RESUMO
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.
Assuntos
Vasos Coronários/efeitos dos fármacos , Hiperóxia/fisiopatologia , Fenilefrina/farmacologia , Serotonina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Vasos Coronários/fisiopatologia , Equipamentos e Provisões , Masculino , Perfusão , Coelhos , Estimulação Química , SuínosRESUMO
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.
Assuntos
Creatina Quinase/metabolismo , Coração/efeitos dos fármacos , Peroxidação de Lipídeos , Mitocôndrias Cardíacas/metabolismo , Oxigênio/farmacologia , Aerobiose , Anaerobiose , Animais , Glutationa/análogos & derivados , Glutationa/farmacologia , Dissulfeto de Glutationa , Técnicas In Vitro , Masculino , Malondialdeído/metabolismo , Miocárdio/metabolismo , Fosforilação Oxidativa , Consumo de Oxigênio , Ratos , Ratos Endogâmicos , Superóxido Dismutase/farmacologiaRESUMO
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.
Assuntos
Circulação Coronária , Coração/fisiologia , Consumo de Oxigênio , Oxigênio/sangue , Aerobiose , Animais , Dióxido de Carbono/sangue , Glicogênio/metabolismo , Hematócrito , Hemodinâmica , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Masculino , Miocárdio/metabolismo , Pressão Parcial , Perfusão , Ratos , Ratos EndogâmicosRESUMO
We studied the effects of moderate changes in red blood cell RBC aggregation on blood flow in the vasodilated vascular bed of an isolated rat heart. We compared a non-aggregating RBC suspension (in Krebs-albumin medium) with RBC suspensions in 1% and 2% Dextran 70 (MW 70000), exhibiting two different degrees of moderate aggregation. Degrees of aggregation were precisely estimated by in vitro laser aggregometry. Each heart was perfused by the non-aggregating RBC suspension and by one aggregating RBC suspensions. Blood flow was measured in a range of perfusion pressure from 40 to 80 mm Hg. For the three RBC suspensions, linear pressure/flow relationships were found. From the comparison between the pressure/flow relationships obtained with Krebs albumin medium and either 1% or 2% Dextran, it was possible to compare in vivo the contribution of RBC to the viscosity (i.e., the relative apparent viscosity) in the 2 aggregating RBC suspensions with that of the non-aggregating RBC suspension. The contribution of RBC to the viscosity was found to be 20% to 25% lower in the 1% RBC suspension than in the non-aggregating RBC suspension. With 2% Dextran which induced a higher degree of aggregation no differences were found between the relative apparent viscosities of the aggregating and the non-aggregating suspension. From the comparison between RBC in 1% Dextran and Krebs-albumin, we concluded that in vivo a moderate RBC aggregation reduces viscous resistance due to the presence of blood in a vascular network. Since no more effect of RBC aggregation per se was found when the degree of aggregation was higher (with RBC in 2% Dextran), this suggests that, in this case, aggregation induces opposite effects along the myocardial vascular network which cancel each other out, thus inducing a nil net balance.
Assuntos
Viscosidade Sanguínea/fisiologia , Vasos Coronários/fisiologia , Agregação Eritrocítica/fisiologia , Animais , Dextranos , Técnicas In Vitro , Soluções Isotônicas , Masculino , Modelos Biológicos , Perfusão , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/fisiologia , ReologiaRESUMO
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.
Assuntos
Permeabilidade Capilar , Modelos Cardiovasculares , HumanosRESUMO
After an analyitical study of mathematical models connected with osmotic or volemic regulations, and the mention of its contribution to the therapeutic act, the authors approach the stimulation, by the mean of an analogical computer, of the complete and non-linear model which associates both types of regulation. So it is possible to attempt to determine the level of adrenal and vasopressin actions according to: 1 degree the sum of the agonistic effects and the difference of their antagonistic effects; 2 degrees the perturbations brought to the system; 3 degrees the parametric values of the model. Theoretical and empirical curves seem to be in favour of such a formulation.
Assuntos
Computadores Analógicos , Modelos Biológicos , Sistema Hipófise-Suprarrenal/fisiologia , Córtex Suprarrenal/fisiologia , Corticosteroides/metabolismo , Homeostase , Neuro-Hipófise/fisiologia , Vasopressinas/metabolismoRESUMO
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.
Assuntos
Permeabilidade Capilar , Modelos Cardiovasculares , Pressão Sanguínea , Proteínas Sanguíneas/análise , Edema/fisiopatologia , Humanos , Pressão Hidrostática , Microcomputadores , SoftwareAssuntos
Coração/efeitos dos fármacos , Oxigênio/farmacologia , Animais , Glutationa/farmacologia , Hipóxia/metabolismo , Técnicas In Vitro , Peróxidos Lipídicos/biossíntese , Masculino , Mitocôndrias Cardíacas/metabolismo , Miocárdio/metabolismo , Consumo de Oxigênio , Perfusão , Ratos , Ratos Endogâmicos , Superóxido Dismutase/farmacologiaAssuntos
Miocárdio/metabolismo , Oxigênio/toxicidade , Animais , Catalase/farmacologia , Circulação Coronária , Creatina Quinase/metabolismo , Metabolismo Energético/efeitos dos fármacos , Radicais Livres , Glutationa/farmacologia , Hipóxia/metabolismo , Lactatos/metabolismo , Ácido Láctico , Masculino , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Superóxido Dismutase/farmacologia , Vitamina E/farmacologiaAssuntos
Capilares/fisiologia , Hemodiluição , Edema/fisiopatologia , Edema/terapia , Hematócrito , HumanosAssuntos
Substitutos Sanguíneos/administração & dosagem , Hemodiluição , Substitutos Sanguíneos/farmacologia , Transfusão de Sangue , Viscosidade Sanguínea , Débito Cardíaco/efeitos dos fármacos , Economia Hospitalar , Hematócrito , Humanos , Oxigênio/fisiologia , Reologia , Resistência Vascular/efeitos dos fármacosRESUMO
Written for pedagogic purpose, this paper describes a Basic program of the alveolar diffusion and shunt effect, for personal computer. Equations and algorythms are described first. Then the program is explained in great detail in order to be easily implemented. Nine typical situations are stimulated and discussed.
