In vitro hemodynamic evaluation of ventricular suction conditions of the EVAHEART ventricular assist pump

Purpose: Mismatches between pump output and venous return in a continuous-flow ventricular assist device may elicit episodes of ventricular suction. This research describes a series of in vitro experiments to characterize the operating conditions under which the EVAHEART centrifugal blood pump (Sun Medical Technology Research Corp., Nagano, Japan) can be operated with minimal concern regarding left ventricular (LV) suction. Methods: The pump was interposed into a pneumatically driven pulsatile mock circulatory system (MCS) in the ventricular apex to aorta configuration. Under varying conditions of preload, afterload, and systolic pressure, the speed of the pump was increased step-wise until suction was observed. Identification of suction was based on pump inlet pressure. Results: In the case of reduced LV systolic pressure, reduced preload (=10 mmHg), and afterload (=60 mmHg), suction was observed for speeds =2,200 rpm. However, suction did not occur at any speed (up to a maximum speed of 2,400 rpm) when preload was kept within 10-14 mmHg and afterload =80 mmHg. Although in vitro experiments cannot replace in vivo models, the results indicated that ventricular suction can be avoided if sufficient preload and afterload are maintained. Conclusion: Conditions of hypovolemia and/or hypotension may increase the risk of suction at the highest speeds, irrespective of the native ventricular systolic pressure. However, in vitro guidelines are not directly transferrable to the clinical situation; therefore, patient-specific evaluation is recommended, which can be aided by ultrasonography at various points in the course of support.

Hemodynamic Modeling of the Intrarenal Circulation

Three dimensional, time dependent numerical simulations of healthy and pathological conditions in a model kidney were performed. Blood flow in a kidney is not commonly investigated by computational approach, in contrast for example, to the flow in a heart. The flow in a kidney is characterized by relatively small Reynolds number (100 < Re < 0.01-laminar regime). The presented results give insight into the structure of such flow, which is hard to measure in vivo. The simulations have suggested that venous thrombosis is more likely than arterial thrombosis-higher shear rate observed. The obtained maximum velocity, as a result of the simulations, agrees with the observed in vivo measurements. The time dependent simulations show separation regimes present in the vicinity of the maximum pressure value. The pathological constriction introduced to the arterial geometry leads to the changes in separation structures. The constriction of a single vessel affects flow in the whole kidney. Pathology results in different flow rate values in healthy and affected branches, as well as, different pulsate cycle characteristic for the whole system.

Increased sensitivity in mapping task demand in visuospatial processing using reaction-time-dependent hemodynamic response predictors in rapid event-related fMRI

Searching for the neural correlates of visuospatial processing using functional magnetic resonance imaging (fMRI) is usually done in an event-related framework of cognitive subtraction, applying a paradigm comprising visuospatial cognitive components and a corresponding control task. Besides methodological caveats of the cognitive subtraction approach, the standard general linear model with fixed hemodynamic response predictors bears the risk of being underspecified. It does not take into account the variability of the blood oxygen level-dependent signal response due to variable task demand and performance on the level of each single trial. This underspecification may result in reduced sensitivity regarding the identification of task-related brain regions. In a rapid event-related fMRI study, we used an extended general linear model including single-trial reaction-time-dependent hemodynamic response predictors for the analysis of an angle discrimination task. In addition to the already known regions in superior and inferior parietal lobule, mapping the reaction-time-dependent hemodynamic response predictor revealed a more specific network including task demand-dependent regions not being detectable using the cognitive subtraction method, such as bilateral caudate nucleus and insula, right inferior frontal gyrus and left precentral gyrus.

Hemodynamic effects of thoracic epidural analgesia in ovine hyperdynamic endotoxemia

BACKGROUND AND OBJECTIVES: Thoracic epidural analgesia (TEA) is increasingly used for perioperative analgesia. If patients with TEA develop sepsis or systemic inflammatory response subsequent to extended surgery the question arises if it would be safe to continue TEA with its beneficial effects of improving gastrointestinal perfusion and augmenting tissue oxygenation. A major concern in this regard is hemodynamic instability that might ensue from TEA-induced vasodilation. The objective of the present study was to assess the effects of TEA on systemic and pulmonary hemodynamics in a sepsis model of hyperdynamic endotoxemia. METHODS: After a baseline measurement in healthy sheep (n = 14), Salmonella thyphosa endotoxin was continuously infused at a rate of 10 ngxkg(-1)xmin(-1) over 16 hours. The surviving animals (n = 12) were then randomly assigned to 1 of 2 study groups. In the treatment group (n = 6), continuous TEA was initiated with 0.1 mLxkg(-1) bupivacaine 0.125% and maintained with 0.1 mLxkg(-1)xh(-1). In the control group (n = 6) the same amount of isotonic sodium saline solution was injected at the same rate through the epidural catheter. RESULTS: In both experimental groups cardiac index increased and systemic vascular resistance decreased concurrently (each P < .05). Functional epidural blockade in the TEA group was confirmed by sustained suppression of the cutaneous (or panniculus) reflex. During the observational period of 6 hours neither systemic nor pulmonary circulatory variables were impaired by TEA. CONCLUSIONS: From a hemodynamic point of view, TEA presents as a safe treatment option in sepsis or systemic inflammatory response syndrome.

