[Is Na+Ca(2+) exchanger expression altered in the endomyocardium of patients with chronic heart valve diseases parallel to myocardial dysfunction?]. / Andert sich die Na+Ca(2+)-Exchanger-Expression im Endomyokard von Patienten mit chronischen Herzklappenfehlern parallel zur Störung der myokardialen Pumpfunktion?

BACKGROUND: Na(+)-Ca2+ exchanger (EXCH) is an important regulator of intracellular calcium homeostasis. To maintain a normal intracellular Ca2+ concentration, EXCH expression may be upregulated before the onset of end-stage heart failure. We tested for a correlation between the EXCH transcription level and the degree of myocardial dysfunction as well as the suitability of EXCH transcription as a molecular marker for early detection of a transition from adequate to inadequate myocardial adaptation to chronic pressure and/or volume overload in valvular heart disease (VHD). METHODS: The level of EXCH transcription was analyzed in myocardial biopsies from eleven patients with aortic stenosis (AS), five with aortic regurgitation (AR) and six with primary mitral regurgitation (MR) of different hemodynamic severity and myocardial impairment using the quantitative rt-PCR technique. In addition, endomyocardial tissue from thirteen explanted hearts with end-stage heart failure and biopsies from seven individuals without heart disease were investigated. RESULTS: The mean level of EXCH transcription in patients with AS was: 1.8 +/- 1.4 amol/ng total RNA, with AR: 1.9 +/- 0.8 amol/ng and with MR: 2.2 +/- +2.1 amol/ng. This was not from different controls (2.6 +/- 1.2 amol/ng total RNA). However, in myocardium from end-stage heart failure, EXCH transcription was increased fourfold amounting to 8.9 +/- 1.9 amol/ng total RNA. No difference in the EXCH transcription was found in VHD with respect to the degree of myocardial dysfunction: cardiac index (CI) > 3.5 l/min/m2 (EXCH 1.4 +/- 1.1 amol/ng total RNA); CI 3.5-2.4 (EXCH 2.5 +/- 1.8); CI < 2.4 (EXCH 1.8 +/- 1.0); EF-angio > 50% (EXCH 1.9 +/- 1.8); EF-angio < or = 50% (EXCH 1.9 +/- 0.9); EF-RNV > 50% (EXCH 2.4 +/- 1.8), EF-RNV < or = 50% (EXCH 1.7 +/- 1.0). CONCLUSION: Myocardial EXCH transcription does not change parallel to the degree of myocardial dysfunction in VHD. Consequently, myocardial EXCH transcription does not appear to be suitable as a parameter indicating the transition from adequate to inadequate myocardial adaptation to chronic volume and/or pressure overload.

Is myocardial Na+/Ca2+ exchanger transcription a marker for different stages of myocardial dysfunction? Quantitative polymerase chain reaction of the messenger RNA in endomyocardial biopsies of patients with heart failure.

OBJECTIVES: This study was designed to determine the stage of myocardial dysfunction at which an upregulation of the Na+/Ca2+ exchanger (EXCH) transcription takes place. BACKGROUND: Because EXCH is an important regulator of intracellular calcium homeostasis, alterations in EXCH expression may occur before the onset of end-stage heart failure (HF) to maintain normal intracellular Ca2+ concentrations. We analyzed whether the EXCH transcription level is correlated to the degree of myocardial dysfunction and whether it can be a suitable molecular marker to define the transition to myocardial decompensation early on. METHODS: By quantitative polymerase chain reaction technique, the level of EXCH transcription was analyzed in myocardial biopsies from 40 patients with various degrees of myocardial dysfunction due to valvular heart disease (VHD; n = 22) or dilated cardiomyopathy (DCM; n = 18). Additionally, biopsies from 7 individuals with excluded heart disease and explanted heart tissue from 13 patients with end-stage HF were investigated. RESULTS: The level of EXCH transcription of controls (2.6 +/- 1.2 attomoles [amol]/ng total RNA) did not differ from that of patients with DCM (2.3 +/- 1.5 amol/ng) or VHD (2.1 +/- 1.5 amol/ng). No alteration in the EXCH transcription was found in VHD and DCM patients with respect to the severity of myocardial dysfunction. However, patients with end-stage HF showed a four-fold increase in EXCH transcription, amounting to 8.9 +/- 1.9 amol/ng (p < 0.05). CONCLUSIONS: The upregulation in EXCH transcription either occurs very late in human heart failure or is a phenomenon of heart transplantation in end-stage HF. Consequently, myocardial EXCH transcription cannot be used as a marker for early myocardial decompensation.

Tissue-specific transcription pattern of the adenine nucleotide translocase isoforms in humans.

Three adenine nucleotide translocase isoforms (ANT1, ANT2 and ANT3) are coded by different genes. The relative amounts of the three ANT isoform mRNAs were determined in detail in various human tissues. ANT isoforms were co-expressed in all tested tissues revealing tissue-specific transcription patterns. The highest ANT1 mRNA proportions were found in terminally differentiated tissues like skeletal muscle, heart and brain, whereas ANT2 was mainly expressed in tissues capable of proliferation and regeneration as in the kidneys, spleen, liver, fibroblasts and lymphocytes. The ANT3 mRNA proportion was not prominently expressed in any of the tissues tested. In conclusion, tissue-specific expression of ANT isoforms is strongly related to the state of cellular differentiation.

