Targeted IgA Fc receptor I (FcαRI) therapy in the early intervention and treatment of pristane-induced lupus nephritis in mice.

The Fc receptor I for IgA (FcαRI) down-regulates humoral immune responses and modulates the risk of autoimmunity. This study aimed to investigate whether FcαRI targeting can affect progression of pristine-induced lupus nephritis. In the first experiment (early intervention), four groups of animals were evaluated: untreated FcαRI/FcRγ transgenic (Tg) mice and Tg mice administered control antibody (Ctr Fab), saline and anti-FcαRI Fab [macrophage inflammatory protein (MIP)-8a], respectively, three times a week for 29 weeks, after being injected once intraperitoneally with 0·5 ml pristane. In the second experiment, antibody injection started after the onset of nephritis and was carried out for 2 months, with similar groups as described above. MIP-8a improved proteinuria, decreased the amounts of glomerular injury markers, serum interleukin (IL)-6, IL-1 and monocyte chemoattractant protein (MCP)-1, and F4/80 macrophages in the interstitium and glomeruli, in both experiments. When MIP-8a was used as early intervention, a decrease in mouse serum anti-nuclear antibody (ANA) titres and reduced deposition of immunoglobulins in glomeruli were observed. This effect was associated with reduced serum titres of immunoglobulin (Ig)G2a but not IgG1, IgG2b and IgG3. Furthermore, pathological analysis showed lower glomerular activity index and less fibronectin in MIP-8a treated mice. This study suggests that FcαRI targeting could halt disease progression and lupus activation by selective inhibition of cytokine production, leucocyte recruitment and renal inflammation. Our findings provide a basis for the use of FcαRI as a molecular target for the treatment of lupus.

On the genesis of heterogeneous photocatalysis: a brief historical perspective in the period 1910 to the mid-1980s.

The concept Photocatalysis and, of greater import here, Heterogeneous Photocatalysis were first introduced in the second decade (1910-1920) of the 20th century according to the CAPLUS and MEDLINE databases (SciFinder). This review reports a brief historical perspective on the origins of the two concepts, whether implied or explicitly stated, in some detail up to about the mid-1980s when heterogeneous photocatalysis witnessed the beginning of an exponential growth, with particular emphasis on the use of nanosized TiO(2) particles in powdered form as the (so-called) photocatalyst of choice in environmental applications because of its inherent properties of abundance and chemical stability in acidic and alkaline aqueous media (in the dark), in contrast to ZnO that had been the metal oxide of choice in the early days. The early workers in this area often used the term photosensitization rather than the current popular term photocatalysis, used since the early 1980s. The term Photocatalysis appeared in the literature as early as 1910 in a book by Plotnikow (Russia) and a few years later it was introduced in France by Landau. The review also reports on contributions during the early years by Terenin at the University of St. Petersburg (previously Leningrad, Soviet Union), and in the decade spanning 1975-1985 contributions by Bard's group at the University of Texas at Austin (USA) as well as those of other groups. Some activities into the conversion of light energy to chemical fuels (e.g. H(2)) during the 1975-1985 decade are also considered.

Negative regulation of inflammatory responses by immunoglobulin A receptor (FcαRI) inhibits the development of Toll-like receptor-9 signalling-accelerated glomerulonephritis.

Myeloid FcαRI, a receptor for immunoglobulin (Ig)A, mediates cell activation or inhibition depending on the type of ligand interaction, which can be either multivalent or monovalent. Anti-inflammatory signalling is triggered by monomeric targeting using anti-FcαRI Fab or IgA ligand binding, which inhibits immune and non-immune-mediated renal inflammation. The participation of Toll-like receptors (TLRs) in kidney pathology in experimental models and various forms of human glomerular nephritis has been discussed. However, little is known about negative regulation of innate-immune activation. In the present study, we generated new transgenic mice that express FcαRI(R209L) /FcRγ chimeric protein and showed that the monovalent targeting of FcαRI exhibited inhibitory effects in an in vivo model of TLR-9 signalling-accelerated nephritis. Mouse monoclonal anti-FcαRI MIP8a Fab improved urinary protein levels and reduced the number of macrophages and immunoglobulin deposition in the glomeruli. Monovalent targeting using MIP8a Fab attenuates the TLR-9 signalling pathway and is associated with phosphorylation of extracellular signal-related protein kinases [extracellular signal-regulated kinase (ERK), P38, c-Jun N-terminal kinase (JNK)] and the activation of nuclear factor (NF)-κB. The inhibitory mechanism involves recruitment of tyrosine phosphatase Src homology 2 domain-containing phosphatase-1 (SHP-1) to FcαRI. Furthermore, cell transfer studies with macrophages pretreated with MIP8a Fab showed that blockade of FcαRI signalling in macrophages prevents the development of TLR-9 signalling-accelerated nephritis. These results suggest a role of anti-FcαRI Fab as a negative regulator in controlling the magnitude of the innate immune response and a new type of anti-inflammatory drug for treatment of kidney disease.

