Vitamin K and vascular calcification

In 1929 a Danish Biochemist work on the cholesterol metabolism in chicken fed on a low-fat diet, free from sterols lead to the discovery of Vitamin K. He noticed subcutaneous and intramuscular hematomas in the chicken fed on a low-fat diet for 6 weeks or more. When he re-fed them fatty food the hemorrhagic effect was not reversed. Instead, he fed them Hempseed and the hemorrhagic effect got reversed. So, he called this antihemorrhagic factor. In German, it is known as Koagulation–vitamin. It has got its name Vitamin K from Koagulation. Vitamin K1 (phylloquinone) is from plant-based foods and Vitamin K2 (MK7 menaquinone) is from other sources. Henrik Dam and Edward Doisy received Nobel prize 1943 for their discovery of Vitamin K.

Vitamin K2 is linked with vascular calcification. Vascular smooth muscle cells produce Matrix Gla Protein (MGP). Vitamin K acts as a cofactor for gamma-carboxylation of MGP after which it inhibits the vascular calcification. When the MGP gene was deleted from the rats there was complete arterial calcification and they died in 6 weeks. Similarly, when rats were treated with Warfarin, they developed vascular calcification. Treating them with high doses of Vitamin K, it resulted in reversal of the calcification.

It was observed that high doses of Vitamin K will reduce the arterial stiffness and increase vascular elasticity. This mechanical effect will improve cardiovascular functions. In a recent paper published, M K Shea et al 2020 (nearly 4000 patients) observed a relation between the all-cause mortality and serum levels of Vitamin K. When serum levels were lower than 0.5 nmol/ L, the all-cause mortality was 19% higher than the patients with higher levels (> 1.0 nmol/ L) of serum vitamin K in 13 years follow up. But surprisingly there was no such association noted between cardiovascular disease and serum levels of vitamin K.

We need more studies to understand the reversal effect on vascular calcification and improvement of haemodynamic effects in the calcified vessels. Currently we are treating diabetic patients with tibial arterial disease with guidewires, balloons and stents in addition to the statins, antiplatelets, CE/ARBs and antidiabetics. Vitamin K2 (menaquinone) induced correction of vascular calcification is an additional benefit to the patients, but this needs to be proved in more number of robust trials.  

M Kyla Shea, Kathryn Barger, Sarah L Booth, Gregory Matuszek, Mary Cushman, Emelia J Benjamin, Stephen B Kritchevsky, Daniel E Weiner. Vitamin K status, cardiovascular disease, and all-cause mortality: a participant-level meta-analysis of 3 US cohorts. The American Journal of Clinical Nutrition, Volume 111, Issue 6, June 2020, Pages 1170–1177,

Cerebral small blood vessel disease

Cerebral small blood vessel disease (in standard preoperative imaging reports) is independently associated with increased risk of CV death following carotid endarterectomy. This statement is produced by an article published in the European Journal of vascular and endovascular surgery2020.

1). What is cerebral small blood vessel disease?

Cerebral small vessel disease (CSVD) is composed of several diseases affecting the small arteries, arterioles, venules, and capillaries of the brain, and refers to several pathological processes and etiologies. Neuroimaging features of CSVD include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. The main clinical manifestations of CSVD include stroke, cognitive decline, dementia, psychiatric disorders, abnormal gait, and urinary incontinence.

2). What are cerebral small blood vessels?

Cerebral small vessels comprise two components. First, the leptomeninges vasoganglion, which is derived from subarachnoid space covering, and the convex surface of the brain. Second, perforating arteries are derived from anterior, middle, posterior cerebral arteries that supply the subcortical parenchyma. The cerebral small vessels are crucial to the maintenance of adequate blood flow to the sub-surface brain structure. They include small arteries, arterioles, venules, and capillaries which are commonly sized at 50–400 µm.

3). What are the outcomes of cerebral small vessel disease (CSVD) of the brain?

Small vessel disease accounts for up to 25% of all ischemic strokes but also put patients at twice the risk for these conditions. In addition, CSVD is a leading cause of functional loss, disability and cognitive decline in the elderly.

