Akira Shiose

Mammalian formin fhod3 regulates actin assembly and sarcomere organization in striated muscles.

Actin filament assembly in nonmuscle cells is regulated by the actin polymerization machinery, including the Arp2/3 complex and formins. However, little is known about the regulation of actin assembly in muscle cells, where straight actin filaments are organized into the contractile unit sarcomere. Here, we show that Fhod3, a myocardial formin that localizes to thin actin filaments in a striated pattern, regulates sarcomere organization in cardiomyocytes. RNA interference-mediated depletion of Fhod3 results in a marked reduction in filamentous actin and disruption of the sarcomeric structure. These defects are rescued by expression of wild-type Fhod3 but not by that of mutant proteins carrying amino acid substitution for conserved residues for actin assembly. These findings suggest that actin dynamics regulated by Fhod3 are critical for sarcomere organization in striated muscle cells.

Usefulness of fasudil, a Rho-kinase inhibitor, to treat intractable severe coronary spasm after coronary artery bypass surgery.

We have recently demonstrated that fasudil, a Rho-kinase inhibitor, is effective in suppressing coronary artery spasm in patients with vasospastic angina. Thus, blockade of Rho-kinase may provide a novel therapeutic strategy to treat ischemic coronary syndrome caused by the spasm. Severe coronary artery spasm still remains a life-threatening serious complication of coronary artery bypass grafting (CABG). In this study, we examined the inhibitory effect of fasudil in patients with intractable severe coronary spasm after CABG. Three patients who underwent CABG showed severe myocardial ischemia resistant to intensive therapy with intravenous conventional vasodilators, including isosorbide dinitrate (ISDN), diltiazem, and nicorandil. Coronary angiography revealed severe coronary spasm in native coronary arteries and/or bypass arterial grafts in all patients. Since intracoronary and/or intragraft administration of ISDN was ineffective to resolve the spasm, we then administered fasudil (1.5 mg/min for 15 minutes) into the spastic arteries. Fasudil successfully resolved the spasm and improved myocardial ischemia in all patients without any systemic adverse effects. In conclusion, the treatment with fasudil may be useful to treat intractable and otherwise fatal coronary spasm resistant to intensive conventional vasodilator therapy after CABG.

Progress on the Design and Development of the Continuous-Flow Total Artificial Heart

Cleveland Clinics continuous-flow total artificial heart has one motor and one rotating assembly supported by a hydrodynamic bearing. The right hydraulic output is self regulated by passive axial movement of the rotating assembly to balance itself with the left output. The purpose of this article is to present progress in four areas of development: the automatic speed control system, self-regulation to balance right/left inlet pressures and flows, hemolysis testing using calf blood, and coupled electromagnetics (EMAG) and computational fluid dynamics (CFD) analysis. The relationships between functions of motor power and speed, systemic flow, and systemic vascular resistance (SVR) were used for the sensorless speed control algorithm and demonstrated close correlations. Based on those empirical relationships, systemic flow and SVR were calculated in the system module and showed good correlation with measured pump flow and SVR. The automatic system adjusted the pumps speed to obtain the target flow in response to the calculated SVR. Atrial pressure difference (left minus right atrial pressure) was maintained within ±10 mm Hg for a wide range of SVR/pulmonary vascular resistance ratios, demonstrating a wide margin of self-regulation under fixed-speed mode and 25% sinusoidally modulated speed mode. Hemolysis test results indicated acceptable values (normalized index of hemolysis <0.01 mg/dL). The coupled EMAG/CFD model was validated for use in further device development.

An outbreak of Pseudomonas aeruginosa infections following thoracic surgeries occurring via the contamination of bronchoscopes and an automatic endoscope reprocessor

An outbreak of Pseudomonas aeruginosa infections occurred after thoracic surgeries performed between May and June 2003. Clinical data of seven patients were reviewed and the fact was revealed that bronchoscopes were used during endotracheal intubation for one-lung ventilation in most patients. P. aeruginosa was recovered from the sputum of these patients at a very early stage post-operation. Environmental samples from bronchoscopes and an automated endoscope reprocessor (AER) were cultured and P. aeruginosa strains were recovered from all of them. All of these strains were confirmed to be identical by pulsed-field gel electrophoresis (PFGE). Inspection of the sterilization cycles of bronchoscopes revealed inappropriate management of bronchoscopes and a flaw in the AER; once its detergent tank was contaminated, it was not possible to disinfect it. After all the bronchoscopes had been disinfected, and the washing machine had been remodeled, with the washing process confirmed to be appropriate, the outbreak finally ended. This outbreak had two causes, a flaw in the AER and inappropriate disinfection procedures. Outbreaks associated with bronchoscopic examinations have been reported elsewhere. Bronchoscopes are widely used to facilitate endotracheal intubation, especially for one-lung anesthesia. Although they are used for only a short time during anesthetic procedures, we should handle them more carefully.

Long-term results of isolated tricuspid valve replacement

The long-term outcome of isolated tricuspid valve replacement is unclear because this procedure is rare and usually performed in combination with replacement of other valves. The results of all 31 isolated tricuspid valve replacements carried out in 23 patients in Kyushu University Hospital between 1975 and 2004 were retrospectively reviewed. A bioprosthesis was used in 27 cases and a mechanical valve in 4. There were 2 operative deaths and 4 late deaths. One patient with a mechanical prosthesis needed redo tricuspid valve replacement due to valve thrombosis 6 months after surgery. The mean cardiothoracic ratio and functional class improved significantly postoperatively. At 15 years after tricuspid valve replacement, actuarial survival was 75.6% and freedom from valve-related events was 84.9%. For bioprostheses, freedom from structural valve deterioration at 5, 10 and 15 years was 95.2%, 95.2% and 85.7%, respectively. The long-term results of tricuspid valve replacement are considered satisfactory, and a bioprosthesis can be recommended due to its good outcome and no need for anticoagulation. We should not wait until the development of endstage cardiac impairment before carrying out tricuspid valve surgery.

