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| 2. |
- Bajc, Marika, et al.
(författare)
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Lung ventilation/perfusion SPECT in the artificially embolized pig.
- 2002
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Ingår i: Journal of Nuclear Medicine. - 0161-5505. ; 43:5, s. 640-647
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Tidskriftsartikel (refereegranskat)abstract
- Planar lung scintigraphy is a standard method used for the diagnosis of lung embolism, but it is hampered by the high incidence of nondiagnostic tests. Ventilation/perfusion SPECT may possibly improve this situation. The objective of this study was to compare planar lung scintigraphy with ventilation/perfusion SPECT using pigs with artificially engendered lung emboli labeled with (201)Tl. METHODS: Sixteen anesthetized pigs were each injected with zero to 4 latex emboli. Cylindric emboli were used in the first 7 pigs and flat 3-tailed emboli were used in the remaining 9 pigs. The pigs spontaneously inhaled 30 MBq (99m)Tc-diethylenetriaminepentaacetic acid aerosol for ventilation scintigraphy. Planar scintigraphy and SPECT were performed using a double-head gamma camera in (99m)Tc and (201)Tl windows. Immediately thereafter, 100 MBq (99m)Tc-labeled macroaggregated albumin were injected intravenously followed by SPECT and, finally, planar scintigraphy. The ventilation background was subtracted from the perfusion tomograms for calculation of a normalized ventilation/perfusion (V/P) quotient image set. RESULTS: The cylindric emboli caused artifacts in the ventilation images; therefore, these were excluded from the final analysis. However, for the planar perfusion images of these pigs, sensitivity and specificity were 71% and 91%, respectively, whereas SPECT yielded 100% for both. For the 3-tailed emboli and ventilation/perfusion images, the sensitivity and specificity were 64% and 79%, respectively, for the planar modality, whereas SPECT yielded values of 91% and 87%, respectively. CONCLUSION: V/P SPECT may improve the diagnostic power of lung scintigraphy.
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| 3. |
- Cunha Goncalves, Doris, et al.
(författare)
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Cardiovascular effects of levosimendan in the early stages of endotoxemia.
- 2007
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322 .- 1540-0514. ; 28:1, s. 71-7
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis-associated myocardial depression is associated with calcium desensitization and adrenergic uncoupling. We conducted a prospective randomized investigation on the effects of the calcium sensitizer, levosimendan, on hemodynamics, myocardial blood flow, and myocardial lactate metabolism during porcine endotoxemia. Twelve pigs were studied. Oxygen consumption was measured by indirect calorimetry, and myocardial blood flow was measured by retrograde thermodilution. Pulmonary, arterial, and venous indwelling catheters allowed measurements of cardiac output, vascular pressures, and blood sampling. Fluids were given at an average of 15 mL . kg . h. After baseline measurements (0 min), an infusion of Escherichia coli LPS (2 microg . kg . min) was started in all animals. Beginning at 100 min, six animals received levosimendan (50 microg . kg . h), whereas six control animals received placebo. The study lasted for 300 min. All animals responded to endotoxin with pulmonary hypertension, a transient decrease in cardiac output, tachycardia, and systemic hypotension. Levosimendan infusion decreased systemic vascular resistance (P = 0.001), coronary vascular resistance (P = 0.004), and mean arterial (P < 0.001) and coronary perfusion pressures (P < 0.001), whereas pulmonary hypertension was unaffected. Heart rate progressively increased in both groups and was significantly higher in the levosimendan group (P = 0.048). Myocardial blood flow remained unchanged in both groups; however, 80 min after the start of levosimendan infusion, left ventricular myocardial hypoxia ensued, as evidenced by a negative myocardial lactate gradient (P = 0.01). Two control and five levosimendan animals died before the end of the study. Early administration of levosimendan during porcine endotoxemia increased heart rate, caused arterial vasodilation, and decreased coronary perfusion pressure, resulting in myocardial hypoxia.
