Human rotavirus genotypes in hospitalized children, South Korea, April 2005 to March 2007.

Availability of new rotavirus vaccines highlights the need to maintain and enhance rotavirus strain surveillance. We collected stool samples from children with gastroenteritis admitted to eight hospitals in South Korea from April 2005 to March 2007. Of the 6057 samples collected, 1337 (22%) were positive for rotavirus by one of several antigen detection assays. G and P genotypes were identified for 1299 (97%) of rotavirus-positive specimens. G1P[8] (36%) was the most prevalent strain, followed by G3P[8] (16%), G4P[6] (8.9%) and G1P[6] (8.2%). G1P[8] was also the most prevalent strain in each hospital. Seasonal peaks of rotavirus infection were noted from November 2005 to April 2006 and January to March 2007. This large-scale surveillance study provides important insights into rotavirus genotype distribution and pattern changes in South Korea.

The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats.

The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor, DA-8159, on erectile function throughout the quantitative analysis of vascular endothelial cell, smooth muscle (SM), TGF-beta1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 (0, 5, 10, 20 mg/kg) was administered orally once a day to diabetic rats. After 8 weeks, immunohistochemistry and computerized image analysis were performed to quantify the percent area within the Corpora Cavernosa occupied by the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure (MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic rats showed a significant decrease in the SM and endothelial cell content, and an increase in the TGF-beta1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-beta1 expression level were 9.7+/-0.7, 4.5+/-0.7 and 17.9+/-2.1%, respectively. DA-8159 prevented reduction of SM (12.3+/-0.4% (5 mg/kg), 13.8+/-0.4% (20 mg/kg)) and endothelial cell content (5.6+/-0.5% (5 mg/kg), 6.3+/-0.6% (20 mg/kg)). Immunoreactivity of TGF-beta1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8+/-1.2% (5 mg/kg), 9.5+/-1.1% (20 mg/kg)). Electrostimulation of the cavernous nerve induced significant increase in maximum ICP (62.2+/-13.6 mmHg in 10 mg/kg vs 37.5+/-17.5 mmHg in diabetic group) and area under the curve of the ratio of ICP/MAP (8891.09+/-1957 in 10 mg/kg vs 6315.87+/-2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED.

DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right ventricular hypertrophy in a rat model of pulmonary hypertension.

This study evaluated the effect of DA-8159, a new phosphodiesterase 5 inhibitor, on the compensatory development of right ventricular hypertrophy in monocrotaline (MCT)-induced pulmonary hypertension (PH). Rats treated with subcutaneous MCT were divided into three groups, which received DA-8159 1 mg/kg, DA-8159 5 mg/kg or saline-vehicle orally, twice daily for 21 days. The vehicle group demonstrated increased right ventricular weight, pulmonary artery medial wall thickening, myocardial fibrosis, increased plasma cyclic guanosine monophosphate (cGMP) concentration and reduced body weight gains. DA-8159, however, markedly attenuated the compensatory development of right ventricular hypertrophy and pulmonary artery medial wall thickening, amplified the increase in plasma cGMP levels and increased lung cGMP concentrations. In addition, DA-8159 prevented myocardial fibrosis induced by MCT. These results demonstrate that DA-8159 attenuates the compensatory development of right ventricular hypertrophy in a rate model of PH. DA-8159 might, therefore, be a useful treatment option for PH, but its efficacy in humans needs evaluating.

Synthesis, characterization and antitumor activity of quinolone-platinum(II) conjugates.

A new series of quinolone-platinum(II) conjugates, [Pt(Q'-NH2)(dmso)X2] and cis-[Pt(Q"-en)X2], where Q' and Q" are quinolones (flumequine, nalidixic acid or oxolinic acid) linked to monodentate and bidentate amine ligands, respectively, and X2 is Cl2 or 1,1-cyclobutanedicarboxylate, have been synthesized with the aim of examining the synergetic antitumor activity of quinolone intercalation and platinum(II) chelation. The complexes were characterized by elemental analyses and IR and multinuclear (1H and 195Pt) NMR spectroscopies, and then subjected to in vitro and in vivo bioassays using the leukemia L1210 cell line.

Biosynthetic pathway of cephabacins in Lysobacter lactamgenus: molecular and biochemical characterization of the upstream region of the gene clusters for engineering of novel antibiotics.

