BACKGROUND: Adrenaline (ADR) is a cornerstone of advanced life support (ALS) in cardiac arrest (CA), although its neurologically favourable survival outcomes remain unclear. ADR increases coronary perfusion pressure (CPP), with levels >15 mmHg associated with successful defibrillation. This study aimed to elucidate the relationship between ADR, myocardial microvascular blood flow, and resuscitation outcomes using a porcine CA model simulating refractory ventricular fibrillation (VF). METHODS: This study involved 24 domestic pigs. After instrumentation, intubation, and baseline measurements, the animals were randomised into the ADR or control (saline) groups. VF was induced, and cardiopulmonary resuscitation was initiated using continuous mechanical chest compressions and ventilation. ADR or saline was administered following ALS guidelines. After 21 min of ALS, defibrillation was performed. Continuous measurements of arterial and venous blood pressures using an electrocardiogram and index of myocardial resistance (IMR) and transit mean time (Tmn) 1 min before and after each injection or peak blood pressure were recorded and compared between the groups. CPP-IMR, amplitude spectrum area (AMSA)-IMR, CPP-Tmn, and AMSA-Tmn correlations were assessed. RESULTS: Compared with six animals in the control group, three in the ADR group achieved a return of spontaneous circulation. No difference was observed in IMR or AMSA; however, significant increases in CPP and arterial end-diastolic blood pressure were observed at several time points. Tmn differed between groups only at two time points. CONCLUSION: Repeated ADR doses during prolonged ALS simulating refractory VF did not improve myocardial microvascular blood flow, as measured using IMR, despite leading to an increase in CPP.

• Publication type
• Journal Article MeSH

Hemodynamické vyšetření koronárních lézí pomocí hyperemických a nehyperemických indexů je v současnosti běžnou součástí vyšetřovacích postupů katetrizačních laboratoří při ozřejmování funkční významnosti angiograficky hraničních lézí. Pomocí frakční průtokové rezervy se posuzuje míra funkčního postižení epikardiálních tepen. K popsání funkce koronárního a mikrocirkulárního řečiště lze využít koronární průtokové rezervy. Samotná mikrocirkulace je pak charakterizována indexem mikrovaskulární rezistence. Díky stále dynamičtějšímu rozvoji techniky a snaze o snížení nákladů a míry invazivity vyšetření dochází k vývoji nových moderních metod umožňujících dosáhnout funkční charakteristiky hraničních lézí pouze na základě obrazových dat, ať už angiografických, či např. dat CT koronarografie.

Hemodynamic examination of coronary lesions using both hyperemic and non-hyperemic indices is currently a routine part of invasive procedures in catheterization laboratories. The most frequent indication for hemodynamic assessment is to clarify the functional significance of angiographically borderline lesions. Fractional flow reserve is used to assess the degree of functional impairment of the epicardial arteries. Coronary flow reserve is used to describe the hemodynamic condition of the coronary vessels and microvasculature. The microcirculation itself is characterized by the index of microvascular resistance. Thanks to the dynamic development of technology and efforts to reduce the costs and the degree of invasiveness of the examination, new modern methods are being developed. They allow to achieve the functional characteristics of borderline lesions on the basis of imaging data only, whether derived from angiography or, for example, CT coronary angiography.

• MeSH
• Fractional Flow Reserve, Myocardial physiology   MeSH
• Heart Function Tests MeSH
• Hemodynamic Monitoring * methods   instrumentation   MeSH
• Coronary Vessels diagnostic imaging   physiopathology   MeSH
• Coronary Circulation * physiology   MeSH
• Humans MeSH
• Blood Pressure Determination MeSH
• Signal Processing, Computer-Assisted instrumentation   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

The present study aimed to evaluate the characteristic influence of physical therapeutic procedures of vacuum-compression therapy (VCT) on microvascular perfusion (MiP) and macrovascular perfusion (MaP) of the lower limb in diabetic patients. A sample of nine patients with a medical history of type 2 diabetes was used for the purpose of this study. Most of the subjects' medical conditions included venous and neurological complications of the lower limb, whereas the rest of the subjects entered the treatment due to injury recovery or their phlebological disease. The PeriFlux System 5000 (Perimed, Sweden) diagnostic device was used to measure MiP. The MaP was evaluated based on the perfusion index (PI) using the Extremiter monitoring device (Embitron, Czech Republic) designed to perform VCT procedures. The study found that MiP and MaP increase as an effect of VCT procedures and at the same time PI clearly reflects the effect of the applied vacuum and compression phases, verifying the method's vital influence on peripheral perfusion disorders.

