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ABSTRACT: We present a very rare case of an acute septic infection and vegetative mycotic aneurysm caused by Neisseria gonorrhoeae in a 52-year old male. The aortic valve was bicuspid and calcified. He was successfully treated by the resection of the ascending aorta and the aortic valve with a replacement by separate prostheses, followed by 2 weeks of intravenous antibiotic therapy. The patient was followed up 18 months postoperatively with no signs of reinfection.
Interactive cardiovascular and thoracic surgery 04/2012; 15(1):183-5.
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ABSTRACT: Myoblast transplantation therapy for chronic heart failure (HF) is impaired by early donor cell death and reduced graft viability. Although epicardial implantation of cell sheets can prevent the initial loss of transplanted cells, limited vascularization subjects the sheets to apoptotic stress. We studied the efficacy of antiapoptotic bcl2 in myoblast sheet therapy for rat chronic HF. Myocardial infarction was induced by left anterior descending coronary artery ligation and HF was allowed to develop for 4 weeks. Thereafter, wild type (L6-WT; n=16) or Bcl-2-expressing (L6-Bcl2; n=19) myoblast sheets were transplanted epicardially. Control rats (n=21) underwent left anterior descending coronary artery ligation and re-thoracotomy. Five rats were sham-operated in both surgeries. Four weeks after transplantation, only the L6-Bcl2 rats showed improved left ventricular ejection fraction. Their vascular density in the damaged myocardium was greater, and they had more proliferating cells. The L6-Bcl2 group had an increased amount of myocytes in the infarct area. Soluble factors from L6-Bcl2 sheets induced a 2.9-fold increase in endothelial cell proliferation, and enhanced endothelial wound healing as compared to the L6-WT sheets. These effects were inhibited by SU5416 and were thus dependent on Flt1/Flk1 signaling. In conclusion, bcl2 improves efficacy of myoblast sheet transplantation and promotes proangiogenic paracrine signaling.
Tissue Engineering Part A 01/2011; 17(1-2):115-25. · 4.64 Impact Factor
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ABSTRACT: After severe myocardial infarction (MI), heart failure results from ischemia, fibrosis, and remodeling. A promising therapy to enhance cardiac function and induce therapeutic angiogenesis via a paracrine mechanism in MI is myoblast sheet transplantation. We hypothesized that in a rat model of MI-induced chronic heart failure, this therapy could be further improved by overexpression of the antiapoptotic, antifibrotic, and proangiogenic hepatocyte growth factor (HGF) in the myoblast sheets. We studied the ability of wild type (L6-WT) and human HGF-expressing (L6-HGF) L6 myoblast sheet-derived paracrine factors to stimulate cardiomyocyte, endothelial cell, or smooth muscle cell migration in culture. Further, we studied the autocrine effect of hHGF-expression on myoblast gene expression profiles by use of microarray analysis. We induced MI in Wistar rats by left anterior descending coronary artery (LAD) ligation and allowed heart failure to develop for 4 weeks. Thereafter, we administered L6-WT (n = 15) or L6-HGF (n = 16) myoblast sheet therapy. Control rats (n = 13) underwent LAD ligation and rethoracotomy without therapy, and five rats underwent a sham operation in both surgeries. We evaluated cardiac function with echocardiography at 2 and 4 weeks after therapy, and analyzed cardiac angiogenesis and left ventricular architecture from histological sections at 4 weeks. Paracrine mediators from L6-HGF myoblast sheets effectively induced migration of cardiac endothelial and smooth muscle cells but not cardiomyocytes. Microarray data revealed that hHGF-expression modulated myoblast gene expression. In vivo, L6-HGF sheet therapy effectively stimulated angiogenesis in the infarcted and non-infarcted areas. Both L6-WT and L6-HGF therapies enhanced cardiac function and inhibited remodeling in a similar fashion. In conclusion, L6-HGF therapy effectively induced angiogenesis in the chronically failing heart. Cardiac function, however, was not further enhanced by hHGF expression.
