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Oral L-Arginine (5 g/day) for 14 Days Improves Microcirculatory Function in Healthy Young Women and Healthy and Type 2 Diabetes Mellitus Elderly Women.
Costa, G, Shushanof, M, Bouskela, E, Bottino, D
Journal of vascular research. 2022;(1):24-33
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Abstract
OBJECTIVE The aim of this study was to investigate the effect of oral supplementation with L-arginine on serum biochemical profile, blood pressure, microcirculation, and vasoreactivity/endothelial function in young controls, and elderly women with and without type 2 diabetes mellitus (T2DM). METHODS Healthy young (n = 25), healthy elderly (n = 25), and elderly women with type 2 diabetes mellitus (T2DME, n = 23, glycated Hb ≥6.4% and mean of 7.7 years for duration of the disease), aged 18-30 and older than 65 years, respectively, were included in the study. All patients underwent biochemical analysis (fasting glycemia and lipidogram), arterial blood pressure, nailfold videocapillaroscopy (capillary diameters, functional capillary density [FCD], peak red blood cell velocity [RBCVmax] after 1 min ischemia, time to reach peak RBCV [TRBCVmax]), and venous occlusion plethysmography (vasoreactivity), before and after 14 days of oral supplementation with L-arginine (5 g/day). RESULTS L-Arginine did not change fasting glycemia and lipidogram, but it decreased systolic, diastolic, and mean arterial pressure in elderly women, increased RBCVmax in all groups, and did not decrease TRBCVmax in T2DME. Capillary diameters and FCD remained unchanged in all groups. L-Arginine improved vasoreactivity during reactive hyperemia and after sublingual nitroglycerin (0.4 mg) in all groups. CONCLUSION L-Arginine supplementation (5g/day during 14 days) was able to improve vascular/microvascular health in the elderly women with or without T2DM.
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Renal haemodynamic and protective effects of renoactive drugs in type 2 diabetes: Interaction with SGLT2 inhibitors.
Scholtes, RA, van Baar, MJB, Kok, MD, Bjornstad, P, Cherney, DZI, Joles, JA, van Raalte, DH
Nephrology (Carlton, Vic.). 2021;(5):377-390
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Abstract
Diabetic kidney disease remains the leading cause of end-stage kidney disease and a major risk factor for cardiovascular disease. Large cardiovascular outcome trials and dedicated kidney trials have shown that sodium-glucose cotransporter (SGLT)2 inhibitors reduce cardiovascular morbidity and mortality and attenuate hard renal outcomes in patients with type 2 diabetes (T2D). Underlying mechanisms explaining these renal benefits may be mediated by decreased glomerular hypertension, possibly by vasodilation of the post-glomerular arteriole. People with T2D often receive several different drugs, some of which could also impact the renal vasculature, and could therefore modify both renal efficacy and safety of SGLT2 inhibition. The most commonly prescribed drugs that could interact with SGLT2 inhibitors on renal haemodynamic function include renin-angiotensin system inhibitors, calcium channel blockers and diuretics. Herein, we review the effects of these drugs on renal haemodynamic function in people with T2D and focus on studies that measured glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) with gold-standard techniques. In addition, we posit, based on these observations, potential interactions with SGLT2 inhibitors with an emphasis on efficacy and safety.
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First-Line Vasopressor and Mortality Rates in ED Patients with Acute Drug Overdose.
Clifford, C, Sethi, M, Cox, D, Manini, AF
Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2021;(1):1-9
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INTRODUCTION While emergency department (ED) visits for acute drug overdose are at an all-time high, the importance of vasopressors to treat circulatory shock in this patient population remains unclear. This study investigated the association between first-line vasopressor and mortality, for both push-dose and infusion, in this patient population. METHODS From a prospective cohort of consecutive ED patients with drug overdose at two urban teaching centers over 5 years, we performed a secondary data analysis of patients with circulatory shock, defined as hypotension requiring either vasopressors, high-dose insulin euglycemia therapy, or both. The first-line vasopressor (push-dose and infusion) was analyzed for associations with the primary outcome (in-hospital mortality) and secondary outcomes (24-hour mortality, ICU LOS). Subgroup analysis of beta-/calcium-channel blocker overdose was performed to evaluate impact of antidotal therapies. Data analysis included multivariable regression. RESULTS Fifty-five patients with circulatory shock were analyzed, in whom there was 20% 24-hour mortality, 42% in-hospital mortality, 730-minute mean vasopressor duration, and 53.4-hour median ICU LOS. On multivariable analysis, there was significantly decreased adjusted odds of in-hospital mortality with first-line push-dose phenylephrine (aOR 0.06, CI 0.01-0.55), and significantly increased adjusted odds of in-hospital mortality with first-line push-dose epinephrine (aOR 60.8, CI 6.1-608). Of the first-line infusions, norepinephrine had the lowest odds of in-hospital mortality (aOR 0.80, CI 0.2-3.1). CONCLUSIONS In ED patients with undifferentiated drug overdose and circulatory shock, the first-line vasopressor is associated with in-hospital mortality. First-line push-dose phenylephrine was associated with the lowest odds of in-hospital mortality. Future randomized studies are warranted for validation.
