This study observed the protective effect of hypercapnic acidosis preconditioning on rabbit heart suffered from ischemia-reperfusion injury. Hypercapnic acidosis was established in animals with mechanical hypoventilation before ischemia-reperfusion. Thirty-two rabbits were randomly divided into 4 groups, with each having 8 animals in term of the degree of acidification: hypercapnic acidosis group A (group A), hypercapnic acidosis group B (group B), hypercapnic acidosis group C (group C), ischemia and reperfusion group (group IR). Animals in group IR were ventilated normally (tidal volume: 15 mL/kg, breathing rate 35 bpm). The PETCO(2) was maintained at the level of 40-50 mmHg for 30 min. Animals in groups A, B, C received low-frequency, low-volume ventilation to achieve hypercarbonic acidosis and the target levels of PETCO(2) were 75-85,65-75, 55-65 mmHg, respectively, with levels being maintained for 5 min. The animals then were ventilated normally to lower PETCO(2) to 40-50 mmHg. The left anterior branch artery of all the animals was ligated for 30 min and reperfused for 180 min. Then the infarct size was calculated. The cardiomyocytes were morphologically observed and ECG and hemodynamics were monitored on continuous basis. Acid-base balance was measured during procedure. Our results showed that the infarct size was (48.5+/-11.5)% of the risk area in the control group and (42.4+/-7.9)% in group C (P>0.05). Mean infarct size was significantly smaller in group B (34.5%+/-9.4%) (P<0.05 vs control group) and group A (31.0%+/-9.1%) (P<0.01 vs control group). It is concluded that HA-preconditioning can effectively protect the myocardium.
Acidosis, Respiratory/*physiopathology ; Hypercapnia/*physiopathology ; Ischemic Preconditioning, Myocardial/*methods ; Myocardial Reperfusion Injury/*prevention & control ; Random Allocation

AIMTo study the effect of chronic hypoxic hypercapnia on expression of COX-2 mRNA in pulmonary arterioles.

METHODSSD rats were randomly divided into two groups: control group and hypoxic hypercapnic group. COX-2 mRNA was observed in pulmonary arterioles by the technique of in situ hybridization.

RESULTSmPAP, weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) and COX-2 mRNA in pulmonary arterioles were much higher in rats of hypoxic hypercapnic group than those of control group. Light microscopy showed that vessel smooth muscle cell hypertrophy and vessel cavity straightness were found in hypoxic hypercapnic group.

CONCLUSIONChanges of expressions of COX-2 mRNA may regulate hypoxic hypercapnic pulmonary hypertension.

Animals ; Cyclooxygenase 2 ; genetics ; metabolism ; Hypercapnia ; metabolism ; physiopathology ; Hypoxia ; metabolism ; physiopathology ; Male ; Pulmonary Artery ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo understand the influence of different sleep stages on respiratory regulation in normal people.

METHODSWe measured ventilation (VE) and occlusion pressure (P0.1) responses to hyperoxia hypercapnia (deltaVE/deltaPaCO2, deltaP0.1/deltaPaCO2) and isocapnic hypoxia (deltaVE/deltaSaO2 and deltaP0.1/deltaSaO2) in eleven non-snoring healthy people during wakefulness and during non-rapid eye movement (NREM) I + II, NREM III+IV, and rapid eye movement (REM) sleep stages.

RESULTSDuring NREM I + II and NREM III+IV, the normal subjects showed no significant decrease in P0.1, deltaP0.1/deltaSaO2 and deltaP0.1/deltaPaCO2 (P > 0.05), but deltaVE/ deltaSaO2 and deltaVE/ deltaPaCO2 decreased significantly (P < 0.05). During REM sleep, P0.1 maintained the level during wakefulness, but both hypoxic and hypercapnic responses decreased significantly (P < 0.05).

CONCLUSIONSSleep has significant influence on respiratory regulation in normal people. The respiratory drive (P0.1) in both NREM and REM sleep stages could maintain the awake level due to an effective compensation to the increase of upper airway resistance. The P0.1 responses to both hypoxia and hypercapnia decrease only in REM sleep stage, which is in consistent with the clinical phenomenon that sleep disordered breathing occurs in REM in normal people.

