Elektrokardiografiset repolarisaatiomuuttujat sydäninfarktin ja iskemian toteamisessa

The aim of the studies was to improve the diagnostic capability of electrocardiography (ECG) in detecting myocardial ischemic injury with a future goal of an automatic screening and monitoring method for ischemic heart disease. The method of choice was body surface potential mapping (BSPM), containing numerous leads, with intention to find the optimal recording sites and optimal ECG variables for ischemia and myocardial infarction (MI) diagnostics. The studies included 144 patients with prior MI, 79 patients with evolving ischemia, 42 patients with left ventricular hypertrophy (LVH), and 84 healthy controls. Study I examined the depolarization wave in prior MI with respect to MI location. Studies II-V examined the depolarization and repolarization waves in prior MI detection with respect to the Minnesota code, Q-wave status, and study V also with respect to MI location. In study VI the depolarization and repolarization variables were examined in 79 patients in the face of evolving myocardial ischemia and ischemic injury. When analyzed from a single lead at any recording site the results revealed superiority of the repolarization variables over the depolarization variables and over the conventional 12-lead ECG methods, both in the detection of prior MI and evolving ischemic injury. The QT integral, covering both depolarization and repolarization, appeared indifferent to the Q-wave status, the time elapsed from MI, or the MI or ischemia location. In the face of evolving ischemic injury the performance of the QT integral was not hampered even by underlying LVH. The examined depolarization and repolarization variables were effective when recorded in a single site, in contrast to the conventional 12-lead ECG criteria. The inverse spatial correlation of the depolarization and depolarization waves in myocardial ischemia and injury could be reduced into the QT integral variable recorded in a single site on the left flank. In conclusion, the QT integral variable, detectable in a single lead, with optimal recording site on the left flank, was able to detect prior MI and evolving ischemic injury more effectively than the conventional ECG markers. The QT integral, in a single-lead or a small number of leads, offers potential for automated screening of ischemic heart disease, acute ischemia monitoring and therapeutic decision-guiding as well as risk stratification.Perinteinen sydäninfarktin ja sepelvaltimotautikohtauksen elektrokardiografinen (EKG) diagnostiikka perustuu laadullisiin piirteisiin 12-kytkentäisessä EKG:ssa. Väitöskirjatutkimuksen tarkoituksena oli parantaa EKG-diagnostiikkaa sydäninfarktin ja iskemian havaitsemisessa.. Lopullisena päämääränä on kehittää iskeemisen sydänsairauden automaattinen seulonta- ja monitorointimenetelmä. Väitöskirjatutkimuksen osatyöt tähtäsivät sydäninfarkti- ja iskemiadiagnostiikassa parhaiden rekisteröintipaikkojen löytämiseen yksittäisissä kytkennöissä ja parhaiden kvantitatiivisten EKG-muuttujien löytämiseen. Tutkimuksen työkaluna käytettiin sydänsähkökäyrän kehokartoitusta (body surface potential mapping, BSPM), jossa sydämen tuottamaa sähköistä potentiaalia rekisteröidään koko ylävartalon alueelta lukuisten elektrodien avulla. Tutkimushenkilöinä oli 144 aiemmin sydäninfarktin sairastanutta potilasta, 79 potilasta, joilla oli äkillinen sepelvaltimotautikohtaus, 42 potilasta, joilla oli vasemman kammion hypertrofia ja 84 tervettä vapaaehtoista. Sydäninfarkti ja sepelvaltimotauti varmennettiin tai paikannettiin sepelvaltimoiden ja vasemman kammion varjoainekuvauksella, sydämen kaikukuvauksella, sydänlihasmerkkiaineilla tai sydämen magneettitutkimuksella. Osatutkimuksissa I-V tarkasteltiin sydämen sähköistä aktivoitumis- ja palautumisvaiheita eli depolarisaatio- ja repolarisaatiovaiheita kuvaavia muuttujia aiemman sydäninfarktin diagnostiikassa sekä paikannuksessa perinteiseen EKG-diagnostiikkaan verrattuna. Kuudennessa osatutkimuksessa näitä muuttujia tarkasteltiin äkillisen sepeolvaltimotautikohtauksen aikana. Sydämen sähköisen palautumis- eli repolarisaatiovaiheen muuttujat EKG:ssa osoittautuivat aktivaatio- eli depolarisaatiovaiheen muuttujia paremmiksi sekä aiemman sydäninfarktin että äkillisen sepelvaltimotautikohtauksen diagnostiikassa Yhdestä kytkennästä rekisteröitävä QT-integraali, joka käsittää sekä sähköisen aktivaatio- että palautumisvaiheen, osoittautui vakaaksi diagnostiseksi muuttujaksi ja riippumattomaksi infarktin iästä, sijainnista, vasemman kammion hypertrofiasta tai mahdollisesta Q-aallosta ja oli perinteisiä EKG:n tulkintatapoja tehokkaampi. Tämä muuttuja tarjoaa mahdollisuuksia sepelvaltimotaudin automaattiseen seulontaan ja äkillisen sepelvaltimotautikohtauksen monitorointiin hoitopäätöksiä ja riskinarviointia ajatellen

