Thoracic Surgery Directors Association Awards
Angiogenesis and growth factor expression in a model of transmyocardial revascularization

Presented at the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26–28, 1998.
https://doi.org/10.1016/S0003-4975(98)00388-9Get rights and content

Abstract

Background. The mechanism by which transmyocardial revascularization (TMR) exerts a beneficial effect remains unknown. We hypothesize that the myocardial punctures of TMR cause a myocardial injury, leading to an angiogenic response mediated by a number of growth factors.

Methods. Fifty-three rats underwent ligation of the left coronary artery. Group I (n = 25) served as controls, whereas group II (n = 28) underwent concomitant TMR by the creation of six transmural channels with a 25-gauge needle in the ischemic zone. Surviving animals in both groups were sacrificed at intervals of 1, 2, 4, and 8 weeks (n = 5 in each subgroup). Immunohistochemistry in the infarct areas was performed for factor VIII to assess vascular density. Immunohistochemistry using specific antibodies was also performed for transforming growth factor-β, basic-fibroblast growth factor, and vasoendothelial growth factor. Growth factor expression was quantitated by comparing areas of staining (in mm2) with computerized morphometric analysis.

Results. Mortality was similar in both groups (5/25 versus 8/28; not significant). Group II had significantly greater vascular density than group I (5.65 versus 4.06 vessels/high-power field; p < 0.001), with a peak at 1 week postoperatively (9.12 versus 5.56 vessels/high-power field; p < 0.0001) in both groups. Overall, levels of both transforming growth factor-β and basic-fibroblast growth factor were significantly higher in the TMR group compared with the control group (0.207 versus 0.141 mm2/mm2, p < 0.05; and 0.125 versus 0.099 mm2/mm2, p < 0.05).

Conclusions. This model of TMR is associated with a significant angiogenic response, which appears to be mediated by the release of certain angiogenic growth factors such as transforming growth factor-β and basic-fibroblast growth factor. With the long-term patency of laser-created myocardial channels in clinical TMR increasingly in doubt, its mechanism of myocardial revascularization may be similar to that observed in our model.

Section snippets

Animals

Male Lewis rats weighing between 250 and 300 g were used for all experiments (Charles River Laboratories, Wilmington, MA). Animals were divided into two groups. Group I (control, n = 25) underwent ligation of the left coronary artery (LCA) only. Group II (experimental, n = 28) underwent ligation of the LCA along with TMR at the same operation. Each group had 20 survivors, which were sacrificed in subgroups of 5 at intervals of 1, 2, 4, and 8 weeks. All animal work was performed in accordance

Mortality

Table 1shows the mortality associated with both the control group (group I, LCA occlusion) and the experimental group (group II, LCA occlusion + TMR). Most deaths were caused by ventricular arrhythmias or asystole after LCA occlusion. In 3 hearts of group I and in 2 hearts of group II, an area of infarct could not be found by histologic criteria.

Angiogenesis

Figure 1 represents an example of an HPF with several small vessels, elliptic areas surrounded by factor VIII staining. The number of capillaries per

Comment

Transmyocardial revascularization is currently being investigated as a surgical option for patients suffering from intractable angina. Early phase I trials have shown that TMR can drastically reduce the severity of angina, as graded by the Canadian Cardiovascular Society score [6]. That report also demonstrated an improvement in subendocardial versus subepicardial resting perfusion in the laser-treated areas at 12 months. A current phase III trial in the United States [18] has shown promising

References (25)

  • A.Y. Zlotnick et al.

    Neovascularization occurs at the site of closed laser channels after transmyocardial laser revascularization

    Surg Forum

    (1996)
  • N. Gassler et al.

    Transmyocardial laser revascularizationhistological features in human nonresponder myocardium

    Circulation

    (1997)

    • Cited by (0)

    View full text
    Copyright © 1998 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.