Pulmonary Microcirculation in Experimental Model of Pulmonary Thromboembolism after Pretreatment with Chloroquine.

Changes of pulmonary microcirculation in response to pulmonary artery embolization after pretreatment with chloroquine were studied on the model of isolated perfused rabbit lungs. The increase in the pulmonary vascular resistance and pre- and postcapillary resistance was less pronounced than after pulmonary thromboembolism after pretreatment with mibefradil (T-type Ca2+ channels blocker) or nifedipine (L-type Ca2+ channels blocker). The shifts of capillary filtration coefficient correlated with changes in the precapillary resistance. When modeling pulmonary thromboembolism after pretreatment with chloroquine combined with glibenclamide (KATP channels blocker), the studied hemodynamics parameters increased to the same extent as after pretreatment with nifedipine. The results indicate that chloroquine exhibits the properties of an L- and T-type Ca2+ channels blocker and an activator of KATP channels.

Changes of Pulmonary Microhemodynamics in Experimental Pulmonary Thromboembolism after Pretreatment with K-Channel Activators.

Changes in pulmonary microhemodynamics in response to pulmonary embolism under conditions of activation of KATP channels with nicorandil, Kv channels with dapagliflozin, and BKCa channels with Evans blue were studied on isolated rabbit lungs. Under conditions of activation of KATP and BKCa channels, the constrictor reactions of the pulmonary arterial vessels during embolization of the pulmonary artery were less pronounced than in the control. Activation of BKCa channels reduced constrictor reactions of the pulmonary venous vessels, while activation of KATP and Kv channels eliminates them. The shifts of the capillary filtration coefficient are determined to a greater extent by the pre-/postcapillary resistance ratio, than by changes of the endothelial permeability. Pretreatment with dapagliflozin led to a decrease in the capillary filtration coefficient. It was established, that nimesulide exhibits properties of a BKCa-channel activator.

[Adrenergic mechanisms of regulation of pulmonary microvessels tonicity and endothelial permeability]. / Adrenergicheskie mekhanizmy reguliatsii tonusa mikrososudov legkikh i pronitsaemosti éndoteliia.

The review contains the data on adrenergic mechanisms of regulation of pulmonary microvessels tonicity and endothelial permeability. On smooth muscle cells of pulmonary vessels there are postsynaptic α1A-, α1B-, α1D- and α2A-, α2B-, α2C-adrenoreceptors whose activation by norepinephrine induces vasoconstriction. Excitation of ß1- and ß2-subtypes of adrenoreceptors leads to vasodilatation, Activation of α1-2- and ß1-3-adrenoreceptors of the endothelium contributes to enhancement of nitric oxide synthesis. The resulting reaction of pulmonary microvessels in response to administration of catecholamines appears be determined by interaction of adrenergic mechanisms of regulation of tonicity of smooth muscle cells and synthesis of nitric oxide by the endothelium. Constrictor and dilator reactions of pulmonary venous vessels in response to activation of α- and ß-adrenoreceptors, respectively, are more pronounced than in pulmonary arteries and make a significant contribution to the shifts of pulmonary vascular resistance. Excitation of α2- and ß2-adrenoreceptors of endothelial cells of microvessels of the lungs contributes to a decrease in their permeability. In order to find out the role of adrenergic mechanisms in shifts of the capillary filtration coefficient in simulating various pathology of pulmonary circulation, it is necessary to carry out integral studies that would make it possible to evaluate alterations in macro- and microhaemodynamics of the lungs.

Changes in pulmonary hemodynamics induced by experimental myocardial ischemia in nitroglycerin- or acetylcholine-treated rabbits.

The responses of cardiovascular parameters to left-ventricular myocardial ischemia induced under control conditions and after administration of nitroglycerin or acetylcholine were examined in rabbits. In nitroglycerine-treated rabbits, experimental myocardial ischemia produced less pronounced depressor BP shifts in the pulmonary artery than those produced by ischemia in controls (prior to pharmacological treatment) or by experimental ischemia provoked after acetylcholine infusion. Control and experimental ischemia (provoked after nitroglycerin or acetylcholine administration) induced the same drop in pulmonary blood fl ow accompanied with insignificant changes in vascular pulmonary resistance. Experimental ischemia produced smaller pressure increase in left atrium of nitroglycerine-treated rabbits (evidencing a smaller drop in left ventricular contractility) than the control ischemia performed prior to pharmacological treatment, or the experimental ischemia in acetylcholine-treated rabbits, which attested to protective effect of nitroglycerin against ischemia.

