The Effect of Cyclic Adenosine Monophosphate (cAMP) on Acute Liver Toxicity in Mice Induced by D-galactosamine and Lipopolysaccharide

The aim of this study was to examine the effect of cyclic adenosine monophosphate (cAMP) and its possible interference/synergism with calcium channel blocker in mice with acute liver injury induced with D-galactosamine (D-GalN) and lipopolysaccharide (LPS). C57Bl/6 mice were given i.p. simultaneously 300 mg/kg D-GalN and LPS 0.01 mg/kg. This treatment induced severe hepatitis, as evidenced by high mortality (80–90%) of control mice and large increase in concentration of aminotransferases in plasma (AST, ALT). Injection of stabile analogue of cAMP (dibutyryl-cAMP, db-cAMP) one hour before hepatotoxic agents increased survival of mice in dose-dependent manner and in medium dose significantly decreased plasma ALT level. Similar (protective) effect had also verapamil, calcium channel blocker, when given in non toxic doses and at the same time schedule as db-cAMP. Combination of db-cAMP and verapamil had not synergistic effect in protection from D-GalN+LPS hepatotoxicity; the survival of mice was similar to that seen in protection caused by each agent alone

Treatment of deep vein thrombosis in elderly patients

Background: Prevalence of deep vein thrombosis (DVT) in octogenarians is increasing according to the demographic trends. ACCP guidelines1 published 2016 dramatically influenced on therapeutic strategies in favor of NOACs versus VKA in DVT/PE treatment. Non inferior efficacy and greater safety if treated with NOACs was the privilege for therapy in elderly. Seniors are vulnerable mostly because of increased risk of bleeding, various comorbidities so they are usually undertreated if VKA was prescribed. Retrospective analysis from our University Center would reveal DVT treatment changes in elderly patients in the past 45 months that might be influenced by new guidelines recommendation. Patients and Methods: Analysis included 97 DVT hospitalized patients aged 83.9±4.34 treated in Department of Cardiovascular diseases, University of Zagreb School of Medicine, in 45 months period (2016-2019). Proximal DVT occurred in 78.2%, 70% DVT was provoked (cancer related in 35%, 21.6% trauma, 7.6% surgery related, 9.6% bed rest, 19.5 % were already treated with anticoagulants because of atrial fibrillation). Results: For the whole observed period (2016-2019) 18% of patients were initially on admission treated with NOACs and 38 % were switched to NOACs on hospital discharge for continued therapy. DVT treatment using non VKA has significantly (p=0.008) positive trend with respect of creatinine clearance values. Only 8.6% population were prescribed NOACs for the extended therapy for DVT or VTE in year 2016. In 2018 and 2019 53% of octogenarians were treated with NOACs for at least 3 months. Conclusions: DVT pharmacotherapy in senior population according to observational study revealed significant changes in the 45 months period according to our Centar data. Long term treatment for DVT in octogenarians was significantly changed, with the positive trend favoring NOACs versus VKA (p=0.008)

Diastolic function changes in hypertensive patients and septal bulge

Background: Hypertensive patients with basal septal hypertrophy (BSH) are known to have high filling pressures comparing to healthy controls, eventually leading to diastolic heart failure and poor outcomes.1-3 Aim: To investigate if occurrence of basal septal hypertrophy is related to diastolic disfunction in younger patients with uncomplicated arterial hypertension (AH) and no comorbidities compared to hypertensive patients with no BSH. Patients and Methods: A total of 138 patients aged 18-65 years (mean 48.51±11.69 years), 47.8% men were enrolled. Complete 2D transthoracic echocardiography according to standardized protocol was performed, as well as deformation study using 2D speckle tracking echocardiography. All patients included in the study had a preserved left ventricular ejection fraction (mean 61.35±5.07%). Basal septal hypertrophy was defined as basal/mid septal thickness ratio >1.3, or thickness of the basal interventricular (iv) septum >2mm compared to mid iv septum, along with visual BSH notification. Results. There were altogether 74 patients (53.6%) with BSH. Patients in this group were older (51.41±9.37 vs 45.16±13.19 years, p=0.006), with longer duration of AH (9.01±9.67 vs 5.95±8.51 years, p=0.009). Echocardiographic measurements revealed normal left ventricular (LV) geometry and left atrial (LA) volumes, as well as normal values of standard indices of diastolic function in the whole population. However, patients with BSH showed incipient concentric LV remodeling and relaxation impairment (RWT 0.38±0.11 vs 0.3±0.08, p<0.001; LVMI 109.15±25.33 vs 89.19±24.59g/m2, p<0.001; E/A 0.96±0.28 vs 1.16±0.39, p=0.001; LAVI 32.68±9.98 vs 30.02±11.37, p=0.05). There were no differences among groups according to global deformation measurements. Longitudinal strain was more impaired in three basal LV segments (basal iv septum -11.38±4.37% vs -14.69±2.54%, p<0.001; mid iv septum -16.44±3.54 vs -18,16±2.9%, p=0.01; basal anteroseptum -13.38±4.19 vs - 15.24±3.23%, p=0.01), correlating with indices of diastolic function shown in Table 1. Conclusion. BSH is shown to be an early sign of LV relaxation impairment, along with incipient geometry and regional longitudinal deformation changes even in younger patients and in early stages of AH

Impact of mild patient prosthesis mismatch on quality of life in patients with preserved ejection fraction after isolated aortic valve replacement for aortic stenosis

AIM: To analyze whether PPM affects QOL and functional status in patients after isolated AVR for aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF). ----- METHODS: Consecutive patients who underwent AVR in University Hospital Center Zagreb for isolated severe symptomatic AS and preserved EF were enrolled. Echo data was obtained from complete transthoracic examinations prior and after surgery by offline analysis. Patients were divided into two groups according to the presence of PPM (effective orifice area (EOA)/body surface area (BSA)<0,85cm2/m2). QOL was assessed by telephone interview using Short Form 36-Item Health Survey (SF-36) along with functional NYHA status estimation. ----- RESULTS: A total of 45 pts were included (23 female), and divided in PPM (n=26), and non-PPM group (n=19). Both groups were similar in pts age, LVEF, AVA/BSA prior surgery. After surgery, 57% of pts had PPM categorized as mild PPM. During follow-up of 2,5years, 3 pts had died and 10 were lost from following. There was no difference in NYHA status after surgery between groups (p=0,758). SF36 results showed no difference between groups. However, there was a significant improvement in Physical functioning (47,50% vs 75,47%,p=0,000) and Role limitation due to physical health (41,41% vs 81,25%, p=0,007) scores in the whole study population after AVR. Males had significantly better Energy/fatigue (p=0,034), Social functioning (p=0,004) and Pain (p=0,017) scores. ----- CONCLUSIONS: Mild to moderate PPM showed no clinical relevance. All patients revealed improvement in QOL after AVR, while male sex was related to better functioning scores irrespectively of PPM