The Research of Renal Denervation by Catheter Ablation on Hypertension Treatment in Dogs

Objective:To evaluate the effect of neurogenic hypertension model transcarotid artery; to assess the validity and safety of the treatment; to investigate the effects of this treatment on kidney; to investigate the neuroendocrinologic mechanism of renal artery denervation on hypertension.Methods:1、We randomly divided18mongrel dogs (weight,15-20kg) of either sex into2groups:a model group of10hypertension-induced dogs, and a control group of8dogs.2、Dogs in the model group were anesthetized by administration of3%sodium pentobarbital (produced by Sigma company) and Sumianxin (produced by Military Medical Institute of Changchun) at dosage levels of30mg/kg and0.1ml/kg, respectively. Then, the dogs were placed in the supine position and the skin of the neck was disinfected using povidone. An incision was made in the neck to expose the left vagus nerve and the cervical carotid artery, and a1-2-mm-long5-0chromic catgut suture was placed around the vagus nerve. After demyelination, the vagus nerve was compressed with a carotid pulse; this model imitated the intracranial pathological environment (vascular compression of the intracranial vagus nerve without myelin). To avoid infections, intramuscular injections of gentamicin were administered for3days.3.After successfully inducing hypertension in the model group, renal denervation by using catheter ablation was performed for both the model group and control group. Dogs were anesthetized using3%sodium pentobarbital (30mg/kg) and Sumianxin (0.1ml/kg) and fixed on the operating table in the supine position. Then, the right femoral artery and the back skin was disinfected and connected to the radiofrequency ablation apparatus (IBI-1500T, produced by the IBI company of United States); the upper limit temperature of the radiofrequency ablation instrument was fixed at60℃. After disinfecting the adjacent operation area, an8F guiding wire was inserted into the punctured right femoral artery through the guiding sheath, and the blood pressure before operation was determined. Renal angiography was performed to determine the location of the renal artery; the ablation electrode (8F ablation catheter tip, electrode length of4mm) was placed at the location of the artery; We applied discrete, radiofrequency ablations lasting up to2min each and of10watts or less to obtain up to six ablations separated both longitudinally and rotationally within each renal artery, and each dog had simultaneous bilateral renal artery denervation, the blood pressure was monitored after the process.4. We measured the blood pressure of the dogs by using an invasive blood pressure monitor (produced by Philips company); to maintain the accuracy and stability of the experiment, an indwelling sheath was inserted in the femoral artery and connected to the blood pressure transducer (produced by Beijing Institute of Aerospace Biomedical Engineering) with the invasive blood pressure monitor. Blood pressure values were obtained at2weeks,4weeks, and10weeks after the procedure. After monitoring, the puncture point was pressed with the hand to arrest bleeding, and intramuscular injections of gentamicin were administered for3days to avoid infections.5. Blood samples were taken before and after the ablation; after centrifugation, serum samples were obtained, and to1ml of each sample,20μl of the inhibitor PMSF (containing Na2EDTA,8-hydroxyquinoline, and2-mercapto-propanol) were added. Angiotensin II concentration was detected by radioimmunoassay, and renin activity and aldosterone concentration were detected by enzyme-linked immunosorbent assay.Results:1、The neurogenic hypertension model had been successfully made.2、Blood pressure decreased significantly in both the control group and blank group after renal denervation at2weeks、4weeks、10weeks3、The level of PRA、AngⅡ and Ald levels decreased gradually along with the time points.4、There was no significant change in the the level of Cr.Conclusion: 1、The method of transcarotid modeling of neurogenic hypertension is simple, it’s suitable for large sample extension.2、The catheter-based renal denervation causes substantial and sustained blood-pressure reduction.it cause no harm to kidney.3、The mechanism of this treatment was suppress the renin-renin-angiotensin-aldosterone system, and lead to lower blood pressure significantly.