Comparative analysis of direction, value, and duration atrial pressure of shifts caused by depressor agents.

Shifts in right- and left-atrial pressure after administration of acetylcholine, histamine, or isoproterenol to cats were oppositely directed in 69% cases; both parameters decreased in 11% cases (changes were more pronounced in the right atrium) and increased in 20% cases (similar shifts). Changes in the left-atrial pressure persisted for a longer time (compared to those in the right atrium) and their dynamics was similar to that of venous return and cardiac output.

Dynamic relations between right and left atrial pressure shifts induced by catecholamines.

Acute experiments on cats showed that injection of catecholamines induced unidirectional shifts in right and left atrial pressure in 70% cases (these shifts were positive in one half of cats and negative in the other half). In 30% cases, the left and right atrial pressures changed in opposite direction: right atrial pressure decreased, while left atrial pressure increased (19%), or vice versa (11%). The pressure changes in the left atrium had greater amplitude and longer duration compared to those in the right atrium.

Role of relative changes in caval flows for evaluation of right atrial pressure shifts induced by nitroglycerin.

Experiments on cats treated with nitroglycerin showed dynamic relationship between changes in caval venous flows: blood flow increased in the superior vena cava and decreased in the inferior vena cava. Blood pressure in the right atrium either decreased, or increased. No significant changes in total venous return were observed during maximum shifts in right atrial pressure, while contractility of the right ventricular myocardium usually decreased. Our findings suggest that the direction of the right atrial pressure shifts induced by nitroglycerin does not depend on venous return, but is determined by the prevalence of flow changes in the superior vena cava or inferior vena cava.

Dynamics of nitroglycerin-induced changes in vena cava flows and right atrial pressure.

In anesthetized cats, nitroglycerin increased blood flow in the superior vena cava and decreased the flow in the inferior vena cava and total venous return. Simultaneous changes in right atrial pressure could be either positive or negative. The shifts in the superior vena cava flow and right atrial pressure preceded the corresponding alterations in the inferior vena cava flow and venous return.

Independence of changes in right atrial pressure and central venous pressure.

Dynamics of changes in right-atrial pressure and venous pressure measured in the inferior and superior vena cava at their orifices (central venous pressure) after bolus injection of 20 ml physiological saline or epinephrine (5.0 mg/kg) was studied in acute experiments on cats. The initial pressure in the right atrium was equal to that in caval veins. Pressor stimuli either increased or decreased the right atrial pressure, but always increased blood pressure in the caval veins. Moreover, right atrial pressure returned to the initial level more rapidly compared to that in caval veins. Our results suggest that the dynamics of the right-atrial pressure does not reflect the shifts in the central venous pressure.

Changes in caval blood flow and right atrial pressure in response to catecholamines.

The type and magnitude of changes in blood flow in the anterior (cranial) and posterior (caudal) caval veins and shifts in the mean right atrial pressure induced by catecholamines (epinephrine and norepinephrine) were studied in acute experiments on cats. It was found that irrespective of right atrial pressure shifts, the increase in the blood flow in the anterior vena cava was more pronounced than in the posterior vena cava and was determined by blood redistribution due to more pronounced increase in vascular resistance in the abdominal aorta basin.

Relationship between venous return and right-atrial pressure.

The dynamics and amplitude of changes in venous return and right atrial pressure (central venous pressure) in response to pressor stimuli were studied in acute experiments on cats. The increase in venous return was accompanied by either increase, or decrease in the central venous pressure. Thus, shifts in systemic venous return were not accompanied by simultaneous and co-directed changes in the central venous pressure. These findings suggest the absence of a direct relationship between these parameters.

Relationships between venous return and blood pressure in caval veins and right atrium during pressor stimulation.

The dynamics of changes in blood flow and pressure in the superior and inferior vena cava, total venous return, and right atrial pressure in response to pressor stimuli were studied in acute experiments on cats. It was shown that blood flow and pressure in caval veins changed synchronously and unidirectionally, while shifts in the right atrial pressure did not depend on direction and magnitude of changes in caval flow and pressure and total venous return. Our results suggest that right atrial pressure does not play a role in the regulation of venous return.