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Notes: Abstract The case of a 30-year-old man with primary systemic amyloidosis is reported. Three months prior to admission the patient developed fever, night sweats, dyspnea, and bilateral ankle swelling. Recurrent left-sided pleural effusion led to further investigation when massive proteinuria with free monoclonal lambda chains in the urine became evident. Abdominal subcutaneous fat aspiration and renal biopsy confirmed the diagnosis of amyloidosis. Bone marrow biopsy and bone scan did not reveal multiple myeloma. Echocardiography showed a sparkling texture of the interventricular septum. Pulsed-wave Doppler recording of the left ventricular inflow profile showed the pattern of advanced cardiac amyloidosis consistent with markedly impaired diastolic heart function. Electrocardiogram-gated magnetic resonance imaging was carried out for noninvasive evaluation of cardiac function. The patient was started on repeated courses of melphalan, prednisone, and colchicine therapy. Despite increasing deterioration of renal function the therapy was tolerated quite well, and the patient is still alive 10 months after initial diagnosis. Although very rare in this age, primary systemic amyloidosis should be considered as a cause of pleural effusion, proteinuria, and congestive heart failure and should lead to further investigation.

Notes: Summary Thrombus formation at the site of atherosclerotic lesions, especially on a ruptured plaque, plays a central role in the “atherothrombosis” hypothesis. An activation of the hemostasis and a disturbed fibrinolysis are known. These alterations are especially marked in patients with acute coronary syndromes. In stable coronary artery disease, fibrinogen is elevated. Furthermore, minor alterations of the contact phase factor VII and consecutively of the thrombin system are detectable depending on the study population. Thrombin generation and activation become marked in patients with unstable angina pectoris or acute myocardial infarction. Possible reasons for this activation are an activation of the contact phase factor XII system and the release of tissue factor both from the ruptured plaque and from stimulated monocytes. The fibrinolytic system is markedly altered already in patients with stable coronary heart disease. Increased levels of tissue-type plasminogen activator and of urokinase-type plasminogen activator/receptor are measurable in atheromas. Tissue-type plasminogen activator mass concentration is systemically elevated already at early stages of atherosclerosis. Especially in patients with increased risk for acute coronary syndromes, the plasminogen activator inhibitor activity is significantly increased. Furthermore, a hypercoagulative state with increased d-dimer levels and plasmin-antiplasmin complexes can be measured. The alterations of hemostasis and especially of fibrinolysis are detectable for prolonged time period and persist much longer than the clinical symptoms of the patients. The increased plasminogen activator inhibitor activity is associated with the metabolic syndrome and constitutes an (in part genetically determined) disturbance in patients with stable or unstable coronary heart disease. However, the large intra- and interobserver as well as diurnal variability of this marker limits its use as a routine measure for risk stratification in patients. Alterations of the hemostasis and disturbances of fibrinolysis are detectable during the chronic as well as the acute phase of atherosclerosis. These changes are best documented for coronary heart disease, whereas less data are available for other manifestations of atherosclerosis. The use of newly developed molecular markers for single reaction steps of pathways instead of global functional tests and of new molecular biological methods did considerably improve the detailed knowledge on the pathomechanisms of the development of atherosclerosis, making the development of targeted therapies, e.g., against receptors possible. Future studies will investigate the quantitative impact of the varios activated pathways (cause or reaction) and the effects of interventions on these pathomechanisms in patients with acute coronary syndromes. Studies will have to focus especially on the meaning of polymorphisms, early changes in the development of atherosclerosis and interactions with inflammatory processes.

Notes: Abstract Background Non-hypertrophied reversibly injured postischemic myocardium can be stimulated for a prolonged period without detrimental effects. Since no data on hypertrophied myocardium are available, our aim was to examine the effects of a prolonged postischemic positive inotropic stimulation on moderately hypertrophied left ventricles. Methods Using a Langendorrf-type isovolumically contracting isolated heart model, moderately hypertrophied (+50% of ventricular mass) hearts from spontaneously hypertensive rats (SHR) were investigated and compared to data from non-hypertrophied hearts of normotensive rats. A 30 minutes noflow ischemia was performed, and in the postischemic period dopamine was continuously administered for 20 minutes in order to stimulate the postischemic hearts to the control level of function. Data were compared to postischemic hearts without stimulation and to non-ischemic controls. After 50 minutes of reperfusion and cessation of the catecholamine steady state function, maximum contractile response, and high energy phosphates were determined. Results 30 minutes ischemia followed by 50 minutes reperfusion caused a significant reduction in developed LVP to 77.8±4.2% in SHR. Dp/dtmax was reduced to 67.0±2.3%. After cessation of dopamine stimulation developed LVP was 64.3±3.5% and dp/dtmax 69.3±3.7% in SHR. The double product was identically reduced in all postischemic groups. The contractile reserve was comparable in stimulated and non-stimulated postischemic SHR hearts. In hypertrophied myocardium, ATP was reduced to 1.1±0.1 μmol/gww (non-ischemic controls 2.5±0.3 μmol/gww) in unstimulated and to 1.0±0.1 μmol/gww in stimulated postischemic hearts. Comparably the ischemia-induced reduction in ATP in non-hypertrophied myocardium was 1.3 μmol/gww. Similar results were obtained for ADP and AMP. Creatine phosphate levels were normal in stimulated and non-stimulated postischemic myocardium of hypertrophied and non-hypertrophied hearts. Conclusion These results indicate that prolonged stimulation of stunned hypertrophied myocardium is feasible without detrimental effects on poststimulation contractile function. The energy generating apparatus is capable to deliver sufficient energy during stimulation of stunned hypertrophied hearts.

