Open access peer-reviewed chapter - ONLINE FIRST
Conventional gasometric criteria used to assess hypoxemia.
Abstract
Hypobaric hypoxia due to altitude is a risk factor for patent ductus arteriosus (PDA). In order to explore a relationship between hypoxia and pulmonary microcirculation hemorheology in pediatric patients with surgically corrected PDA, a clinical case control study was carried out in a single medical center at a mean moderate altitude of 2240 meters above sea level (mASL). Patients were divided in two groups, with hypoxia (problems) and without hypoxia (controls), using conventional gasometric criteria. The problem group showed a higher hematocrit value. This suggests that an increase in blood viscosity due to the higher hematocrit level in response to altitude is a factor that promotes hypoxia in the pulmonary microcirculation. A pathophysiological explanation for this acute response in the problem group is provided.
Keywords
- hypoxia
- microcirculation
- hemorheology
- patent ductus arteriosus
- altitude
1. Introduction
Patent ductus arteriosus (PDA) is one of the most frequent congenital heart diseases in countries located at an altitude above the sea level [1]. Ductus arteriosus is a fetal vascular structure that connects the left pulmonary artery with the descending thoracic aortic isthmus, and its function is to provide oxygen (O2) as well as nutrients to the fetal lungs [2]. Its anatomic and functional closure occurs during the first hours after birth and is usually completed by up to the third month of extrauterine life. When the ductus arteriosis remains open from birth to the sixth week of extrauterine life and thereafter, it is considered as persistent [3]. Closure of PDA is due to the intake of oxygen in the first breath, the increase in blood oxygen partial pressure (PaO2), and the decrease in the newborn prostaglandin E2 level [4, 5, 6]. Hypoxemia can lead to a delayed or non-closure of a PDA, however, developing changes in pulmonary microcirculation related to blood rheological properties [7].
Viscosity is the main rheological property of blood and depends on deformation and aggregation of erythrocytes, hematocrit, and plasma flow velocity in the pulmonary microcirculation. Pathological factors such as increases in leukocyte count and protein levels modify blood rheology [8, 9]. Since red blood cells (erythrocytes) are the most abundant blood components, their structure, function, and concentration are a main factor for blood rheology in the lungs. The function of red blood cells is to provide tissue oxygen
Altitude, considered as more than 1500 meters above the sea level (mASL), is a factor that affects interaction between hemoglobin and O2 at the alveolar capillary level [11]. When ascending to high altitudes, the atmospheric pressure and the partial pressure of oxygen decrease. This leads to a reduction in the oxygen inspiratory fraction and less availability of this gas to be transported by hemoglobin. This condition is known as hypobaric hypoxia [12, 13]. The aim of this study is to analyze the relationship between hypoxia and hemorheology in the pulmonary microcirculation of pediatric patients with PDA operated on at a moderate altitude.
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2. Methodology
A retrospective, observational, analytical, and cross-sectional case-control clinical trial was carried out. This included all pediatric patients with an echocardiographic diagnosis of PDA as the only cardiovascular pathology and who were operated on in a single-, high-, and specialized-level hospital located at a moderate altitude during a seven-year period of time. Exclusion criteria were patients without pre- and postsurgical laboratory data and those who were born at an altitude of less than 1500 mASL.
Patients were divided in two groups: Group 1 (problem: “WITH hypoxia”) and Group 2 (control: “WITHOUT hypoxia”). Conventional gasometric criteria were used in order to include patients in the problem group: Alveolar oxygen pressure (PAO2), arterial oxygen saturation (SAO2), partial oxygen pressure/alveolar oxygen pressure (PaO2/PAO2), and PaO2. Hypoxia was defined as the presence of one or more of the mentioned criteria (Table 1) [14, 15, 16, 17, 18, 19].
| Gasometric criteria | Reference values |
|---|---|
| Arterial SAO2 | Normal: 95–99% Acceptable: 90–95% Severe hypoxemia: <85% |
| PaO2/PAO2 | Normal: >0.75 Hypoxemia: ≤0.75 |
| Quotient PaO2/FiO2 adjusted ratio | Normal: >300 Mild hypoxia: ≤300 and >200 Moderate hypoxia: ≤200 and >100 Severe hypoxia: ≤100 |
| PaO2 | Normal: 80–100 mmHg Acceptable: 60–80 mmHg Critical hypoxemia: 45–60 mmHg Severe hypoxemia: 45 mmHg |
Table 1.
