This study was designed to clarify the dependency of hypoxic coronary vasodilation (HCD) on the endothelium and the role of the K+ channels on HCD in the rabbit coronary artery. HCD was investigated in an isolated left circumflex coronary artery precontracted with prostaglandin F2 alpha. Vascular rings were suspended for isometric tension recording in an organ chamber filled with Krebs-Henseleit (KH) solution. Hypoxia was induced by gassing the chamber with 95% N2 + 5% CO2 and was maintained for 15 approximately 25 min. Hypoxia elicited a vasodilation in the precontracted coronary artery with and without endothelium. There was no difference between the amplitude of the HCD induced by two consecutive hypoxic challenges and the effects of 20% O2 + 5% CO2 + 75% N2 and 95% O2 + 5% CO2 control K-H solution of subsequent responses to hypoxia. Inhibition of the cyclooxygenase pathway by treatment with indomethacin had no effect on HCD. Blockades of the tetraethylammonium chloride-sensitive K+ channel abolished HCD. Apamin, a blocker of the small conductance Ca(2+)-activated K+ (KCa) channel, and iberiotoxin, a blocker of the large conductance KCa channel had no effect on HCD, respectively. Glibenclamide, a blocker of the ATP-sensitive K+ (K+ATP) channel, reduced HCD. Cromakalim, an opener of the K+ATP channel, relaxed the coronary artery precontracted with prostaglandin F2 alpha. The degree of relaxation by cromakalim was similar to that by hypoxia while glibenclamide reduced both hypoxia- and cromakalim-induced vasodilatations. In conclusion, these results suggest that HCD is independent on endothelium and HCD is considered to be induced by activation of K+ATP channel.
Animal ; Anoxia/physiopathology* ; Coronary Vessels/physiopathology* ; Coronary Vessels/drug effects ; Cyclooxygenase Inhibitors/pharmacology ; Enzyme Inhibitors/pharmacology ; Female ; Indomethacin/pharmacology ; Male ; Nitroarginine/pharmacology ; Rabbits ; Tetraethylammonium/pharmacology ; Vasodilation/physiology*

PURPOSE: This study was conducted to compare effects of open and closed suctioning methods on lung dynamics (dynamic compliance, tidal volume, and airway resistance) and hypoxemia (oxygen saturation and heart rate) in mechanically ventilated patients. METHODS: This study was a cross-over repeated design. Participants were 21 adult patients being treated with endotracheal intubation using a pressure-controlled ventilator below Fraction of Inspired Oxygen (FiO2) 60% and PEEP 8 cmH2O. Data were collected at baseline and 1, 2, 3, 4, 5, and 10 minutes after suctioning. Data were analyzed using two-factor ANOVA with repeated measures on time and suctioning type. RESULTS: Effects of the interaction between suction type and time were significant for oxygen saturation and heart rate but not significant for dynamic compliance, tidal volume, or airway resistance. Prior to performance of suctioning, tidal volume and oxygen saturation were significantly lower, but airway pressure and heart rate were significantly higher using the closed suctioning method as compared with the open suctioning method. CONCLUSION: For patients on ventilator therapy below FiO2 60% and PEEP 8cmH2O, open suctioning performed after delivery of 100% FiO2 using a mechanical ventilator may not have as much negative impact on lung dynamics and hypoxemia as closed suctioning.
APACHE ; Adult ; Aged ; Aged, 80 and over ; Anoxia/*physiopathology/therapy ; Female ; Heart Rate/physiology ; Humans ; Intubation, Intratracheal ; Lung/*physiopathology ; Male ; Middle Aged ; Oxygen Consumption/physiology ; Respiration, Artificial/*instrumentation ; Suction

We investigated blood pressure (BP) reactivity of obstructive sleep apnea (OSA) during rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. The influences on BP reactivity of degree of arousal, the lowest O2 saturation (SaO2), and respiratory disturbance (RD) duration were compared. Ten normotensive or borderline hypertensive patients with OSA were studied with one-night polysomnography including non-invasive beat-to-beat BP monitoring (Finapres(R)). We compared baseline BP, pre-apneic BP, and post-apneic BP during both REM and NREM sleep. Also, relationships between delta BP (post-apneic BP minus pre-apneic BP) and degree of arousal, the lowest SaO2, and RD duration were examined. During both REM and NREM sleep, pre-apneic BP was elevated compared with baseline BP. Post-apneic BP elevation was noted compared with pre-apneic BP. The degree of arousal was more significantly correlated with delta BP than the lowest SaO2. RD duration was hardly correlated with delta BP. Pre-apneic BP elevation seems to result from cumulation of sympathetic activation and sympathetic nervous system resetting. The correlation between delta BP and degree of arousal suggests that sympathetic activation causing post-apneic BP elevation may result mainly from an arousal response regardless of hypoxia.
Adult ; Aged ; Anoxia/physiopathology ; Arousal/*physiology ; Blood Pressure/*physiology ; Human ; Male ; Middle Age ; Oxygen/blood ; Sleep Apnea, Obstructive/diagnosis/*physiopathology ; Sleep, REM/*physiology ; Sympathetic Nervous System/physiology