• MeSH
• Diabetes Mellitus, Type 2 complications   diagnosis   physiopathology   MeSH
• Diabetic Retinopathy MeSH
• Lower Extremity physiopathology   MeSH
• Humans MeSH
• Perfusion methods   MeSH
• Vacuum MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Background: We tested whether the level of endothelial dysfunction assessed by digital tonometry, and expressed as reactive hyperemia index (RHI), is related to occurrences of a discrepancy between fractional flow reserve (FFR) and the instantaneous wave free ratio (iFR) (ClinicalTrials.gov identifier: NCT03033810).Methods: We examined patients with coronary stenosis in the range of 40-70%, assessed by both FFR and iFR (system Philips-Volcano) for stable angina. We included consecutive patients with FFR and iFR in one native coronary artery, and who had had no previous intervention.Results: We included 138 patients. Out of those, 24 patients (17.4%) had a negative FFR (with an FFR value >0.8) and positive iFR (with a iFR value ≤0.89) - designated the FFRn/iFRp discrepancy group, and 22 patients (15.9%) had a positive FFR (≤0.8) and negative iFR (>0.89) - designated the FFRp/iFRn discrepancy. RHI was higher in the discrepancy groups compared the group without discrepancy (1.73 ± 0.79 vs. 1.48 ± 0.50, p = 0.025). However, this finding was not confirmed in multivariant logistic regression analyses. Patients with any type of discrepancy differed from the agreement group by having a higher occurrence of diabetes mellitus [9 patients (21.4%) vs. 36 patients (39.6%), p = 0.029], active smoking (23 patients or 54.8% vs. 26 patients or 28.6%, p = 0.003) and lower use of calcium channel blockers (9 patients, 21.4%, vs. 43 patients, 46.7%, p = 0.004).Conclusion: The presence of endothelial dysfunction can be associated with a discrepancy in FFR/iFR. However, RHI correlated with risk factors of atherosclerosis, not with FFR or iFR.

• MeSH
• Endothelium, Vascular physiopathology   MeSH
• Vascular Resistance MeSH
• Fractional Flow Reserve, Myocardial * MeSH
• Coronary Stenosis * diagnosis   physiopathology   MeSH
• Laser-Doppler Flowmetry * instrumentation   methods   MeSH
• Humans MeSH
• Manometry instrumentation   methods   MeSH
• Microcirculation physiology   MeSH
• Software Design * MeSH
• Image Processing, Computer-Assisted MeSH
• Aged MeSH
• Software MeSH
• Myocardial Perfusion Imaging methods   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH

BACKGROUND: There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission. METHODS: In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264. FINDINGS: Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0-3·5). At baseline, 6816 patients (56·8%) had diabetes, 3991 (33·3%) prediabetes, and 1193 (9·9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg (95% CI 2·3-2·9) for those with diabetes, 2·8 kg (2·5-3·2) for those with prediabetes, and 3·3 kg (2·6-4·0) for those with normoglycaemia (p<0·0001 for all analyses). Lorcaserin reduced the risk of incident diabetes by 19% in patients with prediabetes (172 [8·5%] of 2015 vs 204 [10·3%] of 1976; hazard ratio 0·81, 95% CI 0·66-0·99; p=0·038) and by 23% in patients without diabetes (174 [6·7%] of 2615 vs 215 [8·4%] of 2569; 0·77, 0·63-0·94; p=0·012). Lorcaserin resulted in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes (185 [9·2%] vs 151 [7·6%]; 1·20, 0·97-1·49; p=0·093). In patients with diabetes, lorcaserin resulted in a reduction of 0·33% (95% CI 0·29-0·38; p<0·0001) in HbA1c compared with placebo at 1 year from a mean baseline of 53 mmol/mol (7·0%). In patients with diabetes at baseline, severe hypoglycaemia with serious complications was rare, but more common with lorcaserin (12 [0·4%] vs four [0·1%] events; p=0·054). INTERPRETATION: Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health. FUNDING: Eisai.

