Hemodynamic mechanisms of the pulmonary artery pressure and blood flow changes following vasoactive depressor drugs injection

The character and values of changes of the pulmonary hemodynamics and venous return following acetylcholine, histamine and isoproterenol intravenous injection were studied in acute experiments on the anesthetized cats. After depressor drugs injection the character and values of changes of pulmonary artery pressure and flow were different. In 67% cases the pulmonary artery pressure was decreased, and in 33%--it was elevated, meanwhile the pulmonary artery flow was decreased in 48% cases and it was increased in 52%, i.e., in the equal number of observations. Thus, following depressor drugs intravenous injection, hemodynamic mechanisms of the changes of pulmonary artery pressure and flow are different. The character and values of changes of the pulmonary artery pressure are correlated with the changes of pulmonary vascular resistance and are not dependent with the left atrial pressure shifts. The changes of the pulmonary artery blood flow are caused by the changes of the venous return and are not correlated with the changes of the right and left atrial pressure.     

The role of vagus nerves in different changes of the right atrial pressure following intravenous injection of pressor vasoactive drugs

In acute experiments on anesthetized cats, intravenous injection of the norepinephrine and angiotensin caused different changes of right atrial pressure in intact animals (decreasing--I group, of animals, and increasing--II group). After right and left vagus nerves had been cut, the right atrial pressure in the I group of animals decreased, but its changes were lesser than in intact animals due to slowing down of the increase of the right ventricular myocardial contractility and venous return. The latter was the result of severe diminution of the increase of the superior vena cava flow compared with the intact animals, meanwhile the value of the inferior vena cava flow did not change. In the II group animals after vagotomy and intravenous injection of the noripinephrine and angiotensin the sign of the right atrial pressure became negative, i. e. the direction of its shifts changed to the opposite, compared with intact animals. In this case, the changes of the sign of the right atrial pressure was caused by the removal of the reflectory inhibitory vagal influences on the heart, because the values of the right ventricular myocardial contractility and venous return were the same as in intact animals of the group, due to decreasing of the value of the superior vena cava flow and increasing of the shifts of the inferior vena cava flow. The vagotomy alone caused also different changes (decreasing or increasing) of right atrial pressure following increasing of the right ventricular myocardial contractility, meanwhile the changes of the venous return were insignificant. Direct electrical stimulation of both the right and the left vagus nerves caused the increasing of the right atrial pressure and decreasing of the right ventricular myocardial contractility and venous return. Thus we concluded, that different changes of the right atrial pressure in animals following intravenous injection of the pressor vasoactive drugs could be the result of different manifestations of the vagal afferent impulsation, which has influence on the sympathetic tonic discharges on the vessels of the regions of the superior and inferior vena cava, and the vagal reflectory inhibitory influences on the heart.     

Correlations between changes of the right and left atrial pressures following intravenous injections of pressor and depressor drugs in cats

In acute experiments on anesthetized cats, intravenous injection of the pressor drugs (epinephrine and norepinephrine) and depressor drugs (acetylcholine, histamine, isadrin) caused different changes of right and left atrial pressures. Following catecholamine injection, right atrial pressure decreased in most cases, whereas left atrial pressure increased. In case of injection of the depressor drugs, right atrial pressure increased in most cases, and left atrial pressure decreased. Thus, changes of atrial pressures following intravenous injections of pressor and depressor drugs were reciprocal. The percent changes of the right atrial pressure in case of intravenous injections of pressor drugs were lesser than in the left atrial pressure. In case of intravenous injection of depressor drugs, if both right and left atrial pressures were decreased, then the percent changes of the right atrial pressure were more significant than in the left atrial pressure. If both right and left atrial pressure were increased their percent changes were equal. The increasing of inferior vena cava flow following catecholamine injection was less significant if atrial pressures were increased, whereas in case of depressor drugs injection superior vena cava flow was less significant if atrial pressures were increased. The character of changes of the right and left atrial pressures had no linear correlation with the directions of the shifts of the venous return and cardiac output.     

