Hypoxic Pulmonary Vasoconstriction

Hypoxic pulmonary vasoconstriction was originally described in 1946, by Von Euler and Liljestrand – they were studying the effects of hypoxic gas mixtures, and found that PA pressures increased with 10.5% inspired O2 [Von Euler and Liljestrand. Acta Physiol Scand 12: 301, 1946]. Since then, HPV has been well-described in multiple mammalian models, including humans. It is thought to result from a pathway involving NO and/or COOX inhibition [Moudgil R et al. J Appl Physiol 98: 390, 2005]. HPV takes effect over 30 minutes, although peak effect takes up to two hours. Interestingly, HPV sensitization occurs, in which a second incidence of hypoxemia produces a more significant response than the first [Dorrington KL et al. Am J Physiol Heart Circ Physiol 273, H1126, 1997]

In addition to PAO2, HPV is dependent on both PaO2 and PvO2, although in the atelectatic lung only PvO2 matters and overall PAO2 is by far most important. Of note, HPV functions best when 30-70% of the lung is hypoxic – if < 30% of the lung is hypoxic, and there is not enough hypoxic lung to shunt from; conversely, if more than 70% of the lung is hypoxic, there is no place to shunt the hypoxic blood

Because OLV produces hypoxia in the range of 30-70% of the total lung volumes, and because HPV is thought to reduce blood flow to the operative lung by 50% [Miller’s Anesthesia, 7th ed. 2009. p 1847], the effects of various anesthetic agents on HPV must be understood

Propofol at 6-12 mg/kg/hr (100-200 ucg/kg/min) does not affect HPV [Van Keer et al. J Clin Anesth 1: 284, 1989]. Desflurane inhibits HPV at 1.6 MAC [Loer SA et al. Anesthesiology 83: 552, 1995]. All volatile anesthetics inhibit HPV in a dose-dependent fashion [Miller’s Anesthesia, 7th ed. 2009. p 1848], although the effect of some agents (ex. 1.0 MAC) sevoflurane) has been shown to be minimal when at excessive concentrations – Benumof estimates that 1.0 MAC of isoflurane can only attenuate ~ 20% of the HPV response, which translates into a clinically undetectable 4% increase in A-V shunting [Benumof JL. Anesthesiology 64: 419, 1986]

Importantly, during one lung ventilation, volatile anesthetics can only reach the operative lung through the bloodstream (not through the alveoli), which attenuates their HPV-reducing potential. Still, several authors have attempted to compare volatile agents with IV agents in OLV – Kelly et al. compared isoflurane to propofol in 22 patients undergoing OLV and found that during OLV, isoflurane group had a higher shunt fraction (35% vs. 21%) but also had significantly better cardiac index (3.2 vs. 2.3) and RVEF [Kellow NH et al. Br J Anesth 75: 578, 1995]. Slinger et al. compared isoflurane to propofol-alfentanil in 30 patients and found no significant differences in PaO2 values after 20-30 minutes of OLV [Reid CW et al J Cardiothorac Vasc Anesth 10: 860, 1996]. Thus, the data do not support any meaningful clinical differences between volatile and non-volatile techniques for one lung ventilation

Summary of Anesthetic Agents and their Effects on HPV

Inhibit HPV No or minimal effect on HPV Agent Reference Agent Reference Ether Bjertnaes (1978) Thiopental Bjertnaes (1978) Halothane Bjertnaes (1978) Fentanyl Bjertnaes (1978) Halothane (1.0 MAC) Benumof (1987) Propofol (< 200 u/k/m) Van Keer (1989) Desflurane (> 1.6 MAC) Loer (1995) Desflurane (6%) Wang (2000) Isoflurane (< 1.5%) Carlson (1987) Isoflurane (1.0 MAC) Benumof (1987) Isoflurane (1.0 MAC) Wang (2000) Sevoflurane (BIS 40-60) Pruszkowski (2007) Sevoflurane (1.0 MAC) Wang (2000) Sevoflurane (1.0 MAC) Beck (2001)
Other HPV inhibitors include nitroglycerin, nitroprusside, infection, hypocarbia, and alkalemia. Indirect inhibitors (usually act by increasing PA pressures, which overcome vasoconstriction) include vasopressors, volume overload, mitral stenosis, and thromboembolism. Acidosis improves HPV but the difference is not clinically meaningful, as it is accompanied by an overall increase in PVR [Loepply JA et al. J Appl Physiol 72: 1787, 1993]