Combined effects of melatonin and topical hypothermia on renal ischemia-reperfusion injury in rats

Purpose: To evaluate whether their combination was more effective than either alone in decreasing renal damage due to ischemia/reperfusion (I/R) injury in rats. Methods: Thirty-two Wistar rats were assigned to four groups. Following right nephrectomy, their left kidneys were subjected to warm ischemia (IR), cold ischemia (TH+IR), intraperitoneal injection of 10 mg/kg melatonin (MEL+IR), or injection of 10 mg/kg melatonin followed by cold ischemia (MEL+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, left nephrectomy was performed for histopathological evaluation, lipid peroxidation, and measurement of antioxidant enzyme activity. Serum was collected to measure urea and creatinine concentrations. Results: Histopathological damage induced by ischemia and reperfusion was more attenuated in the MEL+TH+IR group than in the MEL+IR and TH+IR groups (p<0.037). Superoxide dismutase activity was significantly higher (p<0.029) and creatinine (p<0.001) and urea (p<0.001) concentrations were significantly lower in the MEL+TH+IR group than in the MEL+IR and TH+IR groups. Conclusion: The combination of melatonin (MEL) and topical hypothermia (TH) better protects against renal I/R injury than does MEL or TH alone

Sedative and cardiorespiratory effects of methadone, alone or in combination with acepromazine or xylazine, in cats

Seis felinos com peso médio de 3,3±0,3 kg foram aleatoriamente submetidos a 6 tratamentos, com intervalo mínimo de 1 semana. Os animais receberam a administração intramuscular de solução fisiológica (controle), metadona (0,3 mg/kg), acepromazina (0,1 mg/kg), xilazina (1,0 mg/kg), acepromazina (0,05 mg/kg) + metadona (0,3 mg/kg) ou xilazina (0,5 mg/kg) + metadona (0,3 mg/kg). As freqüências cardíaca (FC) e respiratória (FR), a pressão arterial sistólica (PAS), a temperatura retal, o grau de sedação e o reflexo interdigital foram avaliados antes (basal) e após a administração dos tratamentos em intervalos específicos por 90 minutos. Nos animais tratados com xilazina ou xilazina/metadona, houve diminuição em FR, FC e na temperatura retal. Nos mesmos tratamentos, 1/6 e 2/6 animais não apresentaram reflexo interdigital em pelo menos um dos momentos avaliados. Nos animais que receberam a administração de 0,1 mg/kg de acepromazina, houve diminuição em PAS. Os escores de sedação foram mais elevados nos animais que receberam a administração de xilazina ou xilazina associada à metadona. A administração da metadona isolada ou associada à acepromazina resultou em sedação considerada insatisfatória e sinais de excitação em alguns animais. O uso da metadona isolado ou em associação à acepromazina foi considerado ineficaz quando se objetiva sedação moderada à intensa. A associação da metadona à xilazina produz sedação moderada à intensa, sendo esse efeito semelhante àquele observado após a administração da xilazina isoladamente em dose mais elevada.Six cats weighting 3.3±0.3 kg were randomly allocated to 6 treatments, with at least one-week intervals. The cats received intramuscular administration of physiological saline (control), methadone (0.3 mg/kg), acepromazine (0,1 mg/kg), xylazine (1.0 mg/kg), acepromazine (0.05 mg/kg) plus methadone (0.3 mg/kg) or xylazine (0.5 mg/kg) plus methadone (0.3 mg/kg). Heart rate (HR), respiratory rate (RR), indirect systolic arterial pressure (SAP), rectal temperature, sedation score and pedal withdrawal reflex were evaluated before (baseline) and at selected intervals after treatment administration for 90 minutes. Respiratory rate, HR and rectal temperature decreased in cats given xylazine or xylazine plus methadone. In 1 out of 6 cats given xylazine and 2 out of 6 cats given xylazine/methadone, pedal withdrawal reflex was absent. In cats given 0.1 mg/kg of acepromazine, SAP decreased compared to baseline. Sedation scores were greater in cats given xylazine or xylazine plus methadone. Methadone alone or in combination with acepromazine did not produce a satisfactory degree of sedation and resulted in signs of excitement in some of the cats. Methadone alone or combination with acepromazine was not considered an effective protocol when moderate to deep sedation is required in cats. Methadone in combination with xylazine produces moderate to deep sedation, being this effect comparable to that achieved with a higher dose of xylazine alone

