Remote Ischemic Conditioning (RIC) in a Rat Model of Testicular Torsion: Does it Offer Testicular Protection?
Yaser El-Hout, MD, Mazen Mansour, MD, Jad Degheili, MD, Ibrahim Khalifeh, MD, Hani Tamim, PhD., Rola Jaafar, PhD..
American University of Beirut Medical Center, Beirut, Lebanon.
Background: Testicular torsion is a surgical emergency mainly affecting adolescent boys, with a relatively high rate of missed torsion and testicular loss secondary to delay in prompt diagnosis and surgical intervention. With ischemic-reperfusion injury as its underlying culprit, testicular torsion may respond favorably to remote ischemic conditioning (RIC) where a non-privileged site (e.g. limb) is concurrently rendered ischemic to divert the cascade of reperfusion injury from the privileged organ (e.g. testicle), thus offering a protective effect in improving salvage. While this mechanism is established for other organs, it has not been evaluated for testis. We sought to evaluate RIC in a rat model of testicular torsion. Methods: Thirty Sprague-Dawley male rats were divided into control group (n=15) and experimental group (n=15). Non-survival surgeries of Right sided spermatic cord torsion (720 degrees counter -clockwise twist) were performed for both groups (45 minutes) followed by detorsion and reperfusion (5 minutes) then orchiectomy. For the experiment group, an intervention of tail clamping, to create remote ischemic conditioning, was applied 5 minutes after torsion then unclamping 5 minutes before detorsion, followed by detorsion and reperfusion for 5 minutes then orchiectomy. The testicles were histologically and immunologically examined using Hypoxia Inducible Factor (HIF-1α) ELISA kit. The histological findings were quantified using a validated grading system (grade 1 to 4): Grade 1 showing normal testicular architecture and Grade 4 showing severe coagulative necrosis. Vascular congestion grading system was used (grade 0=no congestion, grade 1= mild to moderate and grade 2= severe congestion). The HIF-1α immunohistochemistry was graded by 0= no immunoreactivity, 1= faint, 2= moderate and 3= strong immunoreactivity. Results: By histology, there was a significant difference in the appearance of the testicles in both groups. In the control group, 86.7% had grade 3 and 13.3 % had grade 4 necrosis, whereas in the experimental group 93.3% had grade 2 and 6.7% had grade 3 necrosis (p=0.0001). For vascular congestion, the control group had 100% grade 2 congestion compared to 73.3% grade 1 and 26.7% grade 2 congestion in the experimental group (p=0.0001). By immunohistochemistry, the control group was strongly immunoreactive with 100% grade 3 for HIF-1α compared to 75% grade 1 and 25% grade 2 in the experimental group (p=0.029). Conclusions: This is the first study that evaluates the influence of RIC on testicular torsion. When RIC is applied, there is less evidence of hypoxic injury by histology and immunohistochemistry. The applicability of RIC in clinical setting of testicular torsion may be possible with further studies.
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