Pulmonary Vein Pressure Research Articles

Atrial fibrillation cryoablation guided by pulmonary vein pressure: comparison with the standard strategy

Abstract Background Pulmonary vein (PV) isolation is the cornerstone for the treatment of patients with atrial fibrillation (AF). Balloon cryoablation (BCA) is the preferred single-shot option for ablation of PVs using contrast guided occlusion as the standard approach (SA). We have made a simplified procedure, using a pressure-guided approach (PG) aimed to obtain a PV wedge curve. This technique has been described previously(1-3). To our knowledge, no comparison has been made in real life with a mixed patient setting in AF (paroxysmal and persistent) and non-selected anatomy with exclusive PG. Purpose To compare a prospective cohort of patients going into AF BCA, using SA versus PG. Methods Between January 2022 and October 2023, 50 consecutive patients underwent BCA. The first 25 patients were treated with SA protocol and the latter 25 with PG. In both techniques, the aim was to obtain PV isolation with a 240 seconds application and no bonus attempt. A computed tomography angiography or MRI of the left atrium (LA) was performed in all the patients. 28-mm Cryoballoon and Intracardiac echo were used in all the procedures. We compared patients and procedure characteristics between both techniques. Results Both groups (SA vs PG) showed similar baseline characteristics with not significant differences between them: mean age (58±10 vs 61±10 years), median LA diameter (40±8 vs 41±5mm), mean LVEF (60±9 VS 63±7%), Paroxysmal AF (60 vs 56%), average CHA2DS2-VASc score (1.3±1.3 vs 1.8±1.5), One patient is SA group had a previous radiofrequency (RF) ablation with 4/4 veins reconnected, and in the PG group two patients had RF ablation with 7/8 veins reconnected (Table 1). The procedural characteristics between SA and PG, also did not show significant differences: median procedural time (120±20 vs 130±38 min), fluoroscopic time (24±13 vs 30±19 min), and isolation was achieved in 98/99 veins (99%) in each group (Table 2). In the SA group, two patients had complications: one patient with a transient palsy of the phrenic nerve and because of this, only 3/4 veins were targeted, and the second patient had a post-procedure pericarditis. In the PG group, one patient had a pericardial effusion seen at the end of the procedure that did not require drainage. Conclusion In our initial experience, BCA for AF with both strategies proved to be safe and effective in this mixed group with non-selected anatomy. This result reassures the PG as a way to enhance CBA because of the advantage in avoiding the use of intraprocedural IV contrast. Impact in performance during follow-up is yet to be seen in our cohort.Table 2.Baseline characteristicsTable 2.Procedural characteristics

Pulmonary Artery Wedge Pressure Can Underestimate Direct Pulmonary Vein Pressure in Pediatric Pulmonary Vein Stenosis

BackgroundPulmonary artery wedge pressure (PAWP) can underestimate directly measured pulmonary vein pressure (PVP) as demonstrated in animal studies and human case reports. This concept has not been validated in a larger cohort of pediatric patients with pulmonary vein stenosis (PVS). MethodsPediatric patients who underwent cardiac catheterization for PVS at a single center from January 1, 2018, to March 31, 2023, were retrospectively reviewed. Mismatch between the PAWP and directly measured PVP or LA pressure was defined as >3 mm Hg. Preintervention angiography was reviewed and percent stenosis calculated. ResultsTwenty-six patients met inclusion criteria; 51 lower pulmonary veins (34 left, 17 right) from 42 catheterizations were evaluated. Significant PVS (≥30% stenosis) was seen in 38/51 (75%) veins, and 9/51 (18%) veins had no angiographic narrowing (0% stenosis). PAWP-PVP mismatch occurred in 37/51 (73%) veins with a median difference of 8 mm Hg (IQR, 6-12). Of these, PAWP was equal to LA pressure in 26 instances, all of which had significant PVS (median % stenosis 54 [IQR, 45-60]). Six of the cases with PAWP-PVP mismatch, PVS (range, 41%-70% stenosis), and no PAWP-LA mismatch reported both a proximal and distal segmental PAWP. In all 6 instances, there was no distal PAWP-PVP mismatch (median difference 1 mm Hg [range, 0-3]). ConclusionsIn this single-center study of pediatric patients with PVS, PAWP significantly underestimated directly measured PVP in lower pulmonary veins. Balloon wedge or end hole catheter position in a distal lobar segment may more accurately estimate the PVP.

