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Otmar Pachinger

Publications and source records attributed to Otmar Pachinger.

At least 37 records · Page 2Linked to original sources

Transient impairment of flow-mediated vasodilation in patients with metabolic syndrome at moderate altitude (1,700 m).

BACKGROUND: The influence of moderate altitude on the cardiovascular system in patients with metabolic syndrome has not been investigated sufficiently, yet. The aim of this study was to assess the effect of acute and mid-term exposure to moderate altitude (1,700 m) on endothelial function in patients with metabolic syndrome. METHODS: Flow-mediated (FMD) and nitroglycerin-mediated vasodilation (NMD) were assessed in 18 patients with coronary risk factors on 5 occasions: (1) at location A (576 m), (2) on the first day at moderate altitude (location B, 1,700 m), (3) after 3 weeks at moderate altitude, (4) and (5) again at location A (6 and 16 weeks after the stay at moderate altitude, respectively). In addition, markers of lipid metabolism, serum erythropoietin and endothelin were measured. RESULTS: FMD on the first day at moderate altitude was similar compared to baseline FMD at location A (7.0 +/- 3.3 vs. 7.4 +/- 4.6%; NS). A 3-week stay at moderate altitude was associated with a significant reduction in FMD (7.4 +/- 4.6 vs. 3.8 +/- 2.5%; p < 0.05) despite a decrease in baseline diameter (4.5 +/- 0.3 vs. 4.3 +/- 0.4 mm; p < 0.05). Six weeks after returning to location A, FMD was still reduced compared to baseline (4.3 +/- 2.8%; p < 0.05) and after further 16 weeks, FMD returned to baseline values (5.5 +/- 3.5%). However, metabolic parameters improved significantly. In contrast, NMD and endothelin levels remained unchanged. CONCLUSION: In patients with metabolic syndrome, a sojourn of 3 weeks at moderate altitude leads to a prolonged, but reversible impairment of FMD. The discrepancy to improvement of other cardiovascular and metabolic parameters requires further investigation.

Adult↗

Plasma asymmetric dimethylarginine concentrations in newly diagnosed patients with acute myocardial infarction or unstable angina pectoris during two weeks of medical treatment.

A high concentration of plasma asymmetric dimethylarginine (ADMA) has been associated with several risk factors for atherosclerosis, and this may increase the risk for acute coronary syndromes (ACSs). We measured plasma ADMA concentrations in patients who had newly diagnosed ACS (n = 48), and we followed the changes in ADMA concentrations during these patients' short-term medical therapy, which included various combination of drugs with or without percutaneous coronary interventions according to the needs of each patient. Concentrations of plasma ADMA were found to be high in patients who had ACS compared with 48 age-matched healthy control subjects (3.13 +/- 0.85 vs 1.57 +/- 0.85 mumol/L, p <0.0001). Follow-up measurements of ADMA showed dramatic decreases in plasma ADMA concentrations over 2 weeks of medical therapy for ACS (from 3.27 +/- 0.87 to 1.52 +/- 0.47 mumol/L, p <0.0001). Plasma ADMA at baseline showed a significant positive correlation with serum C-reactive protein and plasma insulin and a significant negative correlation with serum levels of high-density lipoprotein and plasma alpha-tocopherol. During therapy, changes in plasma ADMA concentrations were significantly correlated with changes in the ratio of total cholesterol to high-density lipoprotein cholesterol and in serum C-reactive protein concentrations but not with changes in insulin levels. This study provides the first evidence that plasma ADMA concentrations are significantly high in patients who have ACS and that ADMA concentrations rapidly decrease after short-term medical therapy.

Adult↗

Fatal course of parvovirus B19-associated myocarditis in a female liver transplant recipient.

