2003 ACC Abstract submissions.

 

IDIOPATHIC HYPEREOSINOPHILIC SYNDROME OF THE HEART.

F Omar MD,  D Obeid MD, G Krishnamorthy MD.
Sinai-Grace Hospital/Wayne State UniversityDetroit, Michigan.

 

Presented by: Fazal Omar, MD - Sinai-Grace Hospital/Wayne State University

 

Idiopathic Hypereosinophilic Syndrome (Loeffler’s syndrome) is a rare disease characterized by eosinophilia associated with signs and symptoms of end organ dysfunction.  Most commonly it affects the heart, skin, nervous system, lung and spleen.

Here we present a case of Loeffler’s syndrome with a cardiac presentation.

 

The patient is a 30 year old male presented with atypical chest pain.  He had normal physical exam but stress test showed a partially reversible apical defect.  He had high eosinophil count unexplained by any other etiologies.  Cardiac catheterization showed normal coronaries; 2-D echo showed increased endomyocardial echodensity at the apex which suggested Loffler’s syndrome.  Biopsy of the Myocardium revealed eosinophilic infiltrates thus confirming the diagnosis of Loeffler’s syndrome of the heart.  The patient was started on Steroids and experienced significant clinical improvement.

 

It is very important to diagnose Loeffler’s syndrome as early as possible because starting treatment early will decrease mortality and morbidity especially in younger male patients.

 

Submitted for ACC Oral Case Presentation

 

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY/ DYSPLASIA: PRESENTING AS SHOCK, ACUTE RENAL FAILURE AND TRANSIENT MESENTERIC ISCHEMIA.

Manesh Kottapuram, M.D., Barry Lesser, M.D., F.C.C.P., Department of Medicine, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.

 

Presented by: Manesh Kottapuram, MD - Sinai-Grace Hospital/Wayne State University

 

Arrhythmogenic right ventricular (RV) Cardiomyopathy/Dysplasia (ARVC/D) is a rare myocardial disease affecting primarily the RV and characterized histologically by the gradual replacement of cardiomyocytes by fibro-fatty tissue.  It can diffusely involve the whole myocardium and culminate in biventricular heart failure, arrhythmias and sudden death in young patients.

 

We present a forty-five year old African-American man brought to the emergency room (ER) with complaints of fever, abdominal pain, vomiting and bloody diarrhea of four days duration.  He was a smoker and there was no significant past or family medical history.  At admission, he was hypothermic (93oF), tachycardic (130/minute), tachypneic (40/minute) and hypotensive (50/palpable).  He appeared drowsy, dehydrated and had diffusely tender abdomen with decreased bowel sounds.  His stool was positive for occult blood.  Initial labs were significant for Na+ 127, Cl- 82, HCO3- 12 (mmol/L); BUN 70, Creatinine 8.7 (mg/dL); WBC 10.6 (bands 3.8) K/mm3; ALT 162, AST 257 (U/L), and lactic acid 4.9 mmol/L.  Electrocardiogram was significant for sinus tachycardia and abdominal x-ray showed small bowel wall edema with ileus.  He remained hypotensive despite intravenous fluids, vasopressors and broad spectrum antibiotics.  Abdominal CT showed distal small bowel edema with pneumatosis intestinalis and pneumobilia suggestive of bowel infarction.  He underwent laporotomy, during which he sustained cardiopulmonary arrest with asystole and was resuscitated.  No bowel ischemia was detected and he was transferred to the intensive care unit on multiple vasopressors with intestines in a Bogota bag sutured to abdominal wall.  His right heart catheterization showed cardiac index = 2.53 l/min/m2, wedge pressure = 17 mm Hg, central venous pressure = 20 mm Hg and he died after few hours.  Autopsy demonstrated ventricular hypoplasia with fibro-fatty replacement of myocardium consistent with ARVC/D, visceral congestion and normal small intestine and colon.  We believe with our patient, a low flow state had occurred resulting in the constellation of findings described above and we are at a loss to explain the transient nature of the ischemic bowel given the dramatic findings on CT scan.