The cephabacins, one of the beta-lactam antibiotics, are produced by Lysobacter lactamgenus. The previous studies the cephabacin biosynthesis were limited to a gene cluster that encodes the gene products responsible for the biosynthesis of the cephem nucleus. The long-term goal of this research is to elucidate the metabolic diversity and biosynthetic pathway of cephabacins and to design and/or discover new pharmacologically active compounds by engineering the cephabacin biosynthetic pathway in L. lactamgenus. In this study, we have cloned and sequenced a 24-kb fragment of a DNA locus upstream of the previously reported but incomplete putative ORF9 of L. lactamgenus. This contains three putative ORFs (the complete ORF9, ORF10, and ORF11) transcribed in the same direction and one putative ORF (ORF12) in the opposite direction. The isolated DNA locus extends the previously cloned part of the DNA locus containing the genes responsible for biosynthesis of the cephem nucleus up to 45 kb. The 42-kb fragment of the 45-kb gene cluster is located between a potential TATA box just upstream of the ORF11 and a termination loop just downstream of the previously reported bla gene. The complete ORF9 contains three nonribosomal peptide synthetase (NRPS) modules and one polyketide synthase (PKS) module and the ORF11 contains one NRPS module. The complete ORF9 also contains a putative thioesterase domain at the C-terminal end. We predicted the amino acid specificity of the four NRPSs by generating specificity binding pockets and expressed one of the NRPSs to confirm the amino acid specificity. The adenylation domain of the NRPS1, which is the last module of the NRPSs, showed significant amino acid specificity for L-arginine. These findings are in perfect agreement with the composition that was expected for the structure of cephabacins which contain an acetate residue, an L-arginine, and one to three L-alanines at the C-3' position of the cephem nucleus of cephabacins. The ORF10, encoding a putative ABC transporter which might be involved in conferring resistance against cephabacins, was identified between the complete ORF9 and the ORF11. Therefore, the complete ORF9, ORF10, ORF11 reported here and the other genes previously reported constitute an operon for the biosynthesis of cephabacins in L. lactamgenus. Based on our results, the biosynthetic pathways of acetate and elongated peptide moieties and a mechanism by which cephabacins are assembled by connecting the peptide moiety synthesized by the gene products of the complete ORF9 and the ORF11 to the C-3' position of the cephem nucleus synthesized by the gene products of pcbAB, pcbC, cefE, cefF, and cefD have been elucidated.

Immunohistochemical detection of galectin-3 in canine gastric carcinomas.

Galectin-3 was detected immunohistochemically in nine canine gastric carcinomas. In normal gastric tissue adjacent to the neoplasms, the gastric epithelial cells showed faint immunolabelling for galectin-3, but in all the tumours the neoplastic cells showed moderate to strong immunolabelling. Galectin-3 was localized in the cytoplasm of the normal mucosal cells, whereas it was found in both the cytoplasm and the nucleus of the neoplastic cells. Positive cells typically exhibited dark brown coloration of the nucleus or cytoplasm, without background labelling. The results suggest that galactin-3 has a pathophysiological role in canine gastric carcinoma.

Synthesis and antitumor activity of cyclotriphosphazene-(diamine)platinum(II) conjugates.

A new class of water-soluble cyclotriphosphazene-(diamine)platinum(II) conjugate drugs [NP(Am-Li2)(Am.PtA2)]3 (Am: dicarboxylic amino acid; A2: diamine) has been synthesized and characterized by means of elemental analysis, multinuclear (1H, 31P, 13C, 195Pt) NMR and IR spectroscopies. All the title compounds were subjected to both in vitro and in vivo assays against the murine leukemia L1210 cell line and selected human tumor cells. Most of the title compounds have shown higher in vivo antitumor activity than cisplatin and carboplatin, and, in particular, [NP(L-Glu-Li2)(L-Glu.Pt(-dach)]3 (Glu=glutamate, dach=trans(+/-)-1,2-diaminocyclohexane) showed extraordinary high activity (ILS>500%) equally against both parent and cisplatin-resistant leukemia L1210 cell lines. Furthermore, this candidate compound (KI 60606) exhibited a wider spectrum of in vitro activity by showing higher cytotoxicity against all the selected human tumor cells than cisplatin and, therefore, was subjected to preclinical studies which are now near completion.

Lectin-binding capacity of glycoconjugates in Escherichia coli 09:K103:NM, 987P+ST+-infected porcine lower small intestines.

