Vascular postpneumonectomy syndrome: inferior vena cava and pulmonary vein compression as unusual cause for platypnea-orthodeoxia following pneumonectomy

Background: Excessive mediastinal shift into the vacated thoracic cavity after pneumonectomy can result in dyspnea without hypoxemia by compression of the tracheobronchial tree, a phenomenon called postpneumonectomy syndrome. More rarely hypoxemia in upright position (platypnea-orthodeoxia syndrome, POS) after pneumonectomy can result from re-opening of an atrial right-to-left shunt through a patent foramen ovale (PFO) due to mediastinal distorsion. Review of literature also shows a unique report of pulmonary veins stenosis resulting in POS without intracardiac shunt after pneumonectomy. Methods: We report the case of a 32-year-old woman who presented POS 6 months after right pneumonectomy for destroyed lung post tuberculosis. Results: The patient described severe dyspnea disappearing when lying. SpO2 decreased from 94% when lying to 60% sitting. Transthoracic echocardiography (TTE) suspected a possible PFO. We first tried to highlight clinical repercussions of PFO by noninvasive exams. Hyperoxia shunt quantification was not tolerated because of increased dyspnea in sitting position. Contrast bubbles TTE was difficult because of the important mediastinal shift but identified only rare left heart bubbles with/without Valsalva both in lying and sitting position, excluding a significant right-to-left shunt. A lung perfusion scintigraphy (injection while sitting) confirmed the absence of systemic isotope uptake. Computed tomographic pulmonary angiography (angio-CT) revealed a stretched but not stenosed left main bronchus, while the shift of the heart into the right cavity was major. Pulmonary angiography did not show embolism but revealed compression of the inferior vena cava (IVC) with impaired venous return to the right heart, as well as compression of the left pulmonary veins. There was no arteriovenous shunt. Cardiac MRI showed torsion of IVC at the level of the diaphragm, and strong atrial contraction contributing to a passive filling of the RV, while the right ventricle was normal. Right catheterism showed major hemodynamic disturbances with negative diastolic pressure in right heart cavities (atrium -12 mm Hg ventricle pressure -7 mm Hg). SaO2 measured in the pulmonary artery decreased from 58% when lying to 45% sitting. Conclusion: We described here an exceedingly rare and complex mechanism explaining POS after right pneumonectomy. Mediastinal repositioning with a silicone breast implant of appropriate size has been scheduled.

Hypoxia: unique myocardial morphology?

OBJECTIVE: The objective of this study was to investigate the effects of chronic and intermittent hypoxia on myocardial morphology. METHODS: Rats randomly divided into 3 groups (n = 14 per group) were exposed to room air (Fio(2) = 0.21), chronic hypoxia (Fio(2) = 0.10), and intermittent hypoxia (chronic hypoxia with 1 hour per day of room air) for 2 weeks. Weight, blood gas analysis, hematocrit, hemoglobin, red cells, and right and left ventricular pressures were measured. Hearts excised for morphologic examination were randomly divided into 2 groups (9 per group for gross morphologic measurements and 5 per group for histologic and morphometric analysis). The weight ratio of right to left ventricles plus interventricular septum, myocyte diameter, cross-sectional area, and free wall thickness in right and left ventricles were measured. RESULTS: Despite the same polycythemia, the right ventricle pressure (P <.05) and ratio of right to left ventricle pressures (P <.02) were higher after chronic hypoxia than intermittent hypoxia. The ratio of heart weight to total body weight and the ratio of right to left ventricles plus interventricular septum was higher (P <.01) in chronic and intermittent hypoxia than in normoxia. Myocyte diameter was not different between the right and left ventricles in normoxia, whereas right ventricle myocytes were larger than left ventricle myocytes in chronic hypoxia (P <.05) and intermittent hypoxia (P <.0005). There was marked dilatation of right ventricle size (P <.001) and marked reduction of left ventricle (P <.001) size in chronic and intermittent hypoxia compared with normoxia. The total ventricular area (right ventricle plus left ventricle area) remained the same in all groups. The wall thickness ratio in chronic hypoxia and intermittent hypoxia was increased (P <.001) compared with normoxia in the right ventricle but not in the left ventricle. CONCLUSIONS: Intermittent reoxygenation episodes do not induce a lesser ventricular hypertrophic response than observed with chronic hypoxia. The functional myocardial preconditioning consequence of intermittent reoxygenation is not supported by structural differences evident with the available techniques.

The alpha(1A/C)- and alpha(1B)-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse.

