A review of the long-term effects of prazosin and hydralazine in chronic congestive heart failure

In the last two years, six studies using prazosin in doses of 3-32 mg/day for two and 16 months have shown a persistent but variable benefit in 50-80% of those who initially responded favorably. However, serious side-effects occurred in up to 40% and, in many cases, tolerance developed. Mortality was 25-38% in 3-6 months, 50% by one year. In five studies using hydralazine (sometimes combined with long acting nitrates), 150 patients observed from six up to 29 months showed sustained benefit in 26 to 59%, while in many cases hemodynamic values returned to pretreatment values. Again side-effects were considerable, with worsening of angina, fluid retention, gastrointestinal symptomatology and, rarely, lupus erythematodes. Mortality was 28-41% in 10-12 months, higher in non-responders than in responders. Although exercise capacity increased in responders, no data are available today to prove that these vasodilators allow heart failure patients to live longer. Prudence is indicated in patients with congestive heart failure due to coronary artery disease. Furthermore, tolerance development, which only may be surmountable if discontinuation for a few weeks or switching to another drug is possible, is a serious problem limiting chronic vasodilator applicatio

Simultaneous determination of the stroke volume and the left ventricular residual fraction with the fiberoptic- and thermodilution method

Simultaneous measurements of the concentration of dye by a fiberoptic catheter and of the temperature by a thermistor catheter were obtained in dogs. No significant difference for cardiac output and stroke volume was found. The slightly but significant higher residual fraction by thermodilution than by fiberoptic technique is caused by cold transfer between ventricular myocardium and cavity. It becomes evident after the fifth bea

Human episodic memory retrieval is accompanied by a neural contiguity effect

Cognitive psychologists have long hypothesized that experiences are encoded in a temporal context that changes gradually over time. When an episodic memory is retrieved, the state of context is recovered—a jump back in time. We recorded from single units in the MTL of epilepsy patients performing an item recognition task. The population vector changed gradually over minutes during presentation of the list. When a probe from the list was remembered with high confidence, the population vector reinstated the temporal context of the original presentation of that probe during study—a neural contiguity effect that provides a possible mechanism for behavioral contiguity effects. This pattern was only observed for well-remembered probes; old probes that were not well-remembered showed an anti-contiguity effect. These results constitute the first direct evidence that recovery of an episodic memory in humans is associated with retrieval of a gradually-changing state of temporal context—a neural “jump-back-in-time” that parallels the act of remembering

Morphometric versus densitometric assessment of coronary vasomotor tone-an overview

The main advantage of the morphometric approach is that the spatial orientation of the vessel with respect to the image intensifier is not very important. Its most severe limitations are that reasonable accuracy can only be obtained with circular lumina, and that accuracy decreases rapidly with the vessel diameter. The densitometric approach is much less dependent on the shape of the lumen and on the correct identification of the vessel wall in the image. A further essential advantage is that one measures directly the cross-sectional area of the vessel instead of a ‘diameter' of low haemodynamic relevance. Severe requirements must however be met if the potential accuracy of densitometry is to be fully exploited. The morphometric approach seems thus preferable for absolute or relative diameter measurements on intact vessels, while densitometry is superior in case of irregular or small lumina. Morphometric calibration using the injection catheter can induce non-negligible errors in both approaches. Grid calibration is probably more accurate, but also more tedious. In the densitometric approach, ‘3D-calibration' by help of a cube of known size allows also determination of the spatial orientation of the vessel in space. This solution requires however biplane imagin

Digital videodensitometric measurement of aortic regurgitation

A videodensitometric method for quantification of aortic regurgitation which requires neither measurement of cardiac output nor determination of enddiastolic and endsystolic left ventricular volumes has been developed. The injection of 20 ml of contrast medium into the left ventricle is digitally recorded at 25 images s−1 during 20 s using an equipment for digital subtraction angiography (Digitron 2, Siemens). The Digitron computes 2 ‘time dilution curves' (TDC) from the unsubtracted image sequence, for 2 regions of interest drawn around the angiographic enddiastolic and endsystolic left ventricular silhouettes. Enddiastolic and endsystolic points of the TDC are then entered into a VAX-750 computer, which calculates the ejection fraction (EF), the forward ejection fraction (FEF) and the regurgitant fraction (RGF). This is performed by a complex fitting algorithm based on a physical model of the washout process of contrast medium, which reconstructs the two best enddiastolic and endsystolic baselines in the washout parts of the two TDC. The EF, FEF and RGF obtained in 9 regurgitant and 11 nonregurgitant patients have been compared with the corresponding values EFv, FEFv and RGFv obtained by a conventional technique (Cardiogreen and biplane LV area-length volumetry). Regression analysis yielded: EF = 0.88 × EFv (regression line forced through the origin), r = 0.77, FEF = 0.76 × FEFv + 3, r = 0.96, RGF = 0.94 × RGFv + 5, r = 0.98 (v stands for volumetry

State-Dependent Computation Using Coupled Recurrent Networks

Although conditional branching between possible behavioral states is a hallmark of intelligent behavior, very little is known about the neuronal mechanisms that support this processing. In a step toward solving this problem, we demonstrate by theoretical analysis and simulation how networks of richly interconnected neurons, such as those observed in the superficial layers of the neocortex, can embed reliable, robust finite state machines. We show how a multistable neuronal network containing a number of states can be created very simply by coupling two recurrent networks whose synaptic weights have been configured for soft winner-take-all (sWTA) performance. These two sWTAs have simple, homogeneous, locally recurrent connectivity except for a small fraction of recurrent cross-connections between them, which are used to embed the required states. This coupling between the maps allows the network to continue to express the current state even after the input that elicited that state iswithdrawn. In addition, a small number of transition neurons implement the necessary input-driven transitions between the embedded states. We provide simple rules to systematically design and construct neuronal state machines of this kind. The significance of our finding is that it offers a method whereby the cortex could construct networks supporting a broad range of sophisticated processing by applying only small specializations to the same generic neuronal circuit