Abbreviations: SAO2 = oxygen saturation, PaO2 = partial oxygen pressure, PAO2 = alveolar oxygen pressure, FiO2 = oxygen inspired fraction, mmHg = millimeters of mercury.
Sociodemographic, clinical, echocardiographic, presurgical, postsurgical, and gasometric laboratory data were obtained from each patient’s physical and electronic clinical record. According to the specific place of birth, the altitude and barometric pressure in millimeters of mercury (mmHg) corresponding to that geographical area was utilizrd to obtain PAO2 and calculate the arterial-alveolar oxygen quotient.
A complete blood count was obtained as well as the blood gasometry of every patient, mainly within the first few days following their surgery. In neonates, gasometric samples were collected in heparinized capillary tubes. For infant patients, samples were taken in heparinized insulin syringes. Gasometric analysis was performed with the instrumentation Laboratory GEM 5000 premier system. Diagnosis of PDA was made by means of an echocardiogram, using GE Vivid S6 echocardiography equipment with neonatal and pediatric transducers.
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3. Statistical analysis
All the information was recorded in an electronic Excel spreadsheet and later processed with a SPSS v.21.0 statistical software. Continuous variables were expressed as mean ± standard deviation and categorical variables as absolute value and percentage in relation to the population at risk. Student’s t-test was used to compare continuous variables and Fisher’s exact test for categorical variables. A p < 0.05 was considered as statistically significant.
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4. Results
A total of 18 patients (56.2%) were enrolled in the problem group and 14 (43.8%) in the control group. Tables 2 and 3 show data results concerning the sociodemographic, clinical, and echocardiographic variables on both study groups. These are not significantly statistically different. The same is true for the data presented in Tables 4 and 5. These include preoperative clinical variables, postsurgical follow-up details, hemodynamic stability parameters, gasometric criteria, and perioperative laboratory values. This means that both groups are fully comparable.
| Variables | WITHOUT hypoxia n (%)/mean ± SD (min-max) | WITH hypoxia n (%)/mean ± SD (min-max) | p |
|---|---|---|---|
| Age at surgery (years) | 5.4 ± 3.70 (0.0–12.2) | 4.0 ± 3.44 (0.1–11.9) | NS |
| Female | 9 (64.2%) | 14 (77.8%) | NS |
| Preterm | 3 (21.4%) | 6 (33.3%) | NS |
| Address (last 3 months) | |||
| Mexico State | 9 (64.28%) | 16 (88.9%) | NS |
| Mexico City | 4 (28.6%) | 2 (11.1%) | NS |
| Hidalgo | 1 (7.1%) | 0 (0%) | NS |
| Somatometry | |||
| Weight (kg) | 26.6 ± 26.51 (1.1–109.0) | 13.0 ± 7.78 (1.3–31.5) | NS |
| Size (cm) | 113.9 ± 35.2 (36.0–163.0) | 93.8 ± 22.68 (60.0–138.0) | NS |
| BMI (kg/m2) | 16.4 ± 7.54 (8.4–41.0) | 13.6 ± 3.85 (2.3–20.4) | NS |
| Maternal morbidity | 0 (0%) | 6 (33.3%) | NS |
| Medication use in pregnancy | 11 (78%) | 14 (78%) | NS |
| Pregnancies | |||
| Primigravida | 4 (28.6%) | 5 (27.8%) | NS |
| Multigesta | 10 (71.4%) | 13 (72.2%) | NS |
| Delivery way | |||
| Vaginal | 4 (28.6%) | 9 (50.0%) | NS |
| Cesarean | 10 (71.4%) | 9 (50.0%) | NS |
| Type of pregnancy | |||
| Single | 13 (92.8%) | 18 (100.0%) | NS |
| Multiple | 1 (7.1%) | 0 (0%) | NS |
| Fetal comorbidity | 8 (57.1%) | 7 (38.9%) | NS |
Table 2.