• MeSH
• Appetite Depressants therapeutic use   MeSH
• Atherosclerosis complications   drug therapy   MeSH
• Benzazepines therapeutic use   MeSH
• Diabetes Mellitus, Type 2 blood   complications   drug therapy   prevention & control   MeSH
• Double-Blind Method MeSH
• Glycated Hemoglobin analysis   MeSH
• Weight Loss drug effects   MeSH
• Hypoglycemic Agents therapeutic use   MeSH
• Remission Induction MeSH
• Middle Aged MeSH
• Humans MeSH
• Overweight complications   MeSH
• Obesity complications   MeSH
• Prediabetic State complications   drug therapy   prevention & control   MeSH
• Aged MeSH
• Body Weight drug effects   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

BACKGROUND: Cerebral microangiopathy in Alzheimer's disease (AD) causes chronic hypoperfusion and probably accelerates neurodegenerative changes. OBJECTIVE: We hypothesize microvascular impairment could be present already in mild cognitive impairment (MCI) and can be revealed using transcranial color-coded sonography (TCCS) and the breath-holding maneuver. METHODS: Three groups of subjects (AD in the stage of dementia, MCI, and cognitively normal controls) with detailed neuropsychological testing and low cerebrovascular burden (no history of stroke, no intra- or extracranial artery stenoses, and no severe vascular lesions on brain MRI), underwent a TCCS assessment of peak systolic (PSV), mean flow (MFV), and end diastolic velocities (EDV) and resistance and pulsatility indices (RI, PI) in large intracranial vessels bilaterally. Cerebrovascular reserve capacity was assessed using the breath-holding index (BHI) in middle cerebral artery (MCA) bilaterally. The ultrasound parameters were compared between the groups, correlated with neuropsychological tests, and compared between amnestic and non-amnestic MCI subtypes. RESULTS: Fourteen AD (3 males, 67.9±11.1 years, MMSE 18.0±4.6), 24 MCI (13 males, 71.9±7.3 years, MMSE 28.0±1.6), and 24 risk factor-matched controls (14 males, 67.8±6.4 years, MMSE 29.1±1.2) were enrolled. Significant differences were found between AD and controls in MFV, EDV, RI, PI in right MCA after breath holding, in PSV, MFV, EDV in left MCA after breath holding, and in BHI on the left side. The left BHI correlated positively with verbal memory test. CONCLUSION: Results show decreased cerebrovascular reserve capacity in AD as a sign of impaired cerebral hemodynamic status without severe underlying atherosclerosis. This can be identified using TCCS and BHI.

• MeSH
• Alzheimer Disease diagnostic imaging   physiopathology   MeSH
• Hemodynamics * MeSH
• Cognitive Dysfunction diagnostic imaging   physiopathology   MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain blood supply   diagnostic imaging   physiopathology   MeSH
• Cerebrovascular Circulation MeSH
• Neuropsychological Tests MeSH
• Aged MeSH
• Ultrasonography, Doppler, Transcranial MeSH
• Breath Holding MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Teoreticky nejlepším vyjádřením korelujícím se vznikem ischemie myokardu je index odporu stenózy při navozené hyperémii (hyperemic stenosis resistance index), je přesnějším vyjádřením závažnosti koronární stenózy než FFR, podobně i CFR má vysokou prognostickou váhu. Principem iFR (instant wave‑ free ratio) je stanovení poměru distálního a aortálního tlaku během období bez vln u konsekutivních srdečních cyklů. Vzhledem k minimálnímu mikrovaskulárnímu odporu v této fázi není nutné podání adenosinu. Přesnější výsledky iFR jdou především na vrub falešně pozitivních výsledků FFR u nevýznamných stenóz s normální mikrovaskulární funkcí a vysokým CFR. Studie iFR‑SWEDEHEART a DEFINE‑FLAIR ukázaly, že u nemocných s klinickou indikací pro fyziologicky vedené zhodnocení koronárního postižení iFR není inferiorní oproti FFR, pokud jde o výskyt úmrtí, IM a neplánované revaskularizace během 12 měsíců sledování. V následné souhrnné metaanalýze DEFINE‑FLAIR a iFR‑SWEDEHEART, byl prokázán vyšší výskyt úmrtí a infarktů myokardu ve skupině s iFR, rozdíly však nebyly statisticky významné a ačkoliv tedy nevyvracejí hypotézu non‑ inferiority iFR, definitivní posouzení, zda iFR není inferiorní oproti FFR při vedení revaskularizace myokardu bude vyžadovat další výzkum.