We performed 24-hr monitoring of pulse oximetric saturation (SpO2) with ECG and six-minute walk test (6MWT) in 19 patients with fibrotic interstitial lung diseases (ILD) to investigate; 1) The frequency and severity of hypoxemia and dysrhythmia during daily activities and 6MWT, 2) safety of 6MWT, and 3) the parameters of 6MWT which can replace 24-hr continuous monitoring of SpO2 to predict hypoxemia during daily activities. All patients experienced waking hour hypoxemia, and eight of nineteen patients spent > 10% of waking hours in hypoxemic state. Most patients experienced frequent arrhythmia, mostly atrial premature contractions (APCs) and ventricular premature contractions (VPCs). There were significant correlation between the variables of 6MWT and hypoxemia during daily activities. All of the patients who desaturated below 80% before 300 meters spent more than 10% of waking hour in hypoxemia (P = 0.018). In contrast to waking hour hypoxemia, SpO2 did not drop significantly during sleep except in the patients whose daytime resting SpO2 was already low. In conclusion, patients with fibrotic ILD showed significant period of hypoxemia during daily activities and frequent VPCs and APCs. Six-minute walk test is a useful surrogate marker of waking hour hypoxemia and seems to be safe without continuous monitoring of SpO2.
*Activities of Daily Living ; Aged ; Anoxia/*physiopathology ; Arrhythmias, Cardiac/*physiopathology ; Dyspnea/physiopathology ; Electrocardiography, Ambulatory ; Exercise Test ; Exercise Tolerance ; Female ; Humans ; Lung Diseases, Interstitial/*physiopathology ; Male ; Middle Aged ; Motor Activity/*physiology ; Oximetry ; Respiratory Function Tests ; Sleep ; Walking

PURPOSE: A recent study demonstrated that exertional desaturation is a predictor of rapid decline in lung function in patients with chronic obstructive pulmonary disease (COPD); however, the study was limited by its method used to detect exertional desaturation. The main purpose of this study was to explore whether exertional desaturation assessed using nadir oxygen saturation (SpO2) during the 6-minute walk test (6MWT) can predict rapid lung function decline in patients with COPD. MATERIALS AND METHODS: A retrospective analysis was performed on 57 patients with moderate to very severe COPD who underwent the 6MWT. Exertional desaturation was defined as a nadir SpO2 of <90% during the 6MWT. Rapid decline was defined as an annual rate of decline in forced expiratory volume in 1 second (FEV1) > or =50 mL. Patients were divided into rapid decliner (n=26) and non-rapid decliner (n=31) groups. RESULTS: A statistically significant difference in exertional desaturation was observed between rapid decliners and non-rapid decliners (17 vs. 8, p=0.003). No differences were found between the groups for age, smoking status, BODE index, and FEV1. Multivariate analysis showed that exertional desaturation was a significant independent predictor of rapid decline in patients with COPD (relative risk, 6.8; 95% CI, 1.8 to 25.4; p=0.004). CONCLUSION: This study supports that exertional desaturation is a predictor of rapid lung function decline in male patients with COPD.
Aged ; Anoxia/diagnosis/etiology ; Exercise/*physiology ; Female ; Forced Expiratory Volume/physiology ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/*physiopathology ; Respiratory Function Tests ; Retrospective Studies

