| 1. |
- Liuba, Petru, et al.
(författare)
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Acute Chlamydia pneumoniae infection causes coronary endothelial dysfunction in pigs.
- 2003
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Ingår i: Atherosclerosis. - 1879-1484. ; 167:2, s. 215-222
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Tidskriftsartikel (refereegranskat)abstract
- Background: Coronary endothelial dysfunction contributes to the pathogenesis of acute coronary syndromes (ACSs). Acute Chlamydia pneumoniae infection has been epidemiologically associated with ACS. In this study, we investigated whether acute C. pneumoniae infection could alter the endothelial vasomotor function of porcine coronary vessels. Methods and results: Twenty pigs, 7–9 kg in weight, were inoculated intratracheally with C. pneumoniae (n=12) or saline (n=8), and investigated at 3 days (five infected/four non-infected) and 2 weeks (5+2 infected/four non-infected) after inoculation. The endothelium-dependent reactivity of coronary microcirculation was assessed at both time points by measuring peak coronary flow velocity (CFV) in response to bradykinin, before and after infusions with glutathione, an antioxidant, and Image-arginine, a substrate for nitric oxide synthase (NOS). CFV after bradykinin was significantly decreased in infected animals at both time points. At 2 weeks, both glutathione and Image-arginine significantly improved CFV after bradykinin. CFV after sodium nitroprusside (SNP) was similar in both groups. At 3 days, the relaxation responses of bradykinin-induced pre-contracted left anterior descending (LAD) coronary rings to bradykinin were significantly less in infected animals. NG-nitro-Image-arginine-methyl-ester, an NOS inhibitor, had significantly greater inhibitory effect on bradykinin-induced relaxation in infected animals. Plasma nitrate–nitrite and fibrinogen, and NOS activity from LAD coronary samples were significantly increased in infected animals. Conclusion: Acute C. pneumoniae infection causes endothelial dysfunction of both resistance and epicardial coronary vessels, and favours a pro-coagulant status. These effects could in part account for the epidemiologically suggested association between acute infection and ACS.
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| 2. |
- Liuba, Petru, et al.
(författare)
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Co-Infection with CHLAMYDIA PNEUMONIAE and HELICOBACTER PYLORI Results in Vascular Endothelial Dysfunction and Enhanced VCAM-1 Expression in ApoE-Knockout Mice.
- 2003
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Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 40:2, s. 115-122
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Upregulation of proinflammatory endothelial cell adhesion molecules and decreased bioactivity of endothelial nitric oxide (NO) are important in the pathogenesis of atherosclerosis. We investigated the effects of co-infection with <i>Chlamydia pneumoniae</i> and <i>Helicobacter pylori </i>on these two events in apoE-KO mice. <i>Methods:</i> Thirty-two apoE-KO mice, 8 weeks old, were equally divided into 4 groups. The first 2 groups were infected with either <i>C. pneumoniae</i> or <i>H. pylori,</i> while the 3rd group was infected with both <i>C. pneumoniae</i> and <i>H. pylori</i>. Mice from the 4th group and 4 wild-type mice served as controls. Thoracic and abdominal aortas were harvested after 10 weeks, and staining for vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 was analyzed by immunocytochemistry. The endothelial vasomotor responses of thoracic aortas to methacholine were studied in organ chambers in the absence and presence of <i>L</i>-NAME. The plasma levels of nitrate/nitrite were measured. <i>Results:</i> Staining for VCAM-1 was more intense at the branching sites of aortas from mice with co-infection than in mono-infected or noninfected apoE-KO mice. The relaxation responses to methacholine and the plasma levels of nitrate/nitrite were significantly less in the co-infected group than in the other groups (p < 0.05). <i>Conclusion:</i> Co-infection of apoE-KO mice with <i>C. pneumoniae</i> and <i>H. pylori</i> seems to be associated with impaired bioactivity of endothelial NO and increased expression of VCAM-1 at branching sites. The findings may suggest an additive interaction of these pathogens in atherogenesis.
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| 3. |
- Liuba, Petru, et al.
