Search

In the absence of a standardized safe surgical reentry strategy for high-risk patients with large or anterior postoperative aortic false aneurysm (PAFA), we aimed to describe an effective and safe approach for such patients.We prospectively analyzed patients treated for PAFA between 2006 and 2015. According to the preoperative computed tomography scan examination, patients were divided into two groups according to the anatomy and extension of PAFA: in group A, high-risk PAFA (diameter ≥3 cm) developed in the anterior mediastinum; in group B, low-risk PAFA (diameter3 cm) was situated posteriorly. For group A, a safe surgical strategy, including continuous cerebral, visceral, and coronary perfusion was adopted before resternotomy; group B patients underwent conventional surgery.We treated 27 patients (safe reentry, n = 13; standard approach, n = 14). Mean age was 60 years (range, 29 to 80); 17 patients were male. Mean interval between the first operation and the last procedure was 4.3 years. Overall 30-day mortality rate was 7.4% (1 patient in each group). No aorta-related mortality was observed at 1 and 5 years in either group. The Kaplan-Meier overall survival estimates at 1 and 5 years were, respectively, 92.3% ± 7.4% and 73.4% ± 13.4% in group A, and 92.9% ± 6.9% and 72.2% ± 13.9% in group B (log rank test, p = 0.830). Freedom from reoperation for recurrent aortic disease was 100% at 1 year and 88% at 5 years.The safe reentry technique with continuous cerebral, visceral, and coronary perfusion for high-risk patients resulted in early and midterm outcomes similar to those observed for low-risk patients undergoing conventional surgery.

Vitamin D and ω-3 fatty acids (ω-3) co-supplementation potentially improve type 1 diabetes (T1D) by attenuating autoimmunity and counteracting inflammation.This cohort study preliminary to a randomized control trial (RCT) is aimed to evaluate, in a series of T1D children assuming Mediterranean diet and taking cholecalciferol 1000U/day fromT1D onset, if ω-3 co-supplementation preserves the residual endogen insulin secretion (REIS).Therefore, 22 new onsets of 2017 received ω-3 [eicosapentenoic acid (EPA) plus docosahexaenoic acid (DHA), 60mg/kg/day], and were compared retrospectively vs. 37 previous onsets without ω-3 supplementation. HbA1c%, daily insulin demand (IU/Kg/day) and IDAA1c, a composite index (calculated as IU/Kg/dayx4 + HbA1c%) as surrogate of REIS, were evaluated at recruitment (T0) and 12 months later (T12). In the ω-3 supplemented group, dietary intakes were evaluated at T0 and T12. As outcome, decreased insulin demand (p

Background. Postoperative outcomes of a third-generation porcine bioprosthesis for mitral valve replacement (MVR) have been poorly addressed. The objective of this study was to perform an independent, retrospective, multicenter study on outcomes of patients undergoing MVR with a Mosaic (Medtronic Inc, Minneapolis, MN) porcine bioprosthesis.Methods. From 1998 to 2011, 805 patients underwent MVR with a Mosaic porcine valve in 11 cardiac centers. There were 465 female patients (58%), and the overall mean age was 73.5 +/- 7 years. Associated procedures included coronary artery bypass grafting (201 patients; 24.9%), aortic valve replacement (152 patients; 18.9%), tricuspid annuloplasty (187 patients; 22.3%), and other cardiac procedures (116 patients; 14.4%).Results. Median follow-up was 44 months (interquartile range, 16 to 63), with a cumulative duration of 2.769 patientyears. Early mortality for isolated elective MVR was 3.8% (12 of 313), and overall early mortality was 7.8% (n = 63). The rate of late mortality was 3.4%/patient-year (95 late deaths). At 10 years, overall survival was 57.4% (95% confidence interval [CI], 48.8% to 67.5%), and cumulative rates of cardiac- and valve-related death were 7.4% (95% CI, 4.8% to 10.1%) and 1.1% (95% CI, 0.2% to 1.9%), respectively. The 10-year cumulative rates of thromboembolic and hemorrhagic events were 6.6% (95% CI, 1.4% to 11.8%) and 3.9% (95% CI, 0.1% to 8%), respectively, and the 10-year cumulative incidence of prosthetic valve endocarditis was 3%(95% CI, 1.2% to 4.9%). Finally, the 10-year cumulative incidences of structuralvalve degeneration andreoperationswere5.8%(95% CI, 0.2% to 11.5%) and 4.8% (95% CI, 0.7% to 10.3%), respectively.Conclusions. This independent, multicenter, retrospective study indicated that the Mosaic porcine bioprosthesis forMVR provides satisfactory results in terms of both early andlong-termoutcomes upto 14 years fromits implantation. (C) 2020 by The Society of Thoracic Surgeons

