Characteristics of Inoperable Patients with Severe Aortic Valve Stenosis —In the Era of Transcatheter Aortic Valve Replacement

Purpose: Transcatheter aortic valve replacement (TAVR) has emerged as a therapeutic option for severe aortic valvular stenosis (AS). To determine the indication for TAVR, it is mandatory to clarify the characteristics of the patients who were judged as inoperable for conventional aortic valve replacement (cAVR).Methods: Of 185 patients newly diagnosed as severe AS from March 2010 to April 2011, we studied the characteristics of 61 (33%) patients (mean age, 86 ± 8 years) who were judged as inoperable.Results: Younger patients (<85 years old, n = 22) had more major comorbidities and lower left ventricular ejection fraction than older patients (≥85 years old, n = 39). Mean estimated mortality for cAVR by Japan score was 7.0% ± 7.4%. Japan score did not correlate to age and was calculated relatively low in the older age group (6.2% ± 7.0%) than the younger age group (8.3% ± 8.1%).Conclusion: One thirds of severe AS patients were judged as inoperable. In advanced age patients, age itself and other factors, which are not included in the conventional scoring systems, might have contributed to the decision making not to perform cAVR by cardiologists. Further study is necessary to define risk factors except for age.     

Direct Transmission of H. pylori from Challenged to Nonchallenged Mice in a Single Cage

To understand whether direct transmission of H. pylori occurs from infected mouse to noninfected mouse, the system using a mouse model we developed previously was tested. Six nude mice were challenged with H. pylori inocula; one group consisted of one challenged nude mouse 1 week after inoculation raised with four nonchallenged nude mice in a single cage. For the single cage, a polycarbonate cage or a mesh-floor cage was used. Then three groups were kept in a polycarbonate cage and the other three groups kept in a mesh-floor cage to avoid H. pylori transmission through stool. After coraising for 1, 2, or 3 weeks, all mice were sacrificed to determine the existence of H. pylori in the stomach, saliva, and stool by culture or PCR and H. pylori-associated gastritis. RAPD fingerprinting patterns using different primers of isolated strains from challenged and nonchallenged mice were compared to understand the origin of transmitted strains. During 3 weeks after coraising of H. pylori challenged and nonchallenged mice, H. pylori was detected in the stomachs in 3 of 12 nonchallenged mice in the polycarbonate cage and in 2 of 12 nonchallenged mice in the cage with a steel mesh floor. H. pylori was detected from saliva or stool in two nonchallenged, infected mice in the polycarbonate cage. Moreover, RAPD fingerprinting using different primers of the total five strains isolated from five nonchallenged, infected mice in both cages showed the same pattern and concordance with that of the challenged strain and the strains isolated from challenged mice. It is demonstrated that intimate interaction is the cause of H. pylori transmission via saliva and stool.     

Intimal hyperplasia of experimental autologous vein graft in hyperlipidemic rabbits with poor distal run-off

Poor distal runoff and hyperlipidemia are factors affecting the fate of an implanted graft. In the present study, combined effects of poor distal runoff and hyperlipidemia on intimal hyperplasia (IH) of the vein graft were examined in a newly developed poor distal runoff model in rabbits. A poor distal runoff model was prepared in the right hindlimb of 30 rabbits. These animals were divided into two groups, depending on the diet provided; normolipidemic diet group (Group NL, n = 14) and hyperlipidemic 1% cholesterol diet group (Group HL, n = 16). Four weeks after preparing the poor runoff model, the femoral vein was implanted into the ipsilateral femoral artery. At 2, 4 and 6 weeks, the grafts were harvested. IH of the graft was measured and macrophages in the IH were examined immunohistochemically. Intimal cell proliferation was also determined by bromodeoxyuridine (BrdU) incorporation. IH of the vein graft was significantly accelerated in cases of poor distal runoff and hyperlipidemia. There were no macrophages in the IH in the NL group. In the HL group, macrophages infiltrated the outer layer of IH, sometimes just above the internal elastic lamina, and increased with time. In the poor distal runoff limbs at 6 weeks, macrophages also appeared in the subendothelial layer but were absent in that layer in the controls. Intimal cell proliferation expressed as the Brd U labeling index (LI) was maximum at 2 weeks. In the HL group, BrdU LI of 1H in the poor distal runoff limb was higher than in the control at 2 and 4 weeks. Throughout the experiments, BrdU Us in the HL group were significantly higher than in the NL. Hyperlipidemia accelerates intimal cell proliferation to a greater extent, then does 1H. In cases of a poor distal runoff, the enhancement of cell proliferation by hyperlipidemia is augmented. These responses, in the presence of a hyperlipidemia, may be closely related to the migration of macrophages.     