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| 4. |
- Cunha-Goncalves, Doris, et al.
(författare)
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Impact of Body Position on Lung Deposition of Nebulized Surfactant in Newborn Piglets on Nasal Continuous Positive Airway Pressure
- 2020
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 117:4, s. 467-473
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The ideal body position during surfactant nebulization is not known. Objective: The aim of this study was to determine whether body positioning during surfactant nebulization influences surfactant distribution and deposition in the lungs. Methods: Twenty-four 12- to 36-h-old full-termpiglets (1.3-2.2 kg) on nasal continuous positive airway pressure (nCPAP) were randomized into four groups: lateral decubitus with right or left side up, prone or supine positions (n = 6 each). All animals received 200 mg kg-1 of poractant alfa mixed with 200 MBq of 99mtechnetium-nanocolloid via a customized eFlow-Neos investigational vibrating-membrane nebulizer. Surfactant deposition (percentage of the administered dose) was measured by gamma scintigraphy. Results: Comparing all groups, the mean total lung surfactant deposition was significantly higher in the prone position (32.4 ± 7.7%, p = 0.03). The deposition in this group was higher in the right lung (21.0 ± 8.6 vs. 11.3 ± 5.7%, p = 0.04). When nebulization was performed in the lateral decubitus, most of the surfactant was found in the dependent lung, regardless of which side the piglet lay on (right side up 15.3 ± 1.0 vs. 3.4 ± 1.0%, p = 0.06, and left side up 11.2 ± 9.8 vs. 1.8 ± 0.7%, p = 0.04). Conclusions: In spontaneously breathing animals on nCPAP, the prone position yielded the highest lung dose. Higher deposition rates in the dependent lung while on lateral decubitus indicates that deposition was also influenced by gravity.
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| 5. |
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| 6. |
- Cunha Goncalves, Doris, et al.
(författare)
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Inotropic support during experimental endotoxemic shock : part II. A comparison of levosimendan with dobutamine
- 2009
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Ingår i: Anesthesia and Analgesia. - : Ovid Technologies (Wolters Kluwer Health). - 0003-2999 .- 1526-7598. ; 109:5, s. 1576-83
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We compared the association of levosimendan or dobutamine with norepinephrine for the maintenance of systemic and hepatosplanchnic perfusion during early endotoxemic shock. METHODS: Twenty anesthetized pigs (26.8 +/- 0.5 kg) were instrumented with flow probes and catheters to monitor systemic and regional perfusion as described in our companion article in this issue of the journal. Two animals were excluded because of surgical complications. Oxygen consumption (VO(2)) was measured by indirect calorimetry. Starting 1 h after instrumentation, an endotoxin infusion (Escherichia coli lipopolysaccharide, 2 microg x kg(-1) x h(-1)) was administered for 300 min. Sixty minutes after the start of endotoxin, the animals were fluid resuscitated (20 mL/kg dextran 70); at 120 min, they were randomized into three groups of six animals each: levosimendan (25-50 microg x kg(-1) x h(-1)), dobutamine (10-20 microg x kg(-1) x min(-1)), and control. In the first two groups, norepinephrine (0.5-2 microg x kg(-1) x min(-1)) was added when mean arterial blood pressure (MAP) or= baseline. The data were divided into two subsets: before (0-120 min, all animals) and after (120-300 min, three groups) randomization, and analyzed by analysis of variance. P < 0.05 was considered significant. RESULTS: At 120 min, cardiac output was 15% higher (P < 0.001), systemic vascular resistance was 30% lower (P < 0.001), and MAP decreased 12.5% (P = 0.004); blood flow in the hepatic artery, superior mesenteric artery, and portal vein had increased by 100% (P = 0.004), 60% (P < 0.001), and 20% (P < 0.001), respectively. Between 120 and 300 min, cardiac output and systemic oxygen delivery decreased 50% in control animals (P < 0.05), remained unchanged in the levosimendan group, and increased 60% with dobutamine (P = 0.05). MAP (P = 0.043) and VO(2) (P = 0.001) decreased 20% in the control group. Portal vein flow decreased in the control (50%) and