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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

Cornelia Piper, MD^*, Johannes Bilger, MD, Eva-Maria Henrichs, Heinz-Peter Schultheiss, MD, FESC, Dieter Horstkotte, MD, FESC^* and Andrea Doerner, PhD

^* Department of Cardiology, Heart Center North Rhine-Westphalia, University Hospital of the Ruhr University of Bochum, Bad Oeynhausen, Germany
Department of Cardiology, Benjamin Franklin Hospital, Free University of Berlin, Berlin, Germany

View larger version (41K): [in a new window]   Figure 1 Total EXCH mRNA quantification by competitive PCR. A constant amount of total RNA (7.5 ng), isolated from an endomyocardial biopsy from a patient suffering from DCM, was mixed with a decreasing amount of competitor cRNA, reverse transcribed and amplified by PCR.

View larger version (19K): [in a new window]   Figure 2 Plots showing a significant difference (p < 0.05) between the Na+/Ca2+ exchanger mRNA levels of explanted hearts (expl) from patients with end-stage heart failure and those found in endomyocardial tissues of controls (c), of patients with aortic stenosis (AS), aortic or mitral regurgitation (AR/MR), and of dilated cardiomyopathy (DCM).

View larger version (16K): [in a new window]   Figure 3 No significant changes in the Na+/Ca2+ exchanger mRNA transcription level were obtained within patients with chronic heart failure (CHF) irrespective of left ventricular ejection fractions (EFs): EF 50%, EF = 30%–49% or EF < 30%. But a significant (p < 0.01) difference in EXCH transcription was found between patients with severe CHF (EF < 30%) and explanted hearts (expl), although EF was reduced similarly.

View larger version (14K): [in a new window]   Figure 4 Plots showing a significant difference (p < 0.01) in the EXCH transcription level, even between CHF in NYHA IV and expl, although the clinical situation was similar. Otherwise, a nonsignificant tendency toward lower EXCH mRNA levels was found in NYHA I/II compared with NYHA III/IV for VHD, not seen in DCM.

View larger version (18K): [in a new window]   Figure 5 No significant elevation in EXCH transcription level in CHF according to systolic wall stress, a parameter indicating the state of myocardial adaptation to increased workload, is demonstrated.