Pulmonary Branches Research Articles

Neurones in the dorsal motor vagal nucleus of the cat with non‐myelinated axons projecting to the heart and lungs

Extracellular recordings were made from ninety-four single motoneurones in the dorsal motor vagal nucleus of chloralose-anaesthetized or decerebrate cats. Fifty-five neurones had axons in cardiac vagal branches and thirty-nine had axons in pulmonary vagal branches; the conduction velocities of the axons were in the C fibre range, i.e. the axons were non-myelinated. The neurons exhibited little or no spontaneous activity. Excitatory and inhibitory synaptic inputs were demonstrated by electrical stimulation of the vagus nerve or its branches. Twenty-four neurones were tested by carotid sinus distension but only one was excited. Iontophoretic excitation of neurones projecting to cardiac vagal branches had no effect on heart rate. The properties of these neurones and their possible functions are discussed and contrasted with those of cardiac and pulmonary vagal motoneurones in the nucleus ambiguus.

New Surgical Repair for an Anomalous Origin of the Left Coronary Artery Adjacent to the Pulmonary Cusps with Numerous Large Side Branches

A new surgical procedure for anatomical correction of an anomalous origin of the left main coronary artery (LCA) from the pulmonary artery is described for those patients in whom the origin of the LCA is located adjacent to a pulmonary cusp and several side branches are arising immediately behind the ostium of the LCA. Hence the LCA can not be disconnected from the pulmonary artery for either coronary arterial transfer or bypass grafting. A tunnel-type repair may interfere with the movement of the pulmonary leaflets. In those cases our proposed surgical correction consists of an arteriotomy of the pulmonary trunk, end-to-end anastomosis of a vein graft to the ostium of the LCA and its implantation into the ascending aorta. The resulting defect in the pulmonary artery is closed with a pericardial patch avoiding kinking or stenosis of the pulmonary trunk.

Regional distribution of endothelin receptor in porcine cardiovascular tissues

To clarify effecting sites of endothelin (ET) in a circulation system, we have identified specific receptors for porcine ET(ET-1) and investigated the distribution in the porcine cardiovascular tissues. Scatchard analysis of 125I-porcine ET binding indicated the presence of a single class of high-affinity binding sites. The binding was highly specific for ET-1, because (1) none of the other various peptides or Ca 2+-channel antagonists affected the binding, (2) the scission of disulfide bonds, the digestion of the C-terminal 6-amino acid residues, or nitrophenylsulfenylization of the C-terminal Trp 21 of ET-1 markedly reduced the binding ability and, (3) ET-1 showed the highest affinity for the vascular receptor among three ET isopeptides. Cardiac atria possessed the highest density (2.7 pmol/mg protein) of ET receptors of all the tissues examined, including thoracic aorta, cardiac atria and cardiac ventriculi, basilar, renal, coronary and pulmonary branch arteries, coronary, renal and jugular veins, and small vessels of pia mater encephali. Small vessels, renal and coronary arteries also showed relatively high density (0.8–1.4 pmol/mg protein). Various veins examined also showed considerable density (0.45–0.74 pmol/mg protein). The apparent K d of cardiac ET receptors (0.76 nM) was significantly greater than that of the receptors of the other tissue (0.06–0.14 nM). The extensive distribution and the local enrichment of ET receptor in a cardiovascular system strongly suggests that ET is one of the essential endogenous substances to control the tone of the vasculature.

