Interaction between cold and altitude exposure on pulmonary circulation of cattle

1985 ◽  
Vol 58 (3) ◽  
pp. 948-953 ◽  
Author(s):  
M. A. Busch ◽  
A. Tucker ◽  
D. Robertshaw
Keyword(s):  
Pulmonary Hypertension ◽  
Cold Exposure ◽  
Pulmonary Circulation ◽  
Minute Ventilation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Altitude Exposure ◽  
Arterial Ph ◽  
Alveolar Hypoventilation ◽  
Pulmonary Arterial ◽  
End Tidal

Hereford calves were exposed in a temperature-controlled hypobaric chamber to environmental temperatures of -2 to 1 degree C (cold) at altitudes of 1,524 m (resident altitude) and 3,048 m 1) to characterize the effects of cold exposure on the pulmonary circulation; 2) to examine the role of cold-induced hypoventilation on the pulmonary circulation; and 3) to examine the interaction between cold and hypoxia on the pulmonary circulation. Cold exposure produced a significant increase in pulmonary arterial pressure (Ppa), pulmonary arterial wedge pressure (Ppaw), and pulmonary vascular resistance (PVR) at both 1,524 and 3,048 m without affecting cardiac output. Concomitantly, cold exposure caused reductions in minute ventilation, respiratory rate, end-tidal O2 tension (PETO2), and arterial O2 tension (PaO2). Tidal volume, end-tidal CO2 tension, and arterial CO2 tension increased. Neither arterial pH nor O2 consumption changed during cold exposure. These results indicated that both pulmonary arterial and venous vasoconstriction were responsible for the pulmonary hypertension associated with cold exposure. Acute exposure to 3,048 m during cold exposure produced increases in Ppa and PVR that were similar to those elicited by cold exposure at 1,524. It was concluded that altitude exposure neither attenuated nor potentiated the effect of cold exposure on the pulmonary circulation; rather, altitude and cold exposure interacted additively. O2 administered during cold exposure to restore PETO2 and PaO2 to control values partially restored Ppa and PVR to control values. This suggested that a portion of the pulmonary hypertension associated with cold exposure was due to hypoxic pulmonary vasoconstriction elicited by the cold-induced alveolar hypoventilation.

Nitric oxide inhalation: effects on the ovine neonatal pulmonary and systemic circulations

1996 ◽  
Vol 8 (3) ◽  
pp. 431 ◽  
Author(s):  
V DeMarco ◽  
JW Skimming ◽  
TM Ellis ◽  
S Cassin
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Circulation ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Minimum Concentration ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
Inhaled No

Others have shown that inhaled nitric oxide causes reversal of pulmonary hypertension in anaesthetized perinatal sheep. The present study examined haemodynamic responses to inhaled NO in the normal and constricted pulmonary circulation of unanaesthetized newborn lambs. Three experiments were conducted on each of 7 lambs. First, to determine a minimum concentration of NO which could reverse acute pulmonary hypertension caused by infusion of the thromboxame mimic U46619, the haemodynamic effects of 5 different doses of inhaled NO were examined. Second, the effects of inhaling 80 ppm NO during hypoxic pulmonary vasoconstriction were examined. Finally, to determine if tachyphalaxis occurs during NO inhalation, lambs were exposed to 80 ppm NO for 3 h during which time pulmonary arterial pressure was doubled by infusion of U46619. Breathing NO (80 ppm) caused a slight but significant decrease in pulmonary vascular resistance (PVR) in lambs with normal pulmonary arterial pressure (PAP). Nitric oxide, inhaled at concentrations between 10 and 80 ppm for 6 min (F1O2 = 0.60), caused decreases in PVR when PAP was elevated with U46619. Nitric oxide acted selectively on the pulmonary circulation, i.e. no changes occurred in systemic arterial pressure or any other measured variable. Breathing 80 ppm NO for 6 min reversed hypoxic pulmonary vasoconstriction. In the chronic exposure study, inhaling 80 ppm NO for 3 h completely reversed U46619-induced pulmonary hypertension. Although arterial methaemoglobin increased during the 3-h exposure to 80 ppm NO, there was no indication that this concentration of NO impairs oxygen loading. These data demonstrate that NO, at concentrations as low as 10 ppm, is a potent, rapid-action, and selective pulmonary vasodilator in unanaesthetized newborn lambs with elevated pulmonary tone. Furthermore, these data support the use of inhaled NO for treatment of infants with pulmonary hypertension.

scholarly journals Decreased time constant of the pulmonary circulation in chronic thromboembolic pulmonary hypertension

