| 1. |
- Liuba, Petru, et al.
(författare)
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Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets
- 2013
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB. Methods: Barrier-bred piglets (10-12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points. Results: Cyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p<0.01 vs. non-cardioplegia group and pre-surgery). cPFV responses to adenosine, but not to serotonin, tended to decrease (p=0.06) after surgery only in cardioplegia group (p=0.06; p=0.8 in non-cardioplegia group vs pre-surgery). Also, cPFV response to atrial pacing was lower in the cardioplegia than in the non-cardioplegia group (p=0.02). Neither vulnerability nor duration of induced Afib after CPB differed between groups (Chi-square p=0.4). Cyclosporine had no significant effect on coronary indexes or arrhythmia vulnerability (p>0.4). There was no difference in systolic myocardial function between groups at any time point. Conclusion: In piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB.
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| 2. |
- Liuba, P., et al.
(författare)
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Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass surgery of piglets
- 2011
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Ingår i: Cardiology in the Young. - 1467-1107. ; 21:S1, s. 70-70
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Konferensbidrag (refereegranskat)abstract
- Introduction: Cardiopulmonary bypass (CPB) surgery remains associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully clarified. Abnormalities in coronary flow and function have beensuggested to play an important role. A few prior studies suggested protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A prior to CPB surgery. Methods: Barrier-bred piglets (10-12 kg, n=20) were subjected to CPB with (n=10) or without (n=10) antegrade administration for 20 minutes of cardioplegic solution. Prior to surgery, half of animals from each group received 10-minute i.v. infusion of 100 mg/kg cyclosporine A. Left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, respectively. Results: Coronary peak flow velocity (cPFV) rose significantly after surgery, especially in cardioplegia group (p0.4). There was no difference in systolic myocardial function between groups at any timepoint. Conclusions: Cardioplegia during CPB surgery of piglets was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, intracoronary pretreatment with cyclosporine had no observable protective effect on coronary circulation or arrhythmia vulnerability after CPB surgery.
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| 3. |
- Liuba, Petru, et al.
(författare)
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Protective effects of simvastatin on coronary artery function in swine with acute infection.
- 2006
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 186:2, s. 331-336
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Tidskriftsartikel (refereegranskat)abstract
- Background: The risk for coronary events may rise during acute infection. Perturbation in coronary endothelial function emerges as one important link. We investigated whether simvastatin could protect the coronary arterial function from the adverse effects of acute infection in swine. Methods: Coronary endothelium-dependent and -independent vasomotor responses were assessed by Doppler velocimetry in 12 Chlamydia pneunioniae-infected and 6 sham-infected swine 2 weeks after intratracheal inoculation. Half of animals from the infection group were pretreated with simvastatin (80 mg daily), while the remaining animals received placebo. The treatment was started 2 weeks prior to inoculation and Continued until the end of the Study. ANOVA was used for statistical calculations. Data are mean +/- S.D. Results: All animals inoculated with C. pneumoniae developed IgM antibodies against this organism. As compared to noninfected animals, peak-to-baseline coronary flow velocity (CFV) ratio after bradykinin was significantly decreased in infected animals regardless of statin treatment (1,p=0.01). Intracoronary 10(-6) M acetylcholine caused slight dilatory responses in both noninfected and infected-treated animals (CFV ratio: 1.6 +/- 0.2and 1.4 +/- 0.2, respectively: p > 0.1),while a velocity drop (CFV ratio: 0.7 +/- 0.1; p < 0.01 versus noninfected-infected and treated). indicating constriction, was observed in in fected-non treated animals; 10(-5) M acetylcholine caused vasoconstriction in all animals, with a significantly more prolonged response in the infected-non treated group (p < 0.01). Intracoronary adenosine and SNP induced similar dilatory responses in all groups (p > 0.5). There were no differences in markers of systemic inflammation (fibrinogen, amyloid, and CRP) and lipid profile (HDL, LDL and total cholesterol) between the groups (p > 0.2). Conclusion: Acute infection is associated with impairment of the muscarinic and kinin-related reactivity of coronary circulation. These functional abnormalities are in part prevented by simvastatin through mechanisms unrelated to lipid lowering. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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| 4. |
- Lützhøft, Ditte Olsen, et al.
(författare)
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Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model
- 2022
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Ingår i: BMC Microbiology. - : BioMed Central (BMC). - 1471-2180. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gut microbiota dysbiosis is associated with the development of non-alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short-chain fatty acid production. The aim of this study was to describe the impact of a choline-deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH.RESULTS: Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids.CONCLUSIONS: Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.
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| 5. |
- Pesonen, Erkki, et al.
(författare)
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Infections and endothelial cell apoptosis
- 2010
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Ingår i: Cardiology in the Young. - 1467-1107. ; 20:Suppl 1, s. 224-224
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Konferensbidrag (refereegranskat)abstract
- Objectives: Endothelial cells of coronary arteries undergo apoptosis in patients with coronary artery disease. Carotid artery ultrasound studies show that after acute infections intima media thickness is increased. The possible effects of infections on endothelial cell apoptosis and the presence of apoptosis in early life remain unknown. Methods: Chlamydia pneumonia was inoculated three times at three weeks intervals to half of 32 piglets starting at the age of 8 weeks. Half of the piglets received cholesterol feeding. Morphological studies were done at the age of 19 weeks. Right coronary arteries were carefully excised and trimmed for excess tissue. The vessels were cut perpendicular to the long axis and sectioned at 5-μm thickness. TUNEL-assay was based on nick end labelling and staining of internucleosomal DNA fragments that are the biochemical hallmark of apoptosis. The percentage of apoptotic endothelial cells from intact endothe-lial cells was calculated using light microscopy. Results. Endothelial apoptosis appeared in 0.13% (SD 0.30%) of endothelial cells of non-infected piglets but in 0.75% (SD 0.62) of infected piglets (p <0.005, t-test). In piglets fed with normal diet apoptosis appeared in 1.1% but in those on cholesterol rich diet the prevalence of apoptosis was lower 0.43% (SD 0.42). Conclusions: Infections amplify endothelial cell apoptosis. The finding supports the notion that infection has a pro-atherogenic effect particularly in early life. Hypercholesterolemic diet did not further stimulate apoptosis.
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