Effect of Unilateral Pulmonary Vagotomy on Respiratory Control in Man

We studied the breathing pattern and pulmonary function at rest, and ventilatory responses to progressive hypoxia and hypercapnia in 7 awake patients who had undergone esophageal-carcinoma resection with sectioning of the right pulmonary vagal branch by lymphadenectomy. Twelve control patients, who had received the same surgery without vagotomy, were also studied by the same protocol. Two months after the operation, both patient groups demonstrated substantial depressions in FVC and FEV1.0, and slight augmentations in breathing frequency, minute ventilation, and occlusion pressure at 0.2s (P0.2) at rest. In the vagotomized group, the occlusion pressure responses to hypercapnia (delta P0.2/delta PaCO2) and hypoxia (delta P0.2/delta SaO2) in terms of response curve slope increased from 1.3 +/- 1.2 to 1.9 +/- 1.1 cm H2O/Torr and from 0.29 +/- 0.19 to 0.88 +/- 0.53 cm H2O/% (p less than 0.05), respectively. Contrary to the vagotomized patients, the nonvagotomized control group exhibited no significant changes in ventilatory chemosensitivities. Furthermore, when comparing the control and vagotomized groups, postoperative ventilatory chemosensitivity responses in terms of both hypercapnic and hypoxic occlusion pressure responses were significantly higher in the latter. We suggest that (1) due to the development of the substantial mechanical limitation in pulmonary functions, the Hering-Breuer inflation reflex became activated after surgery, and (2) a diminished Hering-Breuer reflex effect to inhibit the respiratory centers by unilateral vagotomy may have resulted in augmented ventilatory chemosensitivities.

Pulmonary venous collaterals secondary to superior vena cava stenosis: A rare cause of right-to-left shunting following repair of a sinus venosus atrial septal defect

We describe a case of unusual pulmonary vein-to-vein collateral formation leading to systemic desaturation years following surgical repair of a sinus venosus atrial septal defect and partial anomalous pulmonary venous return from the right lung. At surgery, a single right upper lobe pulmonary vein branch was left draining high into the superior vena cava (SVC), resulting in a small left-to-right shunt. SVC obstruction developed at the site of the ASD repair and elevated venous pressure above the obstruction caused retrograde flow into the unincorporated pulmonary vein. Pulmonary vein-to-vein collaterals formed between this unincorporated vein and an adjacent pulmonary vein that had been surgically diverted to drain into the left atrium, resulting in a right-to-left shunt within the right lung. Normal pulmonary veins drain multiple bronchopulmonary segments, thus providing potential collateral pathways. Balloon angioplasty of the SVC stenosis successfully relieved the obstruction and abolished the right-to-left intrapulmonary shunt.

Gene Replacement Therapy for Hereditary Emphysema?

FROM 20 000 to 40 000 persons in the United States have α 1 -antitrypsin deficiency, an autosomal recessive disorder that usually leads to emphysema early in life. Recently, therapy has become available that can help prevent the progression of this debilitating, eventually fatal, chronic lung disease. More encouraging, however, are the results of animal studies that suggest human trials of gene therapy to correct this genetic disorder may be only a few years away. Speaking at the American Lung Association's Second Annual Science Writers' Forum in Annapolis, Md, Ronald G. Crystal, MD, chief, Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, Md, offered an explanation of how hereditary emphysema may be more amenable to genetic therapy than possibly such a disease as sickle cell anemia. Most persons who lack a functioning gene for α 1 -antitrypsin will develop emphysema by the third or fourth decade of life. This

Anomalous origin of the left coronary artery from the pulmonary trunk: Anatomic findings in relation to pathophysiology and surgical repair

Anomalous origin of the left coronary artery from the pulmonary trunk, though a discrete anatomic malformation, manifests a spectrum of clinical and pathologic consequences. The objectives of this study were to characterize the primary anatomic findings in a group of specimens with anomalous left coronary artery and the extent of secondary morphologic and pathologic changes. Although the cases studied probably represent the least favorable end of the spectrum, the observed pathogenesis and evolution of secondary changes suggest that reconstruction of a two-coronary arterial system supplied through two coronary arteries would be advantageous to most patients. A high origin of the right coronary artery or location of the left coronary artery adjacent to a pulmonary cusp or branch may complicate the tunnel-type repair. In these cases, transfer of the left coronary artery to the aorta may be preferable.

