PubMed Health⌕ Search

Biomedical subjects

Kerstin Amann

Publications and source records attributed to Kerstin Amann.

At least 55 records · Page 3Linked to original sources
PubMed2004

Effects of portal vein arterialization on regeneration and morphology in liver transplantation: investigations using the rat model.

BACKGROUND: Portal vein arterialization (PVA) has been proposed as a technical variant in liver transplantation in the case of non-recanalizable thrombosis. The present study investigates the effects of the arterialized portal vein on the function, morphology, and regenerative behavior of the liver. METHODS: Different PVA techniques, including orthotopic liver transplantation, were used in a rat model. Portal blood flow was measured using a ultrasonic flowmeter. The regeneration capacity was determined on the basis of the increase of liver weight and the proliferating cell nuclear antigen index. The amount of hydroxyproline and the transcript levels of procollagen I were measured to determine the degree of fibrosis. The extracellular matrix was visualized with Picro-Sirius staining. RESULTS: The measurements obtained with an ultrasonic probe revealed a significant increase in portal blood flow after PVA. The regeneration capacity in the groups after PVA with no flow reduction was comparable to that of the control. Liver transplantation and PVA with no flow reduction was followed by a significant increase (four- to sixfold) in the amount of hydroxyproline and the level of the mRNA for procollagen I. In the Picro-Sirius staining, periportal and perivascular fibrosis with incipient formation of septa was seen. After reduction of the portal blood flow, these effects were significantly less pronounced. CONCLUSIONS: These operative techniques represent an excellent small animal model for studying the mechanism of liver regeneration and the genesis of fibrosis in liver and vessel tissue. The presenting findings indicate that the negative effects of "overarterialization" may be largely avoided by reducing portal blood flow. This implies that permanent PVA in clinical liver transplantation should be performed only in conjunction with a down-regulation of portal flow.

Alanine Transaminase↗
PubMed2004

Characterization of the renal phenotype in a mouse model of Marfan syndrome.

The microfibrillar protein fibrillin-1 is expressed abundantly in the vasculature and the glomerulus of the kidney. Mutations in the fibrillin-1 gene lead to Marfan syndrome. The most common complication of this disease is aortic dilatation due to elastic deficiencies of the vascular wall. Several case reports describe glomerular disease in patients with Marfan syndrome, and fibrillin-1 has been implicated in nephrogenesis. To study the role of fibrillin-1 in renal development and function, we characterized the renal phenotype of fibrillin-1-underexpressing mice. Kidney histology was evaluated by means of morphometry and stereology. Relative kidney weights, daily urine excretion, urinary albumin excretion, serum and urinary creatinine, as well as serum urea were not different than wild-type mice. Glomerular number and renal capillarization were normal. The size of the renal filtration surface was comparable in wild-type and fibrillin-1-underexpressing mice. There was no indication for glomerular, renal vascular, or tubulointerstitial injury. However, glomerular volume and mesangial area were reduced. No changes in glomerular cell numbers were detected, but the cellular volume of mesangial cells was significantly lower in glomeruli of fibrillin-1-underexpressing mice. Thus, despite the high abundance of fibrillin-1 in glomeruli of wild-type animals, underexpression of fibrillin-1 did not lead to functional deficiencies of the glomerulus. Alterations in renal histology were only subtle with a reduced glomerular volume and mesangial area likely due to a reduced mesangial cell volume.

Animals↗
PubMed2004

Modulation of gene expression by moxonidine in rats with chronic renal failure.

