Hypoxia, leukocytes, and the pulmonary circulation.

Data are rapidly accumulating in support of the idea that circulating monocytes and/or mononuclear fibrocytes are recruited to the pulmonary circulation of chronically hypoxic animals and that these cells play an important role in the pulmonary hypertensive process. Hypoxic induction of monocyte chemoattractant protein-1, stromal cell-derived factor-1, vascular endothelial growth factor-A, endothelin-1, and tumor growth factor-beta(1) in pulmonary vessel wall cells, either directly or indirectly via signals from hypoxic lung epithelial cells, may be a critical first step in the recruitment of circulating leukocytes to the pulmonary circulation. In addition, hypoxic stress appears to induce release of increased numbers of monocytic progenitor cells from the bone marrow, and these cells may have upregulated expression of receptors for the chemokines produced by the lung circulation, which thus facilitates their specific recruitment to the pulmonary site. Once present, macrophages/fibrocytes may exert paracrine effects on resident pulmonary vessel wall cells stimulating proliferation, phenotypic modulation, and migration of resident fibroblasts and smooth muscle cells. They may also contribute directly to the remodeling process through increased production of collagen and/or differentiation into myofibroblasts. In addition, they could play a critical role in initiating and/or supporting neovascularization of the pulmonary artery vasa vasorum. The expanded vasa network may then act as a conduit for further delivery of circulating mononuclear cells to the pulmonary arterial wall, creating a feedforward loop of pathological remodeling. Future studies will need to determine the mechanisms that selectively induce leukocyte/fibrocyte recruitment to the lung circulation under hypoxic conditions, their direct role in the remodeling process via production of extracellular matrix and/or differentiation into myofibroblasts, their impact on the phenotype of resident smooth muscle cells and adventitial fibroblasts, and their role in the neovascularization observed in hypoxic pulmonary hypertension.     

Stability,controllability and observability of arterial circulation

Stability, controllability and observability factors of the arterial circulatory system are determined with respect to a non-linearised model of the circulation process. It is found that the circulatory system is stable as well as completely controllable and also observable.     

Hyperventilation, alkalosis, prostaglandins, and pulmonary circulation of the newborn

This study was designed to determine whether the effects of hyperventilation on the pulmonary circulation of the newborn lamb were 1) due to mechanical factors or to respiratory alkalosis; and 2) mediated by prostaglandins. Six control lambs were studied during normal ventilation and during hyperventilation with, and without, decreased carbon dioxide (CO2). Five lambs were given indomethacin and studied similarly. In control lambs, hyperventilation with decreased CO2 decreased pulmonary arterial pressure from 26 +/- 2.2 to 18 +/- 1.0 (SE) Torr (P less than or equal to 0.005) and pulmonary vascular resistance from 0.099 +/- 0.035 to 0.070 +/- 0.011 Torr X kg-1 X min-1 (P less than or equal to 0.015). Hyperventilation with normal CO2 did not affect the pulmonary circulation. Hyperventilation with decreased CO2 increased pulmonary arterial concentrations of 6-ketoprostaglandin F1 alpha, a major metabolite of prostacyclin, in control lambs but not in the indomethacin-treated lambs. However, it affected the pulmonary circulation of the control- and indomethacin-treated lambs similarly. In conclusion, hyperventilation affected the pulmonary circulation by respiratory alkalosis not by mechanical factors and prostaglandins did not mediate its effects.     

Hemodynamics, cerebral circulation, and oxygen saturation in Cheyne-Stokes respiration

Franklin, Karl A., Erik Sandström, GöranJohansson, and Eva M. Bålfors. Hemodynamics, cerebralcirculation, and oxygen saturation in Cheyne-Stokes respiration.J. Appl. Physiol. 83(4): 1184-1191, 1997.Because cardiovascular disorders and stroke may induceCheyne-Stokes respiration, our purpose was to study the interactionamong cerebral activity, cerebral circulation, blood pressure, andblood gases during Cheyne-Stokes respiration. Ten patients with heartfailure or a previous stroke were investigated during Cheyne-Stokesrespiration with recordings of daytime polysomnography, cerebral bloodflow velocity, intra-arterial blood pressure, and intra-arterial oxygensaturation with and without oxygen administration. There weresimultaneous changes in wakefulness, cerebral blood flow velocity, andrespiration with accompanying changes in blood pressure and heart rate~10 s later. Cerebral blood flow velocity, blood pressure, and heartrate had a minimum occurrence in apnea and a maximum occurrence duringhyperpnea. The apnea-induced oxygen desaturations were diminishedduring oxygen administration, but the hemodynamic alterationspersisted. Oxygen desaturations were more severe and occurred earlieraccording to intra-arterial measurements than with finger oximetry. Itis not possible to explain Cheyne-Stokes respiration by alterations inblood gases and circulatory time alone. Cheyne-Stokes respiration maybe characterized as a state of phase-linked cyclic changes in cerebral,respiratory, and cardiovascular functions probably generated byvariations in central nervous activity.

     

Vitamins Q and E, extracorporal circulation and hemolysis

Whole blood vitamin Q (ubiquinone), plasma vitamins Q and E(alpha-(a-)tocopherol) and free cholesterol (FC) were studied before(control or base-line value, sample I) and during open chest surgery andextracorporal circulation (samples II-IV) in 10 male IHD patients. Identityexisted between control whole blood and plasma ubiquinone. During surgery anincreased discrepancy with lower plasma vitamin Q levels were seen. Controlplasma vitamins Q, E and FC averaged 0.88 ± 0.16 (SE), 12.1 ±2.2 mg × 1-1 and 0.75 ± 0.15 g × 1-1. Corresponding molarvalues were 1.02 ± 0.17, 28.1 ± 5.1 µmol × 1-1 and1.94 ± 0.74 mmol × 1-1. Vitamin Q and E decreased continuouslyand averaged 0.64 mg × 1-1 in sample IV (0.74 µmol × 1-1,p < 0.001) and 9.4 mg × 1-1 in sample III (21.8 µmol ×1-1, p < 0.001). Hemolysis in all sample IV vials, ruined all vitamin Edeterminations. When normalized for FC (NQ and NE), decreases were found tobe 17 (IV) and 12% (III), respectively. Large interindividual variationsexisted. High control NQ and NE values allowed a larger antioxidant vitamindepletion. High NQ seemed also to be a prerequisite for NE depletion. Inaddition, signs indicated an active liver vitamin Q release for patientsrich in control antioxidant values. It was suggested that the antioxidantvitamin depletion did not prevent from radical trauma to membrane structurallipids (especially omega-3 fatty acids or vitamin F1), less membranefluidity, erythrocyte fragility and hemolysis.