Myocardial microvascular permeability, interstitial oedema, and compromised cardiac function

**While this is an older article, it is just now available in full text.  Intersitial edema is what we deal with in our lymphedema and a number of us have had situations whereby we experiences interstitial edema in the cardiac cavity itself.  I was really shaken up when I experienced this a couple years ago.  This is very applicable even today.  Pat**

July 2010

Ranjeet M. Dongaonka,  Randolph H. Stewart,  Hans J. Geissler,  and Glen A. Laine

ABSTRACT

The heart, perhaps more than any other organ, is exquisitely sensitive to increases in microvascular permeability and the accumulation of myocardial interstitial oedema fluid. Whereas some organs can cope with profound increases in the interstitial fluid volume or oedema formation without a compromise in function, heart function is significantly compromised with only a few percent increase in the interstitial fluid volume. This would be of little consequence if myocardial oedema were an uncommon pathology. On the contrary, myocardial oedema forms in response to many disease states as well as clinical interventions such as cardiopulmonary bypass and cardioplegic arrest common to many cardiothoracic surgical procedures. The heart's inability to function effectively in the presence of myocardial oedema is further confounded by the perplexing fact that the resolution of myocardial oedema does not restore normal cardiac function. We will attempt to provide some insight as to how microvascular permeability and myocardial oedema formation compromise cardiac function and discuss the acute changes that might take place in the myocardium to perpetuate compromised cardiac function following oedema resolution. We will also discuss compensatory changes in the interstitial matrix of the heart in response to chronic myocardial oedema and the role they play to optimize myocardial function during chronic oedemagenic disease.

Full Text Article

Pub Med - Cardiovascular Rsearch

Volume-dependent effect of perihaematomal oedema on outcome for spontaneous intracerebral haemorrhages.

Jan 2013

Appelboom G, Bruce SS, Hickman ZL, Zacharia BE, Carpenter AM, Vaughan KA, Duren A, Hwang RY, Piazza M, Lee K,Claassen J, Mayer S, Badjatia N, Connolly ES Jr.

Source

Department of Neurological Surgery, The Neurological Institute, Columbia University College of Physicians and Surgeons, , New York, New York, USA.

Abstract

INTRODUCTION:

It is still unknown whether subsequent perihaematomal oedema (PHE) formation further increases the odds of an unfavourable outcome.

METHODS:

Demographic, clinical, radiographic and outcome data were prospectively collected in a single large academic centre. A multiple logistic regression model was then developed to determine the effect of admission oedema volume on outcome.

RESULTS:

133 patients were analysed in this study. While there was no significant association between relative PHE volume and discharge outcome (p=0.713), a strong relationship was observed between absolute PHE volume and discharge outcome (p=0.009). In a multivariate model incorporating known predictors of outcome, as well as other factors found to be significant in our univariate analysis, absolute PHE volume remained a significant predictor of poor outcome only in patients with intracerebral haemorrhage (ICH) volumes ≤30 cm(3) (OR 1.123, 95% CI 1.021 to 1.273, p=0.034). An increase in absolute PHE volume of 10 cm(3) in these patients was found to increase the odds of poor outcome on discharge by a factor of 3.19.

CONCLUSIONS:

Our findings suggest that the effect of absolute PHE volume on functional outcome following ICH is dependent on haematoma size, with only patients with smaller haemorrhages exhibiting poorer outcome with worse PHE. Further studies are needed to define the precise role of PHE in driving outcome following ICH.

PubMed

Rationale for treating edema in Duchenne muscular dystrophy with eplerenone

Rationale for treating oedema in Duchenne muscular dystrophy with eplerenone

May 2012

FRANK LEHMANN-HORN, MARC-ANDRÉ WEBER,¹ ARMIN M. NAGEL,² HANS-MICHAEL MEINCK,³ SIMON BREITENBACH, JOHANNES SCHARRER, and KARIN JURKAT-ROTT

