A rat model of low myocardial blood flow was established to test the hypothesis that post-translational changes to proteins of the thin and thick muscle filaments correlate with decreased cardiac contractility. Following 3 days of low blood flow by constriction of the left anterior descending artery, rat hearts demonstrated a reduction in fractional shortening at rest and a relative decline in fractional shortening when challenged with high dose versus low dose dobutamine, reflecting reduced energy reserves. Permeabilized fibers from low blood flow hearts demonstrated a decline in maximum force per cross-section and Ca 2+ sensitivity as compared to their sham operated counterparts. An examination of sarcomeric proteins by twodimensional gel electrophoresis, mass spectrometry, and phospho-specific antibodies provided evidence for Ser23/24 and Ser43/45 phosphorylation of troponin I (TnI). Total TnI phosphorylation was not different between the groups, but Ser23/24 phosphorylation declined with low blood flow, implying an accompanying increase in phosphorylation at other sites of TnI. Affinity chromatography demonstrated that TnI from low blood flow myocardium had reduced relative affinity to Ca 2+ bound troponin C compared to TnI from sham operated hearts, providing a mechanism for reduced Ca 2+ sensitivity of force production in low bloodCorrespondence to: Ozgur Ogut, ogut.ozgur@mayo.edu. Electronic supplementary material The online version of this article

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Abstract:When initiated by the devastating diagnosis of cancer, post ablative breast restoration has at its core the goal of restoring anatomic normalcy. The concepts of body image, wholeness, and overall well-being have been introduced to explain the paramount psychological influence the breast has on both individuals and society as a whole. Hence, a growing subspecialty has been established to recreate or simulate the lost breast. At least one third of breast cancer victims consider breast reconstruction. Breast reconstruction post mastectomy may be offered at the time of mastectomy or delayed post mastectomy after adjuvant therapy. This may be utilizing autologous tissues or implants and each has risks and benefits, especially when considering adjuvant therapy. In addition, there has been a move away from a traditional mastectomy to less invasive, but still curative procedures, such as skin-sparing and nipple-sparing mastectomy. These procedures provide the breast envelope to facilitate reconstruction. This paper reviews the primary issues in breast reconstruction, as well as their psychologic, oncologic, and social impact. Keywords: breast restoration, body image, breast reconstruction, mastectomy History of breast reconstructionBreast cancer is the second leading cause of cancer-related death among females in the US, and affects one in eight women in their lifetime.1,2 Advances in medical research have dramatically improved the treatment of this disease over the last 50 years. In addition to chemotherapy and radiation therapy, partial and complete mastectomy of diseased and contralateral breasts has become more frequent. However, these surgical modalities often leave patients with anatomical deformities and altered body image, along with the psychologic impact. 3,4 Breast reconstruction is a dynamic and multidisciplinary approach that has grown into a solution for many breast cancer patients treated with surgery. Breast reconstruction began as a means to reduce chest wall complications and deformities from mastectomy, with the goal to recreate symmetry and contour while avoiding delay in adjuvant cancer treatment.1 Breast reconstruction was introduced over a century ago as a surgical modality for rebuilding the anatomic breast using autologous tissues and prosthetic implants. 2,5

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