PLoS ONE 01/2011; 6(4):e19161. · 4.09 Impact Factor
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ABSTRACT: The overall objective of cell transplantation is to repopulate postinfarction scar with contractile cells, thus improving systolic function, and to prevent or to regress the remodeling process. Direct implantation of isolated myoblasts, cardiomyocytes, and bone-marrow-derived cells has shown prospect for improved cardiac performance in several animal models and patients suffering from heart failure. However, direct implantation of cultured cells can lead to major cell loss by leakage and cell death, inappropriate integration and proliferation, and cardiac arrhythmia. To resolve these problems an approach using 3-dimensional tissue-engineered cell constructs has been investigated. Cell engineering technology has enabled scaffold-free sheet development including generation of communication between cell graft and host tissue, creation of organized microvascular network, and relatively long-term survival after in vivo transplantation.
Stem cells international. 01/2011; 2011:679171.
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ABSTRACT: Myoblast sheet transplantation is a promising novel treatment modality for heart failure after an ischemic insult. However, low supply of blood and nutrients may compromise sheet survival. The aim of this study was to investigate the effect of mitochondria-protective Bcl-2-modified myoblasts in cell sheet transplantation therapy. In the Bcl-2-expressing rat L6 myoblast sheets (L6-Bcl2), increased expression of myocyte markers and angiogenic mediators was evident compared to wild-type (L6-WT) sheets. The L6-Bcl2 sheets demonstrated significant resistance to apoptotic stimuli, and their differentiation capacity in vitro was increased. We evaluated the therapeutic effect of Bcl-2-modified myoblast sheets in a rat model of acute myocardial infarction (AMI). Sixty-four Wistar rats were divided into four groups. One group underwent AMI (n = 22), another AMI and L6-WT sheet transplantation (n = 17), and a third AMI and L6-Bcl2 sheet transplantation (n = 20). Five rats underwent a sham operation. Echocardiography was performed after 3, 10, and 28 days. Samples for histological analysis were collected at the end of the study. After AMI, the Bcl-2-expressing sheets survived longer on the infarcted myocardium, and significantly improved cardiac function. L6-Bcl2 sheet transplantation reduced myocardial fibrosis and increased vascular density in infarct and border areas. Moreover, the number of c-kit-positive and proliferating cells in the myocardium was increased in the L6-Bcl2 group. In conclusion, Bcl-2 prolongs survival of myoblast sheets, increases production of proangiogenic paracrine mediators, and enhances the therapeutic efficacy of cell sheet transplantation.
Cell Transplantation 01/2010; 19(5):573-88. · 5.13 Impact Factor
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ABSTRACT: In open or video-assisted thoracic surgery, injury to one to four intercostal sensory nerves is a well-recognized complication. This nerve damage is a well-defined cause for chronic postoperative pain. In this discussion, the motor innervation of the rectus abdominis muscle with the T7 to T12 intercostal nerves has been neglected. Paralysis of rectus abdominis might pose significant burden on patients, delay recovery, and thus warrants exploration.