Modular hybrid total hip arthroplasty. Experimental study in dogs

Background: This prospective experimental study evaluated the surgical procedure and results of modular hybrid total hip arthroplasty in dogs.Methods: Ten skeletally mature healthy mongrel dogs with weights varying between 19 and 27 kg were used. Cemented modular femoral stems and uncemented porous-coated acetabular cups were employed. Clinical and radiographic evaluations were performed before surgery and at 30, 60, 90, 120, 180 and 360 days post-operation.Results: Excellent weight bearing was noticed in the operated limb in seven dogs. Dislocation followed by loosening of the prosthesis was noticed in two dogs, which were therefore properly treated with a femoral head osteotomy. Femoral fracture occurred in one dog, which was promptly treated with full implant removal and femoral osteosynthesis.Conclusions: The canine modular hybrid total hip arthroplasty provided excellent functionality of the operated limb

Farmacologia clínica da metadona peridural e intravenosa em cães

A metadona é um opióide que possui potência analgésica semelhante à da morfina. Doses elevadas de metadona intravenosa (0,5-1,0 mg/kg), apesar de reduzirem a concentração alveolar mínima do isoflurano (CAMISO), resultam em maior depressão cardíaca que a observada com a morfina intravenosa (1,0 mg/kg) em cães. Com a hipótese de que a metadona peridural poderia proporcionar vantagens clínicas em relação à metadona intravenosa (maior potencialização da anestesia inalatória e maior eficácia analgésica), os estudos apresentados objetivaram comparar aspectos farmacocinéticos e farmacodinâmicos destas vias de administração da metadona em cães. Nos dois estudos iniciais (Capítulos 1 e 2), os mesmos seis animais foram anestesiados com isoflurano e tratados com metadona (0,5 mg/kg) peridural ou intravenosa em ocasiões distintas. No primeiro estudo (Capítulo 1), para comparação da farmacocinética destas duas vias de administração, a concentração de metadona foi determinada no plasma e no líquor da cisterna magna antes e durante 450 minutos após a administração do opióide. No segundo estudo (Capítulo 2), a CAMISO foi mensurada antes e após 2,5 e 5 horas da administração da metadona, mediante a aplicação da estimulação nociceptiva em membro pélvico e torácico (via peridural) ou em membro pélvico apenas (via intravenosa). No último estudo (Capítulo 3), cadelas apresentando tumores mamários, após serem tratadas de forma preemptiva com metadona (0,5 mg/kg) peridural ou intravenosa (10 animais por grupo), foram submetidas à mastectomia unilateral. Nesta etapa, avaliou-se a concentração expirada de isoflurano (ETISO) necessária à realização da mastectomia e, no período pós-operatório, avaliou-se os escores de dor, limiares nociceptivos mecânicos (LNM) das cadeias mamárias e requerimento de resgates analgésicos. No estudo do Capítulo 1, a via...Methadone is an opioid that has analgesic potency comparable to that of morphine. High doses of intravenous methadone (0.5-1.0 mg/kg), in spite of reducing the minimum alveolar concentration of isoflurane (MACISO), cause greater cardiac depression than intravenous morphine (1 mg/kg) in dogs. The studies presented here aimed to compare some pharmacokinetic and pharmacodynamic aspects of peridural and intravenous methadone in dogs, testing the hypothesis that peridural methadone could result in clinical advantages when compared to intravenous methadone (greater reduction in anesthetic requirements and greater analgesic efficacy). In the first 2 studies (Chapters 1 and 2), the same six animals underwent isoflurane anesthesia and were treated with methadone (0.5 mg/kg) administered via the peridural or intravenous routes during different occasions. During the first study (Chapter 1), in order to compare the pharmacokinetics of these two administration routes, methadone concentrations were determined in plasma and in the cisternal cerebrospinal fluid before and for 450 minutes after opioid injection. During the second study (Chapter 2), MACISO was measured before, 2.5 and 5 hours after methadone injection via nociceptive stimulation of the thoracic and pelvic limb (peridural) or the pelvic limb (intravenous). During the last series of studies (Chapter 3), bitches presented with mammary gland tumors were preemptively treated with peridural or intravenous methadone (0.5 mg/kg) (10 animals per group) and underwent unilateral mastectomy. The end-tidal isoflurane concentration (ETISO) necessary for maintaining surgical anesthesia was evaluated and, during the postoperative period, parameters evaluated included Glasgow pain scores, mechanical nociceptive thresholds (MNT) in the mammary glands, and requirement for supplemental analgesia. In first study (Chapter 1), peridural methadone prolonged... (Complete abstract click electronic access below)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Efeitos da administração epidural de dexmedetomidina sobre a concentração alveolar mínima do isofluorano em cães

