Methods using the distribution of flow as an index of pulmonary vascular tone

In human studies it is often possible to reduce the number of variables by studying the regional distribution of blood flow rather than pulmonary vascular resistance. One method of studying the hypoxic response is to measure the redistribution of blood flow in response to unilateral hypoxia induced by the administration of 8-10% oxygen through one limb of a double lumen tube. In the earlier studies the distribution of flow was determined by measuring the oxygen consumption of each lung, because this is directly proportional to blood flow. Attempts were also made to use carbon dioxide output in a similar manner, but this technique proved inaccurate because the carbon dioxide output was also affected by the ventilation to each lung.36 A much simpler way of measuring the distribution of blood flow is to infuse a solution of a relatively insoluble gas into the pulmonary artery and to measure the concentration evolved into the alveoli on each side. One method is based on the infusion of sulphur hexafluoride and measurement of its concentration in expired gas with infrared analysis.36 Other methods use a radiolabelled isotope of a relatively insoluble gas such as xenon or krypton.37 This is dissolved in saline and injected into the right side of the circulation. Most of the radiolabelled isotope is evolved into the alveoli during the first passage of the blood through the lungs so that the count rate is directly related to the blood flow. The radioactivity can either be measured in expired gas or detected by scintillation detectors or a gamma camera placed over the chest. The use of the gamma camera has not only enabled blood flow to be measured in areas of collapsed lung, but has also permitted regional variations in perfusion to be studied. The distribution of flow has also been studied by measuring regional radioactivity after the injection of microspheres or macroaggregates labelled with radioactive isotopes. By using radioisotopes with different energies, up to six sequential injections may be made at different stages of the experiment. As the counting may be delayed for several hours, the method has proved to be of great value when studying the distribution of blood flow in stressful environments such as during zero or exaggerated gravity.

Another method of studying the redistribution of blood flow after the administration of a vasoactive drug is to measure the effects on gas exchange. This can be done by the standard method of calculating percentage shunt and dead space/tidal volume ratio from the oxygen and carbon dioxide tensions in arterial and mixed venous blood, and mixed expired gas. Greater precision is, however, obtained by the Wagner inert gas technique in which a solution of six inert gases of different solubilities is infused into the pulmonary circulation at a constant rate, and the retention/excretion ratios are measured from an arterial and mixed expired gas sample. By using a computer to fit the data to a 50 compartment model of the lung, it is possible to derive values for shunt, dead space, and compartments with intermediate ventilation-perfusion ratios.38 As with other in vivo measurements it is important to remember that any alterations in the distribution of blood flow which occur may be caused by changes in lung volume or haemodynamics, as well as by changes in vasomotor tone.

It is obvious that the conditions outlined above severely limit the number of useful observations that can be made. Furthermore, as the normal vascular bed has very little tone, the action of pulmonary vasodilator drugs can only be studied after constriction has been induced by some other agent (such as hypoxia). Obviously, vasodilator drugs must also be studied in the patients in whom they are likely to be used, but such studies often produce variable results owing to differences in the aetiology of the pulmonary hypertension in each patient. For these reasons we will first consider the actions of drugs on the normal pulmonary circulation and on hypoxic pulmonary vasoconstriction. In the last section we shall consider the problem of pulmonary hypertension and the effects of vasodilator drugs.

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