Hydrodynamic characteristics of a membrane oxygenator: modeling of pressure-flow characteristics and their influence on apparent viscosity.

The viscosity obtained from pressure-flow characteristics of an oxygenator may help to detect factors that change oxygenator resistance. The objective of this study was to model pressure-flow characteristics of a membrane oxygenator with an integrated arterial filter and to quantify their influence on apparent viscosity of non-Newtonian fluids. One Newtonian fluid (glycerin solution) and two non-Newtonian fluids (whole bovine blood and a human red blood cell suspension) were perfused through an oxygenator and their pressure-flow characteristics examined systematically. Four resistance parameters for the pressure gradient characteristics approximation equation were obtained by the least squares method from the relational expression of pressure-flow characteristics and viscosity. For all three fluids, a non-linear flow to pressure change was observed with a coefficient of determination of almost 1 by exponential approximation. The glycerin solution had a higher pressure gradient (10-70%) than the other fluids; the apparent viscosity of the non-Newtonian fluids was around 35% lower than the static one measured by a torsional oscillation viscometer. Overall, our study demonstrated that the influence on the apparent viscosity of non-Newtonian fluids can be quantified by pressure gradient differences in a membrane oxygenator with an integrated arterial filter.

Concurrent analysis of human equilibrative nucleoside transporter 1 and ribonucleotide reductase subunit 1 expression increases predictive value for prognosis in cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy.

BACKGROUND: The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC). METHODS: Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated. RESULTS: High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced. CONCLUSIONS: Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC.

A novel measurement and delivery system for synchronizing oxygen gas flow with blood flow during cardiopulmonary bypass.

Monitoring the blood pump and the oxygen gas flow meter are important maneuvers at the initiation of cardiopulmonary bypass (CPB). We present a novel system, designed to improve safety in the heart-lung machine by linking the control of blood flow and the oxygen gas flow meter. This system uses a mass flow controller to provide and control oxygen flow based on the ventilation-perfusion (V/Q) ratio, using the electronic signal of the blood flow. We tested the system, in vitro and in vivo, and examined the resulting level of blood oxygenation. When extracorporeal circulation was initiated, the oxygen flow was instantly linked to the circulating blood flow, providing an adequate V/Q ratio; the partial pressure of oxygen in the blood was maintained at a normal level. Although we have yet to confirm the safety of this system in clinical trials, the new safety assist device can automatically supply oxygen to the oxygenator at the beginning of CPB.

Molecular epidemiology of enteritis-causing methicillin-resistant Staphylococcus aureus.

In the early 1990s, severe enteritis caused by methicillin-resistant Staphylococcus aureus (MRSA enteritis) was prevalent in Japan, but the incidence has since decreased. We compared the genotypes and phenotypes of 12 isolates that caused MRSA enteritis (enteritis isolates), detected between 1990 and 1993, with 186 non-enteritis isolates detected between 1998 and 2002. Organisms were investigated using pulsed-field gel electrophoresis (PFGE), coagulase typing and reverse passive latex agglutination to detect production of staphylococcal enterotoxins (SE) and toxic shock syndrome toxin-1 (TSST-1); and polymerase chain reaction (PCR) for detection of the structural genes entA, entB, entC, entD and tst, which encode proteins SE-A, SE-B, SE-C, SE-D and TSST-1, respectively. The 12 enteritis isolates were classified into four types and four subtypes. Only seven of the 186 non-enteritis isolates had PFGE patterns indistinguishable from the enteritis isolates. Eight of the 12 enteritis isolates had entA, entC and tst, and produced high levels of SE-A and TSST-1, but not SE-C. Of the 186 non-enteritis isolates, 157 produced SE-C and TSST-1, but not SE-A. The seven non-enteritis isolates with a PFGE pattern indistinguishable from the enteritis isolates did not produce SE-A, and showed relatively low levels of TSST-1 production. These isolates may have continued to inhabit our ward since the earlier outbreak, but acquired a different phenotype. In conclusion, the disappearance of MRSA enteritis may have resulted from the decreased incidence of enteritis-causing clones and phenotypical changes.

[Pericardioperitoneal fenestration for chronic exudative pericarditis using a subxiphoidal approach; report of a case].

