Histopathologic changes of acellularized xenogenic carotid vascular grafts implanted in a pig-to-goat model.

INTRODUCTION: The present study was designed to determine the in vivo patency and recellularization pattern of acellularized small-diameter xenogenic arterial grafts. We implanted acellularized porcine carotid arteries in bilateral carotid arteries of goats and microscopically analyzed the recellularization pattern of these grafts with the recipient's cells over time. MATERIAL AND METHODS: Carotid arteries of pigs weighing 30-40 kg were harvested and decellularized with hypertonic saline followed by sodium dodecyl sulfate. Acellularized porcine carotid vascular xenografts (0.4-0.5 cm in diameter) were prepared into 4 cm-long segments and implanted bilaterally in the carotid arteries of 10 black-haired goats. The in vivo patency of the implanted acellularized xenogenic grafts was evaluated at regular intervals by color Doppler ultrasonography. The goats were sacrificed at predetermined intervals (1 week, 1 month, 3 months, 6 months, 12 months after implantation), two animals at each interval. Upon retrieval, visual inspections and histopathologic examinations of the grafts were performed. To identify smooth muscle cells and functioning endothelial cells, immunohistochemical staining for alpha-smooth muscle actin and von Willebrand factor were also performed. RESULTS AND CONCLUSIONS: All experimental animals survived the observation period. Nineteen out of 20 implanted grafts showed patency with no thrombi. Microscopic analysis revealed that the grafts were completely covered with the hosts' endothelial cells, beginning from anastomotic sites. The grafts were gradually recellularized with recipients'cells including fibroblasts, myofibroblasts and smooth muscle cells. In conclusion, this study suggested that acellularized xenogenic vascular grafts can be a good alternative for the small-diameter vascular graft.

New steroidal alkaloids from an undescribed sponge of the genus Corticium.

Two new steroidal alkaloids, along with a previously reported one of the plakinamine class, were isolated from the sponge Corticium sp. collected from Guam. The structures of the new compounds were determined by combined spectroscopic methods. These compounds exhibited moderate cytotoxicity and antifungal activity as well as DNA- and RNA-cleaving activities.

New farnesylhydroquinone glycosides from the gorgonian Euplexaura anastomosans.

Euplexides F (3) and G (4), novel farnesylhydroquinone glycosides, have been isolated as minor constituents of the gorgonian Euplexaura anastomosans. The structures of these compounds have been determined by combined spectroscopic methods. These compounds exhibited moderate cytotoxicity and inhibitory activity against PLA2.

Modified Lecompte procedure for the anomalies of ventriculoarterial connection.

BACKGROUND: The Lecompte procedure for correcting transposition of the great arteries has an advantage because it obviates the need for an extracardiac conduit for the reconstruction of the pulmonary outflow tract. In this study, we evaluated the effectiveness and the application of the Lecompte procedure based on our experiences. METHODS: A retrospective review was conducted of the records of 45 patients who underwent the Lecompte procedure during the past 11 years to achieve direct right ventricle to pulmonary artery continuity. Mean age at operation was 2.4+/-1.7 years (range 3.5 months to 6.9 years). The diagnoses involved anomalies of the ventriculoarterial connection with ventricular septal defect and pulmonary outflow tract obstruction, such as transposition of the great arteries, double-outlet right ventricle, and double-outlet left ventricle. RESULTS: Early mortality was 4.4% (2 of 45 patients) and late mortality was 4.7% (2 of 43). The mean follow-up was 4.9+/-3.1 years. Fourteen patients (34.1% of survivors, n = 41) had pulmonary stenosis (pressure gradient above 30 mm Hg), the main reason for which was a calcified monocusp valve (n = 10, 71.4%). Eight of 45 patients (17.8%) underwent reoperation: 2 for residual ventricular septal defect, 1 for recurrent septic vegetation, and 5 for pulmonary stenosis. The cumulative survival rates were 91.1%+/-4.2% at 10 years. The actuarial probabilities of freedom from reoperation for pulmonary stenosis were 93.8%+/-4.3% and 71.4%+/-11.8% at 5 and 10 years, respectively. CONCLUSIONS: Our review suggests that the Lecompte procedure is an effective treatment modality for anomalies of the ventriculoarterial connection with ventricular septal defect and pulmonary outflow tract obstruction. Repair in early age is possible with acceptable morbidity and mortality, but recurrent right ventricular outflow tract obstruction caused by degeneration of the monocusp valve is a problem that needs resolution.