Comparison of sociodemographic and clinical variables between the studied groups.
Abbreviations: kg = kilograms, cm = centimeters, kg/m2 = kilogram per squared meters, BMI = body mass index.
| Variables | WITH hypoxia | WITHOUT hypoxia | |
|---|---|---|---|
| n (%)/mean ± SD (min-max) | n (%)/mean ± SD (min-max) | p | |
| Smaller PDA mouth (mm) | 6 ± 1.8 (3–10) | 5.4 ± 1.9 (2–8) | NS |
| Smaller PDA mouth | |||
| Pulmonary | 10 (55.6%) | 11 (78.6%) | NS |
| Aortic | 6 (33.3%) | 0 (0%) | NS |
| Same | 2 (11.1%) | 3 (21.4%) | NS |
| Aortic ring (mm) | 11.2 ± 3.2 (7–17) | 12.9 ± 3 (5–16) | NS |
| PDA/aortic ring ratio | 0.6 ± 0.2 (0.3–1) | 0.4 ± 0.1 (0.3–0.7) | NS |
| PDA size/Ao ring ratio | |||
| Short | 2 (11.1%) | 4 (28.6%) | NS |
| Medium/large | 13 (72.2%) | 9 (64.3%) | NS |
| No data | 3 (16.7%) | 1 (7.1%) | NS |
| SPAP/SBP ratio | 0.3 ± 0.1 (0.2–0.6) | 0.3 ± 0.09 (0.2–0.5) | NS |
| PDA size/SPAP ratio | |||
| Short | 10 (55.6%) | 9 (64.3%) | NS |
| Medium/large | 1 (5.5%) | 2 (14.3%) | NS |
| No data | 7 (38.9%) | 3 (21.4%) | NS |
| BP | |||
| Systolic | 99.6 ± 16.8 (67–134) | 101.7 ± 20.4 (57–128) | NS |
| Dastolic | 59.3 ± 15.8 (32–85) | 59.5 ± 16.4 (38–89) | NS |
| Pulse pressure | 40.3 ± 12.5 (21–70) | 42.2 ± 13.8 (19–62) | NS |
| Mitral E/A ratio | 1.5 ± 0.84 (0.7–2.5) | 1.3 ± 0.7 (0.8–1.6) | NS |
Table 3.
Comparison of echocardiographic variables between the studied groups.
Abbreviations: Ao = aortic, Pu = pulmonary, PDA = patent ductus arteriosus, SPAP = systolic pulmonary artery pressure, SBP = systolic blood pressure, BP = blood pressure.
