Lung Microcirculation
John H. Barker, Gary L. Anderson, Michael D. Menger in Clinically Applied Microcirculation Research, 2019
The pulmonary circulation consists of the output of the right ventricle which, via the pulmonary artery and its branches, sends mixed venous blood to the pulmonary capillaries where it undergoes gas exchange, and returns it via the pulmonary veins to the left atrium. Gas exchange is the primary function of the lungs and is achieved by the close approximation of pulmonary capillaries and alveoli. The other blood supply to the lungs is the bronchial circulation, which is a small fraction of the output of the left ventricle. It branches from the thoracic aorta or intercostal arteries and supplies arterial blood to the conducting airways and other structures such as the visceral pleura, esophagus, large blood vessels and nerves, and lymph nodes. Bronchial veins drain into pulmonary veins and also into systemic veins (the azygos and hemiazygos veins, which drain into the superior vena cava). Anastomoses between the bronchial and pulmonary circulations have been found in larger vessels between bronchial and pulmonary arterial branches, and at the microcirculatory level between bronchial and pulmonary capillaries. Further discussion of the pulmonary and bronchial circulation is beyond the scope of this chapter, and the reader is referred to other articles.9,14
Lung transporters and absorption mechanisms in the lungs
Anthony J. Hickey, Heidi M. Mansour in Inhalation Aerosols, 2019
The lung has two separate blood supplies: the pulmonary circulation and the bronchial circulation. The pulmonary arteries carry deoxygenated blood from the right ventricle to the lungs, where a dense network of pulmonary capillaries with very large surface area surrounds the alveoli. This is where removal of CO2 and oxygenation of the blood takes place. After being oxygenated, the blood is returned to the left atrium through the pulmonary vein (3). The bronchial arteries, on the other hand, arise from the aorta and carry oxygenated blood to provide nutrients and oxygen to the conducting airways and lung interstitium and tissues. Only approximately one-third of the blood returns to the right atrium via the bronchial veins; the remaining blood drains into the left atrium through the pulmonary veins (4).
Structure and Function of the Respiratory System
Hans Bisgaard, Chris O’Callaghan, Gerald C. Smaldone in Drug Delivery to the Lung, 2001
The primary function of the bronchial circulation is to supply oxygen and nourishment to the lung, but by maintaining the fluid balance it also facilitates efficient mucociliary clearance. It also responds to inhaled noxious substances by vasodilatation (61). Sympathetic and parasympathetic nerves control the bronchial vasculature. Stimulation of the α receptors causes vasoconstriction, while stimulation of the β receptors results in vasodilatation. Changes in temperature of the inspired airflow will influence blood flow. However, neuromodulators given by aerosol do not have a great effect on blood flow (62). The bronchial circulation is important for the uptake of drugs from aerosols in that any drug passing through the epithelium will diffuse into the bronchial vessels. It will then move downstream to the periphery of the lung or will return to the heart via the bronchial veins and thus into the systemic system. This will lead to modification of effect on peripheral smooth muscle. The bronchial circulation may therefore be of assistance in delivering drugs to other areas in the lung and elsewhere in the body but could also decrease delivery to the more peripheral airways. A vasodilator administered at the same time as aerosol therapy will increase absorbency of a drug that could be exploited therapeutically (63).
Methyl isocyanate inhalation induces tissue factor-dependent activation of coagulation in rats
Published in Drug and Chemical Toxicology, 2019
Raymond C. Rancourt, Jacqueline S. Rioux, Livia A. Veress, Rhonda B. Garlick, Claire R. Croutch, Eric Peters, William Sosna, Carl W. White
Previously we have identified several adverse effects resulting from inhalation of agents similar to MIC, including the alkylating agents half-mustard (2-choroethyl ethyl sulfide) and sulfur mustard. Among these findings were in vitro and in vivo evidence of activation of tissue factor (TF), activation of the clotting cascade, and fibrin deposition in the airways (Rancourt et al.2012). In addition, we found activation of intravascular coagulation resulting in thrombotic events in the lung vasculature (McGraw et al.2017). Leakage of plasma contents, including blood-clotting factors, into airways from the bronchial circulation further contributed to extravascular coagulation there. Finally, the persistence of such fibrinous lesions in airways was assured by the inhibition of multiple fibrinolytic pathways following inhalation of these TICs (Rancourt et al.2014). Here we report an early procoagulant effect, including a rapid, yet transient, expression of TF in the circulating plasma from MIC-exposed rats.