4). What are the neuroimaging findings of CSVD?

Neuroimaging of CSVD primarily involves visualizing recent small subcortical infarcts, lacunar infarct, WMH, microbleeds, enlarged perivascular spaces, and brain atrophy.

5). What are lacunar infarcts?

Gattringer and colleagues recommended the new term ‘recent small subcortical infarct’ instead of the lacunar infarct.

Gattringer T, Eppinger S, Pinter D, Pirpamer L, Berghold A, Wunsch G, Ropele S, Wardlaw JM, Enzinger C, Fazekas F. Morphological MRI characteristics of recent small subcortical infarcts. Int J Stroke. 2015;10(7):1037–1043.

Lacunar stroke accounts for up to a quarter of all acute ischemic strokes. it is a small fluid-filled cavity that was thought to mark the healed stage of a small deep brain infarct. In neuroimaging, a lacuna is a round or ovoid, subcortical, fluid-filled cavity with a similar signal to cerebrospinal fluid (CSF). It measures between 3–15 mm in diameter, which is consistent with a previous acute small deep brain infarct or hemorrhage in the territory of one perforating arteriole. Lacunar infarcts are typically located in the basal ganglia, internal capsule, thalamus, corona radiata, centrum semiovale (CSO), and brainstem. Poirier and colleagues divided the lacunas into three subtypes based on the formation: Subtype I lacunas are secondary to old lacunar infarction; subtype II lacunas secondary to old hemorrhagic lesions; subtype Ⅲ lacunas are secondary to enlarged perivascular spaces. Herve and colleagues classified the lacunar lesions by three-dimensional MRI reconstruction, according to their shapes into four types: Slab, stick, multiple components, or ovoid/spheroid, then proposing that most of the lacunar infarcts (83%) were ovoid or spheroid. Infarct lesions manifest isolated, adjacent to or fused into white matter hyperintensity.

Moreau and colleagues found that lacunas almost always present at 90 days after acute lacunar infarction and appear as a central CSF-like hypointensity with or without a surrounding border of hyperintensity on FLAIR sequence but only CSF-like hypointensity and hyperintensity on T1-weighted and T2-weighted, respectively. Moreover, the sensitivity of FLAIR for cavitation was greatly lower than for T1-weighted sequences.

6). What is the effect of CSVD on people undergoing carotid endarterectomy?

The presence of SVD in pre-operative brain imaging reports can serve as a predictor for the three-year risk of cardiovascular death in symptomatic patients undergoing CEA but does not predict peri-operative or long term risk of stroke. Published: April 21, 2020DOI:https://doi.org/10.1016/j.ejvs.2020.02.004

Nephrogenic Systemic Fibrosis (NSF)

Vascular surgery patients with arterial problems generally require angiograms to evaluate the patency of the vascular lumen. There is always a concern about doing an angiogram ( CT angio or conventional angio) in those patients with decreased eGFR. Some times MRangiogram with gadolinium is recommended in. those patients. But that can result in nephrogenic systemic fibrosis (NSF).

Nephrogenic systemic fibrosis (NSF) incidence was found to be found to be 4.3 cases per thousand patient-years. When gadolinium is used in a patient there is 2.4% risk of nephrogenic systemic fibrosis. NSF is also known as nephrogenic fibrosing dermopathy. This was first described in 2006 in the Journal of American Society of nephrology by Marckmann P et al describing a case series of 13 patients. New contrast agents are introduced with the hope that they have a lesser risk of NSF. Gadobenate dimeglumine is one such newer agent. Clinically NSF looks like scleroderma and eosinophilic fasciitis but histologically it looks like scleromyxedema. Biopsy shows proliferation of dermal fibroblasts, dendritic cells, thickened collagen bundles,   increases elastic fibers and mucin deposition. Toll-Like Receptors (TLR) four and seven seems to play an important role in the development of NSF. 

