Notas del manejo hemodinámico durante la guardia COVID-19 / Notes on hemodynamic management during the COVID-19 watch

Resumen: Todo en medicina debe fundamentarse y equilibrarse en tres pilares. El primero es: un fuerte principio fisiológico; una explicación de qué provoca el fenómeno patológico al que nos estamos enfrentando y con la cual encontremos cómo puede ser revertida dicha patología. El segundo pilar es: una adecuada corroboración estadística; un principio fisiológico puede ser cierto, pero ello no implica que el desenlace que buscamos (disminución de la mortalidad) sea el resultado de nuestras intervenciones. El tercer pilar es un protocolo clínico, lo que implica la parte más importante de todas, el trabajar unidos. De nada sirve creer conocer la verdad, si es que es así, si no se tiene las mismas metas en todos los turnos, corremos el riesgo de caer en la falacia de que «lo que yo hago es lo correcto y los demás se equivocan¼; si no estamos unidos en cada turno de atención al paciente, nunca sabremos qué es lo mejor para él, sólo tendremos un buen pretexto para afirmar que la culpa nunca es nuestra. Durante las crisis emergentes se puede trabajar sin la estadística mientras ésta se va construyendo, pero nunca sin fisiología y unidad (protocolos), la explicación fisiológica aquí vertida es lo más exacta posible, el protocolo es una inducción derivada de dicha fisiológica en espera de tener pronto una estadística que nos diga si lo que hacemos es de utilidad o no. En conclusión, lo que el lector tiene en sus manos son conjeturas en búsqueda de refutaciones. Al momento de escribir este artículo la única respuesta correcta es «Aún no lo sabemos¼.

Abstract: Everything in medicine must be based and balanced on three pillars, the first is: a strong physiological principle; an explanation of what causes the pathological phenomenon that we are facing with which we find how this pathology can be reversed, the second pillar is an adequate statistical corroboration; a physiological principle may be true, but this does not imply that the outcome we seek (decrease in mortality) is the result of our interventions. The third pillar is a clinical protocol, which implies the most important part of all, working together. It is useless to believe that you know the truth, if that is the case, if you do not have the same goals in every shift, we run the risk of falling into the fallacy that «what I do is right and others are wrong¼, if we are not united in each shift of patient care we will never know what is best for the patient, we will only have a good pretext to affirm that the fault is never ours. During emerging crises you can work without statistics while it is being built, but never without physiology and unity (protocols), the physiological explanation given here is as accurate as possible, the protocol is an induction derived from said physiology, waiting to have Soon a statistic will tell us if what we do is useful or not. In conclusion, what the reader has in his hands are conjectures in search of refutations. At the time of writing this article the only correct answer is «We don't know yet¼.

Role of Ca2+ in hypoxic pulmonary vasoconstriction / 中华危重病急救医学

In acute hypoxia, pulmonary vascular will contract and divert blood to better ventilated area to optimize ventilation/perfusion matching, which is known as hypoxic pulmonary vasoconstriction (HPV). In chronic hypoxia, irreversible pulmonary vascular remodeling can be induced, characterized by pulmonary artery middle smooth muscle cells and the outer fiber cell hyperplasia in luminal stenosis and pulmonary artery hypertension (PAH) eventually. Furthermore, PAH can cause increased ventricular afterload, and right heart failure in severe cases. Pulmonary artery smooth muscle cell (PASMC) elevated Ca2+ concentration is one of the most important factors of its contractions, proliferation and migration. Recent studies on Ca2+ promoting in HPV were summarized in order to provide evidence for clinical prevention of hypoxia and therapeutic PAH.

Effects of dexmedetomidine on oxygenation during one-lung ventilation for esophagectomy / 中国医师进修杂志

