Re, Geert Grooteplein 10, 6500 HB Nijmegen, The NetherlandsPhysiological effects of hypercapnic acidosis HCA has a myriad of effects on many physiological processes. The recognition of these effects is important as it will affect the decision whether or not to allow the development of HCA in a specific patient. As outlined below, the final effect of HCA on physiological functions depends on the level of hypercapnia, the context of the subject (healthy versus diseased) and many other factors. Therefore, we will briefly review the physiological effects of HCA.Oxygenation?2010 BioMed Central Ltd?2010 BioMed Central LtdThe beneficial effects of HCA in increasing arterial and tissue oxygenation is evident from multiple in vivo studies [8-16] and has been demonstrated in healthy humans as well [17]. HCA can improve tissue oxygenation by several mechanisms. First, a rightward shift of the oxyhemoglobin dissociation curve during acute respiratory acidosis decreases the affinity of hemoglobin for oxygen and facilitates oxygen release to the tissues (the Bohr effect) [18]. Second, HCA causes vasodilatation in microvessels, promoting oxygen delivery and tissue perfusion. However, high concentrations of PCO2 (>13.3 kPa) will surpass the beneficial vasodilatory effects of HCA and result in vasoconstriction [19]. Third, HCAIjland et al. Critical Care 2010, 14:237 http://ccforum.com/content/14/6/Page 2 ofimproves ventilation-perfusion (V/Q) matching by potentiating hypoxic pulmonary vasoconstriction [15,16]. In contrast, impaired V/Q matching has been demonstrated with HCA in patients with ARDS [20,21]. The differences in V/Q matching in these studies could be explained by the manner in which hypercapnia was achieved – inhaled CO2 [15,16] versus low-volume (pressure-limited) ventilation-induced hypercapnia. In the latter case, atelectasis may develop, leading to increased intrapulmonary shunting [20,21]. As inhaled CO2 theoretically results in a more uniform lung acidosis, it might be superior to low minute ventilation-induced hypercapnia in achieving improved V/Q matching and an anti-inflammatory effect, as has been suggested by Sinclair and colleagues [22]. Fourth, as cardiac output is one of the major determinants of peripheral oxygen delivery, one can expect that a CO2-mediated increase in cardiac output augments peripheral oxygen delivery. However, an increase in cardiac output results in an increase in mixed venous oxygen tension which may lead to an increase in pulmonary shunting due to attenuation of hypoxic pulmonary vasoconstriction [21,23].The lung Pulmonary compliancewith the use of `permissive’ or `therapeutic’ HCA in patients with pulmonary hypertension and depressed right ventricular function.Cardiovascular system Cardiac outputHCA has a Quinoline-Val-Asp-Difluorophenoxymethylketone chemical information direct suppressive effect on cardiac contractility, but it can lead to a net increase in cardiac output by several mechanisms, as has been demonstrated in both animal and human studies [15,17,19,31,33-35]. First, sympathetically mediated release of catecholamines due to neuroadrenal stimulation results in an increase in end-systolic volume and venous return [34,35]. In addition to an increase in heart rate, HCA induces ATPsensitive K+ channel-mediated vasodilation, as has been demonstrated for the brain vasculature and coronary vessels [36,37], which could decreases left ventricular afterload. An increase of 1.33 to 1.60 kPa in PaCO2 increases cardiac index by 14 in the critically ill and healthy PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28381880 mecha.