 

ARVC/D is typically seen in young men as an autosomal dominant trait with multiple factors facilitating gene expression.  Physicians should consider this condition in young subjects with cardiac arrhythmias or unexplained cardiomyopathy. Treatment includes class I antiarrhytmic drugs, beta blockers, amiodarone, radiofrequency ablation and patients with high risk of sudden death should receive an implantable cardioverter/defibrillator.

 

Submitted for ACC Oral Case Presentation

 

Expression of B2 subunit mutants alters localization of L-type calcium channels in rat adult cardiomyocytes

Sinoj K John MD, Sabine Telemaque-Potts MD, Terrie Grain MD, Jeffrey T Potts MD, James D Marsh MD. Sinai-Grace Hospital, Wayne-State University, Detroit, Michigan, Internal Medicine - Cardiology, Wayne-State University, Detroit, Michigan.

 

Presented by: Sinoj k. John, MD - Sinai-Grace Hospital/Wayne State University

 

Introduction:

The a1C subunit of the L-type calcium channel is the pore-forming subunit of the channel, allowing calcium entry into cardiomyocytes and other cells. The intracellular b2a subunit acts as a chaperone and interacts with the intracellular loop of the a1C subunit. We tested the hypothesis that overexpession of mutated b subunits could alter membrane localization and ultimately channel function.

 

Methods:

Isolated rat adult cardiomyocytes were infected with adenovirus constructs. The GFP-fusion constructs encoded either the full-length b2a subunit (GFP-Full) or putative dominant-negative mutants of the beta interaction domain (BID) portion of the subunit (GFP-BID: BID only; GFP-N-BID: N-terminal + BID), under CMV promoter control. After 24 hr, cells were fixed and visualized by epifluorescence microscopy using standard methods.

 

Results:

Analysis of 5 independent cell isolations showed that GFP or GFP-BID are localized to the cytosol of the myocyte. In GFP-N-BID-infected myocytes, a distinct punctate pattern of protein expression was observed in all infected cells, without cell membrane localization. In cells infected with the full-length b2a subunit adenovirus (GFP-Full), the fluorescence was exclusively visible at the cell membrane.

 

Conclusion:

These results suggest that beta subunit decoys can alter localization of the L-type calcium channel to the sarcolemma, which could result in reduced contractile performance.

 

Submitted for ACC Poster Research  Presentation

 

CORONARY ARTERY DISEASE RISK FACTORS AMONG PATIENTS WITH UNRECOGNIZED DEPRESSION. Mehrdad Ghaffari, MD,  Haleh Haerian, MD, Mohamed Karim, MD, Rajika Munasinghe, MD, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.

 

Presented by: Mehrdad Ghafffari, MD - Sinai-Grace Hospital/Wayne State University

 

Introduction: Depression is associated with increased morbidity and mortality in patients with established coronary artery disease (CAD) but the association between depression and CAD risk factors has been found to be variable. The objective of this study was to determine the extent of unrecognized depression in an inner city, primary care internal medicine practice and to evaluate the CAD risk among patients with unrecognized depression.

 

Methods: Patients without a prior diagnosis of depression were screened using the Prime MD questionnaire, a validated screening tool developed to evaluate for depression. Information on CAD risk factors was obtained from chart review. The prevalence of individual CAD risk factors and the composite 10 year CAD risk based on the Framingham equation was calculated. The CAD risk of patients with depression was compared with a control group without depression.

 

Results: Out of a total of 215 patients evaluated, 53 (24.6%) screened positive for unrecognized depression. A total of 103 patients without depression and 39 patients with depression had complete information for a comprehensive assessment of 10 year risk of CAD. Patients with depression were younger (Mean age 51 vs 56 years P<.035) and had higher diastolic blood pressures (DBP 86 vs 76 mmHg, P<.01) compared to patients without depression. The 10 year CAD risk among patients with depression was 9% and comparable to patients without depression (11%, P=.15). Other CAD risk factors were similar between the two groups.

