Disfunción endotelial en la hipertensión pulmonar / Endothelial dysfunction in pulmonary hypertension

No disponible

El alma, razón o no de un ejercicio médico / The soul, reason or not of an exercise physician

La medicina tiene como propósito principal lograr una mejor calidad de vida en los pacientes. Para que esto sea posible no es suficiente conformarse con estudiar y tratar el aspecto físico de estos, también es igualmente importante tener la posibilidad de curar su alma. Luego de explicar y analizar diferentes conceptos y realidades de lo que son el alma y el espíritu, notamos que es perfectamente posible para el médico mejorar la calidad de vida espiritual de su paciente una vez que acepte que, aunque no es algo científicamente comprobable, el alma y el espíritu existen y son esenciales para la óptima sanidad y cura de todo ser humano

Effect of dopamine on platelet activating factor induced-pulmonary edema in isolated and perfused rabbit lungs.

The effect of dopamine over pulmonary edema induced by PAF was studied. Thirty preparations of rabbit lungs were used: six control preparations (CP), six PAF preparations (PP) in which we injected a dose of 1 microg/kg of rabbit weight and eighteen dopamine preparations (DAP) divided in three groups of six pretreated with a dose of 1-5 (dopaminergic range), 10-20 (Beta range) and 20-30 ug/kg/min (Alpha range) of dopamine, respectively for 30 min, followed by an injection of PAF as in the PP. DAP at Beta and Alpha-adrenergic range decreased pulmonary artery pressure (Pap) as compared to CP, with values of 11.66 (CI 95%: 10.83-12.48), 11.66 (CI 95%: 9.87-13.44) versus 17.12 (CI 95%: 16.12-18.11) cm of water, respectively. DAP in Beta and Alpha-adrenergic range prevented Pap increment as compared to PP, with values of 17.16 (CI 95%: 16.37-17.94), 17.5 (CI 95%: 14.93-20.06) versus 84 cm of water (CI 95%: 71.41-96.58), respectively. Dopamine, at its three ranges inhibited the augmentation of the fluid filtration rate observed in PP with values of 1.01 (CI 95%: 0.77-1.24), 0.03 (CI 95%: 0.01-0.04) and 0.02 g/min (CI 95%: -0.0004-0.03) versus 2.13 g/min (CI 95%: 1.56-2.69), respectively. We concluded that dopamine has a vasodilator effect on Pap and exerts an inhibiting action over PAF effects in pulmonary circulation. Such effects seem to be mainly mediated by Beta-receptors, rather than by dopaminergic receptors.

Effect of hydrocortisone on platelet activating factor induced lung edema in isolated rabbit lungs.

The effect of hydrocortisone on platelet activating factor (PAF)-induced pulmonary edema is studied. Thirty four isolated and perfused rabbit lung preparations were used: eight control preparations, eight PAF preparations with two doses of PAF called low dose (LD = 0.5 microg/kg of rabbit weight) and high dose (HD = 1 microg/kg of rabbit weight). Eighteen preparations divided in three groups of six were pretreated with doses of 20, 200 and 2000 mg of hydrocortisone and later given the same doses of PAF as described above. Hydrocortisone significantly decreased (P < 0.05) the effect of PAF LD over the pulmonary arterial pressure (Ppa) in the 200 and 2000 mg groups (58 and 89% decrease, respectively) and it significantly decreased (P < 0.05) the effect of PAF HD over Ppa in all hydrocortisone pretreated groups (48, 70 and 96% decrease, respectively). Fluid filtration rate (FFR) increases mediated by PAF HD were significantly inhibited (P < 0.05) in the 200 and 2000 mg groups (64 and 96% decrease, respectively). We conclude that hydrocortisone inhibits the effect of PAF over the pulmonary circulation.

Effect of platelet activating factor (PAF) on pulmonary circulation in isolated rabbit lung.