Catecholamines and alpha(1)-adrenergic receptors (alpha(1)-ARs) cause cardiac hypertrophy in cultured myocytes and transgenic mice, but heart size is normal in single KOs of the main alpha(1)-AR subtypes, alpha(1A/C) and alpha(1B). Here we tested whether alpha(1)-ARs are required for developmental cardiac hypertrophy by generating alpha(1A/C) and alpha(1B) double KO (ABKO) mice, which had no cardiac alpha(1)-AR binding. In male ABKO mice, heart growth after weaning was 40% less than in WT, and the smaller heart was due to smaller myocytes. Body and other organ weights were unchanged, indicating a specific effect on the heart. Blood pressure in ABKO mice was the same as in WT, showing that the smaller heart was not due to decreased load. Contractile function was normal by echocardiography in awake mice, but the smaller heart and a slower heart rate reduced cardiac output. alpha(1)-AR stimulation did not activate extracellular signal-regulated kinase (Erk) and downstream kinases in ABKO myocytes, and basal Erk activity was lower in the intact ABKO heart. In female ABKO mice, heart size was normal, even after ovariectomy. Male ABKO mice had reduced exercise capacity and increased mortality with pressure overload. Thus, alpha(1)-ARs in male mice are required for the physiological hypertrophy of normal postnatal cardiac development and for an adaptive response to cardiac stress.

Comparaison des réponses hémodynamiques d'un repas modérément salé et d'un repas riche en sel : une hypothèse pour expliquer l'hypertrophie ventriculaire gauche des régimes hypersodés

De nombreuses études cliniques ont révélé une corrélation étroite entre un régime alimentaire riche en sel et le développement d'une hypertrophie ventriculaire gauche. Cette association a été classiquement attribuée aux effets hypertensifs à long terme d'une alimentation riche en sel. Toutefois, les études épidémiologiques ont également démontré que l'hypertrophie ventriculaire gauche peut survenir indépendamment de changements de pression artérielle.¦L'ingestion de sel n'étant pas distribuée de manière homogène durant la journée mais ayant lieu principalement durant les repas, nous émettons l'hypothèse que chaque repas riche en sel induit une augmentation aiguë de la pression artérielle, des pressions de remplissage cardiaque, du volume d'éjection systolique et du débit cardiaque. L'augmentation résultante du travail cardiaque pourrait ainsi à la longue entraîner une hypertrophie cardiaque.¦Pour tester si un repas riche en sel conduit à des modifications hémodynamiques favorisant l'hypertrophie cardiaque, nous avons comparé chez la même personne jeune et en bonne santé la réponse hémodynamique à un repas modérément salé (45 mmol) à celle d'un repas riche en sel (165 mmol de sodium). Les repas ont été pris de manière randomisée à 7 jours d'intervalle. Divers paramètres hémodynamiques ont été mesurés en continu avant et jusqu'à 140 minutes après chaque repas. Nos résultats montrent que les augmentations post-prandiales du volume d'éjection systolique et du travail cardiaque ont été plus prononcées après un repas à haute teneur en sel par rapport à un repas modérément salé.¦Nous spéculons que des apports chroniques en sel induisent des charges hémodynamiques répétées. Etant donné que la concentration plasmatique de sodium, qui est augmentée après un repas salé, est également capable de stimuler la croissance des myocytes cardiaques, il est possible que la combinaison sur des mois ou des années de pics hypernatrémiques post-prandiaux et de charges cardiaques soit responsable de l'hypertrophie cardiaque souvent observée avec une alimentation riche en sel.¦-¦Many clinical studies have shown a close correlation between a chronic high salt diet and the development of left ventricular hypertrophy. This association has been classically attributed to the long-term hypertensive effects of a high salt diet. However, epidemiological studies have also shown that left ventricular hypertrophy may occur independently of changes in arterial pressure.¦Since salt ingestion during a high salt diet is not distributed evenly over a 24-hr period, but occurs essentially during meal periods, we speculate that each acute salt load could lead to greater acute increases in blood pressure, heart filling pressure, stroke volume and cardiac output, putting an additional work load on the heart, promoting in the long run cardiac hypertrophy.¦To test whether a high salt meal leads to hemodynamic changes that may favor cardiac hypertrophy, we compared in the same healthy young individual the response to a moderately salted meal (45 mmol) and to a high-salt meal (165 mmol sodium), given in a random order on separate days, on various cardiovascular parameters that were continuously monitored before and up to 140 minutes after the meal. Our results show that the post-prandial increases in stroke volume, and cardiac work were more pronounced after a high-salt meal than after a low-salt meal.¦We speculate that repetitive salt loads associated with a high salt diet may lead to repetitive hemodynamic loads. Since plasma sodium concentration, which is increased after a salty meal, is also capable to stimulate myocyte growth, it is possible that the combination of post-prandial hypernatremic peaks and of cardiac loads may be responsible, when repeated many times over period of months, of the cardiac hypertrophy often seen with a high salt diet.

