Biomarkers of endothelial dysfunction after operations using homografts for lower limb arterial reconstruction (a pilot study)

• Kalinin R.E.
• Suchkov I.A.
• Karpov V.V.
• Klimentova E.A.
• Egorov A.A.
• Nikiforov A.А.

Abstract

Objective. The purpose of this study was to test a hypothesis about the diagnostic significance of changes in the levels of endothelial dysfunction markers for predicting the progression of atherosclerosis after using homografts in reconstruction of lower limb arteries.

Patients and methods. The study was conducted in accordance with the GCP (Good Clinical Practice) standards and principles of the Declaration of Helsinki. The protocol was approved by the Local Ethics Committee № 4 dated November 9, 2021. The study was registered on the platform ClinicalTrials.gov (identifier NCT05455138), being an independent, prospective, clinical, uncontrolled trial. The first “pilot” data were obtained in treating ten patients with stage III–IV obliterating atherosclerosis of lower limb arteries (according to the classification of A.V. Pokrovsky-Fontaine). The patients were operated on at the Department of Vascular Surgery of the Ryazan Regional Clinical Hospital. The inclusion criteria were as follows: use of a homograft (irrespective of the type) as a material for reconstruction of major arteries, the presence of atherosclerosis of the latter, males of females over 40 years of age, with the following exclusion criteria: another-etiology chronic lower limb ischemia (Buerger’s disease, aortoarteritis, etc.), active cancer or a period of remission less than 5 years, patients’ refusal to participate in clinical research.

The study enrolled a total of ten patients (7 men and 3 women), average age 62.6 (42–78) years. Arterial and venous homografts were used as a material for reconstructive and restorative intervention in all patients. We used 5 alloarteries and 5 alloveins. Blood serum levels of endothelin-1 (ET-1), interleukin-6 (IL-6), endothelial nitric oxide synthase (eNOS) and prostacyclin (PGI2) were measured at various time points (the day before surgery, after 7 days, 1 month, 3 months, 6 months, 1 year). The overall duration of postoperative follow-up amounted to 1 year.

Results. The obtained findings demonstrated an increase in the ET-1 level by 75% on POD 7 (p=0.004) and by 73% (p=0.05) at 3 months versus the baseline values, a 107% increase of the IL-6 level at 1 year (p=0.001), with a three-fold increase of the eNOS level at 3 months (p=0.006) and also a three-fold increase at 1 year (p=0.001). The PGI2 level in blood serum increased multiply at 1 year after surgery vs. the baseline level (p=0.024). Nine patients were discharged with saved extremities and relief of critical ischemia. The progression of atherosclerosis was observed in four patients. There were 2 thromboses of homografts in the position below the knee-joint fissure without development of acute limb ischemia. Two patients were found to have the progression of atherosclerosis on the contralateral extremity – a decrease of the pain-free walking distance to 200 m in one patient, and the appearance of rest pain in the other, thus requiring elective endovascular intervention. These patients were found to have a two-fold increase in the ET-1 (p=0.004) and IL-6 (p=0.02) levels at 1 year compared with those in patients without progression of atherosclerosis.

Conclusion. The levels of endothelin-1, interleukin-6, endothelial nitric oxide synthase and prostacyclin can be used for predicting the progression of atherosclerosis after operations using homografts. Elevated levels of ET-1 and IL-6 are predictors of thrombotic complications. The values of endothelial nitric oxide synthase and prostacyclin also increase in the remote postoperative period. Given the conclusive results of our research, further studies are warranted to confirm our findings in larger cohorts.

Funding. The study had no financial support.

Conflict of interest. The authors declare no conflicts of interest.

Authors’ contribution. Study conception and design – Kalinin R.E., Suchkov I.A.; development of methodology – Suchkov I.A., Karpov V.V.; data collection and handling – Karpov V.V., Nikiforov A.А.; surgical intervention – Karpov V.V., Egorov A.A.; draft manuscript preparation – Karpov V.V., Suchkov I.A..; manuscript revision – Suchkov I.A., Kalinin R.E., Klimentova E.A.

For citation: Kalinin R.E., Suchkov I.A., Karpov V.V., Klimentova E.A., Egorov A.A., Nikiforov A.А. Biomarkers of endothelial dysfunction after operations using homografts for lower limb arterial reconstruction (a pilot study). Angiology and Vascular Surgery. Journal named after Academician A.V. Pokrovsky. 2024; 30 (1): 138–45. DOI: https://doi.org/10.33029/1027-6661-2024-30-1-138-145

Keywords:lower extremity arterial disease; homograft; endothelin-1; interleukin-6; endothelial nitric oxide synthase; prostacyclin