Vascular Failure 2017; 1(1): 39-41 39

Vasc Fail 2017; 1: 39-41CASE REPORT

Effects of prostaglandin E1 infusion on blood flow in a patientwith Buerger’s disease: a case report

Takashi Umemura, MD, PhD1), Kenji Nishioka, MD, PhD1),Kazuaki Chayama, MD, PhD1) and Yukihito Higashi, MD, PhD, FAHA2)3)

Abstract:A 45-year-old male patient with Buerger’s disease presented with intermittent claudication, sharp rest pain in his rightfoot, and several episodes of lower extremity superficial thrombophlebitis. He had no cardiovascular risk factors and hisglucose levels were within normal ranges. However, he had a smoking history of more than 26 years; he had stopped smok-ing 3 years prior. Early treatment with antithrombotic and vasodilating agents as well as intravenous infusion ofprostaglandin E1 did not improve his condition. Intra-arterial infusion of prostaglandin E1 once a day for 2 weeks slightlyincreased blood flow in the areas with previous low blood flow and improved his condition from Fontaine stage III to II.Key words:Buerger’s disease, Prostaglandin E1, Laser doppler perfusion image

Introduction

Thromboangiitis obliterans (Buerger’s disease) is recog-nized as a segmental inflammatory obliterative arteriopathyof small- and medium-sized distal arteries, veins, andnerves. It is distinct from atherosclerosis1,2), and is a rare dis-ease that affects approximately less than 10,000 people inJapan. Although inflammatory processes caused by alteredautoimmune response are thought to contribute to the pa-thology of Buerger’s disease, the precise pathogenesis ofBuerger’s disease remains unclear. The frequency ofBuerger’s disease is greater in men than in women. How-ever, the frequency of Buerger’s disease increases in youngwomen with increased tobacco use, while it is decreasing inmen. Treatment strategies for Buerger’s disease includesmoking cessation, administration of anti-platelet agents, useof vasodilators, revascularization, sympathectomy, and celltherapy. However, some cases of Buergers’ disease progressto critical limb ischemia, requiring major amputation. There-

fore, it is clinically important to improve or control the pro-gression of Buerger’s disease.

Case Report

We report the case of a 45-year-old man with a 13-yearhistory of Buerger’s disease presenting with intermittentclaudication, sharp rest pain in his right foot, and severalepisodes of lower extremity superficial thrombophlebitis. Hehad no cardiovascular risk factors, such as elevated bloodpressure, cholesterol, and glucose, but had a smoking historyof more than 26 years (3.2 pack-years); he had stoppedsmoking 3 years prior. Tests for rheumatoid factor and lupusanticoagulants, and serologic investigations had returnednegative results. Early treatment with antithrombotic andvasodilating agents did not improve his condition. Althoughright lumbar sympathectomy improved his symptoms tran-siently, his symptoms deteriorated within 4 weeks after sym-pathectomy. Intravenous infusion of lipo prostaglandin E1,

1) Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and HealthSciences, Hiroshima University, Hiroshima, Japan2) Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima,Japan3) Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University,Hiroshima, JapanCorresponding author: Yukihito Higashi, MD, PhD, FAHA, yhigashi@hiroshima-u.ac.jpReceived: February 10, 2017, Accepted: February 28, 2017Copyright Ⓒ 2017 Japan Society for Vascular Failure

UMEMURA T et al.

40 Vascular Failure 2017; 1(1): 39-41

Figure　1.　Effects of intra-arterial (A) and intravenous (B) infusion of alprostadil and long-term intra-arterial infusion of alprostadil (C) on blood fl ow of the right dorsum pedis in a patient with Buerger’s disease.

Before 10 min 20 min 30 min 40 min

Before 15 min 30 min 60 min

(Range: 0-2200)

45 min

A

B

C

Before 1 week 2 weeks(Range: 0-2500)

Blood flowLow High

Blood flowLow High

Figure　2.　Digital subtraction angiography in the right lower legin a patient with Buerger’s disease.