Objective To evaluate the effects of dexmedetomidine on hypoxic pulmonary vasoconstriction and oxygenation during one- lung ventilation (OLV) undergoing esophagectomy. Methods Fifty-six adult patients undergoing esophagectomy and requiring OLV were selected.During inhalational anesthesia with sevoflurane, patients were randomized to receive either dexmedetomidine (dexmedetomidine group,28 patients)or saline placebo(control group,28 patients). The bolus dose of 0.3 μg/kg over 10 min followed by a maintenance dose of 0.6 μg/(kg·h)was used in dexmedetomidine group. The arterial blood gas samples were obtained to evaluate the effects of dexmedetomidine on oxygenation in three times:T1:double-lung ventilation 10 min after anesthetic intubation;T2:OLV 10 min;T3:60 min after continuous infusion of dexmedetomidine. Outcomes included differences in hemodynamic parameters(heart rate and mean arterial pressure), end-tidal sevoflurane concentration, ephedrine dose and atropine dose.Results The levels of pH, arterial partial pressure of carbon dioxide(PaCO2)in two groups had no significant differences(P>0.05).The level of oxygenation index in two groups at T3had significant difference: (153.29 ± 19.00) mmHg(1 mmHg=0.133 kPa)vs. (117.79 ± 12.00) mmHg, 1 mmHg = 0.133 kPa, P < 0.01. At T3, the level of heart rate in dexmedetomidine group was significantly lower than that in control group:(68 ± 11)times/min vs.(89±13)tims/min;meanwhile, the level of end-tidal sevoflurane concentration in dexmedetomidine group was significantly lower than that in control group: (2.9 ± 0.8)% vs. (4.2 ± 0.1)%; there were significant differences (P < 0.01). The ephedrine dose in two groups had no significant difference(P>0.05).Conclusions Dexmedetomidine may provide clinically relevant benefits by improving oxygenation and decreasing the requirement of inhalational anaesthetic agents, thereby limiting its effect on hypoxic pulmonary vasoconstriction during OLV in adults undergoing esophagectomy surgical procedures.

Effect of aerosolized iloprost inhalation on pulmonary arterial pressure and hypoxic pulmonary vasocon-striction during one-lung ventilation / 临床麻醉学杂志

Objective To investigate the effect of aerosol inhalation of iloprost on pulmonary arterial pressure and hypoxic pulmonary vasoconstriction (HPV)during one-lung ventilation (OLV) in rats.Methods Thirty male rats were randomly divided into three groups,10 in each group. Models of lung perfusion were established,100% FiO 2 was ensured under the condition of OLV and the atomizers were opened.Atomization inhalation with normal saline was performed in group A,ilo-prost at a concentration of 0.05 μg·kg-1 ·min-1 in group B and iloprost at a concentration of 0.1μg·kg-1 ·min-1 in group C.Mean pulmonary artery pressure (MPAP)and PaO 2 of drainage-fluid from left atrium were recorded at time points of perfusion for 10 min (T1 ),aerosol inhalation for 10 min (T2 )and OLV for 1 h (T3 ).Oxygenation index (OI)was calculated with PaO 2 at each time point.Both lungs were harvested for electronic microscope detection.Results MPAPs at T2 and T3 were higher in contrast with that at T1 (P <0.05).A decrease of MPAP at T2 and T3 showed in group B and C when compared with those in group A (P <0.05).Group C had lower MPAP in comparison with group B at each time point.Considering the time span,we found that OIs at T2 and T3 were lower than that at T1 .In addition,OIs at T2 and T3 in group C were higher than those in group B,respectively.Under elec-tronic microscope,nuclear membranes typeⅡ alveolar epithelial cells of both lungs in group A and of non-ventilated lungs in group B and C bulged out or invaginated and lamellar bodies were evacuated,especially when compared to those in ventilated lungs in groups B and C.Conclusion In rat models of lung perfusion, atomization inhalation with iloprost can decreased MPAP,reduce intrapulmonary shunt and increase oxygen-ation.

Effect of hypoxic pulmonary vasoconstriction on hypoxic pulmonary hypertension / 中国药理学通报

Sustained hypoxic pulmonary vasoconstriction (HPV ) as experienced at high altitude can lead to hypoxic pulmonary hypertension(HPH).HPV,a special physiological phenomenon of lung,is the physiological reflex of organism in hypoxic envi-ronment.However,in high altitude hypoxic environment,the sustained HPV can lead to pulmonary vascular remodeling and right ventricular hypertrophy,at the same time,the degree of hypoxia in alveoli can be aggravated.Vicious circle of hypoxia is formed,further causing the severe high altitude sickness such as pulmonary edema and pulmonary heart disease.HPV appears in preliminary of HPH,but in the chronic phase,irreversible hy-poxic pulmonary vascular remodeling forms.Therefore,studying the mechanism of HPV and the effect of HPV in HPH can pro-vide targets and ideas for the prevention and treatment of high al-titude sickness. Additionally, in preliminary stage of HPV, prompt treatment is critical for the prevention of high altitude sickness.However,the mechanism of HPV and its roles in HPH are still not fully elucidated in current studies.This paper sum-marizes the studies about HPV in HPH of recent years,aiming to provide references for researchers and clinical treatment in this research field.

