The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended ...venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration. The prominent one is reflected in the fact that dynamic impairment in renal function due to dehydratation may lead to haemorragic complications on the one hand, while on the other hand glomerular hyperfiltration may be a possible cause of dabigatran subdosing, hence reducing the drug's efficacy. Furthermore, limitations of the Cockcroft-Gault formula, considered a standard equation for assessing the renal function, may imply that other calculations are likely to obtain more accurate estimates of the kidney function in specific patient populations. Method and Conclusions: Although not routinely recommended, a possibility of monitoring dabigatran in special clinical settings adds to optimization of its dosage regimens, timely perioperative care and administration of urgently demanded thrombolytic therapy, therefore significantly improving this drug's safety profile. Despite the fact that dabigatran has fewer reported interactions with drugs, food constituents, and dietary supplements, certain interactions still remain, requiring considerable caution, notably in elderly, high bleeding risk patients, patients with decreased renal function and those on complex drug regimens. Additionally, upon approval of idarucizumab, an antidote to dabigatran solution, hitherto being a major safety concern, has been finally reached, which plays a vital role in life-threatening bleeding and emergency interventions and surgery.
Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. The present study was undertaken to assess the vasorelaxant effect of procyanidin B2 on ...isolated human saphenous vein (HSV) and its underlying mechanisms. Procyanidin B2 relaxed phenylephrine-induced contraction of HSV rings in concentration-dependent manner. The relaxation was dependent on the presence of endothelium and was strongly affected by l-NAME, hydroxocobalamin or ODQ, the inhibitors of NO/cGMP pathway. Indomethacin significantly affected only the relaxation produced by the highest concentrations of procyanidin B2. Apamin and TRAM-34 combination, in the presence of l-NAME and indomethacin, did not additionally decreased procyanidin B2-induced relaxation. In the presence of K+ channel blockers, relaxation induced by procyanidin B2 was partially attenuated by 4-aminopyridine, significantly inhibited by glibenclamide and almost abolished by iberiotoxin. Procyanidin B2 also relaxed the contractions induced by phenylephrine or caffeine in Ca2+-free solution. Finally, nifedipine slightly, while thapsigargin strongly antagonized HSV relaxation. Our results indicate that procyanidin B2 induces endothelium-dependent relaxation of HSV, which results primarily from stimulation of NO production, as well K+ channels opening, especially BKCa, and partially KATP and KV. Regulation of the intracellular Ca2+ release and inhibition of Ca2+ influx probably contribute to procyanidin B2-induced relaxation.
To evaluate the prevalence of metastatic tumors involving the myocardium and study their presentation in order to increase awareness to their existence.
Pathological reports from Sheba Medical Center ...(Israel, January 1, 2010 through December 31, 2015) and medical records from The Institute for Cardiovascular Diseases of Vojvodina, Sremska Kamenica (Serbia, 23 years period) were screened for cases of metastatic cardiac tumors. Medical, radiological and pathological data of identified cases was retrieved and reviewed.
Out of thousands of registered cardiac surgeries we found less than a dozen cases of metastatic cardiac tumors classified as melanoma, carcinomas of lung, colon and kidney and sarcomas of uterine origin. We found that metastatic cardiac tumors comprised 15.8% of all the cardiac tumors.
Metastatic cardiac tumors are extremely rare. As new diagnostic technologies and improved survival of oncological patients may increase the incidence of metastatic cardiac tumors in the future, awareness to their existence and knowledge of their presentation are key factors in their timely recognition.
In this study, we aimed to investigate relaxant effect of flavanol (−)‐epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms ...underlying this vasorelaxation. (−)‐Epicatechin induced a concentration‐dependent relaxation of HSV pre‐contracted by phenylephrine. Among K+ channel blockers, 4‐aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (−)‐epicatechin. Additionally, (−)‐epicatechin relaxed contraction induced by 80 mM K+, whereas in the presence of nifedipine produced partial relaxation of HSV rings pre‐contracted by phenylephrine. In Ca2+‐free solution, (−)‐epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca2+‐ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (−)‐epicatechin. These results demonstrate that (−)‐epicatechin produces endothelium‐independent relaxation of isolated HSV rings. Vasorelaxation to (−)‐epicatechin probably involves activation of 4‐aminopyridine‐ and margatoxin‐sensitive KV channels, BKCa channels, and at least partly, KATP channels. In addition, not only the inhibition of extracellular Ca2+ influx, but regulation of the intracellular Ca2+ release, via inositol‐trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca2+‐ATPase, as well, most likely participate in (−)‐epicatechin‐induced relaxation of HSV.
As we previously demonstrated the role of different K+ channels in the action of nicorandil on human saphenous vein (HSV) and human internal mammary artery (HIMA), this study aimed to analyse the ...contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K+ channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K+ (KATP) channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K+ (KV) channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca2+-activated K+ (BKCa) channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of KV channels in HSV is probably due to GC activation and increased levels of cGMP.
Recently it has been suggested that resveratrol relaxes different isolated arteries. The present study addressed the question whether different ion channels are involved in the ...endothelium-independent mechanism of vasodilatation induced by resveratrol. For that purpose, we tested the action of resveratrol on the rat mesenteric artery without endothelium. Resveratrol induced concentration-dependent relaxation of rat mesenteric artery. Among the K+-channel blockers, 4-amynopiridine (4-AP) moderately antagonized the resveratrol-induced relaxation, while glibenclamide, tetraethylammonium chloride, charybdotoxin, margatoxin, and barium chloride did not inhibit resveratrol-induced vasorelaxation. In rings, precontracted with 100 mM K+, the relaxant responses to resveratrol were highly significantly shifted to the right compared to those obtained in rings precontracted with phenylephrine, but resveratrol-induced maximal relaxation was only slightly affected. In order to minimize the influence of K+ channels and voltage-gated Ca2+ channels (VGCCs) in vascular smooth muscle, the third contraction was made by 100 mM K+ in the presence of nifedipine. The relaxant response to resveratrol was abolished. Thus, the mechanism of vasorelaxation induced by resveratrol probably involves activation of 4-AP-sensitive K+ channels. Its ability to completely relax the mesenteric artery precontracted with K+-rich solution suggests that K+ channel–independent mechanism(s) are involved in its vasorelaxant effect. It seems that interaction with VGCCs plays a part in this K+ channel–independent effect of resveratrol.
We are currently witnessing the advent of new diagnostic tools and therapies for heart diseases, but, without serious scientific consensus on fundamental questions about normal and diseased heart ...structure and function. During the last decade, three successive, international, multidisciplinary symposia were organized in order to setup fundamental research principles, which would allow us to make a significant step forward in understanding heart structure and function. Helical ventricular myocardial band of Torrent-Guasp is the revolutionary new concept in understanding global, three-dimensional, functional architecture of the ventricular myocardium. This concept defines the principal, cumulative vectors, integrating the tissue architecture (i.e. form) and net forces developed (i.e. function) within the ventricular mass. Here we expose the compendium of Torrent-Guasp's half-century long functional anatomical investigations in the light of ongoing efforts to define the integrative approach, which would lead to new understanding of the ventricular form and function by linking across multiple scales of biological organization, as defined in ongoing Physiome project. Helical ventricular myocardial band of Torrent-Guasp may also, hopefully, allow overcoming some difficulties encountered in contemporary efforts to create a comprehensive mathematical model of the heart.
Numerous limitations and side effects of standard anticoagulants require administering new anticoagulant drugs. New peroral anticoagulants of Factor Xa inhibitor group have more advantages, the key ...ones being: substantial reductions in specific nutrition limitations and drug interaction, no need for routine laboratory monitoring and greatly improved therapy predictability. Rivaroxaban, a selective peroral Factor Xa inhibitor is more effective compared with enoxaparin for venous thromboembolism (VTE) prophylaxis in major orthopedic interventions. Though several single trials demonstrated no difference in hemorrhagic complications, certain meta-analyses with rivaroxaban showed a higher incidence of hemorrhage. Apixaban, a peroral reversible inhibitor of factor Xa approved for the prevention of VTE, compared with European-approved doses of enoxaparin has the efficacy almost equal to the North-American-approved enoxaparin doses without a significant difference in bleeding rates, though ?DVANCE I study points towards lower bleeding rates in patients treated with apixaban. To clarify the contradictory results of the recent meta-analysis related to the comparison between the stated factor X inhibitors and various comparator enoxaparin regimens as well as related to the risk for symptomatic PTE and total bleeding events following major orthopedic surgery, new research will be required. Specificities of rivaroxaban and apixaban, already constituting, according to modern recommendations, an integral part of the VTE prophylaxis protocols after major orthopedic interventions, will enable the establishment of personalized protocols aimed at developing an improved safety profile of each individual patient.
PDF
