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Biomedical subjects

M Duvelleroy

Publications and source records attributed to M Duvelleroy.

At least 19 recordsLinked to original sources

Amplification by phenylephrine and serotonin of coronary vasoconstriction induced by a high arterial blood oxygen tension.

OBJECTIVE: The aim was to investigate the effect on the coronary network of the interaction between high arterial blood oxygen tension (PaO2) and stimulation by the alpha adrenergic agonist phenylephrine or by serotonin in an isolated, blood perfused rabbit heart preparation. METHODS: Fresh pig erythrocytes in Krebs-Henseleit buffer were oxygenated to reach normal PaO2 [19.4(SEM 0.7) kPa] or high PaO2 [53.2(5.5) kPa]. Blood oxygen content was kept constant despite the higher PaO2, by slightly reducing the haemoglobin concentration from 9.3(0.2) to 8.8(0.2) g.100 ml-1 (p < 0.01). Coronary blood flow was kept constant throughout the study, so that the oxygen supply would not vary with the rise in PaO2. Increases in coronary resistance were therefore reflected by increased perfusion pressure. RESULTS: Switching from normal to high PaO2 induced coronary vasoconstriction, reflected by enhanced perfusion pressure of +21(5)%. After pretreatment with the alpha adrenergic agonist phenylephrine, perfusion of a high PaO2 solution increased coronary resistance by +35(7)% (p < 0.05), a value significantly higher than that found without phenylephrine. Oxygen consumption and myocardial performance did not vary throughout the study. To determine whether this amplification of the response was specifically due to alpha agonist stimulation or could be observed with other vasoactive agents, we applied the same protocol using serotonin instead of phenylephrine. Here again, coronary vasoconstriction rose in response to high PaO2 after serotonin infusion [+25(5)% versus +59(10)%]. CONCLUSIONS: The response of the coronary network to high PaO2 is amplified by pretreatment with the alpha adrenergic agonist phenylephrine or with serotonin, regardless of any changes in metabolic status.

Animals

Independent role of arterial O2 tension in local control of coronary blood flow.

The aim of this study of a blood-perfused isolated rabbit heart preparation was to differentiate the effects on coronary resistance of large changes in arterial O2 tension (arterial PO2 = 45-400 Torr) from the effects of variations in arterial O2 content or myocardial O2 delivery. Standard stored human blood was resuspended in Krebs-Henseleit buffer and was oxygenated to obtain normal PO2, high PO2, and low PO2. Hemoglobin concentrations were adjusted to obtain the same arterial O2 content (CaO2) for the three PO2s. In a first set of experiments, in which coronary blood flow (CBF) was free and adapted to a constant perfusion pressure, switching from control [138 +/- 17 (SE) Torr] to high PO2 blood (380 +/- 27 Torr) induced a significant decrease in CBF and myocardial O2 consumption (MVO2). Switching from control (125 +/- 3 Torr) to low PO2 blood (49 +/- 5 Torr) induced a significant increase in CBF and MVO2. In a second set of experiments, the switch from control (159 +/- 5 Torr) to high PO2 (389 +/- 32 Torr) was performed in a preparation in which CBF and consequently O2 delivery were constant. Under these conditions, the increase in perfusion pressure demonstrated that PO2 affected coronary resistance, even though the O2 delivery was constant. No significant change in myocardial performance was observed in any of these experimental procedures. These results show that arterial PO2 may affect coronary blood flow regulation independently of any mediation by the autonomic nervous system and of any associated changes in O2 content or O2 delivery.

Animals

[Capillary permeability. Fundamental problems and modeling].

This brief paper reviewed some of the most currently used mathematical models in the field of transcapillary exchange. Mathematical formalism was reduced to its simplest expression and a special emphasis was given to the principles and simplifying hypotheses of each kind of model. We described the simplified formulation of capillary-tissue exchange used for the multiple indicator methods and its generalization using the equations derived from thermodynamics. "Black box" models taking into account the complexity of microcirculatory hemodynamics were also presented. We stressed the importance of interactions between adjacent portions of tissue and the potential influence of tissue-lymphatic exchange in the transcapillary exchange phenomenon.

