in the STH group than in the HTK and ECC-only groups. The concentration of cTnT was higher in the STH group than in the ECC-only group. At 120 min after ECC shutdown(T5), cTnI and cTnT concentrations were significantly higher in the ECC and HTK groups than before the start of ECC, and CKMB concentration was significantly higher in STH and HTK groups. The concentrations of cTnT, cTnI and CKMB was higher in the STH group than in the HTK and ECC-only groups. The number of TUNEL-positive cells in the HTK and STH groups was higher than in the ECC-only group. The number of TUNEL-positive cells in the STH group was higher than in the HTK group. There was no statistically significant difference among the groups in the heart rate and mean arterial pressure after ECC. CONCLUSION: The HTK preservation solution was significantly better than STH1 in reducing the release of cardiomyocyte injury markers and the number of apoptotic cells in fetal sheep ECC. Fetal sheep receiving ECC-only had an advantage in all indicators, which suggests ECC-only fetal heart surgery is feasible.


Assuntos
Soluções Cardioplégicas/farmacologia , Cardiotônicos/farmacologia , Circulação Extracorpórea/efeitos adversos , Terapias Fetais/métodos , Traumatismos Cardíacos/prevenção & controle , Coração/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Bicarbonatos/farmacologia , Bicarbonatos/uso terapêutico , Biomarcadores/metabolismo , Cloreto de Cálcio/farmacologia , Cloreto de Cálcio/uso terapêutico , Soluções Cardioplégicas/uso terapêutico , Cardiotônicos/uso terapêutico , Glucose/farmacologia , Glucose/uso terapêutico , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/metabolismo , Traumatismos Cardíacos/patologia , Magnésio/farmacologia , Magnésio/uso terapêutico , Manitol/farmacologia , Manitol/uso terapêutico , Miocárdio/metabolismo , Miocárdio/patologia , Cloreto de Potássio/farmacologia , Cloreto de Potássio/uso terapêutico , Procaína/farmacologia , Procaína/uso terapêutico , Distribuição Aleatória , Ovinos , Cloreto de Sódio/farmacologia , Cloreto de Sódio/uso terapêutico , Resultado do Tratamento
3.
Heart Surg Forum ; 24(1): E170-E176, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33635238

RESUMO

BACKGROUND: In cardiac surgery, myocardial protection is required during cross-clamping followed by reperfusion. The use of cardioplegic solutions helps preserve myocardial energy stores, hindering electrolyte disturbances and acidosis during periods of myocardial ischaemia. This study aimed to compare the efficacy and safety between the histidine-tryptophan-ketoglutarate (HTK) solution and blood cardioplegia in various cardiac surgeries. METHODS: Three-hundred-twenty patients aged 30-70 years old undergoing various cardiac surgeries were randomized into the HTK group and the blood cardioplegia group. The ventilation time, total bypass time, cross-clamp time, length of intensive care unit (ICU) or hospital stay, and postoperative complications were analyzed. RESULTS: The total bypass time and cross-clamp time were significantly shorter in the HTK group than in the blood cardioplegia group (P < 0.001). Segmental wall motion abnormalities (SWMA) at postoperative echocardiography were significantly higher in in the blood cardioplegia group (P = 0.008). The number of patients requiring DC Shock was significantly higher in the HTK group (P < 0.001). The number of patients requiring inotropic support was significantly higher in the blood cardioplegia group (P < 0.001). The length of ICU, hospital stay, and ventilation time were significantly longer in the blood cardioplegia group than in the HTK group (P = 0.004, P < 0.001, P < 0.001, respectively). The number of patients requiring prolonged ventilation was significantly higher in the blood cardioplegia group compared with the HTK group (P = 0.022). There was no significant difference between the study groups regarding electrocardiographic changes, 30-day mortality, and 30-day readmission. CONCLUSION: The use of HTK cardioplegia was associated with significantly shorter cross-clamp time, bypass time, duration of mechanical ventilation, length of ICU stay, and length of hospital stay. It is associated with less incidence of postoperative segmental wall abnormalities and less need for inotropic support than blood cardioplegia. Custodiol cardioplegia is a safe and feasible option that can be used as an effective substitute for blood cardioplegia to enhance myocardial protection.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Doença da Artéria Coronariana/cirurgia , Parada Cardíaca Induzida/métodos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Soluções Cardioplégicas , Egito/epidemiologia , Feminino , Glucose/farmacologia , Humanos , Incidência , Masculino , Manitol/farmacologia , Pessoa de Meia-Idade , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Estudos Retrospectivos , Resultado do Tratamento
5.
Asian Cardiovasc Thorac Ann ; 29(2): 77-83, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33530706

