Physiologic Characteristics of Hypoxic Pulmonary Vasoconstriction

In humans and adult animals the alveolar oxygen tension (Po2) needs to reach 60 mmHg or lower to initiate pulmonary vasoconstriction (5, 26). In newborn sheep, however, there is evidence of active hypoxic tone even when being ventilated with 30% F,02 (5). This enhanced sensitivity to alveolar hypoxia in the newborn probably accounts for the well-known flip/flop of the circulation in the newborn when weaning from the ventilator during which suddenly pulmonary vascular resistance is high and the fetal shunts have opened again. At an alveolar oxygen of 60 mmHg or greater, there is little pulmonary vasoconstriction to hypoxemia even when the mixed venous Po2 is as low as 10 mmHg (26). Although as alveolar hypoxia gets more severe, mixed venous hypoxemia may become a more important stimulus to pulmonary vasoconstriction. Nevertheless, the greater responsiveness of lung vessels to alveolar than to vascular hypoxia has led to the assumption that lung vessels autoregulate flow in response to local alveolar ventilation so that poorly ventilated alveoli with low concentrations produce vasoconstriction to shift perfusion to better ventilated alveoli.

HPV characteristically has an onset of action in seconds and can be sustained for hours if the hypoxia is regional (43). Diffuse hypoxia tends to reach an early peak rise in pulmonary artery pressure which then tails off over time (44). HPV can be as focal as a lobule (10) or in a larger area, including one lung or both lungs. The ability of the lung vessels to constrict and shift blood flow from one region to another depends on the size of the area made hypoxic (25). If the whole lung is hypoxic, then the lung vessels constrict diffusely and pulmonary artery pressure rises as the heart pumps harder to overcome the rise in pulmonary vascular resistance, allowing cardiac output and oxygen delivery to the tissues to stay as normal as possible. On the other hand, if the hypoxia is regional then the local vasoconstriction can effectively shift blood flow with only a very small rise in pulmonary artery pressure to other well ventilated areas of the lung which are compliant and can receive more flow. The anesthetized dog in Figure 1A shifted 54% of the perfusion from its left lung to the right well-ventilated lung in response to 100% N2 for 7 mins to the left lung (13). The mean pulmonary artery pressure only increased from 14 to 15 mmHg to achieve this diversion and the stimulus to the HPV was alveolar hypoxia (Pao2, 25 mmHg) since the arterial Pa02 (from the oxygenated lung) was 89 mmHg and the mixed venous P02 was near normal at 34 mmHg (13). The strength of the HPV in this dog exceeded that of most dogs and people where the reduction in blood flow in response to HPV of the lung is usually about 30% (13). The strength of HPV is nevertheless sufficient to divert blood flow from a dependent to a nondependent lung (Fig. 1B) in dogs and man (1, 8, 13).

A Control Hypoxia

A Control Hypoxia

B Control Hypoxia

Figure 1. Examples of positron camera images of the distribution of perfusion in the lung using intravenous injections of 13N at end-tidal expiration in the supine position (A) and in the left side dependent position (B) in the anesthetized dogs. (A) Left picture represents control perfusion on room air and the right picture represents the perfusion after 10 min of ventilation of the left lung with 100% N2 while the right lung was on 100% 02. There was a 54% reduction in perfusion to the hypoxic lung (Pao2 25 mmHg) in this animal. (B) Left picture represents control perfusion with right side down on room air. Right picture is perfusion during ventilation of the dependent lung with 100% N2 and demonstrates in this dog a 56% shift of perfusion away from the dependent lung and, therefore, directly against gravity (Reprinted from Ref. 13).

Figure 1. Examples of positron camera images of the distribution of perfusion in the lung using intravenous injections of 13N at end-tidal expiration in the supine position (A) and in the left side dependent position (B) in the anesthetized dogs. (A) Left picture represents control perfusion on room air and the right picture represents the perfusion after 10 min of ventilation of the left lung with 100% N2 while the right lung was on 100% 02. There was a 54% reduction in perfusion to the hypoxic lung (Pao2 25 mmHg) in this animal. (B) Left picture represents control perfusion with right side down on room air. Right picture is perfusion during ventilation of the dependent lung with 100% N2 and demonstrates in this dog a 56% shift of perfusion away from the dependent lung and, therefore, directly against gravity (Reprinted from Ref. 13).