Estrategias en la ventilación pulmonar selectiva durante la resección pulmonar oncológica / Strategies in the selective lung ventilation during lung cancer resection

Introducción: los avances en la conducta anestésica, técnicas quirúrgicas y cuidados perioperatorios han posibilitado expandir la población que ahora puede ser considerada «operable¼ para la resección pulmonar. La fisiología de la ventilación pulmonar selectiva está conectada íntimamente a sus efectos en la relación ventilación/perfusión pulmonar. Varios factores afectan esta relación debido principalmente a sus efectos en la complacencia pulmonar. El aislamiento pulmonar desacopla el binomio ventilación/perfusión en el pulmón operado y puede producir hipoxemia significativa si no se trata apropiadamente. Objetivo: identificar la administración, basada en evidencias, de la ventilación durante la ventilación pulmonar selectiva enfocada a evitar la hipoxemia y el daño pulmonar posoperatorio. Métodos: revisión exhaustiva de la literatura disponible de las estrategias, basadas en evidencias, de la ventilación durante la ventilación pulmonar selectiva. Conclusiones: para un mejor tratamiento de los disturbios en la relación ventilación /perfusión que se producen en la ventilación pulmonar selectiva es necesario estar familiarizados con los principios básicos que gobiernan la ventilación y la perfusión pulmonar, así como aplicar los métodos para mejorar la oxigenación durante la ventilación pulmonar selectiva y las estrategias ventilatorias protectoras para disminuir la incidencia o severidad del daño pulmonar postoracotomía.

Background: The advances in anaesthetic behaviour, technical techniques and preoperative care have made it possible to expand the population that can now be considered as "operable" for lung resection. The physiology of selective lung ventilation is closely connected to its effects on the pulmonary ventilation-perfusion relation. Several factors affect this relation because of its effects in the lung satisfaction. The lung isolation uncouples the ventilation-perfusion binomial in the operated lung and can produce a significant hypoxemia if it is not treated properly. Objectives: To identify the evidence-based administration of the ventilation during the selective lung ventilation focused to avoid hypoxemia and postoperative lung injury. Methods: A detailed review of the available literature about evidence-based ventilation strategies during the selective lung ventilation was made. Conclusions: To follow a better treatment of the disturbances in relation to the ventilation-perfusion that occur in the selective lung ventilation it is necessary to become familiar with the basic principles that govern pulmonary ventilation-perfusion and apply methods to improve oxygenation during the selective lung ventilation and protective ventilation strategies to diminish the incidence or severity of lung injury after thoracotomy.

Disappearance of Hypoxic Pulmonary Vasoconstriction and O2-Sensitive Nonselective Cationic Current in Arterial Myocytes of Rats Under Ambient Hypoxia

Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated K+ channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane A2 (TXA2) and hypoxia-activated nonselective cation channel (I(NSC)) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d-H). Specifically, the associated electrophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d-H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d-H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d-H and control. In contrast, hypoxia and TXA2-activated I(NSC) was not observed in PASMCs of 2d-H. From above results, it is suggested that the decreased I(NSC) might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.

Anesthetic Management of Whole-Lung Lavage Using Propofol-Remifentanil in a Patient with Pulmonary Alveolar Proteinosis / 대한구급학회지

Pulmonary alveolar proteinosis (PAP) is characterized by the progressive accumulation of phospholipids and proteins within the alveolar sacs without producing an inflammatory response. Whole-lung lavage (WLL) is performed as the standard therapy for this disease because it serves to wash out the proteinaceous material from the alveoli. In this case, we performed sequential WLL using propofol-remifentanil, which is not related to hypoxic pulmonary vasoconstriction during one-lung ventilation. The patient's symptoms and radiologic findings showed improvement without the occurrence of any specific complications. Therefore, we report a case of anesthetic management of WLL performed repeatedly for a patient with recurrent PAP.