 

Discussion: Unrecognized depression among patients surveyed in our practice was comparable to previous estimates reported in the literature. We did not find unrecognized depression to be associated with a higher risk for CAD.  

 

Submitted for ACC Poster Research  Presentation

 

DO PATIENTS WITH UNRECOGNIZED DEPRESSION RESPOND DIFFERENTLY TO CAD RISK MODIFICATION IN THE PRIMARY CARE SETTING? Mehrdad Ghaffari, MD, Haleh Haerian, MD,  Mohamed Karim, MD, Rajika Munasinghe, MD, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.

 

Presented by: Mehrdad Ghafffari, MD - Sinai-Grace Hospital/Wayne State University

 

Introduction: Depression is known to adversely affect compliance with medical therapy and rehabilitation after myocardial infarction. The impact of unrecognized depression on the response of modifiable CAD risk factors to intervention in the primary care setting is less well known.

 

Methods: Established patients in a primary care internal medicine practice were screened for unrecognized depression using the Prime MD questionnaire, a validated tool used to screen for depression. Information on the most recent CAD risk assessment and the predicted 10 risk of CAD based on the Framingham equation was compared with the initial assessment of these variables. The magnitude of change in each of the individual CAD risk factors, and the composite 10 year risk of CAD in patients with unrecognized depression was compared with a control group.

 

Results: The systolic and diastolic blood pressures, the LDL cholesterol level and the Hemoglobin A1c of diabetic patients decreased significantly with treatment. The mean 10 year risk of CAD declined from 13.7% to 11.9% (p<.001). There were no significant differences in the magnitude of change in CAD risk factors and the 10 year CAD risk between patients with unrecognized depression and controls. The power of this study to detect a 5% or greater difference in each of the CAD risk factors was greater than 80%.

 

Conclusion:  Unrecognized depression does not appear to influence the treatment of CAD risk factors in the primary care setting. Independent of this finding both CAD prevention and screening and treatment of depression should be pursed aggressively to improve patient outcomes.

 

 

Submitted for ACC Poster Research  Presentation

 

 

IMPLANTABLE-DEFIBRILLATOR THERAPY IN COXSACKIE VIRUS-INDUCED CARDIOMYOPATHY

Lourin Chahin, MD, Apurva Motivala, MD, Atul Singh, MD, Marc Meissner, MD, FACC, Dept. of Medicine, Sinai-Grace Hospital, Wayne State University - Detroit, Michigan.

 

Presented by: Lourin Chahin, MD - Sinai-Grace Hospital/Wayne State University

 

Case Report

We describe a 20-year-old African-American male presenting with severe symptoms of congestive heart failure (CHF) following an upper respiratory infection.  Physical examination revealed respiratory distress, bilateral rales, summation gallop and mitral regurgitation murmer.  2D-echocardiography revealed left ventricular ejection fraction of 20%, global hypokinesis, mitral and tricuspid regurgitation.  He was discharged after good response to pharmacologic therapy.

 

Hypertension, alcohol, toxins, illicit drugs were excluded as etiologies. His presentation was felt to be due to post-viral myocarditis/cardiomyopathy.  Thus, we requested Coxsackie blood titers. B5 titers returned as 1:320.

 

The patient returned 2 weeks later with CHF exacerbation.  Telemetry tracings variously revealed unsustained atrial tachycardia, AV- block (Wenckebach, high-grade, 4-second ventricular asystole), and rapid unsustained ventricular tachycardia (VT).

 

A dual-chamber implantable defibrillator (ICD) system was placed, to allow safe optimization of medical therapy (eg. use of beta blockers in face of above-noted AV-block), and to protect against sudden death, to which such patients are very vulnerable.  Subsequent ICD testing revealed elevated defibrillation thresholds (DFTs), and the system was modified:  generator change and addition of defibrillation-pacing lead placed in a posterolateral coronary vein via the coronary sinus.  This resulted in successful biventricular pacing and good DFTs.