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No Effects of Different Doses of New Zealand Blackcurrant Extract on Cardiovascular Responses During Rest and Submaximal Exercise Across a Week in Trained Male Cyclists.
Montanari, S, Şahin, MA, Lee, BJ, Blacker, SD, Willems, MET
International journal of sport nutrition and exercise metabolism. 2021;(1):66-72
Abstract
Supplementation with anthocyanin-rich blackcurrant increases blood flow, cardiac output, and stroke volume at rest. It is not known whether cardiovascular responses can be replicated over longer timeframes in fed trained cyclists. In a randomized, double-blind, crossover design, 13 male trained cyclists (age 39 ± 10 years, V˙O2max 55.3 ± 6.7 ml·kg-1·min-1) consumed two doses of New Zealand blackcurrant (NZBC) extract (300 and 600 mg/day for 1 week). Cardiovascular parameters were measured during rest and submaximal cycling (65% V˙O2max) on day 1 (D1), D4, and D7. Data were analyzed with an RM ANOVA using dose (placebo vs. 300 vs. 600 mg/day) by time point (D1, D4, and D7). Outcomes from placebo were averaged to determine the coefficient of variation within our experimental model, and 95% confidence interval (CI) was examined for differences between placebo and NZBC. There were no differences in cardiovascular responses at rest between conditions and between days. During submaximal exercise, no positive changes were observed on D1 and D4 after consuming NZBC extract. On D7, intake of 600 mg increased stroke volume (3.08 ml, 95% CI [-2.08, 8.26]; d = 0.16, p = .21), cardiac output (0.39 L/min, 95% CI [-1.39, .60]; d = 0.14, p = .40) (both +2.5%), and lowered total peripheral resistance by 6.5% (-0.46 mmHg·min/ml, 95% CI [-1.80, .89]; d = 0.18, p = .46). However, these changes were trivial and fell within the coefficient of variation of our study design. Therefore, we can conclude that NZBC extract was not effective in enhancing cardiovascular function during rest and submaximal exercise in endurance-trained fed cyclists.
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Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine.
Ott, C, Jung, S, Korn, M, Kannenkeril, D, Bosch, A, Kolwelter, J, Striepe, K, Bramlage, P, Schiffer, M, Schmieder, RE
Cardiovascular diabetology. 2021;(1):178
Abstract
BACKGROUND Type 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail. METHODS Patients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months. Renal hemodynamics were assessed with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intraglomerular hemodynamics were calculated according the Gomez´ model. RESULTS Treatment with E+L reduced GFR (p = 0.003), but RPF remained unchanged (p = 0.536). In contrast, M+I not only reduced GFR (p = 0.001), but also resulted in a significant reduction of RPF (p < 0.001). Renal vascular resistance (RVR) decreased with E+L treatment (p = 0.001) but increased with M+I treatment (p = 0.001). The changes in RPF and RVR were different between the two groups (both padjust < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (RA) (p = 0.116), but diminished resistance of efferent arterioles (RE) (p = 0.001). In M+I group RA was increased (p = 0.006) and RE remained unchanged (p = 0.538). The effects on RA (padjust < 0.05) and on RE (padjust < 0.05) differed between the groups. CONCLUSIONS In patients with type 2 diabetes and preserved renal function treatment with M+I resulted in reduction of renal perfusion and increase in vascular resistance, in contrast to treatment with E+I that preserved renal perfusion and reduced vascular resistance. Moreover, different underlying effects on the resistance vessels have been estimated according to the Gomez model, with M+I increasing RA and E+L predominantly decreasing RE, which is in contrast to the proposed sodium-glucose cotransporter 2 inhibitor effects. TRIAL REGISTRATION The study was registered at www.clinicaltrials.gov (NCT02752113) on April 26, 2016.
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Inorganic nitrate supplementation attenuates conduit artery retrograde and oscillatory shear in older adults.
