Cardiac microdialysis a powerful tool.

See article by Akiyama et al. [1] (pages 531 –538) in [3] reported the application of an existing technique, this issue. microdialysis, to estimate interstitial adenosine and its metabolites. Microdialysis, which evolved during the prior Tsuyoshi Akiyama and Toji Yamazaki have reported decade, had largely been limited to studies evaluating that norepinephrine inhibits acetylcholine release from neurotransmitter release within the central nervous system. post-ganglionic cardiac vagal efferents [1]. This is hardly a The active generation of mechanical activity within novel idea since the existence of pre-junctional adrenergic myocardial muscle provides some theoretical advantages receptors, presumably located on cardiac parasympathetic and poses some difficult problems that are not as apparent efferents, has been well documented both physiologically in stationary tissues. The high metabolic activity and and pharmacologically. What is unique here is that the repeated motion of the muscle produces a higher lymph authors have actually measured steady-state changes in flow and a faster interstitial turnover. The faster equilibraacetylcholine within the interstitium of the working left tion would theoretically allow the observer to make better ventricle. They have done this with an elegant marriage of dynamic measurements. In contrast, the reciprocal muscle in situ microdialysis and an ultra-sensitive HPLC-electroactivity can break or occlude delicate connections between chemical detection system. dialysis windows and their attached inflow and outflow The report referenced above represents another step lines. If the sampling device is sufficiently rigid, friction forward in the continuing struggle to evaluate the paracrine between the probe and the surrounding tissue is a potential environment within the myocardium. Much of the early source of irritation and inflammation that might obscure work in this regard was focused on quantifying the the very environment one seeks to sample. Although one dynamics of capillary filtration including the osmotic can never eliminate tissue damage completely, these contribution of interstitial constituents and the measuredialysis probes are not much more invasive than surgical ment of interstitial fluid pressure. Every student of physisuture. ology remembers the measurements of interstitial fluid The ability to access the extracellular environment in pressure obtained by Guyton from porous spheres inserted intact tissue makes microdialysis a powerful tool. Cells in into a variety of tissues [2]. Subsequent efforts to explain situ often behave differently when they are isolated from a the regulation of coronary blood flow produced a variety of native environment which includes nerves, blood vessels experimental incursions into the myocardial interstitium. and a variety of accessory cell types. In sampling inInterstitial constituents were estimated from a variety of formation from the intact tissue, the investigator obtains a sources including micropipettes, electrodes, filter disks, better picture of the integrated response. In the process, the lymph cannulas and pericardial perfusions. investigator necessarily gives up a certain degree of The controversies centered on the adenosine hypothesis experimental control. The responses of intact and isolated were responsible for much of the later drive to investigate systems can be predictive of one another, however there the myocardial interstitium. In this regard, Van Wylen et al. also can be substantive differences. Surprisingly, investigators using intact systems are often asked to defend why the responses observed differ from those observed in *Corresponding author. Tel.: 11-817-735-2085; fax: 11-817-735isolated systems (e.g. cultured cells). The differences 5084. E-mail address: [email protected] (J.L. Caffrey) between the responses in intact and isolated systems can be