Exercise in the presence of left ventricular dysfunction is associated with changes in the pulmonary circulation-leading to congestion and edema.
The aim of this investigation is to identify the nature of the receptors which are activated during the initial stages of this process. It is likely that activation of pulmonary receptors contributes to the symptoms associated with left ventricular dysfunction, i.e. wheezing and rapid respiration. Sensory information from the lung is conveyed to the brain by four groups of vagal receptors (1) the slowly adapting receptors (SAR), (2) Rapidly adapting receptors (RAR), (3) Bronchial C and (4) Pulmonary C receptors. Previous investigations have shown that the activity of RAR is modified by small changes in Starling forces which influence the transfer of fluid across capillaries. For instance, increases in hydrostatic pressure of 5- 10 mmHg, change in oncotic pressure resulting from a fall plasma proteins of 12-15% and an increase in peri-microvascular pressure resulting from obstruction of lymph drainage from the lungs, activate RAR but have no significant effect on SAR. The effect of such small stimuli on Bronchial C and Pulmonary C factors receptors have not been examined fully. In the proposed investigation the following hypothesis will be tested initially: a) The bronchial C (Coleridge type) and pulmonary C (Paintal J type) receptors are activated by obstruction of lymphatic drainage from the lung. b) The bronchial C (Coleridge type) and pulmonary C (Paintal J type) receptors are activated by small reductions (12-15%) in the concentration of plasma proteins. The experiments will be done in anesthetized rabbits. The concentration of plasma proteins (i.e., oncotic pressure) will be reduced by batch plasmapheresis while the peri-microvascular pressure will be increased by obstruction lymphatic drainage from the lung. Later, these studies will be extended to Include investigations into the behavior of pulmonary receptors on a model of chronic pulmonary venous congestion. After completion of these studies, further investigations will be undertaken to determine the influence of obstruction of the lymphatic drainage from the lung on renal function (i.e. renal blood flow, sympathetic nerve activity, urine flow and sodium excretion). Concurrent with these studies, additional experiments will be undertaken to measure the changes in extracellular water in the lung and airway following pulmonary venous congestion, plasmapheresis and lymphatic obstruction. These investigations will help to elucidate the role of these receptors in the symptomatology of early left ventricular dysfunction.
| Campbell, H; Ravi, K; Bravo, E et al. (1996) Effect of Diazinon PLUS on rapidly adapting receptors in the rabbit. J Appl Physiol 81:2604-10 |
| Ravi, K; Bonham, A C; Kappagoda, C T (1994) Effect of pulmonary lymphatic obstruction on respiratory rate and airway rapidly adapting receptor activity in rabbits. J Physiol 480 ( Pt 1):163-70 |
