Computational study on hemodynamic effects of left superior pulmonary vein resection and associated physiological changes in the left atrium after left upper lobectomy.

Left upper lobectomy (LUL) with left superior pulmonary vein (LSPV) resection alters the left atrium (LA) physiological states and LA hemodynamics associated with thrombosis, although this underlying mechanism is poorly understood. Therefore, we investigated the effects of LSPV resection and associated LA physiological changes on LA hemodynamics using four-dimensional computed tomography image-based computational simulations. Three cases were considered: the LA before and after LUL extracted from computed tomography images and artificial LSPV resection without physiological changes. Comparisons among the three cases demonstrated that physiological changes associated with LSPV resection are the possible factors that affect the LA hemodynamics after LUL.

A left lateral body position increases pulmonary vein stress in healthy humans.

Pulmonary vein (PV) stretch is proarrhythmic for atrial fibrillation (AF). AF patients often report that a left lateral (LL) body position can trigger arrhythmia symptoms. Because the PV myocardium is thought to trigger AF, we hypothesized that the LL compared to the supine body position increases PV wall stress. Functional cardiac magnetic resonance imaging was performed in supine and LL recumbent body position in awake condition in healthy human volunteers (n = 20). Following a change from supine to LL position, the heart moved in an anterior-LL direction in the thorax. The right superior PV diameter was increased by 19% (24.6 ± 3.1 vs. 20.7 ± 3.2 mm, p = 0.009) and left atrial (LA) volume was larger by 17% (61.7[15.4] vs. 51.0[17.8] ml, p = 0.015) in LL than supine position, respectively. The passive LA conduit fraction (normalized difference between maximum and pre-contraction LA volume) increased by 25% in LL compared to supine position (19.6 ± 9.0 vs. 15.7 ± 7.6%, respectively, p = 0.016). Local wall stress in the PV regions increased in LL compared to supine position (overall mean: 1.01 ± 0.12 vs. 1.10 ± 0.10 arb. unit, LL vs. supine, position effect p = 0.041), whereas this was not the case in the LA walls (overall mean: 1.18 ± 0.31 vs. 1.21 ± 0.21 arb. unit, LL vs. supine, position effect p = 0.381). In conclusion, a left lateral body position increases PV myocardial stress during the atrial relaxation phase of healthy volunteers. These results have implications for the mechanisms of posture-triggered AF.

Fractal analysis of concurrently prepared latex rubber casts of the bronchial and vascular systems of the human lung.

Fractal geometry (FG) is a branch of mathematics that instructively characterizes structural complexity. Branched structures are ubiquitous in both the physical and the biological realms. Fractility has therefore been termed nature's design. The fractal properties of the bronchial (airway) system, the pulmonary artery and the pulmonary vein of the human lung generates large respiratory surface area that is crammed in the lung. Also, it permits the inhaled air to intimately approximate the pulmonary capillary blood across a very thin blood-gas barrier through which gas exchange to occur by diffusion. Here, the bronchial (airway) and vascular systems were simultaneously cast with latex rubber. After corrosion, the bronchial and vascular system casts were physically separated and cleared to expose the branches. The morphogenetic (Weibel's) ordering method was used to categorize the branches on which the diameters and the lengths, as well as the angles of bifurcation, were measured. The fractal dimensions (DF) were determined by plotting the total branch measurements against the mean branch diameters on double logarithmic coordinates (axes). The diameter-determined DF values were 2.714 for the bronchial system, 2.882 for the pulmonary artery and 2.334 for the pulmonary vein while the respective values from lengths were 3.098, 3.916 and 4.041. The diameters yielded DF values that were consistent with the properties of fractal structures (i.e. self-similarity and space-filling). The data obtained here compellingly suggest that the design of the bronchial system, the pulmonary artery and the pulmonary vein of the human lung functionally comply with the Hess-Murray law or 'the principle of minimum work'.

Ion currents, action potentials, and noradrenergic responses in rat pulmonary vein and left atrial cardiomyocytes.

