Regional Blood Flow Distribution Research Articles

Effects of Myocardial Infarction-induced Heart Failure on Diaphragm Arteriolar Vasorelaxation

INTRODUCTION: Diaphragm atrophy and contractile dysfunction are prevalent in heart failure (HF), diminishing physical capacity and quality of life. The delivery of blood flow and oxygen necessary to support the metabolic demand of contractions is largely governed by the resistance vasculature (i.e., arterioles) with the endothelium playing a central role in arteriolar vasorelaxation. Adequate perfusion and blood flow distribution, and thus resistance vessel vasodilation, is a major determinate of diaphragm contractile function. While the mechanistic bases of HF-induced diaphragm dysfunction continue to be elucidated, the impact of HF on diaphragm vasomotor control has not been investigated. METHODS: Adult (6 mo) Sprague-Dawley rats (n=7) were divided into two groups: 1) Healthy Control (HC; n=4) and 2) MI-induced heart failure (HF; n=3). First-order arterioles (1A) from the medial costal diaphragm were isolated, cannulated, and pressurized at 90 cmH2O and allowed to equilibrate for 60 min to develop spontaneous tone. Thereafter, endothelium-dependent and -independent vasorelaxation responses to cumulative doses of acetylcholine (ACh; 10−9 to 10−4M) and sodium nitroprusside (SNP; 10−9 to 10−4M) were determined. RESULTS: There were no differences in spontaneous development (%) or maximal diameter (μm) between HC (20 ± 4%; 178 ± 11 μm) and HF (18 ± 2%; 184 ± 29 μm) diaphragm 1As ( P > 0.05). Maximal ACh-mediated relaxation (%) was significantly reduced in HF rats compared to HC rats (52 ± 2 versus 68 ± 5%; P < 0.05). Maximal endothelial-independent vasorelaxation with SNP, was not different between HC and HF rats (71 ± 3 versus 73 ± 1%; P > 0.05). CONCLUSION: The preliminary data herein demonstrate that HF impaired endothelial function and vasomotor function in the medial costal diaphragm resistance vasculature. This suggests that, in HF, there may be a redistribution of blood flow to less effcient regions of the diaphragm (e.g., ventral costal) to sustain contractile function and compensate for the diminished medial costal vasomotor function demonstrated herein. Studies including a larger sample size are warranted to investigate the impact of HF on regional blood flow distribution and resistance vessel function in the diaphragm. Such investigations would yield novel mechanistic insights into HF-induced diaphragm dysfunction. National Institute of Aging 1R15AG078060, Ruth L. Kirschstein National Research Service Awards from the National Heart, Lung, and Blood Institute 1F31HL167618-01, and Sustained Momentum for Investigators with Laboratories Established (SMILE) Grants at Kansas State University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Magnetic resonance imaging as a noninvasive adjunct to conventional assessment of functional differences between kidneys in vivo and during ex vivo normothermic machine perfusion

Normothermic machine perfusion (NMP) is increasingly considered for pretransplant kidney quality assessment. However, fundamental questions about differences between in vivo and ex vivo renal function, as well as the impact of ischemic injury on ex vivo physiology, remain unanswered. This study utilized magnetic resonance imaging (MRI), alongside conventional parameters to explore differences between in vivo and ex vivo renal function and the impact of warm ischemia on a kidney’s behavior ex vivo. Renal MRI scans and samples were obtained from living pigs (n = 30) in vivo. Next, kidney pairs were procured and exposed to minimal, or 75 minutes of warm ischemia, followed by 6 hours of hypothermic machine perfusion. Both kidneys simultaneously underwent 6-hour ex vivo perfusion in MRI-compatible NMP circuits to obtain multiparametric MRI data. Ischemically injured ex vivo kidneys showed a significantly altered regional blood flow distribution compared to in vivo and minimally damaged organs. Both ex vivo groups showed diffusion restriction relative to in vivo. Our findings underscore the differences between in vivo and ex vivo MRI-based renal characteristics. Therefore, when assessing organ viability during NMP, it should be considered to incorporate parameters beyond the conventional functional markers that are common in vivo.

