Comparison of Ca2+-handling properties of canine pulmonary vein and left atrial cardiomyocytes

Cardiac tissue in the pulmonary vein sleeves plays an important role in clinical atrial fibrillation. Mechanisms leading to pulmonary vein activity in atrial fibrillation remain unclear. Indirect experimental evidence points to pulmonary vein Ca(2+) handling as a potential culprit, but there are no direct studies of pulmonary vein cardiomyocyte Ca(2+) handling in the literature. We used the Ca(2+)-sensitive dye indo-1 AM to study Ca(2+) handling in isolated canine pulmonary vein and left atrial myocytes. Results were obtained at 35 degrees C and room temperature in cells from control dogs and in cardiomyocytes from dogs subjected to 7-day rapid atrial pacing. We found that basic Ca(2+)-transient properties (amplitude: 186 +/- 28 vs. 216 +/- 25 nM; stimulus to half-decay time: 192 +/- 9 vs. 192 +/- 9 ms; atria vs. pulmonary vein, respectively, at 1 Hz), beat-to-beat regularity, propensity to alternans, beta-adrenergic response (amplitude increase at 0.4 Hz: 96 +/- 52 vs. 129 +/- 61%), number of spontaneous Ca(2+)-transient events after Ca(2+) loading (in normal Tyrode: 0.9 +/- 0.2 vs. 1.3 +/- 0.2; with 1 microM isoproterenol: 7.6 +/- 0.3 vs. 5.1 +/- 1.8 events/min), and caffeine-induced Ca(2+)-transient amplitudes were not significantly different between atrial and pulmonary vein cardiomyocytes. In an arrhythmia-promoting model (dogs subjected to 7-day atrial tachypacing), Ca(2+)-transient amplitude and kinetics were the same in cells from both pulmonary veins and atrium. In conclusion, the similar Ca(2+)-handling properties of canine pulmonary vein and left atrial cardiomyocytes that we observed do not support the hypothesis that intrinsic Ca(2+)-handling differences account for the role of pulmonary veins in atrial fibrillation.     

High sensitivity of the sheep pulmonary vein antrum to acetylcholine stimulation.

Isolation of the pulmonary vein antrum can terminate atrial fibrillation, but the rationale has not been elucidated. In the present study, we show that sheep atrial effective refractory period (ERP) was heterogeneously shortened by acetylcholine administration. After perfusion with 15 muM acetylcholine, the shortest ERP occurred in the pulmonary vein antrum, which was recorded with the standard intracellular microelectrode technique (the ERP results in the pulmonary vein antrum, left atrial posterior wall, roof, free wall and appendage, and right atrial free wall were 52.0 +/- 1.6, 75.1 +/- 2.0, 77.2 +/- 1.7, 85.6 +/- 1.7, 64.3 +/- 2.1, and 90.5 +/- 1.3 ms, respectively; P < 0.05). Immunofluorescent staining revealed that muscarinic type 2 receptors (M(2)R) were also distributed heterogeneously in the atrial myocardium, with the highest density in the antrum (the relative fluorescent intensity results of the M(2)R in the pulmonary vein antrum, left atrial posterior wall, roof, free wall and appendage, and right atrial free wall were 62.64 +/- 2.56, 53.12 +/- 2.76, 51.83 +/- 2.45, 47.90 +/- 2.33, 55.27 +/- 2.08, and 45.53 +/- 2.02, respectively; P < 0.05), which was in accordance with the heterogeneity of ERP distribution. Thus the pulmonary vein antrum is a unique electrophysiological region with high sensitivity to acetylcholine, and its intensive response to acetylcholine is most likely associated with the dense M(2)R distribution of this region. Such an acetylcholine-induced ERP heterogeneity is possibly a substrate for atrial fibrillation and hence one of the potential electrophysiological bases for the isolation therapy.     