Requirement of Pretone by Thromboxane A2 for Hypoxic Pulmonary Vasoconstriction in Precision-cut Lung Slices of Rat

Hypoxic pulmonary vasoconstriction (HPV) is physiologically important response for preventing mismatching between ventilation and perfusion in lungs. The HPV of isolated pulmonary arteries (HPV-PA) usually require a partial pretone by thromboxane agonist (U46619). Because the HPV of ventilated/perfused lungs (HPV-lung) can be triggered without pretone conditioning, we suspected that a putative tissue factor might be responsible for the pretone of HPV. Here we investigated whether HPV can be also observed in precision-cut lung slices (PCLS) from rats. The HPV in PCLS also required partial contraction by U46619. In addition, K+ channel blockers (4AP and TEA) required U46619-pretone to induce significant contraction of PA in PCLS. In contrast, the airways in PCLS showed reversible contraction in response to the K+ channel blockers without pretone conditioning. Also, the airways showed no hypoxic constriction but a relaxation under the partial pretone by U46619. The airways in PCLS showed reliable, concentration-dependent contraction by metacholine (EC50, ~210 nM). In summary, the HPV in PCLS is more similar to isolated PA than V/P lungs. The metacholine-induced constriction of bronchioles suggested that the PLCS might be also useful for studying airway physiology in situ.

Effects of ATP and LTC4 on hypoxic pulmonary vasoconstriction in isolated rat lungs / 대한마취과학회지

BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary circulation but the mechanism remains elusive. Red blood cells (RBCs) are known to augment HPV and to release more ATP as oxygen content falls. Leukotrienes constrict smooth muscle and could be important for the regulation of the pulmonary circulation. Hence we hypothesized that ATP and leukotrienes are mediators of HPV produced during acute alveolar hypoxia. METHODS: In forty Sprague-Dawley rats, lungs were isolated and perfused. We administered ATP (10 micrometer) to the ATP group (n = 8), the ATP antagonist, suramin (100 micrometer) to the suramin group (n = 8), leukotriene C4 (LTC4, 5 microgram) to the LTC4 group (n = 8), the LTC4 antagonist, LY171883 (20 micrometer) to the LY171883 group (n = 8), and LTC4 (5 microgram) + ATP (10 micrometer) to the LTC4 + ATP group (n = 8) during normoxic ventilation. HPV responses were induced by three hypoxic challenges for 5 minutes separated by 5 minutes of ventilation with a normoxic gas mixture. Baseline pulmonary artery pressure change after exposure to each drug and hypoxic pressor response between a period 21% normoxic gas ventilation and that of 3% hypoxic gas ventilation were measured. RESULTS: ATP and LTC4 + ATP increased baseline pulmonary artery pressures but LTC4 did not alter it. ATP did not affect hypoxic pressor response. Suramin, LY171883 and LTC4 + ATP inhibited the pressor response to hypoxia. LTC4 increased hypoxic pressor response. CONCLUSIONS: In isolated rat lungs, HPV may be mediated by ATP and LTC4 appears more likely to be a modulator than a mediator of HPV.

Effects of Protein Kinase C on Hypoxic Pulmonary Vasoconstriction in Isolated Rat Lungs / 대한마취과학회지

BACKGROUND: Protein kinase C represents an important component of a signal transduction pathway that regulates vascular smooth muscle contraction. This study was performed with an inhibitor and activators of protein kinase C to determine their effects on hypoxic pulmonary vasoconstriction (HPV) in isolated rat lung model. METHODS: Isolated lungs from Sprague-Dawley rats were ventilated with a normoxic gas (21%O2-5%CO2-balanced N2) and a hypoxic gas (3%O2-5%CO2-balanced N2) alternatively, and then perfused with constant pulmonary blood flow. Baseline hypoxic pressor responses (delta PAP) were measured as the difference of pulmonary artery pressure between normoxic ventilation and hypoxic ventilation. After baseline delta PAP had obtained, rats were randomly divided into a chelerythrine group, an phorbol 12, 13-dibutyrate (PDBu) group, and a farnesylthiotriazole (FTT) group. The different concentrations of each drug were added into the perfusate sequentially. delta PAP in the different concentrations of each drug were calculated as a percentage of the delta PAP in each concentration of drug to the baseline delta PAP in the absence of drug (%delta PAP). RESULTS: The %delta PAP of chelerythrine were 83.7 +/- 19.2%, 71.5 +/- 24.1% and 68.4 +/- 28.3% at 0.1, 1, and 10micrometer, respectively (P < 0.05). The %delta PAP of PDBu were 111.3 +/- 10.1%, 144.4 +/- 37.8% and 168.4 +/- 89.1% at 20, 100, and 300 nM, respectively (P < 0.05). The %delta PAP of FTT were 80.1 +/- 25.1%, 61.0 +/- 17.2% and 30.1 +/- 18.4% at 1, 10, and 30micrometer, respectively (P < 0.05). CONCLUSIONS: The results of this study suggest that regulator of protein kinase C influence HPV.