Platelet activating factor (PAF) has been implicated in the pathophysiology of acute lung injury. The aim of this work is to study the effect of PAF on isolated and perfused rabbit lungs with blood and with a blood-free solution. 24 isolated and perfused rabbit lungs have been used: 8 control preparations (CP), 4 vehicles preparations (VP), 8 PAF preparations (PP) to which we administered PAF (1 microg/Kg of rabbit weight) and 4 acellular preparations (AP) with the same dose of PAF as in PP but dissolved in BSA-Krebs buffer solution. In the preparations pulmonary artery pressure (Ppa), airway pressure (Paw), left atria pressure (Pla) and fluid filtration rate (FFR) were registered. Ppa resulted in a significant difference in AP vs PP, with a value of 21 cm of water (CI 95%: 12-26) vs 205.1 cm of water (CI 95%: 141.3 - 271) respectively. A increase in FFR was observed in PP but it did not occur in AP, the difference being statistically significant: 5.515 g/min (CI 95 %: 2.425 - 8.865) vs 0.049 g/min (CI 95%: 0.008 - 0.32) respectively. Paw was statistically different in PP vs AP, with a value of 14.3 cm of water (CI 95%: 11.57 - 16.7) vs 8.5 cm of water (CI 95%: 8-9) respectively. These results suggest that PAF does not have a direct effect on the endothelium or smooth muscle in the production of lung edema.

Tityus discrepans venom produces a respiratory distress syndrome in rabbits through an indirect mechanism.

It is well known that scorpion venom induces lung lesions and respiratory distress which are usually classified as pulmonary oedema (PO). Tityus discrepans is a scorpion that lives in the north-central area of Venezuela, is the most common source of human envenomation here and produces PO. We studied the action of the venom of Tityus discrepans on whole rabbits and on their isolated lungs perfused with Krebs saline with 1 g/l of bovine serum albumin (Krebs-BSA saline). Two milligram of venom were diluted in 250 ml of solution (approximately the rabbit's total blood volume) and used to perfuse isolated lungs. Lung oedema occurred in rabbits which received 1 mg/kg of scorpion venom i.p., heparin prevented the production of this lung oedema. T. discrepans venom produced PO, in rabbits pretreated with 15 mg/kg of ajoene. Yet, Tityus venom had no effects on isolated lungs perfused with citrated or heparinized blood, and in lungs perfused with Krebs-BSA with normal Ca2+. These result show that Tityus venom does not act directly on lungs. Otherwise, we have observed that abundant microthrombi occurred in all rabbit lungs exposed to venom in vivo, suggesting that these clotting alterations are fundamental to produce PO. The presence of intravascular microthrombi is not characteristic of the usual PO hinting that scorpion venom induced pulmonary alterations are a different clinical entity. We thus propose that the use of the term pulmonary oedema in scorpionism should abandoned in favor of scorpion venom respiratory distress syndrome.

Effect of Fenoterol on PAF-induced lung edema in isolated and perfused rabbit lungs.

We have studied the effects of fenoterol on PAF-induced response in pulmonary circulation. We used 28 isolated and perfused rabbit lungs preparations: eight control preparations (CP), four vehicles preparations (VP), eight PAF preparations (PP) with two doses of PAF, one called low dose (LD = 0.5 microg/kg of weight) and the other high dose (HD = 1 microg/kg of weight) and eight Fenoterol preparations (FP) which we administered 0.05 mg of Fenoterol for 15 min, followed by a LD and HD of PAF. FP prevented elevation of pulmonary artery pressure (Ppa) as compared to PP, at LD of PAF: 12.615 (CI 95%: 8.57-20.885) versus 83.705 (CI 95%: 50.55-114.3) cm of water; and at HD of PAF: 19.38 (CI 95%: 11.235-28.94) versus 205.1 (CI 95%: 141.3-271) cm of water respectively. FP prevented the increase in fluid filtration rate (FFR) observed in PP at both doses of PAF LD: 0.765 (CI 95%: 0.07-3.385) versus 0.01 (CI 95%: -0.05-0.005) g/min; HD: 5.515 (CI 95%: 2.425-8.865) versus 0.03 (CI 95%: 0-0.33) g/min. Our results suggest that PAF has a vasoconstrictor effect that produces lung edema and this effect is inhibited by fenoterol.

