István Szentkirályi

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) II: Albumin Suppresses Angiotensin Converting Enzyme (ACE) Activity in Human

About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7±0.7 and 9.5±1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14±1.34 mN, without HSA: 13.54±2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73±2.17 mN, without HSA: 19.22±3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo.

AMP-Activated Kinase (AMPK) Activation by AICAR in Human White Adipocytes Derived from Pericardial White Adipose Tissue Stem Cells Induces a Partial Beige-Like Phenotype.

Beige adipocytes are special cells situated in the white adipose tissue. Beige adipocytes, lacking thermogenic cues, morphologically look quite similar to regular white adipocytes, but with a markedly different response to adrenalin. White adipocytes respond to adrenergic stimuli by enhancing lipolysis, while in beige adipocytes adrenalin induces mitochondrial biogenesis too. A key step in the differentiation and function of beige adipocytes is the deacetylation of peroxisome proliferator-activated receptor (PPARγ) by SIRT1 and the consequent mitochondrial biogenesis. AMP-activated protein kinase (AMPK) is an upstream activator of SIRT1, therefore we set out to investigate the role of AMPK in beige adipocyte differentiation using human adipose-derived mesenchymal stem cells (hADMSCs) from pericardial adipose tissue. hADMSCs were differentiated to white and beige adipocytes and the differentiation medium of the white adipocytes was supplemented with 100 μM [(2R,3S,4R,5R)-5-(4-Carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate (AICAR), a known activator of AMPK. The activation of AMPK with AICAR led to the appearance of beige-like morphological properties in differentiated white adipocytes. Namely, smaller lipid droplets appeared in AICAR-treated white adipocytes in a similar fashion as in beige cells. Moreover, in AICAR-treated white adipocytes the mitochondrial network was more fused than in white adipocytes; a fused mitochondrial system was characteristic to beige adipocytes. Despite the morphological similarities between AICAR-treated white adipocytes and beige cells, functionally AICAR-treated white adipocytes were similar to white adipocytes. We were unable to detect increases in basal or cAMP-induced oxygen consumption rate (a marker of mitochondrial biogenesis) when comparing control and AICAR-treated white adipocytes. Similarly, markers of beige adipocytes such as TBX1, UCP1, CIDEA, PRDM16 and TMEM26 remained the same when comparing control and AICAR-treated white adipocytes. Our data point out that in human pericardial hADMSCs the role of AMPK activation in controlling beige differentiation is restricted to morphological features, but not to actual metabolic changes.

[Cardiovascular actions of a standardized polyphenol concentrate on patients undergoing coronary bypass grafting: a randomized, double-blind, placebo-controlled study].

In this study the authors analyzed the action of Flavon Max product on the cardiovascular system of patients with severe coronary disease. Two randomized, double-blind, placebo controlled trials were carried out using impedance-cardiography, arteriography, vascular Doppler and biochemical laboratory methods. The results demonstrate that Augmentation Index measured with arteriography and C reactive protein (CRP) levels were significantly ameliorated after 2 x 2 months Flavon Max therapy. In conclusion, this product is beneficial as adjuvant in the treatment of atherosclerotic coronary disease.

Incidence, survival and determinants of mortality following mesenteric angiography and continuous intra-arterial prostaglandin E1 perfusion for non-occlusive mesenterial ischaemia in cardiac surgery

Methods Our aim was to evaluate the incidence of NOMI, to analyze results of treatment and to identify variables associated with mortality. Hospital records and clinical data of patients treated for NOMI during the last 12 years were reviewed. Clinical outcomes and factors influencing mortality were studied. Statistical analysis was performed to determine the significance of risk factors on mortality with Fisher exact test or c2 test in categorical variables. Wilcoxon rank test was used to test the continuous variables.