The electrophysiological properties of pulmonary vein (PV)-cardiomyocytes, and their responses to the sympathetic neurotransmitter, noradrenaline (NA), are thought to differ from those of the left atrium (LA) and contribute to atrial ectopy. The aim of this study was to examine rat PV cardiomyocyte electrophysiology and responses to NA in comparison with LA cells. LA and PV cardiomyocytes were isolated from adult male Wistar rat hearts, and membrane potentials and ion currents recorded at 36°C using whole-cell patch-clamp techniques. PV and LA cardiomyocytes did not differ in size. In control, there were no differences between the two cell-types in zero-current potential or action potential duration (APD) at 1 Hz, although the incidence of early afterdepolarizations (EADs) was greater in PV than LA cardiomyocytes. The L-type Ca2+ current (ICaL ) was ~×1.5 smaller (p = .0029, Student's t test) and the steady-state K+ current (IKss ) was ~×1.4 larger (p = .0028, Student's t test) in PV than in LA cardiomyocytes. PV cardiomyocyte inward-rectifier current (IK1 ) was slightly smaller than LA cardiomyocyte IK1 . In LA cardiomyocytes, NA significantly prolonged APD30 . In PV cells, APD30 responses to 1 µM NA were heterogeneous: while the mean percentage change in APD30 was not different from 0 (16.5 ± 9.7%, n cells/N animals = 12/10, p = .1177, one-sample t test), three cells showed shortening (-18.8 ± 6.0%) whereas nine showed prolongation (28.3 ± 10.1%, p = .008, Student's t test). NA had no effect on IK1 in either cell-type but inhibited PV IKss by 41.9 ± 4.1% (n/N = 23/11 p < .0001), similar to LA cells. NA increased ICaL in most PV cardiomyocytes (median × 2.2-increase, p < .0001, n/N = 32/14, Wilcoxon-signed-rank test), although in 7/32 PV cells ICaL was decreased following NA. PV cardiomyocytes differ from LA cells and respond heterogeneously to NA.

Determination of the effects of cryoablation for atrial fibrillation on esophageal functions.

OBJECTIVE: Periesophageal vagal plexus injury is a complication of cryoablation for atrial fibrillation (AF). The aim of this study is to investigate the effect of cryoablation on esophageal functions and to determine the relationship between esophageal temperature and esophageal motility. METHODS: Twenty patients with symptomatic paroxysmal AF who underwent cryoablation were included in this study. The lowest cryoballoon temperature for each pulmonary vein (PV) was recorded. Esophageal temperature was measured using an esophageal probe during each cryoapplication. Esophageal manometry was performed before the procedure and one day after the procedure for each patient in order to assess the esophageal functions. RESULTS: During the procedure, the highest esophageal temperature change was found in the left-side PVs in 13 patients (65%) and in the right-side PVs in seven patients (35%). No correlation was found between the lowest cryoballoon temperature and esophageal temperature change (r=0.22, p=0.05). It was detected that the lower esophageal sphincter pressure and esophageal contraction amplitude pressure decreased after the procedure (before: 19.7±9.3 mm Hg, after: 14.3±4.9 mm Hg, p=0.001; before: 84.5±28.3 mm Hg, after: 72.7±34.3 mm Hg, p=0.005, respectively). Five patients (25%) developed gastrointestinal symptoms after the procedure. CONCLUSION: During cryoablation, esophageal temperature measurement can be performed to reduce the probability of esophageal injury. Cryoablation affects esophageal motility, and esophageal manometry can be performed to detect esophageal motility impairments in patients with gastrointestinal symptoms.