RESUMO

BACKGROUND: Despite the increasing popularity of single-dose cardioplegia techniques in coronary artery bypass grafting, the time window for successful reperfusion remains unclear. This study aimed to compare different cardioplegic techniques based on early and 30-day clinical outcomes via thorough monitoring. METHODS: This prospective cohort study included high-risk patients undergoing coronary artery bypass grafting and receiving 3 different types of cardioplegia between January 2017 and June 2019. Group 1 (n = 101) had a single dose of del Nido cardioplegia, group 2 (n = 92) had a single dose of histidine-tryptophane-ketoglutarate, and group 3 (n = 119) had cold blood cardioplegia. Patients were examined perioperatively by memory loop recording and auto-triggered memory loop recording for 30 days, with documentation of predefined events. RESULTS: Interleukin-6 and cardiac troponin levels in group 1 were significantly higher than those in groups 2 and 3. The incidence of predefined events as markers of inadequate myocardial protection was significantly higher group 1, with more frequent atrial fibrillation attacks and more hospital readmissions. The readmission rate was 17.6% in group 1, 9% in group 2, and 8% in group 3. CONCLUSIONS: Our data demonstrate the long-term efficacy of cardioplegic techniques, which may become more crucial in high-risk patients who genuinely have a chance to benefit from adjunct myocardial protection. Patients given del Nido cardioplegia had a significantly more prominent inflammatory response and higher troponin levels after cardiopulmonary bypass. This group had issues in the longer term with significantly more cardiac events and a higher rehospitalization rate.


Assuntos
Temperatura Baixa , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Eletrólitos/uso terapêutico , Parada Cardíaca Induzida , Lidocaína/uso terapêutico , Sulfato de Magnésio/uso terapêutico , Manitol/uso terapêutico , Cloreto de Potássio/uso terapêutico , Bicarbonato de Sódio/uso terapêutico , Soluções/uso terapêutico , Idoso , Biomarcadores/sangue , Temperatura Baixa/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Eletrólitos/efeitos adversos , Feminino , Glucose/efeitos adversos , Glucose/uso terapêutico , Parada Cardíaca Induzida/efeitos adversos , Humanos , Interleucina-6/sangue , Lidocaína/efeitos adversos , Sulfato de Magnésio/efeitos adversos , Masculino , Manitol/efeitos adversos , Pessoa de Meia-Idade , Readmissão do Paciente , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/terapia , Cloreto de Potássio/efeitos adversos , Procaína/efeitos adversos , Procaína/uso terapêutico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Bicarbonato de Sódio/efeitos adversos , Soluções/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Troponina/sangue
8.
Anesth Analg ; 132(3): 666-675, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32852294

RESUMO

BACKGROUND: For emergent intrapartum cesarean delivery (CD), the literature does not support the use of any particular local anesthetic solution to extend epidural analgesia to cesarean anesthesia. We hypothesized that 3% chloroprocaine (CP) would be noninferior to a mixture of 2% lidocaine, 150 µg of epinephrine, 2 mL of 8.4% bicarbonate, and 100 µg of fentanyl (LEBF) in terms of onset time to surgical anesthesia. METHODS: In this single-center randomized noninferiority trial, adult healthy women undergoing CD were randomly assigned to epidural anesthesia with either CP or LEBF. Sensory blockade (pinprick) to T10 was established before operating room (OR) entry for elective CD. On arrival to the OR, participants received the epidural study medications in a standardized manner to simulate the conversion of "epidural labor analgesia to surgical anesthesia." The primary outcome was the time to loss of touch sensation at the T7 level. A noninferiority margin was set at 3 minutes. The secondary outcome was the need for intraoperative analgesia supplementation. RESULTS: In total, 70 women were enrolled in the study. The mean onset time to achieve a bilateral sensory block to touch at the T7 dermatome level was 655 (standard deviation [SD] = 258) seconds for group CP and 558 (269) seconds for group LEBF, a difference in means of 97 seconds (90% confidence interval [CI], SD = -10.6 to 204; P = .10 for noninferiority). The upper limit of the 90% CI for the mean difference exceeded the prespecified 3-minute noninferiority margin. There was no meaningful difference in the requirement for intraoperative analgesia between the 2 groups. CONCLUSION: Both anesthetic solutions have a rapid onset of anesthesia when used to extend low-dose epidural sensory block to surgical anesthesia. Data from the current study provide insufficient evidence to confirm that CP is noninferior to LEBF for rapid epidural extension anesthesia for CD, and further research is required to determine noninferiority.