2013 ◽  
Vol 305 (2) ◽  
pp. H259-H264 ◽  
Author(s):  
Robert V. MacKenzie Ross ◽  
Mark R. Toshner ◽  
Elaine Soon ◽  
Robert Naeije ◽  
Joanna Pepke-Zaba
Keyword(s):  
Pulmonary Hypertension ◽  
Time Constant ◽  
Pulmonary Circulation ◽  
Wave Reflection ◽  
Arterial Compliance ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Left Heart Failure ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
Rc Time Constant

This study analyzed the relationship between pulmonary vascular resistance (PVR) and pulmonary arterial compliance ( Ca) in patients with idiopathic pulmonary arterial hypertension (IPAH) and proximal chronic thromboembolic pulmonary hypertension (CTEPH). It has recently been shown that the time constant of the pulmonary circulation (RC time constant), or PVR × Ca, remains unaltered in various forms and severities of pulmonary hypertension, with the exception of left heart failure. We reasoned that increased wave reflection in proximal CTEPH would be another cause of the decreased RC time constant. We conducted a retrospective analysis of invasive pulmonary hemodynamic measurements in IPAH ( n = 78), proximal CTEPH ( n = 91) before (pre) and after (post) pulmonary endarterectomy (PEA), and distal CTEPH ( n = 53). Proximal CTEPH was defined by a postoperative mean pulmonary artery pressure (PAP) of ≤25 mmHg. Outcome measures were the RC time constant, PVR, Ca, and relationship between systolic and mean PAPs. The RC time constant for pre-PEA CTEPH was 0.49 ± 0.11 s compared with post-PEA-CTEPH (0.37 ± 0.11 s, P < 0.0001), IPAH (0.63 ± 0.14 s, P < 0.001), and distal CTEPH (0.55 ± 0.12 s, P < 0.05). A shorter RC time constant was associated with a disproportionate decrease in systolic PAP with respect to mean PAP. We concluded that the pulmonary RC time constant is decreased in proximal CTEPH compared with IPAH, pre- and post-PEA, which may be explained by increased wave reflection but also, importantly, by persistent structural changes after the removal of proximal obstructions. A reduced RC time constant in CTEPH is in accord with a wider pulse pressure and hence greater right ventricular work for a given mean PAP.

Living high-training low increases hypoxic ventilatory response of well-trained endurance athletes

2002 ◽  
Vol 93 (4) ◽  
pp. 1498-1505 ◽  
Author(s):  
Nathan E. Townsend ◽  
Christopher J. Gore ◽  
Allan G. Hahn ◽  
Michael J. McKenna ◽  
Robert J. Aughey ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Endurance Athletes ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Hypoxic Ventilatory Response ◽  
Ambient Conditions ◽  
Altitude Exposure ◽  
End Tidal

This study determined whether “living high-training low” (LHTL)-simulated altitude exposure increased the hypoxic ventilatory response (HVR) in well-trained endurance athletes. Thirty-three cyclists/triathletes were divided into three groups: 20 consecutive nights of hypoxic exposure (LHTLc, n = 12), 20 nights of intermittent hypoxic exposure (four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia, LHTLi, n = 10), or control (Con, n = 11). LHTLc and LHTLi slept 8–10 h/day overnight in normobaric hypoxia (∼2,650 m); Con slept under ambient conditions (600 m). Resting, isocapnic HVR (ΔV˙e/ΔSpO2 , whereV˙e is minute ventilation and SpO2 is blood O2 saturation) was measured in normoxia before hypoxia (Pre), after 1, 3, 10, and 15 nights of exposure (N1, N3, N10, and N15, respectively), and 2 nights after the exposure night 20 (Post). Before each HVR test, end-tidal Pco 2(Pet CO2 ) and V˙e were measured during room air breathing at rest. HVR (l · min−1 · %−1) was higher ( P < 0.05) in LHTLc than in Con at N1 (0.56 ± 0.32 vs. 0.28 ± 0.16), N3 (0.69 ± 0.30 vs. 0.36 ± 0.24), N10 (0.79 ± 0.36 vs. 0.34 ± 0.14), N15 (1.00 ± 0.38 vs. 0.36 ± 0.23), and Post (0.79 ± 0.37 vs. 0.36 ± 0.26). HVR at N15 was higher ( P < 0.05) in LHTLi (0.67 ± 0.33) than in Con and in LHTLc than in LHTLi. Pet CO2 was depressed in LHTLc and LHTLi compared with Con at all points after hypoxia ( P < 0.05). No significant differences were observed for V˙e at any point. We conclude that LHTL increases HVR in endurance athletes in a time-dependent manner and decreases Pet CO2 in normoxia, without change inV˙e. Thus endurance athletes sleeping in mild hypoxia may experience changes to the respiratory control system.

scholarly journals 55th Bowditch Lecture: Effects of chronic hypoxia on the pulmonary circulation: Role of HIF-1