Although NSF occurrence after exposure to newer GBCAs is very rare, the relatively scarce data among patients with acute kidney injury and those with risk factors for chronic kidney disease limit conclusions about safety in these populations (Joseph Lunyera 2020).

Capricious Corona and new normalcy without contact in the coming future?

Return to normalcy, a return to the way of life before World War I, was United States presidential candidate Warren G. Harding's campaign slogan for the election of 1920. Although detractors of the time tried to belittle the word "normalcy" as a neologism as well as a malapropism, saying that it was poorly coined by Harding (as opposed to the more accepted term normality), there was contemporaneous discussion and evidence that normalcy had been listed in dictionaries as far back as 1857. Harding's promise was to return the United States' pre-war mentality, without the thought of war tainting the minds of the American people. To sum up his points, he stated:

America's present need is not heroics, but healing; not nostrums, but normalcy; not revolution, but restoration; not agitation, but adjustment; not surgery, but serenity; not the dramatic, but the dispassionate; not experiment, but equipoise; not submergence in internationality, but sustainment in triumphant nationality.

Harding's position attracted support and was important during the 1920 United States presidential election, which he won with 60.3% of the popular vote.^[3]

During the campaign, Harding addressed the issue of the word's origin, claiming that "normalcy" but not "normality" appeared in his dictionary.

Now our war with Covid19 is coming to a stance(end), what will be our new normalcy in all the spheres of life and medical practice?

Signs of dramatic changes are everywhere even in GP surgeries. The New York Times published an interesting report on how the work of GPs in London is being transformed by the virus. “We’re basically witnessing 10 years of change in one week,” one GP told the paper. “It used to be that 95% of patient contact was face-to-face: you go to see your doctor, as it has been for decades, centuries. But that has changed completely.” Before the virus, video appointments made up only 1% of annual appointments with British GPs and other practice staff. But the NHS has urged thousands of clinics across the country to start switching to remote consultations and has fast-tracked approval of digital providers to ramp up their offerings.

We are seeing a sudden increase in the webinars and online consultations. Many companies are providing these services to the doctors. We are surprised to see the sudden change that has taken place in view of Covid-19 based on the physical distancing slogan. This is the new Normalcy after lifting the lockdowns of covid-19.   

Risk factors for the development of venous ulcers

Venous ulcers are the most common type of chronic lower extremity ulcers, affecting 1% to 3% of the U.S. population. Venous hypertension as a result of venous reflux (incompetence) or obstruction is thought to be the primary underlying mechanism for venous ulcer formation .

Risk factors for the development of venous ulcers include

1.Age 55 years or older,

2.Family history of Chronic venous insufficiency,

3. Higher body mass index,

4.History of pulmonary embolism or superficial/deep venous thrombosis,

5. Lower extremity skeletal or joint disease,

6.Higher number of pregnancies,

7.Parental history of ankle ulcers,

8.Physical inactivity,

9.History of ulcers,

10.Severe lipodermatosclerosis, and

11. Venous reflux in deep veins.

Bonkemeyer Millan S, Gan R, Townsend PE. Venous Ulcers: Diagnosis and Treatment.

Am Fam Physician. 2019 Sep 1;100(5):298-305

Effects of smoking on blood vessels – can we reverse them?

The effects of nicotine replacement therapy (NRT)-aided smoking cessation on vascular function are not fully clarified. We investigated 100 healthy smokers who were motivated to quit and received NRT for a 3-month period. Vascular endothelial function (measured by reactive hyperemia-peripheral arterial tonometry [RH-PAT]), arterial stiffness (measured by augmentation index [AI] and brachial-ankle pulse wave velocity [baPWV]), and systemic inflammation markers (including serum soluble intercellular adhesion molecule-1 [sICAM-1] and interleukin-1β [IL-1β]) were assessed at baseline and 3 and 12 months of follow-up. After 3 months of intervention, endothelial function, arterial stiffness, and inflammatory markers significantly improved (RH-PAT increased, AI and baPWV decreased, sICAM-1 and IL-1β decreased, all P < .05) for the participants who abstained from smoking completely, but for those who did not abstained completely, RH-PAT, AI, baPWV, and IL-1β remained unchanged. At 12 months follow-up, endothelial function (RH-PAT), arterial stiffness (AI and baPWV), and inflammatory markers (sICAM-1 and IL-1β) were further improved in participants who abstained from smoking (P < .001), while the above parameters deteriorated in continued smokers (P < .05). In conclusion, vascular dysfunction can be reversible after NRT-aided smoking cessation in healthy smokers and vascular function could be further damaged if they continue smoking[1].