 

Conclusion

This case highlights several interesting points:  wide range of brady- and tachy-arrhythmias in a young man with Coxsackie cardiomyopathy; technical feasibility and potential therapeutic value of biventricular 3-lead ICD system capable of improving CHF symptoms and protecting against sudden death.

 

Submitted for ACC Oral Case Presentation

 

MASSIVE RIGHT VENTRICULAR THROMBUS PRESENTING AS ACUTE ABDOMEN

Manesh Kottapuram, MD, Shazia Essani, MD,  Department of Internal Medicine, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.

 

Presented by: Manesh Kottapuram, MD - Sinai-Grace Hospital/Wayne State University

 

Acute cor pulmonale due to massive right ventricular thrombus presenting as acute abdomen is a rare event. 

 

We present a 21 year old caucasian woman who presented to the emergency room with sudden onset of abdominal pain and shortness of breath.  Pain was continuous and generalized but mainly in the left upper and lower quadrant.  She had three episodes of vomiting.  Past medical history was significant for asthma.  She was actively using cocaine and heroin at the time of hospital admission.  Her initial blood pressure was 100/60 mm of Hg, pulse rate of 112/minute, respiration of 36/minute and was afebrile.  Her oxygen saturation was 92% on 50% oxygen.  She had diffusely tender abdomen with rebound and guarding but no rigidity.  Bowel sounds were sluggish.  She had 2 cm jugular venous distention and a 2/6 pansystolic murmur in left lower sternal border.  Her labs were significant for ALT 143, AST 214 (U/L), and PT 13.6.  Electrocardiogram was significant for sinus tachycardia, right atrial enlargement and incomplete right bundle branch block.  Her CT scan of abdomen and pelvis showed hepatomegaly, large ascites, and cardiomegaly with dense opacification of cardiac chambers suggestive of delayed circulation.  2D echo showed dilated right atrium and 80% of right ventricle cavity occupied by a heterogeneous echoic mass suggestive of tumor.  She also developed DVT involving left brachial, axillary, internal jugular and subclavian vein during hospitalization.  She underwent open heart surgery and the mass was removed.  Histology of the lesion demonstrated a chronic organized thrombus.  Culture of the thrombus was negative.  Her initial hypercoagulable workup (including antiphospholipid antibody syndrome) was negative.

 

 

Right ventricular thrombus has been described in literature, as they were associated with antiphospholipid antibody syndrome and Behcet’s disease.   In our patient none of these were found.  Also in our patient right ventricular thrombus simulated a cardiac tumor, which is a rare presentati

 

Submitted for ACC Oral Case Presentation

 

MATURATION OF THE MICROVASCULATURE IN HEALING MYOCARDIAL INFARCTS: A POTENTIAL ROLE FOR PDGF.

1KAMAL NASSER, MD, 2GUOFENG REN, PhD AND 2NIKOLAOS FRANGOGIANNIS, MD

1Department of Internal Medicine, Sinai-Grace Hospital, Detroit Medical Center/Wayne State University, Detroit MI, and 2Section of Cardiovascular Sciences, DeBakey Heart Center, Baylor College of Medicine, Houston TX.

 

Presented by: Manesh Kottapuram, MD - Sinai-Grace Hospital/Wayne State University

 

Background: The microvasculature in healing wounds undergoes dynamic changes leading to formation of mature pericyte-coated vessels. Platelet Derived Growth Factor (PDGF) is crucial for the formation of a pericyte coat in the developing embryonic vasculature. We hypothesize an important role for PDGF in vascular maturation of infarct neovessels, critically regulating healing.

 

Aims: To investigate the dynamic changes in the infarct microvasculature and the phenotypic characteristics of smooth muscle cells and fibroblasts in canine and murine models of experimental myocardial infarction, and to study the role of PDGF in maturation of the infarct neovasculature.

 

Methodology: We used established canine and murine models of experimental myocardial infarction. Hearts were processed and used for histological studies. Isolated canine jugular vein endothelial cells were used for in vitro experiments.

