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Jyri Lommi

Publications and source records attributed to Jyri Lommi.

15 recordsLinked to original sources
PubMed2006

Doppler echocardiography markedly underestimates left ventricular stroke work loss in severe aortic valve stenosis.

AIMS: Left ventricular (LV) stroke work loss (SWL) is an index of aortic stenosis (AS) severity based on the energy loss concept. Traditionally known as an invasive measurement, SWL has also been determined noninvasively using Doppler echocardiography. The present work was done to compare the echocardiographic estimate against the standard invasive SWL. METHODS AND RESULTS: We determined SWL in 113 adult patients with AS at cardiac catheterization (mean gradient as percentage of the LV mean systolic pressure) and by Doppler echocardiography (mean gradient as percentage of the sum of systolic cuff blood pressure and mean gradient). SWL averaged 26.5+/-0.6% by echocardiography vs 30.9+/-0.8% by catheterization (p<0.0000001). The underestimation by echocardiography was the worse the higher the invasive SWL was (p<0.00001). Echocardiographic SWL exceeding 25% (previously suggested cutoff) had a sensitivity of 64% and specificity of 74% to identify severe AS (Gorlin valve area<0.5 cm(2)/m(2)). Several patients with severe AS by valve area had echocardiographic SWL suggesting only mild AS. CONCLUSIONS: In AS, echocardiography gives a biased estimate of LV SWL with marked underestimation in severe disease. Echocardiographic SWL may confuse rather than improve the assessment of AS in clinical practice.

Adult↗
PubMed2006

Increased expression of elastolytic cathepsins S, K, and V and their inhibitor cystatin C in stenotic aortic valves.

OBJECTIVE: To investigate the possible role of elastolytic cathepsins S, K, and V and their endogenous inhibitor cystatin C in adverse extracellular matrix remodeling of stenotic aortic valves. METHODS AND RESULTS: Stenotic aortic valves were collected at valve replacement surgery and control valves at cardiac transplantations. The expression of cathepsins S, K, and V and cystatin C was studied by conventional and real-time polymerase chain reaction and by immunohistochemistry. Total cathepsin activity in the aortic valves was quantified by a fluorometric microassay. When compared with control valves, stenotic valves showed increased mRNA expression of cathepsins S, K, and V (P<0.05 for each) and a higher total cathepsin activity (P<0.001). In stenotic valves, cystatin C mRNA was increased (P<0.05), and cystatin C protein was found particularly in areas with infiltrates of inflammatory cells. Both cathepsin S and cystatin C were present in bony areas of the valves, whereas cathepsin V localized to endothelial cells in areas rich of neovascularization. Incubation of thin sections of aortic valves with cathepsins S, K, and V resulted in severe disruption of elastin fibers, and this cathepsin effect could be blocked by adding cystatin C to the incubation system. CONCLUSIONS: Stenotic aortic valves show increased expression and activity of elastolytic cathepsins S, K, and V. These cathepsins may accelerate the destruction of aortic valvular extracellular matrix, so promoting the progression of aortic stenosis.

Aortic Valve↗
PubMed2006

Possible role for mast cell-derived cathepsin G in the adverse remodelling of stenotic aortic valves.

AIMS: Aortic stenosis (AS) is characterized by extensive remodelling of the valves, including infiltration of inflammatory cells, extracellular matrix degradation, and fibrosis. The molecular mechanisms behind this adverse remodelling have remained obscure. In this article, we study whether cathepsin G, an angiotensin II (Ang II)-forming elastolytic enzyme, contributes to progression of AS. METHODS AND RESULTS: Stenotic aortic valves (n = 86) and control valves (n = 17) were analysed for cathepsin G, transforming growth factor-beta1 (TGF-beta1), and collagens I and III with RT-PCR and immunohistochemistry. Valvular collagen/elastin ratio was quantified by histochemistry. In stenotic valves, cathepsin G was present in mast cells and showed increased expression (P < 0.001), which correlated positively (P < 0.001) with the expression levels of TGF-beta1 and collagens I and III. TGF-beta1 was also present in mast cell-rich areas and cathepsin G induced losartan-sensitive TGF-beta1 expression in cultured fibroblasts. Collagen/elastin ratio was increased in stenotic valves (P < 0.001) and correlated positively with smoking (P = 0.02). Nicotine in cigarette smoke activated mast cells and induced TGF-beta1 expression in cultured fibroblasts. Fragmented elastin was observed in stenotic valves containing activated cathepsin G-secreting mast cells and in normal valves treated with cathepsin G. CONCLUSION: In stenotic aortic valves, mast cell-derived cathepsin G may cause adverse valve remodelling and AS progression.