A simple way to decompress the left ventricle during venoarterial bypass

OBJECTIVE: The aim of this investigation was to improve the hemodynamics during venoarterial bypass by remote decompression of the left ventricle (LV). METHODS: Venoarterial bypass was established in 5 bovine experiments (69+/-10 kg) by the transjugular insertion of a self-expanding cannula (smartcanula) with return through a carotid artery. Cardiogenic shock was simulated with ventricular fibrillation induced by an external stimulator. Left ventricular decompression was achieved by switching to transfemoral drainage of the pulmonary artery (PA) with a long self-expanding cannula. RESULTS: Initial pump flow was 4.7+/-0.9 l/min and the aortic pressure accounted for 75+/-21 mmHg. After induction of ventricular fibrillation, the pump flow dropped after 11+/-8 min to 2.5+/-0.1 l/min. Transfemoral decompression increased the pump flow to 5.6+/-0.7 l/min, while the RV pressure decreased from 27+/-9 to 3+/-5 mmHg, the PA pressure decreased from 29+/-7 to 5+/-4 mmHg, the LV pressure decreased from 29+/-6 to 7+/-2 mmHg, and the aortic pressure increased from 31+/-3 to 47+/-11 mmHg. CONCLUSIONS: Remote drainage of the pulmonary artery during venoarterial bypass allows for effective decompression of the left ventricle and provides superior hemodynamics.

Importance of the right ventricle in valvular heart disease.

The importance of the right ventricle as a determinant of clinical symptoms, exercise capacity, peri-operative survival and postoperative outcome has been underestimated for a long time. Right ventricular ejection fraction has been used as a measure of right ventricular function but has been found to be dependent on loading conditions, ventricular interaction as well as on myocardial structure. Altered left ventricular function in patients with valvular disease influences right ventricular performance mainly by changes in afterload but also by ventricular interaction. Right ventricular function and regional wall motion can be determined with right ventricular angiography, radionuclide ventriculography, two-dimensional echocardiography or magnetic resonance imaging. However, the complex structure of the right ventricle and its pronounced translational movements render quantification difficult. True regional wall motion analysis is, however, possible with myocardial tagging based on magnetic resonance techniques. With this technique a baso-apical shear motion of the right ventricle was observed which was enhanced in patients with aortic stenosis.

Biometal muscles to restore contractile function of weak heart

Objectives: Existing VADs are single-ventricle pumps needing anticoagulation. We developed a bi-ventricular external assist device that partially reproduces the physiological muscle function of the heart. This artificial muscle could wrap the heart and improve its contractile force.Methods: The device has a carbon fiber skeleton fitting a 30-40kg patient's heart, to which a Nitinol based artificial muscle is connected. The artificial muscle wraps both ventricles. The Nitinol fibers are woven on a Kevlar mesh surrounding each ventricle. The fibers are electrically driven with a dedicated control unit developed for this purpose. We assessed hemodynamic performances of this device using a previously described dedicated bench test. Volume ejected and pressure gradient have been measured with afterload ranging from 10 to 50mmHg.Results: With an afterload of 50mmHg the system has an ejection fraction of 4% on the right side and 5% on the left side. The system is able to generate a systolic ejection of 2.2mL on the right side and 3.25mL on the left side. With an afterload of 25mmHg the results are reduced of about 20%. The activation frequency can reach 80/minute resulting in a total volume displacement of 176mL/minute on the right side and 260mL/minute on the left side.Conclusions: These preliminary studies confirmed the possibility of improving the ejection fraction of a failing heart using artificial muscle for external cardiac compression avoiding anticoagulation therapy. This device could be helpful in weaning cardio-pulmonary bypass and/or for short-term cardio-circulatory support in pediatric population with cardiac failure.

Reshaping the remodelled left ventricle: a new concept.

