Myocardial perfusion reserve compared with peripheral perfusion reserve: A [13N]ammonia PET study

INTRODUCTION: [13N]ammonia PET allows quantification of myocardial perfusion. The similarity between peripheral flow and myocardial perfusion is unclear. We compared perfusion flow in the myocardium with the upper limb during rest and adenosine stress [13N]ammonia PET to establish whether peripheral perfusion reserve (PPR) correlates with MPR. METHODS: [13N]ammonia myocardial perfusion PET-scans of 58 patients were evaluated (27 men, 31 women, age 64 ± 13 years) and were divided in four subgroups: patients with coronary artery disease (CAD, n = 15), cardiac syndrome X (SX, n = 14), idiopathic dilating cardiomyopathy (DCM, n = 16), and normal controls (NC, n = 13). Peripheral limb perfusion was measured in the muscular tissue of the proximal upper limb and quantified through a 2-tissue-compartment model and the PPR was calculated (stress/rest ratio). MPR was also calculated by a 2-tissue-compartment model. The PPR results were compared with the MPR findings. RESULTS: Mean myocardial perfusion increased significantly in all groups as evidenced by the MPR (CAD 1.99 ± 0.47; SX 1.39 ± 0.31; DCM 1.72 ± 0.69; NC 2.91 ± 0.78). Mean peripheral perfusion also increased but not significantly and accompanied with great variations within and between groups (mean PPR: CAD 1.30 ± 0.79; SX 1.36 ± 0.71; DCM 1.60 ± 1.22; NC 1.27 ± 0.63). The mean difference between PPR and MPR for all subpopulations varied widely. No significant correlations in flow reserve were found between peripheral and myocardial microcirculatory beds in any of the groups (Total group: r = -0.07, SEE = 0.70, CAD: r = 0.14, SEE = 0.48, SX: r = 0.17, SEE = 0.30, DCM: r = -0.11, SEE = 0.71, NC: r = -0.19, SEE = 0.80). CONCLUSION: No correlations between myocardial and peripheral perfusion (reserve) were found in different patient populations in the same PET session. This suggests a functional difference between peripheral and myocardial flow in the response to intravenously administered adenosine stress

Seed quality of crambe (Crambe abyssinica Hochst) submitted to different drying methods 1 Qualidade de sementes de crambe (Crambe abyssinica Hochst) submetidas a diferentes métodos de secagem

ABSTRACT -The objective of this research was to evaluate the effects of different drying methods on physiological quality of crambe seeds. Crambe seeds of FMS Brilhante cultivar were produced in the Lageado experimental farm (UNESP, Botucatu, Brazil) in 2012. The drying methods were: artificial drying with hot air, artificial drying with fresh air, natural yard drying, natural shade drying and natural field drying. The water content of seeds was monitored before, during and after drying. Germination, first germination count, abnormal seedlings, GSI, germination synchronization, frequency and germination mean time, electrical conductivity, fatty acid index and oil content were evaluated in order to know the physiological quality. The experimental design was randomized and the averages compared by the t-test at 5% significance. Results showed that artificial hot air drying favored with higher germination and vigor of crambe seeds when compared to other drying methods and demanded shorter time to reduce the water content. The natural shade drying method is feasible for crambe seeds despite taking longer. Key words: Natural drying. Artificial drying. Crambe seeds vigor. Seeds damage. RESUMO -Objetivou-se nesta pesquisa avaliar o efeito de diferentes métodos de secagem na qualidade fisiológica de sementes de crambe. As sementes de crambe da cultivar FMS Brilhante foram produzidas na Fazenda Experimental Lageado (UNESP -Botucatu) no ano de 2012. As condições de secagem foram: secagem artificial com ar aquecido, secagem artificial com ar natural, secagem natural em terreiro, secagem natural à sombra e secagem na planta. O teor de água foi monitorado antes, durante e após a secagem. Para avaliação da qualidade fisiológica foi realizado o teste de germinação, primeira contagem de germinação, plântulas anormais, IVG, sincronização da germinação, frequência e tempo médio de germinação, teste de condutividade elétrica, índice de acidez graxa e teor de óleo. O delineamento experimental foi inteiramente casualizado e as médias comparadas pelo teste de Tukey a 5% de significância. Pelos resultados obtidos a secagem artificial com alta temperatura favoreceu obtenção de sementes de crambe com alta germinação e vigor em relação aos demais tipos de secagem com um tempo menor para redução do teor de água. A secagem natural na sombra é viável para sementes de crambe apesar de ser longa. Palavras-chave: Secagem natural. Secagem artificial. Vigor de sementes de crambe. Danos em sementes