New triterpenoid saponins from the sponge Erylus nobilis.

Erylosides G--J (1--4), four new triterpenoid saponins, were isolated from the sponge Erylus nobilis collected from Jaeju Island, Korea. On the basis of the results of combined chemical and spectral analyses, the structures of the aglycones were determined to be lanostane-based, modified penasterols. The oligosaccharide portions were composed of one unit each of L-arabinose, D-galactose, and 2-N-acetyl-D-glucosamine (1 and 3) or two units of L-arabinose and one unit of 2-N-acetyl-D-glucosamine (2 and 4). These compounds exhibited moderate cytotoxicty against a human leukemia cell line.

New lactone-containing metabolites from a marine-derived bacterium of the genus Streptomyces.

Six novel metabolites containing a lactone moiety as a common structural feature, along with the previously described (-)-blastmycinolactol, have been isolated from the cultivation broth of a bacterium of the genus Streptomyces isolated from marine sediment. On the basis of the results of combined spectroscopic analysis, the structures of the new compounds have been determined as butenolides and 3-hydroxy-gamma-butyrolactones.

New xenicane diterpenoids from the gorgonian Acalycigorgia inermis.

Eight diterpenes and norditerpenes including five new xenicane metabolites (4--8) have been isolated from the gorgonian Acalycigorgia inermis. The structures of these compounds have been determined by combined spectroscopic analysis. The new compounds exhibited significant cytotoxicity against a human leukemia cell-line.

Analysis of the interventricular pressure waveform in the moving-actuator total artificial heart.

Right and left filling pressures are important parameters in the automatic control of a total artificial heart (TAH) within normal physiologic ranges. Our TAH is composed of a moving actuator, right and left ventricles, and an interventricular space (IVS) enclosed by a semirigid housing. During operation of the TAH, the IVS volume is changed dynamically by the difference between the ejection volume of one ventricle and the inflow volume of the other. We measured the interventricular pressure (IVP) waveform by using a pressure sensor and analyzed the relationship between the IVP and the preload condition. From in vitro and in vivo experiments, we found that the measured filling pressures were linearly related to the negative peak value of the IVP. Additionally, we found that we could use the time interval from actuator start to the positive peak value of the IVP (outflow valve opening) as a useful parameter to estimate the blood filling volume of the diastole ventricle.

New triterpenoid saponins from the sponge Melophlus isis.

Four new triterpenoid saponins were isolated, along with two known 30-norlanostane-type saponins- sarasinosides A(1) (1) and A(3) (2)-from the sponge Melophlus isis collected from Guam. The structures of these new compounds (3-6) proved to be 30-norlanosta-8(14),24-dien-23-ones bearing two hydroxyl groups or the corresponding methoxy groups at the 9alpha,15alpha- and 9alpha, 15beta-positions and the pentasaccharide portion identical with those of 1 and 2 at the 3beta position, by spectral, chemical, and GC analyses.

New xenicane diterpenoids from the gorgonian Acalycigorgia inermis.

Acalycixeniolides D-G [corrected] (1-4), four new diterpenoids of the xenicane class, have been isolated from the gorgonian Acalycigorgia inermis. The structures of these compounds have been determined by combined spectroscopic methods. These compounds exhibited cytotoxicity against a human leukemia cell-line.

The Cox-Maze III procedure for atrial fibrillation associated with rheumatic mitral valve disease.

BACKGROUND: The surgical results of the Cox-Maze III procedure (CM-III) for atrial fibrillation (AF) associated with rheumatic mitral valve (MV) disease are not as good as the results from surgery for AF alone. METHODS: To assess the efficacy and safety of the CM-III in AF associated with rheumatic MV disease, we retrospectively analyzed 75 patients who underwent the CM-III combined with a rheumatic MV procedure between April 1994 and December 1997. Fourteen cases were reoperations because of prosthetic valve failure. RESULTS: Mean aortic cross-clamp (ACC) times and cardiopulmonary bypass (CPB) times were 151+/-43 and 251+/-73 min, respectively. Concomitant procedures were mitral valve replacement (MVR) in 25 patients, MVR and aortic valve replacement (AVR) in 14 patients, MV repair in 10 patients, MVR and tricuspid annuloplasty (TAP) in 6 patients, MVR and AV repair in 3 patients, MVR and coronary artery bypass grafting (CABG) in 2 patients, MVR and AVR and CABG in 1 patient, redo-MVR in 8 patients, redo-MVR and TAP in 4 patients, and redo-MVR and redo-AVR in 2 patients. There were two in-hospital mortalities (2 of 75, 2.7%). Seventy-three survivors were followed for a mean duration of 30+/-13 months (12-56 months). Normal sinus rhythm was restored in 90.4% (66 of 73). Three patients remained in AF and 2 patients were in junctional rhythm. Permanent pacemakers were implanted in 2 patients due to sick sinus syndrome. Right atrial (RA) contractility was demonstrable in 100% (66 of 66) and left atrial (LA) contractility in 62.1% (41 of 66) of the patients in the latest follow-up echocardiography. RA and LA contractilities were restored a mean 69+/-93 and 126+/-136 days after the operation, respectively. LA contractility was restored significantly later at a lower rate than RA contractility in rheumatic MV disease. There were no differences in ACC time, CPB time, incidence of postoperative bleeding complications, and sinus conversion rates between non-redo and redo cases in spite of the significantly longer duration of preoperative AF in redo cases (p<0.05). CONCLUSIONS: The CM-III for AF associated with rheumatic MV disease demonstrated a high sinus conversion rate with acceptable operative risk even in cases of reoperation.

