Pulmonary Microcirculation during Experimental Pulmonary Thromboembolism under Conditions of Activation and Blockade of Muscarinic Acetylcholine Receptors.

Changes in pulmonary microcirculation were studied in isolated perfused rabbit lungs during modelling pulmonary thromboembolism under conditions of acetylcholine infusion against the background of treatment with M1 acetylcholine receptor blocker pirenzepine or blockade of muscarinic acetylcholine receptors with atropine. In the first case, the increase in pulmonary artery pressure was less pronounced than in case of atropine treatment. In response to pulmonary embolism after acetylcholine infusion against the background of pirenzepine pretreatment, the capillary hydrostatic pressure and postcapillary resistance did not change, while after atropine treatment, these parameters increased. In case of pulmonary embolism after acetylcholine infusion combined with selective blockade of M1 muscarinic acetylcholine receptors, the capillary filtration coefficient increased to a greater extent, than in the control and after blockade of muscarinic acetylcholine receptors.

Role of ß3-Adrenoceptor Activation in Changes of Pulmonary Microhemodynamics after Experimental Pulmonary Thromboembolism.

Changes in pulmonary microhemodynamics during modelling of pulmonary thromboembolism against the background of nebivolol and mirabegron pretreatment were studied in isolated perfused rabbit lungs. In both cases, the pulmonary artery pressure and precapillary and pulmonary vascular resistance increased to a greater extent than in control animals, but the increase in capillary hydrostatic pressure was less pronounced. The postcapillary resistance did not change in pulmonary embolism against the background of nebivolol administration and increased in case of mirabegron pretreatment; capillary filtration coefficient after nebivolol pretreatment increased less markedly than after mirabegron administration. The increase in capillary filtration coefficient after activation of ß3-adrenoceptors with the specified drugs depended on the ratio of constriction of pulmonary veins, capillary hydrostatic pressure, and endothelial permeability.

Changes in Pulmonary Circulation in Experimental Model of Pulmonary Thromboembolism after Carvedilol Treatment.

In experiments on isolated perfused rabbit lungs, we studied changes in the pulmonary microcirculation in response to carvedilol injection and after modelling pulmonary thromboembolism under conditions of α1- and ß1,2-adrenoceptor blockade with this drug. Carvedilol had mainly vasodilator effects on the pulmonary arterial vessels; the pulmonary venous resistance increased and the capillary filtration coefficient remained unchanged under these conditions. In case of pulmonary thromboembolism against the background of carvedilol treatment, the increase in precapillary resistance and the capillary filtration coefficient was more pronounced that in the control, but the postcapillary resistance increased to a lesser extent. The increase in the capillary filtration coefficient is a result of elevated precapillary resistance and enhanced endothelial permeability.

Pulmonary Microcirculation in Experimental Model of Pulmonary Thromboembolism under Conditions of α-Adrenoceptor Blockade.

Changes in the pulmonary microcirculation in isolated perfused rabbit lungs during modeling of pulmonary thromboembolism were studied in control animals and against the background of α-adrenoceptors blockade with phentolamine. Intravenous injection of emboli to control animals was followed by an increase in pressure in the pulmonary artery, mean capillary hydrostatic pressure, capillary filtration coefficient, pulmonary vascular resistance, as well as precapillary and postcapillary resistances. Against the background of α-adrenoceptor blockade, the increase in most parameters was less pronounced than in control animals, while capillary filtration coefficient increased more drastically. Thus, adrenergic mechanisms are involved in the constrictor reactions of both arterial and venous pulmonary vessels under conditions of pulmonary thromboembolism.

Peculiarities of Blood Flow Changes in Venae Cavae during Experimental Pulmonary Embolism.

The model of acute pulmonary embolism in rabbits demonstrated reduced pulmonary blood flow, cardiac output, left atrial pressure, and blood flow in venae cavae against the background of elevated left pulmonary artery pressure and increased pulmonary vascular resistance. Simultaneously, the blood flow in the superior vena cava decreased to a lesser extent than that in the inferior vena cava, which was a characteristic feature of the model of pulmonary pathology. In contrast, when histamine was infused into the left jugular vein to equally elevate pressure in pulmonary artery as in the above model, the blood flow in the superior vena cava decreased to a greater extent than that in inferior vena cava. During stenosis of inferior vena cava that decreased the cardiac output to the level observed during modeled pulmonary embolism, the blood flows in both venae cavae dropped equally.