Influence of Preoperative One Lung Ventilation in the Lateral Position on Arterial Oxygenation during Subsequent One Lung Ventilation / 대한마취과학회지

BACKGROUND: There are a few reports with conflicting results regarding the potentiation of hypoxic pulmonary vasoconstriction (HPV) by repeated hypoxic challenges. The aim of this study was to determine if preoperative one lung ventilation (OLV) in the lateral position (LP) for a short time decreases the development of arterial hypoxemia and improves the level of arterial oxygenation via the potentiation of HPV in patients undergoing thoracic surgery with OLV. METHODS: Forty patients were randomly divided into two groups according to presence or absence of preoperative OLV. Preoperative OLV in LP was achieved for 10 minutes with 100% O2 in group P (n = 20). Thereafter, the two lungs were again ventilated with 50% O2 until OLV with 100% O2 had been achieved. In group C (n = 20), the two lungs were continuously ventilated with 50% O2 until OLV with 100% O2 was achieved. The arterial blood samples were obtained 15 minutes after the two lung ventilation in the supine position (baseline) during preoperative OLV in LP, before pulmonary vein ligation, as well as before and after pulmonary artery ligation. The development of arterial hypoxemia (peripheral blood oxygen saturation in pulse oximetry < 95%) in patients undergoing thoracic surgery with OLV was also recorded. RESULTS: Arterial hypoxemia during OLV was observed in 2 cases in group C and 3 cases in group P. There was a similar level of arterial oxygen tension during OLV between the two groups. CONCLUSIONS: This study showed that the preoperative OLV in LP for 10 minutes neither potentiated the HPV response during OLV nor decreased the frequency of arterial hypoxemia during OLV.

Pathophysiology of Persistent Pulmonary Hypertension of the Newborn / 소아과

Persistent pulmonary hypertension of the newborn(PPHN) is a disorder characterized by persistence of the pattern of fetal circulation after birth due to a sustained elevation of pulmonary vascular resistance. The two primary events in the pathophysiology of neonatal pulmonary hypertension are hypoxic pulmonary vasoconstriction(HPV) and hypoxic pulmonary vascular remodeling(HPR). Chronic hypoxemia may cause increased muscularity of the pulmonary arteries and extension of the muscularity to more distal arteries. The mechanisms underlying neonatal hypoxic pulmonary vascular remodeling are complex and multifactorial, requiring the involvement of endothelial, vascular smooth muscle, and adventitial cells. Endothelin-1(ET-1) has strong vasoactive properties, and acts via two different receptors, ETA and ETB. In pulmonary artery, ETA receptors mediate vasoconstriction and are found on vascular smooth muscle cells, while ETB receptors that are mostly located on endothelial cells mediate vasodilation by NO and prostacyclin release. eNOS derived NO is an important mediator of pulmonary vascular response to chronic hypoxia. Atrial natriuretic peptides(ANP) plays an important role in the regulation of pulmonary arterial pressure. Vascular endothelial growth factor (VEGF) release is increased in hypoxic pulmonary arterial smooth muscle cells, and hence may be involved in hypoxic pulmonary artery remodeling and edema. Retinol is essential for fetal lung morphogenesis and subsequent normal neonatal lung growth and maturation. ATP-sensitive potassium channels may be involved in the later stage of hypoxia. Activation of these channels may counteract the vasoconstrictive effect of hypoxia.