Adult ; Female ; Humans ; Hypercapnia ; physiopathology ; Hypoxia ; physiopathology ; Male ; Respiration ; Respiratory Physiological Phenomena ; Sleep Stages ; physiology ; Sleep, REM ; physiology ; Wakefulness ; physiology

OBJECTIVETo investigate the effect of chloride channel blocker--niflumic acid (NFA) on the pathological process of hypoxia hypercapnia-induced pulmonary vasoconstriction in rats.

METHODSWe used the model of hypoxia hypercapnia-induced pulmonary vasoconstriction rats, and divided the second, third branch pulmonary artery rings randomly into four groups (n = 8): control group (N group), hypoxia hypercapnia group (H group), DMSO incubation group (HD group), niflumic acid group (NFA group). Under acute hypoxia hypercapnia conditions, we observed the effects of the three stages of hypoxia hypercapnia-induced pulmonary vasoconstriction (HHPV) incubated by NFA in the second, third brach pulmonary artery rings. At the same time, the values of rings' tension changings were recorded via the method of hypoxia hypercapnia conditions reactivity. And investigated the effect of NFA to HHPV.

RESULTS(1) Under the hypoxia hypercapnia condition, we observed a biphasic pulmonary artery contractile (the phase I rapid contraction and vasodilation; the phase II sustained contraction) response in both the second and the third branch pulmonary artery rings compared with the control group (P < 0.05 , P < 0.01); (2) The second and third pulmonary artery rings incubated by NFA which phase II persistent vasoconstriction were significantly attenuated compared with the H group (P < 0.05 , P < 0.01).

CONCLUSIONThe blocker of the chloride channels attenuates the second and third branch pulmonary artery rings constriction in rat, especially the phase II persistent vasoconstriction, so then have an antagonistic effect on HHPV.

Animals ; Chloride Channels ; antagonists & inhibitors ; Hypercapnia ; physiopathology ; Hypoxia ; physiopathology ; Niflumic Acid ; pharmacology ; Pulmonary Artery ; physiopathology ; Pulmonary Circulation ; Rats ; Vasoconstriction ; drug effects

AIMTo study the effect of chimonin on chronic hypoxia and hypercapnic pulmonary hypertension and to explore its mechanism.

METHODSSD rats were randomly divided into normal control group (A), hypoxic hypercapnic group(B), hypoxic hypercapnia + chimonin group (C). HO-1 and HO-1 mRNA was observed in pulmonary arterioles of rats by the technique of immunohistochemistry and in situ hybridization.

RESULTS(1) mPAP was significantly higher in rats of B group than that of A and C group. Differences of mCAP were not significant in three groups. (2) Blood CO concentration was significantly higher in rats of B group than that of A group, it was significantly higher in rats of C group than that of B group. (3) Light microscopy showed that WA/TA (vessel wall area/total area), SMC (the density of medial smooth muscle cell) and PAMT (the thickness of medial smooth cell layer) were significantly higher in rats of B group than those of A and C group. (4) Electron microscopy showed proliferation of medial smooth muscle cells and collagenous fibers of pulmonary arterioles in rats of B group, and chimonin could reverse the changes mentioned above. (5) HO-1 and HO-1 mRNA in pulmonary arterioles was significantly higher in rats of B group than that of A group, they were significantly higher in rats of C group than that of B group.

CONCLUSIONChimonin can inhibit hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling by further increasing the expression of HO-1 mRNA.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Heme Oxygenase (Decyclizing) ; metabolism ; Hypercapnia ; metabolism ; pathology ; physiopathology ; Hypertension, Pulmonary ; metabolism ; pathology ; physiopathology ; Hypoxia ; metabolism ; pathology ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley

AIMTo investigate the dynamic changes and functions of urotensin II (U lI) receptor (UT) in pulmonary arteries of rats chronically exposed to hypoxia-hypercapnia.

METHODSIn rats with hypoxia-hypercapnia at 1, 2 and 4 weeks U II receptor binding of pulmonary arteries sarcolemma was determined by radioligand assay. U II mRNA and UTmRNA in various grades of pulmonary arterioles were measured by in situ hybridization.

RESULTS(1) Mean pulmonary pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum (RV/LV + S) of 1-week group were higher than those of normal control (NC) group by 26.2% and 21.6% (P < 0.01), respectively, and 2-week group higher than 1-week group by 22.5% and 14.1% (respectively, P < 0.01). However, no significant changes were found between 4-week and 2-week group. (2) U Il receptor (Bmax) of 1-week group was higher than NC group by 38.8%, 2-week group higher than 1-week group by 23.2%, and 4-week group increased 7.3% compared with 2-week group (respectively, P < 0.01). The UT changes were time-dependent, while the affinity to U II (Kd) was no different among each group. (3) UII mRNA in each grade of pulmonary arterioles of 2-week group and 4-week group were higher than NC group (respectively, P < 0.01), and those of 2-week group were higher than 1-week group by 5.9% (P > 0.05), 16.4% and 9.1% (respectively, P < 0.01), while no differences existed between 2-week group and 4-week group. (4) UT mRNA in each grade of pulmonary arterioles of all hypoxia-hypercapnia groups was higher than NC group (respectively, P < 0.01), and those of two abaxial grade vessels in 1-week group were the highest. No differences existed between 2-week group and 4-week group. (5) The pulmonary vessels remodeling were time-dependently aggravated by hypoxia-hypercapnia.

CONCLUSIONThe dynamic changes of UT in pulmonary arterioles might have important contribution to the development of pulmonary hypertension and pulmonary arteriole remodeling induced by chronic hypoxia-hypercapnia in rats.

Animals ; Arterioles ; metabolism ; physiopathology ; Hypercapnia ; metabolism ; Hypertension, Pulmonary ; metabolism ; physiopathology ; Hypoxia ; metabolism ; Male ; Pulmonary Artery ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; metabolism

AIMTo study the effect of aspirin on chronic hypoxia and hypercapnic pulmonary hypertension.

METHODSSD rats were randomly divided into normal control group (A), hypoxic hypercapnic group (B), hypoxic hypercapnia + aspirin group (C). The concentration of TXB2 and 6-keto-PGF1alpha in plasma and in lung were detected by the technique of radioimmunology.

RESULTS(1) mPAP was significantly higher in B group than those of A and C group. Differences of mCAP were not significant in three groups. (2) Light microscopy showed that WA/TA (vessel wall area/total area) and PAMT (the thickness of medial smooth cell layer) were significantly higher in B group than those of A and C group. (3) The concentration of TXB2 and 6-keto-PGF1alpha in plasma and lung as well as the ratio of TXB2/6-keto-PGF1alpha were significantly higher in rats of B group than those of A and C group.

CONCLUSIONAspirin may inhibit hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling.

6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Aspirin ; pharmacology ; Carotid Arteries ; pathology ; physiopathology ; Epoprostenol ; metabolism ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; metabolism ; pathology ; physiopathology ; Hypoxia ; physiopathology ; Male ; Pulmonary Artery ; pathology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Thromboxane A2 ; metabolism

A reduction in diaphragm mobility has been identified in patients with chronic obstructive pulmonary disease (COPD) and has been associated with a decline in pulmonary function parameters. However, little information exists regarding the potential role of diaphragm mobility on hypercapnia in COPD. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. The purpose of the present study was to investigate the relationship between diaphragm mobility and pulmonary function parameters, as well as that between arterial blood gas values and diaphragm mobility, in COPD patients. Thirty seven COPD patients were recruited for pulmonary function test, arterial blood gas analysis and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein. There were significant negative correlations between diaphragmatic mobility and PaCO2 (r = -0.373, P = 0.030). Diaphragmatic mobility correlated with airway obstruction (FEV1, r = 0.415, P = 0.011) and with ventilatory capacity (FVC, r = 0.302, P = 0.029; MVV, r = 0.481, P = 0.003). Diaphragmatic mobility also correlated significantly with pulmonary hyperinflation. No relationship was observed between diaphragm mobility and PaO2 (r = -0.028, P = 0.873). These findings support a possibility that the reduction in diaphragm mobility relates to hypercapnia in COPD patients.
Aged ; Airway Resistance/physiology ; Carbon Dioxide/blood/physiology ; Diaphragm/physiopathology/*ultrasonography ; Female ; Humans ; Hypercapnia/complications/*physiopathology ; Male ; Middle Aged ; Portal Vein ; Pulmonary Disease, Chronic Obstructive/complications/*physiopathology/ultrasonography ; Pulmonary Gas Exchange ; Respiratory Muscles/physiopathology

AIMTo study the expression and effect of TLR4 and NFkappaB protein in hippocampus neuron in rats exposed to chronic hypoxic hypercapnia.

METHODSThe disorder of learning-memory in pulmonary hypertension rat model was reproduced by chronic hypoxic hypercapnia. Thirty rats were randomly divided into three groups: normal control group, hypoxic hypercapnia 2-week and 4-week group. The number of apoptosis neurons in hippocampus CA1/3 was counted by TUNEL method. Activity of TLR4 and NFkappaB in hippocampus CA1/3 was detected by using SP immunocytochemical technique.

RESULTSThe expression of TLR4 protein in hippocampus CA1/3 in group 2HH( CA1: 0.1275 +/- 0.0242, CA3: 0.1156 +/- 0.0376) and 4HH (CA1: 0.1522 +/- 0.0187, CA3: 0.1427 +/- 0.0453) were significantly higher than those in the NC group (P < 0.05, P < 0.01). The positive expression of NFkappaB were showed in cell nucleus in group 2HH (CA1: 0.1326 +/- 0.0324, CA3: 0.1301 +/- 0.0112) and group 4HH (CA1: 0.1612 +/- 0.0428, CA3: 0.1578 +/- 0.0365), and significantly higher than those in the NC group (P < 0.05, P < 0.01). The apoptosis of neural cells in hippocampus CA1/3 gradually increased with the time of exposure, and reached peak at 4 weeks (P < 0.01 vs NC group).

CONCLUSIONThe activation of TLR4 and NFkappaB may play an important role in the apoptosis of hippocampus neural cells in rat exposed to chronic hypoxic hypercapnia.

Animals ; Apoptosis ; Hippocampus ; metabolism ; pathology ; physiopathology ; Hypercapnia ; metabolism ; physiopathology ; Hypertension, Pulmonary ; metabolism ; physiopathology ; Hypoxia ; metabolism ; physiopathology ; Male ; NF-kappa B ; metabolism ; Neurons ; metabolism ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4 ; metabolism

OBJECTIVETo explore the effects of safflower injection on prevention and treatment of hypoxic pulmonary hypertension and clarify the function of the endoplasmic reticulum stress apoptosis pathway during the process.

METHODSThirty male SD rats were randomly grouped as normal control group, hypoxia-hypercapnia group and hypoxia+safflower group. The latter two groups were put in the cabin with oxygen concentration ranged from 9% to 11% and carbon dioxide concentration from 5% to 6%. The pulmonary artery pressure and the index of right ventricular hypertrophy were determined after hypoxia exposure (8 h/dx28 d). Changes in morphology of lung tissue were observed by electron microscopy. To explore the possible mechanisms, we also detected apoptosis and apoptosis-related genes/proteins in lung tissue by TUNEL reactivity and PCR and Western blot.

RESULTSCompared with the normal control group, pulmonary artery pressure and the index of right ventricular hypertrophy in hypoxia group were 45% and 33.4% higher, respectively. Tiny blood vessel wall of lungs was thickened and edema, and proliferation of collagen fibers was obvious under the electron microscope. TUNEL staining of apoptotic cells in lung tissues showed more high brightness green fluorescence (+-++), but less green fluorescence showed in the pulmonary vascular smooth muscle cell layer, and apoptosis index (AI) value was 150% higher; gene and protein expression levels of endoplasmic reticulum stress pathway were increased. Compared with hypoxia-hypercapnia group, pulmonary artery pressure and the index of right ventricular hypertrophy in the hypoxia+safflower group were 18% and 15.6% lower, respectively; collagen fibers were decreased, and smooth muscle cells and epithelial cells were got apoptotic-like changes under the electron microscope. TUNEL staining of apoptotic cells in lung tissues showed brighter green fluorescence (++-+++); the high brightness green fluorescence showed in pulmonary vascular smooth muscle cell layer, and apoptotic index (Al) value was 40% higher; gene and protein expressions of endoplasmic reticulum stress pathway were significantly upregulated.

CONCLUSIONOur findings demonstrate that safflower injection could activate endoplasmic reticulum stress-induced apoptosis and especially promote apoptosis in pulmonary vascular smooth muscle cells.

Animals ; Apoptosis ; drug effects ; Carthamus tinctorius ; chemistry ; Endoplasmic Reticulum Stress ; drug effects ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Hypoxia ; physiopathology ; Lung ; cytology ; physiopathology ; Male ; Myocytes, Smooth Muscle ; drug effects ; Rats ; Rats, Sprague-Dawley