Assuntos
Analgésicos Opioides/uso terapêutico , Anestesia Epidural , Anestesia Obstétrica , Anestésicos Locais/uso terapêutico , Cesárea , Epinefrina/uso terapêutico , Fentanila/uso terapêutico , Lidocaína/uso terapêutico , Procaína/análogos & derivados , Bicarbonato de Sódio/uso terapêutico , Adulto , Analgesia Epidural , Analgesia Obstétrica , Analgésicos Opioides/efeitos adversos , Anestesia Epidural/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Anestésicos Locais/efeitos adversos , Arkansas , Cesárea/efeitos adversos , Procedimentos Cirúrgicos Eletivos , Epinefrina/efeitos adversos , Feminino , Fentanila/efeitos adversos , Humanos , Lidocaína/efeitos adversos , Gravidez , Procaína/efeitos adversos , Procaína/uso terapêutico , Limiar Sensorial/efeitos dos fármacos , Bicarbonato de Sódio/efeitos adversos , Fatores de Tempo , Tato/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
9.
Transplant Proc ; 53(2): 661-664, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33139037

RESUMO

OBJECTIVE: This study aimed to evaluate how cold ischemia time (CIT) interferes with liver graft function in the first 7 days after surgery for Custodiol (HTK) preserved organs. METHODS: This retrospective observational study analyzed the medical records of 38 transplantation patients at Hospital Leforte Liberdade, São Paulo, in 2018. The study population was divided into 2 groups (group A, CIT < 8 hours; group B, CIT > 8 hours). Postoperative parameters-such as international normalized ratio, total bilirubin, aspartate aminotransferase/alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GGT), lactate dehydrogenase, lactate, creatinine, red blood cell transfusion, need for hemodialysis, use of vasoactive drugs, endotracheal intubation time, length of stay in the intensive care unit (ICU), and length of hospital stay-were compared. RESULTS: Group A (CIT < 8 hours) presented less need for red blood cell transfusions (odds ratio 0.29; confidence interval 0.06-0.98; P = .04), had a shorter hospital stay (P = .024), and had lower levels of total bilirubin (P = .05) and GGT (P = .05) in the first 7 postoperative days. The other variables showed no statistically significant difference. CONCLUSION: In livers preserved with Custodiol, CIT > 8 hours generated higher levels of total bilirubin and GGT in the postoperative period, in addition to higher hospital costs; greater need for red blood cell transfusions; and longer hospitalization, including longer stays in the ICU.


Assuntos
Isquemia Fria/métodos , Transplante de Fígado/métodos , Soluções para Preservação de Órgãos/farmacologia , Preservação de Órgãos/métodos , Feminino , Glucose/farmacologia , Humanos , Masculino , Manitol/farmacologia , Pessoa de Meia-Idade , Preservação de Órgãos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Traumatismo por Reperfusão/etiologia , Estudos Retrospectivos
10.
Medicine (Baltimore) ; 99(51): e23584, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371088

