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Biomedical subjects

K Peuhkurinen

Publications and source records attributed to K Peuhkurinen.

At least 19 recordsLinked to original sources
PubMed2006

A 3-year clinical follow-up of adult patients with 3243A>G in mitochondrial DNA.

OBJECTIVE: To follow the clinical course of patients with the mitochondrial DNA mutation 3243A>G for 3 years. METHODS: Thirty-three adult patients with the 3243A>G mutation entered a 3-year follow-up study. They were clinically evaluated annually, audiometry was performed, and samples were drawn for the analysis of blood chemistry and mutation heteroplasmy in leukocytes. Holter recording was performed three times during the follow-up and echocardiography, neuropsychological assessment, and quantitative EEG and brain imaging conducted at entry and after 3 years. RESULTS: The incidence of new neurologic events was low during the 3-year follow-up. Sensorineural hearing impairment (SNHI) progressed, left ventricular wall thickness increased, mean alpha frequency in the occipital and parietal regions decreased, and the severity of disease index (modified Rankin score) progressed significantly. The rate of SNHI progression correlated with mutation heteroplasmy in muscle. The increase in left ventricular wall thickness was seen almost exclusively in diabetic patients. Seven patients died during the follow-up, and they were generally more severely affected than those who survived. CONCLUSIONS: Significant changes in the severity of disease, sensorineural hearing impairment, left ventricular hypertrophy, and quantitative EEG were seen in adult patients with 3243A>G during the 3-year follow-up.

Adult↗
PubMed2004

Inducibility of life-threatening ventricular arrhythmias is related to maximum left ventricular thickness and clinical markers of sudden cardiac death in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene.

We investigated inducibility of life-threatening arrhythmias with programmed ventricular stimulation (PVS) in relation to clinical markers of sudden cardiac death (SCD) in subjects with hypertrophic cardiomyopathy (HCM) attributable to the Asp175Asn mutation in the alpha-tropomyosin gene (TPM1-Asp175Asn). PVS was performed with up to three extrastimuli and distribution of markers of SCD was evaluated in 21 adult subjects with the TPM1-Asp175Asn. Sustained polymorphic ventricular tachycardia (VT) or ventricular fibrillation (VF) was induced in seven of 21 subjects (33%). Inducible subjects had more severe left ventricular hypertrophy (LVH) and an increased number of markers of SCD (family history of SCD, syncope or presyncope, fall in systolic blood pressure (BP) during exercise, documented non-sustained VT (NSVT), and marked LVH) compared to non-inducible subjects (IVS 2.4 +/- 0.3 cm vs. 1.6 +/- 0.5 cm, P < 0.001; and two to three vs. one to two markers of SCD, P = 0.007, respectively). In conclusion, in HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene, life-threatening arrhythmias were induced in one third of the patients. Inducibility was associated with the maximum left ventricular (LV) thickness and the number of markers of SCD, suggesting that in HCM patients with an identical causative mutation, susceptibility to ventricular arrhythmias is related to the cardiomyopathic phenotype.

Adult↗
PubMed2004

Improved adherence to practice guidelines yields better outcome in high-risk patients with acute coronary syndrome without ST elevation: findings from nationwide FINACS studies.