Hemodynamic mechanisms of the pulmonary artery pressure and blood flow changes following vasoactive pressor drugs injection

The character and values of changes of the pulmonary and systemic hemodynamics following epinephrine, norepinephrine and angiotensin intravenous injection were studied in acute experiments on the anesthetized cats. After catecholamines injection pulmonary blood flow was always increased, meanwhile pulmonary artery pressure can be elevated (in the most observations) or decreased. In the cases of angiotensin administration the pulmonary blood flow could be augmented or decreased; pulmonary artery pressure had been increased or decreased independently from the character of changes of pulmonary flow. Thus, linear correlation between shifts of the pulmonary artery pressure and pulmonary blood flow had not been revealed. The changes of the pulmonary artery pressure were not correlated with the pulmonary vascular resistance ones; however they had strong relationship with the changes of the left atrial pressure. If the left atrial pressure was decreased the pulmonary artery pressure elevation was less, comparing with its values in experiments, where the left atrial pressure was increased; in the case of depressor shifts of pulmonary artery pressure, the left atrial pressure was also decreased. The character and values of the pulmonary blood flow changes were strongly correlated with the changes of the venous return; however they had no linear correlations with the right and left atrial pressures and pulmonary vascular resistance changes. Thus we concluded, that hemodynanics mechanisms of the pulmonary artery pressure and flow changes following vasoactive pressor drugs injection changes are different.     

Haemodynamic mechanism of the variety of changes in the right atrial pressure following catecholamines administration

Changes of the right atrial pressure and systemic haemodynamics following action of catecholamines (epinephrine and norepinephrine) were studied in acute experiments on anaesthetised mongrel cats with artificial lung ventilation and opened chest. Maximal changes of the right atrial pressure took place on the 12th-16th second following catecholamine administration. In that case, the atrial pressure could be decreased or increased. At the moment of maximal changes of the right atrial pressure, the venous return and the right ventricular myocardial contractility (the first derivative of the right atrial pressure, dP/dt max) increased more if the right atrial pressure decreased, as compared with the animals whose right atrial pressure augmented. The findings suggest that at the time of the maximal changes of the right atrial pressure following action of catecholamines, there may be a direct connection of the right atrial pressure with interrelation of venous return and the right ventricular contractility. The right atrial pressure, however, is a dependent parameter but it does not determine the venous return.     

Correlations between changes of the right and left atrial pressures and systemic hemodynamics parameters following catecholamines intravenous injections in cats

In acute experiments on anesthetized cats, intravenous injection of epinephrine and norepinephrine caused different changes of right and left artrial pressures. These shifts mostly (82%) had similar directions: in these experiments, both right and left atrial pressures could be decreased (I group of animals) or increased (II group). The number of animals in these groups was equal. However, in 18% of the experiments, right atrial pressure was decreased, while left atrial pressure was increased. The changes of the left atrial pressure was, as a rule, more significant as compared with right atrial pressure shifts. In the I group of animals, systolic right atrial pressure was not changed, and systolic left atrial pressure was decreased. In the II group of animals, systolic pressure in both atria was augmented. Diastolic pressure was decreased in both atria in all the animals. When the atrial pressures were decreased, the increases of the superior and inferior vena cava flows, venous return and cardiac output were more significant as compared with animals in which the atrial pressures had been elevated. The changes of the superior and inferior vena cava flows were more obvious in animals following epinephrine injection as compared with animals in which norepinephrine was injected. The right atrial pressure returned to the initial level more rapidly than the left atrial pressure, and the time dynamics of the shifts of the right atrial pressure was similar to that of the superior vena cava flow. The temporal changes of the left atrial pressure were identical to the time changes of the cardiac output. We concluded that character of changes of the mean, systolic, and diastolic right and left atrial pressures following catecholamines injections was not correlated with the direction of venous return and cardiac output shifts, and was depending on intracardiac hemodynamics.     

Serological changes following a single intravenous Corynebacterium parvum injection in the rat

Summary Changes in circulating levels of immunoglobulins (IgM and IgG), C3, acute-phase reactants, total protein, albumin, iron, and indicators of hepatic and renal function were monitored for up to 3 weeks after a single IV Corynebacterium parvum (C. parvum) injection. In addition to a marked increase in immunoglobulins, there was also evidence of complement activation and of tissue injury typified by a classic acute phase response in levels of ₂-macroglobulin and fibrinogen.A fall in total protein and albumin levels was observed during the first 2 days after C. parvum administration, and significant decreases in serum iron also occurred within the first 4 days. In contrast, increases in serum transaminase and alkaline phosphatase activity were consistent with hepatic injury. Furthermore, raised levels of urea and creatinine suggested mild impairment of renal function.These results indicate the need for serial, serological monitoring of immunological, hepatic and renal function during systemic immunotherapy with C. parvum.     