Gas exchange calculation may estimate changes in pulmonary blood flow during veno-arterial extracorporeal membrane oxygenation in a porcine model.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is used as rescue therapy for severe cardiopulmonary failure. We tested whether the ratio of CO2 elimination at the lung and the V-A ECMO (V˙co2ECMO/V˙co2Lung) would reflect the ratio of respective blood flows and could be used to estimate changes in pulmonary blood flow (Q˙Lung), i.e., native cardiac output. Four healthy pigs were centrally cannulated for V-A ECMO. We measured blood flows with an ultrasonic flow probe. V˙co2ECMO and V˙co2Lung were calculated from sidestream capnographs under constant pulmonary ventilation during V-A ECMO weaning with changing sweep gas and/or V-A ECMO blood flow. If ventilation-to-perfusion ratio (V˙/Q˙) of V-A ECMO was not 1, the V˙co2ECMO was normalized to V˙/Q˙ = 1 (V˙co2ECMONorm). Changes in pulmonary blood flow were calculated using the relationship between changes in CO2 elimination and V-A ECMO blood flow (Q˙ECMO). Q˙ECMO correlated strongly with V˙co2ECMONorm (r2 0.95-0.99). Q˙Lung correlated well with V˙co2Lung (r2 0.65-0.89, P < = 0.002). Absolute Q˙Lung could not be calculated in a nonsteady state. Calculated pulmonary blood flow changes had a bias of 76 (-266 to 418) mL/min and correlated with measured Q˙Lung (r2 0.974-1.000, P = 0.1 to 0.006) for cumulative ECMO flow reductions. In conclusion, V˙co2 of the lung correlated strongly with pulmonary blood flow. Our model could predict pulmonary blood flow changes within clinically acceptable margins of error. The prediction is made possible with normalization to a V˙/Q˙ of 1 for ECMO. This approach depends on measurements readily available and may allow immediate assessment of the cardiac output response.

Selective inhibition of electrical conduction within the pulmonary veins by α1-adrenergic receptors activation in the Rat.

Pulmonary veins (PV) are involved in the pathophysiology of paroxysmal atrial fibrillation. In the rat, left atrium (LA) and PV cardiomyocytes have different reactions to α1-adrenergic receptor activation. In freely beating atria-PV preparations, we found that electrical field potential (EFP) originated from the sino-atrial node propagated through the LA and the PV. The α1-adrenergic receptor agonist cirazoline induced a progressive loss of EFP conduction in the PV whereas it was maintained in the LA. This could be reproduced in preparations electrically paced at 5 Hz in LA. During pacing at 10 Hz in the PV where high firing rate ectopic foci can occur, cirazoline stopped EFP conduction from the PV to the LA, which allowed the sino-atrial node to resume its pace-making function. Loss of conduction in the PV was associated with depolarization of the diastolic membrane potential of PV cardiomyocytes. Adenosine, which reversed the cirazoline-induced depolarization of the diastolic membrane potential of PV cardiomyocytes, restored full over-shooting action potentials and EFP conduction in the PV. In conclusion, selective activation of α1-adrenergic receptors results in the abolition of electrical conduction within the PV. These results highlight a potentially novel pharmacological approach to treat paroxysmal atrial fibrillation by targeting directly the PV myocardium.

Pulmonary venous Doppler patterns and midterm outcomes in fetuses with left-sided obstructive lesions and restrictive atrial septum.

OBJECTIVE: To compare length of stay of the initial neonatal hospitalization and mortality across multiple stages of surgical palliation for infants with left-sided obstructive lesions and severely restrictive or intact atrial septum (I/RAS). METHODS: Retrospective cohort study of patients prenatally diagnosed with left-sided obstructive lesions and I/RAS, defined by fetal pulmonary venous Dopplers. RESULTS: We identified 76 fetal patients with 59 live born intending to pursue intervention. Those with I/RAS had longer durations of mechanical ventilation (P = .031) but no difference in intensive care unit or total length of stay. Survival to discharge from neonatal hospitalization was 41.7% in the I/RAS group and 80.7% in the unrestrictive group (P = .001). There was a higher proportion of deaths between stage 1 and stage 2 in the I/RAS group - 5/9 (55.6%) vs 9/50 (18%) in the unrestrictive group (P = .027). Beyond stage 2 palliation there was trend toward a difference in overall mortality (66.7% in I/RAS vs 35.7% in unrestrictive, P = .05) but no statistically significant difference in transplant-free survival (33.3% in I/RAS vs 53.5% in unrestrictive, P = .11). CONCLUSION: The survival disadvantage conferred by prenatally diagnosed severe atrial septal restriction is most pronounced in the neonatal and early infancy period, with no detectable difference in late midterm transplant-free survival in our cohort.