Capillary Permeability

Enzyme release and mitochondrial activity in reoxygenated cardiac muscle: relationship with oxygen-induced lipid peroxidation.

The aim of this work was to precisely determine the sites of the peroxidative action on unsatured lipids by oxygen-derived free radicals and the lytic cell damage on reoxygenated perfused hearts. The cellular load of lipid peroxidation products (malondialdehyde) during the reoxygenation was dependent on PO2. This unfavorable biochemical response was linked to creatine kinase leakage, alteration of coronary flow and mitochondrial injury. When an enzymatic (superoxide dismutase, 290 IU/minute) or tripeptide scavenger of oxygen radicals (reduced glutathione, 0.5 mmol/l) was administered at the end of hypoxia and during reoxygenation, the abnormal intolerance of hypoxic heart to molecular oxygen was significantly weakened; the load of lipid peroxides load, enzyme release, and vascular alteration were all reduced. Moreover, mitochondrial activity was enhanced and the oxygen-induced uncoupling of mitochondrial remained limited: both the respiratory control ratio (RCR) and the ADP/O ratio were higher than in control reoxygenated hearts. The inhibition by rotenone (100 mumol/l) of reoxidation of electron chain transfer during oxygen readmission also reduced the unfavorable cardiac accumulation of lipid peroxidation products and the release of creatine kinase. These data demonstrate that in the oxygen paradox, the peroxidative attack on lipids plays an important role in inducing alterations of sarcolemmal permeability and mitochondrial activity. An uncontrolled reactivation of oxidative function of mitochondria during reoxygenation enhances the synthesis of oxygen-derived free radicals and triggers the peroxidation of cardiac lipids resulting in irreversible injury to cellular and intracellular membranes.

Aerobiosis

Effects of changes in systemic hematocrit on the microcirculation in rat cremaster muscle.

This work aimed to establish how changes in systemic hematocrit ranging from 0.33 to 0.55, affect capillary red cell velocity (measured by the dual-slit correlator method), capillary volume flow, capillary density and arteriolar diameter. These microcirculatory parameters were determined on rat cremaster muscles surgically prepared for in vivo visualization and bathed with a modified Krebs-Henseleit solution. A significant rise in mean red cell velocity and mean volume flow rate in capillaries was found after hemodilution, and a significant drop after hemoconcentration. A large reduction in the number of capillaries with low flow rate was shown after hemodilution; an opposite effect was found after hemoconcentration. The number of capillaries containing erythrocytes did not change significantly in either state. However after hemoconcentration, the number of capillaries containing stationary erythrocytes was significantly larger. Arteriolar diameter did not alter significantly after either hemodilution or hemoconcentration. We conclude that, in the cremaster muscle, hematocrit is an important rheological factor that determines capillary flows without involving arteriolar regulation.

Animals

Transient responses of coronary flow in the blood-perfused isolated rat heart submitted to changes in oxygen content.

This study examines the transient response of coronary blood flow to acute changes in O2 content at normal and high arterial PO2 (Pa, O2) in the blood-perfused, working isolated rat heart. The perfusion system used in this study presents the following advantages: it eliminates the gas/blood interface, includes a peripheral circulation for control of pre-load and after-load, and allows for rapid change of perfusates and continuous recording of aortic and coronary blood flow. With this system the isolated rat heart is capable of stable haemodynamic performance for periods in excess of 4 h. A sudden decrease in O2 content from 0.147 to 0.067 11(-11) at constant Pa,O2 (133 mmHg; n = 15) was associated with a marked increase in coronary blood flow (QCOR). This increase showed two phases: a rapid phase which reached 200% of the control value in 20 s, followed by a slow phase (235% in 90 s). When the same decrease in O2 content (0.135 to 0.057 11(-1] was associated with an increase in Pa, O2 (n = 22; 143 to 412 mmHg), the response of QCOR was limited both in amplitude (175% rather than 235%) and in rate of onset (response time of 15.6 instead of 9.2 s). These results are consistent with the majority of currently popular hypotheses regarding control of QCOR including the adenosine hypothesis and that of vessel wall PO2 being a direct mediator. The time course of changes in coronary vascular resistance, with a Pa, O2-dependent rapid phase, suggests the simultaneous function of the two mechanisms.