A administracao intravenosa de dexmedetomidina reduz significativamente a concentracao alveolar minima (CAM) dos agentes halogenados. No entanto, esse beneficio e frequentemente acompanhado por efeitos colaterais tipicos dos agonistas 2, como hipertensao, bradicardia e reducao do debito cardiaco. Ha indicios de que a administracao epidural de doses reduzidas de dexmedetomidina pode potencializar e prolongar seu efeito analgesico. Hipotetizou-se que a administracao epidural de dexmedetomidina reduziria a CAM do isofluorano de forma dose e tempo-dependente, sem ocasionar depressao cardiovascular significativa. Objetivou-se tambem caracterizar as alteracoes do indice bispectral (BIS) induzidas pela estimulacao nociceptiva empregada na mensuracao da CAM, bem como o efeito da dexmedetomidina epidural sobre essas alteracoes. Seis caes higidos (18,8}4,0 kg) foram anestesiados com isofluorano em 4 ocasioes distintas, com intervalo de 7 dias. Em cada anestesia, os animais receberam aleatoriamente 1 de 4 tratamentos pela via epidural. No tratamento controle, administrou-se solucao salina, enquanto nos tratamentos DEX1.5, DEX3 e DEX6, administrou-se dexmedetomidina nas doses de 1,5 . 3,0 e 6,0 Êg/kg, respectivamente. A CAM do isofluorano foi mensurada as 2 e 4,5 horas apos os tratamentos epidurais, por meio de estimulacao nociceptiva supramaxima (50V, 50 Hz e 10 ms) no membro pelvico. O valor medio de CAM (} desvio padrao) no tratamento controle foi de 1,57}0,23% e 1,55}0,25% as 2 e 4,5 horas, respectivamente. Quando comparado ao tratamento controle, o valor de CAM observado no tratamento DEX1,5 foi reduzido em 13% as 2 horas (1,35}0,11%), enquanto que a reducao as 4,5 horas (7% de reducao, CAM: 1,43}0,23%) nao foi significativa. No tratamento DEX3, a CAM foi significativamente reduzida em 29% (1,12}0,18%) e 13% (1,33}0,16%) as 2 e 4,5 horas, respectivamente. Reducoes de maior magnitude foram observadas...Intravenous administration of dexmedetomidine significantly reduces the minimum alveolar concentration (MAC) of inhalant anesthetics. However, this beneficial effect is often associated with side effects such as hypertension, bradycardia, and a decrease in cardiac output. There are evidences epidural administration of relatively low doses of dexmedetomidine may result in more prolonged analgesia than intravenous administration of higher doses. The hypothesis of the present study is that epidural administration of dexmedetomidine would reduce isoflurane MAC in a dose and time-related fashion, without causing marked cardiovascular changes. This study aimed also to characterize the changes in bispectral index (BIS) induced by nociceptive stimulation used for MAC determinations and the effects of epidural dexmedetomidine on these changes. Six healthy dogs (18.8 8l4,0 kg) were anesthetized with isoflurane at 4 different occasions with at least 1-week intervals. On each anesthetic procedure, animals received 1 of 4 epidural treatments. Physiologic saline solution was administered in the control treatment, while for the treatments DEX1.5, DEX3, and DEX6, dexmedetomidine was administered at the doses of 1.5, 3.0, and 6.0 ìg/kg, respectively. Isoflurane MAC was assessed at 2 and 4.5 hours after epidural injections by means of supramaximal nociceptive stimulation (50V, 50 Hz e 10 ms) administered to the pelvic limb. Mean (l SD) isoflurane MAC in the control treatment was 1.57l0.23% and 1.55l0.25% at 2 e 4,5 hours, respectively. When compared to controls, mean MAC values observed in the DEX1.5 treatment were significantly reduced by 13% at 2 hours (1.35l0.11%), while the reduction observed at 4.5 hours (7% reduction, MAC: 1.43l0.23%) was not statistically significant... (Complete abstract click electronic access below)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Concentração alveolar mínima do isoflurano em cães tratados com duas doses de morfina