Dissociation between right atrial pressure and plasma atrial natriuretic factor following prolonged high salt intake

The influence of prolonged high salt intake on intravascular volume, right atrial pressure, plasma atrial natriuretic factor, and extra-atrial tissue (lung, kidney, and liver) COOH- and NH2-terminal atrial natriuretic factor content was investigated in normotensive rats. Despite prolonged high salt (8% NaCl) intake for 5 weeks, total intravascular volume was not impaired. However, right atrial pressure was increased by 54% (p less than 0.01) after salt loading. Although this increment in right atrial pressure should favor atrial natriuretic factor release after NaCl intake, plasma atrial natriuretic factor (COOH-terminal) concentrations markedly decreased from 97.8 +/- 27 to 38.9 +/- 8 pg/mL. Sodium and circulatory homeostasis was, however, well preserved. The lungs contained the highest levels of COOH- and NH2-terminal atrial natriuretic factor. Salt loading resulted in increased concentrations of low as well as high molecular weight atrial natriuretic factor in the lung but not in the kidney or the liver. Our study indicates a limited role of atrial natriuretic factor in adaptation to prolonged salt consumption in rats. Dissociation between right atrial pressure and plasma atrial natriuretic factor after salt intake implicates other factors regulating circulating peptide levels. Prolonged salt intake increases lung generation of atrial natriuretic factor.     

Release of atriopeptin in the rat by vasoconstrictors or water immersion correlates with changes in right atrial pressure

Vasopressin, its 1-deamino analog (dAVP), angiotensin II, and phenylephrine, administered intravenously, increased plasma atriopeptin immunoreactivity in chloral hydrate-anesthetized rats. A continuous one hour infusion of either dAVP or phenylephrine caused a sustained elevation in: a) systemic blood pressure; b) right atrial pressure; c) left ventricular end diastolic pressure; and d) plasma atriopeptin immunoreactivity. While continuous infusion of angiotensin II also produced a sustained elevation in left ventricular end diastolic pressure, the changes in right atrial pressure and plasma atriopeptin were only transient. These data suggest that plasma atriopeptin most closely correlates with right atrial pressure. Consistent with this hypothesis, we found that the release of atriopeptin directly correlated with changes in right atrial pressure in anesthetized, water-immersed rats.     

Experimental emphysema following intravenous injection of trypsin

The injection of trypsin provokes a decrease of the circulating antiproteases. Its effect on an elastase-induced emphysema is negligible. Paradoxically, emphysema is quantitatively demonstrated in rats treated with trypsin alone: an influx of polymorphonuclear leucocytes into the lung is observed during the acute phase of experiment.     

Acute prostaglandin E changes in the kidney medulla after intravenous application of blood pressure active drugs in rabbits]

The blood pressure active substances noradrenaline, alpha-methyl-dopa, clonidine, dihydralazine, and reserpine were studied 20 min after i.v. administration to rabbits for their action on blood pressure, heart rate, PGE-content and -synthesis in the renal medulla. Noradrenaline caused increase in blood pressure, and distinctly enhanced the PGE content in the renal medulla. alpha-methyl-dopa raised both PGE-content and -synthesis, without changing blood pressure and heart rate. Clonidine and dihydralazine caused a pronounced fall of the blood pressure, but only did dihydralazine lower PGE-synthesis, while no such effect was produced by clonidine. Reserpine, like dihydralazine, decreased PGE-synthesis, without simultaneously lowering blood pressure. Indomethacine, one of the most potent inhibitors of PG-synthesis, has no effect on blood pressure within 20 min. The results argue against the existence of a simple direct correlation between PGE-synthesis rate in the homogenate of rabbit renal medulla and the instantaneous blood pressure.     

Character of arterial pressure changes under combined action of pressor and depressor agents

It is shown in acute experiments in cats that byphasic arterial pressure changes occurred due to action of two heterodirectional and equivalent humoral stimuli. Magnitudes of both initial depressor and following pressor phases were authentically less than the ones due to separate action of those stimuli. It is noticed that the character of sum reaction depends neither on action mechanisms of vasoactive agents in the blood circulation system nor differences in the latent period of the effect of those drugs, but connected with intensiveness of stimuli. Predominance of depressor phase magnitude was shown to observe due to a rise of stimuli intensiveness down to complete disappearance of pressor reaction.     

Disseminated intravascular coagulation following intravenous Corynebacterium parvum injection in the rat

Summary Corynebacterium parvum (C. parvum) was administered by a single IV injection (14 mg/kg) to rats, and platelet counts, plasma fibrinogen concentrations and thrombin clotting times were monitored for up to 7 weeks. During this time histological and ultrastructural studies were also conducted. Thrombocytopoenia, hypofibrinogenaemia, and prolongation of the thrombin clotting time rapidly followed C. parvum injection and were accompanied by the appearance of platelet clumps and fibrin within blood vessels in a variety of tissues. This initial episode of disseminated intravascular coagulation (DIC) subsided 12–24 h after injection, but a more prolonged second episode of DIC occurred 1–3 days after injection. The results suggest that caution should be observed when systemic immunotherapy with C. parvum is proposed.