---

[1]. Xue C1, Chen QZ1, Bian L1, Yin ZF1, Xu ZJ1, Zhang AL1, Xie YS1, Zhang HL1, Du R2, Wang CQ1. Effects of Smoking Cessation with Nicotine Replacement Therapy on Vascular Endothelial Function, Arterial Stiffness, and Inflammation Response in Healthy Smokers. Angiology. 2019 Sep;70(8):719-725

Inferior vena cava thrombosis

Inferior vena cava thrombosis (IVCT), although rare, has a potential for significant morbidity and mortality. IVCT is often a result of IVC filter thrombosis, but it can also occur de novo. Although anticoagulation remains the standard of care, endovascular techniques to restore IVC patency have become key adjunctive therapies in recent years. This study examines a single-center experience with diagnosis and management of IVCT.

https://www.annalsofvascularsurgery.com/article/S0890-5096(18)30842-2/pdf

Methods

A retrospective Institutional Review Board-approved review of a single-center institutional database was screened to identify IVCT thrombosis using International Classification of Diseases code 453.2 over a 3-year period. Etiology of IVCT was separated into 2 groups: those with IVC thrombosis in the setting of prior IVC filter place and those in whom IVCT occurred de novo. Patient demographics, presenting characteristics, and management of IVCT were examined. Treatment options included expectant management with anticoagulation versus catheter-directed thrombolysis (CDT), mechanical thrombectomy, stenting, or a combination. For those who underwent intervention, technical success, defined as restoration of IVC patency, was assessed.

Results

Forty-one unique patients were identified with radiographically confirmed diagnosis of ICVT (mean age 61, range 25-91; 21 female, 51.2%). Eighteen (43.9%) patients presented with thrombosed IVC filter. Risk factors for venous thromboembolism included tobacco usage, current or prior smoking (n = 17, 41.5%), history of prior deep vein thrombosis (n = 25, 61.0%), malignancy (n = 17, 41.5%), use of hormonal supplements (n = 3, 7.3%), known thrombophilia (n = 4, 9.8%), and obesity (body mass index: mean 29, range 18.8-58.53). Eleven patients (26.8%) presented with pulmonary embolism (PE), and of those 63.6% had IVC filter thrombosis (n = 7). Risk of PE was not significantly different between those patients presenting with a thrombosed IVC filter compared to those with de novo IVCT (38.9% vs. 17.4%, P = 0.12) Management of IVCT included anticoagulation alone (n = 27, 65.9%), CDT (n = 5, 12.2%), mechanical thrombolysis (n = 10, 24.4%), and adjunctive IVC stent (n = 3, 7.3%). Among the 14 (34.1%) patients who had intervention for IVCT, patency was restored in 12 patients (85.7%).

Conclusions

IVCT is a rare event and is associated with known risk factors for venous thromboembolism. PE can occur in roughly 25% of patients presenting with IVCT. Presence of a filter does not appear to confer an advantage in preventing PE when IVCT occurs. Although majority of IVCT is managed with anticoagulation alone, endovascular interventions, including lysis and stenting, can safely restore patency in most properly selected patients.

Carotid body tumors and the outcomes

A Systematic Review and Meta-Analysis of the Presentation and Surgical Management of Patients With Carotid Body Tumours.