PO-01-068 CRYOBALLOON ABLATION FOR ATRIAL FIBRILLATION WITH LEAD-FREE ZERO FLUOROSCOPY APPROACH INTEGRATING PULMONARY VEIN HEMODYNAMICS, INTRACARDIAC IMAGING, AND 3D MAPPING: A FOUR-YEAR SINGLE-CENTER EXPERIENCE

Electrophysiologists have for years been plagued with the dangers of prolonged radiation exposure and associated long-term use of lead aprons. Patients also are exposed to significant amounts of radiation during fluoroscopy-guided catheter ablations. As such, efforts are being made to pioneer techniques which do not require fluoroscopy without sacrificing efficacy, safety, and patient outcomes. To evaluate the acute safety and efficacy of zero fluoroscopy cryoballoon ablation (ZFC) for atrial fibrillation (AF) with guidance from intracardiac echocardiography (ICE), pulmonary vein (PV) hemodynamics, and 3-dimensional (3D) mapping. Contiguous patients in a single center underwent ZFC for AF with ICE guidance, PV occlusion monitoring using hemodynamics, and 3D mapping. The superior vena cava was visualized with ICE, transseptal puncture was performed and LA sheath placement was confirmed with ICE. ICE catheter was then advanced into the LA through the same transseptal puncture. 3D mapping of the LA was performed, cryoballoon was advanced into the PV antrum, and seal was confirmed with ICE, color-flow dopper, and PV pressure waveform monitoring. Wide antral circumferential ablation was performed along all PVs. During ablation of right PVs, the phrenic nerve was monitored using palpation, liver capsule excursion noted on ICE, and pulsed wave doppler of the liver capsule. 3D mapping was used to ascertain entrance and exit blocks and circumferential antral isolation. A retrospective analysis of patients undergoing ZFC for treatment of AF from November 2018 to September 2022 was completed. The sample included 433 patients (219 women [50.6%] with a mean age of 66.5±11.6 years). Mean total procedure time was 49.3±12.0 minutes, mean LA dwell time was 36.5±10.3 minutes, and mean duration of cryoballoon application was 15.9±4.0 minutes. Procedural complication rates were 0.6% for effusions, 1.3% for phrenic nerve dysfunction, 0.8% for phrenic nerve palsy, 0.1% for vascular complications, 0% for esophageal injury, and 0.5% for all-cause mortality. Our single center experience demonstrates the feasibility of safely and effectively completing cryoballoon ablations for atrial fibrillation with a lead-free zero fluoroscopy approach. Additional multi-center studies are needed to ascertain the wide-scale applicability of this approach. The center acknowledges the learning curve associated with this skill set.

Hemoptysis due to progressive scoliosis associated with congenital heart disease: a case report

BackgroundPatients with congenital heart disease (CHD) are associated with an increased incidence of scoliosis, often with severe progression. We report a case of hemoptysis caused by rapid scoliosis progression subsequent to surgery for CHD that was successfully managed by surgical curve correction following coil embolization.Case presentationA 14-year-old girl with scoliosis had undergone open heart surgery for CHD at the age of 1 year. She was first noted to have scoliosis at 12 years of age, which began to progress rapidly. At age 13, her main thoracic curve Cobb angle was 46°, and hemoptysis with high pulmonary vein pressure due to vertebral rotation was detected. Nine months after coil embolization, she received posterior spinal fusion from T5 to L2 for scoliosis correction. Postoperatively, her pulmonary vein diameter was enlarged, with no detectable signs of hemoptysis.ConclusionsWe encountered a case of hemoptysis caused by advanced scoliosis after cardiac surgery that was successfully treated by correction of the scoliotic curve following coil embolization. Patients with secondary scoliosis after surgery for CHD should be carefully monitored for the possibility of cardiovascular system deterioration.

Numerical Simulation of Hemodynamics in Two Models for Total Anomalous Pulmonary Venous Connection Surgery.