Influence of stent type on hemodynamic depression after carotid artery stent placement

PURPOSE: To assess the effect of stent type on hypotension and bradycardia after carotid artery stent placement. MATERIALS AND METHODS: A retrospective analysis on a prospectively maintained database was conducted in 256 patients (126 men; mean age, 71.8 years +/- 8.6; 194 de novo lesions) undergoing carotid artery stent placement between January 1996 and January 2007 by using self-expanding stents. Braided Elgiloy stents (Wallstents) were used in 44 of the 256 patients (17.2%) and slotted-tube nitinol stents were deployed in 212 (82.8%). Bivariate and multivariable logistic regression models were used to determine the influence of stent design on procedural and 24-hour hypotension and bradycardia. RESULTS: Procedural hemodynamic depression (HD) was encountered in 73 of the 256 patients (28.5%) due to hypotension in 24 (9.4%), bradycardia in 12 (4.7%), or both in 37 (14.5%) patients. Rates of procedural hypotension were 11.3% with nitinol stents and 0% with braided Elgiloy stents (P = .0188). Persistent postprocedural HD occurred in 91 of the 256 patients (35.5%) due to hypotension in 40 patients (15.6%), bradycardia in 23 (9.0%), or both in 28 (10.9%). Within a multivariable analysis adjusted for clinically relevant factors affecting rates of HD, the use of braided Elgiloy stents was associated with a decreased rate of procedural hypotension (odds ratio: 0.165; 95% confidence interval: 0.038, 0.721; P = .017). Procedural hypotension and bradycardia were not correlated to incidence of major adverse events but were associated with an increased duration of hospital stay (P = .0059 and P = .0335, respectively). CONCLUSIONS: Nitinol stents are associated with a higher risk of hypotension as compared to braided Elgiloy stents during carotid artery stent placement.

Clinical and hemodynamic predictors of natriuretic peptide elevation among aortic valve disease patients

We investigated the relative contribution of hemodynamic and clinical factors to serum natriuretic peptide elevation in seventy-one patients with either aortic stenosis or aortic regurgitation. We found that pulmonary hypertension, heart failure and renal failure are the most powerful independent predictors of natriuretic peptide elevation in patients with aortic valve disease, irrespective of the type or severity of valvular lesion itself.

Hemodynamic variables and mortality in cardiogenic shock: a retrospective cohort study

INTRODUCTION: Despite the key role of hemodynamic goals, there are few data addressing the question as to which hemodynamic variables are associated with outcome or should be targeted in cardiogenic shock patients. The aim of this study was to investigate the association between hemodynamic variables and cardiogenic shock mortality. METHODS: Medical records and the patient data management system of a multidisciplinary intensive care unit (ICU) were reviewed for patients admitted because of cardiogenic shock. In all patients, the hourly variable time integral of hemodynamic variables during the first 24 hours after ICU admission was calculated. If hemodynamic variables were associated with 28-day mortality, the hourly variable time integral of drops below clinically relevant threshold levels was computed. Regression models and receiver operator characteristic analyses were calculated. All statistical models were adjusted for age, admission year, mean catecholamine doses and the Simplified Acute Physiology Score II (excluding hemodynamic counts) in order to account for the influence of age, changes in therapies during the observation period, the severity of cardiovascular failure and the severity of the underlying disease on 28-day mortality. RESULTS: One-hundred and nineteen patients were included. Cardiac index (CI) (P = 0.01) and cardiac power index (CPI) (P = 0.03) were the only hemodynamic variables separately associated with mortality. The hourly time integral of CI drops <3, 2.75 (both P = 0.02) and 2.5 (P = 0.03) L/min/m2 was associated with death but not that of CI drops <2 L/min/m2 or lower thresholds (all P > 0.05). The hourly time integral of CPI drops <0.5-0.8 W/m2 (all P = 0.04) was associated with 28-day mortality but not that of CPI drops <0.4 W/m2 or lower thresholds (all P > 0.05). CONCLUSIONS: During the first 24 hours after intensive care unit admission, CI and CPI are the most important hemodynamic variables separately associated with 28-day mortality in patients with cardiogenic shock. A CI of 3 L/min/m2 and a CPI of 0.8 W/m2 were most predictive of 28-day mortality. Since our results must be considered hypothesis-generating, randomized controlled trials are required to evaluate whether targeting these levels as early resuscitation endpoints can improve mortality in cardiogenic shock.

Eccentric exercise in coronary patients: central hemodynamic and metabolic responses

With lengthening (eccentric) muscle contractions, the magnitude of locomotor-muscle mass and strength increase has been demonstrated to be greater compared with shortening (concentric) muscle contractions. In healthy subjects, energy demand and heart rate responses with eccentric exercise are small relative to the amount of muscle force produced. Thus, eccentric exercise may be an attractive alternative to resistance exercise for patients with limited cardiovascular exercise tolerance.