 

Results: The proliferative stage of infarct healing is characterized by myofibroblast accumulation and a high number of capillaries critical for sustaining metabolism. In both canine and murine models, infarct maturation is associated with a decreasing capillary density and an increasing number of pericyte coated vessels (p<0.01, 7d reperfusion vs 28 days reperfusion). The muscular coat of infarct vessels stains for a-Smooth Muscle Actin (a-SMAc) and calponin. Only a subset of the vessels exhibits expression of desmin and smoothelin, markers of mature contractile smooth muscle cells. PDGF is highly expressed in infarct neovessels. In addition, PDGF Receptor b is markedly upregulated in pericyte-like cells infiltrating the infarcted myocardium. PDGF receptor a synthesis is found in a subset of myofibroblasts and endothelial cells. Purified PDGF and recombinant PDGF-AA and –BB significantly induce mRNA expression of the matrix cross-linking enzyme tissue transglutaminase (tTG) in canine endothelial cells.

 

Conclusion: The infarct microvasculature undergoes dynamic changes leading to formation of mature pericyte-coated vessels. PDGF may play an important role in maturation of the infarct vasculature through regulation of vascular pericyte coating and by inducing endothelial expression of the cross-linking enzyme tTG, promoting endothelial basement membrane maturation. Further experiments using neutralizing antibodies in mice undergoing infarction protocols will determine the role of PDGF in healing infarcts.

 

Submitted for ACC Poster Research  Presentation

 

RIGHT ATRIAL MASS PRESENTING AS SYNCOPE – A CASE REPORT. Siddhartha Annamraju, MD, Vijayalakshmi Sankaranarayanan, MD, Antonio Carrillo, MD, FACC and Frank Baciewicz, MD, Sinai-Grace Hospital, Detroit Medical Center / Wayne State University, Detroit, Michigan

 

Presented by: Siddhartha Annamraju, MD - Sinai-Grace Hospital/Wayne State University

 

Right atrial masses, viz. myxomas and thrombi are not entirely uncommon clinical occurrences. Thrombi attached to the tip of indwelling intravascular catheters aren’t infrequent either. However, masses attached to the tips of catheters and extending into the right  atrium and ventricle causing syncope, to the best of our knowledge, have not been reported in the literature. We present to you the case of a 45-year old lady who presented to our Emergency Department with syncope and cyanosis. She had a Denver shunt placed earlier for cirrhosis. A trans-thoracic echocardiogram showed a 7 X 3.5 cm cystic mass in the right atrium moving in and out of the right ventricle with each cardiac cycle. An atriotomy was done to remove the mass. This case reveals a unique, hitherto unreported, complication of an indwelling intravascular catheter.

 

Submitted for ACC Oral Case Presentation

 

NON-OBSTRUCTIVE TRIPLE VESSEL CORONARY ARTERY ANEURYSMS CAUSING ST ELEVATION MYOCARDIAL INFARCTION: A CASE REPORT.

Fadi A. Saab, MD, Surendra Marur, MD, and Antonio Carrillo, MD, FACC.  Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.

 

Presented by: Fadi Saab, MD - Sinai-Grace Hospital/Wayne State University

 

Multiple Coronary Artery Aneurysms are rarely seen in adults.  In association with Myocardial Infarction, there are less than ten cases reported since 1967. 

 

A 55 year-old African- American male presented to the emergency department with classical features of myocardial infaction.  Risk factors for coronary artery disease included cigarette smoking and strong family history. EKG displayed ST-elevations in the inferolateral leads.  He was treated with Reteplase, intravenous heparin, intravenous nitroglycerin, beta-blocker, and aspirin.  He continued to have angina and underwent emergency cardiac catheterization which revealed diffuse aneurysmal dilatation of the Right Coronary, Left Anterior Descending and Left Circumflex Arteries with slow flow.  Dilatations ranged from 6 to 8 millimeters.  No occlusions were seen.  Our patient was discharged two days later with standard medical management and Cardiac Rehabilitation Phase II.