Implantable Continuous-Flow Right Ventricular Assist Device: Lessons Learned in the Development of a Cleveland Clinic Device

Although the need for right ventricular assist device (RVAD) support for right ventricular failure after the implantation of a continuous-flow left ventricular assist device has decreased, right ventricular failure still occurs in as many as 44% of patients after continuous-flow left ventricular assist device insertion. Cleveland Clinics DexAide continuous-flow RVAD was implanted in 34 calves during the course of its development. This review discusses lessons learned in the design and development of an implantable continuous-flow RVAD that are drawn from the results of these in vivo studies, our clinical experience with RVAD support, and a review of previously published reports on clinical RVAD use.

Superior Chest Drainage With an Active Tube Clearance System: Evaluation of a Downsized Chest Tube

PURPOSE We developed a small-diameter (20-French [Fr]) chest drainage system that incorporates an active tube clearance (ATC) system, and we evaluated its efficacy in an acute hemothorax model. DESCRIPTION The ATC system includes an internal guidewire that can be advanced into the lumen of the chest tube to keep the tube from clogging. In six pigs, a 20-Fr ATC tube was placed on one side and a 32-Fr standard tube on the other, and 120 mL of fresh blood was infused into each pleural space every 15 minutes for a total of 840 mL. EVALUATION The amount of drainage for 2 hours with a 20-Fr ATC tube was significantly greater than that with the 32-Fr standard tube (525 ± 179 mL vs 183 ± 85 mL; p = 0.0032). CONCLUSIONS This is the first time a smaller diameter tube has been shown to have better drainage in the setting of acute bleeding compared with larger diameter tubes.

Isolated pulmonary valve replacement: analysis of 27 years of experience

The aim of this study was to investigate the longterm results of isolated pulmonary valve replacement using xenobioprostheses or mechanical valves. Twenty-four cases of isolated pulmonary valve replacement carried out at Kyushu University Hospital between 1977 and 2004 were reviewed. Those undergoing Rastelli’s operation were excluded from this study. Bioprostheses were used in 18 patients and mechanical valves in 6. There were no operative deaths. Two patients with mechanical valves needed repeat pulmonary valve replacement due to thrombosed valves. The patients with bioprostheses had no need of repeat replacement postoperatively. The cardiothoracic ratio significantly improved from 60.3% preoperatively to 55.4% postoperatively (P < 0.05), and the New York Heart Association (NYHA) class significantly improved from 2.0 preoperatively to 1.1 postoperatively (P < 0.05). The actuarial survival rate at 15 years was 92.3%. The valve-related event-free ratio at 15 years was 85.7% in the bioprosthesis group and 66.7% in the mechanical valve group, with no significant difference. Isolated pulmonary valve replacement with bioprostheses or mechanical valves can be safely done and showed satisfactory long-term results. The mechanical valve group demonstrated a high ratio of thrombosed valves. A bioprosthesis is recommended for pulmonary valve replacement if a homograft is not available.

Preload Sensitivity in Cardiac Assist Devices

With implantable cardiac assist devices increasingly proving their effectiveness as therapeutic options for end-stage heart failure, it is important for clinicians to understand the unique physiology of device-assisted circulation. Preload sensitivity as it relates to cardiac assist devices is derived from the Frank-Starling relationship between human ventricular filling pressures and ventricular stroke volume. In this review, we stratify the preload sensitivity of 17 implantable cardiac assist devices relative to the native heart and discuss the effect of preload sensitivity on left ventricular volume unloading, levels of cardiac support, and the future development of continuous-flow total artificial heart technology.

In Vivo Biocompatibility Evaluation of a New Resilient, Hard-Carbon, Thin-Film Coating for Ventricular Assist Devices

The purpose of this study was to evaluate in vivo the biocompatibility of BioMedFlex (BMF), a new resilient, hard-carbon, thin-film coating, as a blood journal bearing material in Cleveland Hearts (Charlotte, NC, USA) continuous-flow right and left ventricular assist devices (RVADs and LVADs). BMF was applied to RVAD rotating assemblies or both rotating and stator assemblies in three chronic bovine studies. In one case, an LVAD with a BMF-coated stator was also implanted. Cases 1 and 3 were electively terminated at 18 and 29 days, respectively, with average measured pump flows of 4.9 L/min (RVAD) in Case 1 and 5.7 L/min (RVAD) plus 5.7 L/min (LVAD) in Case 3. Case 2 was terminated prematurely after 9 days because of sepsis. The sepsis, combined with running the pump at minimum speed (2000 rpm), presented a worst-case biocompatibility challenge. Postexplant evaluation of the blood-contacting journal bearing surfaces showed no biologic deposition in any of the four pumps. Thrombus inside the RVAD inlet cannula in Case 3 is believed to be the origin of a nonadherent thrombus wrapped around one of the primary impeller blades. In conclusion, we demonstrated that BMF coatings can provide good biocompatibility in the journal bearing for ventricular assist devices.