Right pulmonary artery development after modified Blalock-Taussig shunt (MBTS) in infants with pulmonary atresia, VSD and confluent pulmonary arteries

The ideal palliation for infants with pulmonary atresia, ventricular septal defect and confluent pulmonary arteries should promote normal development of the pulmonary artery branches. In 26 patients who survived a modified Blalock-Taussig shunt (MBTS) in the first year of life, the right pulmonary artery was measured before and after operation by two dimensional (2D) echocardiography. In each patient its size was compared to the normal value for the same body surface area. The patients were divided according to this ratio and according to the real size (mm). Although increased in all cases but two, the size of the right pulmonary artery remained remarkably less than normal in patients with an initially small right pulmonary artery. In view of these results, early palliative enlargement of the right ventricular outflow tract is probably advisable in infants with diminutive pulmonary arteries who do not show adequate pulmonary branch development after MBTS.

Inhibition of brain stem neuronal activity by cardiac and pulmonary vagal afferent fibres in the cat.

Recordings have been made of the activity of 311 neurones in the nucleus tractus solitarius (NTS) and dorsal motor vagal nucleus (DMVN) which responded to stimulation of the cardiac or pulmonary vagal branches in the anaesthetized cat. Eighty-one neurones showed inhibitory effects to vagal branch or vagal trunk stimulation which were exhibited in three different ways. First, the responses of forty neurones evoked by stimulation of one vagal branch were reduced or abolished by stimulation of another vagal branch or the vagal trunk. Second, the spontaneous activity of six neurones, not excited by branch stimulation, was reduced or abolished by vagal branch stimulation, and third, thirty-five neurones showed evidence of reduced excitability to a second stimulus pulse applied to the same branch. The inhibitory effects were characterized by a long time course (mean 932 ms, range 4-10,000 ms), and the latency to onset suggests that both myelinated and non-myelinated afferents are capable of such actions. Inhibitory effects were observed on neuronal elements activated both synaptically, i.e. interneurones, and non-synaptically, i.e. efferent motoneurones or afferent fibres, although no pattern of branches mediating particular effects could be discerned. The possible physiological implications of these observations are discussed.

Reciprocal action of pulmonary vagal afferents on tracheal smooth muscle tension in dogs

Tracheal smooth muscle usually relaxes when the lungs are transiently inflated, an affect attributed to inhibitory input from pulmonary stretch receptors (PSRs). Relaxation is often followed by contraction, however, and occasionally contraction is the sole response. We attemped to identify the afferents responsible for this reflex contraction. In anesthetized, artificially ventilated dogs with open chest we recorded transverse tension in an upper tracheal segment innervated only by the superior laryngeal nerves and periodically hyperinflated the lungs as the cervical vagus nerves were cooled. Hyperinflation usually evoked tracheal relaxation when vagal temperature was 37°C, but contraction became more frequent as temperature decreased and was the sole response below 8°C. We hypothesise that above 6°C contraction was triggered by rapidly adapting receptors and lung C fibers, whereas below 6°C only C fibers were involved. Contraction, which appeared to represent the bronchomotor counterpart of Head's paradoxical reflex, was abolished below 2°C. Cooling alone without periodic hyperinflation increased baseline tracheal tension to a maximum at 7–8°C; further cooling often decreased tension, sometimes to control levels. Cutting the pulmonary vagal branches abolished these effects. Our results indicate that PSRs and C fibers act reciprocally, one causing bronchodilation, the other bronchoconstriction, and that background activity in C fibers may contribute to bronchomotor tone, an effect unmasked by selectively blocking A fibers.

A gamma-aminobutyric-acid-mediated inhibition of neurones in the nucleus tractus solitarius of the cat.

1. Extracellular recordings were made from 123 synaptically activated neurones in the nucleus tractus solitarius of the chloralose-anaesthetized cat. 2. Ninety-one neurones were activated by electrical stimulation of cardiac or pulmonary vagal branches and thirty-two by stimulation of the aortic nerve. 3. Ionophoretic application of GABA abolished or markedly reduced the evoked or spontaneous activity of each neurone tested. These inhibitory effects were antagonized by the simultaneous ionophoretic application of bicuculline. 4. Glycine inhibited the evoked activity of 60% of neurones tested. This inhibition could be antagonized by the simultaneous application of strychnine. 5. Application of bicuculline alone increased the evoked or spontaneous activity of a large proportion of the neurones; strychnine alone had no significant effect on the evoked or spontaneous activity of the neurones. 6. These results are consistent with the hypothesis that GABA acts as an inhibitory transmitter substance within the nucleus tractus solitarius.

