Visual LV motion and invasive LVdP/dtmax for selection and optimisation of cardiac resynchronisation therapy.

Echocardiography shows that multiphasic septal movement and a septal to lateral apical systolic left ventricular (LV) motion have a high predictive value for dyssynchrony and the response to cardiac resynchronisation therapy (CRT). Presence of dyssynchrony is also the major marker for CRT response in the presence of scar tissue, provided the interventricular (V-V) pacing interval is optimalised. For atrioventricular (AV) interval optimisation, the velocity-time integral of the transmitral flow has an excellent correlation with invasive LVdP/dt(max). In acute haemodynamic measurements, LVdP/dt(max) shows strongly the effect of AV and V-V optimisation. It also illustrates that the haemodynamic effect of LV pacing when associated with intrinsic conduction over the right bundle is equal to or better than biventricular pacing. We found that once AV and V-V interval were optimised, QRS morphology could be used as a template for optimal therapy. Automated continuous optimisation of the pacing intervals will be the big challenge for the future. (Neth Heart J 2008;16(Suppl1):S32-S35.).

Evidence-based recommendations regarding the differential diagnosis and assessment of nasal congestion: using the new GRADE system.

Nasal congestion is an important symptom in nasal pathology and can be defined as an objective restriction of nasal cavity airflow because of mucosal pathology and/or increased mucus secretion (excluding anatomical variants). Using the new Grading Recommendations Assessment, Development and Evaluation system, evidence-based recommendations are made that will encompass different clinical questions regarding diagnostic modalities of nasal congestion: (i) their usefulness in assessment of presence and severity of congestion; (ii) their usefulness in assessment of etiological pathology responsible for congestion; and (iii) their usefulness in follow up and treatment effectiveness evaluation of nasal congestion.

Assessment of ventricular mechanical dyssynchrony by short-axis MRI.

Nowadays, patients with symptomatic heart failure and intraventricular conduction delay can be treated with a cardiac resynchronization therapy. Electrical dyssynchrony is typically adopted to represent myocardial dyssynchrony, to be compensated by cardiac resynchronization therapy. One third of the patients, however, does not respond to the therapy. Therefore, imaging modalities aimed at the mechanical dyssynchrony estimation have been recently proposed to improve patient selection criteria. This paper presents a novel fully-automated method for regional mechanical left-ventricular dyssynchrony quantification in short-axis magnetic resonance imaging. The endocardial movement is described by time-displacement curves with respect to an automatically-determined reference point. These curves are analyzed for the estimation of the regional contraction timings. Four methods are proposed and tested for the contraction timing estimation. They were evaluated in two groups of subjects with and without left bundle branch block. The standard deviation of the contraction timings showed a significant increase for left bundle branch block patients with all the methods. However, a novel method based on phase spectrum analysis shows a better specificity and sensitivity. This method may therefore provide a valuable prognostic indicator for heart failure patients with dyssynchronous ventricular contraction, adding new possibilities for regional timing analysis.

Contrast ultrasound methods for left-ventricle ejection fraction measurements.

The left-ventricle ejection fraction is an important cardiac-efficiency measure that is regularly used in cardiology. Standard estimations are based on time-consuming geometrical analysis and modelling, which requires experienced cardiologists. Alternative methods are very invasive due to the need for cardiac catheterization. In this paper we present and study a minimally-invasive indicator dilution technique for ejection fraction quantification that has recently been developed. It is based on a peripheral injection of an ultrasound contrast agent bolus. Left-atrium and left-ventricle acoustic intensities are recorded versus time by transthoracic echocardiography during contrast bolus passage. The measured curves are corrected for attenuation distortion, filtered to suppress the measurement noise, and processed by an adaptive Wiener deconvolution algorithm for the estimation of the left-ventricle impulse response. The estimated impulse response is interpolated by a mono-compartment exponential model for the ejection fraction assessment. An adaptive search of the interval for the model fitting is also included. The feasibility of the method is tested on 52 measurements in patients with left-ventricle ejection fractions between 10% and 80%. The results are promising and show a 0.83 correlation coefficient with echographic biplane ejection fraction measurements.

Effect of acute adrenalectomy on sympathetic responses to peripheral lipopolysaccharide or central PGE(2).

The impact of plasma corticosterone levels on the sympathetic nervous system (SNS) response to intravenous lipopolysaccharide (LPS) or intracerebroventricular injections of PG was studied in anesthetized (urethan-chloralose) male Sprague-Dawley rats. For this, electrophysiological recordings of splenic and renal nerves were completed in control or adrenalectomized (ADX) rats. LPS (10 microgram iv) similarly increased splenic and renal nerve activity in control rats with a shorter onset latency for the splenic nerve. Acute ADX enhanced the response of both nerves to LPS (P < 0.005) and reduced the onset latency of the renal nerve (P < 0.05). PGE(2) (2 microgram icv) rapidly increased the activity of both nerves but preferentially (magnitude and onset latency) stimulated the renal nerve (P < 0.05). The magnitude of the splenic nerve response to PGE(2) was unaffected by ADX. Unexpectedly, PGE(2) was less effective at stimulating renal nerve activity in ADX animals relative to intact controls (P < 0.05). Pretreatment of ADX rats with a CRF antagonist ([D-Phe(12), Nle(21,38), Calpha-MeLeu(37)]CRF-(12-41)) reversed this effect such that the renal nerve responded to central PGE(2) to a greater extent than the splenic nerve (P < 0.05), as was the case in non-ADX rats. These data indicate that enhanced sensitivity of central sympathetic pathways does not account for the enhanced SNS responses to LPS in ADX rats. Also, a CRF-related process appears to diminish renal sympathetic outflow in ADX rats.