(författare)
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Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice
- 2000
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Ingår i: Circulation. - 1524-4539. ; 102:9, s. 1039-1044
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Arterial relaxation is largely regulated by endothelial nitric oxide (NO). Its diminished activity has been associated with incipient atherosclerosis. We investigated the endothelium-dependent relaxation of aorta in apolipoprotein E-knockout (apoE-KO) mice exposed to single or repeated Chlamydia pneumoniae inoculation. METHODS AND RESULTS: Forty-eight apoE-KO mice, 8 weeks old, were inoculated intranasally with C pneumoniae (n=24) or saline (n=24) every 2 weeks over a 6-week period. Twenty mice (10 infected and 10 controls) were killed at 2 weeks and 6 weeks, respectively, after the first inoculation. The smooth muscle tone of aortic rings was measured in vitro at both time points. The norepinephrine-precontracted thoracic aortic rings were successively exposed to methacholine in the absence and presence of N:(G)-nitro-L-arginine methyl ester (L-NAME) and diclofenac. The methacholine-induced relaxation was attenuated in the infected mice at 6 weeks in both the absence and presence of L-NAME (P:<0.05 and P:<0.01, respectively). When administered together with L-NAME, diclofenac enhanced the relaxation of the L-NAME-pretreated aortas in infected mice at 2 weeks (P:<0.05) but not in noninfected mice. The relaxation response from infected mice tended to differ in the same manner at 6 weeks (P:<0.1). No intimal thickening was detected at either time point. CONCLUSIONS: C pneumoniae impairs arterial endothelial function, and the NO pathway is principally involved. Cyclooxygenase-dependent vasoconstricting products may also account for the infection-induced impaired relaxation. These findings further support the role of C pneumoniae infection in atherosclerosis development.
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| 4. |
- Martoft, L, et al.
(författare)
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CO2 induced acute respiratory acidosis and brain tissue intracellular pH: a P-31 NMR study in swine
- 2003
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Ingår i: Laboratory Animals. - : SAGE Publications. - 0023-6772 .- 1758-1117. ; 37:3, s. 241-248
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Tidskriftsartikel (refereegranskat)abstract
- High concentration carbon dioxide (CO2) is used to promote pre-slaughter anaesthesia in swine and poultry, as well as short-lasting surgical anaesthesia and euthanasia in laboratory animals. Questions related to animal welfare have been raised, as CO2 anaesthesia does not set in momentarily. Carbon dioxide promotes anaesthesia by lowering the intracellular pH in the brain cells, but the dynamics of the changes in response to a high concentration of CO2 is not known. Based on P-31 NMR spectroscopy, we describe CO2-induced changes in intracellular pH in the brains of five pigs inhaling 90% CO2 in ambient air for a period of 60 s, and compare the results to changes in arterial blood pH, P-CO2, O-2 saturation and HCO(3)(-)concentration. The intracellular pH paralleled the arterial pH and P-CO2 during inhalation of CO2; and it is suggested that the acute reaction to CO2 inhalation mainly reflects respiratory acidosis, and not metabolic regulation as for example transmembrane fluxes of H+/HCO3-. The intracellular pH decreased to approximately 6.7 within the 60 s inhalation period, and the situation was metabolically reversible after the end of CO2 inhalation. The fast decrease in intracellular pH supports the conclusion that high concentration CO2 leads to anaesthesia soon after the start of inhalation.
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| 5. |
- Martoft, L, et al.
(författare)
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Effects of CO2 anaesthesia on central nervous system activity in swine
- 2002
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Ingår i: Laboratory Animals. - 0023-6772. ; 36:2, s. 115-126
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to examine the changes in central nervous system (CNS) activity and physical behaviour during induction and awakening from CO2 anaesthesia. Two studies, each using pigs immersed into 90% CO2 gas for a period of 60s were performed. In study 1, we monitored middle latency auditory evoked potentials (changes in latencies, amplitudes and a depth of anaesthesia index), electroencephalographic parameters (delta, theta, alpha and beta electroencephalographic power and 95% spectral edge frequency) and heart rate; and in study 2, we monitored body movements and arterial and venous partial pressure of CO2 and O-2. No behavioural signs of distress were observed during the early part of the induction. The swine exhibited muscular activity from 13-30s after induction-start as well as during awakening from anaesthesia, possibly because of a transitory weaker suppression of the brain stem than of the cortex. The CNS and blood gas parameters started to change from the very start of induction. The CNS suppression lasted only approximately one minute after the end of the induction period. The two studies indicated a good temporal relationship between changes in amplitude, depth of anaesthesia index, spectral edge frequency, and arterial P-CO2 during the induction period.
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