Effects of Glibenclamide and L-NAME on Hypoxic Pulmonary Vasoconstriction in Rats / 대한마취과학회지

BACKGROUND: This study was performed with NW-nitro-L-arginine methyl ester ((L)-NAME), an inhibitor of EDRF production, and glibenclamide, which closes ATP dependent K+ channels, to determine their effects on hypoxic pulmonary vasoconstriction in isolated perfused rat lungs ventilated with normoxia (21% O2, 5% CO2, balanced N2) and hypoxia (5% O2, 5% CO2, balanced N2). METHODS: Thirty male Sprague-Dawley rats (250 - 350 g) were divided into the control group (n = 10), glibenclamide group (n = 10), and (L)-NAME group (n = 10). In the control group, after the lungs were isolated and stabilized, they were exposed to angiotensin II and 3 consecutive hypoxias. In glibenclamide group, they were exposed to angiotensin II and 3 consecutive hypoxias, and exposed to 3 more hypoxias after injection of glibenclamide 10 uM. In the (L)-NAME group, they were exposed to angiotensin II and 3 consecutive hypoxias, and exposed to 3 more hypoxias after injection of (L)-NAME 100 uM. RESULTS: Hypoxic pulmonary vasoconstriction (deltaPpa) after the (L)-NAME 100nM injection was 12.5 +/- 1.1 mmHg, and it was significantly greater than that of the control group 4.2 +/- 1.1 mmHg (P < 0.05). Hypoxic pulmonary vasoconstriction (deltaPpa) after glibenclamide 10nM injection was 5.3 +/- 1.1 mmHg, and there was no difference with the control group, 4.2 +/- 1.1 mmHg. CONCLUSIONS: We concluded that (L)-NAME, an inhibitor of EDRF production, significantly increased hypoxic pulmonary vasoconstriction, but glibenclamide, which closes ATP dependent K+ channels, did not affect hypoxic pulmonary vasoconstriction in this model.

Effects of Metabolism Inhibited by Deoxyglucose on Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Lung / 대한마취과학회지

BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is a defense mechanism to maintain adequate oxygenation. It has been reported that metabolism inhibition augments HPV. The purpose of the present study was, therefore, to determine the effect of metabolism inhibition on HPV in a rabbit model of isolated lung perfusion with exclusion of the influential factors on HPV. METHODS: In adult rabbits, lungs were isolated and perfused with a constant pulmonary perfusate flow. Acid-base status and temperature of perfusate was also constantly maintained. Thirty minutes after, the baseline hypoxic pressor response (HPR) was measured as the difference of pulmonary artery pressure (PAP) between a period of 21% normoxic gas inhalation and that of 3% hypoxic gas inhalation. After another thirty minutes, 2-deoxy-D-glucose 100 mg was mixed with the perfusate, and then HPR was measured three times. After checking metabolism inhibition effects, D-glucose 300 mg was mixed to the perfusate to reverse metabolism inhibition, and then HPR was measured three times again. RESULTS: Metabolism inhibition increased the basal PAP compared to the noninhibition state, but it didn't increase HPV response, so the peak PAP responding to hypoxic gas was the same as the noninhibition state. The absolute HPV response was decreased. After reversal of the inhibition state with a large amount of glucose, the basal PAP decreased to the original value and the HPV response recovered to the previous value. CONCLUSIONS: Deoxyglucose-induced metabolism inhibition increased the PAP ventilated with 21% O2, but it didn't increase the PAP ventilated with 3% O2. As a result, the absolute HPV response was decreased.

