IntroductionHypercapnic acidosis (HCA) that accompanies lung-protective ventilation may be considered permissive (a tolerable side effect), or it may be therapeutic by itself. Cardiovascular effects may contribute to, or limit, the potential therapeutic impact of HCA; therefore, a complex physiological study was performed in healthy pigs to evaluate the systemic and organ-specific circulatory effects of HCA, and to compare them with those of metabolic (eucapnic) acidosis (MAC).MethodsIn anesthetized, mechanically ventilated and instrumented pigs, HCA was induced by increasing the inspired fraction of CO2 (n = 8) and MAC (n = 8) by the infusion of HCl, to reach an arterial plasma pH of 7.1. In the control group (n = 8), the normal plasma pH was maintained throughout the experiment. Hemodynamic parameters, including regional organ hemodynamics, blood gases, and electrocardiograms, were measured in vivo. Subsequently, isometric contractions and membrane potentials were recorded in vitro in the right ventricular trabeculae.ResultsHCA affected both the pulmonary (increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR)) and systemic (increase in mean arterial pressure (MAP), decrease in systemic vascular resistance (SVR)) circulations. Although the renal perfusion remained unaffected by any type of acidosis, HCA increased carotid, portal, and, hence, total liver blood flow. MAC influenced the pulmonary circulation only (increase in MPAP and PVR). Both MAC and HCA reduced the stroke volume, which was compensated for by an increase in heart rate to maintain (MAC), or even increase (HCA), the cardiac output. The right ventricular stroke work per minute was increased by both MAC and HCA; however, the left ventricular stroke work was increased by HCA only. In vitro, the trabeculae from the control pigs and pigs with acidosis showed similar contraction force and action-potential duration (APD). Perfusion with an acidic solution decreased the contraction force, whereas APD was not influenced.ConclusionsMAC preferentially affects the pulmonary circulation, whereas HCA affects the pulmonary, systemic, and regional circulations. The cardiac contractile function was reduced, but the cardiac output was maintained (MAC), or even increased (HCA). The increased ventricular stroke work per minute revealed an increased work demand placed by acidosis on the heart.

Sepsis is the most common cause of acute kidney injury (AKI). There has been a growing body of evidence demonstrating the association between worsening of kidney function during sepsis and the risk of short- and long-term mortality. AKI in sepsis is associated with poor outcome and independently predicts increased mortality. Sepsis-associated AKI may therefore serve as a biomarker of adverse physiological events that portends worse outcome. Conversely, the important role of sepsis among intensive care unit patients with nonseptic AKI is increasingly being recognized. Indeed, sepsis represents a significant contributing factor to the overall mortality and incomplete recovery of kidney function in subjects who developed nonseptic AKI. Because AKI portends such an ominous prognosis in sepsis and vice versa, there has been a surge of interest in elucidating mechanisms underlying the complex and bidirectional nature of the interconnections between AKI, sepsis and multiorgan dysfunction. Accumulating data indicate that AKI can trigger several immune, metabolic and humoral pathways, thus potentially contributing to distant organ dysfunction and overall morbidity and mortality. The expanding population of patients with sepsis and AKI, and the associated excess mortality provide a strong basis for further research aimed at addressing more rigorously all potentially modifiable factors to reduce this burden to patients and health care systems. Better insights into bidirectional and synergistic pathways linking sepsis and AKI might open the window for new therapeutic approaches that interrupt this vicious circle. Here, we discuss the rationale for and the current understanding of the bidirectional relationship between AKI and sepsis.