The impact of crystalloidal and colloidal infusion preparations on coronary vascular integrity, interstitial oedema and cardiac performance in isolated hearts

Zausig et al. Critical Care The impact of crystalloidal and colloidal infusion preparations on coronary vascular integrity, interstitial oedema and cardiac performance in isolated hearts York A Zausig 2 Daniel Chappell 0 Bernhard F Becker 1 Daniel Potschka 2 Hendrik Busse 2 Kathrin Nixdorf 0 Diane Bitzinger 2 Barbara Jacob 0 Matthias Jacob 0 0 Department of Anaesthesiology, University Hospital Munich , Nussbaumstr. 20, 80336 Munich , Germany 1 Walter-Brendel-Center of Experimental Medicine, University of Munich , Schillerstr. 44, 80336 Munich , Germany 2 Department of Anaesthesiology, University Hospital Regensburg , Franz- Josef-Strau-Allee 11, 93053 Regensburg , Germany Introduction: Recent data suggested an interaction between plasma constituents and the endothelial glycocalyx to be relevant for vascular barrier function. This might be negatively influenced by infusion solutions, depending on ionic composition, pH and binding properties. The present study evaluated such an influence of current artificial preparations. Methods: Isolated guinea pig hearts were prepared in a modified Langendorff mode and perfused with KrebsHenseleit buffer augmented with 1g% human albumin. After equilibration the perfusion was switched to replacement of one half buffer by either isotonic saline (NaCl), ringer's acetate (Ri-Ac), 6% and 10% hydroxyethyl starch (6% and 10% HES, resp.), or 4% gelatine (Gel), the artificial colloids having been prepared in balanced solution. We analysed glycocalyx shedding, functional integrity of the vascular barrier and heart performance. Results: While glycocalyx shedding was not observed, diluting albumin concentration towards 0.5g% by artificial solutions was associated with a marked functional breakdown of vascular barrier competence. This effect was biggest with isotonic saline and significantly attenuated with artificial colloids, the difference in the pressure dependent transvascular fluid filtration (basal vs. during infusion in groups NaCl, Ri-Ac, 6% HES, 10% HES and Gel, n = 6 each) being 0.31 0.03 vs. 1.00 0.04; 0.27 0.03 vs. 0.81 0.03; 0.29 0.03 vs. 0.68 0.02; 0.32 0.03 vs. 0.59 0.08 and 0.31 0.04 vs. 0.61 0.03 g/5min, respectively. Heart performance was directly related to pH value (7.38 0.06, 7.33 0.03, 7.14 0.04, 7.08 0.04, 7.25 0.03), the change in the rate pressure product being 21,702 1969 vs. 21,291 2,552; 22,098 2,115 vs. 14,114 3,386; 20,897 2,083 vs. 10,671 1,948; 21,822 2,470 vs. 10,047 2,320 and 20,955 2,296 vs. 15,951 2,755 mmHg bpm, respectively. Conclusions: It appears important to maintain the pH value within a physiological range to maintain optimal myocardial contractility. Using colloids prepared in calcium-containing, balanced solutions for volume replacement therapy may attenuate the breakdown of vascular barrier competence in the critically ill. - Introduction For over 100 years vascular barrier competence was generally acknowledged to be sufficiently explained by the historical principle of Ernest Starling [1]. This stipulated an inwardly directed oncotic gradient between an interstitial space presumably low in protein and the protein rich plasma with percentage albumin at concentrations of around 4 g% as main constituent. This gradient was considered to keep the compartments in balance, despite an intravascular hydrostatic pressure, which forces fluids and solutes outwards. The therapeutical target to prevent interstitial oedema whilst maintaining cardiac preload in the face of an unaffected endothelial cell line would have been, according to this model, to merely maintain the oncotic plasma pressure. The practical answer was the intravenous infusion of isooncotic colloids prepared in isotonic saline, irrespective of their binding properties for electrolytes and membrane coatings. The last decade, however, has brought increasing evidence that things might not be that easy. Various experimental models showed that the interstitial oncotic pressure in most organs is far from zero and, surprisingly, does not relevantly influence transvascular filtration behaviour [2]. This brought attention to the endothelial glycocalyx, a negatively charged layer of proteoglycans and glycosaminoglycans, now identified as an important part of vascular barrier competence [3]. Due to its special biophysical and biochemical properties, the glycocalyx binds plasma constituents, forming the endothelial surface layer with a functional thickness of more than 1 m [4]. It is only the oncotic gradient across this layer, that is, between the protein-loaded glycocalyx and a small space low in protein directly beneath, but completely at the luminal side of the anatomical vessel wall, that helps to limit hydrostatically driven outflow of plasma constituents in high-pressure segments of the circulation [2]. In addition, the endothelial surface layer plays an important role for shear stress transduction to the endothelial cells and also for generating an anti-inflammatory, antithrombotic and anti-adhesive vascular surface by harbouring adhesion molecules [5]. The fragile glycocalyx, however, can be degraded in various pathophysiological situations such as ischaemia/reperfusion, sepsis, hyperglycaemia, trauma or diabetes [6,7]. The integrity of the endothelial surface layer, which seems to be strongly related to oedema formation and cardiac performance [6], is strongly dependent on sufficient concentrations of suitable plasma constituents [8]. Moreover, the binding properties of both glycocalyx and plasma proteins should depend on plasma pH. Thus, acid-base chemistry should be considered when clinicians assess whether the composition of infusion preparations is adequate. Furthermore, some constituents of these preparations might disrupt the competence of the endothelial surface layer. The present study investigated the influence of commercially available crystalloidal and colloidal infusion preparations on coronary vascular integrity, interstitial oedema and cardiac performance of isolated guinea-pig hearts. It extends the insight into what actually happens to microcirculation when diluting natural plasma constituents with artificial substitutes beyond a critical border. Therefore, these data might already help us today to rationally select a substitution solution for a critically ill patient, even in the absence of outcome-based evidence. Beyond that, such basic data may help to sharpen the focus of future developments in the field. Materials and methods The investigation conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996) and was approved by - and licensure of the investigator obtained from - the Government of Upper Bavaria (Regierung von Oberbayern file No. 209.1/2112531.3-3/99). Hearts were prepared in a non-working Langendorff mode comparing basal conditions to intracoronary infusion of different artificial soluti (...truncated)