Assuntos
Computadores , Microcomputadores , Oxigênio/fisiologia , Capacidade de Difusão Pulmonar , Humanos , Modelos BiológicosRESUMO
The risk of contracting certain disorders following a blood transfusion is currently becoming worrisome not only for physicians who are aware of this problem, but also for patients who, with increased media attention on AIDS, are more afraid of this potential risk than of the surgical or anesthetic risks. In fact, hepatitis constitute the major risk involved in homologous transfusion since some 60,000 cases are reported each year in France. Prevention of transmission of disease by blood transfusion is based on decreasing homologous transfusions and especially by saving blood. Indeed, when surgery is planned, units of the patient's blood can be obtained in the weeks prior to it to be used during the operation or the immediate follow-up period. In case of emergency surgery, blood is collected preoperatively making it possible to obtain hemodilution during surgery and an autotransfusion if necessary at the conclusion of the procedure. Finally, there are methods to recover blood at the actual site of the surgical procedure.
Assuntos
Transfusão de Sangue Autóloga , Síndrome da Imunodeficiência Adquirida/transmissão , Hemodiluição , Hepatite/transmissão , Humanos , Período IntraoperatórioRESUMO
The transcapillary exchanges of liquids between vascular and interstitial sections can be described with the help of a mathematical model describing variation in filtration, reabsorption, plasmatic flux and lymphatic flow in relation to the different active pressures, that is to say the arteriolar and venular pressures, the oncotic pressures of the proteins, and interstitial pressure. Also taking into account the modifications of the volemia in relation to blood loss and perfusions, modifications of the essential haemodynamic variables and diuresis, it is possible to reproduce various situations following the reduction in venous or lymphatic return, hypovolemia, and hypoproteinemia. The advantages in these simulations is demonstrated by the example of a blood depletion, compensated or otherwise, as follows: volemia, proteinemia, lymphatic flow. These simulations permit us to follow the sequence of events accompanying haemodilution, and to assess the qualities of a plasmatic substitute: oncotic strength, demi-vie, effect on the extravascular mobilisation of proteins. They also provide a reflexion tool permitting a better comprehension of transcapillary exchanges and the optimisation of strategies of vascular refill.
Assuntos
Líquidos Corporais/fisiologia , Capilares/fisiologia , Espaço Extracelular/fisiologia , Hemodiluição , Humanos , Modelos Biológicos , Volume PlasmáticoRESUMO
The exchange between capillaries and the interstitial spaces are analysed using Wiederhielm's technique, and programmed in Basic language. The physiological variants represented are the hydrostatic pressures: arteriolar, venular and interstitial, and the oncotic, plasmatic and interstitial pressures. This technique enables us to analyses the relations between filtration, reabsorption. Plasmatic protein leaks, and lymphatic flux. It also enables us to simulate oedema of venous obstruction or lymphatic oedema, or protein deficiency oedema.
Assuntos
Permeabilidade Capilar , Modelos Biológicos , Arteríolas/fisiologia , Edema/complicações , Edema/fisiopatologia , Espaço Extracelular/fisiologia , Humanos , Pressão Hidrostática , Hipertensão/fisiopatologia , Hipoproteinemia/complicações , Hipoproteinemia/fisiopatologia , Inflamação/fisiopatologia , Linfedema/fisiopatologia , Veias/fisiopatologia , Vênulas/fisiologiaRESUMO
Ventilation perfusion inequality, is analysed with the help of a program written in Basic language, easily implemented on a personal computer. For a gas exchange unit, the main equation describes a mass balance for oxygen, assuming absence of diffusion barrier. The use of a large number of these units allows for calculation of the resulting arterial PO2 in case of abnormal ventilation blood flow distribution. Several simulations are made to study the effect of local variations of VA/Q ratio, and oxygen inhalation upon arterial PO2.
Assuntos
Computadores , Microcomputadores , Relação Ventilação-Perfusão , Humanos , Modelos BiológicosRESUMO
By definition, rebel post-phlebitic ulcers are very difficult to cure. However, it has recently been apparent that the classic treatments associated with permanent normovolemic haemodilution are more effective. Two research procedures have been implemented simultaneously to try and explain this beneficial effect of haemodilution, one based on an experimental study of isolated rabbit hearts, and the other on a theoretical model of the blood-flow at capillary level. These studies lead us to believe that a better distribution of tissular oxygenation might be one of the mechanisms responsible for the beneficial effect of permanent normovolemic haemodilution in treatment of rebel post-phlebitic ulcers.