Evaluation of Different Contrast Agents for Regional Lung Perfusion Measurement Using Electrical Impedance Tomography: An Experimental Pilot Study.

Monitoring regional blood flow distribution in the lungs appears to be useful for individually optimizing ventilation therapy. Electrical impedance tomography (EIT) can be used at the bedside for indicator-based regional lung perfusion measurement. Hypertonic saline is widely used as a contrast agent but could be problematic for clinical use due to potential side effects. In five ventilated healthy pigs, we investigated the suitability of five different injectable and clinically approved solutions as contrast agents for EIT-based lung perfusion measurement. Signal extraction success rate, signal strength, and image quality were analyzed after repeated 10 mL bolus injections during temporary apnea. The best results were obtained using NaCl 5.85% and sodium-bicarbonate 8.4% with optimal success rates (100%, each), the highest signal strengths (100 ± 25% and 64 ± 17%), and image qualities (r = 0.98 ± 0.02 and 0.95 ± 0.07). Iomeprol 400 mg/mL (non-ionic iodinated X-ray contrast medium) and Glucose 5% (non-ionic glucose solution) resulted in mostly well usable signals with above average success rates (87% and 89%), acceptable signal strength (32 ± 8% and 16 + 3%), and sufficient image qualities (r = 0.80 ± 0.19 and 0.72 ± 0.21). Isotonic balanced crystalloid solution failed due to a poor success rate (42%), low signal strength (10 ± 4%), and image quality (r = 0.43 ± 0.28). While Iomeprol might enable simultaneous EIT and X-ray measurements, glucose might help to avoid sodium and chloride overload. Further research should address optimal doses to balance reliability and potential side effects.

The effect of posture on airflow distribution, airway geometry and air velocity in healthy subjects

BackgroundGravity, and thus body position, can affect the regional distribution of lung ventilation and blood flow. Therefore, body positioning is a potential tool to improve regional ventilation, thereby possibly enhancing the effect of respiratory physiotherapy interventions. In this proof-of-concept study, functional respiratory imaging (FRI) was used to objectively assess effects of body position on regional airflow distribution in the lungs.MethodsFive healthy volunteers were recruited. The participants were asked during FRI first to lie in supine position, afterwards in standardized right lateral position.ResultsIn right lateral position there was significantly more regional ventilation also described as Imaging Airflow Distribution in the right lung than in the left lung (P < 0.001). Air velocity was significantly higher in the left lung (P < 0.05). In right lateral position there was significantly more airflow distribution in the right lung than in the left lung (P < 0.001). Significant changes were observed in airway geometry resulting in a decrease in imaged airway volume (P = 0.024) and a higher imaged airway resistance (P = 0.029) in the dependent lung. In general, the effect of right lateral position caused a significant increase in regional ventilation (P < 0.001) in the dependent lung when compared with the supine position.ConclusionsChanging body position leads to significant changes in regional lung ventilation, objectively assessed by FRI The volume based on the imaging parameters in the dependent lung is smaller in the lateral position than in the supine position. In right lateral decubitus position, airflow distribution is greater in dependent lung compared to the nondependent lung.Trial registration: The trial has been submitted to www.clinicaltrials.gov with identification number NCT01893697 on 07/02/2013.

A comparison of coronary angiography and myocardial perfusion studies, using quantitative scoring systems

Background: Results of myocardial perfusion for screening coronary artery disease (CAD), and angiography for diagnosing CAD, can be quantified using summed difference score (SDS) and Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score, respectively. Aim: The aim is to quantitatively compare myocardial perfusion studies with angiography amongst South African patients using scoring systems. Methods: SDS on myocardial perfusion and SYNTAX score on angiography were compared. Regional scores within each vessel (left anterior descending (LAD), circumflex and right coronary artery (RCA)) were also compared. Scores were further risk categorised and evaluated. Results: The weak correlation between SDS and SYNTAX score (rs=0.210, p=0.015), became slightly negative when SYNTAX scores were stratified into low and intermediate-high risk groups. Regionally, LAD had very slight positive correlation (rs=0.171, p=0.048), circumflex (rs=0.164, p=0.058), and RCA (rs=0.116, p=0.184) no correlation. Conversely, comparison of scores categories was signifi cant (p=0.001). Conclusions: Inherent differences in the design of 2 scoring systems that evaluate the LAD territory may explain these findings. These differences were dominance, regional blood flow distribution and significant luminal diameter reduction. This study highlights the need to interpret myocardial perfusion results contextually during CAD screening.