Acute myocarditis may result in severe hemodynamic compromise with fatal outcome. Furthermore, recent studies suggest myocarditis as a major cause of sudden unexpected death. A variety of cardiotropic viral, rickettsial, and bacterial infectious agents have been identified to date. Parvovirus B19 (PVB19) is usually benign in childhood, but it may also cause death due to myocarditis. We present here the case of an adult female who presented with fatigue, dyspnea on exertion, and orthostatic dizziness 8 months after successful liver transplantation. Cardiologic work-up, including left ventricular endomyocardial biopsy, revealed acute myocarditis secondary to PVB19. Since no specific therapy for this virus is available, the patient was treated symptomatically with an angiotensin-converting enzyme inhibitor plus beta-blocker and diuretics. After a period of stabilization, new-onset rapid atrial fibrillation caused acute low-output syndrome within 14 days after hospital admission. The patient eventually died because of refractory cardiogenic shock. In conclusion, to our knowledge this is the first report of PVB19-induced myocarditis confirmed by detection of viral genome in myocardium in a liver transplant recipient.

Acute Disease↗

An uncommon coronary artery fistula causing survived sudden cardiac death in a young woman.

Although most patients suffering from a coronary artery fistula remain asymptomatic during childhood and adolescence, many of them develop complications in adulthood due to volume overload, endocarditis or ischemia. Here we present a young woman surviving a sudden cardiac death due to myocardial ischemia with subsequent ventricular fibrillation caused by thrombosis of a coronary artery fistula deriving from the left main coronary artery. Parts of the thrombus had been embolized into the circumflex artery causing posterior myocardial infarction. The thrombosis might have been initiated by local compression from a round extracardiac mass of 3 cm with liquid and solid content located between the vena cava superior and the ascending aorta. This structure was suspected to be a hematoma which had been caused by a blunt thoracic trauma while playing soccer 2 weeks before.

Adult↗

Robotic totally endoscopic coronary artery bypass and catheter based coronary intervention in one operative session.

A 56-year-old male patient underwent robotically assisted totally endoscopic left internal mammary artery (LIMA) to left anterior descending artery (LAD) grafting. After protamine administration complete heart block developed in the patient. On intraoperative angiography the LIMA to LAD graft was perfectly patent but an acute occlusion of the right coronary artery (RCA) was noted. We performed an immediate on table percutaneous coronary angioplasty and stent placement to the RCA. The heart regained sinus rhythm and the wall motion abnormalities on the back wall of the heart resolved. No clinical symptoms indicating ongoing myocardial ischemia were noted postoperatively. This case demonstrates that a hybrid procedure of robotic totally endoscopic coronary artery bypass grafting and catheter based coronary intervention is feasible in one simultaneous session.

Angioplasty↗

Chronic heart failure is associated with vascular remodeling of the brachial artery.

AIMS: Endothelial dysfunction has been shown to correlate with severity of congestive heart failure (CHF) and recent data suggest morphological changes of peripheral vasculature to be associated with the syndrome. We therefore investigated the hypothesis that vascular remodeling is associated with functional changes in peripheral conduit arteries and with systemic overexpression of ET-1 in patients suffering from CHF. METHODS AND RESULTS: 57 consecutive patients referred to the Innsbruck Heart Failure and Transplantation Program (EF=23+/-7%) and 16 matched controls (EF=60+/-5%) were studied. Flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), wall thickness (WT), and incremental elastic modulus (Einc) were assessed by high-resolution ultrasound of the brachial artery. FMD (P=0.004) and NMD (P=0.02) were significantly higher in controls as compared to moderate and severe CHF patients. In contrast, brachial artery-wall thickness (BA-WT) was increased in severe CHF patients (P=0.038). BA-WT was significantly correlated with both FMD (r=-0.28; P=0.049) and NMD (r=-0.38; P=0.003), and with the Einc (r=0.45, P=0.001). Lumen diameter was not different among groups. In patients with BA-WT>0.31 mm, bigET-1 was higher compared to BA-WT<0.31 mm (P<0.05). CONCLUSION: CHF is associated with remodeling of the brachial artery, which is characterized by morphological, mechanical and functional changes of the vessel wall. Endothelin-1 may play a role in the vascular remodeling process.