Animals

Hemodynamic and metabolic responses of the working heart in relation to the oxygen carrying capacity of the perfusion medium.

Hemodynamic and metabolic adaptations of isolated working heart perfused alternatively with normal or low oxygen carrying capacity medium were studied in an experimental model. A step change in arterial oxygen content (1.75 to 15.3 ml O2/100 ml) was followed by a decrease in coronary flow, an increase in aortic flow, external work, myocardial oxygen consumption and efficiency, respectively. Metabolic investigations (steady state values) showed the activities of both glycolysis and the Krebs cycle to increase with the oxygen carrying capacity of the perfusion medium. Within the limits of these aerobic conditions, most of the cardiac changes were reversible. The use of reconstituted blood provides physiological conditions of oxygenation, allows a dynamic equilibrium between oxygen supply and oxygen requirements and maintains a near physiological regulation between cardiac dynamic and metabolic functions. These conclusions stress the importance of optimal O2 carrying capacity of perfusion medium in metabolic studies on isolated working heart.

Aerobiosis

Effects of changes in hematocrit on red cell flows at capillary bifurcations.

A theoretical study was developed to evaluate effects of changes in hematocrit on red cell flow partitioning at narrow capillary bifurcations of unequal diameters. Non-Newtonian blood viscosity and non-linear relationships between blood and red cell flows at capillary bifurcations are taken into account. Results suggest that heterogeneity of diameters is a determinant of red cell and blood flows heterogeneity not only due to its influence on geometrical resistance but also as a result of its influence on capillary viscosity. Lowering hematocrit reduces differences in viscosities between the two branches. Then more homogeneous red cell flows are induced. Considering three possible relationships for entering blood flow vs. entering discharge hematocrit, the present study stresses that changes in red cell flow for individual capillaries are not parallel to changes in entering red cell flow. Therefore discussion on effects of hemodilution have to take into account not only red cell flow or oxygen arriving to an organ, but also changes in distribution of capillary flows induced by rheological changes due to lower hematocrit.

Blood Viscosity

Effects of different hematocrits on the isolated working rabbit heart reperfused after ischemia.

Increased blood viscosity has frequently been related to ischemic heart diseases. Since blood viscosity depends mainly on hematocrit (HTC), the effects of hemodilution have been studied on the isolated working rabbit heart perfused initially with 50% HCT, submitted to global ischemia for 10 min and reperfused with two different amounts of HCT: 50 and 30%. When the reperfusion was carried out with 50% HCT (N = 10) aortic flow failed to be restored in 4 hearts. When the reperfusion was performed with 30% HCT, all hearts recovered rapidly, reaching the preischemic cardiac output 20 min later. The ratio between cardiac output (C.O.) 20 min after reperfusion and C.O. before ischemia was 0.30 for the high hematocrit group (H.H.) as compared to 0.89 for the low hematocrit group (L.H.). The ratio of the coronary flow (C.F.) 20 min after reperfusion and that of C.F. before ischemia was 0.83 for the H.H. group as compared to 1.30 for the L.H. group. After reperfusion the myocardial oxygen consumption was not significantly different between both groups. The better recovery of heart performance after ischemia when the hearts were reperfused with a 30% HCT suggests that hemodilution results in a better oxygen distribution.

Animals

[Transcapillary fluid exchanges. A program in Basic].

Transcapillary fluid exchanges are analysed with the Wiederhielm's model programmed in this study in Basic language. The physiological variable which are taken in account are: arterial and venous capillary pressures, interstitial pressure and the colloid osmotic pressure of plasma and tissue proteins. This model shows the relationship between filtration, reabsorption, plasma leakage and the lymph flow. Edema resulting from venous and lymphatic obstruction or from a decrease in plasma oncotic pressure are simulated.

Blood Pressure