| Variables | WITH hypoxia | WITHOUT hypoxia | |
|---|---|---|---|
| n (%)/mean ± SD (min-max) | n (%)/mean ± SD (min-max) | p | |
| Surgery opportunity | |||
| Emergency | 2 (11%) | 2 (14%) | NS |
| Elective | 16 (89%) | 12 (86%) | NS |
| Surgical procedure | |||
| Extrapleural SS | 15 (83%) | 13 (93%) | NS |
| Clip PDA closure | 1 (5%) | 1 (7%) | NS |
| Preoperative medications | 15 (83%) | 12 (86%) | NS |
| Invasive mechanical ventilation | 2 (11%) | 1 (7%) | NS |
| Preoperative vasopressor | 1 (6%) | 0 (0%) | NS |
| Preoperative (NYHA/Ross) | |||
| I | 4 (22%) | 2 (14%) | NS |
| II | 13 (72%) | 12 (86%) | NS |
| III | 1 (5%) | 0 (0%) | NS |
| RACHS-1 | |||
| 1 | 17 (94%) | 13 (93%) | NS |
| 2 | 1 (5%) | 1 (7%) | NS |
| Postoperative (NYHA/Ross) | |||
| I | 18 (100%) | 14 (100%) | NS |
| Surgical follow-up (months) | 21.6 ± 16.4 (0–48) | 10.9 ± 8.4 (2–25) | NS |
| Surgical morbidity/mortality | 3 (17%) | 2 (14%) | NS |
| Hemodynamic stability | |||
| mPAP ≥25 mmHg | 13 (72%) | 10 (71%) | NS |
| Minor size PDA/Pu or Ao ring>1/3 (0.33) | 11 (61%) | 8 (57%) | NS |
| PDA minor diameter > 1.5 mm | 1 (5%) | 1 (7%) | NS |
| P pulse 25–30 mmHg | 1 (5%) | 0 (0%) | NS |
| PDA/Ao ring ratio > 0.5 | 1 (5%) | 0 (0%) | NS |
| Mitral E/A ratio ≥ 1 | 1 (5%) | 0 (0%) | NS |
| LV end-diastolic diameter with > +2 | 1 (5%) | 1 (0%) | NS |
| AI/Ao > 1.3 | 1 (5%) | 1 (0%) | NS |
Table 4.
Preoperative, follow-up, and hemodynamic stability clinical variables of the studied groups.
Abbreviations: NYHA = New York Heart Association, RACHS-1 = risk adjusted classification for congenital heart surgery-1, E/A = E wave/A wave ratio, LV = left ventricle, Ao = aorta.
| Variables | WITH hypoxia | WITHOUT hypoxia | p |
|---|---|---|---|
| n (%)/mean ± SD (Min-Max) | n (%)/mean ± SD (min-max) | ||
| Gasometry | |||
| Preoperative | 6 (33%) | 11 (78%) | NS |
| Postoperative | 11 (61%) | 2 (14%) | NS |
| Unknown | 1 (5%) | 1 (7%) | NS |
| Arterial SaO2 | |||
| Normal | 13 (72.2%) | 11 (78.6%) | NS |
| Hypoxemia | 5 (27.8%) | 0 (0%) | NS |
| Unknown | 0 (0%) | 3 (21.4%) | NS |
| PAO2 | |||
| Hypoventilation | 6 (33%) | 0 (0%) | NS |
| Normal | 7 (39%) | 6 (43%) | NS |
| Unknown | 5 (28%) | 8 (57%) | NS |
| PaO2/PAO2 | |||
| Normal | 8 (44%) | 12 (86%) | NS |
| Hypoxia | 5 (28%) | 0 (0%) | NS |
| Unknown | 5 (28%) | 2 (14%) | NS |
| PaO2/FIO2 | |||
| Normal | 1 (5%) | 6 (43%) | NS |
| Mild | 9 (50%) | 0 (0%) | NS |
| Moderate | 2 (11%) | 0 (0%) | NS |
| Severe | 2 (11%) | 0 (0%) | NS |
| Unknown | 4 (22%) | 8 (57%) | NS |
| PaO2 | |||
| Normal | 5 (28%) | 12 (86%) | NS |
| Acceptable | 6 (33%) | 0 (0%) | NS |
| Critical | 2 (11%) | 0 (0%) | NS |
| Unknown | 5 (28%) | 2 (14%) | NS |
| Hypoxia | 18 (100%) | 0 (0%) | NS |
| Preoperative laboratory | |||
| Leukocytes | 10 ± 3.8 (5.2–17.6) | 7.9 ± 2.5 (4.6–12.9) | NS |
| Platelets | 294.4 ± 71.2 (206–432) | 245.9 ± 78.4 (92–356) | NS |
| Postoperative laboratory | |||
| Hemoglobin | 12.5 ± 1.7 (9.3–14.6) | 12.9 ± 1.3 (9.6–14.7) | NS |
| Leukocytes | 10.2 ± 4.3 (5.2–23.3) | 9 ± 3 (5.9–14.9) | NS |
| Hematocrit | 37.8 ± 4.9 (27.3–43.9) | 39.2 ± 3.3 (31–43.1) | NS |
| Platelets | 290.9 ± 82.6 (171–435) | 298 ± 122.4 (123–521) | NS |
Table 5.