Notes: Abstract Background: A reduction in coronary flow leads to a parallel decrease in contractile function. Thus, a flow/function balance is established in the myocardium under certain circumstances avoiding the development of a necrosis (referred to as “hibernating” myocardium). The impact of a preconditioning period on this critical balance was examined. Methods: In 116 isovolumetrically beating rat hearts, 3 h of hypoperfusion with 15% of control coronary flow were performed followed by 1 h reperfusion; 40 hearts served as controls. As a preconditioning period, in half of the rat hearts a 5 min no-flow ischemia followed by 10 min reperfusion was performed, preceding the prolonged hypoperfusion. Results: Systolic function was identically reduced in both groups after 3 h hypoperfusion (LVP: 39±2 mmHg, 40±2 mmHg vs. controls 90±3 mmHg; p〈0.01). Without preconditioning hypoperfusion resulted in a marked initial decrease in function. This period was followed by an adaptation to a higher steady state level of function compared with non-preconditioned hyperperfused hearts (p〈0.05). After preconditioning hypoperfusion directly resulted in this level of contraction. Contractile reserve was reduced (p〈0.01) identically in both hypoperfusion groups. Adenine nucleotides were decreased (p〈0.01) after 3 h hypoperfusion to 2.1±0.2 μmol/gww vs. controls (4.7±0.2 μmol/gww). After initial preconditioning adenine nucleotides were better preserved (3.2±0.2 μmol/gww) going ahead with a creatine phosphate overshoot of 126% (p〈0.01). After reperfusion, systolic function and contractile reserve were identical in both groups. Conclusion: A period of preceding no-flow ischemia followed by reperfusion modifies functional adaptation to hypoperfusion and preserves high energy phosphates. Therefore, the metabolic balance during hypoperfusion is improved by preconditioning, although no impact on contractile reserve or the functional status of reperfused myocardium after low-flow ischemia can be seen.

Notes: Zusammenfassung Das morphologische Korrelat akuter koronarer Syndrome stellt in der Mehrzahl die Plaquefissur mit aufgelagertem intraluminalem Thrombus dar. Assoziiert ist eine Aktivierung von inflammatorischen und Gerinnungs- bzw. Fibrinolysewegen, einschließlich einer Komplementaktivierung sowie eine Aktivierung von korpuskulären Blutbestandteilen. Marker wie CRP, Fibrinogen, Plasminogenaktivator-Inhibitor bzw. Gewebeplasminogenaktivator-Antigen besitzen prognostische Bedeutung zur Identifizierung von Patienten mit erhöhtem Risiko für ein akutes koronares Ereignis. Histologisch finden sich gehäuft Leukozyteninfiltrate im Bereich der Plaquefissur, zusätzlich sind Assoziationen mit Infektionen durch verschiedene Erreger beschrieben worden. Ungeklärt ist, welchen Anteil die unterschiedlichen Faktoren am Auftreten einer Plaqueruptur und an der konsekutiven Thrombusauflagerung besitzen. Es ist anzunehmen, daß vielfach Plaquerupturen ohne kritische Stenosierung ablaufen und nicht bemerkt werden; dies erschwert die klinische Evaluierung kausaler Zusammenhänge. Zukünftige Studien sollten die komplexe Interaktion der verschiedenen Systeme durch parallele Messung unterschiedlicher Aktivierungsmarker im zeitlichen Verlauf näher untersuchen. Die relative Bedeutung einzelner Faktoren bzw. die Redundanz nach experimentellem Ausschalten eines Faktors für den Ablauf der pathophysiologischen Prozesse bei akuten koronaren Syndromen muß ebenso wie die Bedeutung infektiöser Prozesse weiter geklärt werden.