 

In adults, in addition to congenital aneurysms the etiology of Multiple Coronary Aneurysms includes Systemic Lupus Erythematosis, Neurofibromatosis, Atherosclerosis and Chest Trauma.  Treatment options include lifelong anticoagulation, stenting, and surgery although not all authors agree that any treatment is required.  Our patient had no evidence of any of the above etiologies for Coronary Aneurysm outside of possibly a Congenital cause.

 

Coronary Aneurysms are rare in adults and even more rarely lead to ST-Elevation Myocardial Infarction.  A consensus on any treatment in addition to the standard Myocardial Infarction medical management has yet to be reached.

 

Submitted for ACC Oral Case Presentation

 

Protection of Cardiomyocytes against Metabolic Stress by 17b-Estrogen in Culture

Manesh Thomas Kottapuram, M.D., Department of Internal Medicine, Sinai-Grace Hospital; Dr.Kuo TH, Department of Cell Pathology, Wayne State University School of Medicine, Detroit, Michigan.

 

Presented by: Manesh Thomas Kottapuram, MD - Sinai-Grace Hospital/Wayne State University

 

Objectives:

To understand the mechanism in which estrogen protects cardiomyocytes in culture against metabolic stress injury.          

 

Background:

Recent clinical studies indicate that females are protected from a variety of cardiac events including ischemic injury comparable to the male counterparts (ref.1).  The beneficial effects of estrogen on the cardiovascular system have been traditionally ascribed to decrease in peripheral vascular resistance and antiatherogenic action (ref.2, 3).  However the molecular mechanism for this protection is still poorly understood.

 

Hypothesis:

Estrogen may protect cardiomyocytes by upregulating the Akt kinase signal transduction pathway and by accomplishing Ca2+ homeostasis at cellular level against different metabolic stresses. 

 

Methods:

Ventricular cardiomyocytes isolated from female Sprague- Dawley rats (ref.4) were incubated in serum free culture medium with and without 17 b- estradiol.  Then cells were either lysed to isolate proteins for detection of (a) activation of Akt signal transduction pathway or (b) treated with various agents (2-3 DNP, Thapsigargin, and Ionomycin) to induce chemical hypoxia and Ca2+ loading in cardiomyocytes.  Activation of Akt kinase determined by Western Blot assay (ref.5) using specific anti-phospho-Akt antibody.  Ca2+ loading and its subsequent homeostasis assessed by Fura-2 dye and dual excitation fluorometer (ref.6). 

 

Results: 

Estrogen may upregulate Akt signal transduction pathway in cardiomyocytes.  Pre-treatment with estrogen significantly affects Ca2+ loading in cardiomyocytes either by decreased rate of loading or by facilitating efflux of cytoplasmic Ca2+.

 

Conclusion:
The preliminary reports may support the hypothesis of “protective effect of estrogen on cardiovascular system can be attributed either to the upregulation of Akt kinase signal, which is a well-known ‘antiapoptotic’ cell survival signal or to the efficient cytoplasmic Ca2+ homeostasis in cardiomyocytes”.

 

Submitted for ACC Poster Research  Presentation

 

ICD DEFIBRILLATION THRESHOLD DETRMINATION VIA SINGLE VF INDUCTION

Siddhartha Annamraju, M.D., Randy Lieberman, M.D.,FACC, Marc Meissner, M.D.,FACC, Sinai-Grace Hospital, Wayne State University, Paul DeGroot, Michael RS Hill, Medtronic Research

 

Presented by: Siddhartha Annamraju, MD - Sinai-Grace Hospital/Wayne State University

 

Introduction: Determination of defibrillation threshold (DFT) at the time of ICD implant enables programming the ICD to an energy less than full output. This decreases capacitor charge time and episode duration and conserves battery energy. However, accepted DFT protocols such as Binary Search (BS) or Step-Down methods require multiple VF (ventricular fibrillation) inductions. Fewer VF inductions and an appropriate determination of DFT are clinically desirable. We hypothesized that the DFT can be determined by a single VF induction utilizing a Step-Up (SU) protocol.