Significance of glomerular activation of the alternative pathway and lectin pathway in lupus nephritis.

The objective of the present study was to elucidate the association between glomerular complement depositions belonging to the alternative (AP) and lectin (LP) pathways, and clinical findings of lupus nephritis (LN). Immunofluorescence (IF) was performed on 17 LN patients using antibodies against factor B, factor H, properdin, mannose-binding lectin (MBL) and L-ficolin. Compared with factor B/factor H negative patients (n = 9), positive patients (n = 8) showed longer duration of LN (p < 0.05) and more severe interstitial fibrosis (p < 0.05). Eleven patients had properdin deposition in glomeruli, and in three of them, with a duration of LN of less than 1 month, factor B was undetectable. Compared with properdin negative patients (n = 6), positive patients (n = 11) showed significantly higher urinary protein excretion (p < 0.01). MBL/L-ficolin positive patients (n = 11) also had significantly higher urinary protein excretion (p < 0.05) compared with negative patients (n = 6). An independent association was found between glomerular deposition of properdin and that of MBL/L-ficolin (p < 0.01) in addition to factor B/factor H. Traces of glomerular activation of AP and LP reflected the clinical status of LN. It appears that glomerular deposition of each complement component, especially properdin, may be an index of the histological activity of LN.

Type B insulin resistance syndrome with systemic lupus erythematosus.

Type B insulin resistance syndrome is a rare disease. Auto-antibodies to the insulin receptor frequently appear in the case of systemic lupus erythematosus (SLE). We report herein a case of a 56-year-old man who had presented discoid skin lesions since 1990. He was admitted to the hospital because of unconsciousness and severe hypoglycemia in 2006, and was diagnosed as having Type B insulin resistance syndrome with the presence of insulin receptor antibody. He had frequently repeated hypoglycemic and hyperglycemic episodes in spite of treatment with prednisolone (5 - 10 mg/day), and mild proteinuria of 1.5 g/day was observed. His laboratory findings on admission revealed pancytopenia and positive titer for antinuclear antibody (ANA). From these findings and his past history of skin lesions, we diagnosed him as SLE. We performed renal biopsy and his histological diagnosis was lupus nephritis Class 5 with the findings of podocytic shedding. Prednisolone dosage was increased from 10 to 60 mg/day. Thereafter, his glucose metabolism improved and proteinuria disappeared. The dose of prednisolone was tapered to 30 mg/day without recurrence of hypoglycemia and proteinuria. Early treatment with prednisolone might ameliorate proteinuria and insulin resistance. We experienced a rare case of Type B insulin resistance syndrome with increased activity of SLE, complicated with lupus nephritis. It appears that Type B insulin resistance syndrome should be suspected in differential diagnosis of hypoglycemia in SLE patients.

In situ hybridization reveals temporal and spatial changes in cellular expression of mRNA for a laminin receptor, laminin, and basement membrane (type IV) collagen in the developing kidney.