A 77-year-old woman with a previous history of median sternotomy and collagen disease, presented with chief complaints of resting dyspnea as a result of recurrent pericardial effusions or restrictive ventilatory impairment. She experienced significant symptom amelioration after undergoing pericardioperitoneal fenestration. We weighed the positive against the negative of various pericardial effusion drainage methods in this study. This operative procedure is not innovative, but favorable because it can be carried out conveniently and safely, enabling early rehabilitation without appreciable postoperative complications.

Type 2 angiotensin II receptor is downregulated in cardiomyocytes of patients with heart failure.

BACKGROUND: The human heart expresses type 2 angiotensin (AT(2)) receptor, but the function is poorly defined. METHODS: In the present study, we investigated (1) the cellular localization of the AT(2) receptor and (2) the relationship between the AT(2) receptor protein expression and the cardiac function of patients with ischemic heart disease. The receptor localization was assessed by immunohistochemistry and the protein expression was quantified by Western blotting in atrial tissues freshly obtained from 22 patients undergoing coronary artery bypass graft surgery (63.0+/-11.0 years old; male ratio, 85%). Prior to the surgery, blood was drawn for determination of atrial-natriuretic hormone level and the left ventricular function was assessed by ultrasound cardiography. RESULTS: The results of immunohistochemistry showed that the AT(2) receptor was localized to cardiomyocytes and was not present in fibroblasts, vascular smooth muscles, or vascular endothelium. Atrial tissues showed various degrees of structural remodeling, but the localization of the AT(2) receptor was not altered in any tissue sections. The amount of the AT(2) receptor was negatively correlated with end-diastolic left ventricular diastolic dimension (r=-0.56, P<0.01), calculated left ventricular mass index (r=-0.51, P<0.02) and the plasma atrial natriuretic peptide (ANP) concentration (r=-0. 62, P<0.01) and positively correlated with left ventricular ejection fraction (r=0.48, P<0.05). CONCLUSIONS: (1) The AT(2) receptor is localized to cardiomyocytes independently of the cardiac function. (2) Left ventricular dysfunction is associated with decreased expression of myocardial AT(2) receptor protein.

Ergonovine-induced alterations in coronary flow velocity preceding onset of occlusive spasm in patients without significant coronary artery stenoses.

This study examined serial changes in coronary flow velocity to elucidate the dynamic change of coronary circulation during coronary spasm. Twenty patients with variant angina and 27 control patients were studied. Coronary flow velocity was monitored using a Doppler guidewire following intracoronary ergonovine administration. In the control group, diastolic flow velocity either did not change or increased slightly in response to ergonovine. However, in patients with variant angina, 2 patterns of flow velocity alterations were observed. In the first pattern, flow initially increased and then suddenly decreased (16 of 20 patients). In the second pattern, flow gradually decreased (3 of 20 patients). In the remaining patient, the coronary flow alteration could not be detected because of branch spasm. When abnormally high flow velocity was defined as a 100% increase in flow after ergonovine administration within 1 minute, and abnormally low flow velocity was defined as a 50% decrease in flow to diagnose variant angina, sensitivities of 35%, 75%, and 85% were noted if flow was measured 1.0, 2.0, and 3.0 minutes after ergonovine administration, respectively. These abnormal flow velocities were observed before ischemic ST changes appeared. In conclusion, in patients with variant angina, characteristic serial changes in coronary flow velocity occur before occlusive spasm. Variant angina may be diagnosed earlier by monitoring flow velocity rather than by monitoring for ischemic electrocardiographic changes.

Protection by coenzyme Q10 of canine myocardial reperfusion injury after preservation.

This study was undertaken to assess whether pretreatment of the donor heart with coenzyme Q10 could improve postischemic myocardial recovery. Coenzyme Q10 or its solvent was administered intravenously to donor dogs 1 hour before isolation of the heart. Each heart was stored in Euro-Collins solution at 4 degrees C for 6 or 24 hours and then was reperfused via the aorta with arterial blood of a supporting dog for 3 hours at 37 degrees C in a working mode. During preservation, adenosine triphosphate level was significantly reduced in the placebo group from 21.0 mumol/gm dry weight to 15.1 and 11.9 after 6 and 24 hours of preservation, respectively. Coenzyme Q10 pretreatment maintained the adenosine triphosphate level at 18.9 even after 24 hours of preservation. After reperfusion following 6 and 24 hours of preservation, the adenosine triphosphate level recovered to the original level in the coenzyme Q10 group, but it remained significantly low in the placebo group. Preservation and subsequent reperfusion caused a significant increase in the level of malondialdehyde of hearts in the placebo group, and coenzyme Q10 pretreatment completely suppressed the increase in the malondialdehyde level after reperfusion. Ventricular functions were improved in the coenzyme Q10 group. These results support the concept that free radicals play an important role in myocardial injury during preservation and subsequent reperfusion and suggest that pretreatment of the heart with coenzyme Q10 is effective in preventing such injury that may develop after reperfusion.

