Neural regulation of cardiovascular response to exercise: role of central command and peripheral afferents

During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discusse

The systematic guideline review: method, rationale, and test on chronic heart failure

Background: Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources-especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development-the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF). Methods: A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline. Results: Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) - the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer. Conclusion: The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines

Continuous and accumulated bouts of cycling matched by intensity and energy expenditure elicit similar acute blood pressure reductions in prehypertensive men

The present study investigated differences in postexercise hypotension (PEH) after continuous versus accumulated isocaloric bouts of cycling. Ten pre-hypertensive men, aged 23 to 34 yrs, performed two bouts of cycling at 75% oxygen uptake reserve, with total energy expenditures of 400 kcal per bout. One exercise bout was performed continuously (CONTIN) and the other as two smaller bouts each expending 200 kcal (INTER1 and INTER2). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and cardiac autonomic control were monitored in a supine position for 10 min before and 60 min after each exercise bout, and during a control session. Compared to control, blood pressure was significantly reduced after CONTIN (SBP: ∆-3.4 mmHg, P < 0.001; MAP: ∆-2.5 mmHg, P = 0.001), INTER1 (SBP: ∆-2.2 mmHg, P = 0.045) and INTER2 (SBP: ∆-4.4 mmHg, P < 0.001; DBP: ∆-2.7 mmHg, P = 0.045; MAP: ∆-3.3 mmHg, P = 0.001). The PEH was similar in CONTIN and INTER2, while INTER2 elicited greater PEH than INTER1 (SBP and MAP: ∆-2.0 and ∆-1.8 mmHg, respectively, P < 0.05). Increases in sympathovagal balance from baseline were inversely related to changes in SBP and DBP after CONTIN and INTER2 (r = -0.64 to -0.71; P = 0.021 to P = 0.047). These findings indicate similar amounts of PEH are observed when exercise is performed as a single 400 kcal exercise bout or 2 x 200 kcal bouts and that the exercise recovery pattern of cardiac autonomic activity may be important in eliciting PEH

Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk:Rationale and design of the ODYSSEY DM-INSULIN trial

Aims: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk. Methods: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening. ≥. 70. mg/dL (1.81. mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24. weeks of alirocumab 75. mg every 2. weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C. ≥. 70. mg/dL at week 8 underwent a blinded dose increase to 150. mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety. Results: This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017. Conclusion: The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy

Fibrin clot properties independently predict adverse clinical outcome following acute coronary syndrome: a PLATO substudy

Aims: To determine whether fibrin clot properties are associated with clinical outcomes following acute coronary syndrome (ACS). Methods and results: Plasma samples were collected at hospital discharge from 4354 ACS patients randomized to clopidogrel or ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. A validated turbidimetric assay was employed to study plasma clot lysis time and maximum turbidity (a measure of clot density). One-year rates of cardiovascular (CV) death, spontaneous myocardial infarction (MI) and PLATO-defined major bleeding events were assessed after sample collection. Hazard ratios (HRs) were estimated using Cox proportional hazards models. After adjusting for CV risk factors, each 50% increase in lysis time was associated with CV death/spontaneous MI [HR 1.17, 95% confidence interval (CI) 1.05-1.31; P  0.05). Neither lysis time nor maximum turbidity was associated with major bleeding events. Conclusion: Fibrin clots that are resistant to lysis independently predict adverse outcome in ACS patients. Novel therapies targeting fibrin clot properties might be a new avenue for improving prognosis in patients with ACS

Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery : the Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery of the European Society of Cardiology (ESC) and endorsed by the European Society of Anaesthesiology (ESA)

Non-cardiac surgery; Pre-operative cardiac risk assessment; Pre-operative cardiac testing; Pre-operative coronary artery revascularization; Perioperative cardiac management; Renal disease; Pulmonary disease; Neurological disease; Anaesthesiology; Post-operative cardiac surveillanc