The appearance of extracellular matrix molecules and their receptors represent key events in the differentiation of cells of the kidney. Steady-state mRNA levels for a laminin receptor, the laminin B1, B2, and A chains, and the alpha 1-chain of collagen IV (alpha 1[IV]), were examined in mouse kidneys at 16 d gestation and birth, when cell differentiation is active, and 1-3 wk after birth when this activity has subsided. Northern analysis revealed that mRNA expression of laminin receptor precedes the alpha 1(IV) and laminin B chains whereas laminin A chain mRNA expression was very low. In situ hybridization reflected this pattern and revealed the cells responsible for expression. At 16 d gestation, laminin receptor mRNA was elevated in cells of newly forming glomeruli and proximal and distal tubules of the nephrogenic zone located in the kidney cortex. These cells also expressed mRNA for alpha 1(IV) and laminin chains. At birth, mRNA expression of receptor and all chains remained high in glomeruli but was reduced in proximal and distal tubules. At 1 wk after birth, expression was located in the medulla over collecting ducts and loops of Henle. Little expression was detectable by 3 wk. These results suggest that cellular expression of steady-state mRNA for laminin receptor, laminin, and collagen IV is temporally linked, with laminin receptor expression proceeding first and thereafter subsiding.

Long-term effects of the oral adsorbent, AST-120, in patients with chronic renal failure.

The oral adsorbent AST-120 has been widely used in Japan to delay the initiation of dialysis therapy in patients with chronic renal failure. This study evaluated the long-term effects of AST-120 in patients with chronic renal failure who had not previously undergone dialysis. One hundred out-patients were prospectively enrolled and prescribed 6 g/day oral AST-120 for >or= 1 year. The clinical effectiveness of AST-120 was evaluated by comparing changes in the slope of the reciprocal serum creatinine-time plot (1/sCr slope) before and after AST-120 administration. The 1/sCr slope improved significantly after >or= 1 year of AST-120 treatment and greatest improvement was observed in patients with the longest AST-120 administration period (> 30 months). The results suggest that long-term treatment with AST-120 may be beneficial for chronic renal failure patients in the pre-dialysis stage.

Tubular epithelial cells have the capacity to transdifferentiate into CD68-positive macrophage-like cells by oxidative stress.

OBJECTIVE: The present study was intended to assess transdifferentiation from tubular epithelial cells to macrophage- like cells. METHODS: Puromycin aminonucleoside nephrotic rats were sacrificed at days 4, 8, 24 and 112. We immunohistochemically evaluated CD68, CD163, and cytokeratin AE1/AE3, known as markers for macrophages and tubular epithelial cells. Nitrotyrosine, gp91(phox) and Rac 1 expressions was also analyzed. CD68 expression in cultured murine proximal tubular epithelial cells (mProx) stimulated by crude and pure BSA was examined by flow cytometry and immunofluorescence. RESULTS: The tubular CD68-positive cells were observed on day 112. Immunoelectronmicroscopy revealed that some CD68-positive cells showed brush borders on the cell membrane and some of cytokeratin-positive tubular cells also expressed CD163 in mirror sections. The tubular CD68-positive cells were also positive for nitrotyrosine, gp91 (phox) and Rac 1. They contained lipid in their cytoplasm. Crude BSA, containing free fatty acid, induced CD68 expression in a dose- and time-dependent manner in mProx, but not pure BSA. The surface expression of CD68 was increased by high dose and long term stimulation with crude BSA as shown by immunofluorescence. CONCLUSIONS: We confirmed that tubular epithelial cells have the capacity to transdifferentiate to CD68-positive macrophage-like cells, which may be linked to oxidative stress.

Improvement of peritoneal calcification after parathyroidectomy in a peritoneal dialysis patient.

Peritoneal calcification is one of the complications of peritoneal dialysis (PD). It can become serious, leading to severe abdominal pain and even death. Possible mediators of peritoneal calcification in PD patients are assumed to include acetate buffer, overdosage of vitamin D, repeated peritonitis, hypertonic dialysate, calciphylaxis and secondary hyperparathyroidism (SHPT). However, the mechanism and treatment of peritoneal calcification are controversial. Few reports have appeared on improvement of peritoneal calcification after parathyroidectomy (PTX) for SHPT of long duration. We report herein the case of a 48-year-old man on dialysis for 17 years including PD for 14 years. In 1989, he was admitted to hospital because of end-stage renal disease (ESRD), and started treatment with PD. Abdominal computed tomography (CT) first showed peritoneal calcification in August 2002. Peritoneal calcification did not improve despite conventional treatment including discontinuation of PD, control of calcium phosphate product to less than 55 mg2/dl2, removal of the peritoneal catheter and empirical prednisolone (PSL) usage. The intact parathyroid hormone (i-PTH) level was increased over 1,000 pg/ml and extra-osseous calcification occurred. Total PTX was performed in November 2004. Postoperatively, the i-PTH level decreased immediately and calcium phosphate product was maintained in the reference range. Abdominal CT after PTX showed improvement of peritoneal calcification in September 2005. It appeared that PTX could be used to treat patients with persistent peritoneal calcification not responding to conventional treatment. It was postulated that SHPT might play a crucial role in accelerating peritoneal calcification in PD patients.