Abstract

Key words: Duchenne muscular dystrophy, eplerenone, cytotoxic oedema

Recently we reported a cytoplasmic sodium overload to cause a severe osmotic oedema in Duchenne muscular dystrophy (DMD). Our results suggested that this dual overload of sodium ions and water precedes the dystrophic process and persists until fatty muscle degeneration is complete. The present paper addresses the questions as to whether these overloads are important for the pathogenesis of the disease, and if so, whether they can be treated. As a first step, we investigated the effects of various diuretic drugs on a cell model of DMD, i.e. rat diaphragm strips previously exposed to amphotericin B. We found that both carbonic anhydrase inhibitors and aldosterone antagonists were able to repolarise depolarised muscle fibres. Since carbonic anhydrase inhibitors are known to have acidifying effects and this might be detrimental to the ventilation of DMD patients, we mainly concentrated on the modern spironolactone derivative, eplerenone. This drug had a very high repolarizing power, the parameter considered by us as being most relevant for a beneficial effect. In a pilot study we administered this drug to a 22-yr-old female DMD patient who was bound to an electric wheelchair and has had no corticosteroid therapy before. Eplerenone decreased both cytoplasmic sodium and water overload and increased muscle strength and mobility. We conclude that eplerenone has beneficial effects on DMD muscle. In our opinion the cytoplasmic oedema is cytotoxic and should be treated before fatty degeneration takes place.

Full Text Article

Flash Pulmonary Oedema after Relief of Haemodialysis Graft Stenosis.

Dec 2012 

Vélez-Martínez M, Weinberg BD, Mishkin JD.

Source

Cardiology Division, UT Southwestern Medical Center at Dallas, USA; Department of Internal Medicine, UT Southwestern Medical Center at Dallas, USA. Electronic address: mariella.velez-martinez@phhs.org.

Abstract

Heart failure (HF) and chronic kidney disease (CKD) are undoubtedly very much interrelated, especially in patients with end-stage renal disease (ESRD) who are dependent on renal replacement therapy. Haemodialysis (HD) is of particular interest in cardiovascular patients due to the creation of a haemodialysis vascular access and the haemodynamic changes associated with it. Adequate HD though is very dependent on a properly functioning vascular access. Unfortunately, these surgical vascular accesses are vulnerable to stenoses and occlusions. Percutaneous endovascular treatment of these stenoses is often performed and has been found to be safe and effective. Despite its frequent use, acute medical complications of this percutaneous procedure have not been well-documented. In this report, we describe a patient who developed flash pulmonary oedema after balloon angioplasty treatment of an arteriovenous graft (AVG) stenosis.

Elsevier SciVerse

Glioma-related edema: new insight into molecular mechanisms and their clinical implications.

Dec 2012

Lin ZX.

Source

Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P. R. China lzx1967@sina.com.

Abstract

Glioma-related edema (GRE) is a significant contributor to morbidity and mortality from glioma. GRE is a complicated process involving not only peritumoral edema, but also the water content of the tumor body. In terms of etiology, this condition derives from both GRE in the untreated state and GRE secondary to clinical intervention, and different cell types contribute to distinct components of GRE. Peritumoral edema was previously believed to loosen glioma tissue, facilitating tumor-cell invasion; however, the nutrition hypothesis of the tumor microecosystem suggests that tumor cells invade for the sake of nutrition. Edema is the pathologic consequence of the reconstructed trophic linkage within the tumor microecosystem. Glioma cells induce peritumoral brain edema via an active process that supplies a suitable niche for peritumoral invasive cells, suggesting that glioma-related peritumoral brain edema is determined by the invasive property of tumor cells. There are differences between pivotal molecular events and reactive molecular events in the development of GRE. Molecular therapy should target the former, as targeting reactive molecular events will produce undesired or even adverse results. At present, brain glioma angiogenesis models have not been translated into a new understanding of the features of brain images. The effect of these models on peritumoral brain edema is unclear. Clinical approaches should be transformed on the basis of new knowledge of the molecular mechanism of GRE. Exploring clinical assessment methods, optimizing the existing control strategy of GRE, and simultaneously developing new treatments are essential.

PubMed

Effective Treatment of Edema and Endothelial Barrier Dysfunction With Imatinib.

Oct 2012

Aman J, van Bezu J, Damanafshan A, Huveneers S, Eringa EC, Vogel SM, Groeneveld AB, Vonk Noordegraaf A, van Hinsbergh VW, van Nieuw Amerongen GP.

Source

1 Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands;

Abstract

BACKGROUND:

Tissue edema and endothelial barrier dysfunction as observed in sepsis and acute lung injury carry high morbidity and mortality, but currently lack specific therapy. In a recent case-report, we described fast resolution of pulmonary edema upon treatment with the tyrosine kinase inhibitor imatinib through an unknown mechanism. Here, we explored the effect of imatinib on endothelial barrier dysfunction and edema formation.