RESUMO

ABSTRACT: To compare the difference between University of Wisconsin (UW) solution and histidine-tryptophan-ketoglutarate (HTK) solution in adult living donor liver transplantation (LDLT).This study included LDLT patients at the Liver Transplantation Center of West China Hospital of Sichuan University from November 2001 to June 2018. These patients were classified into 2 groups depending on the use of the different preservation solutions, and the confounding factors between the 2 groups were eliminated by propensity score matching. Finally, the incidence of complications; serum examination at postoperative days 1, 3, 5, 7, 14, 21, and 30; and the overall survival rate of the 2 groups were compared to observe whether there were any differences between the 2 preservation solutions.Of the 298 patients we screened, 170 were treated with UW solution and 128 with HTK solution. After propensity score matching, 106 pairs of patients were selected. In the comparison of the 2 groups, the length of intensive care unit stay in the UW group was significantly longer than that in the HTK group (P = .022), but there was no difference in the total length of hospital stay between the 2 groups (P = .277). No statistically significant difference was observed in the 2 groups in terms of the incidence of complications or postoperative examinations. However, the incidence of early allograft dysfunction in the HTK group was slightly lower than that in the UW group (HTK: UW = 14.1%: 20.7%), although the difference was not statistically significant. In terms of the overall survival rate, the 1, 3, and 5-year survival rates of the HTK group were 85.5%, 70.2%, and 65.1%, respectively, while the 1, 3, and 5-year survival rates of the UW group were 83.1%, 67.2%, and 59.8%, respectively, and there was no significant difference between the 2 groups.In conclusion, our study shows that UW solution and HTK solution are equivalent in perioperative safety, the recovery of transplanted liver function, the occurrence of postoperative complications and overall survival and can be safely and effectively applied in adult LDLT. If economic factors are taken into account, HTK can save costs to a certain extent.


Assuntos
Transplante de Fígado/métodos , Soluções para Preservação de Órgãos/uso terapêutico , Adenosina/uso terapêutico , Adulto , Alopurinol/uso terapêutico , China , Feminino , Glucose/uso terapêutico , Glutationa/uso terapêutico , Rejeição de Enxerto/epidemiologia , Humanos , Insulina/uso terapêutico , Tempo de Internação , Transplante de Fígado/mortalidade , Doadores Vivos , Masculino , Manitol/uso terapêutico , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Cloreto de Potássio/uso terapêutico , Procaína/uso terapêutico , Pontuação de Propensão , Rafinose/uso terapêutico , Análise de Sobrevida
11.
PLoS One ; 15(11): e0241567, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33151993

RESUMO

The aim of the present study was to determine and compare the degree and duration of corneal anesthesia following topical application of 0.4% oxybuprocaine hydrochloride ophthalmic solution and 1% ropivacaine hydrochloride treatment in healthy rats. A randomized, blinded, crossover study was conducted on 20 healthy adult Wistar rats, following complete physical and ophthalmological examination. Baseline corneal touch threshold (CTT) was determined in the central corneal area of both eyes with a Cochet-Bonnet aesthesiometer, in mm filament length. Oxybuprocaine was randomly applied to one eye and 0.9% sterile sodium chloride solution was instilled into the contralateral eye. Subsequent CTT measurements were performed in both eyes 5 minutes after topical application and at 5-minute intervals thereafter for 75-minutes in the anesthetized eye. Following a 2-week washout period, this protocol was repeated with ropivacaine. Quantitative data were summarized as mean ± standard deviation, median and inter-quartile range (Q1-Q3). Repeated measures data were analyzed over time and between treatments using Friedman test and Wilcoxon signed-rank test with Bonferroni adjustment (p < 0.05). Baseline CTT values were 60 mm in all eyes. With oxybuprocaine, CTT values decreased significantly for 65 minutes (0-55 mm; p = 0.002) when compared with baseline; the maximal anesthetic effect (no blink response at 5 mm filament length) was maintained for up to 15 minutes (p < 0.0001). With ropivacaine, CTT values were significantly lower than baseline for 30 minutes (0-55 mm; p = 0.002), with a maximal anesthetic effect recorded at 5 minutes in 18 eyes (p < 0.0001). Oxybuprocaine induced a significantly lower CTT than ropivacaine (p = 0.002) from 10 to 65 minutes following topical application. Both anesthetic agents induced significant corneal anesthesia; however, oxybuprocaine provided a greater and longer anesthetic effect, making it more suitable for potentially painful ophthalmologic procedures.