Distension of the pulmonary vein - atrial junctions and plasma vasopressin in the chloralose-anaesthetized dog

The effects of localized distension of the pulmonary vein - left atrial junctions on plasma arginine vasopressin (AVP) have been examined in chloralose anaesthetized dogs. Pulmonary vein distension caused an increase in heart rate and a decrease in plasma AVP concentration. Cooling the vagosympathetic nerves to 10 degrees C caused an increase in arterial pressure and plasma AVP concentration and prevented the changes in heart rate and plasma AVP concentration caused by pulmonary vein distension. Cooling the vagus nerves to 16 degrees C did not change heart rate, arterial pressure, or plasma AVP concentration but significantly reduced the changes in heart rate and plasma AVP concentration caused by pulmonary vein distension. Propranolol (0.5 mg/kg) decreased heart rate and prevented the increase in heart rate associated with pulmonary vein distension but did not abolish the decrease in plasma AVP concentration. It is concluded that distension of the pulmonary vein - left atrial junctions causes a decrease in plasma AVP concentration by stimulating atrial receptors with myelinated afferent fibres. The decrease in plasma AVP concentration is not secondary to the reflex changes in heart rate caused by pulmonary vein distension.     

Prediction and assessment of the time-varying effective pulmonary vein area via cardiac MRI and Doppler echocardiography

Accurately estimating left atrial (LA) volume with Doppler echocardiography remains challenging. Using angiography for validation, Marino et al. (Marino P, Prioli AM, Destro G, LoSchiavo I, Golia G, and Zardini P. Am Heart J 127: 886-898, 1994) determined LA volume throughout the cardiac cycle by integrating the velocity-time integrals of Doppler transmitral and pulmonary venous flow, assuming constant mitral valve and pulmonary vein areas. However, this LA volume determination method has never been compared with three-dimensional LA volume data from cardiac MRI, the gold standard for cardiac chamber volume measurement. Previously, we determined that the effective mitral valve area is not constant but varies as a function of time. Therefore, we sought to determine whether the effective pulmonary vein area (EPVA) might be time varying as well and also assessed Marino's method for estimating LA volume. We imaged 10 normal subjects using cardiac MRI and concomitant transthoracic Doppler echocardiography. LA and left ventricular (LV) volumes were measured by MRI, transmitral and pulmonary vein flows were measured by Doppler echocardiography, and time dependence was synchronized via the electrocardiogram. LA volume, estimated using Marino's method, was compared with the MRI measurements. Differences were observed, and the discrepancy between the echocardiographic and MRI methods was used to predict EPVA as a function of time. EPVA was also directly measured from short-axis MRI images and was found to be time varying in concordance with predicted values. We conclude that because EPVA and LA volume time dependence are in phase, LA filling in systole and LV filling in diastole are both facilitated. Application to subjects in select pathophysiological states is in progress.     

Distribution of the pulmonary artery and vein in the chimpanzee lung

Lungs of two chimpanzees (Pan troglodytes) were examined. The right pulmonary artery runs across the ventral side of the right upper lobe bronchiole and, then across the dorsal side of the right middle lobe bronchiole. Thereafter, it runs between the dorsal bronchiole system and the lateral bronchiole system, along the right bronchus. During its course, it gives off arterial branches which run along each bronchiole. The left pulmonary artery runs across the dorsal side of the left middle lobe bronchiole and then between the dorsal bronchiole system and the lateral bronchiole system. The branches of the pulmonary artery run mainly along the dorsal or lateral side of the bronchiole. The pulmonary veins run mainly along the ventral or medial side of the bronchioles, and between them. Finally, they enter the left atrium with four large veins, i.e. the common trunk of the right upper lobe vein and the right middle lobe vein, right lower lobe pulmonary venous trunk, left middle lobe vein, and left lower lobe pulmonary venous trunk.     