Combined inhibition of complement C5 and CD14 markedly attenuates inflammation, thrombogenicity, and hemodynamic changes in porcine sepsis

Complement and the TLR family constitute two important branches of innate immunity. We previously showed attenuating effects on inflammation and thromogenicity by inhibiting the TLR coreceptor CD14 in porcine sepsis. In the present study, we explored the effect of the C5 and leukotriene B4 inhibitor Ornithodoros moubata complement inhibitor (OmCI; also known as coversin) alone and combined with anti-CD14 on the early inflammatory, hemostatic, and hemodynamic responses in porcine Escherichia coli-induced sepsis. Pigs were randomly allocated to negative controls (n = 6), positive controls (n = 8), intervention with OmCI (n = 8), or with OmCI and anti-CD14 (n = 8). OmCI ablated C5 activation and formation of the terminal complement complex and significantly decreased leukotriene B4 levels in septic pigs. Granulocyte tissue factor expression, formation of thrombin-antithrombin complexes (p < 0.001), and formation of TNF-α and IL-6 (p < 0.05) were efficiently inhibited by OmCI alone and abolished or strongly attenuated by the combination of OmCI and anti-CD14 (p < 0.001 for all). Additionally, the combined therapy attenuated the formation of plasminogen activator inhibitor-1 (p < 0.05), IL-1β, and IL-8, increased the formation of IL-10, and abolished the expression of wCD11R3 (CD11b) and the fall in neutrophil cell count (p < 0.001 for all). Finally, OmCI combined with anti-CD14 delayed increases in heart rate by 60 min (p < 0.05) and mean pulmonary artery pressure by 30 min (p < 0.01). Ex vivo studies confirmed the additional effect of combining anti-CD14 with OmCI. In conclusion, upstream inhibition of the key innate immunity molecules, C5 and CD14, is a potential broad-acting treatment regimen in sepsis as it efficiently attenuated inflammation and thrombogenicity and delayed hemodynamic changes.

Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis

Septic shock is characterized by increased vascular permeability and hypotension despite increased cardiac output. Numerous vasoactive cytokines are upregulated during sepsis, including angiopoietin 2 (ANG2), which increases vascular permeability. Here we report that mice engineered to inducibly overexpress ANG2 in the endothelium developed sepsis-like hemodynamic alterations, including systemic hypotension, increased cardiac output, and dilatory cardiomyopathy. Conversely, mice with cardiomyocyte-restricted ANG2 overexpression failed to develop hemodynamic alterations. Interestingly, the hemodynamic alterations associated with endothelial-specific overexpression of ANG2 and the loss of capillary-associated pericytes were reversed by intravenous injections of adeno-associated viruses (AAVs) transducing cDNA for angiopoietin 1, a TIE2 ligand that antagonizes ANG2, or AAVs encoding PDGFB, a chemoattractant for pericytes. To confirm the role of ANG2 in sepsis, we i.p. injected LPS into C57BL/6J mice, which rapidly developed hypotension, acute pericyte loss, and increased vascular permeability. Importantly, ANG2 antibody treatment attenuated LPS-induced hemodynamic alterations and reduced the mortality rate at 36 hours from 95% to 61%. These data indicate that ANG2-mediated microvascular disintegration contributes to septic shock and that inhibition of the ANG2/TIE2 interaction during sepsis is a potential therapeutic target.

Cerebral hemodynamic and oxygenation changes induced by inner and heard speech: a study combining functional near-infrared spectroscopy and capnography

The aim of this study was to investigate the effects of inner and heard speech on cerebral hemodynamics and oxygenation in the anterior prefrontal cortex (PFC) using functional near-infrared spectroscopy and to test whether potential effects were caused by alterations in the arterial carbon dioxide pressure (PaCO2). Twenty-nine healthy adult volunteers performed six different tasks of inner and heard speech according to a randomized crossover design. During the tasks, we generally found a decrease in PaCO2 (only for inner speech), tissue oxygen saturation (StO2), oxyhemoglobin ([O2Hb]), total hemoglobin ([tHb]) concentration and an increase in deoxyhemoglobin concentration ([HHb]). Furthermore, we found significant relations between changes in [O2Hb], [HHb], [tHb], or StO2 and the participants’ age, the baseline PETCO2, or certain speech tasks. We conclude that changes in breathing during the tasks led to lower PaCO2 (hypocapnia) for inner speech. During heard speech, no significant changes in PaCO2 occurred, but the decreases in StO2, [O2Hb], and [tHb] suggest that changes in PaCO2 were also involved here. Different verse types (hexameter and alliteration) led to different changes in [tHb], implying different brain activations. In conclusion, StO2, [O2Hb], [HHb], and [tHb] are affected by interplay of both PaCO2 reactivity and functional brain activity.