Water deprivation stimulates transforming growth factor-beta 2 accumulation in the juxtaglomerular apparatus of mouse kidney.

Transforming growth factor-beta (TGF-beta) modulates the growth and differentiation of many cells and often functions in an autocrine or paracrine fashion. The myoepithelial cells of the renal juxtaglomerular apparatus (JGA) synthesize and secrete renin. Under conditions which chronically stimulate renin production, the JGA undergoes hypertrophy and hyperplasia. The molecular factors responsible for these changes in the JGA have not been identified. In the present study, plasma renin activity was stimulated in the mouse by water deprivation. Using immunoperoxidase staining with specific antibodies against TGF-beta 1, beta 2, and beta 3, we found increased TGF-beta 2 accumulation in the JGA and interlobular arteries. Immunostaining with renin antiserum demonstrated colocalization of TGF-beta 2 and renin. TGF-beta 1 and beta 3 expression was not different between control and water-deprived mice. Our results suggest that in the setting of water deprivation, TGF-beta 2 is localized in a manner which would allow it to act either as a growth factor for or as a phenotypic modulator of the JGA and renal arterioles.

Effect of educational hospitalization on chronic kidney disease (CKD) patients.

UNLABELLED: Although dietary control is recommended to chronic kidney disease (CKD) patients, improvement of compliance and education of outpatients are very difficult. The purposes of the present study are to estimate the dietary intake of sodium (Na) and protein by measuring urinary Na and urea nitrogen (UN) excretion, and to evaluate the efficacy of educational hospitalization. METHODS: 70 patients (41 men and 29 women) with a mean age of 58.7+/-15.8 years participated in the present study. Most patients had chronic kidney disease (CKD, Stage 3 or 4). Patients were hospitalized to learn about their diseases and dietary restrictions for 1 week. Patients were given low salt (less than 6 g/day) and low protein (0.6-1.0 g/standard body weight kg/day) diet. 24-hour urine samples were collected at the start (Day 2) and on completion (Day 7) of hospitalization. Salt and protein intakes were estimated using patients' 24-hour urine samples. RESULTS: Estimated salt intake was significantly decreased on completion of the hospitalization (Day 7) (p < 0.05). Estimated protein intake was also decreased slightly, but this was not statistically significant. There were significant differences in the changes of body weight, body mass index (BMI), and systolic and diastolic blood pressure between the start (Day 2) and completion (Day 7) of hospitalization. 89% of the patients showed an improved blood pressure without changes of antihypertensive drugs. CONCLUSIONS: It appears that short-term hospitalization is an effective program for achieving dietary and blood pressure control in CKD patients.

Dose-response to a jelly preparation of calcium polystyrene sulfonate in patients with hyperkalemia--changes in serum potassium levels with or without a RAAS inhibitor.

AIMS: In this study, dose-response of the serum potassium-lowering effect of a calcium polystyrene sulfonate (PS) preparation was investigated. Changes in the serum potassium level were also examined with or without application of a RAAS inhibitor, which is said to increase the serum potassium level. SUBJECTS AND METHODS: 23 patients diagnosed to have hyperkalemia associated with chronic renal failure were enrolled in this study. The study drug, a PS-Ca jelly preparation (Argamate jelly), was started at a daily dose of 1 preparation (5 g as PS-Ca), and the dose was increased by 1 preparation every month to finally reach 3 preparations per day. Blood samples were collected once a month and serum levels of creatinine and electrolytes were measured. RESULTS: PS-Ca jelly decreased serum potassium levels in a dose-dependent manner. Decreases were 0.67 mEq/l at 5 g of PS-Ca/day, 1.06 mEq/l at 10 g/d, and 1.33 mEq/l at 15 g/d. Irrespective of the use of the RAAS inhibitor, serum potassium levels decreased significantly in a dose-dependent manner. Furthermore, no major change in serum creatinine levels occurred in subjects in which the RAAS inhibitor was used, although in subjects in which the RAAS inhibitor was not used, serum creatinine level tended to gradually increase. CONCLUSION: Serum potassium levels were reduced in a dose-dependent manner by administration of 5-15 g/d of PS-Ca, and it appeared that together with control of serum potassium levels, renal function should be maintained by continuous administration of RAAS inhibitor.