Composition of glycoconjugates were investigated in Escherichia coli 09:K103:NM, 987P+ST+-infected lower small intestines of 1-week-old pigs by the use of twenty one biotinylated-labelled lectins with avidin-biotin-peroxidase complex method. Piglets with experimental group were inoculated by feeding 5 ml of culture inoculum (5 x 10(9) colony-forming units/ml) with 15 ml of milk replacer. At the onset of diarrhea, experimental piglets and time-matched control piglets were euthanatized using electrocution, necropsied, and tested by lectin histochemistry. As compared with control, staining intensity of seven lectins altered in ileal villus brush border and goblet cells of pigs inoculated with the pathogen.

Electrophilic substitution of (diamine)tetrahydroxoplatinum(IV) with carboxylic anhydrides. Synthesis and characterization of (diamine)platinum(IV) complexes of mixed carboxylates.

A novel series of (diamine)platinum(IV) complexes of mixed carboxylates have been synthesized by electrophilic substitution of the tetrahydroxoplatinum(IV) complex (dach)Pt(OH)4 (dach = trans-(+/-)-1,2-diaminocyclohexane) with three different carboxylic anhydrides, pivalic, acetic, and trifluoroacetic anhydrides. Consecutive two-step acylations with two different carboxylic anhydrides in acetone or dichloromethane gave the mixed carboxylate complexes (dach)Pt(O2CR)x(O2CR')4 - x (R = C(CH3)3 or CF3, R' = CH3, x = 1-4) including all the possible stereoisomers, which could be separated and identified by means of HPLC, column chromatography, 1H NMR, and X-ray crystallography. From analysis of the reaction products we have found that the positions of electrophilic substitution of (dach)Pt(OH)4 were influenced by the kinds of carboxylic anhydrides exhibiting different electrophilicity or steric effects. The initial substitution by the first reactant occurs more favorably on axial OH, but in the case of pivalic anhydride, equatorial substitution is favored probably because of the bulkiness of the pivalate group. Such a result seems to be related to their stereochemical factors rather than to differences in electrophilicity. The lipophilicity of the title complexes was affected not only by the carbon numbers of substituents but also by the conformation of the resulting compound.

Synthesis and oral antitumor activity of tetrakis(carboxylato)platinum(IV) complexes.

A novel class of tetrakis(carboxylato)platinum(IV) complexes, [Pt(O(2)CR)(4)(dach)] (dach = trans-(+/-)-1,2-diaminocyclohexane; R = C(n)H(2n+1), n = 1 approximately 5), was synthesized and studied for physicochemical properties and oral antitumor activity. Lipophilicity and aqueous solubility of the title complexes were greatly dependent on the alkyl chain length of the carboxylate ligand, and their partition coefficient and solubility changed by 4 or 5 orders of magnitude from acetate to hexanoate complexes. On the other hand, the range of their cathodic reduction potential (-546 approximately -403 mV) depending on the chain length of the carboxylate ligand was relatively small. Among the title complexes, the tetrakis(propionato)platinum(IV) complex, [Pt(O(2)CC(2)H(5))(4)(dach)], with appropriate lipophilicity (log P = 0.18) and aqueous solubility (14.6 mg/mL) was found to exhibit better oral antitumor activity than JM216 against the human ovarian tumor xenograft SKOV3 in nude mice.

The Korean collaborative study on 11,000 prenatal genetic amniocentesis.

Since amniocentesis made prenatal diagnosis feasible in 1967, the method has been remarkably instrumental in obstetrical practice. A recent study conducted between 1980 and 1997 collected 11,000 amniocentesis procedures done at 10 university hospitals and tertiary centers in Korea. The study indicated that the use of amniocentesis on patients has increased steadily since 1980; however, the number has increased sharply for patients in the mid 1990's. In the 1980's, amniocentesis had been used primarily for patients in advanced maternal age groups (at least 35 years or older). In 1995, amniocentesis had been implemented for the detection of abnormal serum markers (37.6%), and by 1997, amniocentesis was involved in such diagnosis even more frequently (44.8%). Of the total number of uses, 270 (2.5%) involved the detection of chromosomal anomaly. In autosomal disorders, 96 Down syndrome, 33 Edward syndrome, and 6 Patau syndrome were diagnosed. In sex chromosomal anomaly, 10 Turner syndrome, and 10 Klinefelter syndrome were diagnosed. Added to that, 83 translocations, and 15 mosaicisms were diagnosed. Of the 322 cases with abnormal ultrasonographic findings, 21 (6.5%) resulted in chromosomal anomaly. The use of genetic amniocentesis as a prenatal diagnostic test for Korean women has risen 10-fold between 1988 and 1998. As stated earlier, amniocentesis had earlier been used primarily for those in advanced maternal age groups. Today, maternal serum markers and highly sensitive ultrasonic technology can detect many fetal anomalies which eventually necessitate amniocentesis.

