Oct 19, 2010

Genetic deletion of NOS3 increases lethal cardiac dysfunction following mouse cardiac arrest

Resuscitation
D G BeiserT L Vanden Hoek

Abstract

Cardiac arrest mortality is significantly affected by failure to obtain return of spontaneous circulation (ROSC) despite cardiopulmonary resuscitation (CPR). Severe myocardial dysfunction and cardiovascular collapse further affects mortality within hours of initial ROSC. Recent work suggests that enhancement of nitric oxide (NO) signaling within minutes of CPR can improve myocardial function and survival. We studied the role of NO signaling on cardiovascular outcomes following cardiac arrest and resuscitation using endothelial NO synthase knockout (NOS3(-/-)) mice. Adult female wild-type (WT) and NOS3(-/-) mice were anesthetized, intubated, and instrumented with left-ventricular pressure-volume catheters. Cardiac arrest was induced with intravenous potassium chloride. CPR was performed after 8min of untreated arrest. ROSC rate, cardiac function, whole-blood nitrosylhemoglobin (HbNO) concentrations, heart NOS3 content and phosphorylation (p-NOS3), cyclic guanosine monophosphate (cGMP), and phospho-troponin I (p-TnI) were measured. Despite equal quality CPR, NOS3(-/-) mice displayed lower rates of ROSC compared to WT (47.6% [10/21] vs. 82.4% [14/17], p<0.005). Among ROSC animals, NOS3(-/-) vs. WT mice exhibited increased left-ven...Continue Reading

  • References46
  • Citations12

Mentioned in this Paper

Neuro-Oncological Ventral Antigen 2
Ischemia
Monoclonal antibodies, antineoplastic
Biochemical Pathway
Whole Blood
S-Nitrosothiols
NOS1 protein, human
Calcium
Left Ventricular Structure
Troponin I

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