RESUMEN
Cardiac ischemia-reperfusion alters sympathetic neurotransmission in the heart, but little is known about its effect on neuropeptide expression in sympathetic neurons. Ischemia followed by reperfusion induces the production of inflammatory cytokines in the heart, including interleukin-6 and cardiotrophin-1. These cytokines and related molecules inhibit the expression of neuropeptide Y (NPY), and stimulate the expression of vasoactive intestinal peptide (VIP), substance P (SubP), and galanin (GAL) in cultured sympathetic neurons. Therefore, we quantified NPY, VIP, SubP, and GAL mRNA in neurons of the stellate ganglia 1 week after ischemia-reperfusion to determine if neuropeptide expression was altered in cardiac sympathetic neurons. NPY, VIP, and SubP mRNAs were unchanged compared to unoperated control animals, but GAL mRNA was increased significantly. The increased GAL mRNA was not accompanied by elevated GAL peptide content in the stellate ganglia. Galanin content was increased significantly in the heart, however, indicating that elevated GAL mRNA led to increased peptide production. GAL content was increased in the left ventricle below the coronary artery ligation, but was not increased significantly in the atria or the base of the heart above the ligation. The buildup of GAL specifically in the damaged left ventricle is consistent with previous reports that GAL is transported to regenerating nerve endings after axon damage.
Asunto(s)
Galanina/genética , Expresión Génica , Corazón/inervación , Infarto del Miocardio/metabolismo , Neuronas/química , Sistema Nervioso Simpático/química , Animales , Vasos Coronarios , Ligadura , Masculino , Isquemia Miocárdica , Reperfusión Miocárdica , Neuropéptido Y/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Sustancia P/genética , Péptido Intestinal Vasoactivo/análisisRESUMEN
OBJECTIVE: We previously demonstrated that administration of 7.5% hypertonic saline (HS) significantly improved spinal cord blood flow and neurological outcomes after spinal cord injury. The aim of this study was to determine whether hypertonicity would enhance the effects of methylprednisolone (MP), further improving neurological function. METHODS: Rat spinal cords were compressed for 10 minutes with 50 g of weight, and neurological function was assessed for 28 days, using the Basso-Beattie-Bresnahan locomotor rating scale. The control group received an intravenous injection of isotonic saline (IS) (5 ml/kg). Group 1 received an intravenous injection of 7.5% HS (5 ml/kg). Group 2 received an intravenous injection of MP (30 mg/kg) and IS (5 ml/kg). Group 3 received an intravenous injection of MP (30 mg/kg) administered with 7.5% HS (5 ml/kg). RESULTS: At 24 hours after spinal cord injury, the combination of MP plus HS provided significant (P < 0.01) neurological improvements, compared with all other treatment groups. At 10 days after injury, the animals that had received MP plus HS exhibited significantly (P < 0.01) higher Basso-Beattie-Bresnahan scores, compared with the MP plus IS and control groups. The median survival time was significantly (P < 0.01) increased for the MP plus HS group (28 d), compared with the MP plus IS group (16 d). Because of the dramatic decrease in survival rates at 28 days after injury, there was a significant (P < 0.01) difference in neurological function only between the MP plus HS group and the control group. CONCLUSION: The results indicate that the administration of HS may enhance the delivery of MP and prevent immunosuppression, leading to improvements in overall neurological function and survival rates after spinal cord injury.
Asunto(s)
Locomoción/efectos de los fármacos , Metilprednisolona/farmacología , Solución Salina Hipertónica/farmacología , Traumatismos de la Médula Espinal/fisiopatología , Animales , Quimioterapia Combinada , Femenino , Inyecciones Intravenosas , Locomoción/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
Gram-negative sepsis and subsequent endotoxic shock after surgery remain problematic in the United States and throughout the world. While morphine is widely prescribed for postoperative trauma pain management, there are reports that morphine may compromise the immune system and contribute to postoperative sepsis. The current study tested the hypothesis that morphine attenuates leukocyte rolling and sticking in both arterioles and venules via nitric oxide production. Nude mice implanted with slow-release morphine pellets were used in this study. The dorsal skinfold chamber model for intravital fluorescence microscopy on awake mice was used. Leukocyte/endothelial interactions were evaluated after bolus injection of oxidized low density lipoprotein. Morphine was found to significantly attenuate leukocyte rolling and sticking in both the arterial and venular side of the microcirculation. This attenuation was reversed by simultaneous implantation of naloxone pellets. The mechanisms of this attenuation were further investigated by administration of the nitric oxide synthase inhibitors NG-nitro-l-arginine (NOLA) and aminoguanidine (AG) in drinking water. NOLA was found to significantly reverse this morphine-induced attenuation of leukocyte rolling and sticking in both arterioles and venules. However, AG did not have the same effect. The results indicate that morphine interferes with leukocyte/endothelial cell interactions via stimulation of nitric oxide production.