Transaortale periarterielle Ethanol-Sympathikolyse zur renalen Denervation mittels endovaskulärem Injektionskatheter im Schweinemodell

Beschreibung

Renal denervation by transaortic periarterial ethanol injection: an experimental study in porcines Arterial hypertension is a serious world wide health problem. Hypertension is a major risk factor for cardiovascular morbidity and mortality like stroke or heart failure. Furthermore it increases the risk for the progression of chronic kidney disease and vision loss. Life style changes and oral medications are prescriped to lower the blood pressure < 140/90 mmHg. Unfortunately there are estimated 10 - 30 % of patients whose blood pressure is uncontrolled despite taking antihypertensive drugs. Such therapy-resistant hypertension is defined as high blood pressure > 140/90 mmHg in spite of taking 3 or more antihypertensive agents at optimal dose, with at least one beeing a diuretic. To find a safe and effective therapy for people with resistant hypertension is essential because of the severe consequences of this illness. The concept of renal denervation with minimal invasive techniques seems a viable option since 2009. The backround is the knowledge of the sympathetic nervous system and its effect on blood pressure regulation in the body. To destroy the afferent and efferent nerves laying in the adventitial space around the renal arteries is the aim of renal denervation. 2010 the first study of the Simplicity catheter was published and seemed promising. A catheter applies radiofrequency energy to the intima of the renal artery. Multiple ablations lead to severe sympathetic nerve damage and drop of blood pressure. 2014 this system suffered a major set back with puplishing the disappointing results of the HTN-3 trial. So scientists were looking for different catheter and non-catheter-based methods to accomplish renal denervation. Next to heat, cold and ultrasound the use of neurotoxic substances seemed promising. Especially ethanol was sucessfully used in preclinical animal studies. Using the Symplicity-catheter inside the renal artery has several anatomical limitations like the length and the diameter of the vessel. To bypass these limitations we are using a new access path to inject the ethanol. This might help to broaden the spectrum of future patients. The aim of this study is to evaluate the safety, feasibility and efficancy of endoluminal transaortal ethanol injektion to denervate renal sympathetic nerves in a porcine model. 11 normotensive pigs underwent general anesthesia. A 7 F steerable sheath was inserted via the femoral arteria and advanced within in the aorta. Then the tip was flexed so it was pointed against the aortal wall just above the origin oft he renal artery. An experimental 21 G needle with an extandable and retractable tip punctured the aortic wall and injected the ethanol into the periarterial space of the renal artery. After 4 weeks the pigs were euthanized and the norepinephrine concentration in the renal parenchyma was determined. Furthermore the renal arteries and the sourrounding tissue were pathohistologically examined to find potential nerve damage. The blood pressure was messured noninvasively straight before and after the procedure as well as after 4 weeks on the day of euthanasia. Our findings were that in 10 of 11 pigs the intervention was technical successfully feasible. One pig got a major complication since a little amount of the ethanol got injected into the renal artery. It caused formation of a thrombus and subsequent infarction of the kidney. Pig 4 died of cardiac arrest while waking up from anesthesia not related to the intervention. Within 3 animals the ethanol mixture ran also onto the contralateral side. Looking at the optimal treated pigs the efficiency was shown by the nerve damage found histologically on the treated side. While the norepinephrine concentration was lower on the treated side, the difference was not significantly. Further preclinical and clinical studies are necessary to discuss whether the transaortic ethanol injection is a reasonable alternative to the percutan or transarterial approach.

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Josephin Scholz

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Denervation Ethanol Histologie Injektion Katheter Niere Nierenfunktionen Norepinephrin Schweine Sympatholytika Tiermodelle animal models catheters histology injection

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