The Annals of thoracic surgery 10/2009; 88(4):1335-7. · 3.74 Impact Factor
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Matti Peura MD,
DSc Jozef Bizik PhD,
Pertteli Salmenperä,
Ariel Noro BM,
PhD Matti Korhonen MD, Tommi Pätilä,
PhD Antti Vento MD,
PhD Antti Vaheri MD,
PhD Riitta Alitalo MD,
PhD Jyrki Vuola MD,
PhD Ari Harjula MD,
PhD Esko Kankuri MD
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ABSTRACT: We previously showed cell–cell contacts of human dermal fibroblasts to induce expression of the hepatocyte growth factor/scatter factor (HGF) in a process designated as nemosis. Now we report on nemosis initiation in bone marrow mesenchymal stem cells (BMSCs). Because BMSCs are being used increasingly in cell transplantation therapy we aimed to demonstrate a functional effect and benefit of BMSC nemosis for wound healing. Nemotic and monolayer cells were used to stimulate HaCaT keratinocyte migration in a scratch-wound healing assay. Both indicators of nemosis, HGF production and cyclooxygenase-2 expression, were induced in BMSC spheroids. When compared with a similar amount of cells as monolayer, nemotic cells induced keratinocyte in vitro scratch-wound healing in a concentration-dependent manner. The HGF receptor, c-Met, was rapidly phosphorylated in the nemosis-stimulated keratinocytes. Nemosis-induced in vitro scratch-wound healing was inhibited by an HGF-neutralizing antibody as well as the small molecule c-Met inhibitor, SU11274. HGF-induced in vitro scratch-wound healing was inhibited by PI3K inhibitors, wortmannin and LY294002, while LY303511, an inactive structural analogue of LY294002, had no effect. Inhibitors of the mitogen-activated protein kinases MEK/ERK1/2 (PD98059 and U0126), and p38 (SB203580) attenuated HGF-induced keratinocyte in vitro scratch-wound healing. We conclude that nemosis of BMSCs can induce keratinocyte in vitro scratch-wound healing, and that in this effect signaling via HGF/c-Met is involved.
Wound Repair and Regeneration 07/2009; 17(4):569 - 577. · 2.91 Impact Factor
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ABSTRACT: Coronary artery aneurysm is a rare condition with primarily conservative treatment. Here, we present a case of saccular left main coronary aneurysm with a successful patch repair and discuss the indications for operative treatment.
The Annals of thoracic surgery 02/2009; 87(1):297-9. · 3.74 Impact Factor
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ABSTRACT: Pericardial adhesions are a significant challenge for reoperative cardiac surgery. There are no established means of prevention. Lately, sprayable glues have been suggested to inhibit and reduce adhesion formation in congenital heart surgery, where repeated cardiac operations are often needed. In this study, we tested a novel, synthetic, sprayable, and resorbable polyglycolic acid glue (DuraSeal; Confluent Surgical, Inc., Waltham, MA) that has been approved by the United States Food and Drug Administration as a dural sealant.
A standard sternotomy and longitudinal pericardiotomy was performed in seven pigs, and polyglycolic acid glue (DuraSeal) was administered randomly on either side of the heart. The pericardium was sutured and autologous blood was instilled into pericardium to augment adhesion formation. After 6 wk, the hearts were photographed and examined in terms of adhesion formation (tenacity, extension, and strength), and visibility of the coronary vessels. A semiquantitative scale 0-3 was used.
All animals produced significant pericardial adhesions. There were no statistically significant differences in tenacity, extension, or strength of adhesions between glued and non-glued sides of the hearts, nor was there any significant variation in the visibility of the coronary vessels between the sides.
The DuraSeal polyglycolic acid glue did not reduce the development of pericardial adhesions in pigs.
Journal of Surgical Research 09/2008; 148(2):181-4. · 2.25 Impact Factor
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ABSTRACT: Bartonella quintana and Bartonella pediococcus infections are very rare causes of endocarditis. Urban trench fever with relapsing febrile illness, headache, leg pain, and endocarditis has now begun to be a more important cause of disease in socially disadvantaged persons. The diagnosis is difficult because the growth of B. quintana in blood culture takes 20-40 days. B. pediococcus may be an opportunistic pathogen in severely compromised hosts, although it has been described as a harmless bacterium. We describe a patient who developed bioprosthetic valve infection with B. quintana and B. pediococcus after valve replacement.
Heart Surgery Forum 02/2008; 11(2):E94-5. · 0.63 Impact Factor
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ABSTRACT: Myocardial gene and cellular therapies have revived the use of porcine ischemic heart models. Commonly applied ameroid-obstruction produces inconsistent coronary stenoses and myocardial lesions, whereas abrupt coronary occlusion causes arrhythmias and sudden death. To produce a constant myocardial lesion after adaptation to ischemia, we surgically modified the ameroid-model by ligation. As a pilot study for further cell therapy research, the spontaneous myocardial response is described.