[Acute myocardial infarct caused by a muscle bridge of the anterior interventricular ramus: complicated course with vascular perforation after stent implantation]. / Akuter Myokardinfarkt bei Muskelbrücke des Ramus interventricularis anterior: Komplizierter Verlauf mit Gefässperforation nach Stent-Implantation.

UNLABELLED: A 47-year-old male patient was admitted to our hospital with acute anterior myocardial infarction. Immediate coronary angiography was carried out, which showed proximal occlusion of the left anterior descending artery (LAD). After mechanical recanalization, a reduction in vessel caliber at the site of occlusion was visible, and balloon angioplasty with consecutive stent implantation because of vessel wall dissection was performed. After the procedure, diameter reduction of the entire vessel segment distal to the stent and muscular bridging with subtotal systolic obliteration of the LAD and one diagonal branch were demonstrated. Diastolic coronary flow did not appear to be limited (TIMI 3). Dipyridamole-thallium cardiac imaging revealed an incomplete perfusion defect of the anteroseptal region and a reversible perfusion reduction of the anterolateral region. For definitive treatment, we decided to implant a 3.0 mm-stent at the site of muscular bridging. Although balloon sizing was adapted to the diameter of the proximal reference segment, measured by quantitative coronary angiography, coronary perforation into the right ventricular outflow tract due to balloon oversizing in the distal dilation segment occurred. The patient remained asymptomatic at rest as well as under exercise testing, and hemodynamics remained stable. Coronary re-angiography after 1 week demonstrated a persistent fistula with complete opacification of the LAD and normal coronary flow (TIMI 3). Within the following 3 months, the coronary fistula closed spontaneously. CONCLUSIONS: Muscular bridging is a rare cause of acute myocardial infarction. Balloon angioplasty and stent implantation in the bridged segment may be complicated by coronary artery perforation due to balloon oversizing. Risks and benefits of this therapeutic option, therefore, have to be critically evaluated, and careful selection of balloon size using measurements of proximal and distal reference diameter assessed by intravascular ultrasound is recommended. Coronary artery perforation into the myocardium with subsequent development of a fistula may be treated conservatively as long as the patient remains asymptomatic. The frequency of spontaneous closure of the fistula is high.

Gene expression of the cardiac Na(+)-Ca2+ exchanger in end-stage human heart failure.

The regulation of cytosolic Ca2+ concentration during excitation-contraction coupling is altered in the failing human heart. Previous studies have focused on disturbances in Ca2+ release and reuptake from the sarcoplasmic reticulum (SR), whereas functional studies of the cardiac Na(+)-Ca2+ exchanger, another important determinant of myocyte homeostasis, are lacking for the failing human heart. Using a cardiac Na(+)-Ca2+ exchanger cDNA recently cloned from a guinea pig cDNA library, we investigated the gene expression of the cardiac Na(+)-Ca2+ exchanger in relation to the SR Ca(2+)-ATPase. Expression of both genes was quantified in left ventricular myocardium from 24 failing human cardiac explants and 7 control heart samples in relation to beta-myosin heavy chain mRNA by slot blot analysis. Compared with patients with nonfailing hearts, patients with dilated cardiomyopathy (DCM, n = 13) showed a 55% increase in Na(+)-Ca2+ exchanger mRNA levels (P < .05 versus control value) and a 41% increase in patients with coronary artery disease (CAD, n = 11). In the same hearts, SR Ca(2+)-ATPase mRNA levels were decreased by 50% in DCM and by 45% in CAD (P < .05 for both versus control value). There was a positive correlation between Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase mRNA levels both in normal and failing human hearts, albeit with different slopes and intercepts of the regression line. The Na(+)-Ca2+ exchanger protein levels as assessed by Western blot analysis and normalized to beta-myosin heavy chain protein were increased in DCM and CAD (P < .05 and P < .01 versus control value, respectively), whereas SR Ca(2+)-ATPase protein levels were reduced (P < .05 for both groups versus control values). Thus, the Na(+)-Ca2+ exchanger gene expression is enhanced in failing human hearts and may, in part, compensate for the depressed SR function with regard to diastolic Ca2+ removal.

Plate fixation for open mandibular fractures.

Eighty-one patients with mandibular fractures were treated between November 1978 and November 1983. Twenty-six of these patients had 47 comminuted open fractures treated with rigid internal fixation utilizing AO compression plating. No infected nonunion, osteomyelitis, or plate extrusion occurred. Occlusal relationships of remaining dentition were maintained with normal mandibular function in all patients. Rigid internal fixation is an excellent method for stabilizing and repairing comminuted open mandibular fractures. The technique provides immediate return of mandibular function which may be critical in the management of the polytraumatized patient.