[THE PULMONARY HEMODYNAMICS FOLLOWING EXPERIMENTAL PULMONARY THROMBOEMBOLISM AND AFTER BLOCKADE OF THE ALPHA-ADRENOCEPTORS].

In acute experiments on the anesthetized rabbits the pulmonary hemodynamics changes following pulmonary thromboembolism were studied in animals with intact circulation and isolated lungs perfusion in the control series and after the blockade of the alpha-adrenoceptors. Following pulmonary embolism in animals with intact circulation in the control group and after the blockade of alpha-adrenoceptors the pulmonary artery pressure and pulmonary vascular resistance increased, but the pulmonary artery flow decreased to the same extent. However, in control animals, the cardiac output decreased more, than the pulmonary flow; the superior vena cava flow was decreased less, than inferior vena cava flow. After the blockade of the alpha-adrenoceptors there were no any imbalance between the decreasing of the cardiac output and pulmonary flow as well as between the decreasing of superior and inferior venae cavae flows. In animals with perfused lungs after the blockade of the alpha-adrenoceptors the pulmonary artery pressure following pulmonary embolism increased to the same level as in animals with intact circulation, however, in the first case the pulmonary vascular resistance increased four times less than in the last one. Thus, we concluded, that following pulmonary thromboembolism the activation of the alpha adrenergic mechanisms could not only promote to increase the resistance of the pulmonary vessels, but these mechanisms are also involved in the changes of the capacitive function of the pulmonary vessels.

[MECHANISMS OF THE PULMONARY CIRCULATORY CHANGES FOLLOWING EXPERIMENTAL PULMONARY THROMBOEMBOLISM].

In acute experiments the pulmonary hemodynamics changes following pulmonary embolism were studied in rabbits with intact circulation and isolated lungs perfusion. In both cases the pulmonary vascular resistance increased to the same extent. The pulmonary artery pressure following pulmonary embolism in intact animals increased less, than in the case of isolated lungs perfusion, because the pulmonary artery flow decreased. The experiments with the restriction of the inferior vena cava flow have revealed that pulmonary artery pressure and flow decreased, where the pulmonary artery flow was reduced in the same level as following pulmonary embolism. At the same time the pulmonary vascular resistance was increased in two times less, than following pulmonary thrombosis. Thus we concluded, that following pulmonary embolism the pulmonary artery pressure is dependent on the pulmonary artery flow and pulmonary vascular resistance. The pulmonary artery flow changes are caused by the venous return and right ventricular contractility changes and not correlated with the pulmonary vascular resistance alterations.

Role of variations in pulmonary and cardiac hemodynamics in the reduction of the venous return during experimental ischemia of the left ventricular myocardium.

During left-ventricular myocardial ischemia, the decrease in the venous return is determined by reduction of cardiac output, which results from heart rate deceleration and decrease in left-ventricular stroke volume. The latter is related to a decrease in myocardial contractility and blood storage in the pulmonary circuit. Blood accumulation in the lungs is not observed during stimulation of the vagus nerve or treatment with propranolol (against the background of the same values of the negative chronotropic and inotropic effects as during myocardial ischemia). The left-ventricular stroke volume increases, while the cardiac output and venous return decrease to a lesser extent under these conditions.

Hemodynamic mechanisms of reduction of venous return and pulmonary circulation during experimental myocardial ischemia.

Ischemia of left ventricular myocardium in cats moderated blood flow in the venae cavae and decreased venous return, which leads to a drop of blood flow and blood pressure in the pulmonary artery. Shifts in the right atrial pressure had no effects on changes in venous returns. After elevation of the left atrial pressure, promoted by a decrease in contractility of the left ventricular myocardium, blood pressure in the pulmonary artery decreased to a lesser extent than pulmonary blood flow, but did not correlate with shifts in pulmonary vascular resistance.

Dynamic relationships between catecholamine-induced shifts of pressure and blood flow in pulmonary artery.

Experiments on cats showed that catecholamines produced maximum changes in pulmonary artery blood pressure during 12-16 sec postinjection, while blood flow in this artery attained maximum only to 40 sec postinjection, i.e. changes in blood flow attained maximum and ended later than blood pressure shifts. Intravenous epinephrine produced bidirectional changes in blood pressure, while norepinephrine always elevated blood pressure in the pulmonary artery; pulmonary circulation increased after injection of both catecholamines.