METHODS AND RESULTS:

We evaluated the effect of imatinib on endothelial barrier function in vitro and in vivo. In human macro- and microvascular endothelial monolayers, imatinib attenuated endothelial barrier dysfunction induced by thrombin and histamine. siRNA knock-downs of the imatinib-sensitive kinases revealed that imatinib attenuates endothelial barrier dysfunction via inhibition of Abl-Related Gene kinase (Arg/Abl2), a previously unknown mediator of endothelial barrier dysfunction. Indeed, Arg was activated by endothelial stimulation with thrombin, histamine and VEGF. Imatinib limited Arg-mediated endothelial barrier dysfunction by enhancing Rac1 activity and enforcing adhesion of endothelial cells to the extra-cellular matrix. Using mouse models of vascular leakage as proof-of-concept, we found that pretreatment with imatinib protected against VEGF-induced vascular leakage in the skin, and effectively prevented edema formation in the lungs. In a murine model of sepsis imatinib treatment (6h and 18h after induction of sepsis) attenuated vascular leakage in the kidneys and the lungs (24h after induction of sepsis).

CONCLUSIONS:

Thus, imatinib prevents endothelial barrier dysfunction and edema formation via inhibition of Arg. These findings identify imatinib as a promising approach to permeability edema, and indicate Arg as novel target for edema treatment.

AHA Journals CIRCULATION

Edema is a symptom that has many possible causes

August 2012

DEAR DOCTOR K: What can I do about my edema? The diuretics my doctor prescribed haven't helped.

DEAR READER: Edema is swelling caused by a buildup of extra fluid. Edema most often affects the feet and legs, but it can affect the hands and even the face. The skin becomes puffy and swollen.

The fluid in your body is in three places: inside each of the 13 trillion cells in your body; in the blood (which means inside all your blood vessels); and in the space between your cells and your blood vessels. Edema occurs when unusual amounts of fluid leak out of the blood vessels and into the space between your blood vessels and cells.

Diuretics, also known as water pills, are often used to treat edema. They help your kidneys eliminate excess fluid in your body.

Edema is a symptom that may be caused by many conditions. Your doctor will need to identify and treat the condition that is causing it. Possible causes include:

-- Prolonged standing or sitting. This can cause edema in your feet and lower legs. That's because gravity is pulling more blood into the blood vessels of your legs. When the blood vessels swell with fluid, some of the fluid leaks out of the vessels and into the tissues.

-- Venous insufficiency from varicose veins. Valves inside the veins of the legs weaken, making it more difficult for the veins to pump blood back to the heart. This leads to fluid buildup.

-- Severe chronic lung diseases. Emphysema and chronic bronchitis weaken the heart's ability to pump, particularly the right side of the heart.

-- Congestive heart failure. The left or right side of the heart can no longer pump efficiently.

-- Pregnancy. The enlarged uterus with the fetus inside can pinch off the veins carrying blood from the legs to the heart.

-- Pre-eclampsia. This serious condition can occur during pregnancy.

-- Low blood-protein levels. These can be caused by malnutrition, kidney and liver disease.

As for treatments, increasing the dose of your diuretic might solve the problem. A low-salt diet usually helps, since salt causes the body to retain fluid. You also should avoid drinking too much fluid.

If the edema is in your feet and legs, prop them up whenever you are sitting. This counters the effect of gravity and encourages more blood to move out of your legs. Compression stockings can help squeeze the edema fluid out of your tissues. Finally, if your edema is caused by varicose veins, traditional surgery or newer laser procedures can treat the condition.

It's important to protect feet and legs swollen by edema from pressure, injury and extreme temperatures. The skin over swollen legs becomes more fragile over time. Cuts, scrapes and burns in areas that have edema take much longer to heal and are more likely to get infected.

(Dr. Komaroff is a physician and professor at Harvard Medical School. To send questions, go to AskDoctorK.com, or write: Ask Doctor K, 10 Shattuck St., Second Floor, Boston, Mass. 02115.)

Souix City Journal

Pathophysiology and treatment of edema following femoropopliteal bypass surgery.

Sept  2012

Te Slaa A, Dolmans DE, Ho GH, Moll FL, van der Laan L.

Source

Department of Surgery, Amphia Hospital, Breda.

Abstract

Substantial lower-limb edema affects the majority of patients who undergo peripheral bypass surgery. Edema has impairing effects on the microvascular and the macrovascular circulation, causes discomfort and might delay the rehabilitation process of the patient. However, the pathophysiology of this edema is not well understood. The Cochrane Library and Medline were used to retrieve literature on edema following peripheral bypass surgery. Factors other than local wound healing alone are suggested in the literature to play a role, given the severity and duration of this edema. Hyperemia, microvascular permeability, reperfusion-associated inflammation and lymphatic disruptions are likely to facilitate the development of edema. 

Preventive methods could be lymphatic-sparing surgery, intraoperative antioxidative therapy and postoperative elevation. Successful treatment strategies to reduce postoperative edema are based on lymph massage and external compression. 