Assuntos
Córnea/efeitos dos fármacos , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/farmacologia , Procaína/análogos & derivados , Ropivacaina/administração & dosagem , Ropivacaina/farmacologia , Administração Tópica , Animais , Feminino , Masculino , Procaína/administração & dosagem , Procaína/farmacologia , Ratos Wistar , Limiar Sensorial/efeitos dos fármacos
13.
Braz J Cardiovasc Surg ; 35(5): 634-643, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33118727

RESUMO

OBJECTIVE: To investigate the effects of Bretschneider's histidine-tryptophan-ketoglutarate (HTK) solution and cold blood cardioplegia on systemic endothelial functions. METHODS: A total of 50 patients who underwent isolated coronary artery bypass surgery between March 2018 and May 2018 were randomly divided into two groups - group 1 (Bretschneider's HTK solution, n=25) and group 2 (cold blood cardioplegia, n=25). Data related to the indicators of endothelial dysfunction were recorded. Flow-mediated dilation was measured together with the assessment of the values of endothelin-1, von Willebrand factor, and asymmetric dimethylarginine to identify endothelial dysfunction. Then, the two groups were compared regarding these values. RESULTS: The most significant result of our study was that the endothelin-1 level was significantly higher in group 2 than in group 1 (P<0.001). The value of flow-mediated dilation was found to increase to a lesser degree on the postoperative days compared to the value at the day of admission in group 1 (P=0.002 and P=0.030, respectively). CONCLUSION: Cardiopulmonary bypass leads to endothelial dysfunction. Our results revealed that Bretschneider's HTK solution causes less severe endothelial injury than cold blood cardioplegia.


Assuntos
Soluções Cardioplégicas , Ponte de Artéria Coronária , Parada Cardíaca Induzida , Soluções Cardioplégicas/uso terapêutico , Feminino , Glucose , Humanos , Masculino , Manitol , Cloreto de Potássio , Procaína , Estudos Prospectivos
14.
Rev. bras. cir. cardiovasc ; 35(5): 634-643, Sept.-Oct. 2020. tab, graf
Artigo em Inglês | LILACS, Sec. Est. Saúde SP | ID: biblio-1137349

RESUMO

Abstract Objective: To investigate the effects of Bretschneider's histidine-tryptophan-ketoglutarate (HTK) solution and cold blood cardioplegia on systemic endothelial functions. Methods: A total of 50 patients who underwent isolated coronary artery bypass surgery between March 2018 and May 2018 were randomly divided into two groups - group 1 (Bretschneider's HTK solution, n=25) and group 2 (cold blood cardioplegia, n=25). Data related to the indicators of endothelial dysfunction were recorded. Flow-mediated dilation was measured together with the assessment of the values of endothelin-1, von Willebrand factor, and asymmetric dimethylarginine to identify endothelial dysfunction. Then, the two groups were compared regarding these values. Results: The most significant result of our study was that the endothelin-1 level was significantly higher in group 2 than in group 1 (P<0.001). The value of flow-mediated dilation was found to increase to a lesser degree on the postoperative days compared to the value at the day of admission in group 1 (P=0.002 and P=0.030, respectively). Conclusion: Cardiopulmonary bypass leads to endothelial dysfunction. Our results revealed that Bretschneider's HTK solution causes less severe endothelial injury than cold blood cardioplegia.


Assuntos
Humanos , Masculino , Feminino , Soluções Cardioplégicas/uso terapêutico , Ponte de Artéria Coronária , Parada Cardíaca Induzida , Cloreto de Potássio , Procaína , Estudos Prospectivos , Glucose , Manitol
15.
BMJ Case Rep ; 13(9)2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32900720

RESUMO

Ensuring respiratory stability with early tracheal extubation and adequate pain control is challenging in premature neonates after thoracotomy. Continuous erector spinae plane (ESP) block, a relatively new truncal nerve block, has the potential to provide analgesia for thoracic surgeries while reducing opioid use. However, there have been only a few reports utilising this technique in infants, and none in preterm neonates. We present the perioperative pain management of a preterm neonate requiring thoracotomy. Epidural analgesia was deemed contraindicated due to coexisting coagulopathy; therefore, an ESP catheter was placed. The patient was extubated at the end of the surgery and had excellent pain control with rectal acetaminophen, chloroprocaine infusion via the ESP catheter and with minimal opioid requirement. Continuous ESP block may be safe and effective for postoperative pain management in coagulopathic premature neonates. Chloroprocaine is an effective local anaesthetic in the erector spinae compartment, which has not been previously reported.