Synthesis, structures and antitumor activity of the first crown ester-linked bipyridyl platinum complexes.

Three new crown ester-linked bipyridine homologs with three, four or five ethylene glycol units, which are bulky and soluble in both hydrophilic and lipophilic media, were synthesized. The reaction of the appropriate macrocycles with K2PtCl4 in water gave yellow cisplatin analogs in good yield. These complexes were converted to carboplatin analogs by exchange of the leaving group. All the compounds were characterized by elemental analysis and various spectroscopic methods. Carboplatin analogs showed good solubility in both hydrophilic and lipophilic media. The crystal structure of 2c, the carboplatin analog with macrocycles containing five ethylene glycol units, was determined by X-ray diffraction: space group P1, a = 9.798(1), b = 12.580(3), c = 13.945(2) A, alpha = 108.61(2), beta = 94.59(1), gamma = 97.42(2) degrees, Z = 2, R = 0.0618. Some of platinum complexes showed a moderate cytotoxic effect on both murine leukemia L1210 and P388 even though they do not have any NH proton.

Presentation of words to separate hemispheres prevents interword illusory conjunctions.

We tested the hypothesis that division of inputs between the hemispheres could prevent interword letter migrations in the form of illusory conjunctions. The task was to decide whether a centrally-presented consonant-vowel-consonant (CVC) target word matched one of four CVC words presented to a single hemisphere or divided between the hemispheres in a subsequent test display. During half of the target-absent trials, known as conjunction trials, letters from two separate words (e.g., "tag" and "cop") in the test display could be mistaken for a target word (e.g., "top"). For the other half of the target-absent trails, the test display did not match any target consonants (Experiment 1, N = 16) or it matched one target consonant (Experiment 2, N = 29), the latter constituting true "feature" trials. Bi- as compared to unihemispheric presentation significantly reduced the number of conjunction, but not feature, errors. Illusory conjunctions did not occur when the words were presented to separate hemispheres.

Disruption of PMR1, encoding a Ca2+-ATPase homolog in Yarrowia lipolytica, affects secretion and processing of homologous and heterologous proteins.

The Yarrowia lipolytica PMR1 gene (YlPMR1) is a Saccharomyces cerevisiae PMR1 homolog which encodes a putative secretory pathway Ca2+-ATPase. In this study, we investigated the effects of a YlPMR1 disruption on the processing and secretion of native and foreign proteins in Y. lipolytica and found variable responses by the YlPMR1-disrupted mutant depending on the protein. The secretion of 32-kDa mature alkaline extracellular protease (AEP) was dramatically decreased, and incompletely processed precursors were observed in the YlPMR1-disrupted mutant. A 36- and a 52-kDa premature AEP were secreted, and an intracellular 52-kDa premature AEP was also detected. The acid extracellular protease activity of the YlPMR1-disrupted mutant was increased by 60% compared to that of the wild-type strain. The inhibitory effect of mutations in secretory pathway Ca2+-ATPase genes on the secretion of rice alpha-amylase was also observed in the Y. lipolytica and S. cerevisiae PMR1-disrupted mutants. Unlike rice alpha-amylase, the secretion of Trichoderma reesei endoglucanase I (EGI) was not influenced by the YlPMR1 disruption. However, the secreted EGI from the YlPMR1-disrupted mutant had different characteristics than that of the control. While wild-type cells secreted the hyperglycosylated form of EGI, hyperglycosylation was completely absent in the YlPMR1-disrupted mutant. Our results indicate that the effects of the YlPMR1 disruption as manifested by the phenotypic response depend on the characteristics of the reporter protein in the recombinant yeast strain evaluated.

Transatrial-transpulmonary tetralogy of Fallot repair is effective in the presence of anomalous coronary arteries.