Casey, DP, Bock, JM
American journal of physiology. Heart and circulatory physiology. 2021;(3):H991-H998
Abstract
Aging causes deleterious changes in resting conduit artery shear patterns and reduced blood flow during exercise partially attributable to reduced nitric oxide (NO). Inorganic nitrate increases circulating NO bioavailability and may, therefore, improve age-associated changes in shear rate as well as exercise hyperemia. Ten older adults (age: 67 ± 3 yr) consumed 4.03 mmol nitrate and 0.29 mmol nitrite (active) or devoid of both (placebo) daily for 4 wk in a randomized, double-blinded, crossover fashion. Brachial artery diameter (D) and blood velocity (Vmean) were measured via Doppler ultrasound at rest for the characterization of shear profile as well as during two handgrip exercise trials (4 and 8 kg) for calculation of forearm blood flow (Vmean × cross-sectional area, FBF) and conductance [FBF/mean arterial pressure, forearm vascular conductance (FVC)]. Plasma [nitrate] and [nitrite] increased following active (P < 0.05 for both) but not placebo (P = 0.68 and 0.40, respectively) supplementation. Neither mean nor antegrade shear rate changed following either supplement (beverage-by-time P = 0.14 and 0.21, respectively). Retrograde (-13.4 ± 7.0 to -9.7 ± 6.8·s-1) and oscillatory (0.20 ± 0.08 to 0.15 ± 0.09 A.U., P < 0.05 for both) shear decreased following active, but not placebo (P = 0.81 and 0.70, respectively), supplementation. The FBF response (Δ from rest) to neither 4-kg nor 8-kg trials changed following either supplement (beverage-by-time P = 0.53 and 0.11, respectively). Similarly, no changes were observed in FVC responses to 4-kg or 8-kg trials (beverage-by-time P = 0.23 and 0.07, respectively). These data indicate that inorganic nitrate supplementation improves conduit artery shear profiles, but not exercise hyperemia, in older adults.NEW & NOTEWORTHY We report for the first time, to our knowledge, that 4 wk of inorganic nitrate supplementation attenuates retrograde and oscillatory shear in the brachial artery of older adults. However, this was not associated with greater hyperemic or vasodilatory responses to exercise. In sum, these data highlight favorable changes in shear patterns with aging, which may reduce the risk of atherosclerotic cardiovascular disease.
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Respiratory and hemodynamic effects of three different sedative regimens for drug induced sleep endoscopy in sleep apnea patients. A prospective randomized study.
Elkalla, RS, El Mourad, MB
Minerva anestesiologica. 2020;(2):132-140
Abstract
BACKGROUND Drug induced sleep endoscopy (DISE) has emerged as a promising tool for customizing the adequate surgical approach to relieve airway obstruction in sleep apnea patients. We aimed to compare propofol, dexmedetomidine or ketofol with regards their efficacy and safety for sedation in patients with obstructive sleep apnea (OSA) undergoing DISE procedure. METHODS Sixty adult OSA patients scheduled for DISE procedure were randomly allocated into three equal groups to receive either propofol (group P), dexmedetomidine (group D), or ketofol (group K). Incidence of oxygen desaturation <90%, hemodynamic variables, time to achieve sufficient sedation level, recovery time, patients' and endoscopists' satisfaction, and incidence of adverse effects were recorded. RESULTS Higher incidence of oxygen desaturation <90% was observed in group P as compared to groups D and K (70%, 35%, and 30% respectively, P=0.021*). Group D showed a significantly longer time to reach target sedation level, prolonged recovery time with more consumption of rescue propofol as compared to group P and group K (P=0.000*, 0.000*, 0.000* respectively). Heart rate values were lower in group D after the loading dose till 30 min postoperative as compared to the other two groups, while blood pressure was lower in both P and D groups at five, 10, 15 min, and on reaching recovery room compared to K group. Two patients in the K group had psychomimetic symptoms with no difference between groups as regards other adverse events or patients' and endoscopist's satisfactions. CONCLUSIONS Dexmedetomidine and ketofol provided a safe respiratory profile compared to propofol during DISE without significant hemodynamic adverse events.
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Effect of nicorandil administration on cardiac burden and cardio-ankle vascular index after coronary intervention.