Pre- and postoperative gasometric and laboratory variables of the studied groups.
Abbreviations: SaO2 = oxygen saturation, PAO2 = oxygen alveolar pressure, PaO2 = oxygen partial pressure, FIO2 = oxygen inspired fraction.
Although there are no statistically significant differences, it should be noted that in both study groups, infants made up the main population age group with the female gender predominating. Also, a higher percentage of patients with term birth live at an average altitude of 2683 mASL. Weight, height, and body mass index (BMI) showed low somatometric levels in the problem group according to child growth patterns established by the World Health Organization (WHO) [20]. According to the Center for Disease Control and Prevention (CDC) [21], however, both study groups had an adequate weight.
Most of the mothers of the problem group presented preeclampsia, and in the control group, the primary medications taken by the mothers during pregnancy were multivitamins and betamethasone. Regarding fetal comorbidity, it should be noted that Down syndrome and congenital hypothyroidism predominated in the problem group. Regarding the preoperative clinical characteristics, the opportunity for surgery was elective in more than 80% of the patients. The primary operative technique used was extrapleural PDA section and suture. Very few patients required mechanical ventilation (18%) or the use of preoperative amines (5%) in either study groups.
It should be noted that 72% of the children in the problem group presented acute respiratory distress syndrome (ARDS) with different severity degrees and remained hypoxic, despite receiving an additional oxygen supply. This is corroborated by the significant increase in oxygen inspired fraction (FIO2) and PAO2 levels in this group. In contrast, patients in the control group did not require O2 breathing since they were not determined to be hypoxic. Table 6 shows the primary variables used to determine the relationship between hypobaric hypoxia and hematocrit in the pulmonary microcirculation. A remarkable finding is the fact that the hematocrit values of the problem group were significantly higher than those of the control group. It can be seen that in addition to the already mentioned gasometric and hematocrit values, lactate also presents higher values in the problem group. Additionally, it can be observed that the echocardiographic diameter of the aorta at its interface with the heart had a statistical tendency to be greater in the problem group.
| Variables | WITH hypoxia n (%)/mean ± SD (min-max) | WITHOUT hypoxia n (%)/mean ± SD (min-max) | p |
|---|---|---|---|
| Demographics | |||
| Altitude (mASL) | 2258.1 ± 47.3 (2200–2400) | 2301.9 ± 119.7 (2235.0–2667.0) | NS |
| Altitude ≥2300 (mASL) | 2 (11.11%) | 3 (21.43%) | 0.432 |
| Barometric pressure (mmHg) | 581.6 ± 2.9 (572–584) | 579.1 ± 7.5 (556–583) | NS |
| Echocardiographic | |||
| Max gradient (mmHg) | 57.2 ± 13.9 (25–80) | 49.9 ± 20.4 (20–82) | NS |
| PDA length (mm) | 9.8 ± 4 (5–24) | 9.3 ± 3 (4–17) | NS |
| Aortic mouth (mm) | 7.1 ± 1.6 (5–10) | 9.1 ± 4.1 (4–17) | NS |
| Pulmonary mouth (mm) | 6.9 ± 3.2 (3–17) | 5.4 ± 1.9 (2–8) | NS |
| SPAP (mmHg) | 29.5 ± 8.3 (20–50) | 33.3 ± 11.2 (20–50) | NS |
| mPAP(mmHg) | 32.1 ± 8.3 (22.6–52.6) | 35.9 ± 11.3 (22.6–52.6) | NS |
| Preoperative laboratory | |||
| Hemoglobin | 13.3 ± 1.5 (10.9–17.3) | 13.2 ± 2 (9.3–17.1) | NS |