Assuntos
Anestésicos Locais/administração & dosagem , Cateterismo , Bloqueio Nervoso , Dor Pós-Operatória/tratamento farmacológico , Músculos Paraespinais , Procaína/análogos & derivados , Toracotomia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Bloqueio Nervoso/métodos , Procaína/administração & dosagem
16.
Int J Mol Sci ; 21(18)2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32938013

RESUMO

Orthotopic liver transplantation (OLT) using allografts from donation after circulatory death (DCD) is potentially associated with compromised clinical outcomes due to ischemia-reperfusion injury (IRI)-induced organ damage and graft-related complications. The aim of this study was to provide in vivo data on the effects of adenosine A2a receptor stimulation in a clinically relevant large animal model of DCD liver transplantation. Cardiac arrest was induced in German Landrace pigs (n = 10; 20-25 kg). After 30 min of warm ischemia, the donor liver was retrieved following a cold flush with 3 L of histidine-tryptophan-ketoglutarate-HTK solution. Animals of the treatment group (n = 5/group) received a standard dose of the selective adenosine receptor agonist CGS 21680 added to the cold flush. All grafts were stored for 4.5 h at 4 °C in HTK-solution before OLT. Hepatocellular injury, apoptosis, protein kinase A-PKA activity, graft microcirculation, liver function, and animal survival were assessed. Compared to untreated livers, adenosine A2a receptor stimulation resulted in improved tissue microcirculation (103% ± 5% vs. 38% ± 4% compared to baseline; p < 0.05), accelerated functional recovery of the graft (indocyanine green-plasma disappearance rate (ICG-PDR) of 75% ± 18% vs. 40% ± 30% after 3 h), increased PKA activity ratio (56% ± 3% vs. 32% ± 3%; p < 0.001 after 1 h), and consequently reduced tissue necrosis and apoptosis. The potent protective effects were clinically manifested in significantly improved survival in the treatment group after 72 h (100% vs. 40%; p = 0.04). The ex vivo administration of adenosine A2a receptor agonist during the back-table flush mitigates IRI-mediated tissue damage and improves functional graft recovery and survival in a large animal model of DCD liver transplantation.


Assuntos
Agonistas do Receptor A2 de Adenosina/farmacologia , Transplante de Fígado/mortalidade , Receptor A2A de Adenosina/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/mortalidade , Adenosina/análogos & derivados , Adenosina/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Glucose/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Doadores Vivos , Manitol/farmacologia , Preservação de Órgãos/métodos , Soluções para Preservação de Órgãos/farmacologia , Fenetilaminas/farmacologia , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Traumatismo por Reperfusão/metabolismo , Suínos , Isquemia Quente/métodos
17.
Int J Mol Sci ; 21(18)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899772

RESUMO

To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.


Assuntos
Soluções para Preservação de Órgãos/química , Preservação de Órgãos/métodos , Alanina , Animais , Arginina , Criopreservação/métodos , Glucose/química , Glucose/metabolismo , Glicina , Humanos , Fígado/efeitos dos fármacos , Manitol/química , Manitol/metabolismo , Transplante de Órgãos , Pâncreas/efeitos dos fármacos , Cloreto de Potássio/química , Cloreto de Potássio/metabolismo , Procaína/química , Procaína/metabolismo , Traumatismo por Reperfusão
18.
Bull Exp Biol Med ; 169(3): 318-323, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32743780

