Stable π-Extended Thio[7]helicene-Based Diradical with Predominant Through-Space Spin-Spin Coupling.

In this work, a novel π-extended thio[7]helicene scaffold was synthesized, where the α-position of the thiophene unit could be functionalized with bulky phenoxy radicals after considerable synthetic attempts. This open-shell helical diradical, ET7H-R, possesses high stability in the air, nontrivial π conjugation, persistent chirality, and a high diradical character (y0 of 0.998). The key feature is a predominant through-space spin-spin coupling (TSC) between two radicals at the helical terminals. Variable-temperature continuous-wave electron spin resonance (cw-ESR) and superconducting quantum interference device (SQUID) magnetometry in the solid state reveal a singlet ground state with a nearly degenerate triplet state of ET7H-R. These results highlight the significance of a stable helical diradicaloid as a promising platform for investigating intramolecular TSCs.

6,6'-Biindeno[1,2-b]anthracene: An Open-Shell Biaryl with High Diradical Character.

We report in situ generation of a 6,6'-biindeno[1,2-b]anthracene (BIA) derivative as an open-shell biaryl with high diradical character, which could be identified by mass spectrometry, NMR spectroscopy, single-crystal X-ray analysis, UV-vis-NIR absorption spectroscopy, and electron paramagnetic resonance (EPR) spectroscopy. Theoretical calculations by various methods and variable-temperature EPR analyses were performed to tackle the elusive ground state of BIA diradical, suggesting a singlet ground state with a nearly degenerate triplet state. These results provide insight into the design of unique open-shell biaryls.

[Transaortic Thoracic Endovascular Aortic Repair Via Right Anterior Mini-thoracotomy;Report of a Case].

An 81-year-old man presented with ruptured thoracic aortic aneurysm under stable condition. He had been suffering from chronic obstructive pulmonary disease, chronic renal failure and rheumatoid arthritis. We performed hybrid thoracic endovascular aortic repair via right anterior mini-thoracotomy inserting a device through a conduit on the ascending aorta. The patient was discharged without aorta-related complications.

Effects of Age-Related Aortic Root Anatomic Changes on Left Ventricular Outflow Tract Pace-Mapping Morphologies: A Cardiac Magnetic Resonance Imaging Validation Study.

INTRODUCTION: Outflow tract ventricular arrhythmias (OT VAs) are common and catheter ablation is an effective treatment option. We sought to investigate the relationship between age-related anatomic aortic root changes and QRS morphology during left ventricular outflow tract (LVOT) pace-mapping using cardiac magnetic resonance (CMR) imaging. METHODS AND RESULTS: Fifty-one patients undergoing CMR imaging were divided into 3 groups based on age (<40, 40-60, >60 years). We measured the angle of the aortic root, the aorta to ventricular septal angle, the distance between the right coronary cusp (RCC) and left coronary cusp (LCC), and the distance between the ascending and descending aorta. Additionally, we evaluated the QRS morphologies obtained during pace-mapping from the LVOT. In older patients, LCC was more superior to the RCC (P < 0.01). Age was positively correlated with the aortic root angle (r2 = 0.481, P < 0.01) as well as the distances between the ascending and descending aorta at a level below the arch (r2 = 0.569, P < 0.01). In older patients, LVOT pace-mapping (performed in 16 patients) demonstrated higher maximal R-wave amplitude, and was greater when pacing from the LCC versus the RCC in lead III (1.8 ± 0.7 vs. 1.0 ± 0.5 mV, P = 0.02). CONCLUSION: The anatomy of the aortic root changes with age, and age-related aortic root changes may affect the QRS morphology during pace-mapping. Understanding the potential anatomic changes that accompany aging is important to maximize the efficacy of catheter ablation of OT VAs.

Base-catalyzed bifunctional addition to amides and imides at low temperature. A new pathway for carbonyl hydrogenation.

