Brain death is a pathophysiological condition associated with major hemodynamic changes, temporary
myocardial ischemia, and histological damage of the heart. These modifications could be related to a major local release of
norepinephrine from myocardial sympathetic nerve endings leading to
norepinephrine cardiotoxicity. This study was designed to evaluate the utility of cardiac microdialysis to measure interstitial myocardial
norepinephrine release resulting from
brain death. The dialysis probe consisted in
a 10 x 0.20-mm dialysis fiber with a 18,000 mol wt cutoff. Dialysis probes were implanted into the right and left ventricular walls of the beating heart in anesthetized pigs and perfused with
Ringer solution at 2 microliters/min.
Dialysate norepinephrine concentration was measured using HPLC with electrochemical detection. The relative recovery rate of
norepinephrine in vivo was 34 +/- 4%. Interstitial fluid concentrations were obtained using the following formula: [C]interstitium = [C]
dialysate/Recovery in vivo. After
brain death, a transient increase in interstitial
norepinephrine concentration was observed (from 0.74 +/- 0.20 to 4.50 +/- 0.60 ng/ml and 0.76 +/- 0.20 to 6.2 +/- 0.9 ng/ml in left and right ventricle, respectively, P < 0.01) which far exceeded plasma level increase (from 0.50 +/- 0.10 ng/ml to 0.91 +/- 0.20 ng/ml, P < 0.05). This increase in myocardial
norepinephrine was, moreover, biphasic, with a second peak occurring 40 min after
brain death. The present study confirms the onset of a dramatic increase in cardiac
norepinephrine release from myocardial nerve endings following
brain death, and demonstrate the utility of the new cardiac microdialysis technique to assess changes in interstitial fluid content.