Characteristics of Regional Cerebral Blood Flow in Alzheimer Disease and Amnestic Mild Cognitive Impairment by Single-Photon Emission Computerized Tomography: A Cross-Sectional Study

Introduction: The regional cerebral blood flow (rCBF) distribution can affect brain functioning, leading to amnestic mild cognitive impairment (aMCI) and mild Alzheimer disease (AD). This study aimed to clarify the detailed characteristics of rCBF distribution in patients with mild AD and aMCI. Methods: This cross-sectional study from April 2015 to March 2018 included 103 older adults (mean age 78.9 years; 60% females), out of a total of 302 adults, and categorized them into 3 groups according to cognitive symptoms. The normal control (NC), aMCI, and mild AD groups included 20, 50, and 33 participants, respectively. The primary outcome was rCBF, which was compared among the 3 groups using a 2-sample t test without correction for multiple comparisons. Results: In the aMCI group, the rCBF decreased in the bilateral parietal and left frontal association cortex and the bilateral premotor cortex (p < 0.01) but increased in the bilateral cerebellum (p < 0.01). In the mild AD group, the rCBF decreased in the bilateral parietal and occipital association cortex, the bilateral premotor cortex, the left temporal and frontal association cortex, and the left limbic lobe (p < 0.01). Conversely, the rCBF increased in some parts of the cerebellum, the bilateral frontal and temporal association cortex, the left occipital association cortex, and the right premotor cortex (p < 0.01). Conclusion: Based on the analysis of the values obtained, it was inferred that the rCBF undergoes reduction and elevation in aMCI and AD patients.

Longitudinal changes in regional cerebral blood flow in late middle-aged and older adults with treated and untreated obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with abnormal cerebral perfusion at wakefulness, but whether these anomalies evolve over time is unknown. Here, we examined longitudinal changes in regional cerebral blood flow (rCBF) distribution in late middle‐aged and older adults with treated or untreated OSA. Twelve controls (64.8 ± 8.0 years) and 23 participants with newly diagnosed OSA (67.8 ± 6.2 years) were evaluated with polysomnography and cerebral 99mTc‐HMPAO single‐photon emission computed tomography during wakeful rest. OSA participants were referred to a sleep apnea clinic and 13 of them decided to start continuous positive airway pressure (CPAP). Participants were tested again after 18 months. Voxel‐based analysis and extracted relative rCBF values were used to assess longitudinal changes. Untreated OSA participants showed decreased relative rCBF in the left hippocampus and the right parahippocampal gyrus over time, while treated participants showed trends for increased relative rCBF in the left hippocampus and the right parahippocampal gyrus. No changes were found over time in controls. Untreated OSA is associated with worsening relative rCBF in specific brain areas over time, while treated OSA shows the opposite. Considering that OSA possibly accelerates cognitive decline in older adults, CPAP treatment could help reduce risk for cognitive impairment.

Effects of notoginseng leaf triterpenes on small molecule metabolism after cerebral ischemia/reperfusion injury assessed using MALDI-MS imaging.

