The long term objectives of this study are to understand mechanical and reflex interactions linking cardiovascular and respiratory systems and to appreciated the relative significances of individual interactions. The rationale is that human responses to exertion and to cardiopulmonary disease depend to variable extents on these interactions for limitation of performance and for the production of signs and symptoms.
The specific aims of the current project are: 1) to determine the role of right atrial reflexes in control of breathing and systemic blood pressure; 2) to show the reflex effects of pulmonary vascular congestion on breathing and to discriminate among ways (such as by edema or arterial pressure, or, by stretch or J-receptors) in which those effects occur, and; 3) to show the reflex influence of left atrial and ventricular pressure and flow loads on breathing, including the influence of impairing ventricular performance. The experimental model uses acutely prepared anesthetized dogs. Observations of respiratory activity, reflected in the electrical actitity of the abdominal diaphragm, and of systemic vasomotion reflected in arterial pressure and flow, are acquired following surgical isolation of the region for reflex provocation. An important part of each protocol is the minimization or controlled introduction of secondary effects, such as changes in blood flow, gas exchange or lung volume, which may occur in the intact animal and override or alter the primary response. This separation requires cardiopulmonary bypass perfusion using an external gas exchanger, control of lung volume and gas composition independent of breathing efforts, and selective denervation by nerve block, transection or pharmacologic means. Stimuli are presented by pressurizing, individual compartments or by varying flow through them using a separate external perfusion system. After demonstrating and quantifying the respiratory and vascular responses to short-term graded stimuli (such as one-minute pressure or flow challenges) in the isolated subsystem, selective interruption of sympathetic and vagal pathways, including selective block of vagal myelinated fibre conduction, will be used to infer the afferent path and the receptors likely to have been involved.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL015694-13
Application #
3335024
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1976-09-01
Project End
1990-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
13
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202