Adult↗

Effects of cardiac resynchronization therapy on ventricular repolarization in patients with congestive heart failure.

INTRODUCTION: Biventricular pacing has been shown to improve the clinical status of patients with congestive heart failure, but little is known about its influence on ventricular repolarization. The aim of our study was to evaluate the effect of biventricular pacing on ECG markers of ventricular repolarization in patients with congestive heart failure. METHODS AND RESULTS: Twenty-five patients with congestive heart failure, sinus rhythm (SR), and complete LBBB (6 females; age 61 +/- 8 years; NYHA class II-III; echocardiographic ejection fraction 21 +/- 5%; QRS > or = 130 ms) underwent permanent biventricular DDDR pacemaker implantation. A high-resolution 65-lead body-surface ECG recording was performed at baseline and during right-, left-, and biventricular pacing, and the total 65-lead root mean square curve of the QRST complex and the interlead QT dispersion were assessed. The QRS duration was increased during right (RV)- and left ventricular (LV) pacing (127 +/- 26% and 117 +/- 40%; P < 0.05), as compared to SR (100%) and biventricular pacing (93 +/- 16%; ns). The QTc interval was increased during RV and LV pacing (112 +/- 12% and 114 +/- 14%; P < 0.05) as compared to SR (100%) or biventricular pacing (99 +/- 12%). There was no effect on JT interval during all pacing modes. The T(peak-end) interval was increased during right (120 +/- 34%; P < 0.01) and LV pacing (113 +/- 29%; P < 0.05) but decreased during biventricular pacing (81 +/- 19%; P < 0.01). A similar effect was found for the T(peak-end) integral and the T(peak) amplitude. QT dispersion was increased during right ventricular (129 +/- 16 ms; P < 0.05) and decreased during biventricular pacing (90 +/- 12 ms; P < 0.01), as compared to SR (114 +/- 22 ms). CONCLUSIONS: Using a high-resolution surface ECG, biventricular pacing resulted in a significant reduction of ECG markers of ventricular dispersion of repolarization.

Aged↗

Capillary deposition of the complement fragment C4d in cardiac allograft biopsies is associated with allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is a long-term threat in heart transplant recipients and its exact pathogenesis remains to be established. As complement activation contributes to early and late allograft dysfunction, we hypothesized that deposition of the complement fragment, C4d, in capillaries of cardiac allograft biopsies may be associated with CAV. A polyclonal anti-C4d antibody was used for immunohistochemistry on endomyocardial biopsies obtained from heart transplant recipients during the first year post-transplantation. CAV was assessed by intracoronary ultrasound performed at 1-year post-transplantation. We were able to show that CAV is highly associated with C4d deposition in capillaries of cardiac allografts and that serial C4d studies may predict development of CAV at 1-year post-transplantation.

Biopsy↗

Cardiac hepatopathy before and after heart transplantation.