The Effect of Isoproterenol, Dobutamine, and Milrinone on Pulmonary Vasoconstriction in Isolated Rat Lungs / 대한마취과학회지

BACKGROUND: Dobutamine, isoproterenol, and milrinone are inotropic agents with vasodilatory properties, and are frequently used perioperatively. We undertook to examine the effects of these three drugs on the pulmonary vasculature, excluding cardiovascular effects, by determining their effects on pulmonary artery pressure and hypoxic pulmonary vasoconstriction in an isolated rat lung model. METHODS: Thirty Sprague-Dawley rats were divided into a dobutamine group (n = 10), an isoproterenol group (n = 10) and a milrinone group (n = 10). Dobutamine 50microgram, 500microgram, and 5,000microgram, isoproterenol 0.4microgram, 4microgram, and 40microgram, and milrinone 2.5microgram, 25microgram, and 250microgram were added to perfusate sequentially during normoxic ventilation (21% O2-5% CO2-balanced N2). Baseline pulmonary artery pressure changes and subsequent hypoxic pressor responses during hypoxic ventilation (5% O2-5% CO2-balanced N2) were observed. RESULTS: Dobutamine, isoproterenol, and milrinone all decreased baseline pulmonary artery pressures and hypoxic pressor responses in a dose-dependent manner (P < 0.05). The last dose listed for each of the three drugs reversed hypoxic pulmonary vasoconstriction nearly completely. The calculated dose required to reduce the hypoxic pressor response to 50% of the initial response before drug administration (ED50) was 155microgram (95% CI: 80-263microgram) for dobutamine, 0.23microgram (95% CI: 0.011-0.75 microgram) for isoproterenol and 6.31microgram (95% CI: 3.1-10.8microgram) for milrinone. The relative potency of the drugs on HPV, based on ED50 was dobutamine 10: isoproterenol 0.015: and milrinone 0.41. CONCLUSIONS: Dobutamine, isoproterenol, and milrinone all reduced pulmonary vascular resistance and hypoxic pulmonary vasoconstriction in a dose dependent manner. (Korean J Anesthesiol 2004; 46: 454~461)

Changes of Hypoxic Pulmonary Vasoconstriction in Isolated Endotoxin-Treated Rat Lungs / 대한마취과학회지

BACKGROUND: Several investigations have studied hypoxic pulmonary vasoconstriction (HPV) during endotoxemia and there is an increase in nitric oxide (NO) in pulmonary vessels. However, these studies yielded conflicting or at times contradictory results, since reference has been made to both enhancement and inhibition of HPV. Our objective was to determine the changes of hypoxic pulmonary vasoconstriction on the isolated blood-perfused lung of endotoxemic rats. METHODS: Pulmonary arterial pressure (PAP) was measured in a blood-perfused lung preparation from Sprague-Dawley rats in normoxia (21% O2, 5% CO2, balanced N2) and hypoxia (5% O2, 5% CO2, balanced N2). We studied the effect of normoxia and hypoxia in a control group, Escherichia coli lipopolysaccharide group (LPS) and LPS with N omega-nitro-L-arginine methyl ester group (L-NAME). RESULTS: The Baseline PAP was higher in LPS (15.0+/-4.0 mmHg) compared with control group (10.9+/-2.9 mmHg) and L-NAME (11.1+/-3.6 mmHg). In hypoxia, HPV was higher in L-NAME (109.6+/-100.2%) compared with control group (59.9+/-31.6%) and LPS (58.8+/-33.8%)(P<0.05). CONCLUSIONS: We conclude that NO is an important factor to impair HPV during endotoxemia.

Effects of Desflurane and Isoflurane on Arterial Oxygenation and Hemodynamics during One-lung Ventilation / 대한마취과학회지

BACKGROUND: Potent inhalational agents are widely used for thoracic anesthesia. They have several desirable properties, including ease of administration, rapid onset and offset, and bronchodilation. One potential drawback is their ability to directly inhibit hypoxic pulmonary vasoconstriction. Desflurane does not directly inhibit hypoxic pulmonary asoconstriction in vivo, in contrast to isoflurane using the same animal model. In this study, we compared the effects of desflurane and isoflurane on arterial oxygenation and hemodynamics during one lung ventilation in a humans. METHODS: Thirty five patients scheduled for coronary artery bypass graft were randomly assigned to one of group D/I and I/D. Group D/I consisted of four steps. Hemodynamics and oxygenation parameters were checked in each step. Step 1 was checked when they received desflurane to an end tidal concentration of 6% in 93% oxygen from induction until the end of 30 min of two lung ventilation. Step 2 was checked at the end of 30 min after starting one lung ventilation. Step 3 was checked at the end of 30 min after receiving isoflurane to an end tidal concentration of 1.2% in 93% oxygen during one lung ventilation. Step 4 was checked at the end of 30 min after restarting two lung ventilation. Group I/D received the two anesthetic agents in reverse order. We used the simple cross-over design methodology for treatment and period effect. RESULTS: We found no significant difference in hemodynamic and oxygenation parameters between the two inhalational agents except for a significant increase in mean pulmonary arterial pressure and pulmonary capillary wedge pressure caused by desflurane. CONCLUSIONS: During one lung ventilation, the choice between desflurane and isoflurane does not significantly influence arterial oxygenation and shunt fraction but desflurane should be administered with great caution if it is used as an alternative anesthetic in patients with ischemic heart disease.

