Juho Jalkanen

Compared to Intermittant Claudication Critical Limb Ischemia Is Associated with Elevated Levels of Cytokines.

Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease (PAD) and associated with an extremely poor clinical outcome. In order to understand the possible role of circulating cytokines and poor outcome associated with CLI we compared the circulating cytokine profile of patients with CLI against patients with intermittent claudication (IC). The levels of 48 circulating cytokines were examined in 226 consecutive patients with peripheral artery disease (PAD) admitted for elective, non-urgent, invasive treatment of IC or CLI. The PAD patient cohort was evenly distributed between subjects with IC (46.5%) and CLI (53.5%). As accustomed in PAD, CLI was associated with higher age, chronic kidney disease and diabetes when compared to IC (P < 0.01 for all). In multivariable linear regression modeling taking into account the baseline differences between IC and CLI groups CLI was independently associated with elevated levels of a large number of cytokines: IL-1β, IL-1ra, IL-2Rα, IL-4, IL-6, IL-10, IFN-γ, GM-CSF, G-CSF (P < 0.01 for all), and IL-2, IL-7, IL-12, IL-13, IL-17, bFGF, VEGF, SCGF-β (P < 0.05 for all). The current findings indicate that CLI is associated with a circulating cytokine profile, which resembles serious medical conditions such as severe pancreatitis, sepsis, or even cancer. Compared to IC, CLI is a systemic inflammatory condition, which may explain the extremely poor outcome associated with it.

Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs

The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI.

Data on amputation free survival of patients with lower limb peripheral artery disease classified according TASC II classification and a new crural index.

The results of amputation free survival (AFS) of a cohort of 887 caucasian patients is shown. The data is based on further analyses of data presented in Jalkanen et al. (2016) [1]. The 36-month amputation free survival of patients divided in new crural vessel disease classification (Crural Index), aortoiliac TASC II classification, femoropopliteal TASC II classification and most severe segment is presented. Also, in depth demographic data is presented for each Crural Index group Jalkanen et al., 2016 [1].

Data on association of ankle pressure and ankle brachial index of symptomatic and contralateral lower extremities with overall and cardiovascular mortality in patients with lower extremity peripheral artery disease

Data on survival curves for overall survival and freedom from cardiovascular death at different ankle brachial index (ABI) and ankle pressure (AP) are shown separately for symptomatic and contralateral lower limbs in 721 patients with lower extremity peripheral artery disease at up to 7 years follow-up. Cox regression analysis with confounding factors for ABI and AP are also shown. Dates and causes of death were collected from the Finnish national statistics registry.

Correlation between increasing tissue ischemia and circulating levels of angiogenic growth factors in peripheral artery disease

HighlightsSystemic levels of VEGF associated growth factors correlate with increasing Rutherford grade.Increasing Rutherford grade correlates with increasing systemic levels of VEGF, HGF and bFGF.Increasing Rutherford grade correlates inversely with decreasing systemic levels of PDGF. Introduction: The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades. Methods: The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle‐brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements. Results: The levels of VEGF (P = 0.009) and HGF (P < 0.001) increased significantly as the ischaemic burden became more severe according to the Rutherford grades. PDGF behaved in opposite manner and declined along increasing Rutherford grades (P = 0.004). A significant, inverse correlations between Rutherford grades was detected as follows; VEGF (Pearson’s correlation = 0.183, P = 0.004), HGF (Pearson’s correlation = 0.253, P < 0.001), bFGF (Pearson’s correlation = 0.169, P = 0.008) and PDGF (Pearson’s correlation = 0.296, P < 0.001). In addition, VEGF had a clear direct negative correlation with ABI (Pearson’s correlation −0.19, P = 0.009) and TP (Pearson’s correlation −0.20, P = 0.005) measurements. Conclusions: Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end‐stage PAD.