Prediction of left ventricular peak ejection velocity by preceding and prepreceding RR intervals in atrial fibrillation: a new method to adjust the influence between two intervals

In atrial fibrillation, cardiac performance is dependent on both preceding RR (RR-1) and prepreceding RR (RR-2) intervals. However, relative contributions were not well defined. Left ventricular outflow peak ejection velocity (Vpe) was measured by echocardiography from 21 patients. The relation between RR-1 and Vpe could be divided into two zones; steep slope in short RR-1 intervals (< or =0.5 sec) and plateau in long RR-1 intervals (> 0.5 sec). RR-2 had a weak negative association with Vpe. The mean squared correlation coefficient (r2) between RR-2 and Vpe was 0.15 +/-0.13 and improved to 0.29+/-0.21 (p<0.001), when coordinates with RR-1 < or =0.5 sec were excluded. The RR-1 was positively associated with Vpe. The mean r2 between RR-1 and Vpe was 0.52+/-0.17 and improved to 0.72+/-0.11 (p<0.001), when adjusted by RR-2. Simple linear regression analysis showed that mean RR interval, age, fractional shortening (FS), and mean peak velocity were negatively correlated with modified r2 between RR-2 and Vpe. Multiple stepwise regression analysis revealed that mean RR interval (r2=0.32) and FS (r2=0.16) were significant. In summary, simple modification could improve the relationship of both RR-1 and RR-2 with cardiac performance. RR-2 might play a more role in cardiac performance than previously expected, and when cardiac function was impaired.     

Modification of alpha1 -adrenoceptors by peroxynitrite as a possible mechanism of systemic hypotension in sepsis

OBJECTIVE: It is well known that nitric oxide synthase is induced by endotoxin or inflammatory cytokines, and consequently large amounts of nitric oxide cause vascular hyporeactivity to vasoconstrictor agents and myocardial dysfunction, hence hypotension. However, there is considerable controversy as to whether these pathologic cardiovascular features are mediated directly by nitric oxide or also through the formation of secondary reaction products such as peroxynitrite (ONOO-1). Our objective was to investigate inhibitory effects of ONOO-1 on alpha1-adrenoceptors. DESIGN: Prospective, controlled, in vitro, laboratory study. SETTING: Laboratory of a health sciences university. SUBJECTS: Chinese hamster ovary cells that expressed the human recombinant alpha1a-, alpha1b-, or alpha1d-adrenoceptors, rat aorta strips. INTERVENTIONS: Binding experiments of [3H]prazosin were done in the Chinese hamster ovary cell membranes pretreated with 100 microM to 3 mM ONOO-1. Displacement experiments with noradrenaline or 3-nitro-l-tyrosine also were conducted. Mobilization of intracellular Ca2+ evoked by 1 nM to 10 microM noradrenaline was monitored in a fluorescence spectrophotometer with dual excitation at 340 nm/380 nm and emission at 500 nm in fura-2/AM-loaded Chinese hamster ovary cells. Contractile force produced by noradrenaline was monitored in rat aorta strips that have alpha1a- and alpha1d-adrenoceptors, pretreated with 1 mM ONOO-1. Either 0.3 N NaOH or the decomposed ONOO-1 was used as the control. MEASUREMENTS AND MAIN RESULTS: The specific binding of [3H]prazosin to alpha1a- and alpha1d-adrenoceptor was inhibited by ONOO-1 in a concentration-dependent manner. We found that 3 mM ONOO-1 decreased maximum binding sites by 40% to 50% in alpha1a- and alpha1d-adrenoceptors. Binding affinities for prazosin and noradrenaline were not affected by 1 mM ONOO-1 in all subtypes. We found that 3-nitro-l-tyrosine did not affect the prazosin binding to three adrenoceptor subtypes. Noradrenaline increased intracellular Ca2+ concentration ([Ca2+]i) concentration-dependently, which was inhibited by ONOO-1 in alpha1a- and alpha1d-adrenoceptors. ONOO-1 had no effect on alpha1b-adrenoceptor. Contractile force produced by noradrenaline decreased significantly in aorta strips pretreated with ONOO-1. CONCLUSION: ONOO-1 reduces the binding capacity of alpha1a- and alpha1d- but not alpha1b-adrenoceptors without changing the affinities. Treatment with ONOO-1 attenuates noradrenaline-stimulated increase in [Ca2+]i in alpha1a- and alpha1d-adrenoceptors but not in alpha1b-adrenoceptor. ONOO-1 also weakens noradrenaline-induced contractions in rat aorta that has alpha1a- and alpha1d-adrenoceptors. Cardiovascular hyporeactivity to catecholamines in septic shock may be caused in part by the inactivation of alpha-adrenoceptors by ONOO-1.     