OBJECTIVE: Based on the law of Laplace, transventricular tension members were designed to diminish wall stress by changing the left ventricle (LV) globular shape to a bilobular one, thus reducing the ventricular wall radius of curvature. This concept was tested in a model of congestive heart failure. METHODS: Seven calves were used for the study (74.3+/-4.2 kg). Treatment efficacy was assessed with sonomicrometric wall motion analysis coupled with intraventricular pressure measurement. Preload increase was applied stepwise with tension members in released and tightened position. RESULTS: Tightening of the tension members improved systolic function for CVP>10 mmHg (dP/dt: 828+/-122 vs. 895+/-112 mmHg/s, P=0.019, for baseline and 20% stress level reduction respectively; wall thickening: 11.6+/-1.5 vs. 13.3+/-1.7%, P<0.001) and diastolic function (LV end-diastolic pressure: 15.9+/-4.8 vs. 13.6+/-2.7 mmHg, P<0.001, for CVP>10 mmHg; peak rate of wall thinning: -12.2+/-2.2 vs. -14+/-2.3 cm(2)/s, P<0.001 and logistic time constant of isovolumic relaxation: 48.4 +/-10.9 vs. 39.8+/-9.6ms, P<0.001, for CVP>5 mmHg). CONCLUSIONS: This less aggressive LV reduction method significantly improves contractility and relaxation parameters in this model of congestive heart failure.

Dose-dependent effect of atrial natriuretic peptide on blood pressure, heart rate, and skin blood flow of normal volunteers.

Synthetic atrial natriuretic peptide, containing 26 amino acids in the rat sequence, L-364, 343 (Ileu-ANP), was infused intravenously at increasing rates (1-40 micrograms/min) into four normal volunteers. Mean intraarterial blood pressure decreased and heart rate increased in cumulative-dose-dependent fashion. Skin blood flow as measured with a laser Doppler device rose already with a cumulative dose of 55 micrograms Ileu-ANP and further rises were directly related to dose. The only side effects observed were those accompanying symptomatic hypotension at higher doses. These findings provide strong evidence that Ileu-ANP acts as a vasodilator in normal volunteers.

Alterations in the local myocardial motion pattern in patients suffering from pressure overload due to aortic stenosis.

BACKGROUND: MR tissue tagging allows the noninvasive assessment of the locally and temporally resolved motion pattern of the left ventricle. Alterations in cardiac torsion and diastolic relaxation of the left ventricle were studied in patients with aortic stenosis and were compared with those of healthy control subjects and championship rowers with physiological volume-overload hypertrophy. METHODS AND RESULTS: Twelve aortic stenosis patients, 11 healthy control subjects with normal left ventricular function, and 11 world-championship rowers were investigated for systolic and diastolic heart wall motion on a basal and an apical level of the myocardium. Systolic torsion and untwisting during diastole were examined by use of a novel tagging technique (CSPAMM) that provides access to systolic and diastolic motion data. In the healthy heart, the left ventricle performs a systolic wringing motion, with a counterclockwise rotation at the apex and a clockwise rotation at the base. Apical untwisting precedes diastolic filling. In the athlete's heart, torsion and untwisting remain unchanged compared with those of the control subjects. In aortic stenosis patients, torsion is significantly increased and diastolic apical untwisting is prolonged compared with those of control subjects or athletes. CONCLUSIONS: Torsional behavior as observed in pressure- and volume-overloaded hearts is consistent with current theoretical findings. A delayed diastolic untwisting in the pressure-overloaded hearts of the patients may contribute to a tendency toward diastolic dysfunction.

Is our heart a well-designed pump? The heart along animal evolution.

A carrier system for gases and nutrients became mandatory when primitive animals grew larger and developed different organs. The first circulatory systems are peristaltic tubes pushing slowly the haemolymph into an open vascular tree without capillaries (worms). Arthropods developed contractile bulges on the abdominal aorta assisted by accessory hearts for wings or legs and by abdominal respiratory motions. Two-chamber heart (atrium and ventricle) appeared among mollusks. Vertebrates have a multi-chamber heart and a closed circulation with capillaries. Their heart has two chambers in fishes, three chambers (two atria and one ventricle) in amphibians and reptiles, and four chambers in birds and mammals. The ventricle of reptiles is partially divided in two cavities by an interventricular septum, leaving only a communication of variable size leading to a variable shunt. Blood pressure increases progressively from 15 mmHg (worms) to 170/70 mmHg (birds) according to the increase in metabolic rate. When systemic pressure exceeds 50 mmHg, a lower pressure system appears for the circulation through gills or lungs in order to improve gas exchange. A four-chamber heart allows a complete separation of systemic and pulmonary circuits. This review describes the circulatory pumping systems used in the different classes of animals, their advantages and failures, and the way they have been modified with evolution.