Chronic cardiac hepatopathy is a common entity in patients evaluated for heart transplantation (HTX). Hepatic injury is caused by severe heart failure resulting from prolonged recurrent congestion and/or impaired arterial perfusion. No data are available on the reversibility of cardiac hepatopathy in patients undergoing HTX. Data of 56 consecutive adult patients undergoing HTX during 2000-02 at the University Hospital of Innsbruck were analysed retrospectively. The following parameters were evaluated at the time of listing and 3, 6 and 12 months after HTX. Plasma levels of gamma-glutamyl transferase (gamma-GT), alkaline phosphatase (AP), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and total plasma protein. When listed for HTX, only 12% of all patients analysed had physiological values throughout the seven laboratory parameters assessed. Elevated levels of gamma-GT, AP, bilirubin, AST, ALT, LDH and total plasma protein were detected in 66.6%, 29%, 50%, 16.7%, 10%, 40% and 18% of all patients respectively. Accordingly, median plasma levels of gamma-GT, bilirubin and LDH were elevated, whereas the mean plasma level of AP was at the upper normal range. In contrast, median plasma level of AST and mean plasma levels of ALT and total plasma protein were within the normal range: gamma-GT (median, 109.0; range, 634.0 U/l; n = 36), AP (mean, 120.2 +/- 78.9 U/l; n = 29), bilirubin (median, 1.3; range, 16.1 mg/dl; n = 32), LDH (median, 226.0; range, 2355.0 U/l; n = 33), AST (median, 29.0; range, 145.0 U/l; n = 36), ALT (mean, 28.3 +/- 20.8 U/l; n = 36) and total plasma protein (mean, 7.2 +/- 1.1 g/dl; n = 25). Within 3 months after HTX, elevated parameters except LDH significantly ameliorated: gamma-GT (median, 59.0; range, 1160.0 U/l; P = 0.011), AP (92.2 +/- 75.2 U/l; P = 0.016), bilirubin (median, 0.9; range, 8.1 mg/dl; P = 0.004), LDH slightly increased (median, 281.0; range, 543.0 U/l; P = 0.039), but there was a delayed improvement of this parameter after 6 and 12 months post-HTX. End-stage heart failure is characterized by a cholestatic liver enzyme profile with elevated plasma levels of gamma-GT and bilirubin. These parameters significantly improve within 3 months after HTX. Therefore, chronic cardiac hepatopathy seems to be a benign, potentially reversible disease.

Alanine Transaminase↗

Relationship of sonographic wall components of the brachial artery to hypertension and coronary atherosclerosis.

The aim of this study was to determine whether sonographically assessed intimal (echodense, ED) or medial (echolucent, EL) thickening of the brachial artery is associated with coronary artery disease (CAD) and/or arterial hypertension (HT). In 201 patients the ED and EL wall components, as well as the total wall thickness of the brachial artery, were measured with high-resolution ultrasound (13 MHz). According to the presence or absence of CAD and HT, the patients were divided into four groups: no HT and no CAD (n = 26, group 1), CAD (> or = 30% diameter stenosis in > or = 1 major branch) only (n = 63, group 2), HT only (n = 34, group 3), and HT and CAD (n = 78, group 4). EL (p < 0.001) and combined wall thickness (p < 0.001), but not the ED wall component, were significantly different between the groups, with the highest values occurring in group 4. On logistic regression analyses adjusting for age, coronary risk factors and body mass index, EL, but not ED, thickness correlated independently with the presence of CAD (p = 0.04) and HT (p < 0.001). High-resolution ultrasound examination of the brachial artery wall structure may contribute to the noninvasive assessment of early atherosclerosis.

Adult↗

Effects of local gene transfer of VEGF on neointima formation after balloon injury in hypercholesterolemic rabbits.

Enhancement of the generation of nitric oxide (NO) and vascular endothelial growth factor (VEGF) are suggested to prevent restenosis after angioplasty. Accordingly, we tested whether the local delivery of L-arginine (L-Arg), a substrate for NO generation and the VEGF gene, alone or in combination, can influence neointima formation in hypercholesterolemic rabbits. Balloon injury of the iliac arteries was performed in 24 New Zealand White rabbits fed a 1% cholesterol diet for 3 weeks followed by a local infusion of: (1) pSG5VEGF165 plasmid alone (1000 microg); (2) pSG5VEGF165 (1000 microg) with L-Arg (800mg); (3) L-Arg (800mg) alone; and (4) L-Arg (800 mg) with naked pSVbeta-gal plasmid (1000 microg). The animals were kept on the hypercholesterolemic diets for a further 28 days, when vessels were taken for morphometric analysis and immunocytochemistry. Endogenous rabbit VEGF concentration in the plasma increased significantly at 7 days after injury (17.06 +/- 1.57 vs 23.01 +/- 1.9 pg/ml; p < 0.02) and remained elevated for up to 28 days (28.46 +/- 5.24; p < 0.01). Injured arteries exhibited strong immunocytochemical staining for rabbit VEGF. Rabbits that received a VEGF gene transfer revealed more prominent neointima formation, whereas treatment with L-Arg was associated with significantly less intimal thickness (p < 0.05). Local transfer of the VEGF gene does not inhibit neointima formation in hypercholesterolemic rabbits. Our results suggest that VEGF gene therapy applied locally in atherosclerotic arteries may not be beneficial.