ObjectiveTo numerically compare the prospective hemodynamic outcomes between a new window surgery and a traditional surgery in the treatment of supracardiac total anomalous pulmonary venous connection (S-TAPVC).MethodsA 3D geometry model, composed of pulmonary vein (PV) and left atrium (LA), was reconstructed based on summarized data with S-TAPVC. Two surgery models were established based on this model. One is the traditional surgery model, where an elliptical anastomosis was created by incising and stitching the LA and the common vein (CV) along the axis of the CV. The other is the new window surgery model, where the CV was incised with an H-shaped orifice, and LA was incised with a transposed H-shaped orifice, and then the orifice edges were stitched like a window. Two models with a relative cross sectional area (RCSA) of 300 mm2/m2 and 500 mm2/m2 were established, which correspond to traditional surgery and window surgery. Numerical simulation of hemodynamics was carried out. The velocity, left atrium and pulmonary vein pressure, the pressure difference of anastomosis and the energy conversion efficiency were analyzed to evaluate the prospective hemodynamic outcomes of these two operations.ResultsWindow surgery presented a lower blood flow velocity, pressure difference, and the WSS at the anastomosis, compared to traditional surgery. In terms of energy loss, the power conversion efficiency of window surgery was significantly higher than that of traditional surgery, with 66.8% and 53.5%, respectively.ConclusionThe new window surgery demonstrates a lower pressure difference of anastomosis and higher energy conversion efficiency, which may be a better choice compared with the traditional surgery for S-TAPVC patient.

DIY Isolated Lung Set‐up: Construction and Troubleshooting

Ex-vivo lung preparations have the advantage of being able to study the responses of the lung to drugs or other interventions in a controlled environment without any hemodynamic changes or confounding variables such as a humoral or neuronal input. Assessments that can be taken over time include pulmonary artery pressure (PAP), pulmonary vein pressure (PVP) and airway pressure (AWP). Figure shows a schematic of the lung set-up (numbers in brackets refer to parts of the set-up). A heated reservoir [1] contains a balanced salt perfusate solution (NaCl 119 mM, NaHCO3 24 mM, Glucose 5.5 mM, CaCl2 1.6 mM, KCl 4.7 mM, MgSO4 1.17 mM, NaPO4 1.18 mM) with 4% bovine serum albumin. A sufficiently high and stable glucose concentration is important for the viability of the lung. Thus, due to its glucose metabolism, glucose concentrations must be monitored continuously, or at least every hour, and adjusted by glucose infusions. Stable temperature of the perfusate (37.0–37.5°C) is achieved with a heating plate [2], heating coil and heated bubble trap, with the coil and bubble trap heated by a separate circulating water bath [3]. A roller pump [4], with speed set to 40 cc · min−1 · kg−1 body weight and controlled manually or remotely, pumps the perfusate through the heating coil [5] and the heated bubble trap [6] to the inflow cannula placed in the pulmonary artery. The temperature of the heating coil and bubble trap needs to be adjusted according to the pump speed. To keep the lung warm and moist, it is hung above a heated water bath (~ 48°C) [7]. An outflow cannula placed into the left ventricle connects the pulmonary circulation back to the reservoir to recycle the perfusate. The lung is positive pressure ventilated by a rodent ventilator with, e.g. 30% O2, 5% CO2 and 65% N2, and a tidal volume VT = 10 cc · kg−1 body weight. The positive end-expiratory pressure (PEEP) is set to 2–3 mmHg by a water lock. The pressure transducers, placed at the same height as the lung, are attached to the inflow, outflow and the ventilator to continuously record PAP, PVP and AWP, respectively. They are connected to a data acquisition system via bio amplifiers. A framework made from aluminium rods and rod clamps provides three-dimensional stability. Weekly cleaning of the setup with 5% bleach and 5% HCl is advised to avoid contamination. In summary, the described self-made isolated lung set-up provides maximal flexibility for future adjustments, while being an affordable alternative to more expensive premade set-ups. Support or Funding Information This work was supported, in part, by institutional funds, NIH grant (5R01 HL123227), and a Merit Review Award (I01 BX003482) from the U.S. Department of Veterans Affairs Biomedical Laboratory R&D Service. Isolated lung set-up This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Implementation of LabVIEW as a Virtual Instrument in a Cost‐Effective Isolated Lung Setup