Structural and functional definition of the pulmonary vein system in a chronic hypoxia-induced pulmonary hypertension rat model.

Unlike the pulmonary artery (PA), the pathophysiological changes of the pulmonary vein (PV) in the development of pulmonary hypertension (PH) remain largely unknown. In this study, we comprehensively investigated the structural and functional changes in the PV isolated from the chronic hypoxia (CH; 10% O2, 21 days)-induced PH rat model (CHPH). Results showed that CH caused an increase in right ventricular pressure but did not affect the mean pulmonary venous pressure and the left atrial pressure. Similar to the PA, vascular lumen stenosis and medial thickening were also observed in the intrapulmonary veins isolated from the CHPH rats. Notably, CH induced more severe loss in the endothelium of intrapulmonary veins than the arteries. Then, the contractile response to 5-HT and U46619 was significantly greater in the intrapulmonary small veins (ISPV) and arteries (ISPA) isolated from CHPH rats than those from normoxic rats but not in the extrapulmonary and intrapulmonary large veins. Treatment with nifedipine (Nif), SKF96365 (SKF), or ryanodine and caffeine either partially attenuated (Nif) or dramatically abolished (SKF or ryanodine and caffeine) 5-HT-induced maximal contraction in ISPV from both normoxic and CHPH rats. Because of the severe loss of endothelium in the PV of CHPH rats, the decrease in acetylcholine (ACh)-induced endothelium-dependent relaxation was significantly larger in ISPV than ISPA, whereas the sodium nitroprusside-induced endothelium-independent relaxation was not altered in both ISPA and ISPV. In conclusion, our results provide fundamental data to comprehensively define the PV system in CHPH rat model.

Effects of ANP on pulmonary vein electrophysiology, Ca2+ homeostasis and adrenergic arrhythmogenesis via PKA.

Atrial fibrillation (AF) is the most common form of arrhythmia and increases the risk of stroke and heart failure (HF). Pulmonary veins (PVs) are important sources of triggers that generate AF, and calcium (Ca2+ ) overload participates in PV arrhythmogenesis. Neurohormonal activation is an important cause of AF. Higher atrial natriuretic peptide (ANP) level predicts paroxysmal AF occurrence in HF patients. However, it is not clear if ANP directly modulates electrophysiological characteristics and Ca2+ homeostasis in the PVs. Conventional microelectrodes, whole-cell patch-clamp, and the Fluo-3 fluorimetric ratio technique were performed using isolated rabbit PV preparations or single isolated PV cardiomyocytes before and after ANP administration. We found that ANP (1, 10, and 100 nmol/L) concentration-dependently decreased spontaneous activity in PV preparations. ANP (100 nmol/L) decreased isoproterenol (1 µmol/L)-induced PV spontaneous activity and burst firing. AP811 (100 nmol/L, NPR-C agonist), H89 (1µmol/L, PKA inhibitor) decreased isoproterenol-induced PV spontaneous activity or burst firing, but successive administration of ANP had no further effect on PV activity. KT5823 (1 µmol/L, PKG inhibitor) decreased isoproterenol-induced PV spontaneous activity but did not change isoproterenol-induced PV burst firing, whereas successive administration of ANP did not change isoproterenol-induced PV burst firing. ANP decreased intracellular Ca2+ transient and sarcoplasmic reticulum Ca2+ content in single PV cardiomyocytes. ANP decreased the late sodium current, L-type Ca2+ current, but did not change nickel-sensitive Na+ -Ca2+ exchanger current in single PV cardiomyocytes. In conclusion, ANP directly regulates PV electrophysiological characteristics and Ca2+ homeostasis and attenuates isoproterenol-induced arrhythmogenesis through NPR-C/cAMP/PKA signal pathway.