| Hematocrit | 40 ± 4.3 (34–53.2) | 39.2 ± 5.5 (30–50.6) | NS |
| Gasometry | |||
| pH | 7.3 ± 0.2 (6.8–7.6) | 7.4 ± 0.1 (7.2–7.6) | 0.098 |
| PaO2 | 100.6 ± 82 (23–305) | 155.8 ± 114.3 (38–397) | NS |
| PaCO2 | 35 ± 8.4 (22–53) | 31.7 ± 6.9 (20–46) | NS |
| SaO2 | 91 ± 10.3 (64–100) | 97 ± 2.4 (92–100) | 0.042 |
| HCO3 | 20.1 ± 3.6 (14.9–28.3) | 19.5 ± 3.4 (14.3–25) | NS |
| BE | −4.4 ± 8.4 (−25.2–10.5) | −3.9 ± 5.8 (−11.7–9.2) | NS |
| Lactate | 1.4 ± 1 (0.5–4.3) | 1 ± 0.4 (0.4–1.8) | NS |
| Hematocrit | 33 ± 1.4 (31–34) | 30.5 ± 4.9 (27–34) | 0.047 |
| FiO2% | 35.2 ± 19.2 (21–72) | 21 ± 0 (21–21) | 0.01 |
| PAO2 | 137.4 ± 101.8 (59.3–322.1) | 74.8 ± 8.6 (64.7–86.1) | 0.03 |
| PaO2/PAO2 | 1 ± 0.7 (0.4–3.2) | 1.9 ± 1.5 (1–5.1) | 0.04 |
| PaO2/FiO2 | 278.9 ± 144.9 (131.7–726.9) | 520.1 ± 445 (313.5–1427.8) | 0.03 |
Table 6.
Demographic, echocardiographic, laboratory, and blood gas variables used to determine the relationship between pulmonary microcirculation and hemorheology.
Abbreviations: mASL = meters above sea level, mmHg = millimeters of mercury, mm = millimeters, SPAP = systolic pulmonary arterial pressure, mPAP = mean pulmonary arterial pressure, PaO2 = oxygen arterial pressure, PaCO2 = arterial carbon dioxide pressure, SaO2 = oxygen saturation, HCO3 = bicarbonate, BE = baseline excess, FIO2 = oxygen inspired fraction, PAO2 = oxygen alveolar pressure.
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5. Discussion
Several reports show that healthy people who live at high altitudes have hypobaric hypoxia [22, 23, 24]. Since the closure of PDA is mainly related to O2 concentrations, the presence of hypobaric hypoxia is an etiopathogenic risk factor for presenting this disease. The high prevalence of PDA in people living in hypoxic environments is associated with a delayed closure of PDA and postnatal pulmonary hypertension. The incidence of PDA therefore is higher in children who live at high altitudes in comparison to those who live at the sea level [25]. Under hypoxic conditions, juxtaglomerular cells of the kidney secrete erythropoietin (EPO), which stimulates bone marrow stem cells to produce red blood cells whose key component is hemoglobin. This increases O2 transport to the different tissues as a hypoxia compensatory mechanism. Hematocrit levels, defined as the percentage fraction of erythrocytes contained in the blood, also increase in direct proportion to red cell count [26, 27].
Hematocrit is the main determinant of blood viscosity. Therefore, when there is a greater red blood cell count, blood viscosity increases [28]. To ensure a proper tissue oxygen and nutrient supply, it is necessary to maintain a normal blood flow rate, which depends on the length of blood vessels and the blood viscosity. Oxygen tissue supply depends on the arterial O2 concentration and the blood flow through the vessels. Resistance is a factor that modifies blood flow velocity. This physiological relationship is stated mathematically by means of Poiseuille’s Law, where the flow velocity of a fluid depends on the pressure and flow resistance. The flow resistance (R) is determined by the length of the blood vessel (L), the radius of the same vessel (r), and the viscosity of the fluid (η), in this case, blood [29, 30]. Any increase in blood viscosity and/or decrease in the diameter of blood vessels therefore leads to a decrease in the blood flow velocity [31].
