Abstract 327: Impaired Mitochondrial Function Following The Metabolic Phase Of Cardiac Arrest And Resuscitation: Differences In Tissue Vulnerability, Site And Severity Of Dysfunction
Introduction: Mitochondrial dysfunction may be critical to reperfusion injury following the metabolic phase of prolonged cardiac arrest. However, specific intra-mitochondrial sites of dysfunction remain uncertain and differential tissue vulnerabilities have not been well characterized.
HYPOTHESIS: The metabolic phase of prolonged cardiac arrest and resuscitation will provoke specific patterns of fixed localized defects in respiratory and phosphorylating activities of mitochondrial function and impact the heart, brain, and kidney differently.
METHODS: A rodent model of prolonged cardiac arrest was employed with 30 min of untreated axphyxial arrest followed by 60 min of emergency cardiopulmonary bypass (ECPB). Electron transport and energy coupling were analyzed under four experimental conditions: no treatment (NORM), 30 min untreated cardiac arrest (CA30), 30 min arrest plus 60 min ECPB reperfusion (CA30R60) and 90 min arrest (CA90). Measurements of O2 consumption (states 3 & 4, and respiratory control ratio), NADH oxidase, and partial electron transport reactions (for Complex I+III, II+III, & IV) were performed.
Results: State 3 O2 consumption (glutamate/malate) for: (a) the heart at NORM, CA30, CA30R60 and CA90 was 153±28, 90±13, 136±22, and 118±20, respectively (mean±s.d., nanoatoms oxygen/min/mg protein); (b) the kidney was128±32, 82±12, 114±18, and 53±8 respectively; and (c) the brain was 68±5, 57±4, 49±16, and 33±6 respectively. Similar patterns for succinate nourished State 3 O2 consumption and for respiratory control ratios were seen. ETC partial complex measures revealed dysfunction in brain > heart > kidney.
CONCLUSION: Distinct mitochondrial defects develops after prolonged ischemia and reperfusion that are tissue specific and show unique intra-mitochondrial sites. Respiratory activities of heart > kidney > brain and this is inversely related to the sensitivity of the tissue to ischemia/reperfusion injury. All tissues demonstrate poor respiratory control ratios after 30 min of ischemia. However with 60 min of reperfusion the kidney and brain recover significantly while the brain does not improve. The vulnerability of the brain and heart to ischemia may be linked to mitochondrial pathways and a target for new therapies.
- © 2013 by American Heart Association, Inc.