Hypoxic Pulmonary Vasoconstriction: Physiologic Significance
The AH PR is an important adaptive mechanism that diverts blood flow away from hypoxic alveoli. This shift in blood flow from poorly ventilated to better ventilated areas improves the matching of ventilation and perfusion which minimizes arterial hypoxemia. The degree of flow diversion away from the hypoxic site with a localized pathologic process depends on the size of the hypoxic segment; the smaller the hypoxic region, the greater the percentage diversion of blood flow away from that segment.
Flow diversion becomes less effective with widespread hypoxia, but still serves the purpose of increasing perfusion of the apices of the lungs via an increase in pulmonary arterial pressure. The apices of the lungs are less well perfused than the bases with a lower pulmonary artery pressure due to the effect of gravity. Increased apical perfusion enhances recruitment of alveolar capillaries which can participate in effective gas exchange, thus improving arterial oxygenation. This effect is seen in residents at high altitude who are subject to global alveolar hypoxia and show a more uniform distribution of perfusion compared to residents at sea level. This may convey an advantage in living in such a rarified environment by providing a larger effective area for gas exchange.
Does the AH PR function as an adaptive mechanism in the normal lung? Maldistribution of ventilation/ perfusion is usually considered an important indicator of lung disease, but subtle abnormalities of the distribution of ventilation to perfusion with each breath occur in the normal lung. Under these circumstances, the AH PR could play an important role in the maintenance of an optimal balance of ventilation to perfusion on a breath-by-breath basis. Evidence supporting this idea emerges from studies of vasodilator drugs which blunt the response. In normal subjects, as well as in patients with lung disease and in animal models of alveolar hypoxia, vasodilator drugs inhibit hypoxic vasoconstriction, produce a widening of the A-a gradient, and a fall of Pa02, suggesting that this adaptive mechanism is present in the normal, as well as the abnormal lung. canadian pharmacy viagra
The physiologic significance of the AH PR is further illustrated by a comparison of the response in animals with differences in collateral ventilation. Species with the least collateral ventilation, such as the cow and pig, are more likely to have the largest AH PR compared to species with well developed collateral ventilation, such as the dog and the sheep. Thus, it appears that a mechanism has evolved for the preservation of ventilation and perfusion matching in species which are susceptible to the development of alveolar hypoxia.
FIGURE 2. Location of small pulmonary arterioles in relation to alveoli. This section of rat lung demonstrates the close proximity of small pulmonary arterioles (A) to alveoli (ALV), alveolar ducts (AD), and terminal bronchioles (ТВ). Elastic tissue-Von Gieson stain, original magnification x 420, bar = 50 P,m. (From J Appl Phsviol 1984; 56:388-96, with permission of the publisher).
In the fetus, hypoxic pulmonary vasoconstriction serves to divert blood flow away from the unventilated alveoli, bypassing the lungs through the ductus arteriosus and foramen ovale. At birth, ventilation of alveoli with air leads to a substantial decrease in hypoxic vasoconstriction as normal gas exchange begins. The factors responsible for fetal hypoxic pulmonary vasoconstriction, and the alleviation of vasoconstriction at birth are an equally active field of investigation which is beyond the scope of this review.
Anatomic Site
It was initially assumed that the major locus of hypoxic vasoconstriction is located at the primary site of gas exchange, the alveoli. Angiographic visualization of the pulmonary vasculature during acute hypoxia demonstrates a decrease in caliber of small pulmonary arteries, but an increase in diameter of the larger proximal vessels, suggesting the small arteries as the major site for the AH PR and that the site of oxygen sensing is not exclusively located in the alveolar capillaries.
Kato and Staub provided histologic confirmation that the major site of hypoxic vasoconstriction is in the small muscular pulmonary arteries at the level of the terminal respiratory bronchioles using the technique of rapid freezing of hypoxic lung segments. Additional studies using this technique show that these same vessels are essentially surrounded by air- filled lung with oxygenated blood in the arterioles. Thus, as illustrated in Figure 2, small pulmonary arteries are appropriately positioned to respond to changes in alveolar oxygen concentration. Apcalis Oral Jelly
In an elegant series of experiments employing the technique of micropuncture of subpleural vessels, Nagasaka et al determined the microvascular pressure profile in the feline lung during normoxia and hypoxia. These experiments confirm that the predominant site of hypoxic vasoconstriction lies in the small pulmonary arteries (30-50 |xm), with the remaining increase in vascular resistance arising from the capillary bed and the venous system.
Although pulmonary veins constrict in response to a variety of physiologic stimuli, several different types of studies, including micropuncture experiments and isolated perfused lungs, demonstrate small changes in venous pressure during hypoxia compared to the arterial segment. Therefore, the pulmonary veins probably make a small contribution to the increase in vascular resistance during the AHPR.
