and tKlinik fur Herz-, Thorax-und Gefdii3chirurgie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Strape 8, 3000 Hannover 61, Germany 1 a1-Adrenoceptor (phenylephrine in the presence of propranolol) andf/2-adrenoceptor (fenoterol)-mediated positive inotropic effects were investigated in human ventricular preparations isolated from five nonfailing (prospective organ donors) and from eight explanted failing hearts with end-stage idiopathic dilative cardiomyopathy (NYHA IV).2 For comparison, the nonselective fJ-adrenoceptor agonist isoprenaline, the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX), the cardiac glycoside dihydroouabain, and calcium were studied. 3 Furthermore, the influence of IBMX on adenosine 3': 5'-cyclic monophosphate (cyclic AMP) PDE activity as well as total #-adrenoceptor density, /J,-andfi2-adrenoceptor subtype distribution, and xl-adrenoceptor density were compared in nonfailing and failing human heart preparations. The radioligands (_)-j[j25I]-iodocyanopindolol for fJ-adrenoceptor binding and [3H]-prazosin for o1-adrenoceptor binding were used. 4 The inotropic responses to calcium and dihydroouabain in failing human hearts were unchanged, whereas the maximal cl-and /12-adrenoceptor-mediated positive inotropic effects were greatly reduced. The inotropic effects of the other cyclic AMP increasing compounds, i.e. isoprenaline and IBMX, were also reduced to about 60% of the effects observed in nonfailing controls. The potency of these compounds was decreased by factors 4-10. 5 The basal PDE activity and the PDE inhibition by IBMX were similar in nonfailing and failing preparations.6 The total fJ-adrenoceptor density in nonfailing hearts was about 70 fmol mg-' protein. In failing hearts the total number of,-adrenoceptors was markedly reduced by about 60%. The l/2-adrenoceptor ratio was shifted from about 80/20% in nonfailing to approximately 60/40% in failing hearts which was due to a selective reduction of /11-adrenoceptors. The 2-adrenoceptor population remaining unchanged. ac-Adrenoceptor density was increased from about 4 fmol mg-' protein in nonfailing to 10 fmol mgprotein in failing hearts. 7 Changes in PDE activity and adrenoceptor downregulation cannot completely explain the reduced positive inotropic effects of ax-and f12-adrenoceptor agonists in failing human hearts. This supports the hypothesis that impairment of other processes such as the coupling between receptor and effector system, i.e. the respective G-proteins, are equally important in end-stage heart failure.

For high sensitive measurements of small magnetic fields a Digital SQUID is superior to conventional analog SQUIDs in terms of dynamic properties, but recent realizations as singleflux-quantum (SFQ) circuit suffers from high complexity. A new kind of Digital SQUID as a full digital sensor device with the advantage of a small number of Josephson junctions and a large slew rate was developed. The circuit consists of basic SFQ cells and an internal digital feedback loop. The operation with a bidirectional clock signal ensures a decreased effort on superconducting electronics. The SFQ/dc converter and an additional voltage driver provides a processable digital output signal for hybrid systems including semiconductor electronics. The sensor circuit was simulated, optimized and fabricated in niobium technology. From investigation of dynamic properties of the circuit we expect a flux slew rate in the gigahertz range.

Digital superconducting quantum interference devices (SQUIDs) have been proposed to extend the dynamic range of analog SQUIDs whenever magnetic fields varying in a wide range need to be measured. We developed a digital SQUID concept, based on the single flux quantum technique, using the reliable 1 kA/cm2 niobium trilayer technology of the FLUXONICS Foundry. We present an extensive experimental analysis to evaluate the digital SQUID magnetometer operation in shielded and unshielded conditions. Bit error rate measurements have shown reliable operation of the digital superconducting circuitry with operation margins of ±11%, confirmed by stable operation in unshielded magnetometer mode for more than 10 h. The best intrinsic magnetic field resolution, corresponding to one magnetic single flux quantum (Φ0), was found to be about 4.2 nT. Peak-to-peak amplitudes of 14 800 and 2810 flux quanta Φ0 could be measured, respectively, for inductively coupled current and magnetic field inputs. A flux noise level of 220 mΦ0/Hz at 0.1 Hz has been measured, corresponding to a dynamic range of 76 dB (e.g., above 12 bits). Furthermore, preliminary experiments have shown that the integration of a digital SQUID with an analog dc SQUID in a hybrid magnetometer is a solution to reach simultaneously a high dynamic range and an increased field sensitivity. Such a device is of utmost importance to detect magnetic fields with high dynamic range to monitor earthquakes in the presence of high amplitude external magnetic perturbations.