小鼠肺静脉起源和肺静脉心肌的形成

目的探讨小鼠胚胎心脏静脉端肺静脉α-横纹肌肌节肌动蛋白（α-SCA）、α-平滑肌肌动蛋白（α-SMA）的表达特征,研究肺静脉起源及肺静脉心肌的形成。方法妊娠小鼠经乙醚麻醉,收集9—17天胎龄胚胎。对小鼠胚胎心脏进行石蜡连续切片,用抗α-SCA、抗α-SMA单克隆抗体对连续切片进行免疫组化PAP法染色。结果小鼠胚胎发育第11天,心背系膜内α-SCA、α-SMA表达皆阴性的内皮性肺静脉出现,肺静脉开口于原始房间隔左侧。小鼠胚胎发育第12天,肺静脉周围出现α-SCA、α-SMA阳性细胞。小鼠胚胎发育第12天以后,伴随肺静脉纵向延伸,α-SMA阳性细胞出现在肺静脉周围的间充质中,肺静脉周围α-SCA、α-SMA阳性细胞逐渐增多,在第12-13天之间增加最明显,小鼠胚胎发育至14、15d两种抗体表达至高峰。胚胎发育第16,17天,开口于左房发育渐成熟的肺静脉。α-SMA表达明显下降,α-SCA的表达还维持在较高水平。结论肺静脉不在静脉窦中发育,肺静脉始基和内皮性肺静脉与原始心房或左心房直接连接;肺静脉心肌来源于周围邻近的间充质细胞。     

Distribution of the pulmonary artery and vein in the lung of the white handed gibbon

The lungs of four white handed gibbons (Hylobates agilis) were examined. The right pulmonary artery runs across the ventral side of the right upper lobe bronchiole, and then traverses the dorsal side of the right middle lobe bronchiole. Thereafter, it runs along the dorso-lateral side of the right bronchus, between the dorsal bronchiole system and the lateral bronchiole system, and gradually follows the dorsal side of the right bronchus. During its course, it gives off arterial branches which run along each bronchiole. The left pulmonary artery runs across the dorsal side of the left middle lobe bronchiole and then along the left bronchus as in the right lung. The branches of the pulmonary artery run mainly along the dorsal or lateral side of the bronchiole, while the pulmonary veins run mainly the medial side of the bronchioles or between them. However, in a few portions, the pulmonary veins run the lateral side of the bronchioles. Finally, they enter the left atrium with four large veins i.e. the common trunk of the right upper lobe vein and right middle lobe vein, right lower lobe pulmonary venous trunk, left middle lobe vein, and left lower lobe pulmonary venous trunk.     

Thromboses néoplasiques et thromboses cruoriques mécaniques compliquant un cancer du testicule gauche en TEP/TDM au 18FDG

We report the case of a 46-year-old patient with pulmonary embolism complicating thrombosis of the left renal vein and inferior vena cava, which came from a malignant tumor of the left testicle. The case has been elucidated by positron emission tomography with ¹⁸FDG coupled to the CT-scan (PET/CT), performed as part of the etiological assessment of this pulmonary embolism, and anatomical and physiological considerations. The examination revealed ¹⁸FDG uptake in thrombus of the left kidney vein and the inferior vena cava. In view of the anatomy of the left spermatic vein, this finding led to the left testicle, which shows no nuclide uptake but was bathed in a large hydrocele visible on CT images. If several cases of pulmonary embolism or thrombosis of the inferior vena cava revealing a testicular cancer have been described in the literature, there has been no report including ¹⁸FDG PET/CT to the best of our knowledge. This case illustrates the imaging differences between bland and malignant thrombus as a consequence of their pathophysiology. It highlights the contribution of CT images from the PET/CT for the diagnosis.     

A novel surgical approach to cardiac autotransplantation in complex cardiac sarcoma resection

A 28-year-old woman was admitted to our institution, reporting progressive dyspnea, cough, and weight loss of 14 kg. Two-dimensional echocardiography revealed a left atrial mass, and cardiac magnetic resonance imaging showed localized involvement of the mass with adjacent structures. These clinical signs and radiographic images were highly suggestive of cardiac sarcoma. The patient underwent emergent mediastinal exploration, and an incisional biopsy of the mass showed high-grade sarcoma. Removing the tumor required radical en bloc resection of the left atrium, including the mitral valve, the left pulmonary vein, and the left lower lobe of the lung. Autotransplantation was necessary for the resection and reconstruction. We report a unique method of handling the right atrium to avoid the potential complications associated with bicaval anastomoses after autotransplantation.     

