Interstitial washdown and vascular albumin refill during fluid infusion: novel kinetic analysis from three clinical trials

Background and aims Increased capillary filtration may paradoxically accelerate vascular refill of both fluid and albumin from the interstitial space, which is claimed to be edema-preventing. We characterized this proposed mechanism, called “interstitial washdown”, by kinetic analyses of the hemodilution induced by intravenous infusion of crystalloid fluid during 3 distinct physiological states. Methods Greater plasma dilution of hemoglobin as compared to albumin during fluid therapy indicated recruitment of albumin, which was compared to the flow of interstitial fluid to the plasma as indicated by population volume kinetic analysis. Data for the comparison were derived from 24 infusions of crystalloid fluid in conscious volunteers, 30 in anesthetized patients, and 31 in patients with ketoacidosis from hyperglycemia. Results “Interstitial washdown” increased the plasma albumin concentration by between 0.3 and 1.0 g/L in the three series of infusions. The initial albumin concentration in the interstitial fluid returning to the plasma was estimated to between 22 g/L and 29 g/L, which decreased to an average of 50–75% lower during the subsequent 2–3 h. Kinetic simulations show that pronounced washdown was associated with increased capillary filtration (high k12) and, in conscious subjects, with greater plasma and interstitial volume expansion and restricted urine flow. During anesthesia, the main effect was an increase in the non-exchangeable fluid volume (“third-spacing”). Conclusions Crystalloid fluid accelerates lymphatic flow that moderately increases plasma albumin, but more clearly helps to maintain the intravascular volume. This “interstitial washdown” mechanism becomes exhausted after a few hours.

Interstitial Washdown and Vascular Albumin Refill During Fluid Infusion: Novel Kinetic Analysis From Three Clinical Trials

Background and Aims. Increased capillary filtration may paradoxically accelerate vascular refill of both fluid and albumin from the interstitial space, which are claimed to be edema-preventing. We characterized “interstitial washdown” by kinetic analyses of the hemodilution induced by intravenous infusion of crystalloid fluid during 3 distinctphysiological states.Methods. The dilution of blood hemoglobin and plasma albumin was compared by population volume kinetic analysis during and after intravenous infusion Ringer´s solution over 30 min in 24 conscious volunteers and 30 anesthetized patients. Data were also retrieved from 31 patients with ketoacidosis from hyperglycemia who received 1 L of0.9% saline. Greater plasma dilution of hemoglobin as compared to albumin indicated recruitment of albumin.Results. “Interstitial washdown” increased plasma albumin concentration by 0.6 g/L in volunteers, by 1.0 g/L during anesthesia, and by 0.3 g/L in ketoacidosis patients. The albumin concentration in extravascular fluid returning to the plasma was approximately 29, 29, and 22 g/L during the respective infusions, but decreased to an average of 50% to 75% lower during the subsequent 2-3 h. Pronounced washdown was associated with increased capillary filtration (high k12) and, in conscious subjects, with fluid retention due to restricted urine flow. During anesthesia, the main effect was an increase the nonexchangeable fluid volume (“third-spacing”).Conclusions. Fluid infusion induces interstitial washdown by accelerated lymphatic flow and an increase in plasma albumin. The mechanism becomes exhausted after 2-3 hours. Albumin refill helps retain infused volume within the vascular compartment.

The peculiarities of pulmonary macro- and microhemodynamics changes after treatment with agonists and blockers of cholinoceptors

Background. The pulmonary arterial and venous vessels are innervated by parasympathetic cholinergic nerves. However, the studies, performed on the isolated rings of pulmonary vessels, can not give answer to the question about the role of cholinergic mechanisms in the changes of pulmonary circulation in full measure. Aim. The comparative analysis of the changes of the pulmonary macro- and microhemodynamics after acetylcholine, atropine, pentamine and nitroglycerine treatment. Materials and methods. The study was carried out on the anesthetized rabbits in the condition of intact circulation with the measurement of the pulmonary artery pressure and flow, venae cavae flows, cardiac output, and also on isolated perfused lungs in situ with stabilized pulmonary flow with measurement of the perfused pulmonary artery pressure, capillary hydrostatic pressure, capillary filtration coefficient and calculation of the pulmonary vascular resistance, pre- and postcapillary resistances. Results. In the conditions of intact circulation after acetylcholine, pentamine and nitroglycerine treatment the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance did not change as a result of decreasing of pulmonary artery flow and left atrial pressure due to diminution of venous return and venae cavaе flows. On perfused isolated lungs acetylcholine caused the increasing of pulmonary artery pressure, capillary hydrostatic pressure, pulmonary vascular resistance, pre- and postcapillary resistance and capillary filtration coefficient. After M-blocker atropine treatment the indicated above parameters of pulmonary microcirculation increased, on the contrary, after N-blocker pentamine treatment they decreased. Nitroglycerine infusion caused less decreasing of the parameters of pulmonary microcirculation in comparison with effects of pentamine, but capillary filtration coefficient decreased to a greater extent. These data indicate that nitroglycerine decreases endothelial permeability of pulmonary microvessels. Conclusion. After activation or blockade of cholinergic mechanisms in the condition of intact circulation the calculated parameter of pulmonary vascular resistance is depended from the ratio of the pulmonary artery pressure and flow and left atrial pressure, which are determined by the venous return. The different character of the changes of pulmonary microcirculatory parameters after M-blocker atropine and N-blocker pentamine treatment is evidence of reciprocal relations of M- and N-cholinoceptors in the nervous regulation of the pulmonary microcirculatory bed.

Comparative Study of Capillary Filtration Coefficient (Kfc) Determination by a Manual and Automatic Perfusion System. Step by Step Technique Review

The purpose of calculating the capillary filtration coefficient is to experimentally evaluate edema formation in models of pulmonary ischemia-reperfusion injury. For many years, the obtaining of this coefficient implies a series of manual maneuvers during ex-vivo reperfusion of pulmonary arterial pressure, venous pressure and weight, as well as the calculation of the Kfc formula. Through automation, the calculation of capillary filtration coefficient could be easier and more efficient. To describe an automatic method designed in our laboratory to calculating the capillary filtration coefficient and compare with traditional determination of capillary filtration coefficient as gold standard method. An automatic three valve perfusion system was constructed, commanded by a mastery module connected to a graphical user interface. To test its accuracy, cardiopulmonary blocks of Wistar rats were harvested and distributed in manual (n=8) and automated (n=8) capillary filtration coefficient determination groups. Physiological parameters as pulmonary arterial pressure, pulmonary venous pressure, weight and capillary filtration coefficient were obtained. Results: Capillary filtration coefficient, pulmonary arterial pressure, venous arterial pressure shown no statistical significance difference between the groups. The automated perfusion system for obtaining Kfc was standardized and validated, giving reliable results without biases and making the process more efficient in terms of time and personal staff.