Effects of bevacizumab administration on the chronic hypoxic pulmonary arterial hypertension animal model

Aim: To establish the interaction of right ventricule pressures; serum, lung and heart tissue VEGF levels and bevacizumab administration in pulmonary arterial hypertension rat model secondary to chronical hypoxia exposure.Method: Wistar-albino rats between 200-250 mg were used. Group1(n=6): room air+serum physiologic (SF); Group2(n=6): room air+bevacizumab; Group3(n=6): hypoxia+SF; Group4(n=6): hypoxia+bevacizumab. 10% oxygen and 90% nitrogen gas mixture was administered to hypoxia groups. SF and bevacizumab administrated in day 5 and under general anesthesia, anterior thoracotomy was applied in day 8. Right and left ventricule pressures were measured directly from heart. After that, whole body blood and lung tissues were taken. Postmortem right venticule/(left ventricule + septum) weight ratios (Fulton index) were measured.Results: Right ventricule pressure means were 10.83±0.48 mmHg in Group1; 11.00±0.37 mmHg in Group2; 37.33±0.95 mmHg in Group3 and 32.00±1.03 mmHg in Group4. Difference of right ventricule pressures between Group3 and 4 was statistically significant (p=0.002). Difference of Fulton index of Group3 (0.31±0.01) and 4 (0.25±0.01) were statistically significant (p<0.0001). Serum VEGF levels were also significantly different (p=0.05) between hypoxic and nonhypoxic groups; but, there was no significant difference with BVC administration (p=0.42). MK values for groups were; 15.33±0.33 µm; 15.49±0.37 µm; 27.30±0.41 µm; 24.97±0.51 µm. Difference of MK values between hypoxic and nonhypoxic groups was significant (p<0.0001) and also; there was a significant decrease in these values with BVC administration (p<0.0001). Interestingly, VEGF tissue score of hypoxia + SF group was significantly higher than the other groups (p<0.0001); but, there wasn?t a statistically significant difference between the VEGF tissue scores of hypoxia + BVC group and nonhypoxic groups (p>0.05).Conclusion: Statistically significant differences in right ventricule pressures, Fulton index, serum VEGF levels, MK and MK% values between nonhypoxic and hypoxic groups represent us that, model has been established successfully. The statistically significant decrease in right ventricule pressures, Fulton index, MK and MK% values and VEGF tissue scores with bevacizumab administration in hypoxic groups is interpretted as bevacizumab?s acute effect is in favour of decreasing the pulmonary arterial hypertension. In our study, we established that bevacizumab which is an antineoplastic agent indeed, can have some effects on pulmonary arterial hypertension mechanisms.