Effects of Acute Normovolemic Hemodilution on Intrapulmonary Shunt and Systemic Oxygen Delivery Balance during One Lung Ventilation in Dogs / 대한마취과학회지

BACKGROUND: The present study was done to elucidate the effects of acute normovolemic hemodilution (ANH) on intrapulmonary shunt (Qs/Qt) and systemic oxygen delivery balance during one lung ventilation (OLV). METHODS: To induce one lung ventilation, an atelectasis of the right lung was produced in anesthetized mongrel dogs. In 6 dogs with OLV, ANH was produced by sequential hemodilution with hydroxyethyl starch. ANH was divided into 3 stages (ANH0: no hemodilition, ANH1: first hemodilution, ANH2: second hemodilution). Qs/Qt was measured by using blood gas analysis. Various hemodynamic parameters, oxygen delivery, and consumption were measured or calculated indirectly. RESULTS: After hemodilution, hemoglobin levels at each stage were 9.9 +/- 1.3 g/dl (ANH0), 7.0 +/- 1.0 g/dl (ANH1), and 5.2 +/- 0.7 g/dl (ANH2). The Qs/Qt of ANH2 stage increased from 25.0 11.4% of ANH0 to 35.4 9.2% (P 0.05). Global oxygen delivery was markedly decreased by hemodilution in OLV (P < 0.05), whereas global oxygen consumption was maintained. CONCLUSIONS: We conclude that global oxygen delivery balance is preserved by ANH in this study. However, extreme ANH has a deleterious effect on pulmonary gas exchange, possibly through the attenuation of hypoxic pulmonary vasoconstriction during one-lung ventilation. On the basis of this study, increased cardiac output generated by ANH might be the cause of inhibition or blunting of hypoxic pulmonary vasoconstriction.

Effects of Desflurane and Isoflurane on Arterial Oxygenation and Intrapulmonary Shunt in One Lung Anesthesia / 대한마취과학회지

BACKGROUND: During one-lung ventilation (OLV) for thoracic surgery, hypoxic pulmonary vasoconstriction (HPV) may reduce the venous admixture and ameliorate the decrease in arterial oxygenation by diverting blood from the non-ventilated to the ventilated lung. Volatile anesthetics (halothane, enflurane, isoflurane, desflurane and sevoflurane) have been shown to depress the HPV with essentially the same potency in vitro. However, clinical studies suggest that isoflurane and sevoflurane provide superior arterial oxygenation during OLV over halothane or enflurane. However, these have not been compared with desflurane. This study compared the effects of desflurane with those of isoflurane on oxygenation & shunt during two lung ventilation (TLV) and OLV in human volunteers. METHODS: Twenty adults who needed OLV with minimal trauma to the nonventilated lung (esophageal surgery) were randomly assigned to receive either 1 MAC desflurane (n = 10) or 1 MAC isoflurane (n = 10) with 100% oxygen in separate groups. Systemic and pulmonary hemodynamic data were recorded, and blood gas values were obtained 30 min after TLV and OLV in lateral position. RESULTS: Reductions in PaO2 (445.2 +/- 72.3 to 125.9 +/- 52.5 and 483.2 +/- 86.2 to 110. 2 +/- 39.8 mmHg, in desflurane and isoflurane respectively) and increases in shunt fraction (Qs/Qt%; 17.2 +/- 3.8 to 33.1 +/- 5.7, 13.4 +/- 4.5 to 32.5 +/- 4.1, in desflurane and isoflurane respectively) at 30 min after the start of OLV were observed, but there were no differences between the groups. The other blood gas data (PaCO2, PCO2, pH, Hb, CaO2, CO2) and systemic and pulmonary hemodynamics (mean arterial blood pressure, heart rate, cardiac output, mean pulmonary arterial pressure, central venous pressure) did not change 30 min after the start of OLV in the two groups. CONCLUSIONS: In clinical practice, there was no difference between desflurane and isoflurane for OLV was no difference in the arterial blood oxygenation and the intrapulmonary shunt.