Specific inhibition of HCN channels slows rhythm differently in atria, ventricle and outflow tract and stabilizes conduction in the anoxic-reoxygenated embryonic heart model.

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed in pacemaker cells very early during cardiogenesis. This work aimed at determining to what extent these channels are implicated in the electromechanical disturbances induced by a transient oxygen lack which may occur in utero. Spontaneously beating hearts or isolated ventricles and outflow tracts dissected from 4-day-old chick embryos were exposed to a selective inhibitor of HCN channels (ivabradine 0.1-10microM) to establish a dose-response relationship. The effects of ivabradine on electrocardiogram, excitation-contraction coupling and contractility of hearts submitted to anoxia (30min) and reoxygenation (60min) were also determined. The distribution of the predominant channel isoform, HCN4, was established in atria, ventricle and outflow tract by immunoblotting. Intrinsic beating rate of atria, ventricle and outflow tract was 164+/-22 (n=10), 78+/-24 (n=8) and 40+/-12bpm (n=23, mean+/-SD), respectively. In the whole heart, ivabradine (0.3microM) slowed the firing rate of atria by 16% and stabilized PR interval. These effects persisted throughout anoxia-reoxygenation, whereas the variations of QT duration, excitation-contraction coupling and contractility, as well as the types and duration of arrhythmias were not altered. Ivabradine (10microM) reduced the intrinsic rate of atria and isolated ventricle by 27% and 52%, respectively, whereas it abolished activity of the isolated outflow tract. Protein expression of HCN4 channels was higher in atria and ventricle than in the outflow tract. Thus, HCN channels are specifically distributed and control finely atrial, ventricular and outflow tract pacemakers as well as conduction in the embryonic heart under normoxia and throughout anoxia-reoxygenation.

Levosimendan as rescue therapy after surgery for congenital heart disease

Objectives: Levosimendan, a calcium-sensitizing agent has been reported as useful for the management of patients with low cardiac output state. We report here our experience, safety and efficacy of use of levosimendan as rescue therapy after surgery for congenital heart disease. Methods: Retrospective cohort study on patients necessitating levosimendan therapy for post operative low cardiac output or severe post operative systolic and diastolic dysfunction. Twelve patients with a mean age of 2.1 years (range 7 days - 14 years old) received levosimendan. Type of surgery: 3 arterial switch, 3 correction of complete abnormal pulmonary venous return, 3 closure of VSD and correction of aortic coarctation, 3 Tetralogy of Fallot, one correction of truncus arteriosus and one palliation for single ventricle. The mean time of ECC was 203 +/- 81min. Ten patients received levosimendan for low cardiac output not responding to conventional therapy in these cases (milrinone, dopamine and noradrenaline) in the first 6 hours following entry in the ICU and 3 patients received levosimendan 3-4 days after surgery for severe systolic and diastolic dysfunction. Levosimendan was given as a drip for 24-48 hours at the dose of 0.1-0.2 mcg/ kg/min, without loading dose. Results: Significant changes were noted on mean plasmatic lactate (3.3 +/- 1.7mmole/L vs 1.8 +/-0.6mmole/L, p+0.01), mean central venous saturation (55 +/- 11% vs 68 +/- 10%, p+0.01) and mean arterio-venous difference in CO2 (9.6 +/- 4.9mmHg vs 6.7 +/- 2.1mmHg, p+0.05) for values before and at the end of levosimendan administration. There was no significant changes on heart rate, systolic pressure or central venous pressure. No adverse effect was observed. Conclusion: Levosimendan, used as rescue therapy after surgery for congenital heart disease, is safe and improves cardiac output as demonstrated with improvement of parameters commonly used clinically.

Connexin 43 expression in human hypertrophied heart due to pressure and volume overload.

Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution.

Reducing Cardiovascular Mortality Through Prevention and Management of Raised Blood Pressure: A World Heart Federation Roadmap.

Prospective epidemiological data have shown that blood pressure has a graded, continuous adverse effect on the risk of various forms of CVD (including stroke, myocardial infarction, heart failure, peripheral arterial disease and end-stage renal disease). 'Raised blood pressure' is frequently considered to be any systolic blood pressure greater than 115 mmHg. It accounts for 45% of all heart disease deaths and 51% of all stroke-related deaths [1], which together are the biggest causes of morbidity and mortality worldwide [2,3,4]. Annually, there are >17 million deaths due to CVD worldwide, of which 9.4 million are attributable to complications of raised blood pressure. This highlights the importance of both high-risk and population-based strategies in blood pressure management and control.