The local expression of adult chicken heart myosins during development. II. Ventricular conducting tissue.

The development of the ventricular conducting tissue of the embryonic chicken heart has been studied using a previous finding that morphologically recognizable atrial conducting tissue coexpresses the atrial and the ventricular myosin isoforms. It is found that, by these criteria, at 9 days part of the ventricular conduction system consists of a myocardial ring located around the infundibula of the aorta and truncus pulmonalis. Part of this ring is formed by the retro-aortic root branch. The ring continues via the septal branch into the atrioventricular bundle and its branches, that all express both myosin isoforms. The retro-aortic root branch could be traced back as a part of the myocardial wall of the truncus arteriosus at the 4 days embryonic stage. At the 16th day of development, the septal branch, atrioventricular bundle and left and right bundle branches no longer express the atrial isomyosin, but two bundles originating from the septal branch still express both isomyosins, one being the retro-aortic root branch, the other being only immunologically recognizable and directed to the ventral side of the truncus pulmonalis; this latter we call the pulmonary root branch. Both bundles are remnants of the myocardial ring.

Neurones in the brain stem of the cat excited by vagal afferent fibres from the heart and lungs.

Extracellular recordings were made from 164 neurones in the nucleus tractus solitarius and dorsal motor vagal nucleus of the chloralose-anaesthetized cat. 139 neurones were excited synaptically and 25 non-synaptically by electrical stimulation of cardiac and pulmonary vagal branches. Synaptically excited neurones fall into two populations, one activated solely by myelinated afferent fibres and a second activated solely by non-myelinated afferent fibres. 94 neurones were synaptically excited by afferent fibres in a single vagal branch while 45 were excited by stimulation of two or three branches. Neurones responding to volleys in myelinated afferent fibres were located in both medial and lateral regions of the nucleus tractus solitarius whilst those excited by non-myelinated afferent fibres were restricted to the medial region. Consistent differences in the locations of neurones excited by stimulation of either cardiac or pulmonary or by single or several branches could not be distinguished.

Vagal chemoreflex coronary vasodilation evoked by stimulating pulmonary C-fibers in dogs.

We performed experiments on anesthetized, open-chest dogs to determine whether the pulmonary chemoreflex (bradycardia and systemic hypotension) evoked by stimulating pulmonary C-fibers also involves reflex changes in coronary vascular resistance. We perfused the circumflex coronary artery at constant pressure (usually 100 mm Hg) and recorded mean circumflex blood flow. Stimulation of pulmonary C-fibers by right atrial injection of capsaicin (10 micrograms/kg) decreased arterial blood pressure and heart rate and increased circumflex blood flow by 32-109% (P less than 0.001). Circumflex blood flow also increased, by 26-100% (P less than 0.001), when heart rate was kept constant by pacing. Coronary vasodilation was not secondary to the reflex decrease in arterial blood pressure. Injecting capsaicin (10 micrograms/kg) into the left atrium did not increase circumflex blood flow. Reflex coronary vasodilation could still be evoked when myelinated nerve fibers were blocked selectively by cooling the cervical vagus nerves to 7-8 degrees C but was abolished by cooling to 0 degrees C, by cutting the pulmonary vagal branches, or by giving atropine. Reducing coronary perfusion pressure shifted the stimulus (dose of capsaicin)-response (increase in coronary blood flow) curve to the right, but, even at low perfusion pressures, significant reflex vasodilation still occurred. Regional (transmural) distribution of myocardial blood flow was measured by the microsphere technique at various perfusion pressures. The endocardial:epicardial blood flow ratio decreased significantly as perfusion pressure was reduced, but was not altered by right atrial injection of capsaicin at any perfusion pressure. Our results indicate that stimulation of pulmonary C-fibers triggers reflex cholinergic vasodilation in all layers of the myocardium.

Inspiratory rhythm in airway smooth muscle tone.