Vaux Robertson

, 

Federica Poli

, 

Ben Hobson

, 

Athanasios Saratzis

, 

A. Ross Naylor∗,Correspondence information about the author A. Ross NaylorEmail the author A. Ross Naylor

The Leicester Vascular Institute, Glenfield Hospital, Leicester UK

Objectives

The aim was to determine the mode of presentation and 30 day procedural risks in 4418 patients with 4743 carotid body tumours (CBTs) undergoing surgical excision.

Methods

This is a systematic review and meta-analysis of 104 observational studies.

Results

Overall, 4418 patients with 4743 CBTs were identified. The mean age was 47 years, with the majority being female (65%). The commonest presentation was a neck mass (75%), of which 85% were painless. Dysphagia, cranial nerve injury (CNI), and headache were present in 3%, while virtually no one presented with a transient ischaemic attack (0.26%) or stroke (0.09%). The majority (97%) underwent excision, but only 21% underwent pre-operative embolisation. Overall, 27% were Shamblin I CBTs; 44% were Shamblin II; and 29% were Shamblin III. The mean 30 day mortality was 2.29% (95% CI 1.79–2.93). The mean 30 day stroke rate was 3.53% (95% CI 2.91–4.29), while the mean 30 day CNI rate was 25.4% (95% CI 24.5–31.22). The prevalence of persisting CNI at 30 days was 11.15% (95% CI 8.42–14.64). Twelve series (544 patients) correlated 30 day stroke with Shamblin status. Shamblin I CBTs were associated with a 1.89% stroke rate (95% CI 0.92–3.82), increasing to 2.71% (95% CI 1.43–5.07) for Shamblin II CBTs and 3.99% (95% CI 2.34–6.74) for Shamblin III tumours. Twenty-six series (1075 patients) correlated CNI rates with Shamblin status: 3.76% (95% CI 2.62–5.35) for Shamblin I CBTs, 14.14% (95% CI 11.94–16.68) for Shamblin II, and 17.10% (95% CI 14.82–19.65) for Shamblin III tumours. The prevalence of neck haematoma requiring re-exploration was 5.24% (95% CI 3.45–7.91). The proportion of patients with a neck haematoma requiring re-exploration was not reduced by pre-operative embolisation (5.92%; 95% CI 2.56–13.08) vs. no embolisation (5.82%; 95% CI 2.76–11.88). Pre-operative embolisation did not reduce drainage losses (639 mL vs. 653 mL).

Conclusions

This is the largest meta-analysis of outcomes after CBT excision. Procedural risks associated with tumour excision were considerable, especially with Shamblin III tumours where 4% suffered a peri-operative stroke and 17% suffered a CNI.

A National Goal: Prevent a Million Heart Attacks and Strokes by 2022

With your cooperation and the support of the medical profession, insurance companies, government agencies and communities throughout the country, the agency hopes to prevent a million heart attacks and strokes by the year 2022.As the centers’ experts estimated last year, if 2016 trends remain constant through 2021, an estimated 16.3 million potentially preventable life-threatening or fatal events, or 3.3 million a year, are projected to occur, including 2.2 million emergency department visits, 2.2 million deaths and 11.8 million hospitalizations, at a projected cost of $170 billion. A third of these preventable events are likely to afflict people aged 35 to 64, these experts, Dr. Janet S. Wright, Hilary K. Wall and Matthew D. Ritchey, calculated.He and his colleagues cited 213 million opportunities to improve cardiovascular risk among Americans by addressing behaviors that are currently standing in the way of progress: 71 million people are physically inactive, participating in no leisure-time exercise. 54 million people are still smoking combustible tobacco products. 40 million adults have uncontrolled high blood pressure.39 million with high cholesterol are not using medication to lower it. 9 million people for whom a daily baby aspirin is appropriate are not taking it.
The as-yet unstoppable epidemic of obesity is most likely the leading cause of preventable cardiovascular disease and deaths. Excess weight can result in high blood pressure, high cholesterol levels, Type 2 diabetes and a reluctance to be physically active, all of which contribute to cardiovascular risk.

