Atherosclerosis, type 1 collagen cross-linking and homocysteine.
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Arteriosclerosis↗
Biomedical subjects
T Juvonen
Publications and source records attributed to T Juvonen.
Is maintained cranial hypothermia the only factor leading to improved outcome after retrograde cerebral perfusion? An experimental study with a chronic porcine model.
BACKGROUND: Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcome after prolonged hypothermic circulatory arrest. Here we have compared two temperatures of retrograde cerebral perfusion (15 degrees C and 25 degrees C) with hypothermic circulatory arrest at systemic hypothermia of 25 degrees C to clarify whether the possible benefit of retrograde cerebral perfusion may only be due to improved cooling effect. METHODS: Eighteen pigs (23-27 kg) were randomly assigned to undergo 15 degrees C retrograde cerebral perfusion at systemic hypothermia of 25 degrees C, 25 degrees C retrograde cerebral perfusion at 25 degrees C systemic hypothermia, or hypothermic circulatory arrest at 25 degrees C for 40 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg during retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were performed until 4 hours after the start of rewarming. Daily behavioral assessment was done until death or until the animals were killed on day 7. Histopathologic analysis of the brain was carried out on all animals. RESULTS: Epidural temperatures were lower in the 15 degrees C retrograde cerebral perfusion group during the intervention (P <.05). In the 15 degrees C retrograde cerebral perfusion group, 4 (67%) of 6 animals survived for 7 days compared with 3 (50%) of 6 in both the 25 degrees C retrograde cerebral perfusion and hypothermic circulatory arrest groups. The median total histopathologic score was 5 in the 15 degrees C retrograde cerebral perfusion group and 7 in the 25 degrees C retrograde cerebral perfusion group (P =.04). CONCLUSIONS: These findings suggest that enhanced cranial hypothermia is the major beneficial factor of retrograde cerebral perfusion when careful attention is paid to its implementation.
Animals↗
Lamotrigine improves cerebral outcome after hypothermic circulatory arrest: a study in a chronic porcine model.
BACKGROUND: Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present studies was to determine the potential efficacy of lamotrigine, an Na(+) channel blocker, to mitigate cerebral injury after hypothermic circulatory arrest. METHODS: Sixteen pigs (21-27 kg) were randomly assigned to receive lamotrigine (20 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest (20 degrees C). Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. S-100beta protein was determined up to the first postoperative morning. Daily behavioral assessment was performed until the animal died or was put to death on day 7. Histologic analysis of the brain was carried out in all animals. RESULTS: Complete behavioral recovery was seen in 5 of 8 (63%) animals after lamotrigine administration, compared with 1 of 8 (13%) in the placebo group (P =.02). Among the animals that survived for 7 days, the median behavioral score was higher in the lamotrigine group (8 vs 7, P =.02). The medians of recovered electroencephalographic bursts in the lamotrigine group were higher than those in the placebo group 4 1/2 hours after the start of rewarming (P =.01). The median S-100beta level was lower in the lamotrigine group (0.01 microg/L) than in placebo controls (0.1 microg/L) 20 hours after the start of rewarming (P =.01). The median of total histopathologic score was 5.5 in the lamotrigine group and 7.5 in the placebo group (P =.06). CONCLUSIONS: The present data suggest that lamotrigine improves neurologic outcome after a prolonged period of hypothermic circulatory arrest.
Analysis of Variance↗
Leukocyte filtration improves brain protection after a prolonged period of hypothermic circulatory arrest: A study in a chronic porcine model.
BACKGROUND: Ischemic cerebral injury follows a well-attested sequence of events, including 3 phases: depolarization, biochemical cascade, and reperfusion injury. Leukocyte infiltration and cytokine-mediated inflammatory reaction are known to play a pivotal role in the reperfusion phase. These events exacerbate the brain injury by impairing the normal microvascular perfusion and through the release of cytotoxic enzymes. The aim of the present study was to determine whether a leukocyte-depleting filter (LeukoGuard LG6, Pall Biomedical, Portsmouth, United Kingdom) could improve the cerebral outcome after hypothermic circulatory arrest. METHODS: Twenty pigs (23-30 kg) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter before and after a 75-minute period of hypothermic circulatory arrest at 20 degrees C. Electroencephalographic recovery, S-100beta protein levels, and cytokine levels (interleukin 1beta, interleukin 8, and tumor necrosis factor alpha) were recorded up to the first postoperative day. Postoperatively, all animals were evaluated daily until death or until electively being put to death on day 7 by using a quantitative behavioral score. A postmortem histologic analysis of the brain was carried out on all animals. RESULTS: The rate of mortality was 2 of 10 in the leukocyte-depletion group and 5 of 10 in control animals. The risk for early death in control animals was 2.5 (95% confidence interval, 0.63-10.0) times higher than that of the leukocyte-depleted animals. The median behavioral score at day 7 was higher in the leukocyte-depletion group (8.5 vs 3.5; P =.04). The median of total histopathologic score was 8.5 in the leukocyte-depletion group and 15.5 in the control group (P =.005). CONCLUSION: A leukocyte-depleting filter improves brain protection after a prolonged period of hypothermic circulatory arrest.
