Acute volume overload elevates T-wave alternans magnitude.

The objective of this study was to determine whether acute volume loading elevates T-wave alternans (TWA) in dogs with structurally normal hearts. TWA predicts sudden cardiac arrest in patients with left ventricular dysfunction and congestive heart failure. However, volume load and ventricular stretch may themselves precipitate arrhythmias. It is unclear to what extent volume load causes TWA. In six male mongrel dogs [25.8 kg (SD 4.2)] under general anesthesia, we measured TWA during progressive atrial pacing to 160 beats/min. Pacing was performed at baseline, at the midpoint and peak of a saline infusion designed to induce acute CHF, and then during diuresis. Dog 1 was hypothermic throughout the protocol and excluded from analysis. For dogs 2-6, 102 ml/kg (SD 30) were infused over 315 min (SD 50), causing pulmonary capillary wedge pressure to rise from 9.6 (SD 3.5) to 21.2 mmHg (SD 1.6) (P < 0.01), and heart rate variability to fall (P < 0.01). TWA magnitude (Valt) rose in all dogs with volume load (P < 0.001). Compared with baseline, TWA at peak infusion had higher magnitude [Valt 3.4 (SD 1.95) vs. 0.5 muV (SD 0.35); P = 0.011] and occurred at lower heart rates [128 (SD 6) vs. 151 beats/min (SD 12); P = 0.008]. Net volume load was linearly related to Valt (P < 0.01), with each 10 ml/kg net volume load increasing Valt by 0.23 muV. Acute volume overload elevates TWA in normal canine hearts. Although dramatic, however, this effect may contribute clinically to abnormal TWA only in patients with marked volume overload. Future studies should examine the interaction of fluid overload, myocardial disease, and arrhythmia susceptibility.

Microelectronic array devices and techniques for electric field enhanced DNA hybridization in low-conductance buffers.

A variety of electronic DNA array devices and techniques have been developed that allow electric field enhanced hybridization to be carried out under special low-conductance conditions. These devices include both planar microelectronic DNA array/chip devices as well as electronic microtiter plate-like devices. Such "active" electronic devices are able to provide controlled electric (electrophoretic) fields that serve as a driving force to move and concentrate nucleic acid molecules (DNA/RNA) to selected microlocation test-sites on the device. In addition to ionic strength, pH, temperature and other agents, the electric field provides another controllable parameter that can affect and enhance DNA hybridization. With regard to the planar microelectronic array devices, special low-conductance buffers were developed in order to maintain rapid transport of DNA molecules and to facilitate hybridization within the constrained low current and voltage ranges for this type of device. With regard to electronic microtiter plate type devices (which do not have the low current/voltage constraints), the use of mixed buffers (low conductance upper chamber/high conductance lower chamber) can be used in a unique fashion to create favorable hybridization conditions in a microzone within the test site location. Both types of devices allow DNA molecules to be rapidly and selectively hybridized at the array test sites under conditions where the DNA in the bulk solution can remain substantially denatured.