This experimental study aimed to evaluate the ex-vivo three-dimensional (3-D) motion of the Inverted Arch Ring (IAR), an innovative new design concept for a flexible incomplete annuloplasty prosthesis with an incorporated stabilizing rigid arch that can be used in correcting mitral valve regurgitation. Twenty explanted porcine hearts were placed in a circulation simulation system. Ultrasonometry transducers implanted in the mitral annulus were used to measure the 3-D valvular motion during a simulated cardiac cycle. Annular distance measurements were recorded and compared in each heart before and after the implantation of the IAR prosthesis at pressures corresponding to mid-systole and mid-diastole. Distances measured in mid-systole and mid-diastole demonstrated no significant differences in annular motion or in valve areas either prior to or after IAR implantation. Therefore, the results of this study confirm the minimal effects exerted by the IAR prosthesis on the mitral valve&rsquo, s 3-D motion during a simulated cardiac cycle.

The dramatic events precipitated by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus pandemic have highlighted the limitations and contradictions of our country’s current health care delivery model plagued by the closure of healthcare delivery structures, staff reductions, privatizations and inadequate funding which have been affecting the Italian National Health System during the past 10 years. The COVID-19 epidemic has a hefty bill: thousands of deaths - mainly elderly, hospitals overwhelmed, residential assistance structures reaching their limits, sick people left alone and uncared in homes, the disruption in life habits and an altered daily way of living never experienced before; all have contributed into making the ongoing tragedy even more painful. Herewith, we present and discuss the information and reflections from our experiences and postulate the rethinking of the established socio-health policies not only in Italy but also in other western countries which have failed to curtail the epidemic via conventional management approaches.

Background Novel surgical approach to repair degenerative mitral regurgitation such as transapical chordae tendineae replacement and "loop in loop" in loop techniques, need of artificial chordae longer than that used in the older techniques of chordae tendineae replacement. This difference in length has been reported as potential critical point for durability of artificial chordae. In the present paper we have investigated the elastic behavior of different diameter and length politetrafluorene (PTFE) suture threads as substitute of native chordae, to identify their reliability to use as long artificial chordae. Methods PTFE suture threads with different diameters were investigated in their mechanical properties at different length from 2 to 14 cm, by a servo hydraulic testing machine, to test the elastic properties of the sample in their use as mitral chordae substitutes. Results Our study shows that the chordae length is an important parameter that can change the performance of chordae itself. The analysis of elastic/properties of suture threads specimen, reveals that long PTFE chords have an optimal mechanical behavior in which elongation is accompanied by a safe elastic properties that make them well resistance during multiple tractions. Conclusions In conclusion the use of PTFE as an artificial chordae may represent a valid choice in case of insertion of artificial chordae with extra anatomic length.

Vitamin D and omega 3 fatty acid (&omega, 3) co-supplementation potentially improves type 1 diabetes (T1D) by attenuating autoimmunity and counteracting inflammation. This cohort study, preliminary to a randomized control trial (RCT), is aimed at evaluating, in a series of T1D children assuming Mediterranean diet and an intake of cholecalciferol of 1000U/day from T1D onset, if &omega, 3 co-supplementation preserves the residual endogen insulin secretion (REIS). Therefore, the cohort of 22 &ldquo, new onsets&rdquo, of 2017 received &omega, 3 (eicosapentenoic acid (EPA) plus docosahexaenoic acid (DHA), 60 mg/kg/day), and were compared retrospectively vs. the 37 &ldquo, previous onsets&rdquo, without &omega, 3 supplementation. Glicosilated hemoglobin (HbA1c%), the daily insulin demand (IU/Kg/day) and IDAA1c, a composite index (calculated as IU/Kg/day &times, 4 + HbA1c%), as surrogates of REIS, were evaluated at recruitment (T0) and 12 months later (T12). In the &omega, 3 supplemented group, dietary intakes were evaluated at T0 and T12. As an outcome, a decreased insulin demand (p &lt, 0.01), particularly as pre-meal boluses (p &lt, 0.01), and IDAA1c (p &lt, 0.05), were found in the &omega, 3 supplemented group, while HbA1c% was not significantly different. Diet analysis in the &omega, 3 supplemented group, at T12 vs. T0, highlighted that the intake of arachidonic acid (AA) decreased (p &lt, 0.01). At T0, the AA intake was inversely correlated with HbA1c% (p &lt, 0.05, r, 0.411). In conclusion, the results suggest that vitamin D plus &omega, 3 co-supplementation as well as AA reduction in the Mediterranean diet display benefits for T1D children at onset and deserve further investigation.