Angioplasty, Balloon↗

Natriuretic peptides as markers of mild forms of left ventricular dysfunction: effects of assays on diagnostic performance of markers.

BACKGROUND: We compared the performance of different natriuretic peptides to diagnose mild forms of left ventricular dysfunction (LVD) and investigated the influence of measuring B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) with different assays on the diagnostic performance of these markers. METHODS: We measured BNP (Triage BNP), NT-proBNP (Biomedica), and N-terminal pro-A-type natriuretic peptide (NT-proANP; Biomedica) in 130 consecutive patients (age range, 28-83 years) with clinically suspected mild LVD. In patients with sufficient sample volume, we measured BNP and NT-proBNP with additional assays (Shionoria and Roche, respectively). RESULTS: For identifying patients with mild systolic LVD, BNP and NT-proBNP were the best markers, with mean (95% confidence interval) areas under the curves (AUC) of 0.78 (0.63-0.89) and 0.75 (0.58-0.87), respectively. However, the diagnostic performance of NT-proANP [AUC, 0.64 (0.48-0.77)] was significantly worse than that of BNP (P = 0.014). Both BNP assays (Triage and Shionoria) and both NT-proBNP assays (Biomedica and Roche) performed equally well for the diagnosis of systolic LVD despite the poor agreement between NT-proBNP assays. In patients with isolated diastolic LVD, the diagnostic performance of the Triage BNP [AUC, 0.70 (0.56-0.81)] was significantly better (P = 0.006) than that of Biomedica NT-proBNP [0.49 (0.34-0.65)]. Furthermore, the performance of the Biomedica NT-proBNP assay was significantly worse (P = 0.03) than that of the Roche NT-proBNP assay for diagnosis of isolated diastolic LVD. CONCLUSIONS: The performance of BNP for the diagnosis of systolic or diastolic LVD is not affected by the assay used, whereas the performance of NT-proBNP for the diagnosis of isolated diastolic LVD is assay dependent.

Adult↗

C-reactive protein plasma levels but not factor VII activity predict clinical outcome in patients undergoing elective coronary intervention.

BACKGROUND: Both vascular inflammation as determined by C-reactive protein (CRP) and extrinsic coagulation as measured by factor VII activity (F VII) may predict clinical restenosis rate in patients with stable angina pectoris undergoing elective percutaneous coronary intervention (PCI). HYPOTHESIS: The primary objective of this study was to investigate the associations between baseline CRP levels, F VII activity, and restenosis rate after elective PCI in a 6-month follow-up period. METHODS: This prospective study included 81 patients aged > or = 19 years undergoing PCI for angiographically significant (> or = 70%) stenosis, with or without stenting, and 49 controls. Factor VII activity and CRP were measured in samples collected at angiography and 16-24 h post procedure after overnight fast. Successful PCI was defined as final diameter of < 50% with TIMI 3 flow and no complication within 1 h. After 6 months all patients who had undergone PCI were evaluated via a standardized questionnaire. Clinical restenosis was defined as the occurrence of a major adverse coronary events (MACE), within the follow-up period. RESULTS: Diagnostic angiography led to a significant increase in CRP levels after 16-20 h in patients with discrete CAD (n = 22) but not in patients without any signs of coronary atherosclerosis (n = 27). During a 6-month follow-up after PCI, 17 of 81 (21%) patients developed MACE. Tertiles of CRP levels independently predicted clinical restenosis, as it developed in 33.3% of patients with the highest CRP levels (0.7-4.8 mg/dl), in 16.6% of patients with second tertile CRP levels (0.23-0.69 mg/dl), and in 7.4% of patients with lowest tertile CRP levels (0.0-0.22 mg/dl). There was a significant difference in the restenosis rate between patients from the first and the third tertiles (p = 0.018). Successful PCI was associated with a significant decrease of mean CRP levels after 6 months, whereas PCI in patients suffering from MACE led to no change in CRP levels. There was no association between factor VII activity and clinical outcome after PCI, and F VII activity did not change over a 6-month period. CONCLUSIONS: In patients with stable angina pectoris undergoing elective PCI, increased preprocedural and 6-month follow-up CRP plasma levels are associated with clinical restenosis. Factor VII plasma activity lacks such correlations.