2012 ◽  
Vol 113 (9) ◽  
pp. 1343-1352 ◽  
Author(s):  
Larissa A. Shimoda
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Circulation ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Arterial ◽  
Expression And Activity

When exposed to chronic hypoxia (CH), the pulmonary circulation responds with enhanced contraction and vascular remodeling, resulting in elevated pulmonary arterial pressures. Our work has identified CH-induced alterations in the expression and activity of several ion channels and transporters in pulmonary vascular smooth muscle that contribute to the development of hypoxic pulmonary hypertension and uncovered a critical role for the transcription factor hypoxia-inducible factor-1 (HIF-1) in mediating these responses. Current work is focused on the regulation of HIF in the chronically hypoxic lung and evaluation of the potential for pharmacological inhibitors of HIF to prevent, reverse, or slow the progression of pulmonary hypertension.

Proximal pulmonary arterial obstruction decreases the time constant of the pulmonary circulation and increases right ventricular afterload

2013 ◽  
Vol 114 (11) ◽  
pp. 1586-1592 ◽  
Author(s):  
Alberto Pagnamenta ◽  
Rebecca Vanderpool ◽  
Serge Brimioulle ◽  
Robert Naeije
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Time Constant ◽  
Pulse Pressure ◽  
Pulmonary Circulation ◽  
Characteristic Impedance ◽  
Ventricular Afterload ◽  
Hydraulic Load ◽  
Distal Obstruction ◽  
Pulmonary Arterial

The time constant of the pulmonary circulation, or product of pulmonary vascular resistance (PVR) and compliance (Ca), called the RC-time, has been reported to remain constant over a wide range of pressures, etiologies of pulmonary hypertension, and treatments. We wondered if increased wave reflection on proximal pulmonary vascular obstruction, like in operable chronic thromboembolic pulmonary hypertension, might also decrease the RC-time and thereby increase pulse pressure and right ventricular afterload. Pulmonary hypertension of variable severity was induced either by proximal obstruction (pulmonary arterial ensnarement) or distal obstruction (microembolism) eight anesthetized dogs. Pulmonary arterial pressures (Ppa) were measured with high-fidelity micromanometer-tipped catheters, and pulmonary flow with transonic technology. Pulmonary ensnarement increased mean Ppa, PVR, and characteristic impedance, decreased Ca and the RC-time (from 0.46 ± 0.07 to 0.30 ± 0.03 s), and increased the oscillatory component of hydraulic load (Wosc/Wtot) from 25 ± 2 to 29 ± 2%. Pulmonary microembolism increased mean Ppa and PVR, with no significant change in Ca and characteristic impedance, increased RC-time from 0.53 ± 0.09 to 0.74 ± 0.05 s, and decreased Wosc/Wtot from 26 ± 2 to 13 ± 2%. Pulse pressure increased more after pulmonary ensnarement than after microembolism. Concomitant measurements with fluid-filled catheters showed the same functional differences between the two types of pulmonary hypertension, with, however, an underestimation of Wosc. We conclude that pulmonary hypertension caused by proximal vs. distal obstruction is associated with a decreased RC-time and increased pulsatile component of right ventricular hydraulic load.

scholarly journals Intensity and quality of exertional dyspnoea in patients with stable pulmonary hypertension

2019 ◽  
Vol 55 (2) ◽  
pp. 1802108 ◽  
Author(s):  
Athénaïs Boucly ◽  
Capucine Morélot-Panzini ◽  
Gilles Garcia ◽  
Jason Weatherald ◽  
Xavier Jaïs ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Minute Ventilation ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Dynamic Hyperinflation ◽  
Exertional Dyspnoea ◽  
Work Effort ◽  
Inspiratory Capacity ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
The Impact

Dynamic hyperinflation is observed during exercise in 60% of patients with clinically stable pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), intensifying exertional dyspnoea. The impact of dynamic changes in respiratory mechanics during exercise on qualitative dimensions of dyspnoea in these patients has not been evaluated.26 patients (PAH n=17; CTEPH n=9) performed an incremental symptom-limited cycle exercise test. Minute ventilation (V′E), breathing pattern, operating lung volumes and dyspnoea intensity were assessed throughout exercise. Dyspnoea quality was serially assessed during exercise using a three-item questionnaire (dyspnoea descriptors). The inflection point of tidal volume (VT) relative to V′E was determined for each incremental test. Changes in inspiratory capacity during exercise defined two groups of patients: hyperinflators (65%) and non-hyperinflators (35%). Multidimensional characterisation of dyspnoea was performed after exercise using the Multidimensional Dyspnea Profile.In hyperinflators, inspiratory capacity decreased progressively throughout exercise by 0.36 L, while remaining stable in non-hyperinflators. The “work/effort” descriptor was most frequently selected throughout exercise in both types of patients (65% of all responses). At the VT/V′E inflection, work/effort plateaued while “unsatisfied inspiration” descriptors became selected predominantly only in hyperinflators (77% of all responses). In the affective domain, the emotion most frequently associated with dyspnoea was anxiety.In pulmonary hypertension patients who develop hyperinflation during exercise, dyspnoea descriptors referring to unsatisfied inspiration become predominant following the VT/V′E inflection. As these descriptors are generally associated with more negative emotional experiences, delaying or preventing the VT/V′E inflection may have important implications for symptom management in patients with pulmonary hypertension.

