Impact of thoracic surgery on cardiac morphology and function in small animal models of heart disease: a cardiac MRI study in rats

Abstract

Background: Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies.

Methods: Female Wistar rats (n = 6 per group) were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition.

Results: Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05) and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05) after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease.

Conclusion: Cardio-thoracic surgical procedures in experimental myocardial infarction cause distinct alterations upon the global integrity of the organism, which in the long term also induce circumscribed repercussions on cardiac morphology and function. This impact has to be considered when analyzing data from respective animal studies and transferring these findings to conditions in patients.

Figure 1. Sham surgery situs and survey arrangement.

MRI was performed 1 and 8 weeks after sham surgery.

Figure 2. Representative full cycle of a cardiac short-axis cine-MRI with 20 frames.

Figure 3. Illustration of left and right ventricular volumetry and determination of wall thickness and systolic function.

Figure 4. Body weight at baseline, 1 week and 8 weeks after sham surgery in both groups (mean ± SD).

* indicates significant differences (p<0.05) between the respective groups.

Figure 5. Left and right ventricular myocardial mass and myocardial mass index 1 week and 8 weeks after sham surgery (mean ± SD).

* indicates significant differences (p<0.05) between the respective groups.

Figure 6. Left and right ventricular enddiastolic volume and enddiastolic volume index normalized to body weight 1 week and 8 weeks after sham surgery (mean ± SD).

* indicates significant differences (p<0.05) between the respective groups.

Figure 7. Left and right ventricular cardiac output and cardiac index normalized to body weight 1 week and 8 weeks after sham surgery (mean ± SD).

* indicates significant differences (p<0.05) between the respective groups.

Figure 8. Time course of various metabolic blood parameters (glucose, urea, triglycerides, and leptin) after sham surgery.