In conclusion, the pathophysiology of edema following peripheral surgery is not fully understood, although reperfusion-associated inflammation and lymphatic disruptions are likely to play a crucial role. When future less-invasive techniques prove to be successful, postoperative edema might be minimized. Until then, a careful lymphatic-sparing dissection should be executed when performing a peripheral bypass reconstruction. Postoperatively, the use of compression stockings and leg elevation are currently the golden standards.

Vascular

Capillary leak syndrome in trauma: what is it and what are the consequences?

2012

Stein DM, Scalea TM.

Source

University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201, USA. dstein@umm.edu

Abstract

TICS is a complex disease that is clearly multifactorial in the traumatically injured patient (Fig. 2). Although systemic inflammation that occurs directly as a result of injury plays the most prominent role, the local tissue and organ injury effects of trauma not only cause local capillary leak and edema but also further amplify the SIRS response. High volume fluid administration and hypoproteinemic states further exacerbate the problem. All of this leads to organ dysfunction and failure, which is the third leading cause of death following injury. Strategies to treat TICS and attenuate its effects once it occurs by targeting inflammatory pathways have been wholly unsuccessful. The mainstay of therapy for TICS is prevention and minimization of its lethal effects. Newer resuscitation strategies such as hemostatic resuscitation and early goal-directed therapies are currently the best available strategies to combat TICS. Whether these result in better outcomes remains to be seen and the authors anxiously await the results of well-designed prospective trials.

PubMed

15th Annual State of GA Lymphedema Education Program

Winship Cancer Institute of Emory University

and The Lighthouse Lymphedema Network

Cordially invite you to the

15th State of Georgia Lymphedema Education & Awareness Conference

Saturday, October 27, 2012

Emory University Hospital Midtown, 550 Peachtree Street, Atlanta, GA 30308

7:30am-4:30pm

Speakers include: Jane Armer, PhD, Richard Mistretta, DPM,

Joseph Feldman, MD, and David W. Chang, MD

The Conference Brochure may be viewed by clicking here:

http://lighthouselymphedema.org/announcements/15th-annual-state-of-georgia-lymph\
edema-education-and-awareness-program

You may register online by clicking here:

http://lighthouselymphedema.org/get-involved/secureregistration.htm

INFO PAGE:

http://lighthouselymphedema.org/announcements/15th-annual-state-of-georgia-lymph\
edema-education-and-awareness-program

Clinical Characteristic Differences between Thrombosis-related Edema and Lymphedema Following Radiotherapy or Chemoradiotherapy Cervical Cancer

The Clinical Characteristic Differences between Thrombosis-related Edema and LymphedemaFollowing Radiotherapy or Chemoradiotherapy for Patients with Cervical Cancer.

2012

Wang PL, Cheng YB, Kuerban G.

Source

Center of Oncology, The Fifth Affiliated Hospital of Xinjiang Medical University.

Abstract

Thrombosis-related edema and lymphedema are two principal types of lower extremity edema results from radiotherapy alone or chemoradiotherapy for patients with cervical cancer. To characterize differences between them, a retrospective study was performed. We collected data including age, race, body weight, FIGO stage, histology type, platelet count, haemoglobin, time of definitely diagnosis, therapeutic regimen, edema type and which leg edema firstly occurred in. Of 40 patients who were eligible for this study, 32 were diagnosed as thrombosis-related edema and 8 diagnosed as lymphedema.

The differences in patient age (p = 0.004), propotion of race (p = 0.021), the latent time (p = 0.002) and the mean platelet count (p = 0.019) were statistically significant. Among 32 patients with thrombosis-related edema, 34.4% were in stage II and 53.1% in stage III, 78.1% were squamous cell carcinoma. Among 8 patients with lymphedema, 87.5% were in stage II and 62.5% were squamous cell carcinoma.

The differences were not statistically significant for weight (p = 0.94), histology type (p = 0.648), edema site (p = 0.236), haemoglobin (p = 0.088) between the two grouping patients. Although the small patient cohort is a limitation, the results suggest that the patients with thrombosis-related edema may have higher proportion, lower age, shorter latent edema time and more platelet count than those with lymphedema.

Also, thrombosis-related edema was likely inclined to Uigur and lymphedema to Han race. We did not find statistical differences in weight, edema site, histology type and haemoglobin between patients with thrombosis-related edema and lymphedema.

Journal of Radiation Research

Swollen extremities (edema) during pregnancy

Reviewed by the BabyCenter Medical Advisory Board

Why are my ankles and feet so swollen?