Adult↗

Intermittent hypoxia increases exercise tolerance in elderly men with and without coronary artery disease.

BACKGROUND: Intermittent hypoxia has been suggested to increase exercise tolerance by enhancing stress resistance and improving oxygen delivery. Because the improvement of exercise tolerance reduces mortality in the elderly with and without coronary artery disease intermittent hypoxia might be a valuable preventive and therapeutic tool. However, controlled studies are lacking. METHODS AND RESULTS: Sixteen males (50-70 years, 8 with and 8 without prior myocardial infarction) were randomly assigned in a double-blind fashion to receive 15 sessions of passive intermittent hypoxia (hypoxia group) or normoxia (control group) within 3 weeks. For the hypoxia group each session consisted of three to five hypoxic (14-10% oxygen) periods (3-5 min) with 3-min normoxic intervals. Controls inhaled only normoxic air in the same way. Exercise tests were performed before and after the 3-week breathing program. After 3 weeks of intermittent hypoxia peak oxygen consumption had increased compared to normoxic conditions (+ 6.2% vs.-3%, p < 0.001). This improvement was closely related to the enhanced arterial oxygen content after hypoxia (r = 0.9, p < 0.001). Both higher haemoglobin concentration and less arterial oxygen desaturation during exercise contributed to the increase in arterial oxygen content. During sub-maximal exercise (cycling at 1 W/kg) heart rate, systolic blood pressure, blood lactate concentration, and the rating of perceived exertion were diminished after intermittent hypoxia compared to control conditions (all p < 0.05). Changes in responses to exercise after intermittent hypoxia were similar in subjects with and without prior myocardial infarction. CONCLUSIONS: Three weeks of passive short-term intermittent hypoxic exposures increased aerobic capacity and exercise tolerance in elderly men with and without coronary artery disease.

Aged↗

Cardiac phosphorus-31 two-dimensional chemical shift imaging in patients with hereditary hemochromatosis.

Hemochromatosis is a hereditary iron overload syndrome characterized by increased iron storage, followed by liver cirrhosis and is often associated with restrictive cardiomyopathy. The purpose of this study was to detect alterations of cardiac high-energy phosphate metabolism in patients with hereditary hemochromatosis (HHC) prior to the development of structural heart diseases. Therefore cardiac phosphorus-31 two-dimensional chemical shift imaging ((31)P 2D CSI) was employed. Twenty-four male patients (mean age 47.2 +/- 12 years) homozygous for the C282Y mutation in the hemochromatosis associated HFE gene and twenty-four male healthy volunteers (mean age 47 +/- 11 years) as age-matched controls were included in this study. Using a 1.5-Tesla whole-body magnetic resonance scanner, electrocardiograph-triggered transversal 31P 2D CSI was performed. Left ventricle mean phosphocreatine (PCr) to beta-adenosine triphosphate (beta-ATP) ratios of patients with HHC (1.60 +/- 0.41) were significantly decreased in comparison to healthy volunteers (1.93 +/- 0.36; p = 0.004). Furthermore, we detected moderate, negative correlations between left ventricular PCr to beta-ATP ratios and transferrin saturation, cholesterol, low-density lipoprotein as well as triglyceride. This study shows that 31P 2D CSI permits the detection of alterations of cardiac high-energy phosphate metabolism in patients with HHC, but without any evidence for heart disease. The decreased PCr to beta-ATP ratios in HHC might be caused by mitochondrial impairment due to cardiac iron overload.