IntroductionIsolated lung experiments allow for ex vivo characterization of lung function and prove to be a valuable model for various fields such as cancer, lung transplantation, and ischemia/reperfusion injury. Unlike other models that require damaging the lung, the isolated lung allows for collection of physiological changes including airway pressure, pulmonary artery and vein pressure, airway flow, and, in our model, ventilated gas concentrations. We describe the use of LabVIEW combined with the free statistical software R for highly flexible, effective, and automated data collection in an isolated lung system.MethodsPressure transducers connected to bioamplifiers allow for collection of dynamic pulmonary artery and vein pressures, while airway pressure and flow are collected from the ventilator with the former used to visualize positive end expiratory pressure. Signals from these devices are connected to an analog‐digital converter from National InstrumentsTM that collects data into LabVIEW software, which is then automatically collected and displayed at 200Hz. Use of a roller pump with analog input/output allows for fully automated control of the perfusion speed. Output from a gas mixer for use in ventilated gas studies is collected and used to generate gas composition data. Additional experimental data that do not have signal output capability can be recorded manually in LabVIEW.ResultsLabVIEW is a reliable alternative to other commercially available data acquisition systems. The creation of a virtual instrument requires significant programming knowledge but allows for completely customizable data collection in a modular isolated lung system. Data become available in an Excel‐compatible file which can then be imported and analysed in R as another affordable alternative to commercial programs.ConclusionWe describe the design and implementation of a LabVIEW virtual instrument as an adjustable alternative to conventional data acquisition systems.Support or Funding InformationThis work was supported, in part, by institutional funds, NIH grant (5R01 HL123227), and a Merit Review Award (I01 BX003482) from the U.S. Department of Veterans Affairs Biomedical Laboratory R&D Service.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Noninvasive determination of the pulmonary artery input impedance

A reliable noninvasive method for the estimation of pulmonary function in healthy and diseased subjects should be of great importance in the prognosis, diagnosis, and treatment of pulmonary hypertension. Here we propose such a method, which is based on the parameter identification of the five-element Windkessel model of pulmonary circulation. The method requires the following input variables: the heart rate, the stroke volume, the Doppler echocardiographic measurements of the tricuspid regurgitation and the pulmonary valve velocity profiles, and estimations of the right atrium and the pulmonary vein pressure. The stroke volume is calculated as a product of the left ventricle outflow tract area and the velocity-time integral measured at the same place. The model parameter identification procedure is based on minimization of the root mean square error between the pulmonary artery root pressure calculated from the aforementioned Doppler velocity profiles (from the Bernoulli equation applied during the ejection phase) and the pressure from the Windkessel model during the same period. The output from the model contains the calculated pulmonary artery input impedance (i.e. the model parameters: pulmonary vascular resistance, pulmonary artery proximal and distal compliances, inertance, and characteristic impedance) and the pulmonary artery pressure profile during the whole heart period. Our method is applied to a subject with pulmonary hypertension. The right heart Swan-Ganz catheterization has been performed in this subject. The results obtained by using this method show that the five-element Windkessel model reconstructs the main features of the pulmonary artery input impedance very well: its modulus shows the minimum where the phase angle changes its sign. The pulmonary vascular resistance, the systolic, diastolic and mean pulmonary artery pressures obtained from the method are in good agreement with the values obtained invasively from the catheterization. Sensitivity analysis shows that the mean pulmonary pressure is fairly insensitive to slight overestimation/ underestimation of all input parameters, except for the right atrium pressure. The absolute error in the mean pulmonary artery pressure is nearly the same as the error in the right atrium pressure. Since the proposed method offers a deeper insight into the pulmonary circulation than the catheterization itself because it provides the proximal and distal compliance, the inertance and the characteristic impedance, it seems that it can serve in clinical practice as a good substitute for catheterization.