Effects of hypothermic perfusion on pulmonary circulation in isolated rabbit lung.

The effects of hypothermic perfusion have been studied by using different perfusates in 24 isolated rabbit lung preparations, divided into three groups: G1, perfused with blood (hematocrit of 10%) and G2 and G3, perfused with erythrocyte-free plasma plus 6% protein in saline. In both G1 and G2 groups left atrial pressures were kept below airway pressure (Zone II conditions), and in G3 it was higher than airway pressure (Zone III conditions). Perfusate flow, pulmonary artery pressure, pulmonary vascular resistance, left atrial pressure, fluid filtration rate, colloid osmotic pressure and temperature were not different (p > 0.1) between G1 and G2 at the beginning of the experiments. Lowering perfusate temperature from 38 degrees C to 28 degrees C produced a significant increase in pulmonary artery pressure and pulmonary vascular resistance in G1 but they decreased in G2 lungs (p < 0.05). Fluid filtration rate increased in both groups during hypothermia. These responses were not inhibited by an alpha-adrenergic receptor blocker or a pulmonary vasodilator. In G3 lungs no changes were observed. The differences in the hemodynamic effects of hypothermia observed in G1 and G2, both in Zone II conditions, could result from the differences in the vessel distention state obtained by each of the perfusate before initiating hypothermia. As perfusate viscosity increase with cold, a greater possibility of vessel distention in G2 lungs occurs. This explains the decrease in pulmonary artery pressure and pulmonary vascular resistance with cold in this group. The increase in fluid filtration rate observed with hypothermia in G1 and G2 may be due to increases in fluid exchange area.

Effect of blood pH on pulmonary artery pressure, left atrial pressure and fluid filtration rate in isolated rabbit lung.

To determine the effects of pH changes on Pulmonary Artery Pressure (PAP), 18 isolated rabbit lung preparations, perfused with autologous blood mixture and constant PaCO2 have been studied. Each preparation was studied under 3 conditions: Baseline: 30 minutes equilibration period. Acidosis: pH was decreased by 0.2 N HCl infusion, the ventilatory rate was changed and different CO2 mixtures were used to maintain the PCO2 within the initial parameters. Compensated Acidosis (CA): pH was returned to normal values by 0.7 N NaHCO3 infusion maintaining PCO2 in its initial values. The decrease in pH (acidosis) from 7.36 +/- 0.05 to 7.18 +/- 0.06 at constant PCO2, generated a significant increase in PAP (13.6 +/- 3.2 cm H2O to 18.8 +/- 5.2 cm H2O, p < 0.01). The pH increase (CA) from 7.18 +/- 0.06 to 7.40 +/- 0.09 caused the PAP to decrease (18.8 +/- 5.2 cm H2O to 15.9 +/- 4.2 cm H2O); the fluid filtration rate remained unchanged during the whole experiment. It is concluded that blood pH changes at constant PCO2 result in significant changes of PAP. Acidemia produces pulmonary vasoconstriction, which may be a contributing factor in the genesis of pulmonary hypertension in clinical conditions with increased hydrogen ion concentration [H+].

[Inflammatory lung pseudotumor]. / Pseudotumor inflamatorio.

We report a 63 years old man presenting with a history of persistent cough and blood streaked sputum. Chest X rays and CAT scans showed a tumoral lesion between the superior and inferior right lobes. The tumor was resected and its pathological examination revealed an inflammatory pseudotumor. It is concluded that this type of tumors must be born in mind in patients with nodular lesions of the lung.

Increase in cardiac output and PEEP as mechanism of pulmonary optimization.

