Organ function during porcine haemorrhage and resuscitation with pre-existing atherosclerosis.

Background and Goal of Study: Haemorrhagic shock causes tissue hypoxia, hyper-inflammation and subsequent multi-organ failure (MOF). Pre-existing cardiac comorbidity increases mortality after trauma1. However, obesity, a risk factor for ischemic heart disease, is associated with reduced ICU mortality2. Therefore, we investigated the impact of atherogenic diet-induced coronary artery disease (CAD)3 on MOF during haemorrhage and resuscitation. 
Materials and methods: 18 anesthetized and instrumented familial LDL-cholesterol-receptor-/- (FBM) pigs with (CAD, n=9) or without (control, n=9) atherogenic diet underwent 3 hours of haemorrhage (removal of 30 % of the calculated blood volume, mean arterial pressure (MAP) = 44 (42-45) mmHg) followed by 48 h of resuscitation comprising re-transfusion of shed blood, crystalloids and noradrenaline (NA) titrated to maintain MAP at pre-shock levels. Before, at the end of and every 12 hours after haemorrhage we assessed systemic, pulmonary and renal haemodynamics (left ventricular (LV) pressure-conductance and pulmonary artery catheterization; renal artery ultrasound flow probes), gas exchange and organ function. Data are median (range).    
Results and Discussion: Survival time (CAD: 48 (26-48) h; control:  38 (24-48) h, p=0.84) and NA requirements needed to reach target haemodynamics (CAD: 1.5 (0.8-3.9) µg•kg-1•min-1; control: 1.1 (0.9-1.7) µg•kg-1•min-1, p=0.39) were comparable. Creatinine clearance was 66 (18-88) ml/min vs. 66 (39-94) ml/min (p=0.60) and 90 (35-105) ml/min vs 70 (28-98) ml/min (p=0.63) in CAD and control groups during 0-24h and 24-48h of resuscitation, respectively. Systemic and pulmonary haemodynamics, gas exchange and LV function (dp/dtmax and min, isovolumic relaxation constant t) did not show significant inter-group differences during 48h of observation either. 
Conclusion: In our model of resuscitated haemorrhagic shock, pre-existing atherosclerosis neither increased mortality nor aggravated the severity of MOF. Aggressive fluid resuscitation and high-dose NoA may have overcome any impact related to pre-existing chronic cardiovascular disease. In addition, putative protective effects due to the “obesity paradox” may have blunted otherwise detrimental influence of pre-existing atherosclerosis. 
References:
1. Ferraris et al: J Trauma 2010;69:645 
2. Pickkers et al: Crit Care Med 2013;41:1878
3. Thim et al: EuroIntervention 2010;6:261