levosimendan (30%) groups (P < 0.001) and was therefore higher in the dobutamine group (P = 0.003) at 300 min. Hepatic and gut oxygen deliveries decreased in the levosimendan (50%, and 30%, respectively, P < 0.001) and control groups (70% and 45%, respectively, P < 0.05); thus, regional oxygen deliveries were greater in the dobutamine group (P < 0.05). In this group, mixed venous and hepatic vein oxygen saturation were maintained; the latter variable was higher than in the other groups (P < 0.05). Although unchanged with dobutamine, arterial (P = 0.020), portal (P = 0.020), and hepatic vein (P = 0.034) lactate concentrations increased twofold with levosimendan. CONCLUSION: In volume-resuscitated endotoxemic pigs, the association of either levosimendan or dobutamine with norepinephrine preserved systemic blood flow, oxygen delivery, and VO(2). However, only dobutamine-norepinephrine maintained portal blood flow, which was associated with preservation of splanchnic and hepatic oxygen homeostasis and stable lactate concentrations.
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| 7. |
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| 8. |
- Harnek, Jan, et al.
(författare)
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Intimal Hyperplasia in Balloon Dilated Coronary Arteries is Reduced by Local Delivery of the NO Donor, SIN-1 Via a cGMP-Dependent Pathway.
- 2011
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA). METHODS: Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents. RESULTS: Luminal diameter after PCI in arteries treated with SIN-1 alone and corrected for age-growth was significantly larger as compared to ODQ + SIN-1 or to controls (p < 0.01). IF/actin ratio after one week in SIN-1 treated segments was not different compared to untreated segments, but was significantly reduced compared to ODQ + SIN-1 treated vessels (p < 0.05). Expression of endothelial NADPH diaphorase activity was significantly lower in untreated segments and in SIN-1 treated segments compared to controls and SIN-1 + ODQ treated arteries (p < 0.01). Restenosis index (p < 0.01) and intimal hyperplasia (p < 0.01) were significantly reduced while the residual lumen was increased (p < 0.01) in SIN-1 segments compared to controls and ODQ + SIN-1 treated vessels. CONCLUSIONS: After PTCA local delivery of high concentrations of the NO donor SIN-1 for 5 minutes inhibited injury induced neointimal hyperplasia. This favorable effect was abolished by inhibition of guanylyl cyclase indicating mediation of a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent pathway. The momentary events at the time of injury play crucial role in the ensuring development of intimal hyperplasia.
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| 9. |
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| 10. |
- Hedin, Ulf, et al.
(författare)
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Resolving the biological paradox of aneurysm formation in children with tuberous sclerosis complex
- 2021
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Ingår i: JVS-Vascular Science. - : Elsevier BV. - 2666-3503. ; 2, s. 72-78
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Tidskriftsartikel (refereegranskat)abstract
- Aortic aneurysms are rare manifestations in children with tuberous sclerosis complex (TSC) with life threating implications. Although an association between TSC, aortic and other aneurysms has been recognized, mechanistic insights explaining the pathophysiology behind aneurysm development and genetic aberrations in TSC have so far been lacking. Here, we summarize existing knowledge on aneurysms in TSC and present a case of a 2-year-old boy with an infrarenal aortic aneurysm, successfully treated with open aortic reconstruction. Histologic examination of the excised aneurysm wall showed distortion of vessel wall structure with loss of elastin and a pathologic accumulation of smooth muscle cells. Until now, these pathologic features have puzzled researchers as proliferating smooth muscle cells would rather be expected to preserve vessel wall integrity. Recent reports exploring the biological consequences of the dysregulated intracellular signaling pathways in patients with TSC provide plausible explanations to this paradox, which may support the development of future therapeutic strategies.
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