The influence of cardiac output (CO) and PEEP on pulmonary shunt (Qs/Qt) has been the subjects of considerable investigation but findings are controversial. The role of CO and PEEP on 19 isolated rabbit lung preparations perfused with hypoxic mixture (6% CO2, 10% O2, and 84% N2), which resulted in a constant oxygen venous pressure (64 +/- 5.6 mmHg) has been studied. The first group of 11 preparations were used to study the influence of CO modifications with room air ventilation on the Qs/Qt when the CO rises in 48%; in the second group simultaneous modifications in CO and PEEP (0.5 and 10 cm H2O) were performed. A positive correlation (p < 0.01) in Qs/Qt (0.048 +/- 0.04 to 0.12933 +/- 0.09) was found when the CO increased in the first experimental group, the fluid filtration rate (FFR) also increased and the pulmonary vascular resistance (PVR) remained stable. In the second group an increase of 5 and 10 cm H2O of PEEP at constant CO reduced the Qs/Qt (0.0361 +/- 0.02 to 0.0184 +/- 0.006) while it increased the arterio-venous oxygen difference, PVR and FFR. During high CO conditions increase of 5 and 10 cm H2O of PEEP reduced the Qs/Qt (0.099 +/- 0.03 to 0.027 +/- 0.02) and FFR. These data suggest that when the Qs/Qt is increased, the use of PEEP can compensate the ventilation/perfusion alterations and restore pulmonary gas exchange.

[Effect of the administration of furosemide on the fluid filtration rate and in pulmonary artery pressure in isolated lungs of rabbits]. / Efecto de la administración de furosemida en la tasa de filtracion de liquido y en la presión de la arteria pulmonar en el pulmón aislado de conejo.

To study the possible effects of Furosemide at the lung level, two groups of isolated rabbit lung preparation were studied. An experimental group underwent a pulmonary hydrostatic oedema when the pressure of the left auricle (PAI) was increased from 0.45 +/- 0.74 t0 11.8 +/- 2.9 cm of H2O, with that increase in PAI we obtained an increase of 0.457 +/- 0.51 g/min in FFR (Fluid Filtration Rate), during this stable and sustained oedema, a 2 mg/Kg dosis of Furosemide was injected every 10 minutes and the possible changes in PAP, PAI, PVA, TFL, PaO2, PaCO2 and pH was observed, but no changes were observed in these parameters during the Furosemide infusion, and the same effect was observed in the control group were the preparations were maintained in basal conditions and without oedema. These results suggests that the Furosemide hat not a direct cardio-pulmonary effects, and the only possible effects could be by increasing diuresis at renal level.

[Effect of the administration of intralipid on liquid filtration rate and pressure of the pulmonary artery in isolated lung of rabbits]. / Efecto de la administración de Intralipid en la tasa de filtración de líquido y en la presión de la arteria pulmonar en el pulmón aislado de conejo.

INTRODUCTION: We study the effect on Intralipid on pulmonary circulation. METHODS: A 10% infusion of Intralipid was administered at a dose of 0.5/kg in 14 isolated rabbit lungs in which constant blood flow infusion was carried out principally in zone 3. The liquid filtration rate (LFR) and the mean pressure of the pulmonary artery were measured. RESULTS: A constant increase of mean pressure of the pulmonary artery was observed following the infusion (from 12.32 +/- 3.66 cm of H2O to 39.92 +/- 07.68 cmH2O (p < 0.01) which was associated to a significant increase in the rate of liquid filtration (from 0.018 +/- 0.01 g/min to 0.198 +/- 0.04 g/min; p < 0.01). CONCLUSIONS: The administration of Intralipid produces a statistically significant increase of mean pressure of the pulmonary artery and the rate of liquid filtration. This is probably caused by vasoconstriction due to metabolic changes produced by Intralipid on pulmonary circulation.

Effect of lipoxygenase and cyclo-oxygenase inhibition on oleic acid-induced lung oedema.