Activity of midbrain reticular formation and neocortex during the progression of human non-rapid eye movement sleep.

To clarify the neural correlates and brain activity during the progression of human non-rapid eye movement (NREM) sleep, we examined the absolute regional cerebral blood flow (rCBF) during light and deep NREM sleep and during wakefulness in normal humans using positron emission tomography with H(2)(15)O. Relative changes in rCBF during light and deep NREM sleep in comparison to the rCBF during wakefulness were also analyzed. During light NREM sleep, the rCBF in the midbrain, in contrast to that in the pons and thalamic nuclei, did not decrease when compared to that during wakefulness, whereas rCBF decreased in the left medial frontal gyrus, left inferior frontal gyrus, and left inferior parietal gyrus of the neocortex. During deep NREM sleep, the rCBF in the midbrain tegmentum decreased, and there was a marked and bilateral decrease in the rCBF in all neocortical regions except for the perirolandic areas and the occipital lobe. There have been three groups of brain structures, each representing one type of deactivation during the progression of NREM sleep. The activity of the midbrain reticular formation is maintained during light NREM sleep and therefore represents a key distinguishing characteristic between light and deep NREM sleep. Selective deactivation of heteromodal association cortices, including those related to language, occurs with increasingly deep NREM sleep, which supports the recent theory that sleep is not a global, but it is a local process of the brain.

Detoxification mechanism of asbestos materials by microwave treatment.

The detoxification mechanism of asbestos materials was investigated through simulations and experiments. The permittivities of pure CaO and Mg3Si4O12, as quasi-asbestos materials, were measured using the cavity perturbation method. The real and imaginary parts of the relative permittivity (ɛr' and ɛr″) of CaO are functions of temperature, and numerical simulations revealed the thermal distributions in an electromagnetic field with respect to both asbestos shape and material configuration based on permittivity. Optical microscopic observation revealed that the thickness of chrysotile fibers decreased as a result of CaO heating. The heating mechanism of asbestos materials has been determined using CaO phase, and the detoxification mechanism of asbestos materials was discussed based on the heating mechanism.

Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients.

Titanium dioxide (TiO2) has been noted (US Federal Register, 43FR38206, 25 August 1978) to be a safe physical sunscreen because it reflects and scatters UVB and UVA in sunlight. However, TiO2 absorbs about 70% of incident UV, and in aqueous environments this leads to the generation of hydroxyl radicals which can initiate oxidations. Using chemical methods, we show that all sunscreen TiO2 samples tested catalyse the photo-oxidation of a representative organic substrate (phenol). We also show that sunlight-illuminated TiO2 catalyses DNA damage both in vitro and in human cells. These results may be relevant to the overall effects of sunscreens.

Independent thallium-201 accumulation and fluorine-18-fluorodeoxyglucose metabolism in glioma.

