Increase in myocardial interstitial adenosine and net lactate production in brain-dead pigs - An in vivo microdialysis study

Background. Brain death-related cardiovascular dysfunction has been documen ted; however, its mechanisms remain poorly understood. We investigated chan ges in myocardial funct;iom and metabolism in brain-dead and control pigs. Methods. Heart rate, systolic (SAP) and mean (MAP) arterial pressure, left ventricular (LV) dP/dt(max), rate-pressure product, cardiac output (CO), le ft anterior descending coronary artery blood flow, lactate metabolism, and interstitial myocardial purine metabolite concentrations, monitored by card iac microdialysis, were studied. A volume expansion protocol was performed at the end of the study. Results. After brain death, a transient increase in heart rate (from 90 [67 -120] to 158 [120-200] beats/min) (median, with range in. brackets), MAP (8 2 [74-103] to 117 [85-142] mmHg), LV dP/dt(max) (1750 [1100-2100] to 5150 [ 4000-62,000] mmHg.sec(-1)), rate-pressure product (9100 [7700-9700] beaks m mHg/min to 22,750 [20,000-26,000] beats mmHg/min), CO (2.2 [2.0-4.0] to 3.3 [3.0-6.0] L/min), and a limited increase in left anterior descending coron ary artery blood flow (40 [30-60] to 72 [50-85] ml/min) were observed. Net myocardial lactate production occurred (27 [4-40] to -22 [-28, -11] mg/L, P <0.05) and persisted for 2 hr. A 6-7-fold increase in adenosine dialysate c oncentration was observed after brain death induction (2.9 [1.0-5.8] to 15. 8 [7.0-50.7] mu mol/L), followed by a slow decline. Volume expansion signif icantly increased MAP, CO, and LV dP/dt(max) in control animals, but decrea sed LV dP/dt(max) and slightly increased CO in brain-dead animals. A signif icant increase in adenosine concentration was observed in both groups, with higher levels (P<0.05) in brain-dead animals. Conclusions. Brain death increased oxygen demand in the presence of a limit ed increase in coronary blood flow, resulting in net myocardial lactate pro duction and increased interstitial adenosine concentration consistent with an imbalance between myocardial oxygen demand and supply. This may have con tributed to the early impairment of cardiac function in brain-dead animals revealed by rapid volume infusion.