Gene therapy of coronary artery disease with phvegf165--early outcome

BACKGROUND: Gene therapy is a new, experimental method of treatment in patients with coronary artery disease (CAD). AIM: To determine the safety and efficacy of gene encoding vascular endothelial growth factor (VEGF165) administered directly into the myocardium as the single treatment or combined with coronary artery by-pass grafting (CABG). METHODS: VEGF gene transfer was performed in 22 patients (20 male, 2 female, ages from 48 to 73 years old). A 200 micro g of the plasmid encoding VEGF165 was injected into the ischaemic myocardium which could not be surgically revascularised in patients undergoing CABG (n=14), and 400 micro g - in patients without CABG (n=8). The value of ejection fraction (EF), myocardial perfusion, angiogram, ventriculography, and nitroglycerine consumption as well as quality of life were evaluated pre- and postoperatively. RESULTS: The majority of patients had no complications and no fatal outcome was observed. Two patients developed acute myocardial infarction. Left ventricular function values improved and the majority of patients were free from angina 6 months after surgery. Patients reported improved quality of life and a reduction in nitroglycerine usage. A reduction in the ischaemic defects detected by SPECT was also observed. In some patients angiography revealed improved collateral filling. CONCLUSIONS: Direct myocardial administration of genes encoding VEGF165 can be an effective method of treatment in patients with chronic and advanced CAD either as a supplementary treatment or as a single therapy.     

Wisconsin syndrome in a patient with interstitial deletion of the long arm of chromosome 3: further delineation of the phenotype

Interstitial deletions of the long arm of chromosome 3 are uncommon. Most cases are related to the blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), which is mapped to 3q23. We report on a case with a de novo chromosomal deletion of 3q23 and 3q25. We review the literature on the reported cases of 3q deletion and find that the condition of our patient is not typical of the BPES. Rather, she shares similarity to a patient with Wisconsin syndrome, first discovered in 1976.     

Histologic changes of pulmonary arteries in congenital heart disease with left-to-right shunt (part 2): emphasis on the significance of pulmonary arterial concentration in the correlation with pulmonary hemodynamics after repair Ed-- the above is an alternative title for your consideration