RESUMO

The study examined effectiveness of pharmaco-cold cardioplegia employing solutions of enhanced buffer capacity during surgery of obstructive hypertrophic cardiomyopathy in adult patients (N=51) operated during 2013-2018. In group 1 (N=28), the cardioplegia was performed with HTK (Custodiol) solution, whereas in group 2 (N=23), it was carried out with Bokeria-Boldyrev ACH solution. The mean, minimum, and maximum ages in group 1 were 46, 21, and 64 years, respectively; in group 2 - 42, 14, and 70 years, respectively. In both groups, the patients were subjected to myoectomy of exit pathway in the left ventricle according to Bokeria-Morrow operation and annuloplasty of tricuspid valve accompanied by reconstructive surgery (or replacement) of mitral valve. Atrial fibrillation (if any) was suppressed with cryoablation (-60°Ð¡) of the openings of the right and left pulmonary veins. The surgery was carried out in hypothermic mode at 28°C. The significant intergroup differences were observed in the asystole latent period after the onset of antegrade or retrograde injection of cardioplegic solution. In group 1, the asystole latent periods determined after antegrade or retrograde injection were 53±7 or 170±30 sec, respectively; in group 2 - 32±6 and 97±11 sec (p<0.0001), respectively. The mean times of aortic cross-clumping in groups 1 and 2 were 66±8 and 64±6 min, respectively; the electromechanical action of the heart restored after aortic unclamping in 35±7 and 30±6 sec, respectively. The biochemical and clinical data revealed no significant intergroup differences. Overall, novel Bokeria-Boldyrev ACH cardioplegic solution secured effective protection of the myocardium against intraoperative ischemia in adult patients with obstructive hypertrophic cardiomyopathy and significantly decreased the asystole latent period.


Assuntos
Cardiomiopatia Hipertrófica/cirurgia , Adulto , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Cardiomiopatia Hipertrófica/tratamento farmacológico , Feminino , Glucose/uso terapêutico , Parada Cardíaca Induzida , Humanos , Masculino , Manitol/uso terapêutico , Pessoa de Meia-Idade , Cloreto de Potássio/uso terapêutico , Procaína/uso terapêutico , Adulto Jovem
20.
Ann Palliat Med ; 9(4): 1476-1487, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32692200

RESUMO

BACKGROUND: Both machine perfusion (MP) of donor hearts with autologous blood and crystalloid perfusates have advantages and disadvantages. Currently, which of the aforementioned preservation strategies can better preserve the coronary endothelium has not yet been determined. We aim to compare the impact of hypothermic continuous MP with histidine-tryptophan-ketoglutarate (HTK) solution versus normothermic continuous MP with autologous blood on coronary endothelium in a porcine ex vivo model of donation following circulatory death (DCD). METHODS: DCD pigs underwent circulatory arrest via asphyxiation followed by 30-minute warm ischemia time. Donor hearts were preserved with either hypothermic MP with HTK solution (MP + HTK group; 4 ℃; n=6), or normothermic MP with blood (MP + blood group; 37 ℃; n=6) for 4 hours. After 2-hour ex vivo reperfusion, the assessment of endothelial-dependent (Edep) and -independent (Eind) relaxation of coronary artery, histopathological analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay were performed. RESULTS: Preservation of DCD hearts with MP + Blood strategy significantly improved both Edep and Eind vasorelaxation of coronary artery compared with MP + HTK strategy (maximum relaxation to bradykinin: MP + HTK 80.9%±2.6% vs. MP + Blood 91.9%±1.9%, P<0.001; maximum relaxation to sodium nitroprusside: MP + HTK 97.1%±1.0% vs. MP + Blood 99.8%±0.2%, P<0.05). MP + Blood strategy significantly decreased nitrotyrosine but increased intercellular adhesion molecule-1 immunoreactivity in the coronary artery. The number of TUNEL-positive cells in MP + Blood group were significantly fewer compared with MP + HTK group. CONCLUSIONS: Compared with MP + HTK strategy, MP + Blood strategy significantly alleviates coronary endothelial dysfunction during donor heart preservation. This protective effect is associated with the inhibition of apoptosis and nitro-oxidative stress in coronary artery.


Assuntos
Transplante de Coração , Coração , Doadores de Tecidos , Animais , Endotélio , Glucose , Humanos , Manitol , Modelos Animais , Perfusão , Cloreto de Potássio , Procaína , Suínos
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