Comparative Study of Capillary Filtration Coefficient (Kfc) Determination by a Manual and Automatic Perfusion System. Step by Step Technique Review.

The purpose of calculating the capillary filtration coefficient is to experimentally evaluate edema formation in models of pulmonary ischemia-reperfusion injury. For many years, the obtaining of this coefficient implies a series of manual maneuvers during ex-vivo reperfusion of pulmonary arterial pressure, venous pressure and weight, as well as the calculation of the Kfc formula. Through automation, the calculation of capillary filtration coefficient could be easier and more efficient. To describe an automatic method designed in our laboratory to calculating the capillary filtration coefficient and compare with traditional determination of capillary filtration coefficient as gold standard method. An automatic three valve perfusion system was constructed, commanded by a mastery module connected to a graphical user interface. To test its accuracy, cardiopulmonary blocks of Wistar rats were harvested and distributed in manual (n=8) and automated (n=8) capillary filtration coefficient determination groups. Physiological parameters as pulmonary arterial pressure, pulmonary venous pressure, weight and capillary filtration coefficient were obtained. Results: Capillary filtration coefficient, pulmonary arterial pressure, venous arterial pressure shown no statistical significance difference between the groups. The automated perfusion system for obtaining Kfc was standardized and validated, giving reliable results without biases and making the process more efficient in terms of time and personal staff.

The local repolarization heterogeneity in the murine pulmonary veins myocardium contributes to the spatial distribution of the adrenergically induced ectopic foci.

An atrial tachyarrhythmias is predominantly triggered by a proarrhythmic activity originate from the pulmonary veins (PV) myocardial sleeves; sympathetic or adrenergic stimulation facilitates PV proarrhythmia. In the present study the electrophysiological inhomogeneity, spatiotemporal characteristics of the adrenergically induced ectopic firing and sympathetic nerves distribution have been investigated in a murine PV myocardium to clarify mechanisms of adrenergic PV ectopy. Electrically paced murine PV demonstrate atrial-like pattern of conduction and atrial-like action potentials (AP) with longest duration in the mouth of PV. The application of norepinephrine (NE), agonists of α- and ß-adrenergic receptors (ARs) or intracardiac nerves stimulation induced spontaneous AP in a form of periodical bursts or continuous firing. NE- or ARs agonists-induced SAP originated from unifocal ectopic foci with predominant localization in the region surrounding PV mouth, but not in the distal portions of a murine PV myocardium. A higher level of catecholamine content and catecholamine fiber network density was revealed in the PV myocardial sleeves relative to LA appendage. However, no significant local variation of catecholamine content and fiber density was observed in the murine PV. In conclusion, PV mouth region appear to be a most susceptible to adrenergic proarrhythmia in mice. Intrinsic spatial heterogeneity of AP duration can be considered as a factor influencing localization of the ectopic foci in PV.

Supine, prone, right and left gravitational effects on human pulmonary circulation.