Adult↗
PubMed2006

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Journal Article↗
PubMed2005

Vascular endothelial growth factor C-induced collateral formation in a model of myocardial ischemia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adenoviridae↗
PubMed2005

Vasoactive intestinal peptide--release from the heart and response in heart failure due to left ventricular pressure overload.

BACKGROUND: Vasoactive intestinal peptide (VIP) is a peptidergic neurotransmitter and a vasodilator with positive inotropic and chronotropic properties. Whether and how VIP contributes to the neuroendocrine response in heart failure (HF) is disputed, and there are no data on VIP in pressure overload-induced HF. METHODS: We studied 129 adults with isolated aortic valve stenosis (AS). Blood was sampled from the aortic root and, in a subset of 48 patients, also from the coronary sinus for determination of VIP by radioimmunoassay. HF was diagnosed according to the European Society of Cardiology criteria. RESULTS: Plasma VIP (mean+/-S.E.M.) was slightly higher in patients with HF (22.6+/-0.9 pmol/l, n=41) than in patients free of HF (21.1+/-0.5 pmol/l, n=88) or in 11 control patients without structural heart disease (20.0+/-1.3 pmol/l, n=11) (p=0.030 across the groups). VIP did not correlate with any measurement of cardiac structure or function in AS. The change in plasma VIP from aortic root to coronary sinus averaged +1.2+/-0.4 pmol/l in the 11 control patients (p=0.021), +1.2+/-0.2 pmol/l in 33 AS patients free of HF (p<0.001) and +0.8+/-0.3 pmol/l in 15 AS patients with HF (p=0.037). CONCLUSIONS: Both structurally normal and diseased hearts release VIP into the coronary sinus. Although marginally elevated in the systemic circulation, VIP is unlikely to contribute significantly to the neuroendocrine activation in HF due to pressure overload.

Adult↗
PubMed2005

Left ventricular hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure?

AIMS: In aortic stenosis (AS), left ventricular (LV) hypertrophy is considered a compensatory response helping maintain systolic function. Recent research in experimental AS suggests, however, that LV hypertrophy is not necessary to sustain LV contractions but may in fact be maladaptive. The present work aimed to clarify the role of LV hypertrophy in AS-related heart failure (HF) in man. METHODS AND RESULTS: We studied 137 adult patients with isolated AS undergoing pre-operative echocardiography and cardiac catheterization. HF was diagnosed by the European criteria and LV hypertrophy by sex-specific limits of echocardiographic LV mass. The higher the LV mass was, the poorer was the LV ejection fraction (beta=-0.26, P< 0.001, linear regression) and the greater the likelihood of HF independent of the severity of AS (P< 0.001, logistic regression). In the subgroup of critical AS (valve area <0.4 cm(2)/m(2), n=85), patients with absent LV hypertrophy (n=19) had better preserved ejection fraction (mean+/-SE, 64+/-3 vs. 57+/-2%, P=0.045) and less HF (16 vs. 48%, P=0.025) than patients with LV hypertrophy (n=66). CONCLUSION: In isolated AS, increased LV mass predicts the presence of systolic dysfunction and HF independent of the severity of valvular obstruction. LV hypertrophy may be maladaptive rather than beneficial in AS in man.

Adaptation, Physiological↗
PubMed2005

Is the pregnancy hormone relaxin an important player in human heart failure?

