1. ¹'Cuore e Grossi Vasi, Attilio Reale' Department, La Sapienza University, Rome, Italy
2. ²IRCCS Ospedale Multimedica, Milan, Italy
3. ³Experimental Medicine and Pathology Department, La Sapienza University, Rome, Italy
4. ⁴IRCCS San Raffaele Pisana, Rome, Italy
5. ⁵IRCCS National Institute for Infectious Diseases, Lazzaro Spallanzani, Rome, Italy

Correspondence: Dr A Frustaci, MD, 'Cuore e Grossi Vasi, Attilio Reale' Department, La Sapienza University, Viale Regina Elena, 324–00161 Rome, Italy. E-mail: biocard@rm.unicatt.it

Received 29 December 2005; Revised 27 February 2006; Accepted 27 February 2006; Published online 31 March 2006.

Abstract

In this study, we evaluate cell death, proliferation and repair in left ventricular endomyocardial biopsies from 20 patients with active lymphocytic myocarditis worsening or recovering from cardiac dysfunction after 6-months immunosuppression. Apoptosis and necrosis were assessed by in situ ligation of hairpin probes, proliferation by Ki67 and MCM5 labelling of myocytes, repair by electron microscopy, morphometric study of percent myofibrillar area and real-time polymerase chain reaction of -and -Myosin Heavy Chain (MHC). Apoptosis and necrosis decreased in post- vs pretreatment biopsies by 85 and 62%, respectively in responders, while increased by 42 and 46% in nonresponders. Ki67 and MCM5-positive myocytes were higher vs controls at baseline and increased by 43 and 38% at follow-up in responders and by 75 and 63% in nonresponders. Myofibrillar area reduced in pretreatment samples, increased by 33% at follow-up in responders, correlated with percent enhancement of ejection fraction and was associated with increased -MHC expression and /-MHC ratio. In follow-up biopsies of nonresponders, myofibrillar area diminished by 36% and correlated with percent decrease of ejection fraction. Our results suggest that recovery of cardiac function in myocarditis responding to immunosuppression is associated with inhibition of cell death, activation of cell proliferation and with newly synthesized contractile material.