BACKGROUND: Body position can be optimized for pulmonary ventilation/perfusion matching during surgery and intensive care. However, positional effects upon distribution of pulmonary blood flow and vascular distensibility measured as the pulmonary blood volume variation have not been quantitatively characterized. In order to explore the potential clinical utility of body position as a modulator of pulmonary hemodynamics, we aimed to characterize gravitational effects upon distribution of pulmonary blood flow, pulmonary vascular distension, and pulmonary vascular distensibility. METHODS: Healthy subjects (n = 10) underwent phase contrast cardiovascular magnetic resonance (CMR) pulmonary artery and vein flow measurements in the supine, prone, and right/left lateral decubitus positions. For each lung, blood volume variation was calculated by subtracting venous from arterial flow per time frame. RESULTS: Body position did not change cardiac output (p = 0.84). There was no difference in blood flow between the superior and inferior pulmonary veins in the supine (p = 0.92) or prone body positions (p = 0.43). Compared to supine, pulmonary blood flow increased to the dependent lung in the lateral positions (16-33%, p = 0.002 for both). Venous but not arterial cross-sectional vessel area increased in both lungs when dependent compared to when non-dependent in the lateral positions (22-27%, p ≤ 0.01 for both). In contrast, compared to supine, distensibility increased in the non-dependent lung in the lateral positions (68-113%, p = 0.002 for both). CONCLUSIONS: CMR demonstrates that in the lateral position, there is a shift in blood flow distribution, and venous but not arterial blood volume, from the non-dependent to the dependent lung. The non-dependent lung has a sizable pulmonary vascular distensibility reserve, possibly related to left atrial pressure. These results support the physiological basis for positioning patients with unilateral pulmonary pathology with the "good lung down" in the context of intensive care. Future studies are warranted to evaluate the diagnostic potential of these physiological insights into pulmonary hemodynamics, particularly in the context of non-invasively characterizing pulmonary hypertension.

Arginine vasopressin modulates electrical activity and calcium homeostasis in pulmonary vein cardiomyocytes.

BACKGROUND: Atrial fibrillation (AF) frequently coexists with congestive heart failure (HF) and arginine vasopressin (AVP) V1 receptor antagonists are used to treat hyponatremia in HF. However, the role of AVP in HF-induced AF still remains unclear. Pulmonary veins (PVs) are central in the genesis of AF. The purpose of this study was to determine if AVP is directly involved in the regulation of PV electrophysiological properties and calcium (Ca2+) homeostasis as well as the identification of the underlying mechanisms. METHODS: Patch clamp, confocal microscopy with Fluo-3 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, Ca2+ homeostasis, and Ca2+ regulatory proteins in isolated rabbit single PV cardiomyocytes incubated with and without AVP (1 µM), OPC 21268 (0.1 µM, AVP V1 antagonist), or OPC 41061 (10 nM, AVP V2 antagonist) for 4-6 h. RESULTS: AVP (0.1 and 1 µM)-treated PV cardiomyocytes had a faster beating rate (108 to 152%) than the control cells. AVP (1 µM) treated PV cardiomyocytes had higher late sodium (Na+) and Na+/Ca2+ exchanger (NCX) currents than control PV cardiomyocytes. AVP (1 µM) treated PV cardiomyocytes had smaller Ca2+i transients, and sarcoplasmic reticulum (SR) Ca2+ content as well as higher Ca2+ leak. However, combined AVP (1 µM) and OPC 21268 (0.1 µM) treated PV cardiomyocytes had a slower PV beating rate, larger Ca2+i transients and SR Ca2+ content, smaller late Na+ and NCX currents than AVP (1 µM)-treated PV cardiomyocytes. Western blot experiments showed that AVP (1 µM) treated PV cardiomyocytes had higher expression of NCX and p-CaMKII, and a higher ratio of p-CaMKII/CaMKII. CONCLUSIONS: AVP increases PV arrhythmogenesis with dysregulated Ca2+ homeostasis through vasopressin V1 signaling.

Localization of Residual Conduction Gaps After Wide Antral Circumferential Ablation of Pulmonary Veins.

Ablation of atrial fibrillation (AF) is the cornerstone therapy for patients with symptomatic AF resistant to anti-arrhythmic drugs or as first-line therapy, and is based on permanent pulmonary vein (PV) isolation. The presence of a conduction gap in a wide antral circumferential ablation lesion around PVs is often sufficient to transform an initially successful ablation into a procedural failure, thus necessitating a redo intervention. The strategy during a redo procedure is based on the detection and ablation of the reconnection gap. Finding gaps is often simple, but also sometimes challenging, because gaps may be difficult to detect, resulting in unnecessary radiofrequency delivery. The present review aimed to describe the various techniques published thus far to detect residual reconnections along the encircling ablation lines around PVs, to help electrophysiologists to detect and ablate reconnection gaps.