In anesthetized paralyzed open-chested cats ventilated with low tidal volumes at high frequency, we recorded phrenic nerve activity, transpulmonary pressure (TPP), and either the tension in an upper tracheal segment or the impulse activity in a pulmonary branch of the vagus nerve. The TPP and upper tracheal segment tension fluctuated with respiration, with peak pressure and tension paralleling phrenic nerve activity. Increased end-tidal CO2 or stimulation of the carotid chemoreceptors with sodium cyanide increased both TPP and tracheal segment tension during the increased activity of the phrenic nerve. Lowering end-tidal CO2 or hyperinflating the lungs to achieve neural apnea (lack of phrenic activity) caused a decrease in TPP and tracheal segment tension and abolished the inspiratory fluctuations. During neural apnea produced by lowering end-tidal CO2, lung inflation caused no further decrease in tracheal segment tension and TPP. Likewise, stimulation of the cervical sympathetics, which caused a reduction in TPP and tracheal segment tension during normal breathing, caused no further reduction in these parameters when the stimulation occurred during neural apnea. During neural apnea the tracheal segment tension and TPP were the same as those following the transection of the vagi or the administration of atropine (0.5 mg/kg). Numerous fibers in the pulmonary branch of the vagus nerve fired in synchrony with the phrenic nerve. Only these fibers had activity which paralleled changes in TPP and tracheal tension. We propose that the major excitatory input to airway smooth muscle arises from cholinergic nerves that fire during inspiration, which have preganglionic cell bodies in the ventral respiratory group in the region of the nucleus ambiguus and are driven by the same pattern generators that drive the phrenic and inspiratory intercostal motoneurons.

Organization within the cranial IX-X complex in ranid frogs: a horseradish peroxidase transport study.

Cranial nerves IX and X in frogs have been described as originating from a nuclear group referred to as the IX-X complex. We studied the central nervous system components of this complex in Rana pipiens and R. catesbiana by labeling peripheral branches of cranial nerves IX and X and identifying the central nervous system contributions of these branches. Various peripheral nerves (IX and the cardiac, gastric, pulmonary, and laryngeal branches of X) were identified and soaked in horseradish peroxidase (HRP). One to 2 weeks later, the frogs were killed and processed for HRP by the tetramethylbenzidine method. Glossopharyngeal efferents originated from a small ventrolateral cell group found at the level of IX root exit. Vagal efferents formed a single column of cells in a ventrolateral position from the level of the brainstem exist of the vagus nerve (approximately 2,000 micrometers above the obex) to 200 micrometers below the obex (values given are for an 80-g frog). This cell group was separate from and just caudal to efferent cells of the glossopharyngeal nerve. Within the vagal portion of the column, cells projecting through the gastric branch were found throughout the rostral-caudal extent of the nucleus. "Cardiac" cells tended to be more rostral than "pulmonary" cells, and both groups of cells were located in the middle of the nucleus. "Laryngeal" cells were located more caudally in the nucleus. This peripheral representation within the vagal nucleus corresponds more closely to the organization found in the mammalian nucleus ambiguus, rather than to the apparent lack of organization found in the mammalian dorsal motor nucleus. Afferents of IX and X entered slightly rostral to the ventral roots of their respective nerves and descended in two tracts. The majority entered the tractus solitarius and descended in a medial position to cervical spinal cord. A portion of the afferents from the vagus nerve crossed the midline in the lower myelencephalon just dorsal to the central canal and ascended a short distance on the contralateral side. Within the solitary tract, vagal afferents were located in a ventrolateral position as they descended to below the obex. Glossopharyngeal afferents filled the remainder of the tract. A smaller portion of afferents from both IX and X did not enter the solitary tract but descended in the spinal tract of V and the dorsolateral funiculus of the spinal cord (Lissauer's tract) to thoracic levels. Afferents of IX also formed a rostral bundle which extended in the solitary tract to the caudal metencephalon.