BACKGROUND: Sympathetic overactivity is a hallmark of chronic renal failure. In a previous experimental study, the sympatholytic drug moxonidine (MOX) had beneficial effects on progression of chronic renal failure. The present study investigates whether moxonidine influences the expression of genes associated with adaptive changes in kidneys of subtotally nephrectomized rats. METHODS: RNA was isolated from remnant kidneys of sham-operated, subtotally nephrectomized (SNX) and moxonidine-treated SNX (SNX-M) rats 12 weeks after operation. Genes that might play a role in renal adaptation processes after subtotal nephrectomy were selected and their expression was analysed by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: After subtotal nephrectomy, there was an increase in gene expression of cysteine protease cathepsin (H + L), ATP receptor subtypes P2Y(2) and P2Y(6), cell cycle regulator p21 and transforming growth factor-beta1 (TGF-beta1), and a decrease of the metalloprotease aminopeptidase-M (APM), membrane transporter megalin, ageing-related klotho, type I TGF-beta receptor, mitochondrial cytochrome oxidase-1, kallikrein, leucine zipper-1, matrix-degrading metalloprotease meprin, the organic anion transporter and the P2 receptor subtypes P2Y(1) and P2Y(4). In SNX-M rats, mRNA levels of APM, megalin, klotho, TGF-beta1, type I TGF-beta receptor, p21, P2Y(1) and P2Y(2) were shifted back towards control levels. CONCLUSIONS: Several genes showing altered expression levels after subtotal nephrectomy were identified in remnant kidneys. These genes might act as candidates to promote disease progression. The sympatholytic drug moxonidine, at a concentration devoid of blood pressure effects, regulates the renal expression of some of these genes back towards control levels. To what extent sympathetic neurotransmitters directly alter expression of these genes in cultured renal cells currently is under investigation.

Animals↗
PubMed2004

Exogenous modulation of TGF-beta(1) influences TGF-betaR-III-associated vascularization during wound healing in irradiated tissue.

BACKGROUND AND PURPOSE: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial cell carcinomas of the head and neck region, wound-healing disorders occur. Previous experimental studies showed altered expression of transforming growth factor-(TGF-)beta isoforms following surgery in irradiated graft beds. Altered levels of TGF-beta(1) are reported to promote fibrosis and to suppress vascularization during wound healing, whereas expression of TGF-beta receptor-III (TGF-betaR-III) is associated with vascularization. The aim of the study was to analyze the influence of anti-TGF-beta(1) treatment on TGF-betaR-III-associated vascularization in the transition area between irradiated graft bed and graft. MATERIAL AND METHODS: Wistar rats (male, weight 300-500 g) underwent preoperative irradiation of the head and neck region with 40 Gy (four fractions of 10 Gy each; n = 16 animals). A free myocutaneous gracilis flap taken from the groin was then transplanted to the neck in all rats. The time interval between operation and transplantation was 4 weeks. Eight animals received 1 micro g anti-TGF-beta(1) into the graft bed by intradermal injection on days 1-7 after surgery. On days 3, 7, 14, 28, 56, and 120, skin samples were taken from the transition area between transplant and graft bed and from the graft bed itself. Immunohistochemistry was performed using the ABC-POX method to analyze the TGF-betaR-III and E-selectin expression. Histomorphometry was performed to analyze the percentage and the area of positively stained vessels. RESULTS: A significantly higher expression of TGF-betaR-III was seen in the irradiated and anti-TGF-beta(1)-treated graft bed in comparison to the group receiving preoperative irradiation followed by transplantation alone. The percentage of TGF-betaR-III positively staining capillaries from the total amount of capillaries in the anti-TGF-beta(1)-treated graft bed was higher than in the group irradiated only. The total area of capillaries was also higher in the TGF-beta(1)-treated group. CONCLUSION: Neutralizing of TGF-beta(1) activity in irradiated tissue undergoing surgery leads to a higher expression of TGF-betaR-III and increased vascularization. TGF-betaR-III seems to be associated with newly formed blood vessels during neovascularization in wound healing.

Animals↗
PubMed2004

Low nephron number--a new cardiovascular risk factor in children?

There is increasing evidence that primary hypertension, coronary heart disease, and other aspects of the so-called metabolic syndrome that develop in adulthood are primed in fetal life or early postnatally. The identification of this phenomenon, also known as prenatal or fetal programming, and the detailed characterization of the underlying pathomechanisms will greatly influence the understanding of these diseases. The present paper reviews recent experimental and clinical evidence that low nephron number, found in patients with renal dysplasia and low birth weight, is a risk factor for cardiovascular disease in later life. Therefore, it is important to identify children at risk as early as possible in order to treat them early and to prevent the development of end-organ damage. This could be an important goal for pediatrics in the near future.

Cardiovascular Diseases↗
PubMed2004

Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques.