Iterative Learning Control of a Left Ventricular Assist Device

Due to the lack of donor organs, the importance of left ventricular assist devices (LVADs) increases. State of the art is to operate the pumps with a constant speed (CS) leading to effects such as underpumping, ventricular suction or the backflow of blood from the aorta in the ventricle. The end-diastolic volume (EDV) is influenced by venous return, as well as diastolic function and systolic pressure development. Thus it is a good medical indicator of ventricular load. In this paper a norm-optimal iterative learning control (NOILC) algorithm is designed to shape the EDV of a pathological ventricle. In addition, further constraints such as for example a uniform filling of the ventricle and the prevention of pumping during the systole are considered. A simplified model of the systemic circulation and the pump is used to study the system response to changes in pulmonary vein pressure and to benchmark controller performance. The results show that the algorithm obtains an excellent tracking performance and prevents the dilation of the ventricle. The approach offers the physician the opportunity to control multiple physiological variables even though the optimal control output trajectory is not known. Future work will focus on the improvement of the controller performance regarding the rejection of instantaneous disturbances and the incorporation of variable cycle duration.

Acute Hemodynamic and Tissue Effects of Cryoballoon Ablation on Pulmonary Vessels: The IVUS-Cryo Study.

BackgroundCryoballoon‐based pulmonary vein isolation (CB‐PVI) has been widely used for the treatment of atrial fibrillation. Although generally safe and effective, the procedure may be associated with pulmonary vein (PV) stenosis and bronchial or esophageal injury. The mechanisms leading to these complications have not been studied in detail. Our aim was to examine acute effects of cryoballoon on the pulmonary vessel and right heart pressures as well as PV wall morphology.Methods and ResultsIn 8 patients (5 men, mean age 55±14 years) undergoing CB‐PVI, pressure in each PV was measured by catheter located inside the PV directly before and after CB‐PVI. The right atrial, right ventricular, and pulmonary artery pressures as well as pulmonary arterial wedge capillary pressure in the pulmonary artery branch corresponding to target PV were also measured. Morphological changes in PVs were assessed using intravascular ultrasonography.There were no significant differences in PV pressures before and after ablation. The pulmonary arterial wedge capillary pressure significantly increased during cryoapplication (left superior: 20±10 versus 29±8.5 mm Hg, P=0.004; left inferior: 24±10 versus 32±6 mm Hg, P=0.012; right superior: 25±9 versus 35±10 mm Hg, P=0.002; right inferior: 24±10 versus 37±12 mm Hg, P=0.0036). The right atrial and pulmonary artery pressures increased significantly after CB‐PVI (9±6 versus 13±8 mm Hg, P=0.004, and 20±9 versus 24±10 mm Hg, P=0.048, respectively). Intravascular ultrasonography showed acute edema and dissection‐like changes causing relative lumen narrowing in 90% of PVs.Conclusions CB‐PVI causes significant rise in pulmonary artery and right atrial pressures as well as PV wall damage. The clinical significance of these findings warrants further investigations.

Controlled Atrial Fibrillation after Pulmonary Vein Stenting.

When there is no pulmonary vein reconnection after catheter ablation for atrial fibrillation, patients can experience recurrence of atrial fibrillation without clear evidence of non-pulmonary vein foci. We describe a patient with significant pulmonary vein stenosis and recurrent atrial fibrillation after four ablation procedures. After successful pulmonary vein stenting, the symptoms were resolved, and sinus rhythm was maintained for 2 years without treatment with antiarrhythmic medication. We believe pulmonary vein stenting potentially controlled atrial fibrillation by providing pulmonary vein pressure relief or by compressing the epicardial triggers occurring at the pulmonary vein ostium.

Genesis of the characteristic pulmonary venous pressure waveform as described by the reservoir-wave model.

Conventional haemodynamic analysis of pulmonary venous and left atrial (LA) pressure waveforms yields substantial forward and backward waves throughout the cardiac cycle; the reservoir wave model provides an alternative analysis with minimal waves during diastole. Pressure and flow in a single pulmonary vein (PV) and the main pulmonary artery (PA) were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading, and positive-end expiratory pressure (PEEP) were observed. The reservoir wave model was used to determine the reservoir contribution to PV pressure and flow. Subtracting reservoir pressure and flow resulted in 'excess' quantities which were treated as wave-related.Wave intensity analysis of excess pressure and flow quantified the contributions of waves originating upstream (from the PA) and downstream (from the LA and/or left ventricle (LV)).Major features of the characteristic PV waveform are caused by sequential LA and LV contraction and relaxation creating backward compression (i.e.pressure-increasing) waves followed by decompression (i.e. pressure-decreasing) waves. Mitral valve opening is linked to a backwards decompression wave (i.e. diastolic suction). During late systole and early diastole, forward waves originating in the PA are significant. These waves were attenuated less with volume loading and delayed with PEEP. The reservoir wave model shows that the forward and backward waves are negligible during LV diastasis and that the changes in pressure and flow can be accounted for by the discharge of upstream reservoirs. In sharp contrast, conventional analysis posits forward and backward waves such that much of the energy of the forward wave is opposed by the backward wave.