Echocardiography-assisted surgery in transaortic endovascular stent grafting: role of transesophageal echocardiography.

OBJECTIVE: Transesophageal echocardiography was applied to visualizing endovascular procedures during transaortic stent grafting for aneurysm and dissection at the distal arch, and the use of transesophageal echocardiography was evaluated. METHODS: The 16 consecutive patients (13 with aneurysms and 3 with dissections) were examined. Transesophageal echocardiography was used for (1) determining graft size, (2) guiding placement of the catheter in the descending aorta at an appropriate position without intimal damage, (3) guiding graft tailoring with a balloon catheter, and (4) examining the results after the procedures. RESULTS: Visualization was disturbed in one patient who had undergone a previous operation. The graft size was appropriate, except in one patient as a result of underestimation. Transesophageal echocardiography was helpful for navigating the graft placement and tailoring without intimal damage. We tried to keep a distance from the diaphragm of 9 cm and an attachment portion of 4 cm. In one patient the graft was placed too distally (7 cm from the diaphragm) to cover the thick atheromatous plaque with the graft. The patient had paraplegia. Transesophageal echocardiographic assessment of endoleak and thromboexclusion was identical to that of postoperative computed tomography or angiography, with a sensitivity of 100% (1/1) and a specificity of 100% (13/13). Leakage at the proximal suture and graft kinking were found in 3 patients. Successful thromboexclusion by transesophageal echocardiographic assessment (13 patients) was predictive of subsequent regression of aneurysm and dissection in the midterm follow-up period: there was complete and partial regression in 5 and 8 patients, respectively. CONCLUSION: Transesophageal echocardiography enables echocardiography-assisted operations with secure step-by-step endoluminal procedures and immediate intraoperative assessment, which is predictive of the postoperative results.

Aortic arch branches are no longer a blind zone for transesophageal echocardiography: a new eye for aortic surgeons.

OBJECTIVES: Branch arteries of the aortic arch have been a blind zone for transesophageal echocardiography. Information regarding blood flow, which is important in both planned and emergency operations on the aorta, has therefore been limited. We have established a technique for visualizing these arteries in nearly all cases. METHODS: In 25 consecutive patients requiring either planned or emergency operations on the aorta, the branch arteries were visualized whenever cerebral malperfusion was suspected. Lateral flexion of the probe tip was used when the trachea interfered with visualization of the arteries. RESULTS: The left subclavian, left and right common carotid, right subclavian, innominate, and left and right vertebral arteries were visualized in 96% (24/25), 92% (23/25), 96% (24/25), 100% (25/25), 84% (21/25), 92% (22/24), and 88% (21/24), respectively. The origin of the innominate artery was visualized in 36% (9/25). In some cases, dissection extended into branch arteries during surgery or during conservative therapy. When the subclavian artery was clamped, retrograde flow was detected in the vertebral artery (steal flow). The cannula for selective cerebral perfusion occasionally was entered into the right common carotid or subclavian artery and obstructed the other branch with a balloon. CONCLUSIONS: The branch arteries of the aortic arch, including the vertebral artery, are no longer a blind zone for transesophageal echocardiography. The information obtained with our new transesophageal echocardiography technique is helpful for diagnosis, monitoring, and decision making during aortic surgery and in critical care medicine. Visualizing these vessels is worth the effort.

Flow velocity of central retinal artery and retrobulbar vessels during cardiovascular operations.