BackgroundNotoginseng leaf triterpenes (PNGL) is believed to have neuroprotective effects via the inhibition of inflammatory response and neuronal apoptosis. However, its mechanisms underlying the anti-ischemia/reperfusion (I/R) injury effects on the regulation of small molecule metabolism in rat brain remains unclear. The purpose of this study was thus to explore the mechanisms of PNGL on the regulation of small molecule metabolism in rat brain after I/R injury using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI).MethodsAs a model of in vivo cerebral I/R injury, male Sprague-Dawley (SD) rats were established with a middle cerebral artery occlusion/reperfusion (MCAO/R) model after PNGL administration with 40 mg·kg-1 through intraperitoneal injection (i.p.) for 7 days. We assessed the neurological behavior, regional cerebral blood flow (r CBF), neuron injury, and spatial distribution of metabolic small molecules.ResultsOur in vivo results suggested that PNGL increased cerebral blood flow and relieved neurological dysfunction. Furthermore, using MALDI-MSI, we demonstrated that PNGL regulated 16 endogenous small molecules implicated in metabolic networks including tricarboxylic acid (TCA) cycle, adenosine triphosphate (ATP) metabolism, malate-aspartate shuttle, metal ions, and antioxidants underwent noticeable changes after reperfusion for 24 h.ConclusionsPNGL is a novel cerebrovascular agent that can improve cerebral blood flow and attenuate adverse neurological disorders. The mechanisms are closely correlated with relative metabolic pathways, which offers insight into exploring new mechanisms in PNGL for the treatment of cerebral I/R injury.

Noninvasive Renal Perfusion Measurement Using Arterial Spin Labeling (ASL) MRI: Basic Concept.

The kidney is a complex organ involved in the excretion of metabolic products as well as the regulation of body fluids, osmolarity, and homeostatic status. These functions are influenced in large part by alterations in the regional distribution of blood flow between the renal cortex and medulla. Renal perfusion is therefore a key determinant of glomerular filtration. Therefore the quantification of regional renal perfusion could provide important insights into renal function and renal (patho)physiology. Arterial spin labeling (ASL) based perfusion MRI techniques, can offer a noninvasive and reproducible way of measuring renal perfusion in animal models. This chapter addresses the basic concept of ASL-MRI.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Awake prone positioning in COVID-19

In the absence of effective targeted therapies for COVID-19, optimisation of supportive care is essential. Lung injury with features of acute respiratory distress syndrome (ARDS) appears to be the principal...

Bio-Inspired Artificial Red Blood Cell: Design, Pre-Clinical Results and Novel Indications

In blood, the primary role of RBCs is to transport oxygen and to regulate regional blood flow distribution, via highly regulated mechanisms. In the setting of exsanguinating haemorrhage or severe anemia, RBC loss may critically restrict tissue oxygenation and result in morbidity and mortality. In such cases, transfusion of whole blood or RBCs can significantly improve survival. However, blood products including RBCs have limited availability and portability and present additional challenges related to type matching, pathogenic contamination risks, and short shelf-life. These issues lead to substantial logistical barriers to their pre-hospital use or in austere battlefield and remote civilian conditions. To date, efforts to develop hemoglobin (Hb) based oxygen carriers (HBOCs) have failed, because of design flaws which do not preserve physiologic interactions of Hb with: O2 (they capture O2 in lungs, but do not release O2 effectively to tissue) and nitric oxide (NO) (they trap NO, causing vasoconstriction). While robust efforts are underway to resolve these issues, recent research breakthroughs have led to bio-inspired engineering of RBC surrogates, using various cross-linked, polymeric and encapsulated Hb in the form of 'bio-synthetic RBC surrogates'. These 'next-generation' Hb-based oxygen carriers (HBOCs) can potentially provide therapeutic oxygenation when whole blood or RBC are not available. This talk will comprehensively review both historical and new HBOC designs, including current state-of-the-art and novel bio-inspired artificial RBC designs in development, along with a critical discussion of successes and challenges in this field. Disclosures Doctor: Biogen: Membership on an entity's Board of Directors or advisory committees; Fresenius Kabi: Honoraria; KaloCyte, Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents &amp; Royalties; Etiometry: Membership on an entity's Board of Directors or advisory committees.

ECMO with vasopressor use during early endotoxic shock: Can it improve circulatory support and regional microcirculatory blood flow?

