If cardiopulmonary resuscitation exceeded 10minutes without ROSC, the cardiopulmonary resuscitation was stopped. evaluated by neurologic deficit score and tape removal test, and improved the 14-day survival rate. Hydrogen sulfide also attenuated CA and CPR-induced increases of matrix metalloproteinase-9 (MMP-9) activity and vascular endothelial growth factor (VEGF) expression, and increased the expression of angiogenin-1 (Ang-1). These results indicate that inhalation of 80-p. p. m. H2S immediately after CPR attenuated BBB permeability and brain edema, and improved neurologic outcome and 14-day survival of rats after CA. The therapeutic benefits of H2S could be associated with suppression of MMP-9 and VEGF expression and increased expression of Ang-1. Keywords: bloodbrain barrier, brain recovery, cardiac arrest, cardiopulmonary resuscitation, hydrogen sulfide, matrix proteins == Introduction == Poor neurologic outcome after cardiac arrest (CA) and resuscitation is a serious public health problem around the world. Even when come back of spontaneous circulation (ROSC) is achieved, more than half of the survivors suffer serious neurologic dysfunction. 1, 2, 3New therapeutic strategies are needed to improve patient survival and outcomes. Hydrogen sulfide (H2S) has been shown to have a variety of protective actions in various models of tissue and organ injury. 4, 5, 6However, the effect of H2S on neurologic outcome after CA and resuscitation, and the underlying mechanism, is not known. Disruption of the bloodbrain barrier (BBB) after ROSC is one of Avermectin B1 the major factors leading to permanent brain damage. 7, 8The BBB is a physical and metabolic barrier that maintains a constant environment around the neurons in the brain. Disruption of the BBB leads to extravasation of serum albumin, other macromolecular proteins, and cellular elements into the brain extracellular space, resulting in vasogenic brain edema, neuronal apoptosis, and cell death. 8, 9Matrix metalloproteinase-9 (MMP-9), 10vascular endothelial growth factor (VEGF), 11and angiogenin-1 (Ang-1)12play important roles in maintaining the integrity of the BBB. Matrix metalloproteinase-9 promotes BBB damage and brain edema in the early period of cerebral ischemia by Avermectin B1 degrading the extracellular matrix of cerebral microvessel basal lamina. This matrix consists of collagen IV, laminin, fibronectin, and interendothelial tight junction proteins such as zonula occludens-1. 13, 14Angiogenin-1 can counteract VEGF-induced vascular permeability by regulating MMP-9 activity. 15 We evaluated the effects of inhalation of H2S gas on neurologic outcome after CA and resuscitation, and examined whether its protective effects were associated with permeability of the BBB. We further examined whether changes in MMP-9, VEGF, and Ang-1 levels were associated with these effects. == Materials and Methods == == Animal Surgical Procedures == This study was approved by the Institutional Pet Care and Use Committee of Harbin Medical University, Harbin, Heilongjiang, China, and followed national guidelines (Guidelines on Supervision of Laboratory Animals in China and Guidelines on the Humane Treatment of Laboratory Animals in China) for the treatment of animals. Male Sprague-Dawley rats weighing 250 to 300 g were used in this study. Food and water were availablead libitumuntil morning of the experiment. Animals were anesthetized with 1% to 2% halothane and 30% oxygen. Ventilation was controlled with a small pet ventilator (Inspira ASV, Harvard Apparatus, MA, USA) to maintain arterial pH at 7. 35 to 7. 45, PaCO2at 35 to 45 mm Hg, and PaO2over 90 mm Hg. Pericranial temperature was monitored using thermistor probes (BIOPAC Systems, Santa Barbara, CA, USA) placed adjacent to the skull and maintained at 37C0. 5C throughout the experiment. A standard lead II electrocardiogram was recorded continuously using subdermal needle electrodes placed in the limbs. The right femoral artery and vein were cannulated using PE-50 catheters (Clay Adams, Parsippany, NJ, USA) for continuous monitoring of blood pressure, measurement of blood gases, infusion of fluid, Rabbit polyclonal to ZNF484 and drug supervision. Physiologic data were monitored and recorded using a BIOPAC MP150 Avermectin B1 physiometer (BIOPAC Systems). == Cardiac Arrest and Resuscitation == After preparation and subsequent stabilization, ventricular fibrillation was induced using an esophageal electrode (5F, Bard Peripheral Vascular, Tempe, AZ, USA) with a.