Role of Left Ventricular Diastolic Dysfunction in Predicting Atrial Fibrillation Recurrence after Successful Electrical Cardioversion.

The role of left ventricular (LV) diastolic dysfunction in predicting atrial fibrillation (AF) recurrence after successful electrical cardioversion is largely unknown. Studies suggest that there may be a link between abnormal LV compliance and the initial development, and recurrence of AF after electrical cardioversion. Although direct-current cardioversion (DCCV) is a well-established and highly effective method to convert AF to sinus rhythm, it offers little else beyond immediate rate control because it does not address the underlying cause of AF. Preservation of sinus rhythm after successful cardioversion still remains a challenge for clinicians. Despite the use of antiarrhythmic drugs and serial cardioversions, the rate of AF recurrence remains high in the first year. Current evidence suggests that diastolic dysfunction, which is associated with atrial volume and pressure overload, may be a mechanism underlying the perpetuating cycle of AF recurrence following successful electrical cardioversion. Diastolic dysfunction is considered to be a defect in the ability of the myofibrils, which have shortened against a load in systole to eject blood into the high-pressure aorta, to rapidly or completely return to their resting length. Consequently, LV filling is impaired and the non-compliant left ventricle is unable to fill at low pressures. As a result, left atrial and pulmonary vein pressure rises, and electrical and structural remodeling of the atrial myocardium ensues, creating a vulnerable substrate for AF. In this article, we review the current evidence highlighting the association of LV diastolic dysfunction with AF recurrence after successful electrical cardioversion and provide an approach to the management of LV diastolic dysfunction to prevent AF recurrence.

Pulmonary venous hypertension or pulmonary hypertension due to left heart disease

Pulmonary venous hypertension may be caused by increased pressure anywhere between the intraparenchymal pulmonary veins and the left ventricle. Pulmonary venous hypertension has different causes in children compared with adults. In adults the most common cause of pulmonary venous hypertension is left ventricular diastolic disease. In children, congenital heart diseases, acquired and congenital cardiomyopathies are the usual causes of pulmonary venous hypertension. There are three important mechanisms in the pathophysiology of pulmonary venous hypertension. Firstly there is a passive rise in pulmonary artery pressure as down stream pressure increases to maintain left sided preload and cardiac output. In this situation the transpulmonary gradient (< 10 mmHg) and pulmonary vascular resistance index are low (< 2.5–5 WU m 2) and the pulmonary artery diastolic pressure is similar to the left atrial, or in the absence of pulmonary vein or mitral valve pathology, the left ventricular end diastolic pressure. Secondly there is reflex vasoconstriction of the pulmonary arteries or veins or both and the diastolic pulmonary artery pressure will be higher than the pulmonary vein, left atrial or left ventricular end diastolic pressure depending on the site of the left sided pressure increase. The transpulmonary gradient will be > 10 mmHg and pulmonary vascular resistance index > 2.5–5 WU m 2. These patients respond to a cautious pulmonary vasodilator challenge with a decrease in both transpulmonary gradient and pulmonary vascular resistance index but with a variable increase in pulmonary venous pressure. Thirdly, there may be fixed pulmonary artery or vein obstruction. Quite often a combination of all three mechanisms (passive, reflex vasoconstriction and fixed) conspire to increase pulmonary artery pressure. Outside of restrictive cardiomyopathies, severe pulmonary hypertension due to isolated left ventricular diastolic disease is not prominent in young children. However, it seems likely that with the emergence of childhood obesity, insulin resistance, systemic hypertension, survivors of left sided congenital heart disease and organ transplantation that diastolic heart disease will assume more prominence in pediatrics. In general the pulmonary hypertension regresses if the left sided obstruction or dysfunction can be addressed adequately.