While extracorporeal membrane oxygenation (ECMO) is effective in preventing further hypoxemia and maintains blood flow in endotoxin-induced shock, ECMO alone does not reverse the hypotension. In this study, we tested whether concurrent vasopressor use with ECMO would provide increased circulatory support and blood flow, and characterized regional blood flow distribution to vital organs. Endotoxic shock was induced in piglets to achieve a 30% decrease in mean arterial pressure (MAP). Measurements of untreated pigs were compared to pigs treated with ECMO alone or ECMO and vasopressors. ECMO provided cardiac support during vasodilatory endotoxic shock and improved oxygen delivery, but vasopressor therapy was required to return MAP to normotensive levels. Increased blood pressure with vasopressors did not alter oxygen consumption or extraction compared to ECMO alone. Regional microcirculatory blood flow (RBF) to the brain, kidney, and liver were maintained or increased during ECMO with and without vasopressors. ECMO support and concurrent vasopressor use improve regional blood flow and oxygen delivery even in the absence of full blood pressure restoration. Vasopressor-induced selective distribution of blood flow to vital organs is retained when vasopressors are administered with ECMO.

Mitochondria in Sepsis-Induced AKI.

AKI is a common clinical condition associated with the risk of developing CKD and ESKD. Sepsis is the leading cause of AKI in the intensive care unit (ICU) and accounts for nearly half of all AKI events. Patients with AKI who require dialysis have an unacceptably high mortality rate of 60%-80%. During sepsis, endothelial activation, increased microvascular permeability, changes in regional blood flow distribution with resulting areas of hypoperfusion, and hypoxemia can lead to AKI. No effective drugs to prevent or treat human sepsis-induced AKI are currently available. Recent research has identified dysfunction in energy metabolism as a critical contributor to the pathogenesis of AKI. Mitochondria, the center of energy metabolism, are increasingly recognized to be involved in the pathophysiology of sepsis-induced AKI and mitochondria could serve as a potential therapeutic target. In this review, we summarize the potential role of mitochondria in sepsis-induced AKI and identify future therapeutic approaches that target mitochondrial function in an effort to treat sepsis-induced AKI.

Effect of Anodal Direct-Current Stimulation on Cortical Hemodynamic Responses With Laser-Speckle Contrast Imaging.

Transcranial direct-current stimulation (DCS) offers a method for noninvasive neuromodulation usable in basic and clinical human neuroscience. Laser-speckle contrast imaging (LSCI), a powerful, low-cost method for obtaining images of dynamic systems, can detect regional blood-flow distributions with high spatial and temporal resolutions. Here, we used LSCI for measuring DCS-induced cerebral blood flow in real-time. Results showed that the change-rate of cerebral blood flow could reach approximately 10.1 ± 5.1% by DCS, indicating that DCS can increase cerebral blood flow and alter cortical hemodynamic responses. Thus, DCS shows potential for the clinical treatment and rehabilitation of ischemic strokes.

Constructive disturbance and abnormal regional cerebral blood flow distribution in amyotrophic lateral sclerosis with dementia

Constructive disturbance and abnormal regional cerebral blood flow distribution in amyotrophic lateral sclerosis with dementia

Altered Regional Cerebral Blood Flow in Idiopathic Hypersomnia.

Idiopathic hypersomnia is characterized by excessive daytime sleepiness, despite normal or long sleep time. Its pathophysiological mechanisms remain unclear. This pilot study aims at characterizing the neural correlates of idiopathic hypersomnia using single photon emission computed tomography. Thirteen participants with idiopathic hypersomnia and 16 healthy controls were scanned during resting wakefulness using a high-resolution single photon emission computed tomography scanner with 99mTc-ethyl cysteinate dimer to assess cerebral blood flow. The main analysis compared regional cerebral blood flow distribution between the two groups. Exploratory correlations between regional cerebral blood flow and clinical characteristics evaluated the functional correlates of those brain perfusion patterns. Significance was set at p < .05 after correction for multiple comparisons. Participants with idiopathic hypersomnia showed regional cerebral blood flow decreases in medial prefrontal cortex and posterior cingulate cortex and putamen, as well as increases in amygdala and temporo-occipital cortices. Lower regional cerebral blood flow in the medial prefrontal cortex was associated with higher daytime sleepiness. These preliminary findings suggest that idiopathic hypersomnia is characterized by functional alterations in brain areas involved in the modulation of vigilance states, which may contribute to the daytime symptoms of this condition. The distribution of regional cerebral blood flow changes was reminiscent of the patterns associated with normal non-rapid-eye-movement sleep, suggesting the possible presence of incomplete sleep-wake transitions. These abnormalities were strikingly distinct from those induced by acute sleep deprivation, suggesting that the patterns seen here might reflect a trait associated with idiopathic hypersomnia rather than a non-specific state of sleepiness.

Fractal Dimension of Tumor Microvasculature by DCE-US: Preliminary Study in Mice

Neoangiogenesis, which results in the formation of an irregular network of microvessels, plays a fundamental role in the growth of several types of cancer. Characterization of microvascular architecture has therefore gained increasing attention for cancer diagnosis, treatment monitoring and evaluation of new drugs. However, this characterization requires immunohistologic analysis of the resected tumors. Currently, dynamic contrast-enhanced ultrasound imaging (DCE-US) provides new options for minimally invasive investigation of the microvasculature by analysis of ultrasound contrast agent (UCA) transport kinetics. In this article, we propose a different method of analyzing UCA concentration that is based on the spatial distribution of blood flow. The well-known concept of Mandelbrot allows vascular networks to be interpreted as fractal objects related to the regional blood flow distribution and characterized by their fractal dimension (FD). To test this hypothesis, the fractal dimension of parametric maps reflecting blood flow, such as UCA wash-in rate and peak enhancement, was derived for areas representing different microvascular architectures. To this end, subcutaneous xenograft models of DU-145 and PC-3 prostate-cancer lines in mice, which show marked differences in microvessel density spatial distribution inside the tumor, were employed to test the ability of DCE-US FD analysis to differentiate between the two models. For validation purposes, the method was compared with immunohistologic results and UCA dispersion maps, which reflect the geometric properties of microvascular architecture. The results showed good agreement with the immunohistologic analysis, and the FD analysis of UCA wash-in rate and peak enhancement maps was able to differentiate between the two xenograft models (p < 0.05).

Selective α1-adrenergic blockade disturbs the regional distribution of cerebral blood flow during static handgrip exercise.

Handgrip-induced increases in blood flow through the contralateral artery that supplies the cortical representation of the arm have been hypothesized as a consequence of neurovascular coupling and a resultant metabolic attenuation of sympathetic cerebral vasoconstriction. In contrast, sympathetic restraint, in theory, inhibits changes in perfusion of the cerebral ipsilateral blood vessels. To confirm whether sympathetic nerve activity modulates cerebral blood flow distribution during static handgrip (SHG) exercise, beat-to-beat contra- and ipsilateral internal carotid artery blood flow (ICA; Doppler) and mean arterial pressure (MAP; Finometer) were simultaneously assessed in nine healthy men (27 ± 5 yr), both at rest and during a 2-min SHG bout (30% maximal voluntary contraction), under two experimental conditions: 1) control and 2) α1-adrenergic receptor blockade. End-tidal carbon dioxide (rebreathing system) was clamped throughout the study. SHG induced increases in MAP (+31.4 ± 10.7 mmHg, P < 0.05) and contralateral ICA blood flow (+80.9 ± 62.5 ml/min, P < 0.05), while no changes were observed in the ipsilateral vessel (-9.8 ± 39.3 ml/min, P > 0.05). The reduction in ipsilateral ICA vascular conductance (VC) was greater compared with contralateral ICA (contralateral: -0.8 ± 0.8 vs. ipsilateral: -2.6 ± 1.3 ml·min(-1)·mmHg(-1), P < 0.05). Prazosin was effective to induce α1-blockade since phenylephrine-induced increases in MAP were greatly reduced (P < 0.05). Under α1-adrenergic receptor blockade, SHG evoked smaller MAP responses (+19.4 ± 9.2, P < 0.05) but similar increases in ICAs blood flow (contralateral: +58.4 ± 21.5 vs. ipsilateral: +54.3 ± 46.2 ml/min, P > 0.05) and decreases in VC (contralateral: -0.4 ± 0.7 vs. ipsilateral: -0.4 ± 1.0 ml·min(-1)·mmHg(-1), P > 0.05). These findings indicate a role of sympathetic nerve activity in the regulation of cerebral blood flow distribution during SHG.