Distribution of the pulmonary artery and vein of the orangutan lung

The distribution of the pulmonary artery and vein of the orangutan lung was examined. The right pulmonary artery runs obliquely across the ventral side of the right bronchus at the caudally to the right upper lobe bronchiole. It then runs across the dorsal side of the right middle lobe bronchiole. Thereafter it runs obliquely across the dorsal side of the right bronchus, and then along the dorso-medial side of the right bronchus. This course is different from that in other mammals. During its course, it gives off branches which run mainly along the dorsal or lateral side of each bronchiole. The left pulmonary artery runs across the dorsal side of the left middle lobe bronchiole, then along the dorso-lateral side of the left bronchus, giving off branches which run along each bronchiole. The pulmonary veins run mainly the ventral or medial side of, along or between the bronchioles. In the left lung, the left middle lobe vein has two trunks; one enters the left atrium, and the other enters the left lower lobe pulmonary venous trunk. This is also different from that found in most mammals. Finally, the pulmonary veins enter the left atrium with four large veins.     

Distribution of atrial natriuretic polypeptide (ANP)-containing cells in the rat heart and pulmonary vein Immunohistochemical study and radioimmunoassay

Summary The distribution of atrial natriuretic polypeptide (ANP) was immunohistochemically surveyed in the rat heart and lung using an antiserum raised against -human ANP. The ANP-immunoreactive cells were seen to be distributed in the atrial walls and proximal portions of the pulmonary vein and venae cavae, but were absent from the aorta, pulmonary arteries, trachea, bronchus, and alveolar cells. The immunoreactive cells were present in a narrow region just beneath the endothelium of the pulmonary vein and vena cavae, and, ultrastructurally and immunocytochemically, were seen to be striated muscle cells with ANP-containing specific granules similar to those seen in atrial cardiocytes. A radioimmunoassay for ANP revealed a content of 604±51 pg/mg wet weight in the pulmonary vein, and 3343±1620 pg/mg wet weight in the venae cavae. In addition to the atrial wall, the proximal portion of both the pulmonary vein and venae cavae are suggested to be constituents of an ANP-producing organ.     

A case of dextrocardia with normal situs.

We report here a case of dextrocardia with normal situs in an 81-year-old man who died from non-pulmonary causes. Removal of the chest wall revealed a large, but otherwise anatomically normal, left lung occupying the entire left hemithorax and extending across the midline to overlap the left border of the heart which was positioned in the right hemithorax. The gross anatomy of the heart was normal save its position and the presence of only 2 pulmonary veins. Dissection of the heart showed all chambers in their classically described position, and there were no valvular defects. The anatomy of the great vessels was also normal. The right lung was hypoplastic and lay posterior to the heart. This lung lacked any lobular structure, but the presence of carbon particles throughout it suggested that it was capable of normal inflation.     

Computational modeling of left heart diastolic function: examination of ventricular dysfunction

A computational model that accounts for blood-tissue interaction under physiological flow conditions was developed and applied to a thin-walled model of the left heart. This model consisted of the left ventricle, left atrium, and pulmonary vein flow. The input functions for the model included the pulmonary vein driving pressure and time-dependent relationship for changes in chamber tissue properties during the simulation. The Immersed Boundary Method was used for the interaction of the tissue and blood in response to fluid forces and changes in tissue pathophysiology, and the fluid mass and momentum conservation equations were solved using Patankar's Semi-Implicit Method for Pressure Linked Equations (SIMPLE). This model was used to examine the flow fields in the left heart under abnormal diastolic conditions of delayed ventricular relaxation, delayed ventricular relaxation with increased ventricular stiffness, and delayed ventricular relaxation with an increased atrial contraction. The results obtained from the left heart model were compared to clinically observed diastolic flow conditions, and to the results from simulations of normal diastolic function in this model [1]. Cases involving impairment of diastolic function were modeled with changes to the input functions for fiber relaxation/contraction of the chambers. The three cases of diastolic dysfunction investigated agreed with the changes in diastolic flow fields seen clinically. The effect of delayed relaxation was to decrease the early filling magnitude, and this decrease was larger when the stiffness of the ventricle was increased. Also, increasing the contraction of the atrium during atrial systole resulted in a higher late filling velocity and atrial pressure. The results show that dysfunction can be modeled by changing the relationships for fiber resting-length and/or stiffness. This provides confidence in future modeling of disease, especially changes to chamber properties to examine the effect of local dysfunction on global flow fields.     