The site of HPV seems to be the precapillary 200-300 (¿m arterioles in pigs and dogs but perhaps as small as 25-50 [im vessels in cats based on microventilatory puncture techniques and sophisticated x-ray arteriography (Fig. 2) (33, 38). The veins may constrict but this seems to be modest and diffuse. This is hard to measure, especially radiologically, because of upstream resistance in the arteries causing less flow and distention of the veins during hypoxia. For years it was thought that the alveolar hypoxia sensor was in lung parenchyma. Now it is known from the work of Madden et al. that isolated pulmonary vessels in diameter) themselves can constrict to hypoxia and further that pulmonary artery smooth muscle cells can contract although weakly in culture in response to hypoxia (23, 32). There is still a possible role for factors exogenous to the vessels to amplify or depress the regional hypoxic vasopressor response as recently reviewed (22). For example, the hypoxic vasoconstrictor response to alveolar hypoxia is less after sympathectomy in lambs though not so in sheep (5) and endothelin may play a role in pigs (21). Thus, exogenous factors may amplify the strength of vasoconstriction endogenous to the pulmonary artery smooth muscle cells.

Control Hypoxia (5% 02)

Control Hypoxia (5% 02)

Figure 2. Typical arteriograms and venograms of left lower lobe under control and hypoxic conditions in the same cat are shown. Arteries constrict nonuniformly in series-arranged vessels, whereas veins constrict almost uniformly. Solid arrows indicate apparent vasoconstriction (Reprinted from Ref. 39).

Figure 2. Typical arteriograms and venograms of left lower lobe under control and hypoxic conditions in the same cat are shown. Arteries constrict nonuniformly in series-arranged vessels, whereas veins constrict almost uniformly. Solid arrows indicate apparent vasoconstriction (Reprinted from Ref. 39).

4. Fetal and Neonatal Pulmonary Circulation

The placenta serves as the main source of oxygenation of fetal blood and it itself serves to autoregulate the distribution of blood flow through hypoxic fetoplacental vasoconstriction mediated viaK+ channels (15). Just prior to birth, blood flow to the airless lung is 8 to 10% of cardiac output and the Po2 of the oxygenated placental blood (17-20 mmHg) is insufficient to decrease resistance to perfusion in the fetal lung. At birth there is a sudden and drastic reduction in pulmonary vascular resistance, a rise in pulmonary venous blood flow with an increase in left atrial pressure so that the patent foramen ovale closes and there is 02-related closure of the patent ductus arteriosus such that there is an 8-10 fold increase in lung blood flow (35-37). The decrease in vascular resistance in the lung at birth is in part related to oxygenation of the lung but not entirely.

Hyperbaric oxygenation of the fetal lung in utero without expanding it, will increase blood flow (16), showing that HPV is active in decreasing lung perfusion. The increase in blood flow at most, though, rose only to 38% of cardiac output. However, the mixed venous Po2 was only 44 mmHg which is probably too low to stop all vasoconstriction. Inflation of the fetal lung with hypoxic gas mixtures will also increase lung blood flow showing physical features of the collapsed lung contribute to pulmonary vascular resistance, and as expected, adding inhaled air to the hypoxic distended lung further reduces the pulmonary vascular resistance (4, 19, 41). Thus, HPV contributes substantially to reducing perfusion to the lung in utero although mechanical factors do so as well.

Figure 3. A: Scintigrams in an erect subject of the distribution of a 250 ml bolus of 13N inhaled from residual volume (BORV) (left), and after rebreathing for 2 min and then breath holding at RV (EQRV) (right). B: Scintigrams were obtained during breath hold at RV as nitrous oxide was streaming into the lung through all patent airways to pulmonary capillary blood. Left scintigram made at 8 sec after injection of bolus of 13N into the nitrous oxide stream shows the bolus in the trachea and major bronchi. Right scintigram 24 sec later shows that the bolus has largely cleared the major airways and is similar in distribution to BORV, both displaying basal decrease in activity compared to EQRV (Reprinted from Ref. 14).

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  • Battista
    What are the characteristics of vasoconstriction?
    8 years ago

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