Misleading Turbulent Flow Through Pulmonary Venous Anastomoses During Lung Transplantation

Misleading Turbulent Flow Through Pulmonary Venous Anastomoses During Lung Transplantation

Teaching the effects of gravity and intravascular and alveolar pressures on the distribution of pulmonary blood flow using a classic paper by West et al.

"Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures" by J. B. West, C. T. Dollery, and A. Naimark (J Appl Physiol 19: 713-724, 1964) is a classic paper, although it has not yet been included in the Essays on the American Physiological Society Classic Papers Project (http://www.the-aps.org/publications/classics/). This is the paper that originally described the "zones of the lung." The final figure in the paper, which synthesizes the results and discussion, is now seen in most textbooks of physiology or respiratory physiology. The paper is also a model of clear, concise writing. The paper and its final figure can be used to teach or review a number of physiological concepts. These include the effects of gravity on pulmonary blood flow and pulmonary vascular resistance; recruitment and distention of pulmonary vessels; the importance of the transmural pressure on the diameter of collapsible distensible vessels; the Starling resistor; the interplay of the pulmonary artery, pulmonary vein, and alveolar pressures; and the vascular waterfall. In addition, the figure can be used to generate discovery learning and discussion of several physiological or pathophysiological effects on pulmonary vascular resistance and the distribution of pulmonary blood flow.

Role of impaired myocardial relaxation in the production of elevated left ventricular filling pressure

Although present in many patients with heart failure and a normal ejection fraction, the role of isolated impairments in active myocardial relaxation in the genesis of elevated filling pressures is not well characterized. Because of difficulties in determining the effect of prolonged myocardial relaxation in vivo, we used a cardiovascular simulated computer model. The effect of myocardial relaxation, as assessed by tau (exponential time constant of relaxation), on pulmonary vein pressure (PVP) and left ventricular end-diastolic pressure (LVEDP) was investigated over a wide range of tau values (20-100 ms) and heart rate (60-140 beats/min) while keeping end-diastolic volume constant. Cardiac output was recorded over a wide range of tau and heart rate while keeping PVP constant. The effect of systolic intervals was investigated by changing time to end systole at the same heart rate. At a heart rate of 60 beats/min, increases in tau from a baseline to extreme value of 100 ms cause only a minor increase in PVP of 3 mmHg. In contrast, at 120 beats/min, the same increase in tau increases PVP by 23 mmHg. An increase in filling pressures at high heart rates was attributable to incomplete relaxation. The PVP-LVEDP gradient was not constant and increased with increasing tau and heart rate. Prolonged systolic intervals augmented the effects of tau on PVP. Impaired myocardial relaxation is an important determinant of PVP and cardiac output only during rapid heart rate and especially when combined with prolonged systolic intervals. These findings clarify the role of myocardial relaxation in the pathogenesis of elevated filling pressures characteristic of heart failure.

The pulmonary vein Doppler flow velocity waveform: feature analysis by comparison of in vivo pressures and flows with those in a computerized fetal physiological model

Doppler flow velocity waveforms (FVW) in fetal veins that discharge into the atria show fluctuations related to atrial events. Pulmonary veins are of particular interest because both ends (atrial and collecting venule) are within the intrathoracic pressure environment reducing fetal breathing artifacts. Indices, such as pulsatility index for veins (PIV), have been suggested to classify FVWs and relate them to fetal well being. We wished to examine the relationship between function and FVW in circumstances which cannot ethically be examined in vivo, by studying the mechanisms which produced altered 'flows' in a detailed fetal computer model. We then related these findings to current flow indices. A computer model of the feto-placental unit, responding to changes in organ oxygenation and regional flow is briefly described. In vivo intracardiac pressures and FVWs obtained from other studies were used to extend detail in the model until matching 'pressures' and 'flows' resulted. The effects of flow redistribution in the hypoxic fetus on pulmonary vein 'Doppler' flow velocity waveforms were then studied. Flow reversal in pulmonary veins during atrial contraction indicates hypoxia, but change of shape of the FVW envelope reflects the changes in the pressure waveform of the left atrium. Of the major veins the pulmonary vein Doppler FVW gave the truest representation of atrial pressure response to both intracardiac and systemic vascular status. Although current indices indicate general fetal condition, more specific indices are needed if pulmonary venous flow is to be used as an end-point. A pulmonary vein pressure gradient index is suggested.