Mono- or dideprotonation at the N-H groups of the Noyori ketone hydrogenation catalyst trans-[RuH2((R)-BINAP)((R,R)-dpen)] (1a) yields trans-M[RuH2((R,R)-HNCH(Ph)CH(Ph)NH2)((R)-BINAP)], where M = K(+)(8-K) or Li(+) (8-Li), or trans-M2[RuH2((R,R)-HNCH(Ph)CH(Ph)NH)((R)-BINAP)], where M = Li(+) (8-M'2), which have unprecedented activity toward the hydrogenation of amide and imide carbonyls at low temperatures in THF-d8. Details of the origins of the enantioselection for the desymmetrization of meso-cyclic imides by hydrogenation with 8-K are also described herein.

Synthesis and characterization of a formal 21-electron cobaltocene derivative.

Metallocenes are highly versatile organometallic compounds. The versatility of the metallocenes stems from their ability to stabilize a wide range of formal electron counts. To date, d-block metallocenes with an electron count of up to 20 have been synthesized and utilized in catalysis, sensing, and other fields. However, d-block metallocenes with more than formal 20-electron counts have remained elusive. The synthesis and isolation of such complexes are challenging because the metal-carbon bonds in d-block metallocenes become weaker with increasing deviation from the stable 18-electron configuration. Here, we report the synthesis, isolation, and characterization of a 21-electron cobaltocene derivative. This discovery is based on the ligand design that allows the coordination of an electron pair donor to a 19-electron cobaltocene derivative while maintaining the cobalt-carbon bonds, a previously unexplored synthetic approach. Furthermore, we elucidate the origin of the stability, redox chemistry, and spin state of the 21-electron complex. This study reveals a synthetic method, structure, chemical bonding, and properties of the 21-electron metallocene derivative that expands our conceptual understanding of d-block metallocene chemistry. We expect that this report will open up previously unexplored synthetic possibilities in d-block transition metal chemistry, including the fields of catalysis and materials chemistry.

Rh(III)-catalyzed directed C-H bond amidation of ferrocenes with isocyanates.

[RhCp*(OAc)(2)(H(2)O)] [Cp* = pentamethylcyclopentadienyl] catalyzed the C-H bond amidation of ferrocenes possessing directing groups with isocyanates in the presence of 2 equiv/Rh of HBF(4)·OEt(2). A variety of disubstituted ferrocenes were prepared in high yields, or excellent diastereoselectivities.

Direct observation of reversible bond homolysis by 2D EXSY NMR.

Bond homolysis is one of the most fundamental bond cleavage mechanisms. Thus, understanding of bond homolysis influences the development of a wide range of chemistry. Photolytic bond homolysis and its reverse process have been observed directly using time-resolved spectroscopy. However, direct observation of reversible bond homolysis remains elusive. Here, we report the direct observation of reversible Co-Co bond homolysis using two-dimensional nuclear magnetic resonance exchange spectroscopy (2D EXSY NMR). The characterization of species involved in this homolysis is firmly supported by diffusion ordered NMR spectroscopy (DOSY NMR). The unambiguous characterization of the Co-Co bond homolysis process enabled us to study ligand steric and electronic factors that influence the strength of the Co-Co bond. Understanding of these factors will contribute to rational design of multimetallic complexes with desired physical properties or catalytic activity.

Experimental investigations of a partial Ru-O bond during the metal-ligand bifunctional addition in Noyori-type enantioselective ketone hydrogenation.

The transition state for the metal-ligand bifunctional addition step in Noyori's enantioselective ketone hydrogenation was investigated using intramolecular trapping experiments. The bifunctional addition between the Ru dihydride trans-[Ru((R)-BINAP)(H)(2)((R,R)-dpen)] and the hydroxy ketone 4-HOCH(2)C(6)H(4)(CO)CH(3) at -80 °C exclusively formed the corresponding secondary ruthenium alkoxide trans-[Ru((R)-BINAP)(H)(4-HOCH(2)C(6)H(4)CH(CH(3))O)((R,R)-dpen)]. Combined with the results of control experiments, this observation provides strong evidence for the formation of a partial Ru-O bond in the transition state.

Myasthenic crisis appearing after resection of intracardiac ectopic thymoma with superior vena cava syndrome.