Reversible truncal vagotomy in conscious dogs

Prior attempts at in vivo reversible vagal denervation of the gastrointestinal tract have been limited to cervical cooling techniques that also denervate both sympathetic and vagal pulmonary and cardiac branches. Denervation of vagal efferent fibers at this level has produced results that are inconsistent with those obtained after surgical truncal vagotomy. We have, therefore, developed a technique to provide reversible vagal denervation below the pulmonary and cardiac branches for the study of gastric motility. Five dogs, previously equipped with gastric strain gages and electrodes, underwent implantation of a tubular cooling jacket around a distal thoracic vagal trunk with contralateral vagotomy (4 dogs), or around both vagal trunks (1 dog). The jacket was made of stainless steel tubing in a “J” design. Its inside channel was lined with a sterling silver sheet, and a thermistor was attached to record temperature change. Silicone tubing coursed externally to a pump and flask to which 95% ethanol at −70 °C was circulated at variable speeds. Thoracic vagal cooling, extending up to 5 h, reversibly blocked gastric contractions induced by insulin hypoglycemia. Contractile waves were terminated at device temperatures of 2 °–6 °C but promptly returned with warming. Dogs were tranquil during denervation, and enclosed nerves remained functional for >40 days.

CT anatomy of hilar lymphadenopathy.

The normal distribution of lymph nodes in the pulmonary hili is diagrammatically shown, with a typical computed tomographic (CT) demonstration of hilar lymphadenopathy. On the basis of observations in anatomic cross sections of cadaver lungs, the lymph nodes in the right lung can be divided into four principal groups (right upper lobe, interlobar, middle lobe, and lower lobe) and in the left lung into three principal groups (left upper lobe, interlobar, and lower lobe). Most of the hilar lymph nodes are situated along the bronchi in close relation with the pulmonary vascular branches. Because of this close proximity, contrast-enhanced CT images are indispensable for precise CT interpretation of a hilar lymphadenopathy.

Reconstruction of the pulmonary outflow tract without prosthetic conduit

New techniques of correction of complex congenital anomalies, avoiding the use of prosthetic conduits, are presented. In transposition of the great arteries (TGA) with ventricular septal defect (VSD) and pulmonary stenosis, the technique comprised the resection of infundibular septum, the suturing of an intraventricular baffle directing blood from the left ventricle to the aorta, and the reconstruction of the pulmonary outflow tract by direct implantation of the posterior rim of the pulmonary arterial trunk on the right ventricle, completed by an anterior patch. In most cases, the pulmonary bifurcation was translated anterior to the ascending aorta. This technique was feasible even in infants and in patients with a small VSD. Thirteen patients, from 3 months to 8 years of age, were treated by this technique, with four deaths, one residual VSD (reoperated), and eight good results (4 to 16 months). A similar repair was used in three cases of double-outlet right ventricle (DORV) with subpulmonic VSD and pulmonary stenosis or pulmonary artery banding, with two operative deaths and one good result. The same technique of pulmonary outflow tract reconstruction was used in four cases of truncus arteriosus. Two deaths were attributed to severe pulmonary regurgitation, a complication which should be prevented in future cases by a reliable method of inserting a valve in the pulmonary outflow tract. In pulmonary atresia with VSD and absent pulmonary trunk, the continuity between the right ventricle and the pulmonary branches was established via an arterial tube resected from the ascending aorta. This technique was successfully used in one child with extremely small pulmonary branches. These preliminary results led us to conclude that many complex congenital cardiac anomalies can be effectively treated without a prosthetic conduit.

Two-dimensional echocardiographic identification of pulmonary artery branch stenosis

Pulmonary artery branch stenosis is a not uncommon congenital lesion, noted in approximately 4% of children at the time of cardiac catheterization. Real-time 2-dimensional echocardiography was used to examine 10 patients with angiographically documented pulmonary branch stenosis. Five cases of pulmonary artery branch narrowing were identified by echocardiography without prior knowledge of angiographic findings. In 5 other patients whose angiographic results were known, the narrowings were identified in 4 of 5 cases. These results demonstrate the feasibility of evaluating pulmonary branch stenosis with the nonionizing, noninvasive method of 2-dimensional echocardiography.