Metabolic and neurohumoral aspects of acute myocardial ischemia in man

This thesis aims at defining the relevance and applicability of some metabolic aspects of acute myocardial ischemia to delineate occurrence and extent of the latter in man. Studies focus on myocardial lactate metabolism and adenine nucleotide catabolism, correlate changes with other markers of ischemia and attempt to define a temporal relation with regional changes in coronary flow. Next, the acute antiischemic properties of different vasoactive compounds are outlined using these metabolites in a properly defined study model. Studies also attempt to differentiate the usefulness of various vasodilator compounds as antiischemic therapy in relation to the underlying cardiac function. In the second part of this thesis the impact of myocardial ischemia on systemic and cardiac neurohormones, i.e. catecholamines and renin-angiotensin system(s), are discussed. The relation between degree of ischemia and neurohumoral activation will be emphasized, potential subsequent systemic and coronary vasoconstrictor effects mentioned, and the usefulness of neurohumoral modulation, i.e. by converting enzyme inhibition in the treatment of myocardial ischemia indicated

The consistency of the treatment effect of an ACE-inhibitor based treatment regimen in patients with vascular disease or high risk of vascular disease: A combined analysis of individual data of ADVANCE, EUROPA, and PROGRESS trials

AimsAngiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using individual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of perindopril-based regimen in patients with vascular disease or at high risk of vascular disease.Methods and resultsWe studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a perindopril-based treatment regimen or placebo. The perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89; 95 confidence interval (CI) 0.82-0.96; P = 0.006], cardiovascular mortality (HR 0.85; 95 CI 0.76-0.95; P = 0.004), non-fatal myocardial infarction (HR 0.80; 95 CI 0.71-0.90; P < 0.001), stroke (HR 0.82; 95 CI 0.74-0.92; P = 0.002), and heart failure (HR 0.84; 95 CI 0.72-0.96; P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure.ConclusionThis study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (perindopril-indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease

Individualized angiotensin-converting enzyme (ACE)-inhibitor therapy in stable coronary artery disease based on clinical and pharmacogenetic determinants: The PERindopril GENEtic (PERGENE) risk model

Background-Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model. Methods and Results-Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 t

Suradnja geodeta sa sudskim vještacima građevinske struke u postupku legalizacije objekata izgrađenih prije 15. veljače 1968. godine

U radu je opisana važnost prilaganja uporabne dozvole prilikom upisa objekata u zemljišne knjige. Iz novog zakona o državnoj izmjeri i katastru nekretnina (»Narodne novine«, broj 16/07) moguće je zaključiti kako će i katastarskim uredima građevna dokumentacija predstavljati važnu ulogu prilikom ovjere geodetskih elaborata upisa građevina. Detaljno je opisan postupak interakcije građevinskih vještaka sa geodetima prilikom evidentiranja građevina koje su izgrađene prije 15.veljače 1968., a nisu evidentirane u službenoj dokumentaciji Državne geodetske uprave. U radu su navedeni i sastavni dijelovi geodestkih elaborata kao i sastavni dijelovi elaborata o utvrđivanju starosti građevina

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Control of a local neural network by feedforward and feedback inhibition

The signal transfer of a neuronal network is shaped by the local interactions between the excitatory principal cells and the inhibitory interneurons. We investigated with a simple lumped model how feedforward and feedback inhibition in.uence the steady-state network signal transfer. We analyze how the properties ofinhibition a1ect the input/output space ofthe network and compare the results with experimental data obtained in the hippocampal CA1 circuit. The speci4c non-linear transfer of the cell populations determine how feedforward and feedback inhibition modulate the gain and/or shift the network signal transfer. An important biological issue is whether the two forms of inhibition can be combined in the same interneurons. Combining both functions in the same interneurons requires highly non-linear addition of their inputs