Peripheral endotoxin increases splenic sympathetic nerve activity via central prostaglandin synthesis.

We tested whether prostaglandin synthesis mediates the lipopolysaccharide (LPS)-induced increase in splenic sympathetic nerve activity. Sprague-Dawley rats were pretreated with intravenous or intracerebroventricular injections of indomethacin, and splenic nerve activity was recorded after intravenous injections of LPS. In vehicle-pretreated rats, 100 micrograms LPS induced a 62.8 +/- 5.6% increase in splenic nerve activity beginning 22.7 +/- 2.7 min postinjection. All vehicle-pretreated animals responded to high (100 micrograms, 5 of 5 animals) and low (10 micrograms, 8 of 8 animals) doses of LPS. Both intravenous (15 mg/kg) and intracerebroventricular (50 micrograms) pretreatments with indomethacin delayed (F1.19 = 30.66, P < 0.001) the increase in nerve activity after 100 micrograms LPS. When given intravenously, 50 micrograms indomethacin (the intracerebroventricular dose) did not delay the response to intravenous LPS, indicating that the effects of intracerebroventricular indomethacin pretreatment were restricted to the central nervous system. Importantly, intracerebroventricular indomethacin reduced (2 of 7 animals) or completely blocked (5 of 7 animals) the splenic nerve response to the low dose of LPS (10 micrograms, iv). The indomethacin effects could not be accounted for by central release of vasopressin because intracerebroventricular injection of indomethacin did not alter baseline nerve activity or blood pressure, whereas intracerebroventricular injection of vasopressin rapidly increased both measures. Additionally, central injection of LPS did not elevate splenic nerve activity, whereas intracerebroventricular injection of prostaglandin E2 induced a rapid (2.2 +/- 2.7 min) increase in splenic nerve activity. These data indicate that central prostaglandin synthesis is an intermediate step whereby systemic LPS elicits an increase in sympathetic outflow to an immune organ.

Effect of sinus denervation and vagotomy on c-fos expression in the nucleus tractus solitarius after exposure to CO2.

Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14-16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50- "mu"m section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.

Technique for repetitive recording from fetal respiratory neurons.

We developed a new method for repetitive recording of medullary neurons in fetal sheep in situ. The technique involves chronically fixing the fetal head to the flank of the ewe by way of a Teflon plate that has a removable window. This window allows direct access of a recording electrode to the floor of the fourth ventricle of the fetus. In four of six fetuses, repetitive recordings lasting 3-4 h were possible for up to 6 days. By operating on younger fetuses and with care, this time span could be extended. This novel method should be useful in the future for extracellular and intracellular recordings of neurons in the developing fetus without disturbing the fetal state and for the study of putative neurotransmitters during development with iontophoretic techniques.

Activation and selectivity of splenic sympathetic nerve electrical activity response to bacterial endotoxin.

Regulatory interactions and neuroanatomic pathways have been described between the sympathetic nervous system and the immune system. It is not clear whether these pathways are activated during immune responses and if target specificity provides selective regulation of immune organs. The present study examined whether systemic injection of endotoxin [lipopolysaccharide (LPS)] induces sympathetic outflow to an immune organ (spleen). Sympathetic nerve activity was recorded from either the splenic or renal nerve of adult male rats after intravenous injections of LPS. Splenic nerve activity increased in a dose-dependent manner up to 175% of control after injection of LPS, with an onset time of 17.1-23.5 min. In contrast, renal nerve recordings showed a significantly slower onset time of 37.1-52.6 min at similar doses. In addition, splenic nerve recordings of 8/8 rats responded to 10 micrograms of LPS, whereas only 4/11 positive renal nerve responses were observed at this dose. The magnitude of the responses of both splenic and renal nerves were comparable. These data suggest that the splenic nerve responds to and is more sensitive to LPS-stimulated sympathetic activation in terms of latency and frequency of responses. Thus sympathetic outflow can be directed to an immune organ in response to a stimulus known to activate the immune system.

Effect of medullary lesions, vagotomy and carotid sinus denervation on fetal breathing.

Chronically prepared fetal sheep were subjected to bilateral surface lesions of the Area "S" on the ventrolateral medulla and/or to peripheral chemoreceptor denervation by section of the vagus, sinus or both nerves. Sino-aortic denervation or Area "S" lesions reduced the incidence of fetal breathing (FB) for several days. Area "S" lesions also disrupted the pattern of FB; diaphragmatic EMG activity initially was mostly tonic and then of very high frequency, up to 7 Hz. Incidence and pattern of FB generally recovered by 7 days, but mean Ti was reduced in Area "S" lesioned fetuses (0.14 +/- 0.01 sec) compared to nonlesioned fetuses (0.19 +/- 0.01 sec) (P < 0.0001). Respiratory sensitivity to CO2 was variable but not different between control, denervated, and Area "S" lesioned groups. Eight of eight fetuses with Area "S" lesions were unable to initiate breathing at birth, but three sham operated fetuses were born normally. These data suggest that the classical peripheral and central chemoreceptors have a negligible influence on the control of FB, and that breathing activity in the fetus is mediated by a different mechanism than during postnatal life.