Mechanisms Underlying Spontaneous Action Potential Generation Induced by Catecholamine in Pulmonary Vein Cardiomyocytes: A Simulation Study.

Cardiomyocytes and myocardial sleeves dissociated from pulmonary veins (PVs) potentially generate ectopic automaticity in response to noradrenaline (NA), and thereby trigger atrial fibrillation. We developed a mathematical model of rat PV cardiomyocytes (PVC) based on experimental data that incorporates the microscopic framework of the local control theory of Ca2+ release from the sarcoplasmic reticulum (SR), which can generate rhythmic Ca2+ release (limit cycle revealed by the bifurcation analysis) when total Ca2+ within the cell increased. Ca2+ overload in SR increased resting Ca2+ efflux through the type II inositol 1,4,5-trisphosphate (IP3) receptors (InsP3R) as well as ryanodine receptors (RyRs), which finally triggered massive Ca2+ release through activation of RyRs via local Ca2+ accumulation in the vicinity of RyRs. The new PVC model exhibited a resting potential of -68 mV. Under NA effects, repetitive Ca2+ release from SR triggered spontaneous action potentials (APs) by evoking transient depolarizations (TDs) through Na+/Ca2+ exchanger (APTDs). Marked and variable latencies initiating APTDs could be explained by the time courses of the α1- and ß1-adrenergic influence on the regulation of intracellular Ca2+ content and random occurrences of spontaneous TD activating the first APTD. Positive and negative feedback relations were clarified under APTD generation.

A novel concept for evaluation of pulmonary function utilizing PaO2/FiO2 difference at the distinctive FiO2 in cellular ex vivo lung perfusion-an experimental study.

For more accurate lung evaluation in ex vivo lung perfusion (EVLP), we have devised a new parameter, PaO2 /FiO2 ratio difference (PFD); PFD1-0.4  = P/F ratio at FiO2 1.0 - P/F ratio at FiO2 0.4. The aim of this study is to compare PFD and transplant suitability, and physiological parameters utilized in cellular EVLP. Thirty-nine human donor lungs were perfused. At 2 h of EVLP, PFD1-0.4 was compared with transplant suitability and physiological parameters. In a second study, 10 pig lungs were perfused in same fashion. PFD1-0.4 was calculated by blood from upper and lower lobe pulmonary veins and compared with lobe wet/dry ratio and pathological findings. In human model, receiver operating characteristic curve analysis showed PFD1-0.4 had the highest area under curve, 0.90, sensitivity, 0.96, to detect nonsuitable lungs, and significant negative correlation with lung weight ratio (R2  = 0.26, P < 0.001). In pig model, PFD1-0.4 on lower and upper lobe pulmonary veins were significantly associated with corresponding lobe wet/dry ratios (R2  = 0.51, P = 0.019; R2  = 0.37, P = 0.060), respectively. PFD1-0.4 in EVLP demonstrated a significant correlation with lung weight ratio and allowed more precise assessment of individual lobes in detecting lung edema. Moreover, it might support decision-making in evaluation with current EVLP criteria.

A novel parameter for pulmonary blood flow during palliative procedures: velocity time integral of the pulmonary vein†.