Dendritic cells (DC), which are critically involved in various immunological disorders, were detected in atherosclerotic plaques in 1995. Since DC might be related to the immunological processes in atherosclerosis (AS), we analyzed the emergence of DC and other inflammatory cells in different stages of AS. Serial cross-sections of 44 carotid specimens were immunohistochemically analyzed for the presence of DC, T cells, macrophages, and HLA-DR. Atherosclerotic specimens were histologically defined as initial lesions, advanced stable, or vulnerable plaques. In initial lesions significantly lower DC numbers were detected than in advanced plaques (P < 0.001). For advanced plaques, DC numbers were significantly higher in vulnerable than in stable plaques (P = 0.005). In contrast to initial lesions, approximately 70% of DC in advanced plaques exhibited a mature phenotype (CD83+, DC-LAMP+), indicating a functional activity of DC. In plaques of patients with acute ischemic symptoms DC numbers were markedly elevated (P = 0.03), whereas significantly lower DC numbers and more often a stable plaque morphology were detected in statin-treated patients (P = 0.02). DC clusters with a strong HLA-DR expression and frequent DC-T cell contacts were located particularly in the rupture-prone plaque regions and at complications. The results of the present study indicate that DC might contribute to plaque destabilization through an activation of T cells.

Aged↗
PubMed2004

Smad-3 and Smad-7 expression following anti-transforming growth factor beta 1 (TGFbeta1)-treatment in irradiated rat tissue.

BACKGROUND AND PURPOSE: Wound healing disorders and the development of fibrosis following surgery in preirradiated tissue are clinically well characterised and may even become more pronounced with increasing use of neoadjuvant radiochemotherapy. The cytokine transforming growth factor beta 1 TGFbeta1 has a key role either in the wound healing process or induction of fibrosis. Following activation of the TGFbeta receptors, intracellular signal transduction is mediated by a variety of Smad proteins. Smad-3 acts as an activator of signal transduction, whereas Smad-7 has an inhibitory effect. This study evaluated the biological effect of neutralizing TGFbeta1 antibodies, the relationship between TGFbeta1 and Smad-3/7 expression and changes of collagen synthesis, following inhibition of TGFbeta1 activity in irradiated rat tissue. PATIENTS AND METHODS: A total of 45 Wistar rats (male, weight 300-450 g) were used. A free myocutaneous gracilis flap was transplanted in all rats and animals were allocated into 3 groups as follows: Group 1 (n = 15 rats) treated with surgery alone (TX); Group 2 (n = 15 rats) preoperative radiotherapy (RT) followed by TX; Group 3 (n = 15 rats) RT+TX+anti-TGFbeta1-treatment. The interval between end of radiotherapy and grafting was 10 days. For anti-TGFbeta1 treatment, 1 microg anti-TGFbeta1/500 microl PBS were locally applied s.c. intraoperatively and on day 1 to 7 after surgery. Tissue samples were collected perioperatively and on days 3, 7, 14, 28 following surgery from the transition area between the graft and the graft bed. ECM synthesis and expression of TGFbeta1, Smad-3, Smad-7, prolyl-hydroxyprolinase-beta were quantitated by immunohistochemistry (labelling indices). Changes in collagen synthesis were assessed qualitatively by polarisation microscopy of sirius red staining and collagen I immunohistochemistry. The different regulation of inhibitory Smad-7 was detected in irradiated and irradiated plus anti-TGFbeta1 treated animals by semiquantitative RT-PCR and the nucleocytoplasmic shuttling of phosphorylated Smad-3 was shown by isolation of nuclear proteins and Western blot analysis. RESULTS: Following anti-TGFbeta1 treatment, an attenuated expression of TGFbeta1, a reduction in EMC synthesis and fibrosis could be observed in irradiated tissue compared to the irradiated tissue without anti-TGFbeta1-treatment. While preoperative RT increases the expression of Smad-3/7 proteins, an upregulation of Smad-7 from day 3 until day 14 following surgery and a downregulation of Smad-3 on day 14 after surgery could be observed following anti-TGFbeta1-treatment. The samples which were irradiated alone displayed a reduced signal for Smad-7 mRNA and an induction of Smad-3 protein phosphorylation shown by nucleocytoplasmic shuttling. In contrast, the anti-TGFbeta1-treated samples showed an increase in Smad-7 mRNA and a downregulation of Smad-3 phosphorylation. Prolyl-hydroxyprolinase-beta expression and collagen I synthesis were reduced following anti-TGFbeta1-treatment. CONCLUSIONS: A reduction of Smad-3 proteins in parallel with an increase of Smad-7 may contribute to the inhibitory effect and the reduction of ECM synthesis after blocking of TGFbeta1 activity by treatment with neutralizing antibodies. This may indicate a molecular mechanism in the therapeutic intervention to reduce fibrosis, hypertrophic scar formation and chronic wound healing disorders.

