Continuous Venovenous Haemofiltration Attenuates Myocardial Mitochondrial Respiratory Chain Complexes Activity in Porcine Septic Shock

Abstract

Increasing evidence indicates that mitochondrial dysfunction plays an important role in modulating the development of septic shock. In the present study, we investigated whether continuous veno-venous haemofiltration (CVVH) with high-volume might improve myocardial mitochondrial dysfunction in a porcine model of peritonitis-induced septic shock. Sixteen male Landrace pigs weighing 31±5 kg were randomly assigned to normal control group (n=4), peritonitis group (n=6) and peritonitis plus CVVH group (n=6). All animals were anaesthetised and mechanically ventilated. After baseline examinations, the peritonitis group and the peritonitis plus CVVH group underwent induction of peritonitis. One hour later, the animals in the peritonitis plus CVVH group received treatment with high-volume CVVH. Twelve hours after treatment, the animals were sacrificed. Animals in the peritonitis group were killed 13 hours after induction of peritonitis. Peritonitis challenge induced septic shock associated with increased blood lactate and high-volume CVVH improved lactate acidosis. Compared with the peritonitis group, cardiac output, stroke volume and mean arterial pressure were better maintained in peritonitis plus CVVH group. More importantly, high-volume CVVH improved myocardial mitochondrial complex I activity (0.22±0.03 vs. 0.15±0.04, P=0.04). These results suggest that high-volume CVVH improves haemodynamics and heart dysfunction in septic shock and the improvement may be attributed to amelioration of myocardial mitochondrial dysfunction.

Mitochondrial function in sepsis

“…Porcine models are often used in intensive care medicine research because of the feasibility of complex hemodynamic measurements. In seven of nine studies, faecal peritonitis or CLP was employed [11,12,[71][72][73][74][75], and in three, a constant LPS infusion (0.4 lg/kg/h) was used [13,74,76]. The majority of porcine models discussed are data from the authors of this review [11][12][13]71,74,76].…”

“…Liver mitochondrial oxygen consumption was either decreased [73][74][75][76] or not affected [11,12,71]. The enzymatic activity of complex I of heart mitochondria was decreased [72]. However, in another study, oxygen consumption of isolated heart mitochondria was not different between septic and control animals [11].…”

Blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration for patients with multiple organ dysfunction syndrome

“…[9,10] The present study showed that the above-mentioned results were related to myocardial depressant factor, inflammatory cytokine removal, and endothelial cell injury. [11,12] We also found that the scavenging capacity of cytokines like TNF-α, IL-1β and IL-6 using HP+CVVH is not more powerful than using CVVH alone. First, this may be related to the design of the study.…”

THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Continuous Renal Replacement Therapy in Sepsis and Multisystem Organ Failure

“…This hypothesis has been complemented by the idea that HVH may have additional pleiotropic effects by interfering with cardiovascular compounds (e.g., myocardial depressant factor, endocannabinoids, and endothelin) (34) and with the coagulation system (e.g., by reducing PAI-1) (35). A recent study in porcine septic shock even suggests improvement in myocardial mitochondrial function (36). To increase convective transport as well as adsorption, the application of HVH with filtration volumes ranging from 45 to 215 ml ⁄ kg ⁄ hour was proposed (37).…”