OBJECTIVES: The study's object was to analyze the outcomes of transatrial-transpulmonary repair in children with tetralogy of Fallot and anomalous coronary artery crossing the right ventricular outflow tract. METHODS: The transatrial-transpulmonary approach was used in 611 consecutive repairs, 36 (5.9%) of which were associated with a surgically relevant coronary artery anomaly. The median age and weight of the patients at repair were 23 months (2.8-170 months) and 9.9 kg (5.2-41 kg), respectively. Anomalies included left anterior descending coronary artery from right coronary artery or single right coronary artery (n = 22), right coronary artery from left coronary artery or left anterior descending coronary artery (n = 8), and large right coronary artery conal branch (n = 6). Diagnosis was established before the operation in 25 of 36 cases by angiography (n = 24) or echocardiography (n = 1). The approach was successful in 34 cases, in 25 of which placement of a limited transannular patch was necessary. Two patients had a right ventricle-pulmonary artery conduit as a result of proximity of the coronary branch to the pulmonary arterial anulus and inability to adequately relieve the right ventricular outflow tract obstruction. RESULTS: There have been no early or late deaths. Mean right ventricle-pulmonary artery gradient at last follow-up was 19 mm Hg (95% confidence interval 14.5-24 mm Hg), compared with 15 mm Hg (95% confidence interval 12.5-17.5 mm Hg) for patients with normal coronary arteries (P = .3). Actuarial freedom from reoperation at 120 months was 96.5% (95% confidence interval 79.8%-99.5%) and was also similar between patients with and without coronary artery abnormalities (P = .92). CONCLUSIONS: Surgically important coronary anomalies in tetralogy of Fallot can be dealt with through the transatrial-transpulmonary approach in most cases without major alterations in technique. Outcomes are similar to those of other patients with tetralogy of Fallot. The presence of anomalous coronary arteries does not impart incremental risk after this surgical strategy.

Arterial switch in hearts with left ventricular outflow and pulmonary valve abnormalities.

BACKGROUND: Pulmonary valve and left ventricular outflow tract abnormalities (LVOT) may not be absolute contraindications to arterial switch operation (ASO). METHODS: In this study we analyze long-term outcome for 26 such transposition patients (6.3% of our ASO cohort). Median age and weight were 69 days (7 to 3,631 days) and 4.5 kg (2.6 to 34 kg). Pulmonary valve abnormalities included bicuspid valve (n = 4) and dysplastic valve (n = 5). The LVOT abnormalities (n = 17) included accessory atrioventricular valve/endocardial cushion tissue, fibromuscular ring, anomalous muscle bands, and septal malalignment. Patients with dynamic LVOT obstruction were excluded. The median preoperative left ventricular to pulmonary artery peak systolic pressure gradient was 30 mm (0 to 93 mm), or 50 mm (16 to 93 mm) if patients with isolated valve abnormalities are excluded. The ASO was performed according to our standard technique with or without LVOT resection or pulmonary valvotomy as required. RESULTS: There were two perioperative deaths (7.7%; 95% confidence interval, 0.9% to 25%), and no late deaths during 1,934 patient-months of follow-up time. Actuarial freedom from reoperation for neoaortic valve or LVOT problems is 87% (+/- 7) at 130 months, representing two reoperations. One was performed for neoaortic insufficiency plus LVOT obstruction, and the other for isolated LVOT obstruction. One patient currently has significant neoaortic insufficiency, and median gradient at last follow-up is 0 mm Hg (range, 0 to 35 mm Hg). CONCLUSIONS: The ASO can be performed in selected patients with transposition of the great arteries and with LVOT abnormalities with early and late survival and functional status similar to that of matched patients with normal pulmonary valves and LVOT (p > 0.05), but with a greater hazard for reoperation (p < 0.05). Selection for ASO should be based on anatomic criteria rather than left ventricular to pulmonary artery gradient alone, to avoid assigning these patients with transposition of the great arteries to treatment strategies less satisfactory than ASO.

Synthesis and antitumor activity of (diamine)platinum(II) complexes of benzylmalonate derivatives.

(Diamine)platinum(II) complexes of benzylmalonate derivatives as a leaving group designed in a wide range of lipophilicity and water-solubility were prepared and their antitumor activities were attempted to correlate to their lipophilicity or solubility. A good relationship was observed between their in vitro toxicity and solubility of the title complexes with the same carrier ligand, DACH (trans-(+/-)-1,2-diaminocyclohexane): The most soluble complexes are most cytotoxic whereas the least soluble complexes are least cytotoxic. However, no relationship could be established between their in vivo activity and their lipophilicity or solubility presumably due to other pharmacokinetic factors involved in vivo. The molecular structure of (IPA)2Pt(DBM).2CH3OH (IPA = isopropylamine; DBM = dibenzylmalonate) was determined by X-ray diffraction: space group P2(1)/n, a = 11.433 (3), b = 14.461 (4), c = 17.478 (4) A, beta = 97.25 (3) degrees, z = 4, R = 0.0437.