Adenosine Triphosphate↗

Comparison of the specificity of implantable dual chamber defibrillator detection algorithms.

The aim of the study was to compare the specificity of dual chamber ICDs detection algorithms for correct classification of supraventricular tachyarrhythmias derived from clinical studies according to their size to detect an impact of sample size on the specificity. Furthermore, the study sought to compare the specificities of detection algorithms calculated from clinical data with the specificity calculated from simulations of tachyarrhythmias. A survey was conducted of all available sources providing data regarding the specificity of five dual chamber ICDs. The specificity was correlated with the number of patients included, number of episodes, and number of supraventricular tachyarrhythmias recorded. The simulation was performed using tachyarrhythmias recorded in the electrophysiology laboratory. The range of the number of patients included into the studies was 78-1,029, the range of the total number of episodes recorded was 362-5,788, and the range of the number of supraventricular tachyarrhythmias used for calculation of the specificity for correct detection of these arrhythmias was 100 (Biotronik) to 1662 (Medtronic). The specificity for correct detection of supraventricular tachyarrhythmias was 90% (Biotronik), 89% (ELA Medical), 89% (Guidant), 68% (Medtronic), and 76% (St. Jude Medical). There was an inverse correlation (r = -0.9, P = 0.037) between the specificity for correct classification of supraventricular tachyarrhythmias and the number of patients. The specificity for correct detection of supraventricular tachyarrhythmias calculated from the simulation after correction for the clinical prevalence of the simulated tachyarrhythmias was 95% (Biotronik), 99% (ELA Medical), 94% (Guidant), 93% (Medtronic), and 92% (St. Jude Medical). In conclusion, the specificity of ICD detection algorithms calculated from clinical studies or registries may depend on the number of patients studied. Therefore, a direct comparison between different detection algorithms based on clinical data is difficult. In contrast, simulation of supraventricular tachyarrhythmias using a uniform database may be a better tool for direct comparison of the specificity of ICD detection algorithms.

Arrhythmias, Cardiac↗

Ischemic preconditioning exaggerates cardiac damage in PKC-delta null mice.

Ischemic preconditioning confers cardiac protection during subsequent ischemia-reperfusion, in which protein kinase C (PKC) is believed to play an essential role, but controversial data exist concerning the PKC-delta isoform. In an accompanying study (26), we described metabolic changes in PKC-delta knockout mice. We now wanted to explore their effect on early preconditioning. Both PKC-delta(-/-) and PKC-delta(+/+) mice underwent three cycles of 5-min left descending artery occlusion/5-min reperfusion, followed by 30-min occlusion and 2-h reperfusion. Unexpectedly, preconditioning exaggerated ischemia-reperfusion injury in PKC-delta(-/-) mice. Whereas ischemic preconditioning increased superoxide anion production in PKC-delta(+/+) hearts, no increase in reactive oxygen species was observed in PKC-delta(-/-) hearts. Proteomic analysis of preconditioned PKC-delta(+/+) hearts revealed profound changes in enzymes related to energy metabolism, e.g., NADH dehydrogenase and ATP synthase, with partial fragmentation of these mitochondrial enzymes and of the E(2) component of the pyruvate dehydrogenase complex. Interestingly, fragmentation of mitochondrial enzymes was not observed in PKC-delta(-/-) hearts. High-resolution NMR analysis of cardiac metabolites demonstrated a similar rise of phosphocreatine in PKC-delta(+/+) and PKC-delta(-/-) hearts, but the preconditioning-induced increase in phosphocholine, alanine, carnitine, and glycine was restricted to PKC-delta(+/+) hearts, whereas lactate concentrations were higher in PKC-delta(-/-) hearts. Taken together, our results suggest that reactive oxygen species generated during ischemic preconditioning might alter mitochondrial metabolism by oxidizing key mitochondrial enzymes and that metabolic adaptation to preconditioning is impaired in PKC-delta(-/-) hearts.

Acetyltransferases↗