The mechanisms contributing to multiorgan dysfunction during cardiogenic shock are poorly understood. Our goal was to characterize the microcirculatory and mitochondrial responses following ≥10 hours of severe left ventricular failure and cardiogenic shock. We employed a closed-chest porcine model of cardiogenic shock induced by left coronary microembolization (n = 12) and a time-matched control group (n = 6). Hemodynamics and metabolism were measured hourly by intravascular pressure catheters, thermodilution, arterial and organ specific blood gases. Echocardiography and assessment of the sublingual microcirculation by sidestream darkfield imaging were performed at baseline, 2±1 and 13±3 (mean±SD) hours after coronary microembolization. Upon hemodynamic decompensation, cardiac, renal and hepatic mitochondria were isolated and evaluated by high-resolution respirometry. Low cardiac output, hypotension, oliguria and severe reductions in mixed-venous and hepatic O2 saturations were evident in cardiogenic shock. The sublingual total and perfused vessel densities were fully preserved throughout the experiments. Cardiac mitochondrial respiration was unaltered, whereas state 2, 3 and 4 respiration of renal and hepatic mitochondria were increased in cardiogenic shock. Mitochondrial viability (RCR; state 3/state 4) and efficiency (ADP/O ratio) were unaffected. Our study demonstrates that the microcirculation is preserved in a porcine model of untreated cardiogenic shock despite vital organ hypoperfusion. Renal and hepatic mitochondrial respiration is upregulated, possibly through demand-related adaptations, and the endogenous shock response is thus compensatory and protective, even after several hours of global hypoperfusion.

Pre-treatment with Hp protects the heart against ischaemia-reperfusion injury. This protection is most likely mediated via mitochondrial mechanisms which initiate a signalling cascade that converges on inhibition of opening of MPTP.

Intravital videomicroscopy of sublingual microcirculation is used to monitor critically ill patients. Existing guidelines suggest averaging handheld video recordings of ∼20 s in duration from five areas. We assessed whether an extended observation time may provide additional information on the microcirculation. Pigs (n = 8) under general anesthesia were divided between two groups, one with manually held camera, in which microcirculation was assessed continuously for 1 min in five areas, and one with a fixed camera, in which the observation time was extended to 10 min in a single area. The microcirculation was challenged by infusing arginine vasopressin (AVP). In the fixed group, ischemic acute heart failure was induced by left coronary microembolization, and the AVP infusion was repeated. All recordings were divided into 20-s sequences, and the small-vessel microvascular flow index (MFI) was scored and averaged for each measurement point. When administering 0.003, 0.006, and 0.012 IU·kg(-1)·min(-1) of AVP, we observed that the small-vessel MFI in the fixed 10-min group was significantly reduced (2.03 ± 0.38, 0.98 ± 0.18, and 0.48 ± 0.11) compared with both the initial 20 s (2.77 ± 0.04, 2.06 ± 0.04, and 1.74 ± 0.06; P < 0.05) and the 1-min total (2.63 ± 0.09, 1.70 ± 0.07, and 1.33 ± 0.16; P < 0.05) in the handheld group. In acute heart failure, the cardiac output decreased to half of the preischemic values. Interestingly, the small-vessel MFI was more affected by the administration of 0.001 and 0.003 IU·kg(-1)·min(-1) of AVP in acute heart failure (1.62 ± 0.60 and 1.16 ± 0.38) compared with preischemic values (2.86 ± 0.09 and 2.03 ± 0.38; P < 0.05). In conclusion, a prolonged recording time reveals temporal heterogeneity that may impact the assessment of microcirculatory function.