Intrapericardial procedures for cardiac regeneration by stem cells: need for minimal invasive access (AttachLifter) to the normal pericardial cavity.

In view of the only modest functional and anatomical improvements achieved by bone marrow-derived cell transplantation in patients with heart disease, the question was addressed whether the intracoronary, transcoronary-venous, and intramyocardial delivery routes are adequate. It is hypothesized that an intrapericardial delivery of stem cells or activators of resident cardiac stem cells increases therapeutic benefits. From such an intrapericardial depot, cells or modulating factors, such as thymosin ß4 or Ac-SDKP, are expected to reach the myocardium with sustained kinetics. Novel tools which provide access to the pericardial space even in the absence of pericardial effusion are, therefore, described. When the pericardium becomes attached to the suction head (monitored by an increase in negative pressure), the pericardium is lifted from the epicardium ("AttachLifter"). The opening of the suction head ("Attacher") is narrowed by flexible clamps which grab the tissue and improve the vacuum seal in the case of uneven tissue. A ridge, i.e.,"needle guidance", on the suction head excludes injury to the epicardium, whereby the pericardium is punctured by a needle which resides outside the suction head. A fiberscope can be used to inspect the pericardium prior to puncture. Based on these procedures, the role of the pericardial space and the presence of pericardial effusion in cardiac regeneration can be assessed.

Inverse shift in serum polyunsaturated and monounsaturated fatty acids is associated with adverse dilatation of the heart.

BACKGROUND: Cardiac dilatation is associated with impaired pump function, progression of heart failure and electrical instability. Risk of sudden death is associated with a low blood level of n-3 polyunsaturated fatty acids. OBJECTIVE: The hypothesis was, therefore, addressed that left ventricular dilatation as assessed by echocardiography is associated with a reduced serum polyunsaturated fatty acid level. METHODS: Fatty acids were determined with gas chromatography/mass spectrometry in serum of 308 patients with dilative heart failure unrelated to myocardial infarction (age 48 (SD12) years, NYHA class 2.2 (0.6), ejection fraction 31% (10%)). RESULTS: The extent of left ventricular dilatation as assessed by left ventricular end-diastolic diameter was associated with a reduction of both n-3 and n-6 polyunsaturated fatty acids. The n-3 docosahexaenoic acid (1.0% (0.5%) vs 1.3% (0.6%), p<0.001) and the n-6 arachidonic acid (4.6% (1.8%) vs 5.2% (1.9%), p<0.01) were reduced in patients with left ventricular dilatation (end-diastolic diameter, 68-90 mm, upper tertile vs 48-61 mm, lower tertile). By contrast, monounsaturated fatty acids were increased (the n-9 oleic acid 26.1% (4.8%) vs 23.9% (4.8%), p<0.01). A low docosahexaenoic acid (0.01-0.9%, lower tertile vs 1.4-3.1%, upper tertile) was associated with greater left ventricular dilatation (end-diastolic diameter, 67 (8) vs 63 (7) mm, p<0.001). The cut-off for the absence of severe dilatation (end-diastolic diameter >70 mm) was set at >1.24% docosahexaenoic acid. In our sample, the negative-predictive value for severe dilatation was 91% and sensitivity was 84%. CONCLUSIONS: Docosahexaenoic acid provides a new sensitive biomarker for monitoring and detecting severe left ventricular dilatation in heart failure patients.

[Metabolism and the hypertrophied heart of the elderly]. / Stoffwechsel und hypertrophiertes Altersherz -- Ein Indikationsziel für die Pharmakagruppe "Fettsäurenoxidationshemmer mit PPARalpha-Aktivierung"?

In elderly patients, an inadequately treated high blood pressure often leads to hypertrophied cardiomyocytes with various defects in gene expression. Due to a decreased expression of the transcription factor PPARalpha, fatty acid oxidation is reduced. If it can be compensated by an increased glucose oxidation, it has been considered as a favorable process. Nonetheless, reduced PPARalpha influences ensue involving e. g. anti-inflammatory mechanisms. The question arises thus whether drugs can normalize reduced PPARalpha effects without increasing fatty acid oxidation. As lead compound of these "fatty acid oxidation inhibitors with PPARalpha activation", the carnitine palmitoyltransferase-1 inhibitor etomoxir was characterized. An increased expression and activity of the Ca (2+) pump of sarcoplasmic reticulum, a faster relaxation and a slowed progression of heart failure was observed in animal experiments. It should, therefore, be examined whether the impaired function of pressure overloaded hypertrophied cardiomyocytes of particularly elderly patients should be a therapeutic target before progression of heart failure, neuroendocrine activation and symptoms such as shortness of breath occur.