OBJECTIVES: Treatment options for acute coronary syndrome (ACS) without ST elevation have evolved rapidly during the recent years, but the successful implementation of practice guidelines incorporating new treatments into practice has been challenging. In this study, we evaluate whether targeted educational intervention could improve adherence to treatment guidelines of ACS without ST elevation. DESIGN, SETTING AND SUBJECTS: A previous study, FINACS I, evaluated the treatment and outcome of 501 consecutive non-ST elevation ACS patients that were referred in early 2001 to nine hospitals, covering nearly half of the Finnish population. That study revealed poor adherence to ESC guidelines, so targeted educational intervention on optimal practice was arranged before the second study (FINACS II), which was performed in the same hospitals using the same protocol as FINACS I. FINACS II, undertaken in early 2003, evaluated 540 consecutive patients. Interventions. Targeted educational programmes on optimal practice. MAIN OUTCOME MEASURES: The use of evidence-based therapies in non-ST elevation ACS patients. In-hospital event-free (death, new myocardial infarction, refractory angina, readmission with unstable angina and transient cerebral ischaemia/stroke) survival, and event-free survival at 6 months. RESULTS: Baseline characteristics and risk markers were similar in both studies, and no significant changes in resources were seen. In 2003, the in-hospital use of statins, ACE-inhibitors, clopidogrel and glycoprotein (GP) IIb/IIIa receptor antagonists increased significantly, and in-hospital angiography was performed more often, especially in high-risk patients (59% vs. 45%, P < 0.05); waiting time also shortened (4.2 +/- 5.5 vs. 5.8 +/- 4.7 days, P < 0.01). Overall no significant change was seen in the frequency of death either in-hospital (2% vs. 4%, P = NS) or at 6 months (7% vs. 10%, P = NS) in FINACS II. However, the survival of high-risk patients improved both in-hospital (95% vs. 90%, P = 0.05) and at 6 months (89% vs. 78%, P = 0.05). CONCLUSION: In patients with non-ST elevation ACS-targeted educational interventions appeared to be associated with improved adherence to practical guidelines, which yielded a better outcome in high-risk ACS patients.

Acute Disease↗
PubMed2002

Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial.

BACKGROUND: Levosimendan, a novel calcium sensitiser, improves myocardial contractility without causing an increase in myocardial oxygen demand. We compared the effects of levosimendan and dobutamine on haemodynamic performance and clinical outcome in patients with low-output heart failure. METHODS: Patients were recruited into a multicentre, randomised, double-blind, double-dummy, parallel-group trial. Under continuous haemodynamic monitoring, an initial loading dose of levosimendan of 24 microg/kg was infused over 10 min, followed by a continuous infusion of 0.1 microg kg(-1) min(-1) for 24 h. Dobutamine was infused for 24 h at an initial dose of 5 microg kg(-1) min(-1) without a loading dose. The infusion rate was doubled if the response was inadequate at 2h. The primary endpoint was the proportion of patients with haemodynamic improvement (defined as an increase of 30% or more in cardiac output and a decrease of 25% or more in pulmonary-capillary wedge pressure) at 24 h. Analyses were by intention to treat. FINDINGS: 103 patients were assigned levosimendan and 100 dobutamine. The primary haemodynamic endpoint was achieved in 29 (28%) levosimendan-group patients and 15 (15%) in the dobutamine group (hazard ratio 1.9 [95% CI 1.1-3.3]; p=0.022). At 180 days, 27 (26%) levosimendan-group patients had died, compared with 38 (38%) in the dobutamine group (0.57 [0.34-0.95]; p=0.029). INTERPRETATION: In patients with severe, low-output heart failure, levosimendan improved haemodynamic performance more effectively than dobutamine. This benefit was accompanied by lower mortality in the levosimendan group than in the dobutamine group for up to 180 days.

Cardiac Output, Low↗
PubMed2001

Reversible ischemic inhibition of F(1)F(0)-ATPase in rat and human myocardium.

The physiological role of F(1)F(0)-ATPase inhibition in ischemia may be to retard ATP depletion although views of the significance of IF(1) are at variance. We corroborate here a method for measuring the ex vivo activity of F(1)F(0)-ATPase in perfused rat heart and show that observation of ischemic F(1)F(0)-ATPase inhibition in rat heart is critically dependent on the sample preparation and assay conditions, and that the methods can be applied to assay the ischemic and reperfused human heart during coronary by-pass surgery. A 5-min period of ischemia inhibited F(1)F(0)-ATPase by 20% in both rat and human myocardium. After a 15-min reperfusion a subsequent 5-min period of ischemia doubled the inhibition in the rat heart but this potentiation was lost after 120 min of reperfusion. Experiments with isolated rat heart mitochondria showed that ATP hydrolysis is required for effective inhibition by uncoupling. The concentration of oligomycin for 50% inhibition (I(50)) for oxygen consumption was five times higher than its I(50) for F(1)F(0)-ATPase. Because of the different control strengths of F(1)F(0)-ATPase in oxidative phosphorylation and ATP hydrolysis an inhibition of the F(1)F(0)-ATPase activity in ischemia with the resultant ATP-sparing has an advantage even in an ischemia/reperfusion situation.

