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Ann Thorac Surg 1998;66:2015-2021
© 1998 The Society of Thoracic Surgeons

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Original Articles

Nitroglycerine reduces neutrophil activation and acute damage in latissimus dorsi muscle grafts

^a Department of Cardiothoracic Surgery, Wythenshawe Hospital, Manchester, United Kingdom
^b Department of Immunology, School of Biological Sciences, University of Manchester, Manchester, United Kingdom
^c Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, United Kingdom
^d Department of Human Anatomy and Cell Biology, University of Liverpool, Liverpool, United Kingdom

Accepted for publication June 7, 1998.

Address reprint requests to Dr Hooper, Department of Cardiothoracic Surgery, Wythenshawe Hospital, Southmoor Rd, Manchester M23 9LT UK

Background. Damage to the latissimus dorsi muscle (LDM) may jeopardize a successful outcome to dynamic cardiomyoplasty. We and others have demonstrated muscle damage in LDM in various species including humans. Ischemia is now recognized to be an important contributory factor. We postulated that glyceryl trinitrate, a nitric oxide donor, might protect against ischemic endothelial dysfunction and so reduce resultant muscle damage.

Methods. In 20 adult rats the left LDM was mobilized on its thoracodorsal neurovascular pedicle and maintained as an orthotopic graft. Half of the animals received glycerol trinitrate intraoperatively and postoperatively for 24 hours. The other half served as untreated controls. Each group was further subdivided into two groups (n = 5 in each): animals in which the LDM was excised after 4 hours for myeloperoxidase studies, and animals in which the LDM was excised at 24 hours for analysis of muscle damage by histology and enzyme macrohistochemistry. Blood samples were taken at 24 hours for assay of plasma nitrite and nitrate as nitric oxide metabolites.

Results. Glycerol trinitrate-treated animals had higher plasma nitric oxide metabolite levels after 24 hours (after nitrate reductase treatment, total nitrite, 78.3 ± 11.8 nmol/mL, mean ± SEM) than controls (42.1 ± 3.7 nmol/mL, p = 0.008). The proportion of viable LDM in glycerol trinitrate-treated animals was greater than in untreated animals, mainly in the middle and distal regions of the graft (middle region, 96.3% ± 0.5% versus 75.7% ± 4.1%, p < 0.001; distal region, 94.4% ± 0.8% versus 40.9% ± 3.1%, p < 0.001). Macrohistochemical findings correlated well with the histologic findings. Myeloperoxidase activity (U/g) was markedly lower in glycerol trinitrate-treated LDMs, mainly in the distal part of the graft (glycerol trinitrate versus control, 20.5 ± 2.1 versus 40.9 ± 3.1 U/g, p < 0.001).

Conclusions. Glycerol trinitrate significantly reduced acute damage to the distal two-thirds of the mobilized LDM, possibly by modifying leukocyte activation and endothelial dysfunction associated with ischemic injury.

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