The hyperemic stenosis resistance index is the best parameter correlating with the induction of myocardial ischemia, it provides amore accurate assessment of the severity of coronary stenosis than FFR, similarly, the CFR has a high predictive value. The principleof the iFR (instant wave-free ratio) is the determination of the ratio of the distal and aortic pressure during the wave-free periodin the consecutive cardiac cycles. Due to the minimal microvascular resistance in this period, administration of adenosine is notrequired. More accurate results of iFR are mainly due to false positive results of FFR in nonsignificant coronary stenoses withnormal microvascular function and a high CFR. iFR -SWEDEHEART and DEFINE-FLAIR studies showed that in patients with clinicalindication for physiologically guided evaluation of coronary artery stenosis, iFR is not inferior to the FFR, as regards the incidenceof death, MI and unplanned revascularization during the 12 months follow-up. In a subsequent meta-analysis of DEFINE-FLAIRand iFR-SWEDEHEART, a higher incidence of death and myocardial infarctions in the iFR group was, however, demonstrated,albeit the differences were not statistically significant. Thus, the iFR non-inferiority hypothesis was not denied, nevertheless thefinal assessment of whether the iFR is non-inferior compared to the FFR in the management of myocardial revascularization willrequire further research.

• MeSH
• Adenosine isolation & purification   MeSH
• Aortic Valve Insufficiency diagnosis   etiology   complications   MeSH
• Diagnostic Techniques, Cardiovascular trends   utilization   MeSH
• Fractional Flow Reserve, Myocardial * physiology   drug effects   MeSH
• Hyperemia diagnosis   etiology   physiopathology   MeSH
• Coronary Circulation * physiology   drug effects   MeSH
• Coronary Stenosis * diagnosis   etiology   MeSH
• Humans MeSH
• Meta-Analysis as Topic MeSH
• Nitric Oxide isolation & purification   MeSH
• Myocardial Revascularization methods   trends   utilization   MeSH
• Statistics as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Hypertension in obesity is associated with increased insulin resistance, vascular mass and body mass index (BMI). The purpose of the study was to visualize endothelin-1 (ET-1) mediated constriction in arteries isolated from subcutaneous adipose tissue from obese hypertensive women previously operated by gastric bypass. Functional studies were conducted in a microvascular myograph. Expressed as percentage of contraction elicited by 124 mM KCl concentration-response curves for ET-1 were shifted leftward in arteries from obese hypertensive patients compared to healthy normotensive subjects. The vasodilator response to the ET-1 antagonist BQ123 (1 microM) was significantly higher in arteries from obese hypertensive patients (p<0.001). BQ123 induced relaxation was inhibited by NO synthase inhibitor L-NAME (0.1 nM). Preincubation with BQ123 enhanced the relaxation induced by acetylcholine (ACh; 0.1 nM - 0.1 mM) (p<0.001), but not that induced by NO donor sodium nitroprusside (SNP; 0.1 nM - 0.1 mM), in arteries from obese hypertensive patients. The present study show that hypertension yet prevail after gastric bypass surgery and the ET(A) receptor antagonist BQ123 may be a useful tool in reducing blood pressure in obese hypertensive patients.