This study aimed to evaluate the effects of intramuscular 0.5mg kg-1 (MOR0.5) and 1.0mg kg-1 (MOR1.0) morphine premedication on the minimum alveolar concentration of isoflurane (ISOMAC) in dogs. Eighteen client-owned female dogs were scheduled for elective ovariohysterectomy. Dogs received intramuscular MOR0.5 or MOR1.0 as premedication and propofol IV for induction of anesthesia. Isoflurane was delivered for maintenance of anesthesia and dogs were maintained under normocapnia and normothermia. Determinations of the ISOMAC were conducted by use of the “up-and-down” method. Noxious stimulus (placement of Backhaus towel clamps, a midline skin incision and subcutaneous tissue dissection) was delivered approximately 50 minutes after premedication with MOR0.5 or MOR1.0. The calculated ISOMAC was 0.98±0.15% in MOR0.5 and 0.80±0.08% in MOR1.0. The ISOMAC was significantly lower in MOR1.0 compared with MOR0.5 (P=0.010). Results of this study suggested that intramuscular premedication with morphine 0.5 and 1.0mg kg-1 decreases the ISOMAC in a dose-related manner in dogs.O presente estudo objetivou avaliar os efeitos da administração intramuscular de 0,5mg kg-1 (MOR0,5) ou 1,0mg kg-1 (MOR1,0) de morfina sobre a concentração alveolar mínima do isoflurano (CAMISO) em cães. Dezoito cadelas de proprietários foram agendadas para ovário-histerectomia eletiva. As cadelas receberam MOR0,5 ou MOR1,0, como medicação pré-anestésica, e propofol IV para indução da anestesia. A manutenção da anestesia foi realizada com isoflurano em condições de normocapnia a normotermia. A determinação da CAMISO foi conduzida de acordo com o método “up-and-down”. O estímulo nociceptivo (colocação de pinças Backhaus, incisão da pele na linha média e dissecção de tecido subcutâneo) foi realizado aproximadamente 50 minutos após a administração de MOR0,5 ou MOR1,0. A CAMISO calculada foi 0,98±0,15% em MOR0,5 e 0,80±0,08% em MOR1,0. A CAMISO foi significativamente menor em MOR1,0 do que em MOR0,5 (P=0,010). Os resultados do estudo sugerem que a medicação pré-anestésica com morfina nas doses de 0,5 e 1,0mg kg-1, pela via intramuscular, resulta em redução dose-dependente na CAMISO em cães

Evaluation of cardiorespiratory effects of combinations of dexmedetomidine and atropine in cats

The cardiovascular effects of dexmedetomidine alone or in combination with atropine were studied in six cats. Cats underwent four treatments in a randomized crossover design as follows: DEX15, saline + dexmedetomidine 15 mu g/kg; DEX30, saline + dexmedetomidine 30 mu g/kg; ADEX15, atropine + dexmedetomidine 15 mu g/kg; ADEX30, atropine + dexmedetomidine 30 mu g/kg. Pulse rate (PR) and systolic arterial pressure (SAP) decreased in DEX15 and DEX30. Premedication with atropine was effective in preventing bradycardia (PR < 100 beats/min) and resulted in a biphasic effect in blood pressure. Hypertension was followed by a gradual decrease in SAP. Rate pressure product decreased in DEX15 and DEX30 whereas in ADEX15 and ADEX30 it remained within baseline values for at least 60 min. Although premedication with atropine in cats sedated with dexmedetomidine prevents bradycardia, it induces hypertension and increases myocardial oxygen consumption. The magnitude of cardiovascular effects produced by dexmedetomidine in cats does not seem to be dose-related. (C) 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved