Calculated whole blood viscosity in non-diabetic subjects with asymptomatic carotid atherosclerosis: How insulin resistance may affect blood viscosity.

BACKGROUND AND OBJECTIVE: Asymptomatic atherosclerosis is an important early marker of vascular damage and, among its risk factors, hemorheological alterations play an important role. PATIENTS AND METHODS: In a cohort of 85 non-diabetic subjects with asymptomatic carotid atherosclerosis (ACA), we have measured whole blood viscosity (cWBV) according to the haematocrit and plasma fibrinogen level. The cWBV distinguish the subgroup of ACA subjects with 3-5 cardiovascular risk factors (CRFs) from that with 1-2 CRFs and the same behavior is present for haematocrit and plasma fibrinogen level. Therefore, we divided the whole group of ACA subjects according to the medians of the four surrogate indexes with an insulin resistance degree of TG/HDL-C, TyG, VAI and LAP. RESULTS: The analysis of the correlation between cWBV and each index of insulin resistance has shown that no correlation is present in the whole group and in the group of ACA subjects with 1-2 CRFs, while in the subgroup with 3-5 CRFs there is a positive correlation between cWBV with TG/HDL-C and TyG at a low degree of statistical significance. CONCLUSIONS: The date underline that subjects with this clinical condition have an unaltered evaluation of the cWBV compared to the other indices.

Changes in RDW according to prognostic predictors in newly diagnosed multiple myeloma.

RDW is an erythrocyte index that increase in multiple myeloma, in which it appears to have an important role in predicting outcome. For this reason, we performed a retrospective analysis to evaluate the relationships of RDW with some important prognostic predictors. Specifically, in a cohort of 190 newly diagnosed multiple myeloma patients, we have examined the behaviour of RDW and its trend in relation to the ISS stage and other prognostic factors, such as albumin, beta-2 microglobulin, LDH and bone marrow plasma cell infiltration. We performed the analysis in the entire cohort of patients and in the three different disease isotypes (Light chain, IgA, and IgG multiple myeloma). The evaluation of RDW in the different isotypes was made with the Kruskal-Wallis test, integrated by the Dunn test. The comparison between the subgroups allocated above and below the median value of each prognostic factor, was made with the Mann-Whitney test. From our analysis, we observed that RDW is higher in the IgA multiple myeloma, and it increases significantly from ISS I to III. Moreover, RDW increases in the presence of lower albumin values, higher levels of beta2-microglobulin and LDH and in the presence of a greater bone marrow plasma cell infiltrate.

The unpredictable erythrocyte deformability alteration in some hematological disorders: How the classification of primary hyperviscosity syndromes could change.

According to Wells classification, it is possible to distinguish the primary hyperviscosity syndromes in polycythemic, sclerocythemic and sieric and/or plasmatic. In polycythemia vera, multiple myeloma, Waldenström's macroglobulinemia, and monoclonal gammopathy of undetermined significance, we have observed an unexpected behaviour of the erythrocyte deformability. This data highlights that the hemorheological alteration present in polycythemia vera has not been related to the increase of RBC mass only, as well as that present in plasmacellular dyscrasias has not been attributable to the increase of plasma viscosity only.The aim of this paper is to suggest some starting points for an accurate reflection, emphasizing the need of a revision of the current classification of primary hyperviscosity syndromes.

An assessment of the hemorheological profile in patients with subclinical carotid atherosclerosis divided in relation to the number of cardiovascular risk factors and different degrees of insulin resistance.

We present a cohort of 100 subjects [43 men and 57 women; median age 66.00(25)] who were tested using carotid ultrasound to identify subclinical carotid atherosclerosis (SCA). We have evaluated the behaviour of whole blood viscosity (WBV) at high (450 s-1) and low (0.51 s-1) shear rates, plasma viscosity (450-1), hematocrit and mean erythrocyte aggregation. When compared to normal control subjects, using the Mann-Whitney test, we observed in SCA patients a significant increase in WBV only. The results were substantial after having divided the SCA subjects according to the cardiovascular risk factors (CRFs) and the degree of insulin resistance; the research was performed using two surrogate indexes such as TG/HDL-C and TyG. With the division carried out according to CRFs, employing the Kruskal-Wallis test, results show a significant increase in WBV (at high and low shear rates), in plasma viscosity, in erythrocyte aggregation and plasma fibrinogen level. Whereas by dividing them into the median of TG/HDL-C and TyG, we noticed a significant increase in WBV (at high and low shear rates) and in erythrocyte aggregation in the two groups with high TG/HDL-C ratio and with high TyG; having found an increased level of plasma fibrinogen in the latter. The data underlines the role of the main hemorheologic aspects in subclinical carotid atherosclerosis being closely correlated to the CRFs and different degrees of insulin resistance.

Haemorheological profile in congenital afibrinogenemia and in congenital dysfibrinogenemia: A clinical case report.

Although the inherited quantitative and qualitative disorders of fibrinogen are rare, in the course of time patients may develop complications including episodes of arterial and venous thrombosis. It can be useful to complete the laboratory assessment of these clinical conditions with the evaluation of the haemorheological profile. The data obtained from this study showed that congenital afibrinogenemia was characterized by a primary plasma hypoviscosity, whereas congenital dysfibrinogenemia by a primary plasma hyperviscosity. Both these haemorheological alterations may concur, with different mechanisms, to the pathogenesis of thrombotic vascular complications.

Erythrocyte deformability and hemorheological profile in multiple myeloma.

The hemorheological profile in multiple myeloma (MM) has been extensively studied. Our investigation regarded the behavior of whole-blood viscosity, plasma viscosity and erythrocyte deformability in MM. We enrolled 24 MM patients; 13 of them had been recently diagnosed and were at the initial stage of therapy, 6 were on consolidation/conservation therapy and 5 had achieved a complete remission. On fasting venous blood we evaluated whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit×100, the ratio between plasma viscosity at low and high shear rate and the erythrocyte deformability examined by using laser diffractometry and expressed as elongation index. A significant increase in plasma viscosity at low shear rate and a marked decrease in haematocrit were observed in MM patients compared with normal controls. Also the ratio between the high shear rate whole-blood viscosity and haematocrit ×100 and the ratio between the low and high shear rate plasma viscosity were significantly increased in MM patients. A significant decrease in erythrocyte deformability, especially at low shear stresses, was found. We discuss some hypotheses that might explain the behavior of red blood cell deformability in MM, considering that its impairment, in addition to the increase of plasma viscosity, can alter the microcirculatory flow in these patients.

Hemorheological parameters in Monoclonal Gammopathy of Undetermined Significance (MGUS).

There is scarcity of information about the hemorheological pattern in subjects with Monoclonal Gammopathy of Undetermined Significance (MGUS). This preliminary research is focused on the behaviour of whole-blood and plasma viscosity, haematocrit and erythrocyte deformability in the above clinical condition. We enrolled 21 MGUS subjects (10 women and 11 men; mean age 66.4 ± 11.6 years). In fasting venous blood we examined whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit × 100, the ratio between plasma viscosity at low and high shear rate, and the erythrocyte deformability expressed as elongation index. By comparing normal controls to MGUS subjects a significant increase in whole-blood viscosity at high shear rate and in plasma viscosity at low shear rate were observed. In MGUS subjects the ratios between the high and low shear rate blood viscosity and haematocrit × 100, as well as the ratio between the low and high shear rate plasma viscosity were significantly higher. In MGUS subjects a marked decrease in erythrocyte deformability was also observed. The alteration of the hemorheological profile found in these subjects might be involved in the pathogenesis of thromboembolic events, which occur with a high frequency in MGUS.

Analysis of electrolyte abnormalities and the mechanisms leading to arrhythmias in heart failure. A literature review.

About 50% of deaths from heart failure (HF) are sudden, presumably referable to arrhythmias. Electrolyte and acid-base abnormalities are a frequent and potentially dangerous complication in HF patients. Their incidence is almost always correlated with the severity of cardiac dysfunction; furthermore leading to arrhythmias, these imbalances are associated with a poor prognosis. The frequency of ventricular ectopic beats and sudden cardiac death correlate with both plasma and whole body levels of potassium, especially in alkalemia. The early recognition of these alterations and the knowledge of the pathophysiological mechanisms are useful for the management of these HF patients.

Erythrocyte deformability, plasma lipid peroxidation and plasma protein oxidation in a group of OSAS subjects.

Considering that obstructive sleep apnea syndrome (OSAS) is usually associated with endothelial dysfunction, atherosclerosis and cardiovascular disorders, our aim was to examine the erythrocyte deformability and the oxidative status in a group of OSAS subjects. We consecutively enrolled 48 subjects with OSAS defined after a 1-night cardiorespiratory sleep study, subsequently subdivided according to the apnea/hypopnea index (AHI) value in two subgroups: Low (L = 21 subjects with AHI<30) and High (H = 27 subjects with AHI>30). We evaluated the erythrocyte deformability, expressed as elongation index (EI) and the parameters of the oxidative status, such as lipid peroxidation (expressed as thiobarbituric acid-reactive substances - TBARS) and protein oxidation (measured as carbonyl groups - PC). In the entire group and in the two subgroups of OSAS subjects we found a decreased erytrocyte deformability at all shear stresses, not correlated with the plasmatic oxidative stress nor with the polysomnographic parameters. Lipid peroxidation was increased in the whole group and in the H subgroup of OSAS while protein oxidation showed a different trend. As in OSAS the osmotic fragility and the metabolism of the red cells seem to be not impaired, the oxidative damage to the red cell membrane proteins might be responsible for the reduced erythrocyte deformability. This rheological alteration, in addition to the increase in whole blood and plasma viscosity and to the erythrocyte hyperaggregation, could influence the microcircolatory profile in OSAS subjects.

Behaviour of the neutrophil to lymphocyte ratio in young subjects with acute myocardial infarction.

In the last years the neutrophil to lymphocyte ratio (NLR) has been examined in cardiovascular disorders and in particular in coronary artery disease and acute myocardial infarction (AMI). Now we examined this parameter in subjects with juvenile myocardial infarction at the initial stage and after 3 and 12 months. We enrolled 123 young subjects (112 men and 11 women, mean age 39.4 ± 5.8 yrs) with AMI. The time interval between the AMI onset and the investigation was 13 ± 7 days. The mean value of NLR observed in young AMI subjects was significantly increased compared to normal controls (N = 1.817 ± 0.711; young AMI subjects = 2.376 ± 0.873, p <  0.0001). NLR does not discriminate STEMI (2.427 ± 0.878) and non STEMI (2.392 ± 0.868) or diabetics (2.604 ± 1.000) and non diabetics (2.324 ± 0.853), but it differentiates smokers (2.276 ± 0.853) and non smokers (2.837 ± 1.072). NLR at the initial stage is not correlated with the number of cardiovascular risk factors or with the extent of the coronary disease. In this study we found a significant decrease of neutrophil count at 3 and 12 months later AMI without any significant variation of lymphocyte and consequently we observed a decrease in NLR at these two intervals of time in comparison with the initial stage. Despite some limitations present in this study, it is interesting to underline that also in juvenile myocardial infarction this low-cost haematological marker may be considered together with other inflammatory indicators.

Matrix metalloproteases as a pharmacological target in cardiovascular diseases.

OBJECTIVE: Matrix metalloproteases (MMPs) are involved in the development and the progression of atherosclerosis and are related to an elevated risk of cardiovascular morbidity and mortality. An altered profile of MMPs and their tissue inhibitors (TIMPs) has been demonstrated in arterial hypertension, diabetes mellitus, obesity, metabolic syndrome and in cardiovascular disorders, such as coronary artery disease, atrial fibrillation, and heart failure. MATERIALS AND METHODS: The aim of this review was to examine the literature data regarding the possible effects of some molecules, commonly employed in subjects with cardiovascular disease, on the expression and the activity of MMPs and TIMPs. A search was conducted with PubMed, Medline, using combinations of the terms "matrix metalloproteases," "TIMP," "activity regulation," "pharmacological therapy," "cardiovascular disease," "antihypertensives," "antidiabetic drugs," "statins" and "antiplatelet agents". Review articles were also searched. RESULTS: Several drugs, and in particular diuretics, calcium-channel blocker, angiotensin receptor blockers, ACE inhibitors, statins, antidiabetic and antiplatelet agents, seem to influence, in different ways, the MMP pattern with beneficial effects on cardiovascular outcomes. CONCLUSIONS: Keeping in mind these findings, the therapeutic strategy must be reconsidered in order to obtain a sensible MMP inhibition.

Employment of vasopressin receptor antagonists in management of hyponatraemia and volume overload in some clinical conditions.

WHAT IS KNOWN AND OBJECTIVE: Hyponatraemia, the most common electrolyte imbalance occurring in hospitalized subjects, is usually classified as hypovolaemic, euvolaemic or hypervolaemic. Hyponatraemia is a predictor of death among subjects with chronic heart failure and cirrhosis. The inappropriate secretion of the antidiuretic hormone (AVP) seems to be of pivotal importance in the decline of serum sodium concentration in these clinical conditions. The objective of this review was to summarize recent progress in management of hyponatraemia in SIADH, cirrhosis and heart failure. METHODS: Literature searches were conducted on the topics of hyponatraemia and vasopressin receptor antagonists, using PubMed, pharmaceutical company websites and news reports. The information was evaluated for relevance and quality, critically assessed and summarized. RESULTS AND DISCUSSION: The initial treatment of severe hyponatraemia is directed towards the prevention or management of neurological manifestations and consists of an intravenous infusion of hypertonic saline. Fluid restriction is indicated in oedematous states. Diuretics alone or in combination with other specific drugs remain the main strategy in the management of volume overload in heart failure. In resistant cases, ultrafiltration can lead to effective removal of isotonic fluid preventing new episodes of decompensation; however, aquapheresis is associated with increased costs and other limits. In several trials, the efficacy of vasopressin receptor antagonists in euvolaemic patients (inappropriate antidiuretic hormone secretion) or in hypervolaemic hyponatraemia (chronic heart failure, cirrhosis) has been evaluated. It was found that vaptans, which promote aquaresis, were superior to a placebo in raising and maintaining serum sodium concentrations in these subjects. WHAT IS NEW AND CONCLUSIONS: Combined with conventional therapy, vasopressin receptor antagonists (AVP-R antagonists) are able to increase the excretion of electrolyte-free water and the sodium concentration. Further studies are needed to assess efficacious outcomes of aquaresis compared with aquapheresis and with conventional therapy.

Analysis of the correlations between oxidative stress, gelatinases and their tissue inhibitors in the human subjects with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is commonly associated with endothelial dysfunction, atherosclerosis and cardiovascular disorders. On the basis of this observation, our aim was to examine the oxidative status and the matrix metalloproteases (MMP) profile in a group of subjects with OSAS. We enrolled 48 subjects with OSAS defined after a 1-night cardiorespiratory sleep study, who were subsequently subdivided in two subgroups according to the severity of OSAS (low grade = L-OSAS; high grade= H-OSAS). We measured the parameters of oxidative stress, such as lipid peroxidation, protein oxidation, total antioxidant status (TAS), nitric oxide metabolites (NOx), and the plasma concentrations of the gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). We found a significant impairment of oxidative status in H-OSAS compared to L-OSAS and higher plasma levels of MMP-9 and TIMP-1 in H-OSAS compared to L-OSAS. In this study we observed a positive correlation between TBARS and MMP-9, a positive correlation between PC and MMP-9, and a negative correlation between NOx and MMP-9, especially in the whole group of OSAS subjects. These data underline how strong interrelationships among some parameters of the oxidative stress, in particular those reflecting lipid peroxidation, protein oxidation and NOx, and MMP-9 are evident in OSAS subjects. All these information may be useful in the clinical practice keeping in mind the cardiovascular complications generally accompanying the obstructive sleep apnea syndrome.

Behaviour of the plasma concentration of gelatinases and their tissue inhibitors in subjects with venous leg ulcers.

Venous leg ulcers are common in subjects with chronic venous insufficiency. The increased intraluminal pressure causes alteration of the skin microcirculation, leukocyte activation and release of proteolytic enzymes leading to ulceration. An impaired expression and activity of matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) might influence extracellular matrix degradation and deposition in chronic venous ulcers with the failure of the healing process. Our aim was to evaluate plasma concentration of gelatinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in subjects with venous leg ulcers before and after the compression therapy. We enrolled 36 subjects (12 men and 24 women, mean age 67.38 ± 12.7 yrs) with non-infected venous leg ulcers (CEAP C6), which underwent a color Duplex scan examination of the veins and arteries of the inferior limbs and were treated with a multi-layer bandaging system. The ulcer healing was obtained in 23 subjects only (9 men and 14 women). We evaluated, on fasting venous blood, the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 using ELISA kit, before and after the treatment. We observed a significant increase in plasma concentration of gelatinases and their inhibitors and in MMP-2/TIMP-2 ratio in subjects with leg ulcers in comparison with normal controls. In subjects with healed ulcers we found a decrease in MMP-9 and TIMP-1 levels and in MMP-2/TIMP-2 ratio compared to the baseline values, although higher levels of all the examined parameters in comparison with normal controls. In conclusion, plasma MMPs profile is impaired in subjects with venous leg ulcers and it improves after the healing, persisting anyway altered in respect to healthy controls.

Protein carbonyl groups in trained subjects before and after a cardiopulmonary test.

Physical exercise influences the body's oxidative status. The modifications can involve lipids, proteins and nucleic acids, and different effects seem to be induced by regular and acute exercise respectively. We examined protein oxidation, expressed as concentration of protein carbonyl groups (PC), in trained subjects before (time 0), 10 min (time 1) and 24 hours (time 2) after a cardiopulmonary test performed on a cycloergometer. We enrolled 38 trained subjects (26 men and 12 women), subdivided in two groups (A1 and B1) of 19 subjects each, according to the median value of VO2max, and in two groups (A2 and B2) of 19 subjects each, according to the median value of PC at baseline. PC concentration was measured by an enzyme-linked immunosorbent assay (ELISA). The groups A1 and B1 did not differ from each other as regards the basal PC level and groups A2 and B2 were not different as regards the VO2max. At time 1 PC showed a significant increase in comparison with baseline in trained subjects as a whole group, as well as in each subgroup. At time 2, PC were decreased in comparison with both times 0 and 1 in the whole group and in subgroups A1 and B2, whereas in subgroups A2 and B1 the PC value at time 2 was not different compared to time 0. The percentage increase of PC at time 1 vs time 0, as well as the percentage decrease at time 2 vs time 1 and time 0 respectively, were not different between subgroups A1 and B1. On the contrary, the percentage variations observed at each interval were significantly different between subgroups A2 and B2. The results suggest a reaction of antioxidant systems to acute exercise in trained subjects, influenced by basal PC levels more than by aerobic fitness.

Study of the correlations among some parameters of the oxidative status, gelatinases, and their inhibitors in a group of subjects with metabolic syndrome.

Our aim was to examine some parameters of oxidative status, gelatinases, and their inhibitors and to evaluate their interrelationships in subjects with metabolic syndrome (MS). We enrolled 65 MS subjects, subdivided according to the presence or not of diabetes mellitus. We examined lipid peroxidation (expressed as thiobarbituric acid reacting substances, TBARS), protein oxidation (expressed as carbonyl groups), nitric oxide metabolites (NO x ), total antioxidant status (TAS), MMP-2, MMP-9, TIMP-1, and TIMP-2. We found that MS subjects, diabetics and nondiabetics, showed an increase in TBARS, PC, and NO x . A significant decrease in TAS was observed only in nondiabetic MS subjects in comparison with diabetic MS subjects. We observed increased concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2, higher in diabetic subjects. Our data showed a positive correlation between TAS and MMP-2, TAS and MMP-9, and TAS and MMP-9/TIMP-1 and a negative correlation between TBARS and MMP-2 in diabetic MS subjects in the entire group. In MS subjects a prooxidant status and increased levels of gelatinases and their inhibitors are evident although the correlations between oxidative stress and MMPs or TIMPs are controversial and need further investigation.

Nitric oxide metabolites (nitrite and nitrate) in several clinical condition.

We determined the concentration of nitric oxide metabolites (NO2-+NO3-), expressed as NOx, in several clinical conditions. Regarding this, we have examined 25 subjects with arterial hypertension, 41 subjects with chronic kidney disease in conservative treatment, 106 subjects with metabolic syndrome subdivided according to the presence (n = 43) or not (n = 63) of diabetes mellitus, 48 subjects with obstructive sleep apnea syndrome (OSAS), 14 women with systemic sclerosis complicated with Raynaud's phenomenon, 42 dialyzed subjects and 105 young subjects with acute myocardial infarction (AMI). In subjects with arterial hypertension, chronic kidney disease, metabolic syndrome, systemic sclerosis, as well as, in dialyzed and AMI subjects, we found at baseline a NOx increase. In dyalized subjects after a standard dialysis session, we observed a decrease in NOx. The increase in NOx in juvenile AMI was significantly influenced by cigarette smoking and less by cardiovascular risk factors and the extent of coronary lesions; at 3 and 12 months later than the initial event, we observed a decrease of NOx that remains significantly higher than the control group. In subjects with OSAS no difference in NOx was noted in comparison with normal controls, although their subdivision according to the apnea/hypopnea index operates a clear distinction regarding NOx concentration.

Lipid peroxidation and protein oxidation are related to the severity of OSAS.

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is associated with elevated cardiovascular morbidity and mortality. Considering that oxidative stress is involved in endothelial dysfunction and atherosclerosis development, our aim was to examine lipid peroxidation and protein oxidation, two parameters of oxidative status, in a group of subjects with OSAS. PATIENTS AND METHODS: We consecutively enrolled 48 patients (36 men and 12 women; mean age 49.7±14.6 yrs) with OSAS, subsequently subdivided according to the apnea/hypopnea index (AHI) value in two subgroups: Low (L= 21 subjects with AHI<30) and High (H= 27 subjects with AHI>30). We examined lipid peroxidation, expressed as TBARS, and protein oxidation, measured as carbonyl groups in plasma samples from fasting venous blood. RESULTS: We observed that TBARS and carbonyl groups were significantly higher in subjects with AHI > 30 in comparison with the L subgroup and the whole group of OSAS subjects. In addition, we found that these parameters were positively correlated with neck and waist circumference, with the AHI value and with the oxygen desaturation index, and negatively correlated with the mean oxygen saturation. CONCLUSIONS: Lipid peroxidation and protein oxidation in OSAS patients are significantly correlated with the severity of the disease.

Marked elevation of transaminases and pancreatic enzymes in severe malnourished male with eating disorder.

We report a case of a 45 year old Caucasian malnourished male with an history of eating disorder who developed severe liver and pancreatic damage and multiorgan disfunction. At admission to our department, his body mass index (BMI) was 11.1. Biochemical evaluation showed elevated serum levels of transaminases (AST= 2291 U/L, ALT= 1792 U/L), amylase (3620 U/L), lipase (4102 U/L), CPK= 1370 U/L, LDH= 2082 U/L. No other cause of acute liver and pancreatic damage was evidenced. Haematological disorders (anemia, thrombocytopenia, leukopenia) found on admission seem related to bone marrow hypoplasia and to gelatinous marrow transformation described in severe state of malnutrition. Although a moderate increase in liver and pancreatic enzymes are a common finding in malnourished patients, only a small number of reports describes severe liver injury and multiorgan dysfunction. After a few days of treatment (hydration and nutritional support) a marked decrease of serum transaminases, lipase, amylase, CPK, LDH occurred, despite a transient increase in these levels secondary to refeeding syndrome. The association of chronic malnutrition and a decrease in systemic perfusion may be responsible for multiorgan dysfunction. In our patient the high levels of transaminases and pancreatic enzymes were the most important biochemical abnormalities normalized after refeeding.

[The role of lactate besides the lactic acidosis]. / Il ruolo del lattato oltre l'acidosi lattica.

Lactic acidosis (LA) is the most common form of metabolic acidosis defined by values of lactate greater than 5 mmol / l and by a pH <7.34. The pathogenesis of LA involves hypoxic (type A) and non hypoxic (type B) causes which are often coexisting. Lactic acidosis is usual in hospitalized population especially in subjects in intensive care units, in which lactate levels on admission could be predictors of mortality even in the absence of organ dysfunction or shock. The outcome is mainly dependent on the cardiovascular effects of acidosis. In subjects with cardiogenic shock, the increased lactate/pyruvate ratio, detectable at onset, is correladed with mortality. An early assessment of blood and tissue lactate levels could play a role in the therapeutic management as well as in outcome. LA could be a unfavorable prognostic factor in cancer. The lactate would act also as "signal molecule" and as a promoting factor in angiogenesis and tumor progression. In the presence of risk factors for LA the role of metformin may be overrated. Despite the doctrinal progress to understand the pathogenesis and pathophysiology, there is not univocal consensus on the therapeutic treatment of LA. The identification and the attempt to remove the cause of acidosis are main aims; treatment with sodium bicarbonate is a matter of debate as the data on the cardiovascular effects and mortality are unclear. The therapy with carbicarb, dichloroacetate or THAM has shown no specific advantages in terms of mortality. In experimental models of LA and shock the use of sodium-hydrogen exchanger-1 (NHE1) selective inhibitors reduces cell damage and inflammatory cytokines synthesis; it also improves cardiac performance and decreases mortality.