In vivo experiment leading to clinical application of an electrohydraulic ventricular assist device with magnetic coupling.

We developed an electrohydraulic ventricular assist device with magnetic coupling. The integrated system consists of a blood pump, a water conduit for pressure transmission, a bellows type pumping sac, an actuator for transforming the circular motion of a motor to the linear motion of a pusher plate attached to the pumping sac with magnetic coupling, and a controller. The purpose of the coupling was to prevent excessive sucking against the atrial wall. Number 21 Medtronic Hall (Irvine, CA) mechanical valves were used in the inflow and outflow ports of the blood pump. Maximum dynamic stroke volume was 48 ml, and against a mean afterload of 100 mm Hg, maximum pump output was 7 L/min. Chronic in vivo experiments were performed in three sheep, and during these evaluations the system showed no noticeable problems related to mechanical or electronic devices. When left atrial pressure decreased below 0 mm Hg, the magnetic coupling system decoupled the pumping sac and pusher plate with satisfactory reliability. The device was clinically applied in a postoperative patient with chronic dilating cardiomyopathy, and no significant device related problems ensued. These results prove that the electrohydraulic ventricular assist system with magnetic coupling is a suitable ventricular assist device.

New acetylenic enol ethers of glycerol from the sponge Petrosia sp.

Ten acetylenic enol ethers of glycerols, including six new compounds (1-6) and a linear acetylenic alcohol (7), have been isolated from a sponge of the genus Petrosia. The structures of the novel compounds were elucidated by spectroscopic methods. The absolute stereochemistry of 1-7 was determined by chemical transformations and the Mosher method. Some of these compounds exhibited weak cytotoxicity against a human leukemia cell-line (K-562).

Restoration of atrial mechanical function after maze operation in patients with structural heart disease.

BACKGROUND: The maze operation is effective for the restoration of sinus rhythm; however, restoration of atrial mechanical function has not been demonstrated in all patients. METHODS: Maze operations were performed in 32 patients (13 men, 19 women; mean age 47.1 +/- 9.0 years) combined with valvular surgery (n = 25), coronary artery bypass graft (CABG) (n = 3), and others (n = 4). At 1 week, 3 months, 6 months, and 1 year after the operation, prospective serial Doppler echocardiographic examination was carried out to determine the presence of atrial mechanical function. RESULTS: Sinus rhythm was restored and maintained during the follow-up period in 26 (81%) patients; in 22 patients this was due solely to the operation, whereas in four patients an antiarrhythmic agent was needed to maintain sinus rhythm. Another four patients showed paroxysmal atrial fibrillation (AF) despite treatment with an antiarrhythmic agent. Right atrial mechanical function was restored in all 30 patients with sinus rhythm or paroxysmal AF; in 19 (63%) of these, left atrial mechanical function was restored. In patients with restored left atrial mechanical function, peak A velocity (A) and A/E ratio (A/E) of mitral inflow were significantly lower than in the 16 postoperative control patients (A: 0.46 +/- 0.14 m/sec vs 0. 75 +/- 0.29 m/sec, p < 0.01; A/E: 0.40 vs 0.80, p < 0.01). In patients with left atrial mechanical function, the duration of AF was significantly shorter than in patients without left atrial mechanical function (1.9 +/- 2.9 years vs 7.1 +/- 3.0 years, p < 0. 01), but there were no significant differences in left atrial size and volume. CONCLUSIONS: The maze operation could be safely added to standard open heart surgery for the correction of underlying structural heart disease. The rate of conversion to sinus rhythm resulting solely from the operation might be lower than the rates previously reported with only the duration of AF adversely affecting the restoration of left atrial mechanical function. Considering the fact that not all patients converted to sinus rhythm show atrial mechanical function, the role of the maze operation in the prevention of systemic embolism, with subsequent improvement in survival, requires further study.