UNLABELLED: SPECT with 201TI is an effective procedure for evaluating the malignancy of glioma. Our goal was to investigate the diagnostic relevance of both 201TI SPECT and [18F]fluorodeoxyglucose (FDG) PET and the relation between 201TI uptake and glucose metabolism in glioma using comparative SPECT and PET studies. METHODS: Thallium-201 SPECT and FDG dynamic PET studies were performed in 20 patients with untreated glioma (5 with glioblastoma, 5 with anaplastic glioma, 10 with low-grade glioma). Thallium-201 uptake in the tumor was estimated using the 201TI index, defined as the ratio of 201TI uptake in the tumor to that in the contralateral normal brain on SPECT images obtained 15 min after intravenous injection. We measured regional glucose metabolic parameters, including rate constants and regional cerebral metabolic rate of glucose utilization (rCMRgl), in the tumor. We then compared the regional 201TI index and glucose metabolic parameters with the histologic characteristics, malignancy and computed tomographic/ magnetic resonance imaging findings. In addition, we investigated the correlation between the 201TI index and glucose metabolic parameters. RESULTS: Thallium-201 SPECT showed abnormal 201TI uptake in all patients with glioblastoma and anaplastic glioma. Thallium-201 indices of glioblastoma (202.6 +/- 22.1%) and anaplastic glioma (176.6% +/- 26.6%) were significantly higher than that for low-grade glioma (106.7% +/- 13.8%). The rCMRgl value of glioblastoma (17.6 +/- 3.5 mumole/100 g/min) was also significantly higher than that for low-grade glioma (10.8 +/- 4.5 mumole/100 g/min), although rCMRgl showed a large variability in both high- and low-grade glioma. Rate constants of FDG kinetics had no correlation with histological grade of glioma. Some patients with high-grade glioma, however, showed false-negative results with FDG-PET because of high normal brain uptake of FDG. Conversely, most low-grade glioma could not be localized by 201TI SPECT. There was no correlation between the 201TI index and glucose metabolic parameters. CONCLUSION: Thallium-201 indices and rCMRgl values for glioblastoma were higher than those for low-grade glioma. Thallium-201 uptake in the tumor may be independent of increased glucose transport or metabolism. Thallium-201 SPECT and FDG-PET are complementary in the diagnosis of glioma, although 201TI SPECT is more significantly correlated with the malignancy of glioma.

Epstein-Barr virus detection in kidney biopsy specimens correlates with glomerular mesangial injury.

To determine the relationship between the detection of Epstein-Barr virus (EBV)-specific DNA and glomerular injury, 33 renal needle-biopsy specimens that had been formalin-fixed and paraffin-embedded were analyzed using polymerase chain reaction (PCR) with subsequent nonradioactive Southern blot technique. Light microscopic examination and immunofluorescence were also performed. In 30 of 33 renal biopsy specimens, the beta globin gene could be successfully amplified as integrity controls. These 30 patients consisted of 12 patients with immunoglobulin A nephropathy (IgAN), 10 patients with minor glomerular abnormalities, 6 patients with membranous nephropathy, and 2 patients with focal/segmental lesions. EBV was detected in 7 of 12 patients with IgAN (58%), 3 of 6 patients with membranous nephropathy (50%), 0 of 10 patients with minor glomerular abnormalities (0%), and 2 of 2 patients with focal/segmental lesions. EBV detection was not disease specific. The EBV detection ratio of the group with glomerular mesangial lesions (64%; 9 of 14 patients) was significantly greater than those without (19%; 3 of 16 patients; P < 0.012, chi-square test). The EBV detection ratio of the group with glomerular lesions (60%; 12 of 20 patients) was significantly greater than those without (0%; 0 of 10 patients; P < 0.0016, Fisher's exact test), and the EBV detection ratio of the group with fibrinogen deposits observed in immunofluorescence (73%; 11 of 15 patients) was significantly greater than those without (7%; 1 of 15 patients; P < 0.0002, chi-square test). The EBV detection ratio of the group with immunoglobulin deposits (57%; 12 of 21 patients) was also significantly greater than those without (0%; 0 of 9 patients; P < 0.0040, Fisher's exact test). These data suggest that EBV can damage the glomerular mesangium beyond disease units and be mediated by immunoglobulin in patients with various chronic glomerulonephritides.

Evidence of organ damage after cardiopulmonary bypass. The role of elastase and vasoactive mediators.