 

Methods: After informed consent was obtained, paired DFTs were determined in patients undergoing initial ICD implant for approved indications using an active Can + transvenous RV lead system. In the SU protocol, energies of 3-6-10-12-15-18 joules were delivered sequentially after a single VF induction until VF was terminated. SU DFT was defined as the energy that terminated VF. DFT was also measured using BS protocol starting at 12 J with 6 J and then 3 J steps. VF not terminated by highest protocol energy was shocked externally and a DFT of 24 J assigned.

 

Results: 25 patients were enrolled. Age – 54 ± 15 years, EF 25 ± 9 % and CAD 65%. SU DFT and BS DFT were identical in 15/25 patients. In 5 patients, SU DFT was 3 J < BS DFT. In 5 patients, SU DFT was 3 J  > BS DFT. On a second repeated VF episode, SU DFT was identical to the first in 21/25 patients.

 

Conclusions: SU DFT highly correlates with BS DFT and is highly reproducible. SU protocol reduces the number of VF inductions needed to determine DFT. SU protocol reduces total time in VF compared to the BS protocol. Further clinical research is required to verify the suitability of determining DFT and programming ICDs based on a single VF induction via SU protocol.

 

Submitted for ACC Poster Research  Presentation

THE ROLE OF FINE PARTICULATE AIR POLLUTION AND ELEVATION OF CIRCULATING ASYMMETRIC DIMETHYLARGININE (ADMA) LEVELS
Sanjay Rajagopalan, MD1, Robert D. Brook, MD1, Gerald J. Keeler, PhD1, J. Timothy Dvonch, PhD1, Frank J. Marsik, PhD1, Masako Morishita, PhD1, Jeff R. Brook, PhD2, Lou D’Alecy, PhD1, Apurva Motivala, MD3, Edward J. Timm4, James Wagner4, and Jack R. Harkema, DVM PhD41The University of Michigan, Ann Arbor, 2University of Toronto, Canada, 3Sinai-Grace Hospital/Wayne State University, Detroit, 4Michigan State University, East Lansing.

Presented by: Apurva Motivala, MD - Sinai-Grace Hospital/Wayne State University

Background and Aim: The health effects of fine ambient particulate matter (PM2.5) and its potential impact on vascular endothelial function have not been thoroughly investigated. As endothelial dysfunction plays an important role in atherosclerosis and cardiovascular disease, we examined the effects of concentrated fine ambient particles (CAPs) on the plasma levels of asymmetric dimethylarginine (ADMA) in a pilot study. ADMA is an endogenous inhibitor of nitric oxide synthase that is associated with impaired vascular function and an increased risk of cardiovascular events.

Methods: A mobile air research laboratory (AirCARE 1), equipped with whole body inhalation chambers and a Harvard type ambient fine particle concentrator, was used in the study. AirCARE 1 was designed and constructed collaboratively by Michigan State University and the University of Michigan. The CAPs exposures for this study were conducted in the urban community of southwest Detroit. Fourteen Brown Norway rats were exposed to filtered air (FA) (n=7) or CAPs (0.1-2.5 µm) (n=7) for 3 consecutive days (8h/day) in July, 2002. Rats were exposed during these periods to average particle mass concentrations of 367 µg/m3. Rat plasma samples were collected 24h post-exposure.

Results: Plasma concentrations of ADMA were significantly elevated in the rats exposed to CAPs versus those exposed to FA (1.49 ± 0.18 vs 1.29 ± 0.26 *M, p*0.05 by 1 tailed t-test).

Conclusion: Fine particulate air pollution exposure at high concentrations triggers an acute increase in circulating ADMA level. This could potentially cause impaired vascular endothelial function and enhance the risk for cardiovascular disease. 

Submitted for ACC Poster Research  Presentation