BACKGROUND: We describe herein an extremely rare case of intracardiac ectopic thymoma-only two pure cases have been reported to date-associated with myasthenia gravis, an infrequent complication of ectopic thymoma. CASE PRESENTATION: A 71-year-old woman with superior vena cava syndrome was found to have a large mass mainly located in the right atrium. Tumor resection under cardiopulmonary bypass was performed. The pathological diagnosis was type AB ectopic thymoma. The postoperative course was complicated by progressive respiratory failure, and she was diagnosed with myasthenic crisis based on clinical signs and the edrophonium test. The patient recovered and was weaned from prolonged mechanical ventilation after receiving intravenous immunoglobulin, and was subsequently discharged uneventfully. CONCLUSIONS: This is the first report of myasthenic crisis due to intracardiac ectopic thymoma. Residual thymoma is a risk factor for the development of post-thymectomy myasthenia gravis, and long-term follow-up is required.

Desymmetrization of meso-cyclic imides via enantioselective monohydrogenation.

meso-Cyclic imides are monohydrogenated to form the corresponding hydroxy lactams in 88-97% ee using trans-[Ru((R)-BINAP)(H)(2)((R,R)-dpen)] and related compounds as catalysts with base in THF. The hydrogenation proceeds with high enantiogroup- and chemoselectivity, and it is a desymmetrization reaction, forming up to five stereogenic centers in one reaction. Conversion of a hydroxy lactam into the corresponding iminium ion followed by addition of indene extended the number of stereogenic centers from 5 to 7.

Rescue of pulmonary hypertension with an oral sulfonamide antibiotic sulfisoxazole by endothelin receptor antagonistic actions.

Pulmonary hypertension (PH) is a disease of unknown etiology that ultimately causes right ventricle heart failure with a lethal outcome. An increase in circulating endothelin (ET)-1 levels may contribute to disease progression. This study aimed to examine the possible effects of an orally active ET receptor antagonist, sulfisoxazole (SFX), for the rescue of PH, right ventricular hypertrophy, and eventual right ventricular failure. PH rats (single injection of monocrotaline [MCT]) were treated with an ET antagonist, SFX, an orally active sulfonamide antibody. Effects of SFX on PH rats were assessed in terms of survival rate, pulmonary artery blood pressure (PABP), autonomic nerve activity, and atrial natriuretic peptide (ANP) concentration in right ventricular myocytes and plasma. SFX did not change systemic blood pressure, however, it significantly suppressed the elevation of PABP. SFX maintained the derangement of autonomic nerve control, blunted an increase in ANP in myocytes and plasma, and significantly improved survival in right heart failure and/or related organs dysfunction in PH rats. The ET antagonistic action of the antimicrobial agent, SFX, was experimentally confirmed for treatment of PH in rats.

Perioperative management for iatrogenic aortocoronary dissection during percutaneous coronary intervention.

Aortocoronary dissection is a rare but serious complication. We report the case of a 72-year-old female with angina. Percutaneous coronary intervention was performed for right coronary artery disease. Manipulation of the guiding catheter led to aortocoronary dissection. A drug-eluting stent was immediately implanted in the right coronary ostium to seal the entry of the dissection. Computed tomography (CT) showed ascending aortic dissection. The patient was observed without surgery. CT performed the following day and showed the contrast in the false lumen which had disappeared. Clinicians are more likely to avoid surgical treatment if stenting successfully seals the entry of the coronary dissection.

Simplified elephant trunk technique promotes thrombo-occlusion of the false lumen in acute type A aortic dissection.

OBJECTIVE: We developed a "simplified elephant trunk (SET) graft technique" as a refinement of the original elephant trunk. A cuff is created in a single 4-branched graft, which is used for the distal anastomosis; the residual distal graft is used as the trunk. We expected the SET would secure the anastomosis and promote the thrombo-occlusion of the false lumen in the down stream of the aorta. In this paper, we highlight the usage of the SET for arch replacement of acute aortic dissection cases in comparison with the same arch replacement without the SET method. PATIENTS AND METHODS: Between March 1996 and March 2002, 35 patients underwent arch replacement for acute aortic dissection. Twenty-two of them had a patent false lumen in the downstream aorta at the operation and 17 (SET: 8, non-SET (NSET) : 9) out of 22 underwent enhanced computed tomography (CT) scan 2 weeks after and 1 year after operation. We calculated the ratio of the false lumen in the aorta (F ratio) and the ratio of the patent false lumen in the whole false lumen (E ratio) by CT scan. These values were calculated every 3 cm down to 15 cm below the anastomosis, thus resulting in 5 segments. RESULTS: The false lumen throughout all segments disappeared (F ratio =0) in none of both group 2 weeks after operation. One year thereafter, in 5 (63%) patients in the SET group, no false lumen in any segment existed, while in contrast a false lumen still existed in some of the segments in all NSET patients. Although neither the F and E ratio of the NSET group change during this period in any segments, those of the SET group decreased significantly in all the segments except for the E ratio of segment 5. CONCLUSION: The SET promoted thrombo-occlusion thus leading to the disappearance of the residual false lumen, possibly by avoiding persistent endoleakage at the anastomotic site.