Peak CK-MB has a strong association with chronic scar size and wall motion abnormalities after revascularized non-transmural myocardial infarction - a prospective CMR study

Background: Large myocardial infarction (MI) is associated with adverse left ventricular (LV) remodeling (LVR). We studied the nature of LVR, with specific attention to non-transmural MIs, and the association of peak CK-MB with recovery and chronic phase scar size and LVR. Methods: Altogether 41 patients underwent prospectively repeated cardiovascular magnetic resonance at a median of 22 (interquartile range 9-29) days and 10 (8-16) months after the first revascularized MI. Transmural MI was defined as >= 75% enhancement in at least one myocardial segment. Results: Peak CK-MB was 86 (40-216) mu g/L in median, while recovery and chronic phase scar size were 13 (3-23) % and 8 (2-19) %. Altogether 33 patients (81%) had a non-transmural MI. Peak CK-MB had a strong correlation with recovery and chronic scar size (r >= 0.80 for all, r >= 0.74 for non-transmural MIs; p = 0.75 for all, r >= 0.73 for non-transmural MIs; p <0.001). There was proportional scar size and LV mass resorption of 26% (0-50%) and 6% (-2-14%) in median. Young age (<60 years, median) was associated with greater LV mass resorption (median 9% vs. 1%, p = 0.007). Conclusions: Peak CK-MB has a strong association with chronic scar size and wall motion abnormalities after revascularized non-transmural MI. Considerable infarct resorption happens after the first-month recovery phase. LV mass resorption is related to age, being more common in younger patients.Peer reviewe

Somatostatin Receptor Expression Is Associated With Metastasis and Patient Outcome in Pulmonary Carcinoid Tumors

Context: Pulmonary carcinoids (PCs) belong to neuroendocrine tumors that often overexpress somatostatin receptors (SSTRs). This overexpression provides a molecular basis for tumor imaging and treatment with somatostatin analogs. Objective: To evaluate SSTR1 to SSTR5 distribution in a large set of PC tumors and to investigate whether the expression is associated with clinicopathological and outcome data. Design, Setting, and Patients: This retrospective study was conducted at Helsinki University Hospital and University of Helsinki. It included 178 PC tumors coupled with patients' clinical data retrieved through Finnish biobanks. After histological reclassification, tissue specimens were processed into next-generation tissue microarray format and stained immunohistochemically with monoclonal SSTR1 to SSTR5 antibodies. Main Outcome Measure: SSTR1 to SSTR5 expression in PC tumors. Results: Expression of SSTR1 to SSTR5 was detected in 52%, 75%, 56%, 16%, and 32% of the tumors, respectively. Membrane-bound staining was observed for all receptors. SSTR2 negativity and SSTR4 positivity was associated with lymph node involvement at the time of surgery (P = 0.014 and P = 0.017, respectively) and with distant metastasis (P = 0.027 and P = 0.015, respectively). SSTR3 and SSTR4 expression was associated with increased risk of shorter survival [P = 0.046, hazard ratio (HR) 4.703, 95% CI 1.027 to 21.533; and P = 0.013, HR 6.64, 95% CI 1.48 to 29.64, respectively], whereas expression of SSTR1 and SSTR2 was associated with improved outcome (P = 0.021, HR 0.167, 95% CI 0.037 to 0.765; and P = 0.022, HR 0.08, 95% CI 0.01 to 0.70, respectively). Conclusion: SSTR1 to SSTR5 expression is observed in PCs. As SSTR expression is associated with the tumor's metastatic potential and patient outcome, these receptors may offer the possibility for individualized prognosis estimation.Peer reviewe

Low MMP-8/TIMP-1 reflects left ventricle impairment in takotsubo cardiomyopathy and high TIM P-1 may help to differentiate it from acute coronary syndrome