What you're experiencing is edema — that's when excess fluid collects in your tissue. It's normal to have a certain amount of swelling during pregnancy because you're retaining more water. Changes in your blood chemistry also cause some fluid to shift into your tissue.

In addition, your growing uterus puts pressure on your pelvic veins and your vena cava (the large vein on the right side of the body that carries blood from your lower limbs back to the heart). The pressure slows the return of blood from your legs, causing it to pool, which forces fluid from your veins into the tissues of your feet and ankles.

Edema is most often an issue during the third trimester, particularly at the end of the day. It may be worse during the summer.

You can help relieve the increased pressure on your veins by lying on your side. Since the vena cava is on the right side of your body, left-sided rest works best.

After you have your baby, the swelling will disappear fairly rapidly as your body eliminates the excess fluid. You may find yourself urinating frequently and sweating a lot in the first days after childbirth.

When should I be concerned about swelling?

A certain amount of edema is normal in the ankles and feet during pregnancy. You may also have some mild swelling in your hands.

Call your midwife or doctor if you notice swelling in your face or puffiness around your eyes, more than slight swelling of your hands, or excessive or sudden swelling of your feet or ankles. This could be a sign of preeclampsia, a serious condition.

Also call your caregiver if you notice that one leg is significantly more swollen than the other, especially if you have any pain or tenderness in your calf or thigh.

What can I do to minimize the puffiness?

Here are a few tips:

• Put your feet up whenever possible. At work, it helps to keep a stool or pile of books under your desk. At home, lie on your left side when possible.
• Don't cross your legs or ankles while sitting.
• Stretch your legs frequently while sitting: Stretch your leg out, heel first, and gently flex your foot to stretch your calf muscles. Rotate your ankles and wiggle your toes.
• Take regular breaks from sitting or standing. A short walk every so often will help keep your blood circulating.
• Wear comfortable shoes that stretch to accommodate the swelling.
• Don't wear socks or stockings that have tight bands around the ankles or calves.
• Try waist-high maternity support stockings. Put them on before you get out of bed in the morning so blood doesn't have a chance to pool around your ankles.
• Drink plenty of water. Surprisingly, this helps your body retain less water.
• Exercise regularly, especially by walking, swimming, or riding an exercise bike. Or try a water aerobics class — immersion in water may temporarily help reduce swelling, particularly if the water level is up near your shoulders.
• Eat well, and avoid junk food.

Try not to let pregnancy swelling get you down. The sight of your swollen ankles will probably add to your feeling of ungainliness, but edema is a temporary condition that will pass soon after you give birth.

Validating Imaging Biomarkers of Cerebral Edema in Patients with Severe Ischemic Stroke.

Feb 2012

Yoo AJ, Sheth KN, Kimberly WT, Chaudhry ZA, Elm JJ, Jacobson S, Davis SM, Donnan GA, Albers GW, Stern BJ,González RG.

Source

Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.

Abstract

BACKGROUND:

There is no validated neuroimaging marker for quantifying brain edema. We sought to test whether magnetic resonance imaging (MRI)-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints.

METHODS:

Serial MRI studies from patients in the Echoplanar Imaging Thrombolytic Evaluation Trial with initial diffusion-weighted imaging (DWI) lesion volume >82 cm(3) were analyzed. Two independent readers outlined the hemisphere and lateral ventricle on the involved side and calculated respective volumes at baseline and days 3 to 5. We assessed interrater agreement, volume change between scans, and the association of volume change with early neurologic deterioration (National Institutes of Health Stroke Scale score worsening of ≥4 points), a 90-day modified Rankin scale (mRS) score of 0 to 4, and mortality.

RESULTS:

Of 12 patients who met study criteria, average baseline and follow-up DWI lesion size was 138 cm(3) and 234 cm(3), respectively. The mean time to follow-up MRI was 62 hours. Concordance correlation coefficients between readers were >0.90 for both hemisphere and ventricle volume assessment. Mean percent hemisphere volume increase was 16.2 ± 8.3% (P < .0001), and the mean percent ventricle volume decrease was 45.6 ± 16.9% (P < .001). Percent hemisphere growth predicted early neurologic deterioration (area under the curve [AUC] 0.92; P = .0005) and 90-day mRS 0 to 4 (AUC 0.80; P = .02).

CONCLUSIONS:

In this exploratory analysis of severe ischemic stroke patients, statistically significant changes in hemisphere and ventricular volumes within the first week are consistent with expected changes of cerebral edema. MRI-based analysis of hemisphere growth appears to be a suitable biomarker for edema formation