#190101 Radnoti Isolated Lung System

The lungs are important not only for respiration, but also as a target organ for drugs that include volatile anesthetics, biochemical and biological agents, are involved in drug metabolism and distribution and are involved in a number of pathological scenarios, including ischemia, edema, various diseases and trauma. The isolated lung system has both similarities and differences to the isolated heart system. Both systems require maintenance of the organ at physiological temperatures and perfusion with crystalloid solutions, such as Kreb’s or Tyrode’s solutions, or admixtures containing blood. Like the isolated heart system, the vasculature of the lung can be perfused in a constant pressure or a constant pressure mode and the lung is cannulated on an artificial trachea, just as the heart is cannulated on an artificial aorta. This perfusion, can be in either retrograde, as in the Langendorff, or anterograde to normal blood flow.

The respiratory performance of the lung can be measured in terms of respiratory volumes exchanged at a given rate, while cardiac mechanical performance is measured by its developed pressure or stroke volume multiplied by its rate in beats per minute. Unlike the heart, the isolated lung does not have an intrinsic pacemaker, so its mechanical activity must be generated through one of two ways. In the positive pressure method, air is forced into the artificial trachea and then into the lung via a respirator. In the negative pressure method, the lungs are placed in a sealed chamber that mimics the situation in the subject’s chest cavity. In vivo, it is the action of the diaphragm muscle that creates a reduction of internal pressure, while in vitro a vacuum is generated by a respirator in the sealed chamber that permits air to follow its pressure gradient into the lung. To remove the air, the respirator then pushes air into the chamber, deflating the lungs.

  

The Radnoti isolated lung system permits a wide variety of experimental formats to be explored. Through the use of water-jacketed reservoirs and peristaltic pumps, constant pressure and constant flow perfusion can occur in both re-circulating and non-re-circulating modes. Perfusion solutions can be aerated through the use of sintered glass frits or through a silicone tubing gas exchange system, the latter best for solutions containing proteins or blood. Perfusion pressure is measured via inline pressure transducers and perfusion flow can measured via inline flow meters.  A variable speed and volume respirator delivers humidified air or other gasses to the lungs (positive pressure) or creates a cycling negative/positive pressure change in the lung chamber (negative pressure). Pressure sensors are used to determine inspiration and expiration pressures and the gasses passed into the lung are humidified using a gas chamber. Expired air or perfusate can also be collected for metabolic studies. For experimenters interested in measuring lung edema, the lung cannula is attached to a force transducer with a +/- 5 volt readout that can be linked to a data acquisition system. Perfusate pH, oxygen and carbon dioxide can be measured with inline ion selective electrodes.  By changing artificial tracheas and the lung chamber in concert with respirator settings and control valves, lungs from subjects from mice to rabbits or larger can be used.

 

Radnoti Modification for Heart/Lung Perfusion (HLP) in Vivo

The advantage of the Heart Lung preparation is that the left and right heart regions of the heart can be investigated independently in a single system configuration. The heart-lung preparation does not consist of an isolated organ removed from the body, since heart and lung remain in the open thorax of the donor animal.

The lung is ventilated using a small animal respirator that maintains oxygenation of the blood or perfusion buffer.

Heart and lung are supplied with heperinised whole blood or a buffer solution from a Water-Jacketed temperature controlled reservoir. The reservoir is adjustable in height in order to vary the pressure in the right atrium (preload). After load resistance can be adjusted by variation in the elevation of the outflow compliance chamber. The Radnoti system is easily instrumented for a wide range of experimental parameters.

The Heart Lung preparation is adapted from the Radnoti 190101 Isolated lung system by removal of the membrane oxygenator and the Isolated lung chamber. In place of the isolated lung chamber, a rodent surgical table is used (sold separately).