Hypoxic pulmonary vasoconstriction (HPV), a unique response of pulmonary circulation, is critical to prevent hypoxemia under local hypoventilation. Hypoxic inhibition of K+ channel is known as an important O2-sensing mechanism in HPV. Carbon monoxide (CO) is suggested as a positive regulator of Ca2+-activated K+ channel (BK(Ca)), a stimulator of guanylate cyclase, and an O2-mimetic agent in heme moiety-dependent O2 sensing mechanisms. Here we compared the effects of CO on the HPV (Po2, 3%) in isolated pulmonary artery (HPV(PA)) and in blood-perfused/ventilated lungs (HPV(lung)) of rats. A pretreatment with CO (3%) abolished the HPV(PA) in a reversible manner. The inhibition of HPV(PA) was completely reversed by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. In contrast, the HPV(lung) was only partly decreased by CO. Moreover, the partial inhibition of HPV(lung) by CO was affected neither by the pretreatment with ODQ nor by NO synthase inhibitor (L-NAME). The CO-induced inhibitions of HPV(PA) and HPV(lung) were commonly unaffected by tetraethylammonium (TEA, 2 mM), a blocker of BK(Ca). As a whole, CO inhibits HPV(PA) via activating guanylate cyclase. The inconsistent effects of ODQ on HPV(PA) and HPV(lung) suggest that ODQ may lose its sGC inhibitory action when applied to the blood-containing perfusate.
Animals ; Anoxia/*physiopathology ; Carbon Monoxide/*pharmacology ; Guanylate Cyclase/antagonists & inhibitors/metabolism ; NG-Nitroarginine Methyl Ester/chemistry/pharmacology ; Nitric Oxide Synthase/antagonists & inhibitors/metabolism ; Oxadiazoles/chemistry/pharmacology ; Pulmonary Artery/*physiopathology ; Quinoxalines/chemistry/pharmacology ; Rats ; Tetraethylammonium/chemistry/pharmacology ; Vasoconstriction/*drug effects/physiology

Although hypoxic pulmonary vasoconstriction (HPV) has been recognized by many researchers, the precise mechanism remains unknown. As isolated pulmonary arteries will constrict in vitro in the response to hypoxia, the oxygen sensor/transduction mechanism must reside in the pulmonary arterial smooth muscle or in the endothelium, or in both. Unfortunately, much of the current evidence is conflicting, especially as to the dependency of HPV on the endothelium and the role of a K+ channel. Therefore, this experiment was attempted to clarify the dependency of HPV on the endothelium and the role of a K+ channel on HPV in rat pulmonary artery. The effects of hypoxia were investigated in isolated main pulmonary arteries precontracted with norepinephrine. Vascular rings were suspended for isometric tension recording in an organ chamber filled with a Krebs-Henseleit solution. Hypoxia was induced by gassing the chamber with 95% N2 + 5% CO2 and this was maintained for 20 min. Hypoxia elicited a vasoconstriction in arteries with endothelium. Mechanical disruption of the endothelium abolished HPV. There was no difference between the amplitude of the HPV induced by two consecutive hypoxic challenges and the effect of normoxic and hyperoxic control Krebs-Henseleit solution on a subsequent response to hypoxia. Inhibition of NO synthesis by treatment with N(omega)-nitro-L-arginine reduced HPV, but inhibition of a cyclooxygenase pathway by treatment with indomethacin had no effect on HPV. Blockades of a tetraetylammonium chloride-sensitive K+ channel abolished HPV. Verapamil, a Ca2+ entry blocker reduced HPV. In conclusion, these results suggest that HPV was dependent on the endothelium and that HPV can be considered to be induced by inhibition of the mechanisms of NO-dependent vasodilation such as the opening of a K+ channels.
Animal ; Anoxia/physiopathology* ; Blood Vessels/physiopathology ; Calcium Channel Blockers/pharmacology ; Cyclooxygenase Inhibitors/pharmacology ; Enzyme Inhibitors/pharmacology ; Indomethacin/pharmacology ; Nitroarginine/pharmacology ; Pulmonary Circulation/physiology* ; Pulmonary Circulation/drug effects ; Rats ; Tetraethylammonium/pharmacology ; Vasoconstriction/physiology* ; Vasoconstriction/drug effects ; Verapamil/pharmacology

Contribution of histamine H1- and H2-receptors to the effect of compound 48/80, a potent histamine releaser, upon asphyxiation and body temperature in mice was investigated in the present experiments. Compound 48/80 showed an apparent protective potency against hypoxia and significantly prolonged the latencies for convulsions and death in a dose-dependent manner. Compound 48/80 also decreased the body temperature, which was in relation with the antihypoxic effect. Both the H1-receptor antagonist, dimethindene, and the H2-receptor antagonist, ranitidine, attenuated the hypothermic effect of compound 48/80, indicating the involvement of central histamine through both the H1- and H2-receptors. Ranitidine had no effect on the protective effect of compound 48/80 against hypoxia-induced lethality, whereas dimethindene completely antagonized it. These results suggest that the protective effect of compound 48/80 against hypoxia is mediated through histamine H1-receptors and is not related to its ability to induce hypothermia.
Animal ; Anoxia/*drug therapy/physiopathology ; Body Temperature/*drug effects ; Convulsions/prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; Receptors, Histamine H1/*physiology ; Receptors, Histamine H2/*physiology ; p-Methoxy-N-methylphenethylamine/*pharmacology