In this study the causes of organ damage after cardiopulmonary bypass were multifactorial. The concentration of the proteolytic enzyme elastase, which was released from activated granulocytes in the milieu of significantly reduced levels of alpha 1-protease inhibitor (p less than 0.01), increased during cardiopulmonary bypass (p less than 0.01). In addition, bypass initiated platelet aggregation, which both altered the eicosanoid metabolism and caused the level of thromboxane A2 to increase and surpass the level of prostaglandin I2. Because thromboxane A2 dominance subsided immediately after cardiopulmonary bypass, the effect of thromboxane A2 (vasoconstriction) on the development of organ damage may have been influential only during bypass. Both during and after bypass, the increase in endothelin excretion (p less than 0.01 to 0.05) was believed to induce a further vasoconstriction in the microvasculature. On completion of the cardiopulmonary bypass, the elevation of the lysosomal enzyme beta-glucuronidase, which is a sensitive indicator of cellular damage, was influenced by the concentrations of elastase (r = 0.8) and endothelin (r = 0.52). As evidenced by leuko-sequestration in the lung after cardiopulmonary bypass, the increase in the alveolar-arterial oxygen tension difference correlated with the elastase concentration (r = 0.68). Renal damage, which was detected by an increase in renal tubular enzymes (N-acetyl-beta-D-glucosaminidase and gamma-glutamyltranspeptidase) was affected by the endothelin (r = 0.68, 0.56) and elastase levels (r = 0.58, 0.68), respectively, but not by the ratio of thromboxane B2 to prostaglandin F1 alpha. The elastase level influenced the pulmonary vascular resistance (r = 0.56). However, neither the cardiac index nor the systemic and pulmonary vascular resistances were influenced by the endothelin level and the ratio of thromboxane B2 to prostaglandin F1 alpha.

Full-thickness dynamic cardiomyoplasty of the left ventricle with free revascularized latissimus dorsi myografts. An experimental feasibility study.

Dynamic cardiomyoplasty, with use of a free latissimus dorsi myograft revascularized by the internal thoracic artery and vein, was performed in eight dogs subjected to electrical preconditioning for 8 to 12 weeks (group I) and in six unconditioned dogs (group II). The procedure was performed after the resection of the anterior wall of the left ventricle. Cardiac output and left ventricular stroke work were augmented by 23.7% +/- 9.4% and 44.1% +/- 15.9% after graft pacing with 50 Hz burst stimulation at a 1:1 synchronization ratio, while left atrial pressure ranged from 8 to 12 mm Hg. Analysis of the left ventricular function curve showed that graft pacing at rates of 1:1, 2:1, and 3:1 augmented global left ventricular function. Hemodynamic benefit by continuous pacing at a 3:1 ratio was seen for 1.97 +/- 1.90 hours (0.5 to 6.1 hours) in group I until complications unrelated to the graft terminated the study, while it lasted for only 0.19 +/- 0.09 hour in group II. During the stimulation, the ratio of the lactate output to the oxygen consumption of the graft in group I, a possible indicator of metabolic shift, was significantly less than in group II, (0.46 +/- 0.58 and 6.34 +/- 1.73; p < 0.01). We conclude that free grafts of transformed latissimus dorsi muscle can augment global left ventricular performance, with a physiologic preload by oxidative metabolism, and provide a viable option in full-thickness dynamic cardiomyoplasty.

Perfusion pressure control by adenosine triphosphate given during cardiopulmonary bypass.

Administration of exogenous adenosine triphosphate (ATP) as a vasodilator during cardiopulmonary bypass was assessed in consecutive adult patients (n = 24) who demonstrated a high arterial perfusion pressure (mean, > 90 mm Hg). The action of ATP was characterized by rapid induction and stabilization of the blood pressure level. The dose of ATP ranged from 0.68 to 2.68 mg/min. Within 1 minute after the administration, there was a significant reduction in the perfusion pressure from 102 +/- 18 mm Hg (mean +/- standard deviation) to 72 +/- 19 mm Hg. The ATP was then able to maintain the desired pressure of 69 +/- 12 mm Hg at 5 minutes, 67 +/- 12 mm Hg at 10 minutes, and consistent values thereafter. After the ATP administration was discontinued, there was a prompt recovery of pressure without bradyarrhythmia. The frequency and amount of inotropes used were consistent with the control group (n = 26). Although the administration of ATP reduced the increase in serum catecholamine concentration, there were no significant changes in other vasoactive mediators (eicosanoid, angiotensin II, endothelin) between the two groups during cardiopulmonary bypass. There was neither an accumulation of metabolic products (uric acid, phosphate) nor a decrease in the level of divalent cation (Ca2+), which is observed when the cations combine with phosphates or adenosine nucleotides. This study confirmed the efficacy and safety of ATP infusion during cardiopulmonary bypass.