Sato, S, Takahashi, M, Mikamo, H, Kawazoe, M, Iizuka, T, Shimizu, K, Noro, M, Shirai, K
Heart and vessels. 2020;(12):1664-1671
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Myocardial injury is a problem associated with percutaneous coronary intervention (PCI). This study aimed to clarify the role of nicorandil administration in preventing myocardial injury. This study included patients with stable angina who underwent PCI from November 2013 to June 2016. Of 58 consecutive patients, the first 20 patients received only saline infusion after PCI (control group); the other 38 patients received a continuous intravenous infusion of nicorandil and saline after PCI (nicorandil group). Troponin I and brain natriuretic peptide (BNP) levels were measured. Vascular parameters, such as blood pressure (BP), cardiac output, cardio-ankle vascular index (CAVI), and estimated systemic vascular resistance (eSVR), were measured. Troponin I of both groups increased 12 h after PCI. Changes in BNP levels between immediately after PCI and 12 h after PCI were significantly higher in the control than in the nicorandil group (10.8 ± 44.2 vs. - 2.6 ± 14.6 pg/ml, p = 0.04). In the nicorandil group, BP, eSVR, and CAVI decreased significantly at 12 h after PCI compared with those immediately after PCI (p < 0.0001), whereas no change was observed in the control group. In a single linear analysis, the change in BP (r = 0.36, p < 0.01) and nicorandil administration (r = - 0.47, p < 0.001) was significantly correlated with the change in CAVI, multiple regression analysis revealed that the changes in CO and eSVR were significant contributing factors for the changes in CAVI. PCI could result in myocardial injury and/or cardiac burden in patients with stable angina. Nicorandil administration after PCI may be effective in relieving the burden by decreasing arterial stiffness (CAVI).
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The Cardiorenal Syndrome in Heart Failure.
Costanzo, MR
Heart failure clinics. 2020;(1):81-97
Abstract
Abnormal fluid handling leads to physiologic abnormalities in multiple organ systems. Deranged hemodynamics, neurohormonal activation, excessive tubular sodium reabsorption, inflammation, oxidative stress, and nephrotoxic medications are important drivers of harmful cardiorenal interactions in patients with heart failure. Accurate quantitative measurement of fluid volume is vital to individualizing therapy for such patients. Blood volume analysis and pulmonary artery pressure monitoring seem the most reliable methods for assessing fluid volume and guiding decongestive therapies. Still the cornerstone of decongestive therapy, diuretics' effectiveness decreases with progression of heart failure. Extracorporeal ultrafiltration, an alternative to diuretics, has been shown to reduce heart-failure events.
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Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring.
Panagiotopoulou, O, Syngelaki, A, Georgiopoulos, G, Simpson, J, Akolekar, R, Shehata, H, Nicolaides, K, Charakida, M
American journal of obstetrics and gynecology. 2020;(2):246.e1-246.e10
Abstract
BACKGROUND Maternal obesity increases the risk for pregnancy complications and adverse neonatal outcome and has been associated with long-lasting adverse effects in the offspring, including increased body fat mass, insulin resistance, and increased risk for premature cardiovascular disease. Lifestyle interventions in pregnancy have produced no or modest effects in the reduction of adverse pregnancy outcomes in obese mothers. The Metformin in Obese Pregnant Women trial was associated with reduced adverse pregnancy outcomes and had no effect on birthweight. However, the long-term implications of metformin on the health of offspring remain unknown. OBJECTIVE The purpose of this study was to assess whether prenatal exposure to metformin can improve the cardiovascular profile and body composition in the offspring of obese mothers. STUDY DESIGN In 151 children from the Metformin in Obese Pregnant Women trial, body composition, peripheral blood pressure, and arterial pulse wave velocity were measured. Central hemodynamics (central blood pressure and augmentation index) were estimated with the use of an oscillometric device. Left ventricular cardiac function and structure were assessed by echocardiography. RESULTS Children were 3.9±1.0 years old, and 77 of them had been exposed to metformin prenatally. There was no significant difference in peripheral blood pressure, arterial stiffness, and body composition apart from gluteal and tricep circumferences, which were lower in the metformin group (P<.05). The metformin group, compared with the placebo group, had lower central hemodynamics (mean adjusted decrease, -0.707 mm Hg for aortic systolic blood pressure, -1.65 mm Hg for aortic pulse pressure, and -2.68% for augmentation index; P<.05 for all) and lower left ventricular diastolic function (adjusted difference in left atrial area, -0.525 cm2, in isovolumic relaxation time, -0.324 msec, and in pulmonary venous systolic wave, 2.97 cm/s; P<.05 for all). There were no significant differences in metabolic profile between the groups. CONCLUSION Children of obese mothers who were exposed prenatally to metformin, compared with those who were exposed to placebo, had lower central hemodynamic and cardiac diastolic indices. These results suggest that the administration of metformin in obese pregnant women potentially may have a beneficial cardiovascular effect for their offspring.