Local Nitric Oxide Donor Delivery Prevents Acute Arterial Occlusion

Jeong, Myung Ho; Kang, Jung Chaee; Schwartz, Robert S; Holmens, David R

Abstract

Nitric oxide(NO) is known as a vasodilator and anti-platelet agent. Local NO donor releases NO spontaneously and has potential utility in the treatment of coronary artery disease. We investigated the effects of local NO delivery after arterial injury on acute platelet deposition and arterial occlusion following arterial injury. Platelet deposition was measured by 111-In tropolone-labeled platelets injected one day before porcine carotid artery crush injury. Normalized blood flow was measured and recorded continuously by Transonic Doppler flowmeter. NO donor (Dansylpiperazine nonoate), saline, Dansyl compound (donor without NO) and SNP(sodium nitroprusside) were infused identically by the Dispatch Catheter. Six groups were studied. A(10 arteries): crush, local saline, B(10 arteries):crush, local NO donor(10 ml/3x10-4 mol over 10 min), C(9 arteries): crush, systemic NO(3x10-4 mol), D(6 arteries):crush, systemic NO, local saline, E(3 arteries): crush, local Dansyl, F(3 arteries): crush, local SNP(2 g/Kg/min). Each was studied at 1 hour and 24 hours later. The number of patent stents was 8/10 in A, 9/10 in B, 3/9 in C, 5/6 in D, 1/3 in E, and 1/3 in F at one hour after injury(p<0.05: B vs C). Six of 10 in A, 9/10 in B,1/9 in C, 4/6 in D, 1/3 in E and 1/3 in F at 24 hours after injury were patent at 24 hours after injury(p<0.05: B vs C). Normalized blood flow(NBF) at one hour was 0.25+/-0.13 in A, 0.73+/-0.15 in B, 0.18+/-0.12 in C, 0.59+/-0.27 in D, 0.09+/-0.09 in E and 0.34+/-0.34 in F(p<0.05: A vs B, C vs D). NBF at 24 hours after injury was 0.26+/-0.14 in A, 0.75+/-0.21 in B, 0.07+/-0.07 in C, 0.18+/-0.17 in D, 0.09+/-0.09 in E and 0.34+/-0.34 in F(p<0.05: A vs B, B vs C). Platelet deposition counts of injured arteries was 5.5+/-2.2 x105/cm2 in A, 1.3+/-0.4 x105/cm2 in B, 4.9+/-1.0x105/cm2 in C, 7.6+/-3.1x105/cm2 in D, 1.5+/-0.45 x105/cm2 in E and 4.0+/-1.1 x105/cm2 in F(p<0.05: A vs B, B vs C). Local NO Donor delivery after arterial injury reduces acute arterial occlusion and limits platelet deposition.