Effects of Body Temperature Changes on Hypoxic Pulmonary Vasoconstriction in Isolated Lungs of Rabbits / 대한마취과학회지

BACKGROUND: We studied the effects of body temperature changes and repeated hypoxic stimulation on hypoxic pulmonary vasoconstriction (HPV). METHODS: We isolated lungs from 15 rabbits and perfused them at a constant flow of 30 ml/kg/min with a 3% albumin-physiologic salt solution containing autologous blood. After a 30-minute stabilization, the temperature of the perfusate was changed from 38oC to 32oC gradually. The lungs were ventilated for 15 minutes with a hyperoxic gas mixture consisting of 95% oxygen and 5% carbon dioxide and then for 5 minutes with a hypoxic gas mixture consisting of 3% oxygen and 5% carbon dioxide with the balance being nitrogen. We repeated the hypoxic stimulation 3 times at the same temperature. The mean pulmonary artery pressure changes and ventilation-related parameters were measured at each hypoxic stimulation. RESULTS: With the first hypoxic stimulation, the hypoxic pressure response at the end of the 5-minute hypoxic period decreased significantly at 32oC. With the second and the third hypoxic stimulations, the hypoxic pressure responses at the end of the 5-minute hypoxic period decreased significantly at both 34oC and 36oC. With repeated hypoxic stimulations, the hypoxic pressure responses potentiated significantly at all temperatures. The baseline mean pulmonary artery pressure increased significantly below 34oC. CONCLUSION: The HPV decreased with the reduction in body temperature and was potentiated by repeated intermittent hypoxia; also, the pulmonary vascular resistance increased with the reduction in the body temperature.

Comparison of the Effects of Nitroglycerin and Nitroprusside on Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Lung / 대한마취과학회지

BACKGROUND: It has been reported that two common vasodilators, nitroglycerin (NTG) and sodium nitroprusside (SNP), inhibit regional HPV and decrease arterial oxygenation as a result. The purpose of the present study was, therefore, to determine the comparative effect of NTG and SNP on HPV in a rabbit model of isolated lung perfusion with exclusion of the influential factors on HPV. METHODS: In adult white rabbits (n=20), lungs were isolated and perfused with the constant pulmonary blood flow. The acid-base status and temperature of perfusate was also constantly maintained. Thirty minutes later, baseline hypoxic pressor response (HPR) was measured as the difference of pulmonary artery pressure (PAP) between a period of 95% hyperoxic gas inhalation and that of 3% hypoxic gas inhalation. ED50 of NTG and SNP was calculated from the hypoxic pressor response measured in the same way, according to changes of doses (0.5, 1.0, 2.0, and 5.0 microgram/kg). RESULTS: Both NTG and SNP significantly decreased the baseline PAP in the doses of 1.0 microgram/kg and above, and also decreased the HPR in a dose-related manner. ED50 of SNP was significantly lower than that of NTG. CONCLUSIONS: NTG and SNP dilated directly the pulmonary vasculature and inhibited HPV in a dose- related manner. SNP had a greater inhibiting effect on HPV than NTG.

Does Phenylephrine Affect Hypoxic Pulmonary Vasoconstriction and Arterial Oxygenation during One Lung Ventilation? / 대한마취과학회지

BACKGROUND: Vasoconstricting drugs such as dopamine, phenylephrine (PE) and epinephrine constrict normoxic lung vessels preferentially, thereby disproportionately increasing normoxic lung pulmonary vascular resistance (PVR) and inhibit hypoxic pulmonary vasoconstriction (HPV). In this study, we evaluated the effect of PE on HPV and arterial oxygenation. METHODS: This study was performed on 21 patients undergoing thoracotomy. After induction of anesthesia, Swan-Ganz catheter was inserted. After one lung ventilation was started, systolic blood pressure (SBP) of the patient was reduced to 100 mmHg using inhalation anesthetic agent and then the blood pressure was raised up to 140 mmHg by PE infusion. Hemodynamic variables were measured and arterial blood gas was analyzed at the start of one lung ventilation (control), SBP of 100 mmHg and SBP of 140 mmHg. RESULTS: The mean dose of PE infused was 5.9 +/- 3.8 microgram/kg. Infusion of PE did not increase pulmonary vascular resistant index (PVRI) significantly and did not reduce arterial PO2. There was no statistically significant difference in intrapulmonary shunt fraction (Qs/Qt) between the time of low and high blood pressures. CONCLUSION: Pulmonary vasomotor changes induced by PE are minimal and so should not affect the distribution of blood flow during one lung ventilation. On the basis of this result, PE appears to a reasonable vasoconstrictor to be used in patients undergoing thoracotomy.