Simultaneously with ameroid application, a loose loop of nonabsorbable thread was placed around the left circumflex artery (LCx) on 11 domestic piglets. Three weeks later, the loop was tightened. Coronary arteriograms with Rentrop collateral grading from 0 to 3, and 99mTc-single photon emission computerized tomography studies were performed 1 to 5 wk after ligation. At autopsy, the hearts were analyzed macroscopically, histologically, and with von Willebrandt factor-staining.
LCx-banding was well-tolerated in nine animals, of which angiographic occlusion was gained in eight. Postmortem analysis revealed a 5 to 10 cm(2) transmural or subendocardial lateral myocardial infarction in all except one heart. One week after occlusion, LCx showed well-developed collateral filling (Rentrop-grade 2.7 +/- 0.4), which remained unchanged at 5 wk. On single photon emission computerized tomography-scans, lateral wall perfusion increased spontaneously between 1 and 5 wk (P = 0.02), and von Willebrandt factor revealed clusters of neovascularization at the borders of infarct areas.
This new modification of ameroid model standardizes myocardial lesion, which might reduce animal number in preclinical studies, thus having ethical aspect. The remarked potential for spontaneous recovery in ischemic porcine myocardium should be considered in preclinical therapeutic studies.
Journal of Surgical Research 10/2007; 142(1):195-201. · 2.25 Impact Factor
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Johan Back,
Esko Kankuri,
Tuija Ikonen, Tommi Pätilä,
Juha Sinisalo,
Mika Laine,
Heikki Vapaatalo,
Jonna Koponen,
Mika Hukkanen,
Seppo Ylä-Herttuala,
Riitta Alitalo,
Markku Kupari,
Ari Harjula
Duodecim; lääketieteellinen aikakauskirja 02/2007; 123(4):398-405.
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ABSTRACT: Organ dysfunction evaluation using Sequential Organ Failure Assessment (SOFA) has been shown to predict mortality and morbidity in adult cardiac surgical patients with prolonged recovery. The purpose of this study was to evaluate the utility of SOFA in prediction of mortality and morbidity in a cohort of heterogeneous consecutive adult cardiac surgical patients.
A prospective study of 857 consecutive patients entering in a single cardiac postoperative intensive care unit was assigned during the year 2004. The European System for Cardiac Operative Risk Evaluation (EuroSCORE) of each patient was assessed preoperatively. SOFA was calculated daily until intensive care unit discharge or for a maximum of 7 days. SOFA change between the first and the third postoperative day, maximum SOFA during the first 3 days, and maximal SOFA were calculated. Length of intensive care unit stay and 30-day mortality were assessed.
Maximum SOFA during the first 3 days and maximal SOFA-predicted 30-day mortality (area under the curve, 0.763 and 0.779, respectively) also correlated with the length of intensive care unit stay (p < 0.001 and p < 0.001, respectively). The EuroSCORE predicted both mortality and intensive care unit stay (p < 0.0001 and p < 0.0001). The correlation coefficient between the EuroSCORE and maximum SOFA during the first 3 days or maximal SOFA was low (r = 0.34 and 0.33, respectively, p < 0.0001 and p = 0.0001).
The SOFA score is an independent predictor of mortality and length of stay in cardiac surgical patients. The SOFA score is associated with mortality and morbidity even when assessed in the early postoperative period after adult cardiac surgery.
The Annals of thoracic surgery 01/2007; 82(6):2072-8. · 3.74 Impact Factor
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Tommi Pätilä,
Tuija Ikonen,
Juha Rutanen,
Aapo Ahonen,
Jyri Lommi,
Kimmo Lappalainen,
Leena Krogerus,
Leo Ihlberg,
Taina A Partanen,
Liisa Lähteenoja,
Kari Virtanen,
Kari Alitalo,
Seppo Ylä-Herttuala,
Ari Harjula
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ABSTRACT: Besides being a known lymphangiogenic activator, vascular endothelial growth factor (VEGF)-C may express angiogenic potential by proteolytic cleavage and activation of endothelial cells. We assessed myocardial collateral formation and functional changes after adenovirus-mediated VEGF-C gene transfer in an ischemic porcine model.