Background Matrix metalloproteinase 8 (MMP-8) is the most potent type-I collagen protease. Such collagen mainly constitutes the transient fibrosis in takotsubo cardiomyopathy (TTC) endomyocardial biopsies. High MMP-8 and tissue-inhibitor of matrix metalloproteinase-1 (TIMP-1) levels are implicated in acute coronary syndrome (ACS). We compared MMP-8 and TIM P-1 levels in consecutive TTC and ACS patients, and their association to TTC severity. Methods and results In 45 acute serum samples of TTC, 2072 ACS and 1000 controls, TI MP-1 differed between ACS 146.7ng/mL (115.0-186.3) (median (interquartile range)), TTC 115.7 (94.3-137.7) and controls 80.9 (73.2-90.4), (p Conclusions Even with other differing factors considered, TIMP-1 differentiated TTC from ACS better than TnT. In TTC, the low MMP-8/TIM P-1 molar ratio may reflect decreased proteolysis and increased transient fibrosis, perhaps in part explaining the left-ventricle impairment.Peer reviewe

Performance of Finnish biobanks in nationwide pulmonary carcinoid tumour research

Finnish hospital-integrated biobanks administer millions of formalin-fixed paraffin-embedded tissue samples collected within the clinical diagnostics. According to the Finnish Biobank Act, these samples can be coupled with patients’ clinical follow-up data and the data retrieved from national health registries. We collected a nationwide pulmonary carcinoid tumour series from Finnish biobanks to study prognostic factors as well as to explore how the number of tumours found in the Finnish biobanks corresponds to the number of tumours registered by the Finnish Cancer Registry (FCR). Finnish biobanks identified 88% of the tumours registered by the FCR and were able to deliver 63%. The main reasons for lacking samples were paucity of resected primary tumour tissue, incompatible primary diagnosis, and the absence of tissue blocks in the archives. The main bottleneck in the sample application process was retrieving patient data. Altogether, we received 224 tumour samples with appropriate patient data and identified six prognostic factors for shorter disease-specific survival: age over 56 years at the time of diagnosis, tumour size over 2.5 cm, atypical histology, Ki-67 proliferation index higher than 2.5%, hilar/mediastinal lymph node involvement at the time of diagnosis, and the presence of metastatic disease. In conclusion, the Finnish biobank infrastructure offers excellent opportunities for tissue-based research. However, to be able to develop the biobank operations further, involving more medical knowledge in the sample and data acquisition process is a necessity. Also, when working with tissue samples collected over decades, histological expertise is essential for re-evaluation and re-classification of the samples.Peer reviewe

Allochthony, fatty acid and mercury trends in muscle of Eurasian perch (Perca fluviatilis) along boreal environmental gradients

Environmental change, including joint effects of increasing dissolved organic carbon (DOC) and total phosphorus (TP) in boreal northern lakes may affect food web energy sources and the biochemical composition of organisms. These environmental stressors are enhanced by anthropogenic land-use and can decrease the quality of polyunsaturated fatty acids (PUFAs) in seston and zooplankton, and therefore, possibly cascading up to fish. In contrast, the content of mercury in fish increases with lake browning potentially amplified by intensive forestry practises. However, there is little evidence on how these environmental stressors simultaneously impact beneficial omega-3 fatty acid (n3-FA) and total mercury (THg) content of fish muscle for human consumption. A space-for-time substitution study was conducted to assess whether environmental stressors affect Eurasian perch (Perea fluviatilis) allochthony and muscle nutritional quality [PUPA, THg, and their derivative, the hazard quotient (HQ)]. Perch samples were collected from 31 Finnish lakes along pronounced lake size (0.03-107.5 km(2)), DOC (5.0-24.3 mg L-1), TP (5-118 mu g L-1) and land-use gradients (forest: 50.7-96.4%, agriculture: 0-32A%). These environmental gradients were combined using principal component analysis (PCA). Allochthony for individual perch was modelled using source and consumer delta H-2 values. Perch allochthony increased with decreasing lake pH and increasing forest coverage (PC1), but no correlation between lake DOC and perch allochthony was found. Perch muscle THg and omega-6 fatty acid (n6-FA) content increased with PC1 parallel with allochthony. Perch muscle DHA (22:6n3) content decreased, and ALA (18:3n3) increased towards shallower murkier lakes (PC2). Perch allochthony was positively correlated with muscle THg and n6-FA content, but did not correlate with n3-FA content. Hence, the quality of perch muscle for human consumption decreases (increase in HQ) with increasing forest coverage and decreasing pH, potentially mediated by increasing fish allochthony.Peer reviewe

Gene Expression Alterations in the Cerebellum and Granule Neurons of Cstb(-/-) Mouse Are Associated with Early Synaptic Changes and Inflammation

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