Role of endothelium-derived hyperpolarizing factor in ACE inhibitor-induced renal vasodilation in vivo

Although the angiotensin-converting enzyme (ACE) inhibitor-induced bradykinin enhances nitric oxide (NO) release, bradykinin may also stimulate the production of an additional vasodilator, endothelium-derived hyperpolarizing factor (EDHF). This study examined the role of EDHF in mediating the NO-independent action of ACE inhibitors in canine renal microcirculation in vivo. We used intravital CCD camera videomicroscopy that allowed direct visualization of renal microcirculation in superficial and juxtamedullary nephrons in an in vivo, in situ, and relatively intact setting. In the presence of E4177 (an angiotensin receptor blocker), cilazaprilat (30 microg/kg) had no effect on diameter of superficial afferent arterioles (Aff), but it increased renal contents of bradykinin and nitrate plus nitrite, and it elicited dilation of juxtamedullary Aff (from 24.0+/-0.2 to 28.2+/-0.8 microm), juxtamedullary efferent arterioles (Eff) (from 24.2+/-0.2 to 28.0+/-0.8 microm), and superficial Eff (from 18.2+/-0.2 to 19.7+/-0.2 microm). These changes in diameters were prevented by N(alpha)-adamantaneacetyl-d-Arg-[Hyp(3),Thi(5,8),D-Phe(7)]bradykinin, a bradykinin receptor antagonist. The pretreatment with nitro-l-arginine methylester (l-NAME) plus E4177 eliminated the dilator response of juxtamedullary/superficial Eff and the increase in renal nitrate plus nitrite levels induced by cilazaprilat. In contrast, in the presence of E4177+l-NAME, cilazaprilat still caused 8%+/-3% dilation of juxtamedullary Aff, which was completely eliminated by proadifen, a cytochrome-P450 and K(Ca) channel blocker. Collectively, the ACE inhibitor exerts multiple vasodilator mechanisms, including the inhibition of angiotensin II formation; blockade of angiotensin II activity appears to be a dominant mechanism in superficial Aff, whereas the bradykinin-induced NO acts on superficial Eff and juxtamedullary Aff/Eff. Furthermore, a putative EDHF is an additional mechanism for the ACE inhibitor-induced vasodilation of juxtamedullary Aff in vivo.     

Predictors of left ventricular remodeling in patients with acute myocardial infarction participating in cardiac rehabilitation.

BACKGROUND: This study was designed to determine the factors influencing the development of left ventricular (LV) remodeling in patients participating in a comprehensive cardiac rehabilitation (CR) program after acute myocardial infarction (AMI), with special reference to exercise intensity and frequency. METHODS AND RESULTS: A total of 72 patients with AMI participated in CR consisting of exercise training of moderate intensity (heart rate reserve 40-60%) and education for 12 weeks. Plasma concentration of brain natriuretic peptide (BNP) was measured at the beginning and the end of CR. Echocardiography was performed before and 1 year after CR. An increase in LV end-diastolic dimension (delta-LVDd) from baseline was used as an index of remodeling. Delta-LVDd was significantly greater in patients with an anterior AMI than with other infarct locations (p<0.05) and correlated significantly with baseline BNP concentration (p<0.05). Delta-LVDd >5 mm occurred exclusively in patients with baseline BNP >150 pg/ml. Variables representing the intensity and frequency of exercise training did not correlate with delta-LVDd. CONCLUSIONS: In patients with AMI participating in CR, those having both anterior infarction and baseline BNP concentration >150 pg/ml are at high risk for subsequent LV remodeling, whereas neither exercise intensity nor participation frequency in CR appears to be associated with LV remodeling.