Zuzana Hlubocka

Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors.

The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Wilebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.

Association of 344/T/C Aldosterone Synthase Polymorphism (CYP11B2) with Left Ventricular Structure and Humoral Parameters in Young Normotensive Men

Background: Aldosterone plays an important role in development of left ventricular (LV) hypertrophy and myocardial fibrosis. We assessed the influence of the T‐344C polymorphism of aldosterone synthase – the rate‐limiting enzyme in aldosterone biosynthesis – on the structure of the left ventricle in young normotensive men. Design and methods: The population included 113 normotensive mid‐European Caucasian men aged 18–40 years (mean 27 ± 5 years). The genotype was assessed using polymerase chain reaction with subsequent cleavage with restriction enzyme HAEIII (restriction fragment length polymorphism method) and visualization with ethidium bromide. Plasma renin activity (PRA) and plasma aldosterone were measured. All subjects were examined by echocardiography and LV mass was assessed by using M‐mode based ASE formula. Results: The distribution of the genotypes was TT 23%:TC 55%:CC 22%. There were no differences in blood pressure among the groups. Men with the TT genotype had significantly higher levels of PRA (2.7 ± 1.7 vs 1.8 ± 1.0 vs 1.8 ± 1.1 ng/ml/h, p < 0.01) and slightly higher plasma levels of aldosterone (113 ± 64 vs 93 ± 43 vs 87 ± 39 pg/ml, p = 0,12). In the whole population, LV mass index (LVMI) did not differ significantly among the genotypes (92 ± 16 vs 86 ± 18 vs 84 ± 16 g/m 2 , p = 0.20). In the population divided according to PRA, subjects with high renin had significantly higher LVMI in presence of the TT genotype (95 ± 17 vs 84 ± 16 vs 81 ± 15 g/m 2 , p < 0.05). Conclusions: In agreement with previous studies, we found that the TT genotype of T‐344C polymorphism of aldosterone synthase gene was associated with significantly higher levels of PRA in normotensive men. In subjects with high PRA, the TT genotype was associated with higher values of the LVMI.

Association Analysis of Arg16Gly Polymorphism of the β 2 -Adrenergic Receptor Gene in Offspring from Hypertensive and Normotensive Families

Objective: Since g 2 -adrenergic receptors ( g 2 AR) can influence blood pressure not only by vasodilation, but also participate in noradrenaline release from sympathetic nerve endings, we have studied whether Arg16Gly polymorphism of the g 2 AR gene is associated with predisposition to essential hypertension and increased plasma noradrenaline concentration in offspring from normotensive (SN) and hypertensive parents (SH). Design and methods: The study population consisted of 105 young SN and 101 SH subjects matched for age and body mass index. Arg16Gly polymorphism of the g 2 AR gene was determined by polymerase chain reaction (PCR) technique and subsequent incubation with NcoI restriction enzyme. Resulting fragments were separated using electrophoresis on a 4.2% Metaphor agarose gel. Results: SH already had significantly higher systolic BP, and a tendency to higher diastolic BP than the SN group. The frequency of Arg/Arg homozygotes was significantly increased in SH when compared to SN (25% vs 15%). Results of logistic regression analysis showed the highest relative risk for the Arg/Arg genotype and suggested a recessive action of the Arg16 variant. There was an increased diastolic BP in Arg/Arg homozygotes of the SN group ( p = 0.029). This genotype also had a tendency to increased heart rate in both groups ( p = 0.049). There was no relationship of this polymorphism with plasma noradrenaline concentration. Conclusion: Our findings suggest that genetic variability of the g 2 AR gene is implicated in predisposition to essential hypertension. However, the contradictory results between individual studies indicate that the action of the g 2 AR gene is indirect, through multiple intermediate phenotypes and gene interactions.

Structural changes arising from different thawing protocols on cryopreserved human allograft’s aortic valve leaflets

BACKGROUND The aim of our experimental work was to assess the impact and morphological changes that arise during different thawing protocols on human aortic valve (AV) leaflets resected from cryopreserved aortic root allografts (CARAs). OBJECTIVES Two thawing protocols were tested: 1. CARAs were thawed at a room temperature (23°C); 2. CARAs were placed directly into a water bath at a temperature of 37°C. After all the samples were thawed, non-coronary AV leaflets were sampled from each specimen and fixed in a 4% formaldehyde solution before they were sent for morphological analysis. MATERIAL AND METHODS All the samples were washed in distilled water for 5 min and dehydrated in a graded ethanol series (70%, 85%, 95%, and 100%) for 5 min at each level. The tissue samples were then immersed in 100% hexamethyldisilazane (HMDS) for 10 min, and then air-dried in an exhaust hood at room temperature. Processed samples were mounted on stainless steel stubs and coated with gold. Histological analysis was performed with the use of an electron microscope on a scanning mode operating at 25 kV - BS 301. RESULTS Thawing protocol 1 (room temperature at 23°C): 6 (100%) samples showed loss of the endothelial covering of the basal membrane with no damage to the basal lamina. Thawing protocol 2 (water bath at 37°C): 5 (83%) samples showed loss of the endothelial covering of the basal membrane with no damage to the basal lamina. One (17%) sample showed loss of the endothelial covering the basal membrane with significant damage to the basal membrane. CONCLUSIONS Based on our experimental work, we can clearly conclude that cryopreserved AV leaflet allografts show identical structural changes at different rates of thawing.

Heart Failure Caused by Misdiagnosed Subaortic Stenosis in Adulthood: Lesson for Daily Practice

Acomplaints of worsening shortness of breath. She had a history of heart murmur detected during childhood. During the eighth month of her pregnancy, she experienced presyncope and heart failure. There was a progression of symptoms 6 months after delivery. A transthoracic echocardiogram showed normal LV function and tiny valves, including a three leaflet–shaped aortic valve, but pressure gradient within the left ventricular outflow tract (LVOT) was greater than 80 mm Hg. There was a tiny membrane in the LVOT, initially overlooked by transthoracic but well seen by transesophageal echocardiography (Fig 1). The presence of this obstruction was then confirmed on cardiac computed tomography (Fig 2) that demonstrated a fibromuscular shelf located at the area of aortomitral continuity with the extension toward the septum. Revision of the LVOT and aortic valve was performed, and an abnormal membrane in the LVOT was resected (Fig. 3). There were no perioperative complications. Subvalvular aortic stenosis is the second most common form of aortic stenosis. Among children, it accounts for 14% of cases [1], and there are few reports about surgery for SAS among adults [2].

Cryopreserved human aortic root allografts arterial wall: Structural changes occurring during thawing

Background The aim of our experimental work was to assess morphological changes of arterial wall that arise during different thawing protocols of a cryopreserved human aortic root allograft (CHARA) arterial wall. Methods The experiment was performed on CHARAs. Two thawing protocols were tested: 1, CHARAs were thawed at a room temperature at +23°C; 2, CHARAs were placed directly into a water bath at +37°C. Microscopic samples preparation After fixation, all samples were washed in distilled water for 5 min, and dehydrated in a graded ethanol series (70, 85, 95, and 100%) for 5 min at each level. The tissue samples were then immersed in 100% hexamethyldisilazane for 10 minutes and air dried in an exhaust hood at room temperature. Processed samples were mounted on stainless steel stubs, coated with gold. Results Thawing protocol 1: All 6 (100%) samples showed loss of the endothelium and damage to the subendothelial layers with randomly dispersed circular defects and micro-fractures without smooth muscle cells contractions in the tunica media. Thawing protocol 2: All 6 (100%) samples showed loss of endothelium from the luminal surface, longitudinal corrugations in the direction of blood flow caused by smooth muscle cells contractions in the tunica media with frequent fractures in the subendothelial layer Conclusion All the samples thawed at the room temperature showed smaller structural damage to the CHARA arterial wall with no smooth muscle cell contraction in tunica media when compared to the samples thawed in a water bath.

Failed TAVI in TAVI Implantation: TAVI Dislocation Followed by Ensuing Surgical Graft Resection

We are presenting a case report of failed valve-in-valve treatment of severe aortic stenosis. A control ultrasonography after TAVI implantation revealed a severe aortic regurgitation of the graft which was subsequently unresolved with postimplantation dilatation. Second TAVI was implanted with cranial dislocation to the aortic root. Patient underwent a CT examination to clarify the TAVI in TAVI position. Patient underwent a surgical resection of TAVI with implantation of biological aortic valve prosthesis. In situations where TAVI treatment fails or is complicated beyond the possibility of endovascular repair, surgical intervention despite its higher risks is the preferred choice.

Pulmonary artery pulsatility indexes in differentiating chronic pulmonary thromboembolism from pulmonary arterial hypertension

ABSTRACT Background: The differentiation between chronic pulmonary thromboembolic hypertension (CTEPH) and pulmonary arterial hypertension (PAH) remains a clinical challenge. Recently, it has been suggested that pulmonary artery pulsatility indexes, determined either invasively or noninvasively, could enable the discrimination between CTEPH and PAH. Aim of the study: To evaluate the usefulness of both echocardiographically- and invasively-derived pulmonary artery pulsatility indexes in the etiologic differentiation of patients with CTEPH and PAH. Methods: We retrospectively analyzed the results of echocardiographic and invasive hemodynamic examinations in 97 patients with either CTEPH (n = 48) or PAH (n = 49). Using echocardiography, pulmonary artery systolic (PASP), diastolic (PADP) and mean (PAMP) pressures were estimated from velocities of tricuspid regurgitation and pulmonary regurgitation, respectively. Invasive data were obtained in 39 patients with CTEPH and 44 patients with PAH using a fluid-filled system that included a balloon-tipped flow catheter. Pulse pressure (PP) was calculated as a difference between PASP and PADP. To obtain pulmonary artery pulsatility indexes, we normalized PP by PASP (PP/PASP), by PAMP (PP/PAMP) and by PADP (PP/PADP). Results: Pulsatility indexes assessed by echocardiography did not differ between CTEPH and PAH patients. Invasively-derived pulsatility indexes were significantly higher in subjects with CTEPH (0.59 ± 0.09 vs. 0.52 ± 0.10 for PP/PASP; 0.95 ± 0.23 vs. 0.77 ± 0.19 for PP/PAMP; 1.52 ± 0.53 vs. 1.14 ± 0.37 for PP/PADP; all p < 0.01). The areas under the receiver-operating characteristic curves analysis were 0.68 (95% CI 0.55–0.79), 0.7 (95% CI 0.58–0.81), and 0.68 (95% CI 0.55–0.79) for invasively-derived PP/PASP, PP/PAMP and PP/PADP, respectively. Conclusions: Invasively-derived PP and pulmonary artery pulsatility indexes are higher in CTEPH compared to PAH. However, due to the important overlap, no optimal threshold values of these parameters can be given to allow satisfactory discrimination between the two diseases. Therefore, these indexes do not permit clear etiologic differentiation of CTEPH and PAH in clinical practice.