The 80% overall survival rate achieved in this group of patients with severe acute respiratory distress syndrome may in part reflect the additive beneficial effects of combined treatment methods, such as airway pressure control, nitric oxide inhalation, prone position, and early triage of nonresponders to extracorporeal membrane oxygenation.

Adding posterior pharyngeal oxygen insufflation to conventional preoxygenation prolonged the period of adequate oxygen saturation in infants and small children by an amount that is potentially clinically important.

Supernormal conduction (SNC) in excitable cardiac tissue refers to an increase of pulse (or action potential) velocity with decreasing distance to the preceding pulse. Here we employ a simple ionic model to study the effect of SNC on the propagation of action potentials (APs) and the phenomenology of alternans in excitable cardiac tissue. We use bifurcation analysis and simulations to study attraction between propagating APs caused by SNC that leads to AP pairs and bunching. It is shown that SNC stabilizes concordant alternans in arbitrarily long paced one-dimensional cables. As a consequence, spiral waves in two-dimensional tissue simulations exhibit straight nodal lines for SNC in contrast to spiraling ones in the case of normal conduction. Propagation of pulse trains in excitable media is usually characterized by a so-called dispersion curve that gives the velocity of a pulse in a periodic train as a function of its wavelength [1]. In cardiac tissue the dispersion properties are often summarized in the conduction velocity (CV) restitution curve that relates the velocity of an action potential (AP) to its diastolic interval (DI), that is, the time between two consecutive APs (see, e.g., Ref.[2]).Since a pulse typically is followed by a refractory zone of decreased excitability, the pulse velocity monotonically increases with increasing wavelength (=normal dispersion). In the context of excitable cardiac tissue, normal dispersion corresponds to normal conduction. In this paper we focus on the alternative situation where the velocity of a pulse is decreasing with increasing wavelength. In generic excitable media this case is known as anomalous dispersion. For excitable cardiac tissue it corresponds to supernormal conduction (SNC) [3]. Normal and supernormal conduction may appear for a different wavelength in the same systems, then the dispersion curve has to be nonmonotonic.The simplest case of a nonmonotonic dispersion relation is a curve with a single maximum separating anomalous dispersion at long wavelength from normal dispersion at short wavelength. Such behavior has been discovered in various experiments in chemical reaction-diffusion systems [4,5]. It has been found to coincide with attractive long-range interaction between pulses that may lead to stable bound states [6] merging or bunching of pulses [7]. While most excitable cardiac tissues and related models exhibit normal conduction, nevertheless examples of SNC are frequent (for a short review see, e.g., Ref.[8]). SNC is found, for example, in the Iyer-Mazhari-Winslow [9] or in the Drouhard-RobergeBeeler-Reuter (DRBR) model [10,11] employed in the study here, and it is often observed under conditions of low extracellular potassium concentration [12]. Recently, it has been shown to potentiate the onset of alternans in cultured cardiac cell strands [13] and also in generic models of spiral wave formation [14].Alternans is an oscillation in the duration of the AP that usually occurs at short stimulation periods [15]. In a paced cable or tissue alternans ...

Cardiac propagation is investigated by simulations using a realistic three-dimensional (3D) geometry including muscle fiber orientation of the ventricles of a rabbit heart and the modified Beeler-Reuter ionic model. Electrical excitation is introduced by a periodic pacing of the lower septum. Depending on the pacing frequency, qualitatively different dynamics are observed, namely, normal heart beat, T-wave alternans, and 2:1 conduction block at small, intermediate, and large pacing frequencies, respectively. In a second step, we performed a numerical stability and bifurcation analysis of a pulse propagating in a one-dimensional (1D) ring of cardiac tissue. The precise onset of the alternans instability is obtained from computer-assisted linear stability analysis of the pulse and computation of the associated spectrum. The critical frequency at the onset of alternans and the profiles of the membrane potential agree well with the ones obtained in the 3D simulations. Next, we computed changes in the wave profiles and in the onset of alternans for the Beeler-Reuter model with modifications of the sodium, calcium, and potassium channels, respectively. For this purpose, we employ the method of numerical bifurcation and stability analysis. While blocking of calcium channels has a stabilizing effect, blocked sodium or potassium channels lead to the occurrence of alternans at lower pacing frequencies. The findings regarding channel blocking are verified within three-dimensional simulations. Altogether, we have found T-wave alternans and conduction block in 3D simulations of a realistic rabbit heart geometry. The onset of alternans has been analyzed by numerical bifurcation and stability analysis of 1D wave trains. By comparing the results of the two approaches, we find that alternans is not strongly influenced by ingredients such as 3D geometry and propagation anisotropy, but depends mostly on the frequency of pacing (frequency of subsequent action potentials). In addition, we have introduced numerical bifurcation and stability analysis as a tool into heart modeling and demonstrated its efficiency in scanning a large set of parameters in the case of models with reduced conductivity. Bifurcation analysis also provides an accurate test for analytical theories of alternans as is demonstrated for the case of the restitution hypothesis.