Unique Technique for Open Surgical Repair after Failed Endovascular Aneurysm Repair with Proximal Anastomoses.

Endovascular aortic aneurysm repair (EVAR) has revolutionized the management of abdominal aortic aneurysms (AAAs), with lower perioperative morbidity and mortality compared to conventional surgical repair. However, late secondary re-interventions after EVAR are still needed before aneurysm rupture in many cases. A patient with impending rupture of an AAA associated with a type I endoleak 7 years after EVAR who was successfully treated with a unique technique of fixation of the proximal aortic neck taking into account the structure of the stent graft is reported. This technique offers a safe solution to late open conversion after failed EVAR.

How Local Annular Force and Collagen Density Govern Mitral Annuloplasty Ring Dehiscence Risk.

BACKGROUND: Annuloplasty ring dehiscence is a well described mode of mitral valve repair failure. Defining the mechanisms underlying dehiscence may facilitate its prevention. METHODS: Factors that govern suture dehiscence were examined with an ovine model. After undersized ring annuloplasty in live animals (n = 5), cyclic force (FC) that acts on sutures during cardiac contraction was measured with custom transducers. FC was measured at ten suture positions, throughout cardiac cycles with peak left ventricular pressure (LVPmax) of 100, 125, and 150 mm Hg. Suture pullout testing was conducted on explanted mitral annuli (n = 12) to determine suture holding strength at each position. Finally, relative collagen density differences at suture sites around the annulus were assessed by two-photon excitation fluoroscopy. RESULTS: Anterior FC exceeded posterior FC at each LVPmax (eg, 2.8 ± 1.3 N versus 1.8 ± 1.2 N at LVPmax = 125 mm Hg, p < 0.01). Anterior holding strength exceeded posterior holding strength (6.4 ± 3.6 N versus 3.9 ± 1.6 N, p < 0.0001). On the basis of FC at LVPmax of 150 mm Hg, margin of safety before suture pullout was vastly higher between the trigones (exclusive) versus elsewhere (4.8 ± 0.9 N versus 1.9 ± 0.5 N, p < 0.001). Margin of safety exhibited strong correlation to collagen density (R(2) = 0.947). CONCLUSIONS: Despite lower cyclic loading on posterior sutures, the weaker posterior mitral annular tissue creates higher risk of dehiscence, apparently because of reduced collagen content. Sutures placed atop the trigones are less secure than predicted, because of a combination of reduced collagen and higher overall rigidity in this region. These findings highlight the inter-trigonal tissue as the superior anchor and have implications on the design and implantation techniques for next-generation mitral prostheses.

Injectable Shear-Thinning Hydrogels for Minimally Invasive Delivery to Infarcted Myocardium to Limit Left Ventricular Remodeling.