Adenosine Triphosphate↗
PubMed2001

Clinical relevance of ischemic preconditioning.

The mechanisms of ischemic cell death and reperfusion injury in the myocardium and the ways to limit these have been under extensive research for decades. The discovery of the phenomenon of ischemic preconditioning, i.e. endogenous protection against ischemia-reperfusion injury obtained by one or more brief preceding episodes of ischemia, really boosted this research 15 years ago. Even though extensive research in experimental animals has provided data on the cellular mechanisms of ischemic preconditioning, such as adenosine receptor activation, opening of mitochondrial adenosine triphosphate (ATP)-sensitive potassium channels and production of endogenous protective stress proteins, direct clinical applications are still missing. The purpose of this study is to summarize the latest progress in solving the cellular and molecular mechanisms of the phenomenon, as well as the evidence for the existence of this phenomenon in humans and its clinical relevance.

Adaptation, Physiological↗
PubMed2000

Effectiveness of amiodarone as a single oral dose for recent-onset atrial fibrillation.

The efficacy of amiodarone has been proved in long-term maintenance of sinus rhythm (SR) in patients with paroxysmal atrial fibrillation (AF). The present study evaluates the efficacy and safety of a single oral dose of amiodarone in patients with recent-onset AF (<48 hours). Seventy-two patients were randomized to receive 30 mg/kg of either amiodarone or placebo. Conversion to SR was verified by 24-hour Holter monitoring. Ten patients were excluded because of SR in the beginning of monitoring or technical failure during Holter monitoring. The remaining study groups were comparable (n = 31 for each), except that in the placebo group beta blockers were more common. The patients receiving amiodarone converted to SR more effectively than those receiving placebo (p<0.0001). At 8 hours, approximately 50% of patients in the amiodarone group and 20% in the placebo group (Holter successful) had converted to SR, whereas after 24 hours the corresponding figures were 87% and 35%, respectively. The median time for conversion (8.7 hours for amiodarone and 7.9 hours for placebo) did not differ in the groups. Amiodarone was hemodynamically well tolerated, and the number of adverse events in the study groups was similar. Amiodarone as a single oral dose of 30 mg/kg appears to be effective and safe in patients with recent-onset AF.

Administration, Oral↗
PubMed2000

Adaptation to myocardial ischemia during repeated ventricular pacing in patients with coronary artery disease.

OBJECTIVE: The purpose of our study was to evaluate whether repeated ventricular pacing is able to induce adaptation against ischemia in coronary artery disease patients. DESIGN: Fifteen patients with documented coronary artery disease were subjected to two successive periods of rapid ventricular pacing (150 bpm) of equal length (295+/-33 s), the first being limited by intolerable anginal pain. The second pacing period, of the same length as the first, was initiated after the disappearance of angina and ST depression, the mean resting time being 433+/-30 s. Blood samples for the determination of transcardiac differences in glucose, lactate, free fatty acids, K+, pCO2, pH, oxygen saturation and noradrenaline were taken from the femoral artery and coronary sinus before and at the end of each pacing period. The mechanical performance of the hearts was followed by continuous monitoring of intra-arterial blood pressure and pulmonary capillary wedge pressure, and the observed adaptation in the measured variables during the successive pacing tests was correlated with the duration of angina, severity of coronary artery disease and degree of collateralization. RESULTS: Changes in the transcardiac pH and K+ differences, ST segment and pulmonary capillary wedge pressure were less pronounced during the second pacing period. The subgroup with net lactate production before or after the first pacing period demonstrated metabolic adaptation manifested as improved lactate extraction during the second pacing period. Rate-pressure product and oxygen extraction, and thus presumably also overall oxygen consumption and oxygen delivery, were similar during both tests. The magnitude of adaptation did not correlate with the duration of angina, severity of coronary artery disease or overall collateral score. CONCLUSION: Rapid ventricular pacing is able to induce adaptation to myocardial ischemia, but the exact mechanisms in this process remain to be elucidated.