The contribution of cyclo-oxygenase and 5-lipoxygenase metabolites on hemodynamics and oedema formation was investigated in 21 isolated rabbit lungs after a 10 min Oleic Acid (OA) infusion, by recording the changes on Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP). Lungs (n = 7) were pre-treated with indomethacin (cyclo-oxygenase inhibitor) 50 min prior to OA or with Diethylcarbamazine (5-lipoxygenase inhibitor) (n = 7) or not pre-treated at all (control group, n = 7). The FFR in the indomethacin group was significantly greater than in the control and Diethylcarbamazine (DEC) groups 12 min after OA (7.6 +/- 2.3 mg.min-1 vs. 2.3 +/- 0.8 mg.min-1 and 0.96 +/- 0.8 mg.min-1 respectively) (P < 0.01). The FFR in the control lungs 20 min after OA was significantly greater than the corresponding DEC value (4.2 +/- 0.5 mg.min-1 vs. 1.6 +/- 1.0 mg.min-1) (P < 0.01). Mean Pulmonary Artery Pressure (MPAP) increased both in control and indomethacin groups (16.0 +/- 2.0 Torr to 24.3 +/- 3.7 Torr after 20 min OA and 14.4 +/- 2.5 Torr to 24.6 +/- 3.6 Torr at 10 min after OA, respectively), but MPAP value in DEC group did not significantly change 30 min after OA (14.7 +/- 1.5 Torr to 16.0 +/- 2.3 Torr) (P > 0.05). So we conclude that the selective inhibition of the 5-lipoxygenase metabolites (leukotriene-5hete) may play a protective role in OA induced oedema, whereas the selective inhibition of the cyclo-oxygenase pathway may have a deleterious effect on the hemodynamics and endothelial permeability in our experimental condition.

Effect of lipoxygenase and cyclo-oxygenase inhibition on oleic acid-induced lung oedema.

The contribution of cyclo-oxygenase and 5-lipoxygenase metabolites on hemodynamics and oedema formation was investigated in 21 isolated rabbit lungs after a 10 min Oleic Acid (OA) infusion, by recording the changes on Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP). Lungs (n = 7) were pre-treated with indomethacin (cyclo-oxygenase inhibitor) 50 min prior to OA or with Diethylcarbamazine (5-lipoxygenase inhibitor) (n = 7) or not pre-treated at all (control group, n = 7). The FFR in the indomethacin group was significantly greater than in the control and Diethylcarbamazine (DEC) groups 12 min after OA (7.6 +/- 2.3 mg.min-1 vs. 2.3 +/- 0.8 mg.min-1 and 0.96 +/- 0.8 mg.min-1 respectively) (P < 0.01). The FFR in the control lungs 20 min after OA was significantly greater than the corresponding DEC value (4.2 +/- 0.5 mg.min-1 vs. 1.6 +/- 1.0 mg.min-1) (P < 0.01). Mean Pulmonary Artery Pressure (MPAP) increased both in control and indomethacin groups (16.0 +/- 2.0 Torr to 24.3 +/- 3.7 Torr after 20 min OA and 14.4 +/- 2.5 Torr to 24.6 +/- 3.6 Torr at 10 min after OA, respectively), but MPAP value in DEC group did not significantly change 30 min after OA (14.7 +/- 1.5 Torr to 16.0 +/- 2.3 Torr) (P > 0.05). So we conclude that the selective inhibition of the 5-lipoxygenase metabolites (leukotriene-5hete) may play a protective role in OA induced oedema, whereas the selective inhibition of the cyclo-oxygenase pathway may have a deleterious effect on the hemodynamics and endothelial permeability in our experimental condition.

Effect of lipoxygenase and cyclo-oxygenase inhibition on oleic acid-induced lung oedema.

The contribution of cyclo-oxygenase and 5-lipoxygenase metabolites on hemodynamics and oedema formation was investigated in 21 isolated rabbit lungs after a 10 min Oleic Acid (OA) infusion, by recording the changes on Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP). Lungs (n = 7) were pre-treated with indomethacin (cyclo-oxygenase inhibitor) 50 min prior to OA or with Diethylcarbamazine (5-lipoxygenase inhibitor) (n = 7) or not pre-treated at all (control group, n = 7). The FFR in the indomethacin group was significantly greater than in the control and Diethylcarbamazine (DEC) groups 12 min after OA (7.6 +/- 2.3 mg.min-1 vs. 2.3 +/- 0.8 mg.min-1 and 0.96 +/- 0.8 mg.min-1 respectively) (P < 0.01). The FFR in the control lungs 20 min after OA was significantly greater than the corresponding DEC value (4.2 +/- 0.5 mg.min-1 vs. 1.6 +/- 1.0 mg.min-1) (P < 0.01). Mean Pulmonary Artery Pressure (MPAP) increased both in control and indomethacin groups (16.0 +/- 2.0 Torr to 24.3 +/- 3.7 Torr after 20 min OA and 14.4 +/- 2.5 Torr to 24.6 +/- 3.6 Torr at 10 min after OA, respectively), but MPAP value in DEC group did not significantly change 30 min after OA (14.7 +/- 1.5 Torr to 16.0 +/- 2.3 Torr) (P > 0.05). So we conclude that the selective inhibition of the 5-lipoxygenase metabolites (leukotriene-5hete) may play a protective role in OA induced oedema, whereas the selective inhibition of the cyclo-oxygenase pathway may have a deleterious effect on the hemodynamics and endothelial permeability in our experimental condition.