BACKGROUND: Injectable, acellular biomaterials hold promise to limit left ventricular remodeling and heart failure precipitated by infarction through bulking or stiffening the infarct region. A material with tunable properties (eg, mechanics, degradation) that can be delivered percutaneously has not yet been demonstrated. Catheter-deliverable soft hydrogels with in vivo stiffening to enhance therapeutic efficacy achieve these requirements. METHODS AND RESULTS: We developed a hyaluronic acid hydrogel that uses a tandem crosslinking approach, where the first crosslinking (guest-host) enabled injection and localized retention of a soft (<1 kPa) hydrogel. A second crosslinking reaction (dual-crosslinking) stiffened the hydrogel (41.4±4.3 kPa) after injection. Posterolateral infarcts were investigated in an ovine model (n≥6 per group), with injection of saline (myocardial infarction control), guest-host hydrogels, or dual-crosslinking hydrogels. Computational (day 1), histological (1 day, 8 weeks), morphological, and functional (0, 2, and 8 weeks) outcomes were evaluated. Finite-element modeling projected myofiber stress reduction (>50%; P<0.001) with dual-crosslinking but not guest-host injection. Remodeling, assessed by infarct thickness and left ventricular volume, was mitigated by hydrogel treatment. Ejection fraction was improved, relative to myocardial infarction at 8 weeks, with dual-crosslinking (37% improvement; P=0.014) and guest-host (15% improvement; P=0.058) treatments. Percutaneous delivery via endocardial injection was investigated with fluoroscopic and echocardiographic guidance, with delivery visualized by magnetic resonance imaging. CONCLUSIONS: A percutaneous delivered hydrogel system was developed, and hydrogels with increased stiffness were found to be most effective in ameliorating left ventricular remodeling and preserving function. Ultimately, engineered systems such as these have the potential to provide effective clinical options to limit remodeling in patients after infarction.

Implantation of the Medtronic Harmony Transcatheter Pulmonary Valve Improves Right Ventricular Size and Function in an Ovine Model of Postoperative Chronic Pulmonary Insufficiency.

BACKGROUND: Pulmonary insufficiency is the nexus of late morbidity and mortality after transannular patch repair of tetralogy of Fallot. This study aimed to establish the feasibility of implantation of the novel Medtronic Harmony transcatheter pulmonary valve (hTPV) and to assess its effect on pulmonary insufficiency and ventricular function in an ovine model of chronic postoperative pulmonary insufficiency. METHODS AND RESULTS: Thirteen sheep underwent baseline cardiac magnetic resonance imaging, surgical pulmonary valvectomy, and transannular patch repair. One month after transannular patch repair, the hTPV was implanted, followed by serial magnetic resonance imaging and computed tomography imaging at 1, 5, and 8 month(s). hTPV implantation was successful in 11 animals (85%). There were 2 procedural deaths related to ventricular fibrillation. Seven animals survived the entire follow-up protocol, 5 with functioning hTPV devices. Two animals had occlusion of hTPV with aneurysm of main pulmonary artery. A strong decline in pulmonary regurgitant fraction was observed after hTPV implantation (40.5% versus 8.3%; P=0.011). Right ventricular end diastolic volume increased by 49.4% after transannular patch repair (62.3-93.1 mL/m2; P=0.028) but was reversed to baseline values after hTPV implantation (to 65.1 mL/m2 at 8 months, P=0.045). Both right ventricular ejection fraction and left ventricular ejection fraction were preserved after hTPV implantation. CONCLUSIONS: hTPV implantation is feasible, significantly reduces pulmonary regurgitant fraction, facilitates right ventricular volume improvements, and preserves biventricular function in an ovine model of chronic pulmonary insufficiency. This percutaneous strategy could potentially offer an alternative for standard surgical pulmonary valve replacement in dilated right ventricular outflow tracts, permitting lower risk, nonsurgical pulmonary valve replacement in previously prohibitive anatomies.

Development of off-pump mitral valve replacement in a porcine model.

PURPOSE: We describe our initial experience with on-bypass and off-bypass (off-pump) mitral valve replacement with the modified version of our novel catheter-based sutureless mitral valve (SMV) technology, which was developed to atraumatically anchor and seal in the mitral position. DESCRIPTION: The SMV is a self-expanding device consisting of a custom designed nitinol framework and a pericardial leaflet valve mechanism. For the current studies, our original device was modified (SMV2) to reduce the delivery profile and to allow for controlled deployment while still maintaining the key principles necessary for atraumatic anchoring and sealing in the mitral valve position. EVALUATION: Ten Yorkshire pigs underwent successful SMV2 device implantation through a left atriotomy (on-pump, n = 6; off-pump, n = 4). Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Postmortem examination demonstrated that the SMV2 devices were anchored securely. CONCLUSIONS: This study demonstrates the feasibility and short-term success of off-pump mitral valve replacement using a novel, catheter-based device in a porcine model.