The endothelin system in pulmonary hypertension

2003 ◽  
Vol 81 (6) ◽  
pp. 542-554 ◽  
Author(s):  
René P Michel ◽  
David Langleben ◽  
Jocelyn Dupuis
Keyword(s):  
Clinical Trials ◽  
Pulmonary Hypertension ◽  
Pulmonary Circulation ◽  
Tissue Expression ◽  
Vascular Endothelial ◽  
Receptor Antagonists ◽  
New Class ◽  
Endothelin System ◽  
Pulmonary Arterial ◽  
Medial Hypertrophy

Pulmonary hypertension (PH) may result from numerous clinical entities affecting the pulmonary circulation primarily or secondarily. It is recognized that vascular endothelial dysfunction contributes to the development and perpetuation of PH by creating an imbalance between vasodilating and antiproliferative forces and between vasoconstric tive and proliferative forces. In that context, endothelin-1 (ET-1) overproduction was rapidly targeted as a plausible contributor to the pathogenesis of PH. The lung is recognized as the major site for ET production and clearance. In all animal models of PH studied, circulating plasma ET-1 levels are elevated, accompanied by an increase in lung tissue expression of the peptide. The use of selective ETA and dual ETA–ETB receptor antagonists in these models both in prevention and in therapeutic studies have confirmed the contribution of ET-1 to the rise in pulmonary vascular tone, pulmonary medial hypertrophy, and right ventricular hypertrophy. This is found consistently in models affecting the pulmonary circulation primarily or producing PH secondarily. Recent clinical trials in patients with pulmonary arterial hypertension have confirmed the therapeutic effectiveness of ET-receptor antagonists in humans. We offer a systematic review of the pathogenic role of the ET system in the development of PH as well as the rationale behind the preclinical and ongoing clinical trials with this new class of agents.Key words: pulmonary circulation, pulmonary pathology, receptor, preclinical studies, clinical studies, antagonist.

Augmented hypoxic ventilatory response in men at altitude

1992 ◽  
Vol 73 (1) ◽  
pp. 101-107 ◽  
Author(s):  
M. Sato ◽  
J. W. Severinghaus ◽  
F. L. Powell ◽  
F. D. Xu ◽  
M. J. Spellman
Keyword(s):  
Sea Level ◽  
Ventilatory Response ◽  
Hypoxic Ventilatory Response ◽  
Co2 Response ◽  
Altitude Exposure ◽  
Arterial Ph ◽  
Ventilatory Drive ◽  
Normal Males ◽  
End Tidal ◽  
Arterial O2 Saturation

To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1–5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P′CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P′CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4–7). HVR was independent of test SaO2 (range 60–90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Sex differences in the pulmonary circulation: implications for pulmonary hypertension

2014 ◽  
Vol 306 (9) ◽  
pp. H1253-H1264 ◽  
Author(s):  
Yvette N. Martin ◽  
Christina M. Pabelick
Keyword(s):  
Pulmonary Hypertension ◽  
Sex Differences ◽  
Sex Hormones ◽  
Pulmonary Circulation ◽  
Vascular Remodeling ◽  
Complex Disease ◽  
New Developments ◽  
Disease Outcomes ◽  
Pulmonary Arterial ◽  
Recent Attention

Pulmonary arterial hypertension (PAH), a form of pulmonary hypertension, is a complex disease of multifactorial origin. While new developments regarding pathophysiological features and therapeutic options in PAH are being reported, one important fact has emerged over the years: there is a sex difference in the incidence of this disease such that while there is a higher incidence in females, disease outcomes are much worse in males. Accordingly, recent attention has been focused on understanding the features of sex differences in the pulmonary circulation and the contributory mechanisms, particularly sex hormones and their role in the pathological and pathophysiological features of PAH. However, to date, there is no clear consensus whether sex hormones (particularly female sex steroids) are beneficial or detrimental in PAH. In this review, we highlight some of the most recent evidence regarding the influence of sex hormones (estrogen, testosterone, progesterone, dehydroepiandrosterone) and estrogen metabolites on key pathophysiological features of PAH such as proliferation, vascular remodeling, vasodilation/constriction, and inflammation, thus setting the stage for research avenues to identify novel therapeutic target for PAH as well as potentially other forms of pulmonary hypertension.

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