Pulmonary reflexes after human heart-lung transplantation

Area of Science:

• Pulmonary Medicine
• Transplantation Immunology
• Respiratory Physiology

Background:

• Heart-lung transplantation (HLT) results in significant denervation of pulmonary structures below the tracheal anastomosis.
• This denervation impacts various respiratory reflexes and responses, including the cough reflex and airway reactivity.

Purpose of the Study:

• To investigate the functional consequences of pulmonary denervation after HLT.
• To assess airway responsiveness to different stimuli and explore underlying mechanisms in HLT recipients.

Main Methods:

• Evaluation of cough reflex to inhaled substances (ultrasound nebulized distilled water - USNDW).
• Assessment of bronchoconstriction and bronchodilation responses.
• Measurement of airway responsiveness to methacholine and histamine.
• Correlation of responses with acute lung rejection and inflammation status.

Main Results:

• Loss of cough reflex to USNDW suggests Rapidly Adapting Receptors (RARs) are in central airways.
• Bronchoconstriction to USNDW occurred only in HLT recipients with acute lung rejection, indicating a possible vascular response.
• Hyperresponsiveness to methacholine and histamine was observed, independent of inflammation or rejection, suggesting denervation hypersensitivity.
• Histamine-induced hyperresponsiveness correlated with methacholine response, implying direct smooth muscle action.
• Bronchodilation to capsaicin suggests unopposed release of vasoactive intestinal peptide (VIP) from preserved nerves.

Conclusions:

• HLT-induced pulmonary denervation leads to altered airway reflexes and reactivity.
• Hyperresponsiveness to bronchoconstrictors may result from denervation hypersensitivity.
• Specific responses like capsaicin-induced bronchodilation highlight the role of remaining efferent nerves.