BACKGROUND: The pregnancy hormone relaxin has been raised as a new compensatory mediator of cardiac origin in heart failure (HF). We set out to assess the role of relaxin in pressure overload-induced human HF. METHODS: We studied 129 adult patients undergoing cardiac catheterization for isolated aortic valve stenosis (AS). Blood was sampled from the aortic root and, in a subset of 49 patients, from the coronary sinus for the determination of plasma relaxin by enzyme immunoassay. HF was diagnosed when the patient had dyspnea or fatigue on ordinary effort in association with pulmonary wedge pressure >14 mm Hg at catheterization. RESULTS: Forty-one patients had HF, which was systolic (ejection fraction <50%) in 16 patients and diastolic in 25 patients. The median plasma relaxin was 32 pg/ml (<12-297 pg/ml) in 88 AS patients without HF, 28 pg/ml (<12-825 pg/ml) in the 41 AS patients with HF, and 42 pg/ml (range, <12-100 pg/ml) in 11 control patients free of heart disease (p=0.82). Plasma relaxin did not correlate with any measurement of cardiac structure or function. The concentration gradients of relaxin from the aortic root to the coronary sinus indicated relaxin extraction by the heart in the control patients (median change, -5 pg/ml, p=0.038) vs. relaxin production in patients with systolic HF (median change, +6 pg/ml, p=0.028) (p=0.002 between groups). CONCLUSIONS: Although the heart may release relaxin into the circulation in certain forms of HF, this does not translate into elevated systemic concentrations. Relaxin is not a major player in human HF.

Adult↗
PubMed2005

Transcardiac gradients of N-terminal B-type natriuretic peptide in aortic valve stenosis.

BACKGROUND: Plasma B-type natriuretic peptide (BNP), as well as the N-terminal part of the prohormone (Nt-BNP), are frequently elevated in aortic valve stenosis (AS). Yet, their release from the heart into the circulation has never been directly studied in AS. AIM: To assess the release of Nt-BNP in AS with focus on the identification of its main determinants. METHODS: We studied 49 adult patients undergoing preoperative cardiac catheterization for isolated AS. Blood was sampled from the aortic root and the coronary sinus for Nt-BNP determination by immunoassay. RESULTS: The mean (+/-S.E.) transcardiac Nt-BNP step-up averaged 79+/-53 pmol/l in 11 control patients free of structural heart disease, 75+/-32 pmol/l in 31 AS patients free of heart failure (HF), 236+/-62 pmol/l in 8 AS patients with diastolic HF (ejection fraction > or = 50%, pulmonary wedge pressure > 14 mm Hg) and 469+/-66 pmol/l in 7 AS patients with systolic HF (ejection fraction < 50%, wedge pressure > 14 mm Hg) (p<0.001). The transcardiac Nt-BNP gradient was independently associated with left ventricular (LV) end-diastolic pressure (beta=0.47, p<0.001) and ejection fraction (beta=-0.29, p<0.019) and with co-existent coronary artery disease (beta=0.23, p=0.050). CONCLUSION: LV diastolic and systolic dysfunction along with coronary artery disease are likely to be the key determinants of cardiac Nt-BNP release in AS. The transcardiac Nt-BNP gradient increases on average three-fold with the development of diastolic HF and six-fold in systolic HF.

Aged↗
PubMed2005

A prospective study comparing cytomegalovirus antigenemia, DNAemia and RNAemia tests in guiding pre-emptive therapy in thoracic organ transplant recipients.

We evaluated the usefulness of DNAemia and mRNAemia tests in guiding the pre-emptive therapy against cytomegalovirus (CMV) infections in thoracic organ transplant recipients using antigenemia test as the reference. Seven lung (LTR) and 14 heart (HTR) transplant recipients were prospectively monitored for CMV by antigenemia, DNAemia (Cobas Amplicor PCR Monitor) and pp67-mRNAemia (NASBA) tests. However, only the antigenemia test guided pre-emptive therapy with cut-off levels of >or=2 and >or=5-10 pp65-positive leukocytes/50 000 leukocytes in the LTRs and HTRs, respectively. CMV DNAemia was detected in 26/28 (93%) and RNAemia in 17/28 (61%) of the CMV antigenemias requiring antiviral therapy (P = 0.01). Optimal DNAemia levels (sensitivity/specificity) estimated from receiver-operating characteristic curve to achieve maximal sum of sensitivity and specificity were 400 (75.9/92.7%), 850 (91.3/91.3%) and 1250 (100/91.5%) copies/ml for the antigenemia of 2, 5 and 10 pp65-positive leukocytes, respectively. The sensitivities of nucleic acid sequence-based amplification (NASBA) were 25.9%, 43.5% and 56.3% in detecting the same cut-off levels of antigenemia. In thoracic organ transplant recipients, the Cobas PCR assay is comparable with the antigenemia test in guiding pre-emptive therapy against CMV infections when threshold levels of over 5 pp65-antigen-positive leukocytes are used as the reference. In contrast, the low sensitivity of NASBA limits its usefulness in the guidance of pre-emptive therapy.