Effect of Sevoflurane and Isoflurane on Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Lung / 대한마취과학회지

BACKGROUND: In vitro and in vivo studies have shown that inhalation anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV). The aim of this study was to investigate the effect of isoflurane and sevoflurane on HPV in the isolated rabbit lungs. METHODS: Isolated constant-flow perfused lungs from New Zealand white rabbit were randomly allocated to treatment with either isoflurane (n=8) or sevoflurane (n=8). HPV, defined as an increase in pulmonary arterial pressure at constant flow, was elicited by decreasing inspiratory oxygen concentration from 95% to 3% for 5 min. This effect was determined without and with increasing concentration of anesthetics (at 0.5, 1.0, and 2.0 MAC of isoflurane, and at 0.6, 0.9, and 1.2 MAC of sevoflurane). The HPV response in the presence of anesthetics was expressed as a percentage of the pressor response in the absence of anesthetics and dose-response relationship were calculated using the nonlinear least-squares method. RESULTS: The percent hypoxic pressor response (%deltaP) of isoflurane were 100%, 78.4%, 45.1%, and 19.6% at 0, 0.5, 1.0, and 2.0 MAC, respectively. The %deltaP of sevoflurane were 100%, 66.6%, 40.0%, and 22.2% at 0, 0.6, 0.9, and 1.2 MAC, respectively. Values (mean+/-SD) for the half-inhibition values (ED50) were 0.90+/-0.14 and 0.81+/-0.15 MAC, and for the slopes were 1.97+/-0.52 and 1.84+/-0.59 for isoflurane and sevoflurane, respectively. There were no statistical difference between the values for ED50 or between the values for slope. CONCLUSIONS: We conclude that sevoflurane and isoflurane inhibit the HPV reponse in a dose-related manner with same potency and slope.

The Pulmonary Hemodynamic Effects of Nitric Oxide Inhalation on Hypoxic Pulmonary Vasoconstriction / 대한마취과학회지

BACKGROUND: Nitric Oxide (NO) has been discovered to be an important endothelium-derived relaxing factor. The exogenous inhaled NO may diffuse from the alveoli to pulmonary vascular smooth muscle and produce pulmonary vasodilation, but any NO that diffuses into blood will be inactivated before it can produce systemic effects. To examine the effects of NO on pulmonary and systemic hemodynamics, NO was inhaled by experimental dogs in an attempt to reduce the increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) induced by hypoxia in dogs. METHODS: Eight mongrel dogs were studied while inhaling 1)50% O2 (baseline), 2)12% O2 in N2 (hypoxia), 3)followed by the same hypoxic gas mixture of O2 and N2 containing 20, 40 and 80 ppm of NO, respectively. RESULTS: Breathing at FIO2 0.12 nearly doubled the pulmonary vascular resistance from 173 56dyn sec cm-5 to 407 139dyn sec cm-5 and significantly increased the mean pulmonary artery pressure from 16 3mmHg to 22 4mmHg. After adding 20~80 ppm NO to the inspired gas while maintaining the FIO2 at 0.12, the mean pulmonary artery pressure decreased (p<0.05) to the level when breathing oxygen at FIO2 0.5 while the PaO2 and PaCO2 were unchanged. The pulmonary vascular resistance decreased significantly and the right ventricular stroke work index returned to a level similar to breathing at FIO2 0.5 by addition of NO into the breathing circuit. Pulmonary hypertension resumed within 3~5 minutes of ceasing NO inhalation. In none of our studies did inhaling NO produce systemic hypotension and elevate methemoglobin levels. CONCLUSIONS: Inhalation of 20~80 ppm NO selectively induced pulmonary vasodilation and reversed hypoxic pulmonary vasoconstriction without causing systemic vasodilation and bronchodilation. Methemoglobin and NO2 were within normal limit during the study.