Animals↗
Brain protection during aortic arch surgery.
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Aorta, Thoracic↗
Intermittent retrograde cerebral perfusion during prolonged period of hypothermic circulatory arrest: a study in a chronic porcine model.
Previous studies have shown that although retrograde cerebral perfusion (RCP) improves cerebral outcome during hypothermic circulatory arrest (HCA), RCP exposes the brain to subsequent edema. In this study, we have compared intermittent RCP (I-RCP) with continuous RCP (C-RCP) and HCA alone to determine whether the rate of fluid sequestration can be decreased without losing the beneficial effects of RCP. Eighteen pigs were randomly assigned to undergo 75 min of I-RCP, C-RCP or HCA at 20 degrees C. Hemodynamic and metabolic measurements were carried out for upto 20 h. Behavioral assessments were examined until day 7, when histopathologic analysis of the brain was performed. The median amount of fluid sequestered was 145 ml after C-RCP and -50 ml after I-RCP (p = 0.04). The mean brain weight of the animals that died within the first postoperative day was significantly higher than that in electively sacrificed animals in the C-RCP group (p = 0.04). These data suggest that if RCP is implemented intermittently, the rate of cerebral edema can be decreased, without compromising the benefits of this strategy.
Animals↗
Serum S-100beta protein predicts brain injury after hypothermic circulatory arrest in pigs.
OBJECTIVE: Serum S-100beta protein is suggested to be a neurobiochemical marker of brain injury after cardiac and aortic arch surgery. The aim of the present study was to investigate the predictive value of S-100beta protein with respect to histopathological analysis of the brain after a prolonged period of hypothermic circulatory arrest (HCA). METHODS: Eighteen pigs (21 to 31 kg) underwent a 75 min period of HCA at 20 degrees C. Serum concentrations of S-100beta were assayed in mixed venous blood before and 2, 4, 7 and 20 h after HCA. A semiquantitative post-mortem histopathological analysis scoring all main regions of the brain was carried out in every animal. RESULTS: All animals were stable during and after cardiopulmonary bypass (CPB) and survived at least to the first postoperative day. Ten of the 18 animals survived 7 days after surgery and were electively sacrificed. Animals with severe histopathological injury showed higher serum S-100beta protein levels at every time point after HCA. The strongest correlation between the total histopathologic score and serum S-100beta levels was found at 7 h after HCA (tau = 0.422 and p = 0.023). CONCLUSION: Serum S-100beta protein levels correlate with histopathological injury after a prolonged period of HCA in pigs. This finding supports the results of previous studies suggesting the potential accuracy of S-100beta in the prediction of brain injury after cardiac surgery.
Animals↗
Detection of Chlamydia pneumoniae-reactive T lymphocytes in human atherosclerotic plaques of carotid artery.
Linkage between Chlamydia pneumoniae infection and atherosclerosis has been confirmed in several studies, but the precise role of this organism in the disease process is not known. We investigated the relation and reactivity of T lymphocytes of human carotid plaques to C pneumoniae antigens. Tissue specimens were obtained from 17 patients who underwent carotid endarterectomy. Immunohistological staining and/or in situ hybridization revealed the presence of C pneumoniae in 11 (64%) of the 17 of the cases. Inflammatory infiltration seen in the vessel walls consisted primarily of CD45RO+ T-memory lymphocytes (median 80%, range 50% to 90%), whereas CD20+ B cells and monocytes were in minor proportion. In vivo activated T lymphocytes were propagated from the specimens with interleukin-2, and the antigen specificity of the established T-cell lines (TLLs) was analyzed against C pneumoniae elementary body antigen. TLLs were established from all 17 carotid tissues but none from the control specimens of ascending aorta. C pneumoniae was recognized as a specific T-cell-stimulating antigen in 7 (41%) of 17 cases. Further analyses of the C pneumoniae-reactive TLLs showed that chlamydial 60-kDa heat-shock protein induced specific proliferation in 5 (71%) of 7 cases and revealed 2 haplotype (DRB1*1502 and DQB1*06) binding motifs in human 60-kDa heat-shock protein. C pneumoniae was identified as a specific microbial antigen recognized by 41% of TLLs propagated from in vivo activated plaque T cells. Our results suggests that cell-mediated immunity to C pneumoniae plays a role in the atherosclerotic process and that this response may involve autoimmunity.
Aged↗
Genetic analysis of MMP3, MMP9, and PAI-1 in Finnish patients with abdominal aortic or intracranial aneurysms.
MMP3, MMP9, and PAI-1 are present at increased levels in abdominal aortic aneurysms (AAAs). The promoters of these genes contain polymorphisms, with alleles that exhibit different transcriptional activities in vitro. Association studies were performed using these polymorphisms and DNA isolated from 47 AAA patients, 57 intracranial aneurysm (IA) patients, and 174 controls, all from Finland. PAI-1 and MMP9 genotypes did not associate with aneurysms. The frequency of the 5A MMP3 allele was somewhat higher in the AAA than that in the control group (P = 0.0609 after Bonferroni correction), whereas the MMP3 allele frequencies in the IA group did not differ from those of the controls (P = 0.9667). These findings suggest that the transcriptionally more active 5A MMP3 allele might be a genetic risk factor for AAA among Finns. They are in agreement with previous studies demonstrating higher level of MMP3 expression in AAA than in control tissues.
Adult↗
Cold retrograde cerebral perfusion improves cerebral protection during moderate hypothermic circulatory arrest: A long-term study in a porcine model.
BACKGROUND: Deep hypothermic circulatory arrest is an effective method of cerebral protection, but it is associated with long cardiopulmonary bypass times and coagulation disturbances. Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcomes after prolonged hypothermic circulatory arrest. We tested the hypothesis that deep hypothermic retrograde cerebral perfusion could improve cerebral outcome during moderate hypothermic circulatory arrest. METHODS: Twelve pigs (23-29 kg) were randomly assigned to undergo either retrograde cerebral perfusion (15 degrees C) at 25 degrees C or hypothermic circulatory arrest with the head packed in ice at 25 degrees C for 45 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg throughout retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were carried out until 4 hours after the start of rewarming. Daily behavioral assessment was performed until elective death on day 7. A postmortem histologic analysis of the brain was carried out on all animals. RESULTS: In the retrograde cerebral perfusion group, 5 (83%) of 6 animals survived 7 days compared with 2 (33%) of 6 in the hypothermic circulatory arrest group. Complete behavioral recovery was seen in 4 (67%) animals after retrograde cerebral perfusion but only in 1 (17%) animal after hypothermic circulatory arrest. Postoperative levels of serum lactate were higher, and blood pH was lower in the hypothermic circulatory arrest group. There were no significant hemodynamic differences between the study groups. CONCLUSIONS: Cold hypothermic retrograde cerebral perfusion during moderate hypothermic circulatory arrest seems to improve neurologic outcome compared with moderate hypothermic circulatory arrest with the head packed in ice.
Animals↗
Risk factors for rupture of chronic type B dissections.
OBJECTIVE: This study was an attempt to determine risk factors for rupture and to improve management of patients with type B aortic dissection who survive the acute phase without operation. METHODS: We studied 50 patients by means of serial computer-generated 3-dimensional computed tomographic scans. All patients who did not undergo operative treatment before the completion of at least 2 computed tomographic scans a minimum of 3 months apart after an acute type B dissection were included in the study. The median duration of follow-up was 40 months (range 0.9-112 months). Only 1 patient died of causes unrelated to the aneurysm during follow-up. Nine patients had fatal rupture (18%); 10 patients underwent elective aneurysm resection because of rapid expansion or development of symptoms, and 31 patients remained alive without operation or rupture. Possible risk factors for rupture in patients in the rupture, operative, and event-free groups were compared, as were dimensional data from first follow-up and last computed tomographic scans. RESULTS: Older age, chronic obstructive pulmonary disease, and elevated mean blood pressures were unequivocally associated with rupture (rupture versus event-free survival, P <.05), and pain was marginally significantly associated. Analysis of dimensional factors contributing to rupture was complicated by the fact that patients who underwent elective operation had significantly larger aneurysms and faster expansion rates than did either of the other groups, leaving comparisons of aneurysmal diameter between groups with and without rupture showing only marginal statistical significance. The last median descending aortic diameter before rupture in the rupture group was 5.4 cm (range 3.2-6. 7 cm). CONCLUSIONS: In an environment in which patients with large and rapidly expanding aneurysms are usually referred for surgical treatment, older patients with chronic type B dissections, especially if they have uncontrolled hypertension and a history of chronic obstructive pulmonary disease, are significantly more likely to have rupture than are younger, normotensive patients without lung disease. Neither the presence of a persistently patent false lumen nor a large abdominal aortic diameter appears to increase the risk of rupture. Overall, our nondimensional data strikingly resemble the natural history of patients with nondissecting aneurysms, suggesting that calculations derived from data on chronic descending thoracic and thoracoabdominal aneurysms would provide an overly conservative individual estimate of rupture risk for patients with chronic type B dissection, who tend toward earlier rupture of smaller aneurysms. A more aggressive surgical approach toward treatment of patients with chronic type B dissection seems warranted.
Age Factors↗
Chlamydia pneumoniae reactive T lymphocytes in the walls of abdominal aortic aneurysms.
BACKGROUND: The presence of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms (AAAs) has been demonstrated recently, but its role in the cause and/or maintenance of aortic wall inflammation is not known. In the present study, we have investigated the possible relationship between C. pneumoniae and the antigen specificity of T lymphocytes mediating inflammation in AAA tissue. MATERIALS AND METHODS: Tissue specimens were obtained from 22 consecutive AAA patients undergoing elective surgery (mean age 67 +/- 1 year). Immunohistochemical analysis of the formalin-fixed tissue was performed using the streptavidin-biotin-peroxidase method. In vivo activated T lymphocytes were propagated from the specimens with interleukin (IL) 2, and antigen specificity of the established T-cell lines was analysed in the presence of autologous antigen-presenting cells using radioactive thymidine labelling. RESULTS: Immunohistological staining of AAA tissue showed the presence of C. pneumoniae antigen in 55% (6/11) of the samples studied. The inflammatory cell infiltrate of the AAA tissue contained 60-90% T (CD45RO) and 0-10% B (CD20) cells. When the tissue specimens were cultured without antigen in the presence of IL-2, lymphocyte propagation was achieved in 17 out of the 22 samples. Chlamydia pneumoniae antigen was found to induce a positive proliferative response in 8 of the 17 lines. CONCLUSIONS: The presence of C. pneumoniae specific T lymphocytes among in vivo activated cells from the AAA tissue specimens suggests that C. pneumoniae participates in the maintenance of the inflammatory response in the tissue and may thus be involved in the progression of the disease.
Aged↗
Apolipoprotein A-I in bile inhibits cholesterol crystallization and modifies transcellular lipid transfer through cultured human gall-bladder epithelial cells.
BACKGROUND: Apolipoprotein A-I (Apo A-I), conventionally purified by several steps including organic solvent-delipidation from plasma, inhibits cholesterol crystallization in bile. To observe a significant effect in vitro, however, supraphysiological concentrations above 100 microg/mL are required. For this reason, this protein has not been considered to play a physiological role in vivo. In the present study, we examined the cholesterol crystal growth-inhibiting effect of biliary Apo A-I at its physiological concentration, the modification of transcellular transfer of biliary lipids through cultured human gall-bladder epithelial cells (GBEC) by Apo A-I at its physiological concentration and the binding and secretion of Apo A-I by GBEC. METHODS AND RESULTS: We purified biliary Apo A-I to near homogeneity using immobilized artificial membrane chromatography. At 5 microg/mL, biliary Apo A-I reduced cholesterol crystal mass by 50%, whereas plasma-derived, solvent-delipidated Apo A-I had no effect. Using an antibody-capture enzyme-linked immunosorbent assay, we found reduced Apo A-I concentrations in bile samples from gallstone patients when compared with bile samples from gallstone-free controls (medians, 2.35 and 9.4 microg/mL, respectively). In a GBEC line, Apo A-I (5 microg/mL) enhanced transfer of phospholipid and cholesterol from the mucosal to the serosal side of cell monolayers by approximately 50%. These cells appear to bind Apo A-I reversibly in a dose- and time-dependent manner, compatible with receptor-type binding. Cultured human gall-bladder epithelial cells also showed basal secretion of Apo A-I, which was greatly increased by exposure to model bile solutions. CONCLUSIONS: Apolipoprotein A-I in bile, thus, has both a direct effect on cholesterol crystal formation and enhances lipid removal from gall-bladder bile by GBEC. This effect may be specific and receptor mediated. These observations support two separate roles for human biliary Apo A-I and suggest that this protein may be important in preventing the formation of cholesterol crystals (the initial step in gallstone formation) in supersaturated bile.
Apolipoprotein A-I↗
Multiple endocrine neoplastic-associated thymic carcinoid tumour in close relatives: octreotide scan as a new diagnostic and follow-up modality. Two case reports.
Thymic carcinoid tumours constitute less than 1% of all carcinoids, and differ markedly from true thymomas in natural history, morphology, prognosis and therapeutic options. New clinical and diagnostic modalities are described in two brothers with thymic carcinoid associated with multiple endocrine neoplasia syndrome. Octreotide scintigraphy proved useful for diagnosis and follow-up, and somatostatin receptor positivity may provide new prospects for treatment of non-resectable or recurrent tumour.
Carcinoid Tumor↗
Is vasculitis a significant component of atherosclerosis?
Although atherosclerosis was linked to infections many decades ago, only recently there has been a renewed interest to study this association further. These research endeavors have provided a substantial amount of knowledge concerning the mechanisms that may link inflammation, immunity, and infections to the molecular and cellular events in the arterial wall leading to atherosclerotic lesions.
Animals↗
Complete processing of type III collagen in atherosclerotic plaques.
The extent of processing of type III collagen is assessed, and the proportions of type I and III collagens are estimated in atherosclerotic plaques obtained from the carotid artery, common femoral artery, and aorta. The fraction of type III collagen that had retained its amino-terminal propeptide (pN-collagen) was 42% in the soluble extract but only 0.0081% in the insoluble residue. Taken together, only 0.011% of the type III collagen in whole plaques was in the form of type III pN-collagen. Together with the small amounts of the free propeptides of type I procollagen, this finding indicates a low rate of collagen turnover. The amounts of solubilized telopeptides of type I and III collagens were measured, after heat denaturation and trypsin digestion of the collagenous helix, by specific immunoassays for the corresponding trypsin-generated antigens. The mean proportion of type III collagen was 61% (95% confidence interval, 58% to 65%) in the carotid and femoral artery plaques and 56% (95% confidence interval, 44% to 68%) in the aortic specimens. The completely processed and cross-linked type III collagen seems to be the major collagen type in atherosclerotic plaques.
Adult↗
Detection of Chlamydia pneumoniae by colorimetric in situ hybridization.
Chlamydia pneumoniae causes chronic infections, which have been associated with cardiovascular diseases. The antigenic structures of the organism have been detected in atherosclerotic lesions by immunohistochemistry. We wanted to further evaluate the presence and localization of C. pneumoniae in different tissues by in situ hybridization. We established a new colorimetric in situ hybridization method using a digoxigenin-labelled probe and studied the localization of C. pneumoniae in formalin-fixed, paraffin-embedded lungs of infected mice. We also used the method to study its presence in 12 abdominal aortic aneurysms. In C. pneumoniae-infected mice, the organism was first detected in bronchial epithelial cells, and later in pneumocytes and endothelial cells. C. pneumoniae was also present in five of eight abdominal aortic aneurysms previously shown to be positive by immunohistochemistry. The findings are in accordance with the invasive nature of C. pneumoniae, and confirm its presence in abdominal aortic aneurysms.
Animals↗
Can degenerative aortic valve stenosis be related to persistent Chlamydia pneumoniae infection?
BACKGROUND: The cause of age-related degenerative (tricuspid) aortic valve calcification is largely unknown, but one typical characteristic is an active inflammatory process. The presence of Chlamydia pneumoniae in aortic valve stenosis was recently shown. OBJECTIVE: To test the hypothesis that if persistent C. pneumoniae infection plays an active role in the development of aortic stenosis, the organism can be detected in the healthy aortic valves of young persons. DESIGN: A cadaver study. SETTING: Oulu University Hospital, Oulu, Finland. SUBJECTS: 46 consecutive cadavers undergoing autopsy. MEASUREMENTS: Macroscopic and histologic pathology of aortic valves was determined. The presence of C. pneumoniae was determined by immunohistochemistry. RESULTS: 34 of 46 valves were macroscopically normal. Early lesions of aortic valve disease were found in 12 valves (no lesions in valves from persons 20 to 40 years of age [n = 15], 4 lesions in valves from persons 41 to 60 years of age [n = 16], and 8 lesions in valves from persons older than 60 years of age [n = 15]; P = 0.004). Fifteen of 34 normal valves (44%) and 10 of 12 valves with early lesions (83%) had positive results on staining for C. pneumoniae (P = 0.02). In persons older than 60 years of age, the chance of an early lesion was higher if the valve tested positive for C. pneumoniae (7 of 8 valves with C. pneumoniae infection compared with 1 of 7 valves without C. pneumoniae infection; P = 0.01). CONCLUSIONS: Chlamydia pneumoniae is frequently present in aortic valves and is associated with early lesions of aortic valve stenosis in elderly persons.
Adult↗