Animals↗
PubMed2004

Transforming growth factor beta 1 dependent regulation of Tenascin-C in radiation impaired wound healing.

BACKGROUND: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial cell carcinomas of the head and neck region fibrocontractive wound healing disorders occur. Tenascin-C is significantly increased in fibrotic tissue conditions and can be stimulated by the transcription factor NF kappa B p65. Previous studies showed a reduction of irradiation induced fibrosis during the wound healing process by anti-TGF beta(1)-treatment. The aim of the study was to clarify the question whether Tenascin-C expression is elevated in radiation impaired wounds and whether anti-TGF beta(1)-treatment is capable to influence Tenascin-C and NF kappa B expression. MATERIAL AND METHODS: Wistar rats (male, weight 300-500 g) underwent preoperative irradiation of the head and neck region with 40 Gy, fractionated four times 10 Gy (16 animals), whereas 8 non-irradated animals served as a control. Four weeks after irradiation a free myocutaneous gracilis flap taken from the groin was transplanted to the neck. Eight animals additionally received 5 microg anti-TGF beta(1) into the graft bed by intradermal injection prior to each fraction of irradiation and on days 1-7 post-operation. On day 14 and 28 following surgery immunohistochemistry (ABC-POX method) was performed assessing the cytoplasmic NF kappa B and Tenascin-C staining in the transition area between transplant and graft bed. For quantitative considerations the labeling index (ratio: positive cells/total cells) was determined. RESULTS: A significantly altered expression of Tenascin-C in the preirradiated tissue was observed following anti-TGF beta(1)-treatment. NF kappa B protein was upregulated in irradiated animals and was significantly reduced in the anti-TGF beta(1) treated group on day 28 after transplantation. CONCLUSIONS: Tenascin-C expression is prolonged in irradiated animals as compared to non-irradiated tissue. Tenascin-C seems to be regulated by TGF beta(1) as the application of TGF beta(1)-neutralizing antibodies reduces Tenascin-C expression. Tenascin-C is a potentially useful marker for tissue remodeling due to its restricted distribution in adult and healthy tissue and a hallmark for developing fibrosis.

Animals↗
PubMed2004

Human homozygous R403W mutant cardiac myosin presents disproportionate enhancement of mechanical and enzymatic properties.

Familial hypertrophic cardiomyopathy (FHC) is associated with mutations in 11 genes encoding sarcomeric proteins. Most families present mutations in MYBPC3 and MYH7 encoding cardiac myosin-binding protein C and beta-myosin heavy chain. The consequences of MYH7 mutations have been extensively studied at the molecular level, but controversial results have been obtained with either reduced or augmented myosin motor function depending on the type or homogeneity of myosin studied. In the present study, we took advantage of the accessibility to an explanted heart to analyze for the first time the properties of human homozygous mutant myosin. The patient exhibited eccentric hypertrophy with severely impaired ejection fraction leading to heart transplantation, and carries a homozygous mutation in MYH7 (R403W) and a heterozygous variant in MYBPC3 (V896M). In situ analysis of the left ventricular tissue showed myocyte disarray and hypertrophy plus interstitial fibrosis. In vitro motility assays showed a small, but significant increase in sliding velocity of fluorescent-labeled actin filaments over human mutant cardiac myosin-coated surface compared to control (+18%; P<0.001). Mutant myosin exhibited a large increase in maximal actin-activated ATPase activity (+114%; P<0.05) and Km for actin (+87%; P<0.05) when compared to control. These data show disproportionate enhancement of mechanical and enzymatic properties of human mutant myosin. This suggests inefficient ATP utilization and reduced mechanical efficiency in the myocardial tissue of the patient, which could play an important role in the development of FHC phenotype.