Effects of Pinacidil, Tetrathylammonium and Glibenclamide on Hypoxic Vasoconstriction in Isolated Perfused Rabbit Lungs / 대한마취과학회지

BACKGROUND: This study investigated the effects of the K+ channel opener, pinacidil on hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs. In order to evaluate the vasodilatation mechanism of K+ channel opener, we also studied the effects of two K+ channel blocker, tetraethylammonium (TEA), a Ca2+ activated K+ channel blocker and glibenclamide (GLB), an ATP-sensitive K+ channel blocker. METHODS: Isolated lungs from white rabbits were ventilated with a normoxic gas (21%O2-5%CO2-74%N2) and a hypoxic gas (3%O2- 5%CO2-92%N2) alternatively, and then perfused with blood-containing perfusate solution. After a hypoxic pressor response (HPR) had been obtained, various drugs were added to the perfusate reservoir to achieve the predetermined circulating concentration, and the influences of the drugs on HPR were then tested. RESULTS: Pinacidil (0.3-6.0 mcM) produced a dose-dependent pulmonary vasodilation on hypoxic ventilation challenge. TEA (1 mM) caused pulmonary vasoconstriction in normoxic ventilation and potentiated a hypoxic pressor response. When the hypoxic pressor response was potentiated by TEA, pinacidil (1.0, 3.0 mcM) reduced the contraction, but GLB did not cause pulmonary vasoconstriction under normoxic ventilation, potentiate a hypoxic pressor response. CONCLUSIONS: Piacidil is capable of opposing the pulmonary responses of acute hypoxia. Moreover the effects of TEA and GLB suggest that HPV might be mediated through Ca2+ activated K+ channels, not through ATP-sensitive K+ channels.

The Effect of Angiotensin II on Hypoxic Pulmonary Vasoconstriction in Isolated Rabbit Lung / 대한마취과학회지

BACKGROUND: The isolated lung model is a very useful model in investigation of hypoxic pulmonary vasoconstriction (HPV), and angiotensin II is extensively used in this model. But the exact role of angiotensin II in HPV is not clear in the isolated rabbit lung. Thus we were concerned about the role of angiotensin II in the blood-perfused rabbit lung. METHODS: New Zealand white rabbits (n = 28) lungs were isolated and perfused with a constant pulmonary perfusate flow; acid-base status and temperature were maintained at constant levels. Deoxyglucose (DOG group, n = 7), angiotension II and deoxyglucose (AG-DOG group, n = 7), calcium (CA group, n = 7), angiotensin II and calcium (AG-CA group, n = 7) were administered, and then hypoxic responses were measured. Three ratios were calculated and compared (P alpha: ratio of hypoxic response to pulmonary arterial pressure at normoxia, P beta: ratio of hypoxic response to baseline hypoxic response, P gamma: ratio of pulmonary arterial pressure at hypoxia to pulmonary arterial pressure at baseline). RESULTS: Angiotensin II increased the pulmonary arterial pressure by 14%, and increased HPV. Baseline pulmonary pressure was increased in the AG-DOG group and in the AG-CA group (P<0.05). P gamma significantly increased in the AG-DOG and AG-CA groups (P<0.05). The first HPV increased but the second HPV decreased in the AG-DOG group (P alpha: P<0.05) and in the AG-CA group. P beta showed no difference between groups. CONCLUSIONS: Angiotensin II resulted in an increase of pulmonary arterial pressure in the isolated rabbit lung. One may misinterpret this as an potentiation of HPV, but HPV was not changed by angiotensin II. Therefore we deny the necessity for angiotensin II in the isolated rabbit lung model.