OBJECTIVE: Both blood flow monitoring and pressure monitoring are necessary to avoid inadequate cerebral perfusion during cardiovascular operations. Inasmuch as transcranial Doppler ultrasonography does not provide a consistently good signal, especially during cardiopulmonary bypass, we examined the blood flow through the central retinal artery, which has proved to reflect an obstruction of the carotid artery. METHOD: Twenty-eight consecutive cases were examined with a 5 or 7.5 MHz conventional echocardiographic probe. Correlation between the maximal velocity at the central retinal artery and systolic blood pressure was examined. The blood flow of the central retinal artery and retrobulbar vessels was examined during selective or retrograde cerebral perfusion or intraaortic balloon pumping. RESULTS: Blood flow could be clearly visualized but disappeared below a certain pressure in every case. With data from 478 measuring points, systolic blood pressure correlated with maximal velocity (r = 0.6902, p < 0.0001). The blood pressure-axis intercept, known as "critical closing pressure," was 35.8 +/- 14.8 mm Hg, varying among individuals and bilateral eyes. Pulsatility index increased after cardiopulmonary bypass (1.095 +/- 0.245 to 1.525 +/- 0.268, p < 0.0001). Patency of the circle of Willis was confirmed by the blood flow during anastomosis of the ipsilateral artery. During retrograde cerebral perfusion, blood flow was detectable at the retrobulbar vessels. During intraaortic balloon pumping, the central retinal artery flow was augmented on inflation of the balloon. CONCLUSION: Orbital vessel monitoring provides the critical closing pressure of the central retinal artery and confirms patency of the circle of Willis. The eye can be "an acoustic window" into intracranial blood flow during cardiovascular surgery.

Contractile cardiac grafts using a novel nanofibrous mesh.

Cardiomyoctes are terminally differentiated cells and therefore unable to regenerate after infarction. The use of autologous bioengineered cardiac grafts has been suggested to replace infarcted myocardium and enhance cardiac function. Here we report the development of an in vitro system for engineered myocardium. Cardiac nanofibrous meshes (CNM) were developed by culturing cardiomyocytes from neonatal Lewis rats on electrospun, nanofibrous polycaprolactone (PCL) meshes. The mesh had an ECM-like topography and was suspended across a wire ring that acted as a passive load to contracting cardiomyocytes. The cardiomyocytes started beating after 3 days and were cultured in vitro for 14 days. The cardiomyocytes attached well on the PCL meshes and expressed cardiac-specific proteins such as alpha-myosin heavy chain, connexin43 and cardiac troponin I. The results demonstrate the formation of contractile cardiac grafts in vitro. Using this technique, cardiac grafts can be matured in vitro to obtain sufficient function prior to implantation. It is conjectured that cardiac grafts with clinically relevant dimensions can be obtained by stacking CNMs and inducing vascularization with angiogenic factors.

Effects of FC43 emulsion against hyperacute rejection in rodent discordant xenotransplantation.

BACKGROUND: FC43 emulsion is one of several perfluorochemical-based artificial blood compounds developed as a red blood cell substitute. However, these compounds are not promising as red blood cell substitutes because of their immunosuppressive effects. Therefore we used FC43 emulsion as an immunosuppressive agent and not as a red blood cell substitute. METHODS: We assessed the effect of FC43 emulsion treatment on the survival of the grafted hearts in guinea pig-to-rat discordant transplantations. RESULTS: In rats treated with FC43 emulsion (5 microliters/gm body weight), rhythmic beating of the heart was maintained for 433.3 +/- 40.0 minutes, whereas the untreated heartbeat lasted for only 15.3 +/- 5.1 minutes. In the xenografted hearts treated with FC43 emulsion, no pathologic changes such as multiple coronary thromboses caused by hyperacute rejection had occurred by 300 minutes after reperfusion. CONCLUSIONS: FC43 emulsion can prolong the survival time of guinea pig heart xenografts by inhibiting thrombus formation in the xenografted heart.

The significance of atrial monophasic action potentials for monitoring rat cardiac allograft rejection.

