The Acute Phase of Experimental Cardiogenic Shock Is Counteracted by Microcirculatory and Mitochondrial Adaptations

Abstract

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.

Protective Effects of Ivabradine (Alone and Combined With Atenolol or Enalapril) on Experimentally-Induced Acute Myocardial Infarction in Albino Rats

“…These findings are in accordance with those obtained by Liu et al [22] , which could be explained by development of cardiogenic shock or low cardiac output state associated with MI [23,24] . In the present study, pretreatment of rats with ivabradine, atenolol, enalapril, ivabradine with atenolol and ivabradine with enalapril did not significantly reduce the MABP in comparison with their baseline values.…”

Recruitment of non‐perfused sublingual capillaries increases microcirculatory oxygen extraction capacity throughout ascent to 7126 m

“…In other conditions, such as in a pig model of acute heart failure, recruitment of the sublingual microcirculation has been observed (Stenberg et al . ), indicating a compensation mechanism intrinsic to the intact microcirculation to improve microcirculatory function independent of dysfunction of the systemic circulation. Similarly, our data are consistent with a mechanism induced by exposure to high altitude where an increase in TVD is identified as an intrinsic capillary compensation response to the observed decrease in arterial oxygen content and global delivery of oxygen, as a means of increasing oxygen availability in the microcirculation alongside an increase in haematocrit.…”

A total closed chest sheep model of cardiogenic shock by percutaneous intracoronary ethanol injection

“…The number of injected sites depended on the systemic hemodynamic consequences of necrosis extension. In accordance with previous animal models 5,8,9,12 , CS obtention was defined as a drop of more than 30% in mean arterial pressure and/ or cardiac index associated to a rise of lactate concentration above 2.5 mmol L −1 in the hour following the last alcoholisation. Twenty-four animals underwent intracoronary alcoholisation (SHOCK group) and eight sham animals underwent interventricular coronary artery catheterization without any alcoholisation (SHAM group).…”