Abstract 2051: Preservation of Mitochondrial Function with Cardiopulmonary Resuscitation (CPR) in Prolonged Cardiac Arrest
Background: CPR generated perfusion pressure, and consequently myocardial oxygen delivery, is very low during cardiac arrest. It is not known whether oxygen delivery under these circumstances protects or further impairs mitochondrial function. Using an in vivo rat CPR model, we tested the hypothesis that CPR generated perfusion does preserve heart mitochondrial function.
Methods: Male Sprague-Dawley rats (400~450gm) were anesthetized with ketamine/xylazine, mechanically ventilated and instrumented for central venous access and arterial pressure monitoring. Animals were randomly divided into three groups (n=8/ group):
instrumented without cardiac arrest for 20 min (Baseline group)
25 min KCl-induced cardiac arrest without CPR (CA group), and
15 min KCl-induced cardiac arrest
with 10 min CPR ventilated with 100% O2 (CPR group). After removal of the heart, mitochondria were immediately isolated by differential centrifugation and the mitochondrial respiration profiles were measured by a Clark-type oxygen electrode. The enzymatic activities of mitochondrial electron transport chain complexes were then determined by spectrophotometric assays.
Results: A 64% reduction of the respiratory control ratio (RCR = ratio of state 3/4 respiration with glutamate/malate) in isolated mitochondria was noted in the CA group (1.905 ± 0.23) compared to Baseline group (5.239 ± 0.13, p < 0.001). In the CPR group RCR recovered to 80% of baseline (4.229 ± 0.18 vs CA group, p < 0.001). The RCR measured by adding succinate also exhibited a similar pattern. The electron transfer of complex I is highly correlated with the changes of RCR (Baseline: 353.3 ± 13.2, CA: 147.1 ± 17.1, CPR: 253.3 ± 28.7, nmol NADH oxidized/min/mg protein). Complex II activity in the CPR group was decreased 39% compared to the Baseline and CA groups (Baseline: 72.98 ± 5.5, CA: 68.71 ± 7.3, CPR: 44.45 ± 4.0, nmol dichlorophenolindophenol (DCPIP) reduced/min/mg protein). There were no statistical differences in complex III and IV activities among groups.
Conclusions: CPR after prolonged cardiac arrest preserves heart mitochondrial function via the maintenance of complex I activity. This support in mitochondrial function likely extends the heart viability during resuscitation.
This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).