BACKGROUND: Changes in the monophasic action potential may be used for detecting early acute rejection in the transplanted rat heart. METHODS: Heterotopic heart transplantations were performed in allogeneic and syngeneic rats. During atrial pacing, monophasic action potentials were simultaneously recorded in the right atrium and ventricle of the transplanted hearts on postoperative days 1, 3, and 5. The amplitude and duration of monophasic action potentials, atrioventricular conduction time, and cardiac intervals were analyzed. Histopathologic examination for rejection was performed on postoperative days 1, 3, and 5. RESULTS: In the allogeneic group, monophasic action potential amplitude progressively decreased, and monophasic action potential duration gradually increased after heart transplantation in the atrium and ventricle. With rejection, the amplitude decreased to a greater extent, and monophasic action potential duration increased to a greater extent in the atrium than in the ventricle on day 3. The atrioventricular conduction time increased on day 5, but the cardiac interval did not change. An inverse correlation between histopathologic grade and the monophasic action potential amplitude, and a positive correlation between histopathologic grade and the monophasic action potential duration existed for both the atrium and ventricle. These electrophysiologic and histopathologic changes were not observed in the syngeneic group. CONCLUSIONS: We conclude that right atrial monophasic action potentials may be a useful and reliable indicator of early acute heart transplant rejection.

Oxidative ring cleavage of cyclic acetals with hypervalent tert-butylperoxy-lambda(3)-iodanes.

[reaction: see text] Exposure of cyclic acetals to 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in the presence of tert-butyl hydroperoxide and potassium carbonate in benzene at room temperature results in oxidative ring cleavage to glycol monoesters via intermediate tert-butylperoxy ortho esters.

Effect of venous valves on grafts for coronary artery bypass.

The effect of venous valves on blood flow and patency in grafts of the long saphenous vein for coronary artery bypass is examined. Our experimental model involved both diastolic-predominant blood flow and transient systolic regurgitation, and the waveform was similar to that of in vivo coronary circulation. In this model, blood flow was assessed in the presence or absence of venous valves. It was found that coronary artery blood flow was significantly greater in the presence of venous valves. Angioendoscopy showed that the movement of the graft valves was strong and rhythmic. It seems that valve preservation may be desirable in grafts for coronary artery bypass.

Cardioprotective effects of FK409, a nitric oxide donor, after isolated rat heart preservation for 16 hours.

BACKGROUND: We examined the cardioprotective effects of FK409, a nitric oxide donor, after isolated rat heart preservation. METHODS: FK409 was administered to the hearts in pretreatment (FK409-1 group), during ischemia (FK409-2), or during reperfusion (FK409-3). The combined nitrate and nitrite level, coronary flow, cardiac function, coronary vasodilatory response, creatine kinase (CK), and myocardial water content were evaluated after the hearts had been preserved in University of Wisconsin solution at 0 degrees C for 16 hours. RESULTS: The release of nitrate and nitrite increased in reperfusion between the 20-to-40-second measurement and the measurement at 40 minutes, and the recovery of cardiac function was significantly improved in the FK409 groups. The coronary vasodilatory response to acetylcholine chloride was enhanced in the FK409-1 and FK409-2 groups. CK release decreased in FK409 groups after 15 minutes in reperfusion. CONCLUSIONS: This study suggests that FK409 has the best protective effect on cardiac function and coronary endothelial function when it is administered in the ischemic period, a less protective effect when administered during pretreatment, and the least protective effect when FK409 is given during reperfusion after heart preservation for 16 hours.

Stent-grafting to descending thoracic aorta during coronary artery bypass grafting.

We report on 2 patients who underwent successful concomitant operation of coronary artery bypass grafting and stent grafting to descending thoracic aortic aneurysms. The device was inserted through a small linear incision on the anterior wall of the aortic arch. Intraoperative stent grafting to descending thoracic aortic aneurysms is an alternative therapeutic option for patients who require concomitant coronary artery bypass grafting and descending aortic replacement.

Clinical analysis of results of a simple left atrial procedure for chronic atrial fibrillation.

BACKGROUND: We have performed a simple left atrial procedure for eliminating chronic atrial fibrillation (AF) associated with mitral valve disease. This article analyzes the midterm results of this procedure. METHODS: Thirty-two patients were enrolled in this study concomitant with mitral valve operations. Patients were divided into two groups (AF- and AF+). We examined the efficacy of this operation and atrial function for more than 12 months of follow-up. RESULTS: In a total of 98.5 patient years of follow-up, AF was absent 3 years after operation in 74%. Of preoperative and intraoperative variables, only long duration o

Pulmonary vein orifice isolation for elimination of chronic atrial fibrillation.

We present a 61-year-old woman with chronic atrial fibrillation (AF) associated with mitral valve disease. Chronic AF was successfully treated by simple isolation of pulmonary vein orifices concomitant with mitral valve replacemen