Mechanism of pulmonary venous pressure and flow waves.

The pulmonary venous systolic flow wave has been attributed both to left heart phenomena, such as left atrial relaxation and descent of the mitral annulus, and to propagation of the pulmonary artery pressure pulse through the pulmonary bed from the right ventricle. In this study we hypothesized that all waves in the pulmonary veins originate in the left heart, and that the gross wave features observed in measurements can be explained simply by wave propagation and reflection. A mathematical model of the pulmonary vein was developed; the pulmonary vein was modeled as a lossless transmission line and the pulmonary bed by a three-element lumped parameter model accounting for viscous losses, compliance, and inertia. We assumed that all pulsations originate in the left atrium (LA), the pressure in the pulmonary bed being constant. The model was validated using pulmonary vein pressure and flow recorded 1 cm proximal to the junction of the vein with the left atrium during aortocoronary bypass surgery. For a pressure drop of 6 mmHg across the pulmonary bed, we found a transit time from the left atrium to the pulmonary bed of tau approximately 150ms, a compliance of the pulmonary bed of C approximately 0.4 ml/mmHg, and an inertance of the pulmonary bed of 1.1 mmHgs2/ml. The pulse wave velocity of the pulmonary vein was estimated to be c approximately 1m/s. Waves, however, travel both towards the left atrium and towards the pulmonary bed. Waves traveling towards the left atrium are attributed to the reflections caused by the mismatch of impedance of line (pulmonary vein) and load (pulmonary bed). Wave intensity analysis was used to identify a period in systole of net wave propagation towards the left atrium for both measurements and model. The linear separation technique was used to split the pressure into one component traveling from the left atrium to the pulmonary bed and a reflected component propagating from the pulmonary bed to the left atrium. The peak of the reflected pressure wave corresponded well with the positive peak in wave intensity in systole. We conclude that the gross features of the pressure and flow waves in the pulmonary vein can be explained in the following manner: the waves originate in the LA and travel towards the pulmonary bed, where reflections give rise to waves traveling back to the LA. Although the gross features of the measured pressure were captured well by the model predicted pressure, there was still some discrepancy between the two. Thus, other factors initiating or influencing waves traveling towards the LA cannot be excluded.

Haemostatic changes in the pulmonary blood during cardiopulmonary bypass.

Pulmonary injury may result from the use of cardiopulmonary bypass (CPB). We investigated changes in the haemostatic system in the pulmonary vein during CPB compared with blood that circulated through the bypass circuit. Paired samples were taken from the pulmonary vein and central venous pressure (CVP) line during the peri-operative period from ten patients. Plasma levels of factor VII (P < 0.001), prekallikrein (P < 0.05), antithrombin III (P < 0.001) and heparin cofactor II (P < 0.005) were decreased in the pulmonary vein after 20 min of bypass compared with pre-operative levels. In the pulmonary vein there was a significant increase in neutrophil expressed CD11b (P < 0.001), neutrophil elastase: alpha 1-antitrypsin complexes (P < 0.001), endothelin-1(P < 0.001) and thrombin-antithrombin complexes (P < 0.001) by the end of bypass compared with pre-operative levels. There was no significant change in monocyte expressed CD11b, factor XII or C1-esterase inhibitor in the pulmonary vein for the study period. None of these variables were significantly different in the pulmonary vein compared with CVP line. In the pulmonary vein plasma levels of activated factor VII decreased following heparin administration (P < 0.001) in the majority of patients which was coincidental to an increase (P < 0.001) in tissue factor pathway inhibitor (TFPI). This increase in TFPI was significantly higher in the pulmonary vein compared with CVP line (P < 0.05) There was a decrease in neutrophil count by 20 min on CPB in both the pulmonary vein and CVP line (P < 0.001) and this did not return to pre-operative levels in the pulmonary vein. Soluble thrombomodulin levels decreased by 20 min on CPB in the CVP line (P < 0.05) but tended to increase in the pulmonary vein, although this was not statistically significant. In conclusion we found evidence of thrombin generation and possible endothelial damage together with increased neutrophil activation and adhesion molecule expression in the pulmonary vein during CPB which may play an important role in the development of post-CPB pulmonary injury.