Adolescent↗
PubMed2004

Induction of local angiotensin II-producing systems in stenotic aortic valves.

OBJECTIVES: The purpose of this study was to investigate the expression of angiotensin II (Ang II)-producing enzyme systems in normal and stenotic aortic valves. BACKGROUND: Chronic inflammation and fibrosis are involved in the pathogenesis of aortic stenosis (AS), but the detailed molecular mechanisms of this atherosclerosis-like process remain obscure. Angiotensin II, a powerful mediator of inflammation and fibrosis, may participate in AS progression. METHODS: Stenotic aortic valves (n = 86) were obtained from patients undergoing valve replacement surgery, and control valves (n = 11) were obtained from patients undergoing cardiac transplantation. Angiotensin-converting enzyme (ACE) and mast cell (MC)-derived chymase were quantified by reverse-transcription polymerase chain reaction, autoradiography, and immunostaining. The MCs, macrophages, and T lymphocytes were detected by immunohistochemistry, and angiotensin II type 1 receptor (AT-1R) by autoradiography. RESULTS: Compared with control valves, stenotic aortic valves showed a significant increase in both messenger ribonucleic acid (mRNA) (p = 0.001) and protein (p < 0.001) expression of ACE, which colocalized with macrophages. Similarly, the expression of AT-1R protein and chymase mRNA and protein was upregulated (p < 0.001), and the number of MCs was six-fold higher in stenotic than in normal valves. The MCs were associated with the calcified areas, and-in contrast to control valves-showed an increased degree of degranulation, a prerequisite for chymase secretion and action. CONCLUSIONS: Angiotensin-converting enzyme and chymase, two Ang II-forming enzymes, are locally expressed in aortic valves, and owing to infiltration of macrophages and MCs, are further upregulated in stenotic valves. These novel findings, implicating chronic inflammation and an increased expression of local Ang II-forming systems, suggest that therapeutic interventions aiming at inhibiting these processes may slow AS progression.

Adult↗
PubMed2004

Clinical usefulness of bronchoalveolar lavage in heart transplant recipients with suspected lower respiratory tract infection.

BACKGROUND: Bronchoscopy with bronchoalveolar lavage (BAL) is the recommended initial invasive diagnostic procedure when lower respiratory tract infection is suspected in solid-organ transplant recipients. In this study, we evaluated the clinical impact and safety of bronchoscopy with BAL in heart transplant recipients. METHODS: We reviewed all 44 consecutive diagnostic bronchoscopies with BAL that were performed in 35 heart transplant recipients at Helsinki University Central Hospital between May 1988 and December 2001. RESULTS: Bronchoscopy findings established specific microbiologic diagnoses in 18 of 44 (41%) cases, and 14 of 44 (32%) bronchoscopic findings led to changes in therapy. The diagnostic yield of bronchoscopy from 1 to 6 months after transplantation was 73%, significantly better (p = 0.002) than diagnostic yield during the first month (18%) and after 6 months (28%). Pneumocystis carinii and cytomegalovirus were the most frequently detected pathogens in the BAL fluid. Cytomegalovirus pneumonia carried a high mortality rate (44%), whereas all patients with P carinii pneumonia recovered. Fourteen episodes were diagnosed as bacterial pneumonia, but because of empiric antibiotic therapy that was started widely before bronchoscopy, a microbiologic diagnosis was established in only 1 case. However, all patients with community-acquired pneumonia responded to empiric therapy. Four cases of major complications occurred after bronchoscopy, all cardiovascular but none fatal. CONCLUSIONS: Bronchoscopy with BAL is a useful diagnostic tool in heart transplant recipients, especially between 1 and 6 months after transplantation.

Adolescent↗