IV infusão contínua é a Rota escolha no tratamento da arginina-vasopressina Receptor Blocker conivaptan em camundongos para Estudar evocadas por acidente vascular cerebral Edema
Summary
Our studies have revealed that the beneficial effects of conivaptan are dependent on the method of delivery after experimental stroke in mice. We have developed a research protocol for delivery of the receptor blocker via IV catheter on stroke-evoked brain edema formation in mice.
Abstract
AVC é uma das principais causas de morbidade e mortalidade no mundo. AVC é complicada por edema cerebral e outros eventos fisiopatológicos. Entre os jogadores mais importantes no desenvolvimento e evolução do edema cerebral evocada-acidente vascular cerebral é a hormona arginina-vasopressina e seus receptores, V1a e V2. Recentemente, o V1a e V2 bloqueador do receptor conivaptan tem atraído a atenção como um potencial medicamento para reduzir o edema cerebral após acidente vascular cerebral. No entanto, os modelos animais que envolvem aplicações conivaptan em pesquisa AVC precisa ser modificada com base em rotas viáveis de administração. Aqui os resultados de 48 h intravenosa contínua (IV) são comparados com os tratamentos por via intraperitoneal (IP) conivaptan após acidente vascular cerebral experimental em ratinhos. Foi desenvolvido um protocolo em que a oclusão da artéria cerebral média foi combinado com a passagem do cateter na veia jugular para o tratamento de IV conivaptan (0,2 mg) ou veículo. Diferentes grupos de animais foram tratados com 0,2mg bolus de conivaptan ou veículo IP diariamente. edema cerebral evocada tempos experimental foi avaliada em ratinhos após IV contínua e tratamentos IP. A comparação dos resultados revelou que a administração IV contínua de conivaptan alivia edema cerebral pós-isquêmica em ratos, ao contrário da administração IP de conivaptan. Conclui-se que o nosso modelo pode ser utilizado para estudos futuros de aplicações conivaptan no contexto de acidente vascular cerebral e edema cerebral.
Introduction
Stroke continues to be an enormous burden for patients and clinicians. Animal stroke models have been used in the laboratory setting for nearly two decades.1 Nevertheless, experimental treatments that work in animals often fail in humans.2 This discrepancy in treatment outcomes may be due to various factors, such as administration routes for drugs used in animal research, drug metabolism and elimination rate, and many other aspects. One of the major complications of stroke, brain edema, is a focus of current research in neuroscience. Mechanisms of brain edema formation involve disturbances in water and electrolyte balance triggered by the arginine-vasopressin (AVP) response to ischemic brain injury.3 Therefore, AVP and its receptors (V1a and V2) are a major focus of research studies of post-ischemic brain edema formation.3
We have developed a methodology to study the effects of mixed arginine-vasopressin (V1a and V2) receptor blocker conivaptan on post-ischemic brain edema in mice.4 Molecular targets of conivaptan5 make the drug a suitable candidate for exploration of its properties in alleviation of brain edema. Furthermore, conivaptan needs to be studied in the context of pathophysiological events of stroke.6 In designing this study, we considered comparing treatment outcomes using two different routes of administration for conivaptan: intravenous (IV)4 and intraperitoneal (IP).7 Effects of the treatments on stroke-induced brain edema were evaluated. Here detailed protocols are described for surgical induction of experimental stroke by middle cerebral artery occlusion (MCAO), and followed by continuous conivaptan treatment using the installation of a jugular IV catheter. After induction of stroke, animals were randomly allocated into the following groups: vehicle or conivaptan (0.2 mg/day) treated IV or IP.
Protocol
Representative Results
Discussion
Este estudo tem um valor importante para a investigação pré-clínica acidente vascular cerebral. Este estudo revela que a infusão IV contínua de conivaptan (0,2 mg / dia) depois de acidente vascular cerebral experimental em ratinhos reduz eficazmente o edema cerebral após 48 horas de tratamento. O efeito da injecção IP do mesmo na dose de conivaptan edema cerebral também foi investigada. tratamento conivaptan por ambas as vias IP e IV produz aquarese em ratos, tal como indicado por: 1) aumento da osmolalidade d…
Declarações
The authors have nothing to disclose.
Acknowledgements
Agradecemos a Swedish Medical Center for fornecer o financiamento e instalações. Agradecemos também Craig Hospital para o uso generoso de espaço de laboratório.
Materials
| Heated Pad | K&H Manufacturing Inc | 1060 | |
| Temperature Monitor with Rectal Probe | Physitemp | 7029 | |
| Silk Suture Spool, 6-0 | Surgical Specialties Corporation | SP114 | |
| Silk Suture on a Needle, 3-0 | Ethicon | 1684G | |
| Nylon Suture, 7-0 | Ethicon | 1696G | |
| Dental Resin Polysiloxane with Hardener | Heraeus Kulzer | 65817930 | |
| Microinfusion IV Pump | Kent Scietific | GT0897 | |
| Swivel 22GA | Instech | 375/22PS | |
| Laboratory Tubing, 0.94 x 0.51 mm | Dow Corning | 508-002 | |
| Laboratory Tubing, 3.18 x 1.98 mm | Dow Corning | 508-009 |
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