PURPOSE: Hypoxemia during one-lung ventilation (OLV) remains a serious problem, particularly in the supine position. We investigated the effects of alveolar recruitment (AR) and positive end-expiratory pressure (PEEP) on oxygenation during OLV in the supine position. MATERIALS AND METHODS: Ninety-nine patients were randomly allocated to one of the following three groups: a control group (ventilation with a tidal volume of 8 mL/kg), a PEEP group (the same ventilatory pattern with a PEEP of 8 cm H2O), or an AR group (an AR maneuver immediately before OLV followed by a PEEP of 8 cm H2O). The tidal volume was reduced to 6 mL/kg during OLV in all groups. Blood gas analyses, respiratory variables, and hemodynamic variables were recorded 15 min into TLV (TLVbaseline), 15 and 30 min after OLV (OLV15 and OLV30), and 10 min after re-establishing TLV (TLVend). RESULTS: Ultimately, 92 patients were analyzed. In the AR group, the arterial oxygen tension was higher at TLVend, and the physiologic dead space was lower at OLV15 and TLVend than in the control group. The mean airway pressure and dynamic lung compliance were higher in the PEEP and AR groups than in the control group at OLV15, OLV30, and TLVend. No significant differences in hemodynamic variables were found among the three groups throughout the study period. CONCLUSION: Recruitment of both lungs with subsequent PEEP before OLV improved arterial oxygenation and ventilatory efficiency during video-assisted thoracic surgery requiring OLV in the supine position.
Adult ; Aged ; Anoxia ; Female ; Humans ; Lung/physiopathology ; Lung Compliance/physiology ; Male ; Middle Aged ; One-Lung Ventilation/*methods ; Oxygen/*blood ; Positive-Pressure Respiration/*methods ; Pulmonary Alveoli/*physiology ; Pulmonary Gas Exchange ; Respiratory Mechanics/*physiology ; *Supine Position ; Thoracic Surgery, Video-Assisted ; Tidal Volume

PURPOSE: To investigate the effects of resveratrol on the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in human adult retinal pigment epithelial (ARPE-19) cells, and on experimental choroidal neovascularization (CNV) in mice. MATERIALS AND METHODS: ARPE-19 cells were treated with different concentrations of resveratrol and then incubated under hypoxic conditions with subsequent evaluation of cell viability, expression of HIF-1alpha, and expression of VEGF. The effects of resveratrol on the synthesis and degradation of hypoxia-induced HIF-1alpha were evaluated using inhibitors of the PI3K/Akt/mTOR and the ubiquitin proteasome pathways. In animal studies, CNV lesions were induced in C57BL/6 mice by laser photocoagulation. After 7 days of oral administration of resveratrol or vehicle, which began one day after CNV induction, image analysis was used to measure CNV areas on choroidal flat mounts stained with isolectin IB4. RESULTS: In ARPE-19 cells, resveratrol significantly inhibited HIF-1alpha and VEGF in a dose-dependent manner, by blocking the PI3K/Akt/mTOR signaling pathway and by promoting proteasomal HIF-1alpha degradation. In mice experiments, orally administered resveratrol significantly inhibited CNV growth in a dose-dependent manner. CONCLUSION: Resveratrol may have therapeutic value in the management of diseases involving pathological neovascularization.
Adult ; Animals ; Anoxia/metabolism/physiopathology ; Cell Survival/drug effects ; Choroidal Neovascularization/*metabolism/pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*drug effects/metabolism ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/antagonists & inhibitors/*physiology ; Proteasome Endopeptidase Complex ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*physiology ; Retinal Pigment Epithelium/*drug effects/metabolism ; Signal Transduction ; Stilbenes/administration & dosage/*pharmacology ; TOR Serine-Threonine Kinases/antagonists & inhibitors/*physiology ; Ubiquitin ; Vascular Endothelial Growth Factor A/*drug effects/metabolism