Cardiac Pacing, Artificial↗
PubMed1999

Plasma vasoactive peptides after acute myocardial infarction in relation to left ventricular dysfunction.

We measured plasma concentrations of vasoactive peptides in 32 patients with acute myocardial infarction and evaluated their value as markers of left ventricular dysfunction. Plasma levels of atrial natriuretic peptide (ANP), the N-terminal fragment of proANP (NT-proANP), B-type natriuretic peptide (BNP) and endothelin-1 were measured serially by radioimmunoassays. The infarct size was estimated from the creatine kinase MB release curve. Coronary angiography and left ventricular cineangiography were performed in all patients during hospitalization and 6 months later in 15 patients. Myocardial infarction caused an increase in vasoactive peptides, the highest values for ANP (36.5+/-6.79 pmol/l), NT-proANP (1130+/-170 pmol/l) and endothelin-1 (9.72+/-0.68 pmol/l) being found on admission and those for BNP (56.0+/-7.13 pmol/l) on Day 2. Plasma levels of natriuretic peptides were dependent on infarct size, its location and degree of myocardial dysfunction and that of BNP also on infarct artery patency. Plasma endothelin-1 level was higher in patients with TIMI 3 than TIMI 0-2 flow. Plasma vasoactive peptides remained elevated during the 6-month follow-up period and they were dependent on the degree of myocardial dysfunction. BNP measured on any day of hospitalization showed the best correlation with ejection fraction measured during the acute phase of infarction or at 6 months. The results show that BNP is the best indicator of left ventricular dysfunction after myocardial infarction and its reliability is not dependent on the time point of measurement.

Analysis of Variance↗
PubMed1999

Vasoactive peptide release in relation to hemodynamic and metabolic changes during rapid ventricular pacing.

Plasma atrial natriuretic peptide (ANP) concentration increases during ventricular arrhythmias and rapid ventricular pacing but less is known about plasma brain natriuretic peptide (BNP) and endothelin (ET-1). In the present study concentrations of ANP, the amino terminal part of the proANP (NT-proANP), BNP, and ET-1 were measured in the coronary sinus and femoral artery before and at the end of rapid ventricular pacing in 15 patients with coronary arterial disease. The changes were compared with the changes in mean arterial blood pressure, pulmonary capillary wedge pressure (PCWP), transcardiac differences in pH, pCO2, lactate, and norepinephrine. There was an increase in PCWP and a transient decrease in blood pressure after initiation of pacing. Pacing caused a decrease in ST-segment, transcardiac difference of norepinephrine, lactate extraction, pCO2 difference, and an increase in pH difference. Concentration of ANP in the coronary sinus and femoral artery and its transcardiac difference increased during pacing (P < 0.001), whereas changes in NT-proANP were small and BNP and ET-1 levels remained unchanged. The change in transcardiac ANP difference correlated with the change in lactate (r = 0.53, P < 0.05) but not that of norepinephrine, PCWP, or blood pressure. The results show that the plasma concentration of ANP increases more than that of NT-proANP during rapid ventricular pacing. Ischemia-induced release of ANP and its diminished elimination may contribute to the increased plasma ANP level.

Aged↗
PubMed1997

Collagen scar formation after acute myocardial infarction: relationships to infarct size, left ventricular function, and coronary artery patency.