We performed this study to assess the correlation of residual pulmonary hypertension in the immediate postoperative period with that in the late follow-up period, to assess the histologic changes of pulmonary arteries (PA) at the time of repair for patients with congenital heart disease consisting of left-to-right shunt, and to clarify the role of lung biopsy in determining the operability and reversibility of pulmonary vascular changes. Lung biopsy was performed during repair in 38 patients, with a wide range of age, who had congenital left to right shunt and pulmonary hypertension. All were Heath-Edward grade III or less. Morphometric study included measurement of medial wall thickness (MWT) and decrease rate of pulmonary arterial concentration (PAC). Mean PA pressure in the immediate postoperative period was measured in all 38 patients. Follow-up cardiac catheterization was performed in 15 patients (average 3.8 years after repair). At operation, 5 patients of this late follow-up group were under 2 years of age and the other 10 were 2 or more. During catheterization, pulmonary hemodynamic reaction was observed both under room air inhalation and after inhalation of hypoxic gas FiO2 0.15. Mean PA pressure and pulmonary vascular resistance (PVR) in the immediate postoperative period had a significant correlation with PA pressure and PVR values before the operation, but not with morphometry, Heath-Edward grade, or with pulmonary hemodynamics in late follow-up. During the late follow-up study, 5 of the 15 patients had pulmonary hypertension (defined as mean PA pressure > or = 15 mmHg) under room air inhalation, and PA hypertension was induced in 4 additional patients after hypoxic gas inhalation. There was no incidence of PA pressure or PVR values registering above the preoperative level. The degree of PA hypertension showed a correlation with the rate of PAC decrease and also with patients' age-at-operation. Multiple regression analysis showed that both the rate of PAC decrease and the age-at-operation contributed significantly to the degree of PA hypertension. Some of the patients over age 2 had a decreased rate of PAC above the regression line, which none of the patients under age 2 experienced. In patients with Heath-Edward grade III or less, residual pulmonary hypertension in the immediate postoperative period was not correlated with histology, but in late follow-up, it was with PAC and the age-at-operation. Therefore, a decrease of PAC is assumed to be a totally or partially irreversible pulmonary vascular change depending on the patient's age-at-operation, while medial hypertrophy is thought to be a reversible pulmonary vascular change. Lung biopsy could play an important role in determining the reversibility of pulmonary vascular obstruction, particularly in patients older than 2 years. Ed- re highlights above: such hyphenation is optional, but if used then it should be applied consistently throughout the paper. As 3 of the 4 entries in the abstract use it, I have maintained it consistently below.     

Localization of intestinal intraepithelial T lymphocytes involves regulation of alphaEbeta7 expression by transforming growth factor-beta

Induction of alphaEbeta7 expression on T cells by transforming growth factor (TGF)-beta is thought to be important for intestinal intraepithelial T lymphocyte (IEL) entry into the epithelial compartment. However, there has been no in vivo evidence that up-regulation of alphaEbeta7 expression on T cells by TGF-beta is critical for the selective localization of intestinal IEL in the epithelial area. We have recently established transgenic mice expressing Smad7 under the control of a distal lck promoter where TGF-beta/Smad signaling is specifically blocked in mature T cells. Here we showed that TGF-beta-mediated up-regulation of alphaEbeta7 was impaired on T cells isolated from the Smad7 transgenic mice associated with reduced numbers of intestinal IEL when compared with that in wild-type littermates. These results indicated that failure to induce alphaEbeta7 on T cells by TGF-beta resulted in reduced numbers of intestinal IEL, suggesting the importance of alphaEbeta7 expression by TGF-beta in selective localization of intestinal IEL.     

Comparison between conventional cystometry and stimulated filling cystometry by diuretics in a neurogenic bladder after spinal cord injury

OBJECTIVE: To determine in the neurogenic bladder whether cystometry performed under near physiologic condition by filling stimulation using diuretics reveals different findings compared with conventional cystometry (CMG). DESIGN: One group of subjects from a university teaching hospital was tested in two conditions. The maximum detrusor pressure (MPdet) and compliance of the bladder in CMG and furosemide-stimulated filling cystometry (FCMG) were compared in 27 patients with neurogenic bladder after spinal cord injury. The MPdet was estimated. Compliance was calculated. For CMG, the bladder was filled. FCMG was performed 3 hr after CMG. For FCMG, furosemide was injected after infusion of normal saline. Recording intravesical pressure started after emptying the bladder immediately after furosemide injection. RESULTS: Significant differences were found between CMG and FCMG in hyperreflexic neurogenic bladders with respect to a decrease in MPdet and increase in compliance with FCMG. However, there were no significant differences in MPdet and compliance in hyporeflexic or areflexic neurogenic bladders between the two techniques. CONCLUSION: We have found that FCMG is useful in evaluating both genuine MPdet and compliance in patients with hyperreflexic neurogenic bladder dysfunction. FCMG provides more reliable information on detrusor characteristics than CMG in hyperreflexic neurogenic bladder. We suggest that FCMG is an alternative, effective, and near physiologic diagnostic method, having short assessment time for improving evaluation of the detrusor characteristics of hyperreflexic neurogenic bladder.