BACKGROUND: Brain death-related cardiovascular dysfunction has been documented; however, its mechanisms remain poorly understood. We investigated changes in myocardial function and metabolism in brain-dead and control pigs. METHODS: Heart rate, systolic (SAP) and mean (MAP) arterial pressure, left ventricular (LV) dP/dtmax, rate-pressure product, cardiac output (CO), left anterior descending coronary artery blood flow, lactate metabolism, and interstitial myocardial purine metabolite concentrations, monitored by cardiac 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 (82 [74-103] to 117 [85-142] mmHg), LV dP/dtmax (1750 [1100-2100] to 5150 [4000-62,000] mmHg x sec(-1), rate-pressure product (9100 [7700-9700] beats mmHg/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 coronary 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 concentration was observed after brain death induction (2.9 [1.0-5.8] to 15.8 [7.0-50.7] micromol/L), followed by a slow decline. Volume expansion significantly increased MAP, CO, and LV dP/dtmax in control animals, but decreased LV dP/dtmax and slightly increased CO in brain-dead animals. A significant 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 limited increase in coronary blood flow, resulting in net myocardial lactate production and increased interstitial adenosine concentration consistent with an imbalance between myocardial oxygen demand and supply. This may have contributed to the early impairment of cardiac function in brain-dead animals revealed by rapid volume infusion.
BACKGROUND: Brain death-related cardiovascular dysfunction has been documented; however, its mechanisms remain poorly understood. We investigated changes in myocardial function and metabolism in brain-dead and control pigs. METHODS: Heart rate, systolic (SAP) and mean (MAP) arterial pressure, left ventricular (LV) dP/dtmax, rate-pressure product, cardiac output (CO), left anterior descending coronary artery blood flow, lactate metabolism, and interstitial myocardial purine metabolite concentrations, monitored by cardiac 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 (82 [74-103] to 117 [85-142] mmHg), LV dP/dtmax (1750 [1100-2100] to 5150 [4000-62,000] mmHg x sec(-1), rate-pressure product (9100 [7700-9700] beats mmHg/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 coronary 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 concentration was observed after brain death induction (2.9 [1.0-5.8] to 15.8 [7.0-50.7] micromol/L), followed by a slow decline. Volume expansion significantly increased MAP, CO, and LV dP/dtmax in control animals, but decreased LV dP/dtmax and slightly increased CO in brain-dead animals. A significant 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 limited increase in coronary blood flow, resulting in net myocardial lactate production and increased interstitial adenosine concentration consistent with an imbalance between myocardial oxygen demand and supply. This may have contributed to the early impairment of cardiac function in brain-dead animals revealed by rapid volume infusion.