Sesquiterpenoids of the drimane class from a sponge of the genus Dysidea.

Ten sesquiterpenoids, including seven new ones, have been isolated from an undescribed sponge of the genus Dysidea. Compounds 1-8 are sesquiterpenoids of the drimane class, while 9 and 10 are 12-norsesquiterpenoids of the same structural class. The structures of novel compounds have been determined by combined spectroscopic methods. These compounds exhibited moderate antimicrobial and enzyme inhibitory (Na+/K(+)-ATPase and PLA2) activities.

Moving actuator type total artificial heart with reverse position of the aortic and pulmonary conduits.

Adequate intrathoracic anatomical compatibility is one of the most important considerations in designing a fully implantable total artificial heart (TAH). We have recently developed an innovative concept of reverse positioning of the aortic and pulmonary conduits to facilitate anatomical compatibility of the moving actuator type TAH. The pulmonary conduit of this TAH is designed to be located posterior to the aortic conduit, which results in a substantial reduction in the anteroposterior diameter of this heart, as well as the virtual elimination of the compression of the low pressure pulmonary conduit. In ovine orthotopic implantation experiments with this model of the TAH, we consecutively achieved 3 day survival in 1 sheep and 2 day survival in another. To the best of our knowledge, these were the first significant short-term survival cases in the orthotopic implantation of electric TAHs in sheep.

Surgical management of type A aortic dissection: evaluation of predisposing factors for postoperative neurologic complication and late reoperation.

The technique of cerebral protection during hypothermic circulatory arrest remains controversial. Forty-seven patients underwent operations for type A aortic dissection in the past 9 years. During hypothermic circulatory arrest, selective cerebral perfusion and retrograde cerebral perfusion was applied in 12 and seven patients, respectively. The mortality rate was 28.6% in patients without adjunctive cerebral perfusion, 25.0% in selective cerebral perfusion patients, and zero in the retrograde cerebral perfusion group (P > 0.05). However, there was no mortality by cerebral injury in cerebral perfusion groups (P = 0.03). Age (P = 0.001), hypothermic circulatory arrest time (P = 0.012), and acuity (P = 0.013) were predisposing factors for cerebral injury, but cerebral perfusion has not yet been found to be a protective factor (P = 0.56). Nine late reoperations and three deaths occurred during the follow-up period. Marfan syndrome was the only predisposing factor for late reoperation (P = 0.016). In summary, although further studies are still required, retrograde cerebral perfusion is a possible cerebral protective factor. In addition, periodic follow-up is mandatory, especially in patients with Marfan syndrome.

Do sheep really have problems with cardiopulmonary bypass for total artificial heart implantation?

Although the use of sheep in total artificial heart (TAH) implantation has many advantages, they are known to show a significant morbidity rate on cardiopulmonary bypass (CPB); this has been considered to be a major limiting factor in using them for TAH experiments. We conducted a series of ovine CPB experiments to evaluate the sheep's pathophysiological response to CPB. CPB-related hemolysis, bleeding, and lung dysfunction were analyzed in 5 sheep, which had undergone CPB, used at our hospital for TAH implantation. Four of the 5 sheep survived the experimental procedures, and 3 of them survived on a long-term basis. Unacceptable degrees of hemolysis related to CPB were not observed. Postoperative bleeding was not remarkable, and coagulation test results did not show significant abnormal findings. Acute lung injuries of a mild to moderate degree were found mainly at the microscopic level, but rarely had clinical significance. In conclusion, this experiment suggests that sheep can be used for the animal model for TAH implantation with acceptable risk on CPB circuits and techniques are used.

Isolation of guaianoid pigments from the gorgonian Calicogorgia granulosa.

Three pigments of the guaiazulene class have been isolated from the gorgonian Calicogorgia granulosa. Structures of these compounds have been determined as guaiazulene, 2,2'- diguaiazulenylmethane, and a new compound, 2,2'-biguaiazulenyl, by combined chemical and spectroscopic methods. 2,2'-Biguaiazulenyl exhibited moderate antimicrobial activity.