Doctors and Disclosures

Doctors work hard not only in diagnosing diseases and treating them but also conduct research and help in improving the understanding of the diseases and their origins. This is possible through their association with other scientists, organizations and other medical industries. But this process needs to be transparent and one has to disclose conflict of interest. There can be serious objections if there are undisclosed links between the doctors and medical industries. In the Western countries this is taken seriously if the doctors at the helm of affairs fail to disclose search associations and especially when they are receiving honorariums. This is going to be considered equally seriously in the developing nations also soon. 

Academic journals are the way the world learns about medical breakthroughs, and companies benefit greatly when research about their products is published in them. Prestigious journals require authors to list any potential conflicts of interest. But dozens of doctors have failed to disclose significant relationships with health care and drug companies that pay them for consulting work, sitting on corporate boards and other roles.

https://www.nytimes.com/interactive/2018/12/08/health/journal-conflicts-of-interest.html 

Can we reduce the Cardiovascular risk and cancer risk by supplementing omega-3 fatty acids 1gm per day and Vitamin D3 2000 units/day-?

When we were medical students, omega-3 fatty acids were talked about among the senior citizens as better nutritional supplements to protect them from the illnesses. Now, we are aware that the higher intake of these omega-3 fatty acids has been associated with reduced risks of cardiovascular disease and cancer in several observational studies. Similarly, in the last few years, vitamin D levels were found to be very low in many people in our society. Some association was also noted between the low levels of Vitamin D and CV disease and cancer. This leads us to think that supplementation of these (omega-3 fatty acids and vitamin D) may be more effective in reducing the CV disease and cancers. If that is proved we may be finding new medication (fixed drug combinations)

A study was conducted and the results were published by J E Manson et al (2019). In this study the benefits of using the combination (Vitamin D₃ 2000units/day + Omega -3 fatty acids 1gm per day) were assessed. This is a randomized placebo-controlled trial. This study focuses a primary prevention of CV disease and cancer among men older than 50 years and women older than 55 years. Primary endpoints were major CV events (a composite of myocardial infarction, stroke or death from cardiovascular causes) and invasive cancer of any type. Secondary end points included individual components of the composite cardiovascular end point, the composite end point plus coronary revascularization (expanded composite of cardiovascular events), site-specific cancers, and death from cancer. A total of 25,871 people participated in this trial, out of them 5106 were blacks. All these patients were followed for 5.3 years.

At the end, it is disappointing to note that  supplementation of this combination did not result in lower incidence of major cardiovascular events or cancer than placebo.

https://www.nejm.org/doi/full/10.1056/NEJMoa1811403?query=featured_home

Myocardial injury after non-cardiac surgery

Perioperative myocardial injury in patients undergoing non-cardiac surgery is a major challenge in the vascular surgical practice. It can be missed if we don’t look for it, but it was found to be associated with early (30-day) and late (1 yr) morbidity and mortality. Puelacher C et al defined Perioperative Myocardial Infarction (PMI) as an absolute high-sensitivity cardiac troponin T increase of ≥14 ng/L from preoperative to postoperative measurements. In their large study (2546 surgeries) PMI occurred in 16%, but it was accompanied by chest pain only in 6%, any type of ischemic symptoms in 18%. Crude 30-day mortality was 8.9%  in patients with PMI versus 1.5% in patients without PMI. There is a potential to help many of the 8 million adults globally who have PMI(MINS) to reduce their risk of a major vascular complication. If only we can identify these patients and apply appropriate medications, we can prevent this mortality and morbidity.

Reference

Puelacher C, Lurati Buse G, Seeberger D, Sazgary L, Marbot S, Lampart A, Espinola J, Kindler C, Hammerer A, Seeberger E, Strebel I, Wildi K, Twerenbold R, du Fay de Lavallaz J, Steiner L, Gurke L, Breidthardt T, Rentsch K, Buser A, Gualandro DM, Osswald S, Mueller C; BASEL-PMI Investigators. Perioperative Myocardial Injury After Noncardiac Surgery: Incidence, Mortality, and Characterization. Circulation. 2018;137(12):1221-1232. 

