Splanchnic hyperemia and hypervolemia during Valsalva maneuver in postural tachycardia syndrome.

Prior work demonstrated dependence of the change in blood pressure during the Valsalva maneuver (VM) on the extent of thoracic hypovolemia and splanchnic hypervolemia. Thoracic hypovolemia and splanchnic hypervolemia characterize certain patients with postural tachycardia syndrome (POTS) during orthostatic stress. These patients also experience abnormal phase II hypotension and phase IV hypertension during VM. We hypothesize that reduced splanchnic arterial resistance explains aberrant VM results in these patients. We studied 17 POTS patients aged 15-23 yr with normal resting peripheral blood flow by strain gauge plethysmography and 10 comparably aged healthy volunteers. All had normal blood volumes by dye dilution. We assessed changes in estimated thoracic, splanchnic, pelvic-thigh, and lower leg blood volume and blood flow by impedance plethysmography throughout VM performed in the supine position. Baseline splanchnic blood flow was increased and calculated arterial resistance was decreased in POTS compared with control subjects. Splanchnic resistance decreased and flow increased in POTS subjects, whereas splanchnic resistance increased and flow decreased in control subjects during stage II of VM. This was associated with increased splanchnic blood volume, decreased thoracic blood volume, increased heart rate, and decreased blood pressure in POTS. Pelvic and leg resistances were increased above control and remained so during stage IV of VM, accounting for the increased blood pressure overshoot in POTS. Thus splanchnic hyperemia and hypervolemia are related to excessive phase II blood pressure reduction in POTS despite intense peripheral vasoconstriction. Factors other than autonomic dysfunction may play a role in POTS.

The role of trans-membrane signal transduction in turing-type cellular pattern formation.

The Turing mechanism (Phil. Trans. R. Soc. B 237 (1952) 37) for the production of a broken spatial symmetry in an initially homogeneous system of reacting and diffusing substances has attracted much interest as a potential model for certain aspects of morphogenesis (Models of Biological Pattern Formation, Academic Press, London, 1982; Nature 376 (1995) 765) such as pre-patterning in the embryo. The two features necessary for the formation of Turing patterns are short-range autocatalysis and long-range inhibition (Kybernetik 12 (1972) 30) which usually only occur when the diffusion rate of the inhibitor is significantly greater than that of the activator. This observation has sometimes been used to cast doubt on applicability of the Turing mechanism to cellular patterning since many messenger molecules that diffuse between cells do so at more-or-less similar rates. Here we show that Turing-type patterns will be able to robustly form under a wide variety of realistic physiological conditions though plausible mechanisms of intra-cellular chemical communication without relying on differences in diffusion rates. In the mechanism we propose, reactions occur within cells. Signal transduction leads to the production of messenger molecules, which diffuse between cells at approximately equal rates, coupling the reactions occurring in different cells. These mechanisms also suggest how this process can be controlled in a rather precise way by the genetic machinery of the cell.

Applications of nonequilibrium response spectroscopy to the study of channel gating. Experimental design and optimization.

A novel experimental technique known as non-equilibrium response spectroscopy (NRS) based on ion channel responses to rapidly fluctuating voltage waveforms was recently described (Millonas & Hanck, 1998a). It was demonstrated that such responses can be affected by subtle details of the kinetics that are otherwise invisible when conventional stepped pulses are applied. As a consequence, the kinetics can be probed in a much more sensitive way by supplementing conventional techniques with measurements of the responses to more complex voltage waveforms. In this paper we provide an analysis of the problem of the design and optimization of such waveforms. We introduce some methods for determination of the parametric uncertainty of a class of kinetic models for a particular data set. The parametric uncertainty allows for a characterization of the amount of kinetic information acquired through a set of experiments which can in turn be used to design new experiments that increase this information. We revisit the application of dichotomous noise (Millonas & Hanck, 1998a, b), and further consider applications of a more general class of continuous wavelet -based waveforms. A controlled illustration of these methods is provided by making use of a simplified "toy" model for the potassium channel kinetics.