BACKGROUND: Left ventricular function after acute myocardial infarction (AMI) is determined by the expansion of the infarct zone and remodeling of the noninfarcted myocardium. An occluded infarct-related artery (IRA) is an independent risk factor for remodeling. METHODS AND RESULTS: Changes in myocardial collagen metabolism were evaluated in 36 patients with suspected AMI. The plasma creatine kinase MB fraction and myoglobin release curves were analyzed for assessment of early reperfusion and infarct size. Collagen scar formation was evaluated by measurement of serum concentrations of the aminoterminal propeptide of type III procollagen (PIIINP), the aminoterminal propeptide of type I procollagen (intact PINP), and the carboxyterminal propeptide of type I procollagen (PICP). Plasma renin activity and urine excretion of cortisol and aldosterone were also measured. Coronary angiography and left ventricular cineangiography were performed during early hospitalization. The serum concentration of PIIINP increased from 3.50+/-0.20 to a maximum of 5.08+/-0.36 microg/L (n=32) in the patients with AMI, whereas the concentrations of intact PINP and PICP tended to decrease. The area under the curve (AUC) of PIIINP during the first 10 postinfarction days was larger in patients with severe heart failure or ejection fractions < or = 40% than in those with no heart failure or with an ejection fraction > 40% (P<.05 and P<.01, respectively), and it was also larger in the patients with TIMI grade 0 to 2 flows than in those with TIMI 3 flows (P<.05), despite similar enzymatically determined infarct sizes. No significant correlations between PIIINP and neurohumoral parameters were observed. The AUC of PIIINP and the change in PIIINP during the first 4 days were significantly correlated with indices of cardiac function. CONCLUSIONS: Collagen scar formation after AMI can be quantified by measurement of serum PIIINP concentrations. Scar formation is more prominent in large infarctions causing left ventricular dysfunction and in patients with occluded IRAs.

Adult↗
PubMed1996

No evidence for ischemic preconditioning during repeated vessel occlusion in coronary angioplasty.

Coronary angioplasty has been the favoured model in studying ischemic preconditioning in humans, but results have remained controversial, possibly due to some artefacts related to coronary balloon angioplasty as an ischemia model. We examined this issue by monitoring the sequential metabolic, functional and neurohumoral changes during repeated vessel occlusion in coronary angioplasty performed in patients with chronic angina pectoris. Two groups of patients undergoing two successive balloon inflations of approximately 2 min duration were studied. These balloon inflations were preceded by a short inflation performed immediately after introduction of the balloon into the stenosis. The aim of this primary inflation was to establish adequate coronary blood flow with the deflated balloon in the stenosis and to guarantee that the subsequent two balloon inflations were truly comparable in time. Group I consisted of 23 patients, in whom the changes in the degree of angina, pulmonary capillary wedge pressure (PCWP), atrial natriuretic peptide (ANP) and circulating catecholamines during the procedure were studied. The sequential changes in myocardial metabolism were monitored in group II of nine patients by determining the lactate extraction ratios and femoroarterial coronary sinus (Fa-CS) differences in pH and pCO2 before and after each balloon inflation. In group I, PCWP and total catecholamines increased similarly during both balloon inflations, but ANP remained unchanged. In group II patients the lactate extraction ratios turned negative, the Fa-CS pH-differences increased and the pCO2-differences decreased during vessel occlusions, the changes being somewhat more prominent during the second balloon inflation. To study adaptation to ischemia, the group I patients were divided into two subgroups with and without signs of ischemic dysfunction during balloon inflations (PCWP increase > 5 mmHg and < 5 mmHg, respectively), and the group II patients were divided into two subgroups with and without metabolic ischemia (lactate-producers and non-producers). The ANP levels were constantly higher in the patients demonstrating ischemic dysfunction during balloon inflations, but catecholamine levels increased only after the second balloon inflation. The anginal pain experienced by the patients and the signs of metabolic ischemia were identical during both balloon inflations. We conclude that acute ischemic preconditioning does not occur in patients with repeated vessel occlusions of approximately 2 min duration. The patients without ischemia during the procedure had more critical stenoses and pre-existing collaterals. However, other protective mechanisms, such as chronic adaptation at the cellular level or recruitment of new collaterals, cannot be excluded.

Angioplasty, Balloon, Coronary↗