Recurrent myocardial infarction in a patient with Prinzmetal's angina and normal coronary arteries

A 55-year-old man was referred for the evaluation of frequent chest pain and syncope. While in the hospital, he experienced severe chest pain accompanied by transient ST segment elevation and a slight elevation of cardiac enzyme levels. Multiple coronary arteriograms were recorded at various times during an interval of 2 months. On one occasion, the results were normal; on another occasion, they showed total occlusion of the left anterior descending, diagonal, and circumflex coronary arteries. The occlusion was completely relieved with sublingual nitroglycerin. Because the patient's clinical condition deteriorated rapidly, double aortocoronary saphenous vein bypass was performed to the left anterior descending and circumflex coronary arteries. During the induction of anesthesia, ventricular fibrillation occurred, and the patient died from refractory recurrent fibrillation 4 hours after surgery. Postmortem examination revealed normal coronary arteries, patent vein grafts, and multiple focal areas of recent and old myocardial fibrosis. Thus, it appears that coronary spasm, in the presence of otherwise normal coronary arteries, can produce myocardial infarction with necrosis, and that medical management may provide a more successful method of treating such patients.     

Comparative effects of leukotrienes on porcine pulmonary circulation in vitro and in vivo

The present study examined the effect of leukotrienes on porcine pulmonary vasculature both in vivo and in vitro. In vitro studies using isolated vascular strips demonstrated that pulmonary arterial smooth muscle contracted to leukotriene C4 (LTC4), whereas pulmonary vein smooth muscle did not. Pulmonary arterial contraction was due to both the direct action of LTC4 and secondarily generated thromboxane A2 (TxA2). In vivo, LTC4 injection caused a pronounced but transient increase in pulmonary arterial pressure and pulmonary arterial wedge pressure (Ppw), with a smaller effect on left ventricular end-diastolic pressure. Effects of LTD4 were smaller with comparable pressure changes at all three sites, suggesting a primary cardiac effect. Like LTC4, histamine caused a disproportionate increase in Ppw vs. left ventricular end-diastolic pressure. These observations suggest that LTC4 causes pulmonary venoconstriction in vivo despite its lack of effect on pulmonary vein smooth muscle in vitro. This discrepancy may be due to venoconstrictor effects of TxA2 generated from upstream pulmonary arterial vessels.     

MRI and echocardiographic assessment of the diastolic dysfunction of normal aging: altered LV pressure decline or load?

Changes in diastolic indexes during normal aging, including reduced early filling velocity (E), lengthened E deceleration time (DT), augmented late filling (A), and prolonged isovolumic relaxation time (IVRT), have been attributed to slower left ventricular (LV) pressure (LVP) decay. Indeed, this constellation of findings is often referred to as the "abnormal relaxation" pattern. However, LV filling is determined by the atrioventricular pressure gradient, which depends on both LVP decline and left atrial (LA) pressure (LAP). To assess the relative influence of LVP decline and LAP, we studied 122 normal subjects aged 21-92 yr by Doppler echocardiography and MRI. LVP decline was assessed by color M-mode (V(p)) and the LV untwisting rate. Early diastolic LAP was evaluated using pulmonary vein flow systolic fraction, pulmonary vein flow diastolic DT, color M-mode (E/V(p)), and tissue Doppler (E/E(m)). Linear regression showed the expected reduction of E, increase in A, and prolongation of IVRT and DT with advancing age. There was no relation of age to parameters reflecting the rate of LVP decline. However, older age was associated with reduced E/V(p) (P = 0.008) and increased pulmonary vein systolic fraction (P < 0.001), pulmonary vein DT (P = 0.0026), and E/E(m) (P < 0.0001), all suggesting reduced early LAP. Therefore, reduced early filling in older adults may be more closely related to a reduced early diastolic LAP than to slower LVP decline. This effect also explains the prolonged IVRT. We postulate that changes in LA active or passive properties may contribute to development of the abnormal relaxation pattern during the aging process.     