Management of severe hemoptysis
Published in Expert Review of Respiratory Medicine, 2018
Antoine Parrot, Sebastian Tavolaro, Guillaume Voiriot, Antony Canellas, Jalal Assouad, Jacques Cadranel, Muriel Fartoukh
There are a few relative contraindications to BAE. Among them, we find major hemostatic disorders (which in theory will be corrected), severe kidney failure, allergies to iodine, a significantly atheromatous aorta or an aorta at risk of dissection (Marfan disease), an anterior spinal or esophageal branch, and a shunt owing to a proximal obstruction of a pulmonary artery branch. Indeed, in this latter setting, bronchial circulation usually supplies the distal pulmonary circulation.
Inhaled cytotoxic chemotherapy: clinical challenges, recent developments, and future prospects
Published in Expert Opinion on Drug Delivery, 2021
Nathalie Wauthoz, Rémi Rosière, Karim Amighi
Inhalation, or pulmonary drug delivery, is an advantageous route of administration to treat pulmonary disorders. It has become the main route of administration of treatment against asthma or chronic obstructive pulmonary disease (COPD) and is used also to treat some pulmonary infections often encountered in cystic fibrosis or to treat pulmonary hypertension [13,14]. This noninvasive route of administration presents many advantages over systemic deliveries such as the oral or intravenous (iv) routes. These have a favorable pharmacokinetic profile because they limit systemic adverse effects and the first-pass metabolism by concentrating the drug into the site of action. This route of administration allows a lower dose to have a rapid onset and to have the same effect as a higher dose delivered by systemic routes [13,14]. These numerous advantages have led to this route of administration being evaluated for lung cancer therapy. The drug can be deposited topically, close to or on the tumors, which creates a favorable drug concentration gradient to diffuse into the tumor. Moreover, it allows the tumor to be reached another way than by vascularization, which is the main route in systemic treatments [15]. Some zones of tumors are poorly or non-vascularized, which renders them hypoxic [16]. A hypoxic environment favors invasive and resistant cancer cells or clonogenic cells responsible for tumor cell repopulation [7,16,17]. Moreover, as these zones are more distant from blood vessels, the cells are exposed to a much lower drug concentration from systemic routes even though they need a higher drug concentration to be killed [17–19]. Moreover, drug deposited into the lung is mainly absorbed into the local bloodstream and can also be drained by the lymphatic system [20,21]. This has been proven for a nebulized cisplatin (CIS) solution (dose of 40 mg) delivered to two stage II NSCLC patients two hours before surgery, evaluated by quantification of platinum in their lymph nodes (subcarinal node: 2.09 µg/g) and blood samples (0.13 µg/g) at 90 min post aerosol administration [22]. Therefore, lung deposited drug can follow the same routes as potential invasive cancer cells from a solid lung tumor (i.e. micrometastases) [7,20]. Moreover, depending on their localization, lung tumors are vascularized from either bronchial vascularization from bronchial arteries in the conducting zone (i.e. generation 0 to 16) or from pulmonary circulation in the transitional and respiratory zone (i.e. generation 17 to 23) [23]. As the pulmonary circulation receives the bronchial circulation, the tumors in the respiratory zone can also be reached from local blood circulation by the drug deposited in the larger airways, which represents a second access that can intensify the therapeutic response [21]. Therefore, lung tumors or metastases can be exposed to the drug topically or after it is absorbed or drained into the blood circulation and lymphatic system. In these cases, there is a favorable drug gradient concentration between the target tissue (tumor, lung, lymph node) and the blood (Figure 1).