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Nr.4 din luna 2012

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Autor L.Fehérvári, C.Podoleanu, A.M agdás, E.Carașca, A.Incze

Titlu articol
PROS TAGLANDINA INTRAVENOAS A (PGE1) S I PENTOXIFILINA IN TRATAMENTUL CLAUDICATIEI INTERMITENTE, LA
PACIENTII VARS TNICI

Cuvinte cheie
ateroscleroză cronică obliterantă (PAD), claudicație intermitentă (IC), perfuzie periferică (PP), fotopletismografie digitală (PPG).

Articol

L.Fehérvári, C.Podoleanu, A.M agdás, E.Carașca, A.Incze

Internal M edicine Department IV
University of M edicine and Pharmacy Târgu M ureș, România
Coresponding author:
Fehérvári Lajos
Internal M edicine Department IV, Târgu M ureș
0040745372390, fehervari.lajos@yahoo.com

Introduction
Symptomatic and asymptomatic peripheral arterial disease (PAD) is a common problem in elderly ages. The management of PAD includes
the prevention of cardiovascular events and relief of symptoms, most commonly intermittent claudication (IC). Prevention of cardiovascular
events include smoking cessation(over 80% of patients being current or ex-smokers), exercise, antiplatelet therapy, and the treatment of
dyslipidemia, hypertension, and diabetes. The benefit of numerous drugs in the treatment of IC has been assessed. The results have generally
been disappointing, but there is some evidence that prostaglandins are of benefit, especially in elderly patients, with good collateral
circulation.
The prevalence of symptomatic and asymptomatic PAD increases markedly with age, smoking, and diabetes. The prevalence of IC increases
from about 5% in those aged 50–54 years to 14,5% in those aged 70–74 years(¹). Only about one third of patients with PAD defined as an
Ankle Brachial Pressure Index (ABPI) <0.9 are symptomatic, because of co-morbidities that limit walking distance such as arthritis, heart
failure and pulmonary disease(¹).
The aim of this study was to compare the effect of a vasoactive substance, iv. PGE1 and iv. pentoxifyllinum in PAD with intermittent
claudication on elderly patients, using digital photopletismography to measuring the peripheral perfusion (PP) at the level of the first toe of
the leg and the maximal walking distance before and after the treatment.

Material and Methods

Photoplethysmography (PPG) is an optical measurement technique that can be used to detect blood volume changes in the microvascular bed
of the peripheral tissues. The PPG technology requires only a few opto-electronic components: a light source to illuminate the tissue, and a
photodetector to measure the small variations in light intensity associated with changes in perfusion in the catchment volume. PPG is a non-
invasively technique, the most recognized waveform feature is the peripheral pulse, and it is synchronized to each heartbeat and can provide
information about the cardiovascular system. The pulsatile component depending on the heart rate is related to the tissues and to the average
blood volume and influences by respiration variability, vasomotor activity, and thermoregulation.
The interaction of light with biological tissue is complex and includes the optical processes of absorption, reflection and transmission. They
have highlighted the key factors that can affect the amount of light received by the photodetector: the blood volume. The recorded pulse is in
direct relationship with perfusion, and blood volume. PPG can provide information about capillary blood flow.
The appearance of the pulse was defined as two phases: first phase is primarily concerned with systole, and the second phase with diastole
and wave reflections from the periphery. PPG has been applied in many different clinical settings, including vascular assessment in
peripheral arterial disease. The PPG technique have a great potential use in clinical measurements and it is a low cost, simple and portable
technology(²).
Regular walking exercise is of critical importance in the basic treatment of intermittent claudication. The muscular agonist-antagonist exercise
leads to an increased number of mitochondria and increased vascular proliferation with formation of collaterals and subsequent improvement
in exercise tolerance of the affected extremity. Numerous studies have established the efficacy of iv. Prostaglandin El (PGE1) in stages IIb
and III of peripheral arterial occlusive disease (PAOD)(5,6).
A total of 47 patients (30 men and 17 women) with stage lIb and III PAOD (age range, 47 to 87 years, mean 68,633±10.47 years) were
included in study. M ean body weight was 76,33±9.848 kg, and mean height was 175±8.141 cm. Systolic average blood pressure was
130±14.2 mmHg, and heart rate averaged 75±11.34 beats per minute. All patients had arteriography, duplex Doppler or spiral CT
examination. The mean AB-Doppler Index was 0.545±0.253.
Included in the study were patients with PAOD of the lower extremities who were stable and in stage IIb or III of the disease, according to
Fontaine's classification. Exclusion criteria were defined as decompensated heart failure, decompensated renal failure, hemodynamically
relevant aortic or iliac arterial occlusion, presence of necrosis or pain at rest, respiratory insufficiency, joint problems affecting walking
distance, myocardial infarction within the past 6 months, indispensable therapy with vasoactive drugs or drugs affecting peripheral
perfusion.
The most important exclusion criteria was the peripheral perfusion(PP) increase lack after 30 minutes of the 10 ng/kg/min intravenous
prostaglandin(PGE1) infusion. This response can be the marker of total arterial obstruction or the absence of collaterals.
Patients were divided in two groups and administered: Group I (16 patients), iv. pentoxifyline 200 mg/day (20 µg/kg/minute). Group II (31
patients) received 20 µg/day (10 ng/kg/min) iv. prostaglandin(PGE1).
Using digital photopletismography were determined the peripheral perfusion(PP) on the first toe of the lower extremity and maximum
walking distances before and after the therapy. Blood pressure and heart rate were monitored during the infusion, and ECG was checked
daily.

Results

In group I, there was a non-significant increase in maximum walking distance. After the additional administration of pentoxifylline, there was
an average increase from 210.0 ±35.42 m at the beginning to 253.3±41.05 m at the end of treatment ( p=0.4309,n=15,t=0.7993).
With PGE1 therapy, the maximum walking distance increased from an average of 179.3±10.36 to 565±8 m (p<0.0001,n=30,t=19.62).
Between-group comparison with regard to maximum walking distance revealed significant superiority of PGE1 (Figure 1,2).
Figure 1. M aximum walking distance (m) increase before and after 10 day of treatment with iv. Pentoxifylline (200 mg/day, 20 μg/kg/minute)

Figure 2. M aximum walking distance (m) increase after 10 day of treatment with PGE1 (20 μg/day, 10 ng/kg/minute)

The acute effect of iv. PGE1 (10 ng/kg/minute), was determined at each patient, by measuring the peripheral perfusion(PP) infusion with
photopletismograph (PPG) after 30 minutes of infusion. PP increased from 1.223±0.247 mV/V to 3.467±0.5937 mV/V
(p<0.0001,n=30,t=3,488). The 100% increase of PP after 30 minute of infusion with PGE1 was considered the marker of good collateral
circulation at the responders group, and they will have positive results after chronic treatment with PGE1(26 patients)(Figure 3).
Figure 3. Peripheral perfusion (mV/V) before and after 30 minutes of iv. PGE1 (10 ng/kg/minute)

After 10 days of treatment with Pentoxifyline (200 mg/day, 20 µg/kg/minute) the increase of PP was non-significant, from 0.98±0.3212
mV/V to 1.553±0.3946 mV/V (p=0.2694,n=16,t=1.127) (Figure 4).
In contrast, we see a highly significant increasing of PP after10 days of treatment with PGE1 (20 µg/day, 10 ng/kg/minute), from
1.223±0.247 mV/V to 5.697±0.8238 (p<0.0001,n=30,t=5.201) (Figure 5).

Figure 4. Peripheral perfusion (mV/V) increase after 10 day of treatment with (20 μg/day, 20 μg/kg/day)
Figure 5. Peripheral perfusion (mV/V) increase after 10 day of treatment with iv PGE1 (20 μg/day, 10 ng/kg/minute)

During the therapy, there were no clinically relevant changes in routine laboratory investigations. Blood pressure, heart rate, and resting
ECG also showed no clinically relevant abnormalities. No serious side effects were observed. Harmless side effects were flush (n=5), reading
of the infusion vein (n=10), and transient diarrhea (first day of infusion) in one patient of the PGE1 group.

Discussion and conclusion

The therapeutic aim in treating a patient with intermittent claudication is to increase the walking distance. Aside from this physical method
of treatment, it is a possible therapeutic alternative in the conservative treatment of PAOD especially in old patients
This study was designed to investigate whether drug therapy with PGE1 or pentoxifylline can be considered a rational addition to walking
exercise. The therapeutic effect of both PGE1 and pentoxifylline in intermittent claudication has been shown, but PGE1 produces an
impressive increase in maximum walking distance and peripheral perfusion (PP).
According to available studies, intravenous PGE1 treatment in combination with concomitant vascular training is a useful therapeutic option
for stage IIb PAOD according to Fontaine's classification.
In patients with good collateral reserve (PP increase after 3o minutes of iv. PGE1 over 100%), prostaglandins increase the maximal walking
distance, the quality of life and could be the first medical option for treatment of intermittent claudication and safe to use in the elderly
patients. The lack of PP increase at 30 minute shows the absence of good collateral circulation, they were non-responders and considered an
exclusion criteria for a long term treatment with PGE1.

References

1. Inter-Society Consensus for the M anagement of Peripheral Arterial Disease (TASC II)
L. Norgren,1* W.R. Hiatt,2* J.A. Dormandy, M .R. Nehler, K.A. Harris and F.G.R. Fowkes
on behalf of the TASC II Working Group 1Department of Surgery, University Hospital, O ¨ vebro, Sweden, 2University of Colorado School
of M edicine and Colorado Prevention Center, Denver, USA. Eur J Vasc Endovasc Surg, 2007, vol 33, S1-S70
2. Allen J, Oates C P, Lees T A and M urray A. Photoplethysmography detection of lower limb peripheral arterial occlusive disease: a
comparison of pulse timing, amplitude and shape characteristics Physiol. M eas.(2005), 26 811–21.
3. L.Fehervari, A.Incze, J.Buzogany, H.Pop, E.Branzaniuc, Cs.Szabados, E.Carasca: Assesment of collateral circulation in peripheral
vascular disease- Erdelyi M uzeum egyesulet, Orvostudomanyi Ertesito,(2010), 83 kotet, 1. kulonszam.
4. Creutzig A, Caspary L, Radeke U, Specht S, Ranke C, AlexanderK. Prospektive randomisierte Doppelblindstudie zur Wirksamkeit von ia
Prostaglandin El bei der schweren Claudicatio intermittens. In: Heidrich H, Bohme H, Rogatti W, eds. Prostaglandin El.
Wirkungen und Therapeutische Wirksamkeit. Berlin/Heidelberg/NewYork/London/Paris/Tokyo: Springer-Verlag; (1988):95.
5. Hepp W, v Bary S, Corovic D, Diehm C, M uhe E, Rudofsky G, Scheffier P, Trubestein G, Vogelpohl M . Therapeutic efficacy of
intravenous prostaglandin El versus pentoxifylline in patients with intermittent claudication. In: Prostaglandin El: New Aspects on
Pharmacology, M etabolism and Clinical Efficacy. Berlin/New York/ London/Paris/Tokyo: Springer-Verlag; (1991):101.
6. Trubestein G, v Bary S, Breddin K, Diehm C, Gruss JD, Heidrich H, Horsch S, Kriessmann A, M aass U, M artin M , M aurin N, Scheffier
P. Intravenous prostaglandin El versus pentoxifylline
therapy in chronic arterial occlusive disease - a controlled randomized multicenter study. VASA. (1989);suppl 28:44.
7. A.Incze, A.Pszota, M onica Dorgo, M irela Orosan, C. Podoleanu, Kincső M átyás, Jázmin Buzogány, E. Carasca: Distensibilitatea
arterelor mari determinată cu ajutorul fotopletismografiei digitale şi a fluxmetriei Doppler în artera radială.- M edicină Internă (2006) (4) p.19-
21.
8. Incze A.,Lazar T.,KissT.,Carasca E.,Podoleanu C.,Bodo A.,Frigy A.,Cotoi S.-Baroreceptor Sensitivity Assessed with the Finger Pulse
Wave Alpha Index,Light Reflection Rheography and Ambulatory Blood Pressure M onitopring aty Two M inutes. Rom.J.Intern.M ed.
(2004),42,1,137-142.

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