INCREASED RESISTANCE AGAINST SHORTENING IN MYOCARDIUM FROM RECIPIENT HEARTS OF 7 PATIENTS TRANSPLANTED FOR DILATED CARDIOMYOPATHY

The contractile behaviour of demembranized atrial and ventricular myoc ardium of 7 patients transplanted for end-stage heart failure (ESHF) w as analyzed. Atrial muscle specimens of patients undergoing coronary a rtery bypass surgery (n=9) and pig papillary muscle were used as refer ence preparations (n=9). Extreme care was taken for dissection and mou nting the muscle fibres (0.3 x 6 mm) in order to keep the passive seri es compliance small. Calcium sensitivity, cross-bridge cycling rate (e stimated by the force-clamping technique and calculation of the shorte ning velocity at zero load [Vmax]) and isometric force development wer e measured. Analysis on light- and electronmicroscopic level was carri ed out. Results: 1) Calcium sensitivity was not altered in ESHF patien ts; 2) the velocity of the force generating process (cross-bridge cycl ing rate) was normal in ventricular and reduced in atrial ESHF myocard ium, 3) maximum isometric force development was reduced in ventricular , but not in atrial myocardium of ESHF patients, and 4) Vmax was signi ficantly reduced in ventricular and atrial ESHF myocardium (p < 0.0001 ). Perimysial and endomysial fibrosis was present in ventricular, not in atrial myocardium of ESHF patients. Conclusion: A normal cross-brid ge cycling rate in left-ventricular ESHF myocardium combined with a de creased capability of muscle shortening indicates the presence of a re sistance against shortening localized either on the cross-bridge level or/and due to intra- and pericellular fibrosis. Left-ventricular cont ractile dysfunction in patients with end-stage heart failure may be re lated to a normal contractile apparatus contracting within an abnormal intracellular or interstitial environment.