CARDIAC LYMPHATIC OBSTRUCTION IMPAIRS LEFT VENTRICULAR FUNCTION AND INCREASES PLASMA ENDOTHELIN-1 AND ANGIOTENSIN II IN RABBITS

Abstract

The treatment of end-stage heart failurecan include heart transplantation. During thisprocedure, cardiac lymphatics are disrupted,which has been demonstrated in animalmodels to alter left ventricular function, andthis compromise itself can cause an increasein endothelin-1 and angiotensin II. Weundertook a study in rabbits to assess theeffect of cardiac lymphatic obstruction on leftventricular function and plasma levels ofendothelin-1 and angiotensin II. Sixty-threeNew Zealand white rabbits were divided intostudy (n=41) and control (n=22) groups.Plasma levels of endothelin and angiotensin IIwere measured before, and at 3, 7, 14, 30, 90and 180 days following the obstruction ofcardiac lymphatic vessels. Left ventricularfunction was assessed by echocardiography.Six months following the surgery, 18 studyand 6 control animals survived. In the studygroup, a significant decrease was seen in leftventricular ejection fraction within the firstthree months following the lymphaticobstruction (0.76±0.04 vs 0.72±0.01, p<0.01).Levels of plasma endothelin-1 and angiotensinII were elevated following ligation of cardiaclymphatic vessels with a peak between 3-7days following lymphatic obstruction (allp<0.05). Plasma endothelin-1 and angiotensinII began to decline 14 days after lymphaticobstruction and returned to almost baselinelevels in 6 months. The left ventricularejection fraction, plasma endothelin-1 andangiotensin in the control group remainedunchanged (all p>0.05). We conclude thatcardiac lymphatic obstruction reduces leftventricular function in the first three monthsfollowing obstruction. Cardiac lymphaticobstruction also increases plasma levels ofendothelin-1 and angiotensin II. The clinicalsignificance of these transitory changesrequires further investigation.