Effect of polidocanol foam on pulmonary parenchyma?

Phlebology. 2018 Mar;33(2):122-127. doi: 10.1177/0268355516683922. Epub 2017 Jan 16.

Effect of polidocanol foam administration into rat peripheral veins 

on pulmonary parenchyma.

de Moraes Silva MA¹, Ferreira RG¹, de Jesus-Silva SG¹, Cardoso RS¹, Miranda F Jr.¹

Abstract

Background Sclerotherapy has been gaining increased acceptance and popularity as an effective therapy for the treatment of varicose veins. This attention has fed growing interest into the safety and potential complications of this procedure. There is no evidence of pulmonary complications from foam sclerotherapy in humans; however, animal studies have shown possible damage. The aim of this study is to show the changes in rat pulmonary parenchyma after the injection of 1% polidocanol Tessari foam into the peripheral vein using histological analysis of the inflammatory and fibrosis processes. Methods Twenty-four Wistar rats were divided into the following four groups: 24 h polidocanol, seven-day polidocanol, 28-day polidocanol, and control group. After the foam was injected into the lateral saphenous vein, the lungs of the rats were removed for histological analysis. Results Alveolar edema was observed in only the 24 h group (P < 0.005). Vessel thickening was observed in the seven-and 28-day groups (P < 0.001). Interstitial fibrosis was found in only the 28-day group (P = 0.006). There was no evidence of venous or arterial thrombosis in either group. Conclusion Polidocanol Tessari foam injection into rat peripheral veins causes alveolar edema, vessel thickening, and interstitial fibrosis.

Diosmin along with other active Flavanoids is more effective in treating the venous disease.

Eur J Vasc Endovasc Surg. 2018 Mar 24. pii: S1078-5884(18)30106-0. doi: 10.1016/j.ejvs.2018.02.009. [Epub ahead of print]

Protective Effects of Micronized Purified Flavonoid Fraction (MPFF)

on a Novel Experimental Model of Chronic Venous Hypertension.

das Graças C de Souza M¹, Cyrino FZ², de Carvalho JJ³, Blanc-Guillemaud V⁴, Bouskela E

CONCLUSION:

 MPFF was more effective than diosmin in improving all microvascular

variables. The superiority of MPFF over diosmin alone can be explained by the synergistic

beneficial effects of the association between diosmin and active flavonoids of MPFF.

PGE-1 infusion and PET Scan to see increase in the muscular blood flow!

Increase of blood flow in the ischaemic leg is believed to represent the main action of prostaglandin E1 (PGE1) in the therapy of peripheral vascular disease (PVD). There is no reliable data in man concerning the amount of increase in muscular blood flow (MBF) of the calf, and the difference between intra-arterial and intravenous application. We conducted a positron emission tomography (PET) study of MBF with 15O-water as flow tracer. Fifteen patients with PVD and three healthy volunteers were given 5 micrograms PGE1 intra-arterially over 50 min; PET scans were taken at 0, 25 and 50 min.  

Additionally, eight of the patients were investigated during an intravenous infusion of 40 micrograms PGE1 over 120 min; PET scans were taken at 0, 30, 60 and 120 min.  

Increase of muscular blood flow by intra-arterial PGE1 averaged 80%. A steal phenomenon was not observed. The amount of flow enhancement depended on whether or not the femoral artery was patent. During intravenous PGE1, muscular blood flow remained unchanged. In man, the pharmacodynamic profile of intra-arterial PGE1 differs clearly from intravenous PGE1. The flow-enhancing property is lost during metabolization in the lung. Since no difference exists between the therapeutic efficacy of intraarterial and intravenous PGE1, the impact on muscular blood flow is not as important as suggested previously.  Prostaglandin E1 in peripheral vascular disease: A PET study of muscular blood flow. Available from: https://www.researchgate.net/publication/13697266_Prostaglandin_E1_in_peripheral_vascular_disease_A_PET_study_of_muscular_blood_flow [accessed Sep 15, 2017]. 

Pinjala R K