alprostadil alfadex (20 μg) for 30 minutes twice a day for 2weeks also did not improve his condition.Laser Doppler perfusion imaging (LDPI) showed very

low blood flow areas at the great, second, and third toes andmultiple low blood flow areas in the dorsum pedis (Figure1A, 1B, 1C). Alfadex was intra-arterially infused through a24-gauge catheter into the right femoral artery. Blood flowof the right dorsum pedis immediately increased andreached a peak level at 10 minutes after intra-arterial infu-sion of alprostadil (0.5 ng/kg/min) for 5 minutes (Figure 1A, arrow) and returned to the baseline level at 30 minutesafter alprostadil infusion. However, blood flow of the rightdorsum pedis did not change during and after intravenousinfusion of alprostadil (10 ng/kg/min) for 60 minutes (Fig-ure 1B). Intra-arterial infusion of alprostadil (10 ng/kg/min)for 10 minutes once a day for 2 weeks slightly increasedblood flow in the previous low blood flow areas (Figure 1C, arrow) and improved his condition from Fontaine stageIII to II.

Discussion

LDPI enables non-invasive and repeated determination ofnot only blood flow but also distribution of blood flow inextremities3). We confirmed that ischemic extremities in pa-tients with peripheral diseases (n=38, 34 males and 4 fe-males) can be divided into 3 types according to observationby LDPI during and after the intravenous infusion of al-prostadil (10 ng/kg/min) for 60 minutes. First, in most cases(n=32, 29 males and 3 females), intravenous infusion of al-prostadil immediately increased blood flow in ischemic ex-

Prostaglandin E1 and Buerger’s Disease

Vascular Failure 2017; 1(1): 39-41 41

tremities, as shown in previous studies4,5). Second, as in thiscase (n=5, 4 males and 1 female), blood flow did notchange during and after alprostadil infusion. Finally, in onecase (n=1, male), blood flow decreased only during andboth during and after intravenous alprostadil infusion (so-called steal phenomenon and borrowing-lending phenome-non)6,7). The two latter types compared with the former typemay have more serious symptoms and arteriographic find-ings. Indeed, our patient had rest pain (Fontaine stage III) inhis lower right leg. Digital subtraction angiography showedavascular areas at the tip of the great toe and multiple occlu-sions of the distal arteries with collateralization around thearea of occlusions in his lower right leg (Figure 2). It isexpected that intra-arterial infusion of prostaglandin E1 ismore effective compared with intra-venous infusion ofprostaglandin E1. However, reproducibility and safety ofintra-arterial infusion of prostaglandin E1 are not guaranteedyet. Future studies are needed to confirm the effectivenessand safety of intra-arterial infusion of prostaglandin E1 inpatients with peripheral arterial diseases.

Conclusion

Although intra-arterial infusion of prostaglandin E1 isworth trying in patients for whom intravenous prostaglandinE1 infusion is not effective, we must keep in mind the pres-ervation capacity of blood supply in collateral arteries whenvasodilators are intravenously or intra-arterially administeredin patients with severe peripheral arterial diseases. LDPI, anon-invasive approach for observation, is expected to play

an important role in screening for safety and usefulness ofthe administration of vasodilators, including intravenous in-fusion of prostaglandin E1, in patients with peripheral arte-rial diseases.

Conflicts of InterestNone.

References1. Szuba A, Cooke JP. Thromboangiitis obliterans. An update onBuerger’s disease. West J Med 1998; 168: 255-60.

2. Olin JW. Thromboangiitis obliterans (Buerger’s disease). N Engl JMed 2000; 343: 864-9.

3. Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, ShintaniS, Masaki H, et al. Theraputic angiogenesis for patients with limbischaemia by autologous transplantation of bone-marrow cells: apilot study and a randomized controlled trial. Lancet 2002; 360:427-35.

4. Hirai M, Nakayama R. Haemodynamic effects of intra-arterial andintravenous administration of prostaglandin E1 in patients with pe-ripheral arterial disease. Br J Surg 1986; 73: 20-3.

5. Gschwandtner ME, Koppensteiner R, Maca T, Minar E, SchneiderB, Schnürer G, et al. Spontaneous laser doppler flux distributionin ischemic ulcers and the effect of prostanoids: a crossover studycomparing the acute action of prostaglandin E1 and iloprost vs sa-line. Microvasc Res 1996; 51: 29-38.

6. Mörl H. The special hemodynamics and metabolism in severe dis-turbances of peripheral blood flow and their treatment. Atheroscle-rosis 1977; 26: 617-27.

7. Brevetti G, Chiariello M, Verrienti S, Spena M, Desiderati M,Condorelli M. Beneficial effect of papaverine plus raubasine in pe-ripheral arterial insufficiency. Angiology 1983; 34: 517-26.