Browsing by Subject "Cardiac Arrest"
Now showing 1 - 3 of 3
- Results Per Page
- Sort Options
Item EXAMINING PYRUVATE S ANTI-INFLAMMATORY ACTIONS IN BRAIN FOLLOWING CARDIAC ARREST(2013-04-12) Nguyen, AnhPurpose: Approximately 0.5 million Americans suffer cardiac arrest each year. Cardiac arrest is usually lethal, and survivors often face severe neurological disability due to irreversible brain injury inflicted by global ischemia/reperfusion. Brain ischemia and reperfusion activates matrix metalloproteinases (MMPs) that disrupt the blood-brain barrier (BBB), enabling inflammatory cells to invade the brain parenchyma. We have shown that pyruvate, a metabolic intermediate and antioxidant, prevents death of hippocampal and cerebellar neurons and preserves neurobehavioral function in dogs after cardiac arrest. However, pyruvate's neuroprotective mechanism is elusive. We are testing the hypothesis that pyruvate preserves BBB integrity following cardiac arrest by suppressing MMPs and evoking expression of protective proteins hypoxia-inducible factor (HIF)-1ɑ and heat shock protein (Hsp)-70. Methods: Yorkshire swine (30-40 kg) were subjected to cardiac arrest-resuscitation or non-arrest sham protocols. Ventricular fibrillation was induced by a train of electric impulses transmitted to the right ventricle via a pacing wire. Precordial compressions were given at 6-10 min arrest, and then sinus rhythm was restored with defibrillatory transthoracic countershocks. NaCl or Na-pyruvate was infused iv at the rate of 0.1 mmol/kg/min during chest compressions and the first 60 min post-defibrillation. Cerebral cortex was snap-frozen in liquid nitrogen for immunoblot or fixed in 4% paraformaldehyde for immunohistochemistry (IHC) at 4 h after defibrillation. HIF-1ɑ and Hsp-70 contents were assessed by immunoblots and IHC. Four groups were studied: cardiac arrest + NaCl (n = 9) or Na-pyruvate (n = 7), or sham + NaCl (n = 5) or Na-pyruvate (n = 5). Results: Although immunoblots did not reveal appreciable differences in temporal cortex HIF-1ɑ content among the groups, IHC revealed increased HIF-1ɑ content in pyruvate-treated compared to NaCl-treated sham and cardiac arrest groups. Hsp-70 content also was similar among the groups, suggesting that this cytoprotective protein was not augmented within 3 h after 60 min pyruvate treatment. Conclusions: Current studies are examining neurobehavioral function and brain proteins over 7 days post-arrest. MMP activities in brain are being measured by gel zymography. Future experiments will determine plasma concentrations of neurofilament light chain, which, when elevated up to 7 days post-cardiac arrest, is associated with poor neurological outcomes.Item INTRAVENOUS PYRUVATE FOR CARDIAC ARREST DOES NOT CAUSE PERSISTENT HYPERNATREMIA(2013-04-12) Cherry, BrandonPurpose: Intravenous infusion of sodium pyruvate can protect internal organs from ischemia-reperfusion imposed by cardiac arrest and resuscitation, but may produce hypernatremia due to the sodium load. The purpose of this study was to examine the effects of Na-pyruvate infusion on plasma pyruvate, bicarbonate and sodium concentrations in order to test the hypothesis that pyruvate infusion does not cause persistent hypernatremia. Methods: Swine were subjected to 6 min cardiac arrest, 4 min closed-chest CPR, defibrillation and 4 h recovery. Na-pyruvate (n=7) or NaCl control (n=9) were infused iv (0.1 mmol/kg/min) during CPR and the first 60 min recovery. Results: Pyruvate infusion produced a sustained increase in plasma bicarbonate concentration (44.2 ± 1.2 mM in pyruvate-treated vs. 27.5 ± 2.6 mM in NaCl-treated group at 3 hours post-treatment; P<0.05), which may potentially offset post-arrest acidemia. Although pyruvate and NaCl infusions similarly increased plasma sodium concentrations (146 ± 2 mM and 148 ± l mM, respectively), the hypernatremia resolved to pre-arrest concentrations by 3 h post-pyruvate (140 ± 1 mM), but persisted 3 h post-NaCl (147 ± 2 mM; P<0.05). Conclusions: This study confirms the hypothesis that pyruvate administration after cardiac arrest did not cause persistent hypernatremia.Item VASOPRESSIN INSTEAD OF EPINEPHRINE ENHANCES EFFICACY OF CPR WITHOUT CAUSING TACHYCARDIA(2014-03) Cherry, Brandon H.; Nguyen, Ahn Q.; Williams, Arthur G. Jr.; Scott, Gary F.; Hollrah, Roger A.; Ryou, Myoung-Gwi; Hoxha, Besim; Olivencia-Yurvati, Albert H.; Mallet, Robert T.Survival from cardiac arrest is highly dependent on the arterial pressure generated by cardiopulmonary resuscitation (CPR). To increase efficacy of precordial compressions, the potent vasoconstrictor epinephrine (EPI) is administered. However, EPI also elicits a robust, β1-adrenoceptor-mediated tachycardia following defibrillation, depleting the myocardium of the energy reserves it requires for recovery. We proposed that the adrenoceptor-independent vasoconstrictor vasopressin (AVP) increases arterial pressure as effectively as EPI without producing tachycardia. After 6 min pacing-induced cardiac arrest, domestic swine (25-35 kg; 10 boars, 11 sows) received precordial compressions (100/min) for 4 min, and either EPI (0.1 mg; n=5) or AVP (10 U; n=24) was injected iv at 1 min CPR. EPI and AVP similarly increased mean arterial pressure from 31±3 to 66±4 mmHg vs. 34±3 to 59±3 mmHg after 4 min CPR. The AVP-treated pigs required less countershock energy (12±2 J) to achieve defibrillation vs EPI-treated pigs (16±4 J). Post-arrest tachycardia was less intense in AVP- (133±11 bpm) than EPI-treated (174±14 bpm) pigs. Thus, AVP is as effective as EPI at enhancing CPR, but avoids EPI-induced tachycardia. Purpose (a): The purpose of this study was to test the hypothesis that the adrenoceptor-independent vasoconstrictor vasopressin increases arterial pressure as effectively as epinephrine without producing tachycardia during cardiopulmonary resuscitation (CPR). Methods (b): After 6 min pacing-induced cardiac arrest, domestic swine (25-35 kg; 10 boars, 11 sows) received precordial compressions (100/min) for 4 min, and either epinephrine (0.1 mg; n=5) or vasopressin (10 U; n=24) was injected iv at 1 min CPR. Results (c): Epinephrine and Vasopressin similarly increased mean arterial pressure from 31±3 to 66±4 mmHg vs. 34±3 to 59±3 mmHg after 4 min CPR. The vasopressin-treated pigs required less countershock energy (12±2 J) to achieve defibrillation vs epinephrine-treated pigs (16±4 J). Post-arrest tachycardia was less intense in vasopressin- (133±11 bpm) than epinephrine-treated (174±14 bpm) pigs. Conclusions (d): Vasopressin is as effective as epinephrine at enhancing CPR, but avoids epinephrine-induced tachycardia.