The excessive uncontrolled activation of inflammatory cells and mediators after trauma or major surgery plays a key role in the development of adult respiratory distress syndrome and multiple organ system failure (MOSF). In the past elevated cytokine levels were shown to influence the outcome of these patients adversely. There are diverging results regarding the removal of circulating cytokines by various methods of hemopurification for clinical improvement of MOSF. Seven patients after trauma or major surgery underwent continuous venovenous hemofiltration (CVVH) for the treatment of severe organ failure of the heart and lungs (Murray score 2.74) but not for renal or liver failure. The cytokine levels were measured at the beginning and 15, 60, 120, and 240 minutes after initiation of CVVH (measure points MP1-5). Clinical improvement during the treatment was monitored, and correlation with cytokine levels was evaluated. Arterially measured tumor necrosis factor alpha rose from 11.14 ng/ml to 17.86 ng/m1 (p < 0.05). Arterial interleukin-6 (IL-6) levels significantly decreased during CVVH from 1284.7 ng/m1 to 557.9 ng/m1; IL-8 levels simultaneously decreased from an initial peak of up to 154.4 ng/m1 at MP3 to 97.3 ng/m1 at MP5. The drop in serum IL-6 and IL-8 levels closely correlated with clinical improvement. After 2 hours of CVVH the hemodynamic situation improved significantly, as revealed by a decrease in catecholamine expenditure, an increase in arterial pressure, and a decrease in pulmonary artery pressure. Moreover, 2 hours after the initiation of CVVH the oxygenation index rose significantly and correlated well with the drop in shunt fraction. The Murray score significantly fell to 1.86. The removal of IL-6 and IL-8 by CVVH after initial stimulation correlates with clinical improvement, which was demonstrated by significantly improved oxygenation and hemodynamics from 2 hours after the initiation of CVVH onward. The elimination of cytokines and several mediators by CVVH may contribute to the cardiopulmonary improvement of critically ill patients. In comparison with the clinical control group (n = 7), which was comparable in terms of MOSF, no intervention led to a similar improvement in cardiorespiratory failure, and overall two of these patients died. Moreover, patients of the control group experienced a significant longer stay at in the intensive care unit.

Objective-To assess whether long term treatment with epoprostenol might restore primary non-responsiveness to nitric oxide (NO) in patients with primary pulmonary hypertension. Methods-Seven patients with primary pulmonary hypertension receiving intravenous epoprostenol continuously because of failure of NO to influence pulmonary haemodynamics during initial testing were followed over a period of 13-29 months. Afterwards, acute vascular reactivity towards NO was tested again during right heart catheterisation. Results-Administration of NO after continuous epoprostenol treatment for a mean period of 18 months improved arterial oxygen saturation (p < 0.01) and cardiac index (p < 0.05), and decreased mean pulmonary artery pressure (p < 0.01) and total pulmonary vascular resistance (p < 0.01) in patients previously unresponsive to NO. Conclusions-Long term treatment with epoprostenol reverts initial refractoriness to NO in patients with primary pulmonary hypertension. Thus the addition of NO to epoprostenol treatment might cause further improvement in the course of the disease. (Heart 2000;83:406-409) Keywords: primary pulmonary hypertension; epoprostenol; vascular reactivity Primary pulmonary hypertension is a rare disease of unknown aetiology leading to the development of severe precapillary pulmonary hypertension characterised by impaired regulation of both pulmonary haemodynamics and vascular growth.

SummaryResistive heating is an alternative to forced-air warming which is currently the most commonly used intra-operative warming system. We therefore tested the hypothesis that rewarming rates are similar with Hot Dog Ò (Augustine Biomedical) resistive and Bair Hugger Ò (Arizant) forced-air heating systems. We evaluated 28 patients having major maxillary tumour surgery. During the establishment of invasive monitoring, patients became hypothermic, dropping their core temperature to about 35°C. They were then randomly assigned to rewarming with lower-body resistive (n = 14) or forced-air (n = 14) heating, with each system set to 'high'. Our primary outcome was the rewarming rate during active heating over a core temperature range from 35 to 37°C. Morphometric characteristics were comparable in both groups. Temperature increased at twice the rate in patients assigned to forced-air warming, with an estimated mean (SE) slope of 0.49 (0.03)°C.h )1 vs 0.24 (0.02)°C.h )1 (p < 0.001). Resistive heating warmed at half the rate of forced air.

We investigate the dispersion relations of nonlinear periodic wave trains in excitable systems which describe the dependence of the propagation velocity on the wavelength. Pulse interaction by oscillating pulse tails within a wave train leads to bistable wavelength bands, in which two stable and one unstable wave train coexist for the same wavelength. The essential spectra of the unstable wave trains exhibit a circle of eigenvalues with positive real parts which is detached from the imaginary axis. We describe the destruction of the bistable dispersion curve and the formation of isolas of wave trains in a sequence of transcritical bifurcations unfolding into pairs of saddle-node bifurcations. It turns out that additional dispersion curves of unstable wave trains play an important role in the destruction of the bistable dispersion curve.