Isometric handgrip as an adjunct for blood pressure control: a primer for clinicians

Considered a global health crisis by the World Health Organization, hypertension (HTN) is the leading risk factor for death and disability. The majority of treated patients do not attain evidence-based clinical targets, which increases the risk of potentially fatal complications. HTN is the most common chronic condition seen in primary care; thus, implementing therapies that lower and maintain BP to within-target ranges is of tremendous public health importance. Isometric handgrip (IHG) training is a simple intervention endorsed by the American Heart Association as a potential adjuvant BP-lowering treatment. With larger reductions noted in HTN patients, IHG training may be especially beneficial for those who (a) have difficulties continuing or increasing drug-based treatment; (b) are unable to attain BP control despite optimal treatment; (c) have pre-HTN or low-risk stage I mild HTN; and (d) wish to avoid medications or have less pill burden. IHG training is not routinely prescribed in clinical practice. To shift this paradigm, we focus on (1) the challenges of current HTN management strategies; (2) the effect of IHG training; (3) IHG prescription; (4) characterizing the population for whom it works best; (5) clinical relevance; and (6) important next steps to foster broader implementation by clinical practitioners

Feasibility and safety of high-dose adenosine perfusion cardiovascular magnetic resonance

<p>Abstract</p> <p>Introduction</p> <p>Adenosine is the most widely used vasodilator stress agent for Cardiovascular Magnetic Resonance (CMR) perfusion studies. With the standard dose of 140 mcg/kg/min some patients fail to demonstrate characteristic haemodynamic changes: a significant increase in heart rate (HR) and mild decrease in systolic blood pressure (SBP). Whether an increase in the rate of adenosine infusion would improve peripheral and, likely, coronary vasodilatation in those patients is unknown. The aim of the present study was to assess the tolerance and safety of a high-dose adenosine protocol in patients with inadequate haemodynamic response to the standard adenosine protocol when undergoing CMR perfusion imaging.</p> <p>Methods</p> <p>98 consecutive patients with known or suspected coronary artery disease (CAD) underwent CMR perfusion imaging at 1.5 Tesla. Subjects were screened for contraindications to adenosine, and an electrocardiogram was performed prior to the scan. All patients initially received the standard adenosine protocol (140 mcg/kg/min for at least 3 minutes). If the haemodynamic response was inadequate (HR increase < 10 bpm or SBP decrease < 10 mmHg) then the infusion rate was increased up to a maximum of 210 mcg/kg/min (maximal infusion duration 7 minutes).</p> <p>Results</p> <p>All patients successfully completed the CMR scan. Of a total of 98 patients, 18 (18%) did not demonstrate evidence of a significant increase in HR or decrease in SBP under the standard adenosine infusion rate. Following the increase in the rate of infusion, 16 out of those 18 patients showed an adequate haemodynamic response. One patient of the standard infusion group and two patients of the high-dose group developed transient advanced AV block. Significantly more patients complained of chest pain in the high-dose group (61% vs. 29%, p = 0.009). On multivariate analysis, age > 65 years and ejection fraction < 57% were the only independent predictors of blunted haemodynamic responsiveness to adenosine.</p> <p>Conclusions</p> <p>A substantial number of patients do not show adequate peripheral haemodynamic response to standard-dose adenosine stress during perfusion CMR imaging. Age and reduced ejection fraction are predictors of inadequate response to standard dose adenosine. A high-dose adenosine protocol (up to 210 mcg/kg/min) is well tolerated and results in adequate haemodynamic response in nearly all patients.</p

Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome

Rationale: Orthostatic hypotension is a common clinical problem, but the underlying mechanisms have not been fully delineated. Objective: We describe two families, with four patients in total, suffering from severe life-threatening orthostatic hypotension due to a novel cause. Methods and Results: As in dopamine β-hydroxylase deficiency (DβH), concentrations of norepinephrine and epinephrine in the patients were very low. Plasma DβH activity, however, was normal and the DBH gene had no mutations. Molecular genetic analysis was performed to determine the underlying genetic cause. Homozygosity mapping and exome and Sanger sequencing revealed pathogenic homozygous mutations in the gene encoding cytochrome b561 (CYB561); a missense variant c.262G>A, p.Gly88Arg in exon 3 in the Dutch family and a nonsense mutation (c.131G>A, p.Trp44*) in exon 2 in the American family. Expression of CYB561 was investigated using RNA from different human adult and fetal tissues, transcription of RNA into cDNA and real-time quantitative polymerase chain reaction. The CYB561 gene was found to be expressed in many human tissues, in particular the brain. The CYB561 protein defect leads to a shortage of ascorbate inside the catecholamine secretory vesicles leading to a functional DβH deficiency. The concentration of the catecholamines and downstream metabolites was measured in brain and adrenal tissue of six CYB561 knockout mice (reporter-tagged deletion allele (post-Cre), genetic background C57BL/6NTac). The concentration of norepinephrine and normetanephrine was decreased in whole brain homogenates of the CYB561(-/-) mice compared to wild type mice (p<0.01) and the concentration of normetanephrine and metanephrine was decreased in adrenal glands (p<0.01), recapitulating the clinical phenotype. The patients responded favorably to treatment with L-dihydroxyphenylserine, which can be converted directly to norepinephrine. Conclusions: This study is the first to implicate cytochrome b561 in disease by showing that pathogenic mutations in CYB561 cause an as yet unknown disease in neurotransmitter metabolism causing orthostatic hypotension. as yet unknown disease in neurotransmitter metabolism causing orthostatic hypotension

Chronic ethanol attenuates centrally-mediated hypotension elicited via alpha-2-adrenergic, but not I1-imidazoline, receptor activation in female rats

Aims—This study dealt with the effect of chronic ethanol administration on hemodynamic responses elicited by α2-adrenergic (α-methyldopa) or I1-imidazoline (rilmenidine) receptor activation in telemetered female rats. Main methods—The effects of α-methyldopa or rilmenidine on blood pressure (BP), heart rate (HR) and their variability were investigated in rats that received liquid diet without or with ethanol (5% w/v) for 12 weeks. To evaluate the effect of each drug on cardiovascular autonomic control (BP and HR variability) in the absence or presence of ethanol, three time-domain indices of hemodynamic variability were measured: (i) standard deviation of mean arterial pressure (SDMAP), (ii) standard deviation of beat-to-beat intervals, and (iii) root mean square of successive differences in R-R intervals. Key findings—In liquid diet-fed control rats, i.p. rilmenidine (600 μg/kg) or α-methyldopa (100 mg/kg) reduced BP along with decreases and increases, respectively, in HR. Both drugs had no effect on HR variability but reduced BP variability (SDMAP), suggesting a reduced vasomotor sympathetic tone. Ethanol feeding attenuated reductions in BP and SDMAP evoked by α-methyldopa but not by rilmenidine. Significance—We conclude that chronic ethanol preferentially compromises α2- but not I1- receptor-mediated hypotension in female rats probably via modulation of vasomotor sympathetic activity. These findings highlight the adequacy of rilmenidine use to lower BP in hypertensive alcoholic females