Fifteen Landrace piglets underwent Ameroid-induced gradual occlusion of the left circumflex artery (LCx) and consequent progressive myocardial ischemia. Three weeks after Ameroid placement, the animals underwent gated 99mTc SPECT during rest and stress, in vivo angiography and 18FDG PET. Pigs were randomized to intramyocardial injections of adenoviruses encoding vascular endothelial growth factor (VEGF-C; n = 7) or control beta-galactosidase (LacZ; n = 5). Four weeks later, the examinations were repeated and histology was analyzed.
Angiography showed significant progression of LCx stenosis in both groups during the treatment period. Left ventricular wall thickening (LVWT) at the LCx area in gated 99mTc SPECT remained unchanged in the VEGF-C group, indicating that VEGF-C prevented progression of myocardial ischemia, whereas LVWT deteriorated in the LacZ group (p = 0.042). Semi-quantitative assessment of 18FDG PET suggests more reduction in ischemia in the adVEGF-C group than in controls (p = 0.052). Angiography showed significant clustering of collaterals in the adVEGF-C gene transfer area compared that in LacZ (p = 0.004). von Willebrand factor staining revealed a significantly (p = 0.03) greater number of microvessels in the adVEGF-C-treated myocardium.
This appears to be the first large-animal study in which, during progressive ischemia, functional and metabolic benefits of intramyocardial VEGF-C gene transfer were apparent. VEGF-C-induced collateral formation occurred at the site of gene transfer. The angiogenic potency of VEGF-C deserves further study as a therapeutic option.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 03/2006; 25(2):206-13. · 3.54 Impact Factor
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Matti Peura,
Jozef Bizik,
Pertteli Salmenperä,
Ariel Noro,
Matti Korhonen, Tommi Pätilä,
Antti Vento,
Antti Vaheri,
Riitta Alitalo,
Jyrki Vuola,
Ari Harjula,
Esko Kankuri
[show abstract]
[hide abstract]
ABSTRACT: We previously showed cell-cell contacts of human dermal fibroblasts to induce expression of the hepatocyte growth factor/scatter factor (HGF) in a process designated as nemosis. Now we report on nemosis initiation in bone marrow mesenchymal stem cells (BMSCs). Because BMSCs are being used increasingly in cell transplantation therapy we aimed to demonstrate a functional effect and benefit of BMSC nemosis for wound healing. Nemotic and monolayer cells were used to stimulate HaCaT keratinocyte migration in a scratch-wound healing assay. Both indicators of nemosis, HGF production and cyclooxygenase-2 expression, were induced in BMSC spheroids. When compared with a similar amount of cells as monolayer, nemotic cells induced keratinocyte in vitro scratch-wound healing in a concentration-dependent manner. The HGF receptor, c-Met, was rapidly phosphorylated in the nemosis-stimulated keratinocytes. Nemosis-induced in vitro scratch-wound healing was inhibited by an HGF-neutralizing antibody as well as the small molecule c-Met inhibitor, SU11274. HGF-induced in vitro scratch-wound healing was inhibited by PI3K inhibitors, wortmannin and LY294002, while LY303511, an inactive structural analogue of LY294002, had no effect. Inhibitors of the mitogen-activated protein kinases MEK/ERK1/2 (PD98059 and U0126), and p38 (SB203580) attenuated HGF-induced keratinocyte in vitro scratch-wound healing. We conclude that nemosis of BMSCs can induce keratinocyte in vitro scratch-wound healing, and that in this effect signaling via HGF/c-Met is involved.
Wound Repair and Regeneration 17(4):569-77. · 2.91 Impact Factor
