Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse

Borges JB, Suarez-Sipmann F, Bohm SH, Tusman G, Melo A, Maripuu E, Sandstrom M, Park M, Costa EL, Hedenstierna G, Amato M. Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse. J Appl Physiol 112: 225-236, 2012. First published September 29, 2011; doi: 10.1152/japplphysiol.01090.2010.-The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology that provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT)-based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6%, with a SD of 2.9%. This method outperformed the estimates of lung perfusion based on impedance pulsatility. In conclusion, we describe a novel method based on EIT for estimating regional lung perfusion at the bedside. In both healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this study has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.

Decompressive craniectomy and cerebral blood flow regulation in head injured patients: A case studied by perfusion CT

Previous studies have reported increased cerebral blood flow (CBF) velocity after decompressive craniectomy in traumatic brain injury (TBI) patients. A 27-year-old man presented with clinical and tomographic signs of cerebral herniation secondary to TBI. Prior to decompressive craniectomy, hemodynamic study by perfusion computed tomography (CT) indicated diffuse cerebral hyperperfusion. Following surgical decompression, the patient recovered neurologically and perfusion CT disclosed a decrease in the intensity of cerebral perfusion. The patient's blood pressure levels were similar at both pre- and postoperative perfusion CT examinations. This finding provides indirect evidence that decompressive craniectomy may improve mechanisms of CBF regulation in TBI, providing pathophysiological insights in the cerebral hemodynamics of TBI patients. This is the first report analyzing the hemodynamic changes through perfusion CT (PCT) in a patient with decompressive craniotomy due to TBI. (C) 2012 Elsevier Masson SAS. All rights reserved.

Strength Training with Blood Flow Restriction Diminishes Myostatin Gene Expression

LAURENTINO, G. C., C. UGRINOWITSCH, H. ROSCHEL, M. S. AOKI, A. G. SOARES, M. NEVES JR, A. Y. AIHARA, A. DA ROCHA CORREA FERNANDES, and V. TRICOLI. Strength Training with Blood Flow Restriction Diminishes Myostatin Gene Expression. Med. Sci. Sports Exerc., Vol. 44, No. 3, pp. 406-412, 2012. Purpose: The aim of the study was to determine whether the similar muscle strength and hypertrophy responses observed after either low-intensity resistance exercise associated with moderate blood flow restriction or high-intensity resistance exercise are associated with similar changes in messenger RNA (mRNA) expression of selected genes involved in myostatin (MSTN) signaling. Methods: Twenty-nine physically active male subjects were divided into three groups: low-intensity (20% one-repetition maximum (1RM)) resistance training (LI) (n = 10), low-intensity resistance exercise associated with moderate blood flow restriction (LIR) (n = 10), and high-intensity (80% 1RM) resistance exercise (HI) (n = 9). All of the groups underwent an 8-wk training program. Maximal dynamic knee extension strength (1RM), quadriceps cross-sectional area (CSA), MSTN, follistatin-like related genes (follistatin (FLST), follistatin-like 3 (FLST-3)), activin IIb, growth and differentiation factor-associated serum protein 1 (GASP-1), and MAD-related protein (SMAD-7) mRNA gene expression were assessed before and after training. Results: Knee extension 1RM significantly increased in all groups (LI = 20.7%, LIR = 40.1%, and HI = 36.2%). CSA increased in both the LIR and HI groups (6.3% and 6.1%, respectively). MSTN mRNA expression decreased in the LIR and HI groups (45% and 41%, respectively). There were no significant changes in activin IIb (P > 0.05). FLST and FLST-3 mRNA expression increased in all groups from pre- to posttest (P < 0.001). FLST-3 expression was significantly greater in the HI when compared with the LIR and LI groups at posttest (P = 0.024 and P = 0.018, respectively). GASP-1 and SMAD-7 gene expression significantly increased in both the LIR and HI groups. Conclusions: We concluded that LIR was able to induce gains in 1RM and quadriceps CSA similar to those observed after traditional HI. These responses may be related to the concomitant decrease in MSTN and increase in FLST isoforms, GASP-1, and SMAD-7 mRNA gene expression.