Excision of the calcified mitral valve with ultrasound scalpel

Mitral valve excision using ultrasound device has not been a routine procedure yet. We used an ultrasonic scalpel for the excision of the calcified mitral valves, which shorten operation time. Further, this technique permits an excision of the valve without applying traction or elevation of the valve from the level of the annulus. This method was first tested on twenty fresh porcine hearts. Subsequently, this technique was carried out with very good results in 15 consecutive patients with calcified or scarred, and distorted mitral valves. Histological samples were taken from the excised human and porcine valves. In porcine histological specimens the destructive effect of the ultrasonic scalpel was measured of an average of 0.7 mm (minimum 0.5 mms, maximum 0.8 mms). However, in the human heart, this effect was an average of 1.1 mms (minimum 0.6 mms, maximum 2.2 mms). There were no early or late complications observed in any case. The authors recommend this technique for excision of calcified mitral valves in cardiac surgery.

A meszes mitralis billentyű sebészi kimetszése ultrahangvágóvalr

Mitral valve excision using ultrasound device has not been a routine procedure yet. We used an ultrasonic scalpel for the excision of the calcified mitral valves, which shorten operation time. Further, this technique permits an excision of the valve without applying traction or elevation of the valve from the level of the annulus. This method was first tested on twenty fresh porcine hearts. Subsequently, this technique was carried out with very good results in 15 consecutive patients with calcified or scarred, and distorted mitral valves. Histological samples were taken from the excised human and porcine valves. In porcine histological specimens the destructive effect of the ultrasonic scalpel was measured of an average of 0.7 mm (minimum 0.5 mms, maximum 0.8 mms). However, in the human heart, this effect was an average of 1.1 mms (minimum 0.6 mms, maximum 2.2 mms). There were no early or late complications observed in any case. The authors recommend this technique for excision of calcified mitral valves in cardiac surgery.

Standardizált polifenol-koncentrátum keringési hatásai koszorúérműtéten átesett betegeken: randomizált, kettős vak-, placebokontrollos vizsgálatr

In this study the authors analyzed the action of Flavon Max product on the cardiovascular system of patients with severe coronary disease. Two randomized, double-blind, placebo controlled trials were carried out using impedance-cardiography, arteriography, vascular Doppler and biochemical laboratory methods. The results demonstrate that Augmentation Index measured with arteriography and C reactive protein (CRP) levels were significantly ameliorated after 2 x 2 months Flavon Max therapy. In conclusion, this product is beneficial as adjuvant in the treatment of atherosclerotic coronary disease.

Kiegészítő klinikai módszer a nyitott szívműtéteknél fellépő légembolisatio csökkentésére A complementary clinical method to minimize air embolism during open-heart surgery

Air from the left heart is ejected even up to several hours after cardiopulmonary bypass (CPB) despite the use of CO2. The following method is complementary in addition to surgical de-airing in order to further reduce the chance of air embolism, especially from the pulmonary veins. After re-expanding the lungs with standard bag inflation, the ventilation is restarted in consultation with the surgeon. The ventilator is set to the respiratory minute volume used before the CPB but at a respiratory frequency of 10/minutes whereas the regularly beating heart is filled from the heart lung machine. Transoesophageal echocardiography (TEE) reliably controls the effect.

[A complementary clinical method to minimize air embolism during open-heart surgery].

Air from the left heart is ejected even up to several hours after cardiopulmonary bypass (CPB) despite the use of CO2. The following method is complementary in addition to surgical de-airing in order to further reduce the chance of air embolism, especially from the pulmonary veins. After re-expanding the lungs with standard bag inflation, the ventilation is restarted in consultation with the surgeon. The ventilator is set to the respiratory minute volume used before the CPB but at a respiratory frequency of 10/minutes whereas the regularly beating heart is filled from the heart lung machine. Transoesophageal echocardiography (TEE) reliably controls the effect.

Kiegészítő klinikai módszer a nyitott szívműtéteknél fellépő légembolisatio csökkentésérer

Air from the left heart is ejected even up to several hours after cardiopulmonary bypass (CPB) despite the use of CO2. The following method is complementary in addition to surgical de-airing in order to further reduce the chance of air embolism, especially from the pulmonary veins. After re-expanding the lungs with standard bag inflation, the ventilation is restarted in consultation with the surgeon. The ventilator is set to the respiratory minute volume used before the CPB but at a respiratory frequency of 10/minutes whereas the regularly beating heart is filled from the heart lung machine. Transoesophageal echocardiography (TEE) reliably controls the effect.