Hemodynamics and right-ventricle functional characteristics of a swine carotid artery-jugular vein shunt model of pulmonary arterial hypertension: An 18-month experimental study

The continuous changes in pulmonary hemodynamic properties and right ventricular (RV) function in pulmonary arterial hypertension (PAH) have not been fully characterized in large animal model of PAH induced by a carotid artery–jugular vein shunt. A minipig model of PAH was induced by a surgical anastomosis between the left common carotid artery and the left jugular vein. The model was validated by catheter examination and pathologic analyses, and the hemodynamic features and right-ventricle functional characteristics of the model were continuously observed by Doppler echocardiography. Of the 45 minipigs who received the surgery, 27 survived and were validated as models of PAH, reflected by mean pulmonary artery pressure ≥25 mmHg, and typical pathologic changes of pulmonary arterial remodeling and RV fibrosis. Non-invasive indices of pulmonary hemodynamics (pulmonary artery accelerating time and its ratio to RV ventricular ejection time) were temporarily increased, then reduced later, similar to changes in tricuspid annular displacement. The Tei index of the RV was elevated, indicating a progressive impairment in RV function. Surgical anastomosis between carotid artery and jugular vein in a minipig is effective to establish PAH, and non-invasive hemodynamic and right-ventricle functional indices measured by Doppler echocardiography may be used as early indicators of PAH.     

Double-gap-in-roof reentrant tachycardia following surgical thoracoscopic atrial fibrillation ablation

A case of macro-reentrant tachycardia associated with a box lesion after thoracoscopis left atrial surgical atrial fibrillation (AF) ablation yet to be described. The goal was to clarify the mechanisms and electrophysiological characteristics of this type of tachycardia.A patient was admitted for an EP study following surgical thoracoscopic AF ablation (box lexion formation by right-sided Cobra thoracoscopic ablation). Thoracoscopic ablation was done as the first step of the hybrid ablation approach to the persistent AF; the second step was the EP study. At the EP study, he presented with incessant regular tachycardia (cycle length of 226 ms). An EP study with conventional, 3D activation and entrainment mapping was done to assess the tachycardia mechanism. Two conduction gaps in the superior line (roofline) between the superior pulmonary veins were discovered. The tachycardia was successfully treated with a radiofrequency application near the gap close to the left superior pulmonary vein; however, following tachycardia termination, pulmonary vein isolation was absent. A second radiofrequency application, close to the roof of the right superior pulmonary, vein closed the gap in the box and led to the isolation of all 4 pulmonary veins. No atrial tachycardia recurred during the 6-month follow-up.Conduction gaps in box lesion created by thoracospcopic ablation can present as a novel type of man-made tachycardia after surgical ablation of atrial fibrillation. Activation and entrainment mapping is necessary for an accurate diagnosis.     

Expression of TGFβ1 in pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs

The development of pulmonary vein stenosis has recently been described after radiofrequency ablation (RF) to treat atrial fibrillation (AF). The purpose of this study was to examine expression of TGFβ1 in pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs. About 28 mongrel dogs were randomly assigned to the sham-operated group (n = 7), the AF group (n = 7), AF + RF group (n = 7), and RF group (n = 7). In AF or AF + RF groups, dogs underwent chronic pulmonary vein (PV) pacing to induce sustained AF. RF application was applied around the PVs until electrical activity was eliminated. Histological assessment of pulmonary veins was performed using hematoxylin and eosin staining; TGFβ1 gene expression in pulmonary veins was examined by RT-PCR analysis; expression of TGFβ1 protein in pulmonary veins was assessed by Western blot analysis. Rapid pacing from the left superior pulmonary vein (LSPV) induced sustained AF in AF group and AF + RF group. Pulmonary vein ablation terminated the chronic atrial fibrillation in dogs. Histological examination revealed necrotic tissues in various stages of collagen replacement, intimal thickening, and cartilaginous metaplasia with chondroblasts and chondroclasts. Compared with sham-operated and AF group, TGFβ1 gene and protein expressions was increased in AF + RF or RF groups. It was concluded that TGFβ1 might be associated with pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs. Shufeng Li and Hongli Li contributed equally to the work.