Effects of Non-selective NO Inhibition on Hypoxia-, Acetylcholine- and Bradykinin-induced Vasoconstriction in Septic Isolated Rat Lungs / 대한마취과학회지

BACKGROUND: Endotoxin stimulates nitric oxide synthase (NOS) and the free radical nitric oxide (NO) is produced by NOS, which vasodilates the smooth muscle of pulmonary vessels. Otherwise, endotoxemia stimulates the release of cyclooxygenase (COX) products, which may modify hypoxic pulmonary vasoconstriction (HPV). We also observed the effect of nonselective NOS inhibition by NG-nitro-L-arginine methyl ester (L-NAME) on receptor-mediated acetylcholine (Ach)/bradykinin (BK) induced vasoconstriction and receptor independent HPV in E.coli lipopolysaccharide (LPS) induced septic isolated rat lungs. METHODS: Four hours before surgical instrumentation for lung isolation, we administered saline (1 ml) to the control group (n = 15), E.coli LPS (20 mg/kg) to the LPS group (n = 14) and LPS (30 mg/kg) the nitric oxide synthase inhibitor, L-NAME (15 mg/kg) to the LPS + L-NAME group (n = 14), intraperitoneally. In 43 isolated rat lungs perfused with physiologic salt-albumin- blood mixture, angiotensin II 0.2 microgram was injected into the perfusion circuit, to confirm pulmonary vascular reactivity in each isolated lung. HPV responses were induced by three hypoxic challenges for 5 minutes separated by 5 minutes of ventilation with a normoxic gas mixture. We observed the pulmonary arterial pressure at each challenge, ten minutes after the last HPV, 0.01, 0.1, 1.0 microgram of Ach and 1, 3, 10 microgram of BK were injected. PAP and static lung compliance were measured. RESULTS: The baseline pulmonary artery pressure in the LPS group higher than in the controls and HPV in the LPS group was changed compared to the controls but in the LPS + L-NAME it was higher than in the controls. The administration of Ach 0.1, 1.0 microgram and BK 3, 10 microgram causedpulmonary vasoconstriction and the vasoconstrictions of BK were dosage-dependent. Lung stiffness in the LPS and LPS + L-NAME groups were higher than those of the controls. CONCLUSIONS: Vascular constriction of pulmonary vessels and increased lung stiffness by Ach and BK might be the result of the endothelial injury. But pulmonary vasoconstriction and stiffness by Ach and BK were similar in the LPS and LPS + L-NAME groups, showing that factors other rather than excessive NO production might be involved in endothelial injury.

A Comparison of the Effects of Isoflurane Verus Propofol Anesthesia on Blood Gas Parameters during One Lung Ventilation for Lung Surgery / 대한마취과학회지

BACKGROUND: During one-lung ventilation (OLV) for thoracic surgery, hypoxic pulmonary vasoconstriction (HPV) may reduce venous admixture and ameliorate the decrease in arterial oxygenation by diverting blood from the non-ventilated to the ventilated lung. Volatile anesthethics are the drugs of choice in thoracic surgery despite numerous experimental data showing their inhibiting effect on the HPV. The object of the present study was to compare the effects of propofol with those of isoflurane on oxygenation and shunt during two lung ventilation (TLV) and OLV in human volunteers. METHODS: Thirty patients who needed OLV for an elective thoracic surgery were randomly assigned to receive either isoflurane (1 MAC isoflurane + fentanyl + vecuronium, n = 15) or propofol (2 - 3ng/ dl propofol + fentanyl + vecuronium, n = 15) with 100% oxygen in separate groups. Systemic hemodynamic data was recorded, and blood gas values were obtained 30 min after the start of TLV (TLV-30) and 30, 45 and 60 min after the start of OLV (OLV-30, 45, 60) in the lateral position. RESULTS: A significant reduction in PaO2 and increase in shunt fractions at all study times after the start of OLV compared with TLV were observed in both groups at OLV-30, 45 and 60. Percent changes of PaO2 and shunt of OLV-60 to those of TLV-30 were less in the propofol group than the isoflurane group. Other blood gas data (SaO2, SO2, PaCO2, PCO2, pH, Hb, CaO2 and CO2) and systemic hemodynamics (mean arterial blood pressure, heart rate and central venous pressure) were not different after the start of OLV compared with TLV in either group. CONCLUSIONS: TIVA with propofol was superior than isoflurane anesthesia in terms of arterial blood oxygenation and pulmonary shunting during OLV for lung surgery.