OBJECTIVES: The main goal of palliative procedures for congenital heart defects is adequate pulmonary blood flow (PBF), but precise intraoperative PBF evaluation is sometimes difficult. The purpose of this preliminary study was to investigate the usefulness of velocity time integral of the pulmonary vein (PV-VTI) measured by transoesophageal echocardiography (TOE) at the time of palliative procedure as a parameter for PBF. METHODS: Case histories of 63 patients who underwent palliative procedures (bilateral pulmonary artery banding in 18 patients, main pulmonary artery banding in 22 patients and systemic-to-pulmonary artery shunt in 23 patients) and whose intraoperative PV-VTI was measured by TOE from 2011 to 2017 at our centre were retrospectively reviewed. Low-body-weight infants, cases in which cardiopulmonary bypass was used and cases that were anatomically difficult to measure were excluded. RESULTS: PV-VTIs measured at 4 orifices of the pulmonary veins were all significantly decreased in both the bilateral pulmonary artery banding and main pulmonary artery banding groups and increased in the systemic-to-pulmonary artery shunt group immediately after the procedure. There were significant correlations between the velocity time integrals of both right and left pulmonary veins and arterial oxygen saturation (r = 0.564 and 0.703). Nine patients (6 bilateral pulmonary artery banding and 3 systemic-to-pulmonary artery shunt) required unplanned early reoperation due to inadequate PBF; their PV-VTIs were significantly different from those of patients not requiring reoperation. No major complications related to TOE occurred postoperatively. CONCLUSIONS: The PV-VTI measured by TOE during palliative procedures reflected the change of PBF and could help identify patients at higher risk of early reoperation due to inadequate PBF. This parameter may be a useful additional tool for evaluating intraoperative PBF.

Diastolic dysfunction evaluated by cardiac magnetic resonance: the value of the combined assessment of atrial and ventricular function.

OBJECTIVES: We sought to evaluate the role of cardiac magnetic resonance imaging (CMR) in the evaluation of diastolic function by a combined assessment of left ventricular (LV) and left atrial (LA) function in a cohort of subjects with various degrees of diastolic dysfunction (DD) detected by echocardiography. METHODS: Forty patients with different stages of DD and 18 healthy controls underwent CMR. Short-axis cine steady-state free precession images covering the entire LA and LV were acquired. Parameters of diastolic function were measured by the analysis of the LV and LA volume/time (V/t) curves and the respective derivative dV/dt curves. RESULTS: At receiver operating characteristic (ROC) curve analysis, the peak of emptying rate A indexed by the LV filling volume with a cut-off of 3.8 was able to detect patients with grade I DD from other groups (area under the curve [AUC] 0.975, 95% confidence interval [CI] 0.86-1). ROC analysis showed that LA ejection fraction with a cut-off of ≤36% was able to distinguish controls and grade I DD patients from those with grade II and grade III DD (AUC 0.996, 95% CI 0.92-1, p < 0.001). The isovolumetric pulmonary vein transit ratio with a cut-off of 2.4 allowed class III DD to be distinguished from other groups (AUC 1.0, 95%CI 0.93-1, p < 0.001). CONCLUSIONS: Analysis of LV and LA V/t curves by CMR may be useful for the evaluation of DD. KEY POINTS: • Combined atrial and ventricular volume/time curves allow evaluation of diastolic function. • Atrial emptying fraction allows distinction between impaired relaxation and restrictive/pseudo-normal filling. • Isovolumetric pulmonary vein transit ratio allows distinction between restrictive and pseudo-normal filling.

Impact of Pulmonary Venous Inflow on Cardiac Flow Simulations: Comparison with In Vivo 4D Flow MRI.

Blood flow simulations are making their way into the clinic, and much attention is given to estimation of fractional flow reserve in coronary arteries. Intracardiac blood flow simulations also show promising results, and here the flow field is expected to depend on the pulmonary venous (PV) flow rates. In the absence of in vivo measurements, the distribution of the flow from the individual PVs is often unknown and typically assumed. Here, we performed intracardiac blood flow simulations based on time-resolved computed tomography on three patients, and investigated the effect of the distribution of PV flow rate on the flow field in the left atrium and ventricle. A design-of-experiment approach was used, where PV flow rates were varied in a systematic manner. In total 20 different simulations were performed per patient, and compared to in vivo 4D flow MRI measurements. Results were quantified by kinetic energy, mitral valve velocity profiles and root-mean-square errors of velocity. While large differences in atrial flow were found for varying PV inflow distributions, the effect on ventricular flow was negligible, due to a regularizing effect by mitral valve. Equal flow rate through all PVs most closely resembled in vivo measurements and is recommended in the absence of a priori knowledge.