Examining the regional and cerebral depth-dependent BOLD cerebrovascular reactivity response at 7 T

Changes in cerebral blood flow (CBF) in response to hypercapnia induced changes in vascular tone, known as cerebrovascular reactivity (CVR), can be measured using the Blood Oxygenation Level Dependent (BOLD) MR contrast. We examine regional differences in the BOLD-CVR response to a progressively increasing hypercapnic stimulus as well as regional BOLD characteristics for the return to baseline normocapnia. CVR across 9 subjects was highest in the cerebral lobes and deep gray matter. Peak CVR in these regions was measured at 3.6±1.6mmHg above baseline end-tidal CO2. White matter CVR was generally reduced compared to that of the gray matter (peak white matter CVR was ~48% lower). A positive relationship between the end-tidal CO2 value at which peak CVR was measured and white matter depth is observed. Furthermore, the time required for the BOLD signal to return to baseline after cessation of the hypercapnic stimulus, was also related to white matter depth; the return, expressed as a time constant, was ~25% longer in white matter. To explain the observed differences in regional CVR response, a model is proposed that takes into account the local architecture of the cerebrovascular, which can result in changes in regional blood flow distribution as a function of end-tidal CO2.

Role of Transfused Red Blood Cells for Shock and Coagulopathy Within Remote Damage Control Resuscitation

The philosophy of damage control resuscitation (DCR) and remote damage control resuscitation (RDCR) can be summarized by stating that the goal is to prevent death from hemorrhagic shock by "staying out of trouble instead of getting out of trouble." In other words, it is preferred to arrest the progression of shock, rather than also having to reverse this condition after significant tissue damage and organ injury cascades are established. Moreover, to prevent death from exsanguination, a balanced approach to the treatment of both shock and coagulopathy is required. This was military doctrine during World War II, but seemed to be forgotten during the last half of the 20th century. Damage control resuscitation and RDCR have revitalized the approach, but there is still more to learn about the most effective and safe resuscitative strategies to simultaneously treat shock and hemorrhage. Current data suggest that our preconceived notions regarding the efficacy of standard issue red blood cells (RBCs) during the hours after transfusion may be false. Standard issue RBCs may not increase oxygen delivery and may in fact decrease it by disturbing control of regional blood flow distribution (impaired nitric oxide processing) and failing to release oxygen, even when perfusing hypoxic tissue (abnormal oxygen affinity). Standard issue RBCs may assist with hemostasis but appear to have competing effects on thrombin generation and platelet function. If standard issue or RBCs of increased storage age are not optimal, then are there alternatives that will allow for an efficacious and safe treatment of shock while also supporting hemostasis? Studies are required to determine if fresh RBCs less than 7 to 10 days provide an outcome advantage. A resurgence in the study of whole blood stored at 4°C for up to 10 days also holds promise. Two randomized controlled trials in humans have indicated that following transfusion with either whole blood stored at 4°C or platelets stored at 4°C there was less clinical bleeding than when blood was reconstituted with components or when platelets were stored at 22°C. Early reversal of shock is essential to prevent exacerbation of coagulopathy and progression of cell death cascades in patients with severe traumatic injuries. Red blood cell storage solutions have evolved to accommodate the needs of non-critically ill patients yet may not be optimal for patients in hemorrhagic shock. Continued focus on the recognition and treatment of shock is essential for continued improvement in outcomes for patients who require damage control resuscitation and RDCR.