Abnormal resting state corticolimbic blood flow in depressed unmedicated patients with major depression: A 15O-H2O PET study

We investigated the differences in the resting state corticolimbic blood flow between 20 unmedicated depressed patients and 21 healthy comparisons. Resting state cerebral blood flow (CBF) was measured with H215O PET. Anatomical MRI scans were performed on an Elscint 1.9 T Prestige system for PET-MRI coregistration. Significant changes in cerebral blood flow indicating neural activity were detected using an ROI-free image subtraction strategy. In addition, the resting blood flow in patients was correlated with the severity of depression as measured by HAM-D scores. Depressed patients showed decreases in blood flow in right anterior cingulate (Brodmann areas 24 and 32) and increased blood flow in left and right posterior cingulate (Brodmann areas 23, 29, 30), left parahippocampal gyrus (Brodmann area 36), and right caudate compared with healthy volunteers. The severity of depression was inversely correlated with the left middle and inferior frontal gyri (Brodmann areas 9 and 47) and right medial frontal gyrus (Brodmann area 10) and right anterior cingulate (Brodmann areas 24, 32) blood flow, and directly correlated with the right thalamus blood flow. These findings support previous reports of abnormalities in the resting state blood flow in the limbic-frontal structures in depressed patients compared to healthy volunteers. Hum Brain Mapp, 2012. (C) 2011 Wiley Periodicals, Inc.

Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus

OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA(1) levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing.

Pulmonary root translocation in malposition of great arteries repair allows right ventricular outflow tract growth

Objective: Optimal surgical treatment of patients with transposition of the great arteries (TGA), ventricular septal defect (VSD), and pulmonary stenosis (PS) remains a matter of debate. This study evaluated the clinical outcome and right ventricle outflow tract performance in the long-term follow-up of patients subjected to pulmonary root translocation (PRT) as part of their surgical repair. Methods: From April 1994 to December 2010, we operated on 44 consecutive patients (median age, 11 months). All had malposition of the great arteries as follows: TGA with VSD and PS (n = 33); double-outlet right ventricle with subpulmonary VSD (n = 7); double-outlet right ventricle with atrioventricular septal defect (n = 1); and congenitally corrected TGA with VSD and PS (n 3). The surgical technique consisted of PRT from the left ventricle to the right ventricle after construction of an intraventricular tunnel that diverted blood flow from the left ventricle to the aorta. Results: The mean follow-up time was 72 +/- 52.1 months. There were 3 (6.8%) early deaths and 1 (2.3%) late death. Kaplan-Meier survival was 92.8% and reintervention-free survival was 82.9% at 12 years. Repeat echocardiographic data showed nonlinear growth of the pulmonary root and good performance of the valve at 10 years. Only 4 patients required reinterventions owing to right ventricular outflow tract problems. Conclusions: PRT is a good surgical alternative for treatment of patients with TGA complexes, VSD, and PS, with acceptable operative risk, high long-term survivals, and few reinterventions. Most patients had adequate pulmonary root growth and performance. (J Thorac Cardiovasc Surg 2012;143:1292-8)

Increased vascular contractility and oxidative stress in beta(2)-adrenoceptor knockout mice: the role of NADPH oxidase

Background/Aims: beta(2)-adrenoceptor (beta(2)-AR) activation induces smooth muscle relaxation and endothelium-derived nitric oxide (NO) release. However, whether endogenous basal beta(2)-AR activity controls vascular redox status and NO bioavailability is unclear. Thus, we aimed to evaluate vascular reactivity in mice lacking functional beta(2)-AR (beta 2KO), focusing on the role of NO and superoxide anion. Methods and Results: Isolated thoracic aortas from beta 2KO and wild-type mice (WT) were studied. beta 2KO aortas exhibited an enhanced contractile response to phenylephrine compared to WT. Endothelial removal and L-NAME incubation increased phenylephrine-induced contraction, abolishing the differences between beta 2KO and WT mice. Basal NO availability was reduced in aortas from beta 2KO mice. Incubation of beta 2KO aortas with superoxide dismutase or NADPH inhibitor apocynin restored the enhanced contractile response to phenylephrine to WT levels. beta 2KO aortas exhibited oxidative stress detected by enhanced dihydroethidium fluorescence, which was normalized by apocynin. Protein expression of eNOS was reduced, while p47(phox) expression was enhanced in beta 2KO aortas. Conclusions: The present results demonstrate for the first time that enhanced NADPH-derived superoxide anion production is associated with reduced NO bioavailability in aortas of beta 2KO mice. This study extends the knowledge of the relevance of the endogenous activity of beta(2)-AR to the maintenance of the vascular physiology. Copyright (C) 2012 S. Karger AG, Basel

A high-fat meal impairs muscle vasodilatation response to mental stress in humans with Glu27 β2-adrenoceptor polymorphism

Abstract Background Forearm blood flow responses during mental stress are greater in individuals homozygous for the Glu27 allele. A high-fat meal is associated with impaired endothelium-dependent dilatation. We investigated the impact of high-fat ingestion on the muscle vasodilatory responses during mental stress in individuals with the Glu27 allele and those with the Gln27 allele of the β2-adrenoceptor gene. Methods A total of 162 preselected individuals were genotyped for the Glu27Gln β2-adrenoceptor polymorphism. Twenty-four individuals participated in the study. Fourteen were homozygous for the Gln27 allele (Gln27Gln, 40 ± 2 years; 64 ± 2 kg), and 10 were homozygous for the Glu27 allele (Glu27Glu, 40 ± 3 years; 65 ± 3 kg). Forearm blood flow was evaluated by venous occlusion plethysmography before and after ingestion of 62 g of fat. Results The high-fat meal caused no changes in baseline forearm vascular conductance (FVC, 2.2 ± 0.1 vs. 2.4 ± 0.2; P = 0.27, respectively), but reduced FVC responses to mental stress (1.5 ± 0.2 vs. 0.8 ± 0.2 units; P = 0.04). When volunteers were divided according to their genotypes, baseline FVC was not different between groups (Glu27Glu = 2.4 ± 0.1 vs. Gln27Gln = 2.1 ± 0.1 units; P = 0.08), but it was significantly greater in Glu27Glu individuals during mental stress (1.9 ± 0.4 vs. 1.0 ± 0.3 units; P = 0.04). High-fat intake eliminated the difference in FVC responses between Glu27Glu and Gln27Gln individuals (FVC, 1.3 ± 0.4 vs. 1.2 ± 0.4; P = 0.66, respectively). Conclusion These findings demonstrate that a high-fat meal impairs muscle vasodilatation responses to mental stress in humans. However, this reduction can be attributed to the presence of the homozygous Glu27 allele of the β2-adrenoceptor gene.

Small volume of hypertonic saline as the initial fluid replacement in experimental hypodynamic sepsis

Abstract Introduction We conducted the present study to examine the effects of hypertonic saline solution (7.5%) on cardiovascular function and splanchnic perfusion in experimental sepsis. Methods Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over 30 minutes. After 30 minutes, they were randomized to receive lactated Ringer's solution 32 ml/kg (LR; n = 7) over 30 minutes or 7.5% hypertonic saline solution 4 ml/kg (HS; n = 8) over 5 minutes. They were observed without additional interventions for 120 minutes. Cardiac output (CO), mean arterial pressure (MAP), portal and renal blood flow (PBF and RBF, respectively), gastric partial pressure of CO2 (pCO2; gas tonometry), blood gases and lactate levels were assessed. Results E. coli infusion promoted significant reductions in CO, MAP, PBF and RBF (approximately 45%, 12%, 45% and 25%, respectively) accompanied by an increase in lactate levels and systemic and mesenteric oxygen extraction (sO2ER and mO2ER). Widening of venous-arterial (approximately 15 mmHg), portal-arterial (approximately 18 mmHg) and gastric mucosal-arterial (approximately 55 mmHg) pCO2 gradients were also observed. LR and HS infusion transiently improved systemic and regional blood flow. However, HS infusion was associated with a significant and sustained reduction of systemic (18 ± 2.6 versus 38 ± 5.9%) and mesenteric oxygen extraction (18.5 ± 1.9 versus 36.5 ± 5.4%), without worsening other perfusional markers. Conclusion A large volume of LR or a small volume of HS promoted similar transient hemodynamic benefits in this sepsis model. However, a single bolus of HS did promote sustained reduction of systemic and mesenteric oxygen extraction, suggesting that hypertonic saline solution could be used as a salutary intervention during fluid resuscitation in septic patients.