The effects of graded administration of positive end expiratory pressure on the fluid filtration rate in isolated rabbit lungs, using normal lungs, hydrostatic oedema lungs and oleic acid induced oedema.

The influence of positive end expiratory pressure (PEEP) on the fluid filtration rate (FFR) in the pulmonary circulation has been the subject of considerable investigation but data are conflicting. We studied twenty-nine isolated rabbit lung preparations, FFR was sensed by a force transducer. Autologous blood was used to prime the perfusion circuit. Hydrostatic oedema was achieved by increasing the left atrial pressure to 16 mmHg. In order to bring about increased membrane permeability oleic acid was injected through the pulmonary artery. Increasing and decreasing levels of PEEP at 0, 5, 10 and 15 cm H2O were each used for ten minutes in each of three experimental models. The FFR, pH, mean pulmonary arterial pressure (MPAP), mean left atrial pressure (MLAP), PaO2, PaCO2 and oncotic pressure were measured in each experiment. There was a significant correlation between PEEP and FFR (+0.94) in non-oedema lungs. With no PEEP the FFR was 0 g/min and with 15 cm of PEEP it increased to 0.07 g/min, on removing the PEEP the FFR returned to 0 g/min. In the hydrostatic lung oedema model the correlation was also significant but negative (r = -0.94). With no PEEP the FFR was 0.33 g/min, with PEEP of 15 cm H2O it decreased to 0.08 g/min. No correlation between PEEP and FFR was found in the oleic acid preparation. In the normal lung PEEP increases capillary hydrostatic pressure and total lung vascular area and decreases interstitial pressure. It is by these mechanisms that PEEP causes an increase in FFR. In the hydrostatic oedema model PEEP decreases FFR by increasing the interstitial pressure and by decreasing the total lung vascular area. In the oleic acid preparation the coefficient of filtration is so large that small changes in pressure or vascular area do not modify the FFR. We suggest that PEEP may be beneficial by decreasing FFR in hydrostatic lung oedema, but it may increase the FFR in the normal lung, while having no effect in oleic acid lung injury.

Effect of high frequency oscillatory ventilation on fluid filtration rate in isolated perfused rabbit lungs.

We have studied the effect of changing ventilatory frequency (VF) of high frequency oscillatory ventilation (HFOV) on fluid filtration rate (FFR) in twelve isolated rabbit lungs perfused at constant blood flow. Mean pulmonary artery pressure (Ppa), mean left atrial pressure (Pla), airway pressure (Paw), pulmonary vascular resistance (PVR), pH, O2 and CO2 partial arterial pressures (PaO2 and PaCO2) and plasma colloid osmotic pressure (COP), were measured. We ventilated the lungs with a modified Bird Mark 7 ventilator which could achieve HFOV (range 5-30 Hertz). In each experiment VF was randomly varied on ten different occasions, maintaining each variation for ten minutes. The first group of six rabbits was ventilated under normal haemodynamic conditions. The other six rabbits were ventilated after the production of hydrostatic lung oedema. Blood gas exchange in both groups of rabbits was satisfactory. There was no statistically significant correlation between VF and FFR. We conclude that variations in VF using HFOV does not alter lung fluid balance in normal and in hydrostatic oedema rabbit lungs.