• MeSH
• Endothelin A Receptor Antagonists pharmacology   therapeutic use   MeSH
• Endothelium, Vascular drug effects   metabolism   MeSH
• Peptides, Cyclic pharmacology   therapeutic use   MeSH
• Hypertension drug therapy   metabolism   surgery   MeSH
• Middle Aged MeSH
• Humans MeSH
• Obesity drug therapy   metabolism   surgery   MeSH
• Organ Culture Techniques MeSH
• Receptor, Endothelin A physiology   MeSH
• Adipose Tissue blood supply   drug effects   metabolism   MeSH
• Vasodilation drug effects   physiology   MeSH
• Dose-Response Relationship, Drug MeSH
• Gastric Bypass trends   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Presence of macro- and microvascular complications in patients with diabetes mellitus (DM) is not only related to chronic hyperglycemia represented by glycated hemoglobin (HbA1c) but also to acute glycemic fluctuations (glycemic variability, GV). The association between GV and DM complications is not completely clear. Aim of our study was to evaluate GV by MAGE index in patients with type 2 DM and to verify association of MAGE index with presence of macro- and microvascular DM complications. METHODS: 99 patients with type 2 DM were included in the study. Every patient had done big glycemic profile, from which MAGE index was calculated. Anthropometric measurements, evaluation of HbA1c and fasting plasma glucose (FPG) and assessment for macrovascular (coronary artery disease - CAD; peripheral artery disease - PAD; cerebral stroke - CS) and microvascular (diabetic retinopathy - DR; nephropathy - DN; peripheral neuropathy - DPPN) DM complications were done. RESULTS: Average MAGE index value was 5.15 ± 2.88 mmol/l. We found no significant differences in MAGE index values in subgroups according to presence of neither CAD, CS, PAD nor DR, DN, DPPN. MAGE index value significantly positively correlated with FPG (p < 0.01) and HbA1c (p < 0.001) and negatively with weight (p < 0.05). CONCLUSION: In our study we failed to show association of MAGE index with presence of macrovascular and microvascular complications in patients with type 2 DM. However, this negative result does not necessarily disprove importance of glycemic variability in pathogenesis of diabetic complications.

• MeSH
• Analysis of Variance MeSH
• Diabetes Mellitus, Type 2 blood   diagnosis   MeSH
• Diabetic Angiopathies diagnosis   epidemiology   MeSH
• Glycemic Index * MeSH
• Glycated Hemoglobin analysis   MeSH
• Risk Assessment MeSH
• Incidence MeSH
• Cohort Studies MeSH
• Blood Glucose analysis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Retrospective Studies MeSH
• Sex Distribution MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Severity of Illness Index MeSH
• Age Distribution MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION: Obstructive sleep apnea (OSA) is the most common form of sleep disordered breathing and has been associated with major cardiovascular comorbidities. We hypothesized that the microcirculation is impaired in patients with OSA and that the magnitude of impairment correlates to OSA severity. METHODS: Subjects were consecutive patients scheduled for routine diagnostic polysomnography (PSG). OSA was defined by paradoxical rib cage movements together with abdominal excursions and by the apnea-hypopnea index (AHI) (events/hour; no apnea AHI<5; mild apnea 5≤AHI<15; moderate apnea 15≤AHI<30; severe apnea AHI ≥30). Sidestream darkfield imaging was used to assess the sublingual microcirculation. Recordings of sublingual microcirculation (5 random sites) were performed before and after overnight PSG. Data are summarized as mean (±SD); p values <0.05 were considered statistically significant. RESULTS: Thirty-three consecutive patients were included. OSA was diagnosed in 16 subjects (4 moderate, 12 severe). There was no significant difference in microcirculation between subjects with moderate OSA and without OSA. However, compared to subjects without OSA, subjects with severe OSA (AHI≥30) showed a significant decrease of microvascular flow index (-0.07±0.17 vs. 0.08±0.14; p = 0.02) and increase of microvascular flow index heterogeneity (0.06±0.15 vs. -0.06±0.11; p = 0.02) overnight. Multiple regression analysis (adjusted for age and gender) showed both decrease of flow and increase of flow heterogeneity associated with AHI (b = -0.41; F = 1.8; p = 0.04 and b = 0.43; F = 1.9; p = 0.03, respectively). CONCLUSION: Acute overnight microcirculatory changes are observed in subjects with severe OSA characterized by decreased flow and increased flow heterogeneity.

• MeSH
• Video Recording MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Microcirculation * MeSH
• Sleep Apnea, Obstructive blood   MeSH
• Polysomnography MeSH
• Regression Analysis MeSH
• Aged MeSH
• Software MeSH
• Severity of Illness Index MeSH
• Sleep Apnea Syndromes blood   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH