Erythropoietin Prevention effect on Induced Apoptosis

Original Article

Erythropoietin Prevention effect on Induced Apoptosis by IschemiaReperfusion in Myocytes of Rat Leila Javadi MS 1, Masood Pezeshkian MD2, Abbas Afrasiabi MD2, Alireza Garjani PhD 1, Leila Roshangar PhD 1 Zahra Golmohammadi MS 3, Mohammad Nouri PhD 1* 1. Dept. of Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Dept. of Cardiac Surgery, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

(Received 29 Jan 2010; Accepted 3 March 2010)

Abstract Background: Ischemia- reperfusion is the common cause of apoptosis in most of cells specially myocytes. Prevention and reduction of apoptosis in myocardium can be one of the main medical goal before surgical operation, angioplasty and after infarction. Erythropoietin receiving effect 24 hours before hypoxia beginning on myocytes apoptosis rate and inflammatory process following half an hour hypoxia and 1.5 hour reperfusion are aims of this study. Methods: 40 Rats were divided randomly into two groups. 24 hours before surgical operation, 5000 Iu/Kg erythropoietin was injected to experimental group. During operation 12 rats from experimental group and 11 rats from control group were lost. After anesthesia, using ligation in left coronary artery for 30 minutes hypoxia and 1.5 hours reperfusion were applied. Then Thorax was opened and after bleeding, the animal’s heart was isolated and two tissue samples of infarct and non infarct area were separated and fixed. Then blood serum samples separated and incubated in -760C. Apoptosis intensity in heart tissue was measured by tunel method, CK-MB level by method and DGKC, hsCRP by Elisa using Immunodiagnostic kit. The results were calculated Mean± SD. Then using paired student’s t- test their difference were shown. Level of statistical significant was considered P< 0.05. Results: Activity level of CK-MB (1550U/L to 340) in experimental group was less than control group (P 10 identifies a pulmonary capillary wedge pressure (PCWP) > 15 mm Hg with a sensitivity of 92% and a specificity of 80% 3. In addition to chronic CHF, a higher E/E' also has been shown to be correlated with a worse prognosis in acute myocardial ischemia and hypertension 4-8. Here, in this study our aims were to evaluate mitral valve annular velocities in different left ventricular segments in patients with first anterior myocardial infarction by means of TDI and to compare them with matched healthy control group.

Methods

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echoes to pass through the clutter filter and remove the blood signals, i.e. to accommodate high echoamplitude and low Doppler velocity signals. The Doppler velocity range was also reduced to correspond to the known velocities of the ventricular wall. Doppler gain and filters were adjusted to obtain the best spectral recordings and the transmitral peak rapid filling velocity (E), peak atrial filling velocity (A) and E-wave deceleration time. Indices derived from TDI, including systolic velocity (S'), early (E') and late (A') diastolic velocities of the lateral, septal, anterior and inferior mitral annulus. Study group 81 consecutive patients with first acute anterior myocardial infarction having normal sinus rhythm and no bundle branch block, diabetes mellitus, hypertension, previous myocardical infarction (MI) and valvular heart disease were included to participate in the study. The diagnosis of acute myocardial infarction had been confirmed by electrocardiographic features, a rise in creatine kinase MB and Troponin-I enzymes and a marked segmental asynergy at conventional echocardiography. Echocardiographic images were recorded within the first week after the onset of myocardial infarction. All patients in the group received Streptokinase (SK). The control group comprised 30 matched healthy volunteers who had normal conventional echocardiographic findings and no history of prior cardiomyopathy, angina, arrhythmias, systemic hypertension or diabetes mellitus. The two groups were similar with respect to baseline demographics, cardiovascular risk factors, and 2D echocardiographic parameters. The basic clinical and conventional echocardiographic parameters for the patients and the healthy subjects are shown in Table 1 and 2, respectively. Table 1- Basic clinical parameters of the subjects

Doppler tissue imaging system We used conventional ultrasound equipment (Vivid 7, GE, U.S.A.) with a phased array transducer 2.5 to 4 MHz and software modifications which allowed the display of regional velocities within the myocardium by M-mode colour Doppler tissue imaging. The concept and technical aspects of the imaging system used in this study have been described in detail elsewhere 15. To permit the acquisition of velocity information, the sensitivity of the scanner has been reduced to allow the tissue

10 /J Cardiovasc Thorac Res

Subjects

Age

male

female

Healthy subjects (n=30)

55.73±17.74

17

13

Subjects with MI which survived one month after MI (n=72)

60.99±13.98

51

21

Subjects with MI which died within one month after MI (n=9)

64.78±10.61

8

1

Tabriz University of Medical Sciences

Evaluation of Systolic and Diastolic Function …

Table 2 - conventional echocardiographic findings of 3 groups LVEF

Healthy subjects (n=30) Subjects with MI which survive one month after MI (n=72) Subjects with MI which dead within one month after MI (n=9)

56.81 ±2.52*

37.57±7*

26± 3.04

Diastolic dysfunction normal

mild

30

-

-

-

-

53

20

8

-

4

3

2

RWMSI

MPI

١*

0.46±0.03*

1.56±0.15*

0.66± 0.16*

1.91±0.19*

0.96± 0.14*

moderate severe

*Identifies significant difference between 3 groups (p38°C) and moderate (6 kg) weight loss. Investigations with CT scan of the chest revealed a cavitary lesion in the lower lobe of the left lung suggesting the presence of a pulmonary aspergilloma, the remaining lung fields being clear. There was no history of any pulmonary infections. Surgical excision of the affected lobe was performed .During surgical exploration we found that the affected lobe receives its blood supply by a large artery from the thoracic aorta. During follow-up his clinical status is excellent. J Cardiovasc Thorac Res 2010; Vol.2 (1): 43-46

Keywords: Aspergilloma ý Pulmonary Sequestration ý Aberrant Artery

*Corresponding Author: Manouchehr Aghajanzadeh MD, Departement of Thoracic Surgery, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran Tel: +98 131-5550028 Fax: +98 9119063079 Email: [email protected]

J Cardiovasc Thorac Res / 43

Journal of Cardiovascular and Thoracic Research

Introduction Bronchopulmonary sequestration (BPS) sometimes referred to simply as pulmonary sequestration, is a rare congenital malformation of the lower respiratory tract. It consists of a nonfunctioning mass of lung tissue that lacks normal communication with the tracheobronchial tree, and that receives its arterial blood supply from the systemic circulation 1. Sequestrations are classified anatomically, as follows: Intralobar sequestration (ILS, also known as intrapulmonary sequestration), in which the lesion is located within a normal lobe and lacks its own visceral pleura; Extralobar sequestration (ELS, also known as extrapulmonary sequestration), in which the mass is located outside the normal lung and has its own visceral pleura. Both types are composed of normal lung tissue, including airway and alveolar elements. A rare variant of sequestration is bronchopulmonaryforegut malformation (BPFM). In this anomaly, the sequestered lung tissue is connected to the gastrointestinal tract. Rare complications include heart failure due to excessive flow through the aberrant artery, massive hemothorax and massive hemoptysis 2-4. Cases have been reported of fibrous mesothelioma and carcinoma Nocardia asteroides infection and aspergillum Arising within Intralobar sequestration (ILS) 5-7. Intralobar pulmonary sequestration associated with asymptomatic aspergillosis is a rare case. We describe the case of a 35-year-old man with undiagnosed intralobar pulmonary sequestration with aspergilloma. A 35-year-old man presented with a 4-month history of cough, hemoptsis, malaise, and fever (>38°C). Moderate (6 kg) weight loss was also reported. He was a current heavy smoker (40 packs/year). His past medical history included only a depression treated with tricyclic drugs. On admission he had no respiratory distress. Pulse was regular at 78 beats/min and blood pressure was 140/80 mm Hg. Physical examination was normal. There was neither cyanosis nor digital clubbing. With the patient breathing room air, arterial bloodgas analysis showed a pH of 7.40, an arterial carbon dioxide tension of 37 mm Hg, and an arterial oxygen tension of 77 mmHg. Blood laboratory


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studies disclosed no further abnormalities. Chest radiography and computed tomographic scanning revealed a left-sided basal cavitary pattern (Fig 1).

Fig 1- Computed tomographic scan of the thorax showing a cavitary lesion in the left lower lobe

Broncscopy with aspiration was not diagnostic. With diagnosis of a symptomatic pulmonary aspergilloma, the patients was candidated for thoracotomy. The patient underwent left posterolateral thoracotomy. At exploration, a gross mass was found in the left lower lobe. Careful separation of adhesions between the lobe and the diaphragm and chest wall allowed the identification of an aberrant large artery of descending thoracic aorta origin. The artery was double ligated and divided (Figure 2, 3). A left lower lobectomy was performed without further difficulty. Histopathologic study revealed the wall of an aspergilloma, a partially eroded lining of metaplastic squamous epithelium, overlying chronic inflammation, lung parenchyma with evidence of atelectasis and bronchectasis and cystic changes (Figure 3). During follow-up the patient was asymptomatic, with no radiographic signs of disease. He has also regained his body weight.


Intralobar Pulmonary Sequestration with …

Discussion

B

Fig 2- (A, B):Show Large Aberrant Artery and Involved Lobe.

Fig 3 pathology of the patient- The wall of the aspergilloma shows a partially eroded lining of metaplastic squamous epithelium, overlying chronically inflamed granulation tissue and scar. Note the large vascular channels with little smooth muscle in their walls. These branches of the bronchial artery can be a source of bleeding.

A pulmonary sequestration refers to nonfunctioning lung tissue with no direct communication with the tracheobronchial tree and with an anomalous blood supply from the systemic vessels. Prycein first described this entity, and subdivided it morphologically into ILS and ELS. ILSs comprises 75% of sequestrations, and are encountered in young adults, usually by the age of 20 years8 .The ILS shares the visceral pleura with the normal lung tissue, and receives its blood supply from the aorta in 94% of cases and it drains into the pulmonary venous system in 95% of cases. Extralobar sequestration is almost exclusively discovered in infancy, due to early onset of symptoms4. The sequestered lung has its own visceral pleura, and may even occur outside the thorax. The ELS blood supply is usually systemic, from branches of the aorta (80% of cases); however, the venous drainage is mainly via the azygos-hemiazygos system (80% of cases) 2-4. The association of ELS with other congenital anomalies (65% of the cases), such as bronchopulmonary foregut malformation, supports an embryonic origin of this entity1. In contrast, ILS may be acquired, with endobronchial supply to the infected area and subsequent hypertrophy of small systemic arteries that supply this area7,9. As our case which had a large and hypertrophied artery. Obstruction triggers recurrent pneumonias. Both forms are usually located in the posterobasal segment of the left lower lobe and in the posterior vascular costodiaphragmatic sulcus between the left lower lobe and the hemidiaphragm, but may occur anywhere in the thorax, or even below the diaphragm1,2,8. Pathologic characteristics include extensive fibrosis and chronic inflammation and cystic changes replacing the lung parenchyma8 . Contrast CT of the chest reveals the complex character of the lesion with its anomalous blood supply. Preoperative aortogram may confirm the diagnosis and identify the vascular supply, in order to avoid catastrophic intraoperative bleeding10. The standard treatment is resection of the segment or lobe that contains the sequestered tissue8,11. Other options are ligation or embolization of the Vascular pedicle. Some authors advocate conservative



antibiotic treatment with surgical intervention only in cases of repeated infections; however, this strategy is rarely used because of the potential of bleeding complications from repeated infections8,10,12. Infection is the major complication of pulmonary sequestration and the sequestered tissue is frequently infected with bacterial pathogens.12 Infection may present as an acute or chronic respiratory illness, with clinical and radiographic findings consistent with pneumonia or abscess. An aspergilloma usually arises in a preexisting cavity in the lungs. A number of infections and other conditions can produce these cavities including tuberculosis, sarcoidosis, neoplasms, cystic fibrosis other fungal infections such as histoplasmosis or coccidioidomycosis, nocardia or invasive aspergillosis. Thus, any condition that causes cavitation in the lungs may subsequently be associated with the development of an aspergilloma. There is only few previous reports of aspergilloma species infection with intralobar bronchopulmonary sequestration11,12. One of them was a 65-year-old woman with intrapulmonary sequestration, anomalous systemic arterial supply to the left lower lobe and aspergillosis who underwent left lower lobectomy and ligation of an anomalous artery by Video-Assisted Thoracoscopic surgery (VATS) 11. During 15 year of my practice I operated three cases of intralobar pulmonary sequestration without preoperative diagnosis. Two of them with symptoms and signs of bronchectasis in right lower lobe and other with left lower lobe mass and their blood supply in two cases was from thoracic aorta and in another case from abdominal aorta.

Conclusion Our patient demonstrated that aspergillos infection can occur in the intralobar pulmonary sequestration. In such conditions an underlying lung malformation, such as pulmonary sequestration, should be suspected. Prompt imaging with attention to vascular anatomy will lead to early diagnosis and treatment.


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References 1. Gerle RD, Jaretzki A III, Ashley CA, Berne AS. Congenital bronchopulmonary-foregut malformation: Pulmonary sequestration communicating with the gastrointestinal tract. N Engl J Med 1968; 278: 14131419. 2. Levine, MM, Nudel, DB, Gootman, N, et al. Pulmonary sequestration causing congestive heart failure in infancy: a report of two cases and review of the literature. Ann Thorac Surg 1982; 34:581. 3. Avishai, V, Dolev, E, Weissberg, D, et al. Extralobar sequestration presenting as massive hemothorax. Chest 1996; 109:843. 4. Rubin, EM, Garcia, H, Horowitz, MD, Guerra, JJ Jr. Fatal massive hemoptysis secondary to intralobar sequestration. Chest 1994; 106:954. 5. Paksoy, N, Demircan, A, Altiner, M, Artvinli, M. Localised fibrous mesothelioma arising in an intralobar pulmonary sequestration. Thorax 1992; 47:837. 6. Gatzinsky, P, Olling, S. A case of carcinoma in intralobar pulmonary sequestration. Thorac Cardiovasc Surg 1988; 36: 290. 7. Muhammad Shibli, MD, Cliff Connery, MD, Janet M. Shapiro, MD Intralobar and Extralobar Bronchopulmonary Sequestration Complicated by Nocardia asteroids. Infection South Med J 2003: 96: 78-80. 8. Pryce DM. Lower accessory pulmonary artery with intralobar sequestration of lung: A report of seven cases. J Pathol 1946; 58: 457-467. 9-Stocker JT, Malczak HT. A study of pulmonary ligament arteries: Relationship to intralobar pulmonary sequestration. Chest 1984; 86: 611-615. 10.Frazier AA, Rosado de Christenson ML, Stocker JT, Templeton PA. Intralobar sequestration: Radiologic-pathologic correlation. Radiographics 1997; 17: 725-745. 11. Sato H, Watanabe A, Yamaguchi T, Harada N, Yamauchi A, Inoue S, Abe T. Pulmonary Sequestration Associated With Asymptomatic Aspergillosis. Ann Thorac Cardiovasc Surg. 2005; 11:41-44. 12. Tanaka M., Miyamoto H., Sakao Y., Harada R., Hata E. A case report of intralobar sequestration associated with lung aspergillus. Nippon Kyobu Geka Gekkai Zasshi 1995; 43: 366-370.


Case Report

A Complicated Radial Artery Pseudoaneurysm Babak Nasiri MD1*, Azin Alizadehasl MD2, Issa Billejani MD3, Rasoul Abdolrahman MD1, Mehdi Toluey MD2 1.Dept. of Cardiac Surgery, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Dept.of Cardiology, Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Dept of Anaesthesiology, Tabriz University of Medical Sciences, Tabriz, Iran.

(Received 6 Jan 2010; Accepted 27 Feb 2010)

Abstract This report presents a case of right radial artery pseudoaneurysm complicated by arterio-venous fistula and absence of ulnar artery. The patient had history of deep vein thrombosis 18 months earlier and was receiving oral warfarin anticoagulation therapy. Doppler study and angiography finding showed poor collateral supply to distal arterial bed. The etiology of this complication and its treatment is controversial. J Cardiovasc Thorac Res 2010; Vol.2 (1):47-50

Keywords: Arterio-venous Malformation ý Pseudoaneurysm ý Radial Artery ý Thenar Mass

*Corresponding Author: Babak Nasiri MD, Department of Cardiac Surgery, Tabriz University of Medical Sciences, Tabriz, Iran. Tel: +98 411 - 3357768 Fax: +98 411 - 3344021 Email: [email protected]



Nasiri et al

Introduction The radial artery is the most frequently used arterial line access with relative safety. Pseudoaneurysm (PA) is a rare complication, and there are reports that it can develop in the setting of the arterial line infection (Ref). Other complications include rupture with bleeding, dissection, thrombosis, hematoma, distal embolization, hand ischemia, local infection, and bactremia (Ref). Arteriovenous malformations have the presence of arteriovenous shunts in multiple capillary beds both on the skin but also involving internal organs (Ref). They are usually accompanied by a bruit and hyperemia with prominent venous out flow.

Case Reoprt A 45 year old woman presented with a painful mass in her right palm. She complained of pain at the same site that worsens by usual daily activity. She had a history of deep vein thrombosis (DVT) 18 months ago and was receiving oral anticoagulation since then. She didn't have other medical illness in her past medical history. She complained of pain upon applying pressure on the thenar side of the palm, resulting limitation in ordinary daily activities. There was no history of penetrating trauma, which is usually the cause of a PA. On the other hand, true aneurysms are mostly associated with repeated mechanical trauma. On examination a swollen mass could be seen over the thenar side of the palm. This diffuse pulsatile swelling was palpable in thenar at the palmar and dorsal side. Sensation of all the fingers was normal. Color Doppler of the right hand showed an evidence of pulsatile flow into the swelling mass in connection with the deep palmer arch suggestive of PA and multiple abnormal tortuosity of the vessels between thenar and intrinsic muscles. In angiography the ulnar artery was cut from origin and radial artery was the main supplying vessel of the hand. Radial artery in distal point was connected to a 3 to 4 cm PA and connected to an abnormal tortuous arteriovenous (A-V) fistula. Cephalic vein was filled immediately through the A-V fistula. Filling defects in the PA suggested the presence of thrombus in it.


Fig 1. The swollen area due to aneurysm of the right radial artery

Fig 2. Angiography showing the aneurysm an A-V fistula and occlusion of the ulnar artery.

Fig 3. Colour doppler of hand showing blood turbulence in the aneurysm and A-V fistula

A Complicated Radial Artery Pseudoaneurysm …

Discussion PA is a pulsatile hematoma in communication with an artery, via disruption of the vessel wall. PAs are well documented complications after surgery, arterial puncture and trauma, and develop after any procedure that causes partial disruption of vessel wall1. Radial artery PAs are being increasingly reported because of widespread use of invasive monitoring2,3. Symptoms occur either due to mass effect by the aneurysm, digital ischemia or nerve suppression. A traumatic PA begins as a sac-like outpouching of the arterial wall. This often starts as an extra-arterial hematoma that undergoes organization. Typically, there is a thinner intimal layer, with fibrosis and decreased vasculature within the medium. This weakened artery is more susceptible to rupture than is the native vessel. Acute exploration of a penetrating injury prevents the formation of a PA by obliterating the site of penetration. The most common causes of radial PA in children and adolescents are penetrating trauma and iatrogenic arterial injury4. This creates an abnormal low-resistance circuit that steals from the high-resistance normal capillary bed. Flow in the afferent artery and efferent vein increases, causing dilatation, thickening, and tortuosity of the vessels. The parasitic circulation causes decreased arterial pressures in the distal capillary beds and can cause tissue ischemia. The increased flow into the venous circulation does not necessarily cause higher venous pressures. However, it can cause vessel wall abnormalities such as thickening of the media and fibrosis of the wall. These changes are known as arterialization. Clinically, PA simulates subcuticular abscess and hematoma and high index of suspicion is necessary to diagnose this condition. Allen’s test and its modifications are widely performed to evaluate adequacy of collateral hand circulation5. The examiner compresses both radial or ulnar arteries for about one minute, while the patient closes both hands as tightly as possible to exanguinate the hands. Subsequently, the patient extends his or her fingers while the examiner maintains compression of the artery. The return of colour to the hand indicates absence of lesions in the artery not compressed. Unfortunately, the traditional Allen’s test carries significant false


positive and false negative results, and additional studies are needed to define the accuracy of some innovative non-invasive tests6. Therefore, the gold standard investigation to assess an efficient collateral flow is still angiography, which is invasive and expensive. Contrast enhanced computerized tomography, conventional angiography and high-resolution duplex color Doppler are useful to confirm the diagnosis. Arteriography is an excellent means of defining the arterial anatomy. Duplex color Doppler has been the only noninvasive investigation of choice with a sensitivity and specificity of 100% in differentiating PA from periarterial hematoma. The blood flow into the venous circulation causes turbulence, which is responsible for the palpable thrill. The thrill is dependent on the geometry of the fistula and does not represent volume of flow accurately. Most radial artery aneurysms are asymptomatic. Known risk factors to the development of PA are abnormal state of the vessel wall (atherosclerosis), multiple attempts at cannulation, hematoma formation, and infection at the cannulation site. Infection lasting more than 48 hours and infection with the bacterium S. Aureus correlate strongly with PA formation7. Some authors support simple ligation of radial artery and excision of the PA if adequate collateral flow can be shown. This treatment strategy is considered satisfactory even in the paediatric population. Indeed, studies on lacerations of the arteries at the wrist, and radial artery harvesting for coronary artery bypass, have shown that the radial artery can be safely sacrificed in adults. Available non-surgical measures rely on thrombus formation, and include ultrasound guided compression repair, reapplication of a compression bandage, and clinical observation of the natural course8. Ultrasound guided compression repair is a non-invasive technique characterised by manual compression of the PA with the transducer probe, maintained for 10 minute intervals, after which time the PA is rechecked for occlusion9. If flow is still present, compression is quickly re-established for additional 10 minute intervals, until occlusion is achieved10,11. Furthermore, restriction of physical activity alone may be curative. Surgery may be reserved for expanding, actively bleeding, or otherwise complicated lesions.



References 1. Kerr CD, Duffey TP. Traumatic false aneurysm of the radial artery. J Trauma 1988; 28:1603–1604. 2. Gaertner WB, Santilli SM and Reil TD. Radial Artery Pseudoaneurysm in the Intensive Care Unit. Ann Vasc Surg. 2010;24:554.e13-6. 3. 3. Afshar A, Nasiri B. Radial Artery Pseudoaneurysm at the Previous Site of Invasive Monitoring. J Teh Univ Heart Ctr 2009; 3: 193-196. 4. Cozzi DA, Morini F, Casati A, Pacilli M, Salvini V, Cozzi F. Radial artery pseudoaneurysm successfully treated by compression bandage. Arch Dis Child 2003; 88:165-166. 5. Allen EV. Thromboangiitis obliterans: methods of diagnosis of chronic occlusive arterial lesions distal to the wrist with illustrative cases. Am J Med Sci 1929; 178:237–244. 6. Almany SL, O'Neill WW. Radial Artery Access for Diagnostic and Interventional Procedures. 1999 by Accumed Systems, Inc. Ann Arbor, Michigan. PAGE 7.


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7. Ganchi PA, Fujita K, Lee WP. Wilhelmi BJ. Ruptured pseudoaneurysm complicating an infected radial artery catheter: case report and review of the literature. Ann Plast Surg. 2001; 46: 647- 650. 8. Esfe AR, Bozorg SM, Yazdi HR.. Pseudoaneurysm of a high origin radial artery treated by ultrasoundguided compression. Singapore Med J. 2009;50:e2502. 9. Dean SM, Olin JW, Piedmonte M, Grubb M, and Young JR. Ultrasound-guided compression closure of postcatheterization pseudoaneurysms during concurrent anticoagulation: A review of seventy-seven patients cases. J Vasc Surg 1996; 23: 28-35. 10. Schaub F, Theiss W, Busch R, Heinz M, Paschalidis M, and Schomig A. Management of 219 consecutive cases of postcatheterization pseudoaneurysm. J Am Coll Cardiol, 1997; 30: 670-675. 11. Sheikhzadeh A, Hakim H, Ghabusi P, Ataii M. Right pulmonary artery-to-left atrial communication: recognition and surgical correction. Am Heart J 1984; 107: 396-398.


Case Report

Cardiac Arrest in a Case of Mucopolysaccharidosis after Tracheostomy Mahin Seyedhejazi MD1*, Daryoush Sheikhzadeh MD1, Behzad Aliakbari Sharabiani MD1 1. Dept. of Anesthesiology, Tabriz Children Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.

(Received 29 Sep 2009; Accepted 23 Jan 2010)

Abstract Airway management during induction of anesthesia is difficult in some metabolic disorders like mucopolysaccharidosis (MPS). In this article we report an 11 years old child with Hurler-Scheie syndrome how was admitted to operating room for thracheostomy under general anesthesia. Mask ventilation was difficult and endotracheal intubation was impossible and anesthesiologist ventilated the patients lung by inserting laryngeal mask airway. The purpose of this article is to increase awareness among anesthetists and surgeons about the anatomical and pathophysiological changes in these syndrome which may lead to severe airway problems and complications in perioperative period. J Cardiovasc Thorac Res 2010; Vol.2 (1): 51-53

Keywords: Mucopolysaccharidosis ý Hurler-Scheiesyndrome ý Difficult Intubation

Corresponding Author: Mahin Seyedhejazi MD, Department of Anesthesiology, Tabriz Children Hospital, Tabriz University of Medical Sciencs, Tabriz, Iran.

Tel: +98 411 -5262250

E-mail: [email protected]



Introduction Mucopolysaccharidosis (MPS) are a group of inherited disorders of connective tissue metabolism in which lysosomal enzyme deficiency leads to deposition of mucopolysaccharides or glycosaminoglycans in the airway, cornea, brain, heart, liver, spleen, bones,… producing different symptoms. The perioperative management of a case of MPS is considered as a challenge to the anesthetist. It represents one of the worst airway problems in pediatric anesthesia. Case An 11 years old male (weight 19 kg) child of Hurler-Scheie Syndrome was exposed to general anesthesia for tracheostomy. He was diagnosed as MPS at the age one. The features of Mucopolysaccharidosis gradually progressed over the years. He developed stiffness of joints of upper and lower limbs. He was short in stature (85cm) and had an apathetic face with saddle deformity of nose, antimonogolian eyes, small lower jaw, glossoptosis and a normal mental function. He had a history of sleep apnea, respiratory distress, inspiratory and expiratory stridor from the age of two. He had surgery for cleft palate repair, adenotonsilectomy and ear ventilation tube (VT) replacement and inguinal hernia repair when was 4, 6, and 7 years old respectively in our center without any event (difficult intubation). His age was not correlated with his appearance. He had multiple hospitalizations because of respiratory problems. He had severe respiratory distress in supine position. His tongue was very large with limited mouth opening and malampatti grade 4 views. He had a short neck with limited extension. ECG, NIBP and SpO2 monitors were attached. He was preoxygenated with 100% oxygen in sitting position. Anesthesia was induced with fentanyl 10 µg, midazolam 1mg, propofol 20 mg, lidocaine 10mg. He had spontaneous ventilation. Mask ventilation was difficult and endotracheal intubation was impossible with direct laryngoscopy. It wasn't possible to pass fibroptic bronchoscope transducer through mouth and nose because of huge tongue. The patient ventilated through larynged mask airway (LMA) No 2 and was stable during


Seyedhejazi et al

tracheostomy. Maintenance of anesthesia was with halothane 1-1.5%. The LMA was removed when he was awake. In recovery room the general condition of patient was deteriorated and Spo2 declined. We couldn't ventilate the patient through tracheostomy tube and because of airway obstruction the patient had cardiac arrest that did not respond to complete sequence of CPR with early defibrillation.

Discussion Hurler syndrome or MPS 1 H is the prototype of MPS and is the most severe form of it. It has been described, as posing worst airway problem in pediatric anesthesia. MPS are rare conditions, incidence varying from 1 in 24,000-500,000 population2,3. Knowledge of the anesthetic implications of the disease is essential to prevent any catastrophe. The anesthesiologist may face diverse problems while anesthetizing these patients. The most important and life threatening problem is difficulty in maintaining airway while anaesthetizing such patients because of the anatomical changes in upper airway due to deposition of mucopolysacchrides in tongue, tonsils, adenoid, epiglottis, glottis and trachea 2, 3, 4, 5. They also have excessive tracheobronchial secretions with frequent upper respiratory infection. Chest deformity along with deposits in lower respiratory tract and lung interstitium may cause obstructive lung disease and diffusion defects leading to hypercapnia, hypoxia and elevated airway pressures. In preanesthesia survey the type of MPS syndrome should be confirmed as it has a great implication for the degree of difficulty anticipated during airway management. Child’s intelligence and behavior are important. In Children with MPS, behavior may vary from uncooperative belligerent to placid, cooperative and lovable. Child’s favorable sleeping position should be inquired, since this may be the position in which airway is held open. History of snoring and sleep apnea should be asked. Thorough examination of cardiovascular system and respiratory system is required. Cardiovascular defects and its implications in anesthesia should be taken care. Lung function should be optimized preoperatively by energetic physiotherapy and

Cardiac Arrest in a Case of Mucopolysaccharidosis …

antibiotic treatment of preexisting pulmonary infection. In all cases of MPS excessive deposition of mucopolysaccharides continues throughout the life with a special predilection for tracheal cartilages, therefore clinical features worsen in all of them as age advances. In children with MPS, maintaining airway with facemask is difficult as they have macroglossia, narrow upper airway and limited temporomandibular joint mobility. Airway management often becomes more difficult by insertion of an oropharyngeal airway as it pushes their long high anterior epiglottis over the laryngeal inlet or may buckle the posterior end of large tongue causing occlusion of the airway. Nasopharyngeal airway may sometime improve the airway but there is often difficulty in inserting it due to deposits in the nasopharynx. Kempthome et al. used tongue suture in a patient to pull the enlarged tongue forward to relieve obstruction. Laryngoscopy may be unduly difficult in patients with MPS as they have oral and laryngeal deformity, rigidity of the area and copious viscous oral secretion. A high laryngeal inlet (C2) and an anteriorly inclined larynx will usually make intubations difficult. Awake fiberoptic intubation is the method of choice in these children. But because of subnormal mental function, it will not be easy to perform awake fiberoptic intubation in these children 4. In our case it was impossible because of huge tongue. Blind nasal intubation, was also tried. LMA has been used successfully in these patients specially when intubation failed (as our case). It was also considered as an excellent aid to fiberoptic intubation in more difficult cases of MPS. Tracheostomy is difficult in these children as they have short neck, mucopolysaccharide deposits anterior to trachea and a relatively narrow trachea. In a case report it was found to be impossible even at postmortem. Cricothyrotomy is not recommended in MPS patients as their cricothyroid membrane, cricoid cartilage and thyroid cartilage are often thickened and deformed by mucopolysaccharides deposits making rapid dissection difficult and vocal cord damage likely2. Distal tracheal obstruction can not be bypassed by endotracheal intubation or tracheostomy and may prove fatal 1, 2, 4. Thus severe


airway difficulty can occur while anaesthetizing such children. In all cases inhalation induction with maintenance of spontaneous ventilation is preferred but in mentally retarded and uncooperative patient intravenous induction is more satisfactory. In all these patients spontaneous ventilation should be maintained until adequate airway control is achieved 1, 4. Therefore as a rule of thumb spontaneous ventilation should be maintained until the airway is secured. Recovery after GA in patients with MPS is often slow and accompanied by periods of breath holding, apnea, bronchospasm, cyanosis and respiratory arrest. Therefore anesthetic sequences which ensure early return of consciousness and airway reflexes were strongly recommended. Regional anesthesia offer a valuable and a safe alternative for children with MPS undergoing lower abdominal, perineal, upper and lower extremity 5. In conclusion, in children with MPS, anesthesiologist and surgeons should be aware of the expected complications. The benefit of the surgical procedure should be balanced against the risk of exposing the child to general anesthesia. The parents of the patient should properly be informed of the risk involved. Anesthesia should ideally be given by the anesthesiologists who are experts in handling pediatric airway problems and resuscitation, in a center in which pediatric intensive care facilities are available.

References 1. Moores C, Rogers JG, McKenzie IM, Brown TCK. Anaesthesia for children with Mucopolysaccharidosis. Anaesth Intensive Care 1996; 24: 459-463. 2. Diaz JH, Belani KG. Perioperative management of children with Mucopolysaccharidosis. Anesth Analg 1993; 77: 1261-1270. 3. Herrick IA, Rhine EJ. The Mucopolysaccharidosis and Anesthesia. A report of clinical experience. Can JAnaesth 1988; 35: 67-73. 4. Kempthome PM, Brown TCK. Anesthesia and Mucopolysaccharidosis. Anaesth Intensive Care 1983; 11: 203-207. 5. Sjogren P, Pedersen T, Steinmetz H. Mucopolysaccharidosis and Anesthetic risks. Acta Anaesthesiol Scand 1987; 31:214-218.

