Time course of the human pulmonary vascular response to 8 hours of isocapnic hypoxia

Abstract

To examine the hypothesis that the human pulmonary vascular response to hypoxia has a component with a slow time course, we measured pulmonary vascular resistance (PVR) in six healthy adult males during 8 h of isocapnic hypoxia. A balloon-tipped pulmonary artery catheter with thermistor was introduced via a forearm vein and used to derive PVR. The subjects were seated in a chamber in which the oxygen and carbon dioxide concentrations were adjusted to maintain an end-tidal Po2 of 50 Torr and an end-tidal Pco2 equal to the subject's normal prehypoxic value. PVR was measured before and at 0.5-h intervals during 8 h of hypoxia, the following 3 h of isocapnic euoxia (end-tidal Po2 100 Torr), and a subsequent 1-h reexposure to hypoxia. PVR rose from 1.23 +/- 0.26 (SE) Torr-min.1(-1) under euoxia [time (t) = 0] to 1.77 +/- 0.21 Torr.min.1(-1) at t = 0.5 h, reached a maximum at 2 h (2.91 +/- 0.33 Torr.min.1(-1)), and remained fairly constant between 2 and 8 h. Restoration of euoxia at 8 h led to a reduction in PVR with a slow component. Reexposure to hypoxia at 11 h resulted in a greater increase in PVR than at 1 h. Systemic vascular resistance had a similar slow component to its response, falling from 18.6 +/- 1.3 Torr.min.1(-1) at t = 0 to 17.3 +/- 1.4 Torr.min.1(-1) at t = 0.5 h, 14.4 +/- 0.6 Torr.min.1(-1) at t = 4 h, and 13.8 +/- 0.8 Torr.min.1(-1) at t = 8 h. The human pulmonary and systemic vascular responses to hypoxia extend over at least several hours.

Cardiovascular effects of 8 h of isocapnic hypoxia with and without beta-blockade in humans

“…However, there was a progressive increase in heart rate with hypoxia, as has been previously reported Dorrington et al 1997). The present study found no effect of â-blockade on the progressive increase in heart rate with hypoxia, or on either of its underlying components (GHR and HR100%).…”

“…We will therefore only consider the Doppler measurements of cardiac output further in this section. In a previous study (Dorrington et al 1997), a gradual increase in cardiac output was observed over an 8 h exposure to the same level of hypoxia as employed in the present study. From the raw data associated with the previous study, the rise in cardiac output between 1 and 8 h can be calculated as 0.98 l min¢ (95% confidence interval (CI) 0.36 to 1.34 l min¢, P < 0.05, one-sample t test).…”

“…The present study focuses mainly on those responses that occur over a period of hours, after the initial acute (seconds to minutes) responses are complete. In relation to this time scale, Dorrington et al (1997) recently demonstrated that there was a progressive rise in cardiac output over an 8 h period of steady hypoxia. This increase in cardiac output was associated with an increase in heart rate, with stroke volume remaining relatively constant.…”

Endocannabinoid anandamide mediates hypoxic pulmonary vasoconstriction

“…This is most likely due to the slower onset of strong hypoxia in spontaneously breathing mice kept in 10% O 2 . A similar time course for the development of HPV has been also reported for humans (17). The specificity of the elevation of AEA was further demonstrated by 2-AG measurements that displayed no change upon hypoxia exposure (n ≥ 5, *P > 0.05 for 0 h vs. 1, 2, 6, and 24 h).…”

Na+/H+ Exchange and Hypoxic Pulmonary Hypertension

“…72,73 HPV arises acutely upon exposure to hypoxia, with a significant increase in pulmonary vascular resistance (PVR) within 30 minutes and, if the hypoxic exposure remains brief (minutes to a few hours), largely reverses rapidly with return to normoxia. 74 The onset of HPV occurs in phases, with an initial phase occurring within 5 minutes that reflects Ca 2+ -dependent smooth muscle contraction and a later phase of increasing PA pressure that appears to be Ca 2+ independent. 73 The initial hypoxic increase in intracellular Ca 2+ in PASMCs is mediated by Ca 2+ release from the sarcoplasmic reticulum and Ca 2+ entry through voltage-gated L-type Ca 2+ channels, Ca 2+ permeable nonselective cation channels, and receptor-operated Ca 2+ channels; in addition, hypoxia increases the sensitivity of the myofilament contractile apparatus to Ca 2+ .…”