The increase in blood viscosity causes a decrease in blood flow velocity in different organs such as the brain, heart, intestines, and lungs [32]. The slowdown in blood flow is a proven factor that promotes formation of microthrombi and alters the ventilation/perfusion ratio (V/Q) in the pulmonary microcirculation. This establishes a pattern in which there is ventilation without perfusion. The V/Q ratio in these circumstances tends to infinity. Such tissue is called physiological dead space and corresponds to areas of the lung that have adequate ventilation but not perfusion. Thus, they do not participate in gas exchange. The decreased oxygen concentration in blood leads to hypoxia and respiratory failure [33]. This is the reason why, despite the fact that the problem group has higher hematocrit values and therefore a greater oxygen transport capacity, hypoxia persists. Although it is true that the O2 concentration is the same at different altitude levels, barometric pressure and therefore FiO2 are lower as one ascends to higher altitudes. This value can also be modified if O2 is supplied to the patient [34]. This is the case of the problem group, who, in addition to hypoxia, presented clinical data of respiratory failure for which additional oxygen was supplied. This increased the FiO2 values in comparison to the control group and was therefore not an effect related to hypobaric hypoxia. Despite the fact that both groups presented similar altitude levels and barometric pressures, hypoxia and increased hematocrit values were only evidenced in the problem group.
The impact of blood viscosity in relation to hypoxia is a poorly studied parameter and is rarely considered in daily clinical practice. In this study, we showed that blood viscosity is a factor that significantly influences the pulmonary microcirculation, favoring hypoxia. It seems that the increase in erythrocyte number and hematocrit level develops in order to improve hypoxia. This apparent compensatory mechanism, however, actually tends to perpetuate hypoxia rather than relieve it. The change in hemodynamics associated with increased viscosity promotes microthrombi as blood stasis is one of the factors that is part of Virchow’s triad and is the main mechanism associated with thrombus genesis. Increased blood viscosity causes endothelial injury and affects blood flow turbulence, factors that contribute to platelet aggregation [35]. Pulmonary microcirculation is altered by the presence of microthrombi, which act as perpetuators of abnormal blood flow and therefore thrombosis promoters. Blood hyperviscosity, thrombosis and decreased pulmonary microcirculation, as well as endothelial injury and inflammation trigger the process of remodeling and interstitial fibrosis in the alveoli capillary unit in a medium- to long-term period of time. In hemodynamic terms, this factor produces a progressive increase in pulmonary vascular resistance and the consequent development of chronic thromboembolic disease as well as secondary pulmonary arterial hypertension [36].
On the other hand, it was additionally determined that in both of our study groups, most of the patients had a medium or large PDA diameter. Individuals who live permanently at moderate altitudes had increased pulmonary pressure and a larger diameter of PDA. This caused overload of pulmonary and left ventricular blood flow. A moderate or large PDA tends to be associated with moderate and severe pulmonary hypertension, respectively. More than 70% of the patients in both groups in our study had a mean pulmonary artery pressure > 25 mmHg, suggesting pulmonary hypertension. Thus, our study corroborates the literature [35, 36] that living at a moderate altitude predisposes to a greater diameter of the ductus arteriosus and therefore a greater probability of developing pulmonary hypertension. The diameter of the PDA, however, was not the most important factor associated with the presence of hypoxia in our problem group.
Finally, it is important to mention that our study has certain limitations such as the sample size and the retrospective nature of its design. Despite this, the trend of our results show a clear relationship between hypoxia and hemorheology in the pulmonary microcirculation produced by the increase in blood viscosity due to hematocrit level. If we increased the size of our sample, this tendency would likely be reinforced. In any case, it is highly recommended that future research should be carried out in this field in order to reliably confirm the tendencies identified in this study.
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6. Conclusion
Though not statistically significant, the results of this study show a clear relationship between hypoxia and higher hematocrit values. This suggests that the increase in blood viscosity due to a higher hematocrit level in response to altitude, instead of controlling its hypobaric effects and being a compensatory mechanism, is a factor that promotes hypoxia in the pulmonary microcirculation. More clinical trials are needed to confirm this finding with statistical significance.
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