Hemodynamic and humoral conditions in stepwise reduction of pulmonary blood flow during venoarterial bypass in awake goats.

The effects of reduced pulmonary arterial blood flow (PAF) during venoarterial bypass (VAB) on hemodynamic and humoral conditions were investigated in a series of experiments in a chronic animal model. A biventricular bypass system was installed in five adult goats weighing 49.8 +/- 1.1 kg. Two weeks later, the extracorporeal circuitry was changed to VAB without anesthesia. The PAF was reduced stepwise from 100% to 50, 25, 10, and 0% of total systemic flow. The mean aortic pressure and systemic vascular resistance decreased from 110 +/- 14 to 66 +/- 3 mmHg and from 1,288 +/- 77 to 740 +/- 73 dyne.sec/cm5, respectively, in proportion to the decrease in PAF from 100 to 0%. The prostaglandin E2 concentration increased from 1.5 +/- 0.6 to 8.8 +/- 0.6 pg/ml following the decrease in PAF from 100 to 0%. The renin-angiotensin system increased in proportion to the decrease in PAF. In contrast, the epinephrine and norepinephrine concentrations (60 +/- 10 and 227 +/- 80 pg/ml, respectively, at 100% PAF) did not change appreciably even at 10% PAF, but were markedly elevated to 335 +/- 117 and 2,088 +/- 1,503 pg/ml at 0% PAF. The antidiuretic hormone level similarly changed. In conclusion, decrease in PAF during VAB exerts significant effects on hemodynamics in a proportional manner and on vasoactive humoral factors in a diverse manner.

In vitro and in vivo heat dissipation of an electrohydraulic totally implantable artificial heart.

The authors evaluated the heat transfer characteristics of an electrohydraulic totally implantable artificial heart (EH-TAH) developed at our institute. In three in vitro experiments, the heat dissipation of the EH-TAH was investigated. First, the EH-TAH was connected to a closed mock circuit filled with 1 L of saline, and driven at an input power of 20 W. The estimated heat conducted to the blood was approximately 10.3 W, which was almost half of the input power. Second, we simulated heat transfer with the circulation of a calf by using a heat exchanger. The amount of heat dissipating directly from the EH-TAH surface was calculated to be 10 W. Third, the temperature of the actuator examined with thermography was found to be almost uniform, and no prominent high temperature area was observed. In an in vivo study, the EH-TAH was implanted for 10 days in a calf weighing 62 kg. The input power was 18 +/- 2 W, the temperature of the actuator-tissue contacting surface was 39.4 +/- 0.8 degrees C, and that of the pump blood chamber was 39.8 +/- 0.4 degrees C. This slight temperature elevation was thought to be attributable to heat dissipation to the blood. On histologic study of the chest wall and the lung in contact with the actuator, vascularized connective tissue envelopes were observed, but unfavorable side effects, such as tissue necrosis, were not observed. These results suggest that the thermal effect of this system is acceptable at the input power used.

In vitro and in vivo evaluation of a left-right balancing capacity of an interatrial shunt in an electrohydraulic total artificial heart system.

The authors evaluated the basic performance of an interatrial shunt (IAS) made by punching a hole in the atrial septum, in accommodating the left-right imbalance in our electrohydraulic total artificial heart (EHTAH) system. In an in vitro study conducted in a closed mock circuit connected with the EHTAH, the interatrial pressure gradient changed in compliance with the amount of bronchial flow and the size of the IAS. The IAS of 4.4 mm diameter or larger maintained the interatrial pressure gradient within physiologically permissible limits when the amount of bronchial flow was 5% of cardiac output or less. A left-to-right one-way valve made of a piece of pericardium, a possible option in this IAS method, successfully prevented right-to-left reverse shunt flow through the IAS. In a chronic in vivo study using a calf implanted with the EHTAH for 10 days, a 4.5 mm IAS without the one-way valve demonstrated satisfactory dynamic left-right balancing capacity with a stable interatrial pressure gradient of 4 +/- 1 mmHg over a wide range of atrial pressures. No thrombus was found in or around the IAS at autopsy. The authors conclude that the IAS is a simple and promising means of left-right balancing in the EHTAH system.