Actin Cytoskeleton↗
PubMed2004

Anti-TGFbeta1 antibody for modulation of expression of endogenous transforming growth factor beta 1 to prevent fibrosis after plastic surgery in rats.

The cytokine transforming growth factor beta 1 (TGFbeta1) substantially influences synthesis of extracellular matrix, fibrosis, and neoangiogenesis during wound healing in a dose dependent manner. We carried out experiments in rats to measure the degree of reduction of disorders of wound healing and fibrosis produced by inhibition of endogenous TGFbeta1 by polyclonal antibodies (poAB). A free myocutaneous gracilis flap was transplanted from the groin to the neck region in 30 Wistar rats (300-450 g body weight). In 15 animals intraoperatively and daily from days 3 to 7 postoperatively, 1 microg anti-TGFbeta1 poAB in 500 microl of phosphate buffered saline (PBS) were injected into the neck region. Fifteen animals served as controls. On postoperative days 3, 4, 5, 7, 14, and 28 the expression of endogenous TGFbeta1 in cytoplasm was analysed by immunohistochemistry (ABC-POX; AEC), in situ hybridisation of TGFbeta1-mRNA, and Sirus Red staining of collagen matrix; it was quantified using labelling indices. Neutralisation of the TGFbeta1 activity by specific poAB resulted in inhibition of the cytoplasmatic expression compared with untreated animals. In the transition area between grafted tissue and graft bed, a significant reduction of TGFbeta1 expression (mean (S.D.) 34.7 (6.5)) was found from day 5 in the group treated with anti-TGFbeta1 poAB compared with the control group (mean (S.D.) 48.1 (6.6)) (P <0.03). Up to day 14 the endogenous expression of TGFbeta1 (mean (S.D.) 30.0 (2.8)) was reduced after the application of TGFbeta1 poAB compared with the control group (mean (S.D.) 44.0 (12.3)). Sirus Red staining indicated a more complex packed structure and generally more prominent collagen types I-IV fibres in untreated animals than in animals that were given anti-TGFbeta1 poAB. Expression of TGFbeta-mRNA by in situ hybridisation was reduced in fibroblasts in animals that were given anti-TGFbeta1 poAB. The results indicate that anti-TGFbeta1 might improve the healing of free flaps in the graft beds of patients who are prone to excessive fibrosis.

Anastomosis, Surgical↗
PubMed2004

No aggravation of renal injury in apolipoprotein E knockout mice (ApoE(-/-)) after subtotal nephrectomy.

BACKGROUND: There is substantial experimental evidence that various forms of dyslipidaemia aggravate the course of renal failure and that reversal of dyslipidaemia ameliorates progression of renal failure. The apolipoprotein E knockout mouse (ApoE(-/-)) is an established model of accelerated atherogenesis. We investigated whether the course of renal disease after uninephrectomy (UNX) and subtotal nephrectomy (SNX) is altered in ApoE(-/-) mice compared with their genetic controls. METHODS: Ten-week-old, male ApoE(-/-) mice (body weight 25+/-2 g) were subjected either to sham operation (sham), UNX or SNX. C57BL/6 sham, UNX and SNX mice served as controls (body weight 26+/-3 g). The food intake of ApoE(-/-) and C57BL/6 mice was kept identical by a pair-feeding protocol. After 12 weeks, mean arterial blood pressure and heart rate were measured in awake resting mice, the kidneys were perfusion fixed and analysed using quantitative histological methods, immunohistochemistry and RT-PCR. RESULTS: At baseline, the sham ApoE(-/-) mice had significantly higher (P<0.05) serum cholesterol and triglycerides than the controls. In parallel, mean arterial blood pressure was significantly elevated in sham ApoE(-/-) mice compared with controls (137+/-15 vs 116+/-4 mmHg; P<0.05). In the sham groups, the glomerulosclerosis index was significantly higher in the ApoE(-/-) mice (1.05+/-0.14 vs 0.57+/-0.07; P<0.05), whereas the tubulointerstitial damage score was comparable (0.06+/-0.04 vs 0.04+/-0.02; n.s.). After SNX there was a significant increase in glomerulosclerosis index, but no difference could be detected between ApoE(-/-) and controls (1.75+/-0.16 vs 1.61+/-0.01, n.s.). The same was true for the tubulointerstitial damage index. CONCLUSIONS: Despite some glomerulosclerosis and elevated mean arterial blood pressure at baseline, no acceleration of progression of renal disease was found in this genetic model of hyperlipoproteinaemia. This observation suggests that despite the known spontaneous histological changes in untouched kidneys, however, the presence of hyperlipidaemia in the ApoE(-/-) mouse does not cause more severe progression in the present models of moderate renal disease.

Animals↗
PubMed2004

Progression of renal disease: new insights into risk factors and pathomechanisms.

PURPOSE OF REVIEW: Progression of renal failure, irrespective of the primary cause, is characterized by modification of renal structure, which culminates in terminal renal insufficiency. Interfering with progression continues to be a major challenge and is at the forefront of renal research. This review focuses on recent progress in the understanding of the mechanisms of progression and efforts to interfere with this process. RECENT FINDINGS: In addition to the long-known risk factors (hypertension and inadequate activation of the renin-angiotensin system), several novel risk factors and pathomechanisms, such as obesity, hyperglycemia, smoking, and several hormones, have recently been identified and investigated. Furthermore, the specific and blood pressure-independent pathogenetic roles of the sympathetic nervous system and the endothelin system in progression have been further clarified. Finally, novel animal models and techniques for studying specific aspects of progression have been developed and introduced. SUMMARY: Recently, considerable progress has been made concerning novel risk factors, understanding the underlying pathomechanisms, and interfering with the course of progression of renal diseases. Such improved insights will undoubtedly lead to new strategies in the future.

Animals↗
PubMed2004

Beneficial Effects of Estrogens on Indices of Renal Damage in Uninephrectomized SHRsp Rats.

Renal diseases tend to be less severe among premenopausal female patients, compared with male patients. Experimental data on the effects of estrogens on renal damage are controversial, and potential underlying mechanisms have not been fully clarified. Three-month-old, female, uninephrectomized (UNX), sham-operated or ovariectomized (OVX) SHRsp rats were left untreated or received either 17beta-estradiol 3-benzoate (25 micro g/d) or estriol (0.02 mg/d) daily. After 3 mo, indices of renal damage (glomerulosclerosis index and tubulointerstitial damage index) and glomerular geometric parameters were investigated. The expression of desmin, TGF-beta, endothelin-1, collagen IV, endothelial nitric oxide synthase, and estrogen receptors alpha and beta in the glomeruli and tubulointerstitium was immunohistochemically evaluated. Estradiol and estriol did not significantly affect kidney weights or BP. Estradiol and estriol caused significant reductions in albuminuria (vehicle-treated UNX/OVX animals, 25.4 +/- 8.52 mg/24 h; estradiol-treated UNX/OVX animals, 15.37 +/- 6.12 mg/24 h; estriol-treated UNX/OVX animals, 6.54 +/- 2.24 mg/24 h). The glomerulosclerosis index was significantly lower in estriol- and estradiol-treated animals (estradiol-treated UNX/OVX animals, 0.69 +/- 0.16; estriol-treated UNX/OVX animals, 0.21 +/- 0.12; P < 0.05), compared with vehicle-treated animals (1.46 +/- 0.09); the tubulointerstitial damage index exhibited a similar pattern. The mean glomerular volume was significantly less in estrogen-treated animals. UNX/OVX animals demonstrated significantly greater expression of TGF-beta and endothelin-1 in immunohistochemical, in situ hybridization, and reverse transcription-PCR assays. This increase was abrogated by estriol but not estradiol. Similarly, significantly higher glomerular and tubulointerstitial expression of proliferating cell nuclear antigen and collagen IV was observed in UNX/OVX animals, and expression was decreased by estriol but not estradiol. It was concluded that, in the UNX model of spontaneous renal damage, glomerular lesions and glomerular hypertrophy were reduced by estriol but less consistently by estradiol. In parallel, loss of podocytes, evidence of podocyte injury (i.e., desmin expression), and expression of mediator systems of glomerular damage were decreased, pointing to a major renoprotective action of estriol.

Animals↗
PubMed2004

Increased infarct size in uremic rats: reduced ischemia tolerance?

In patients with renal failure, myocardial infarction (MI) is more frequent and the rate of death from acute MI is very high. It has been argued that ischemia tolerance of the heart is reduced in uremia, but direct evidence for this hypothesis has not been provided. It was the purpose of this study (1) to ligate the left coronary artery and to measure the nonperfused area (risk area: total infarction plus penumbra) as well as the area of total infarction in subtotally nephrectomized (SNX) rats compared with sham-operated pair-fed control rats and (2) to examine the effects of potential confounders such as BP, sympathetic overactivity, and salt retention. The left coronary artery was ligated for 60 min, followed by reperfusion for 90 min. For visualizing perfused myocardium, lissamine green ink was injected. The nonperfused area (lissamine exclusion) and the area of total infarction (triphenyltetrazolium chloride stain) were assessed in sections of the left ventricle using image analysis. Groups of SNX rats also received: antihypertensive treatment (nadolol plus hydralazine); moxonidine; high salt diet or low salt diet (1.58% versus 0.015%). In surviving animals, the nonperfused area at risk (as the proportion of total left ventricular area), presumably determined by the geometry of vascular supply, was similar in sham-operated and SNX animals (0.38 +/- 0.13 versus 0.45 +/- 0.09; NS). In contrast, the infarcted area, given as a proportion of the nonperfused risk area, was significantly (P < 0.003) higher in SNX (0.68 +/- 0.09) compared with sham-operated (0.51 +/- 0.11) rats and was not altered by any of the above interventions. The finding that a greater proportion of nonperfused myocardium undergoes total necrosis is consistent with the hypothesis of reduced ischemia tolerance of the heart in renal failure. The findings could explain the high rate of death from MI in patients with impaired renal function.

Animals↗
PubMed2004

Reversal of glomerular lesions involves coordinated restructuring of glomerular microvasculature.

There is increasing evidence from both human and experimental studies that at least partial reversal of glomerulosclerosis can be achieved by glomerular remodeling. This requires substantial changes in glomerular architecture, specifically of glomerular capillaries. It was the purpose of the present study to characterize the stereologic and topologic characteristics of glomerular capillaries when partial reversal of glomerular lesions is achieved by high-dose angiotensin-converting enzyme inhibitor treatment. Sham-operated male Sprague-Dawley rats were compared with subtotally nephrectomized (SNX) rats. The latter were kept untreated for 8 wk and subsequently randomly divided into one group that was continued without treatment and another group that was treated with enalapril (48 mg/kg body wt per d administered in the drinking fluid for 4 wk). Renal morphology was evaluated after 8 or 12 wk, respectively, by stereologic techniques after pressure-controlled perfusion fixation. In SNX rats at 8 and particularly at 12 wk, the glomerulosclerosis index was significantly higher than in sham-operated rats. At 12 wk, it was lower in rats that had been treated for 4 wk with enalapril compared with untreated SNX rats, suggesting partial reversal of glomerular lesions. This was associated with a decrease in mean glomerular volume and mean glomerular tuft volume, a reduced number of capillaries per glomerulus, and reduced total length of capillaries per glomerulus but without any significant change in the length of individual capillaries. The numerical capillary density (Euler number density) as an index of topologic complexity did not change. The total capillary surface area per glomerulus was strikingly increased after subtotal nephrectomy and partially reversed after enalapril. This was accounted for primarily by fewer capillaries without any change in diameter. In parallel, the number of endothelial cells per glomerulus was strikingly increased after subtotal nephrectomy and decreased with enalapril treatment, but endothelial cell volume remained elevated. The study shows harmonious coordinate remodeling of the entire glomerulus during regression of glomerular lesions after subtotal nephrectomy. Proportionate reduction of glomerular volume and capillary number without change of individual capillary length were found. The numerical capillary density of the tuft therefore remained unchanged.

Angiotensin-Converting Enzyme Inhibitors↗