Background and aim of the study We investigated the dimensional and mechanical properties of polyetetrafluorene (ePTFE) sutures used as artificial chordae during mitral valve repair. Methods Mechanical properties of ePTFE synthetic chordae tendineae were tested with a servo hydraulic testing machine. Several different lengths from 2 to 14 cm were studied under both single and multiple mechanical traction. Results The mechanical behavior of artificial chordae reveals that three centimeters is the length over which we observe a significant increase in stiffness. The chordae stiffness grows further at the length greater than seven centimeters following a low number of traction cycles. Conclusion The increase of the length of artificial ePTFE chordae is accompanied by an increasing stiffness that compromises the long-term resistance of the chordae. ePTFE length can alter the performance of artificial chordae. This suggests that mitral valve repairs which anchor ePTFE neochordae to the ventricular apex may have less durability than when anchored to the tips of the papillary muscles.

The molecular background of the Ca(2+)-sensitizing effect of levosimendan relates to its specific interaction with the Ca(2+)-sensor troponin C molecule in the cardiac myofilaments. Over the years, significant preclinical and clinical evidence has accumulated and revealed a variety of beneficial pleiotropic effects of levosimendan and of its long-lived metabolite, OR-1896. First of all, activation of ATP-sensitive sarcolemmal K(+) channels of smooth muscle cells appears as a powerful vasodilator mechanism. Additionally, activation of ATP-sensitive K(+) channels in the mitochondria potentially extends the range of cellular actions towards the modulation of mitochondrial ATP production and implicates a pharmacological mechanism for cardioprotection. Finally, it has become evident, that levosimendan possesses an isoform-selective phosphodiesterase-inhibitory effect. Interpretation of the complex mechanism of levosimendan action requires that all potential pharmacological interactions are analyzed carefully in the framework of the currently available evidence. These data indicate that the cardiovascular effects of levosimendan are exerted via more than an isolated drug-receptor interaction, and involve favorable energetic and neurohormonal changes that are unique in comparison to other types of inodilators.

Ischemia/reperfusion (I/R) injury is an important cause of acute renal failure because of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine any possible protective effects of levosimendan in an in vivo pig model of renal I/R injury. In 40 anesthetized pigs (eight groups of five pigs each), I/R was induced by clamping-reopening the left renal artery. During ischemia, in three groups of pigs, levosimendan and the multiorgan preservation solution Custodiol, alone or in combination with levosimendan, were infused in the renal artery. In two other groups of animals, levosimendan in combination with Custodiol was administered after the intrarenal nitric-oxide (NO) synthase blocker N(ω)-nitro-L-arginine methyl ester (L-NAME) or the mitochondrial ATP-sensitive K(+) channel (K(ATP) channel) inhibitor 5-hydroxydecanoate (5-HD). In the other animals, saline, L-NAME, or 5-HD were administered alone. Throughout the experiments, urinary N-acetyl-β-glucosaminidase (NAG) release was measured, and renal function was assessed. Moreover, renal biopsy samples were taken for the detection of apoptosis and tissue peroxidation. In pigs treated with levosimendan or the combination of levosimendan and Custodiol, NAG, peroxidation, and apoptotic markers were lower than in animals treated with Custodiol alone. In addition, renal function was better preserved, and cell survival and antioxidant systems were more activated. All beneficial effects were prevented by L-NAME and 5-HD. In conclusion, levosimendan alone or in combination with Custodiol exerted better protection against renal I/R injuries than Custodiol alone through antioxidant, antiapoptotic, and prosurvival actions depending on mitochondrial K(ATP) channels and NO-related mechanisms.

In anesthetized pigs gastrin-17 increased coronary blood flow through CCK1/CCK2 receptors and β(2)-adrenoceptors-related nitric oxide (NO) release. Since the intracellular pathway has not been investigated the purpose of this study was to examine in coronary endothelial cells the CCK1/CCK2 receptors-related signaling involved in the effects of gastrin-17 on NO release. Gastrin-17 caused a concentration-dependent increase of NO production (17.3-62.6%; p

Background: Atrial fibrillation (AF) is a common complication of coronary artery bypass grafting (CABG). However, limited information is available about the role of preoperative echocardiographic left atrial evaluation to predict AF occurrence after CABG. Thus, we prospectively compared the ability of echocardiographic measurements of left atrial volume to predict AF in this setting. Methods: From January to December 2009, 220 patients (75% males, 66.8 ± 10.0 years) met the inclusion criteria of our study (isolated and elective CABG, no valve surgery, no permanent AF, or other chronic atrial arrhythmias). The day before CABG a complete echocardiographic evaluation was performed with left atrial volume measurements. The primary endpoint of the study was postoperative AF (POAF) lasting >30 seconds. Results: POAF was observed in 61 patients (27.7%). POAF patients showed increased left atrial M-mode anteroposterior dimension (41.2 ± 6.4 mm vs. 43.6 ± 7.3 mm; p = 0.020) and increased left atrial volume (59.0 ± 18.3 mL vs. 70.6 ± 28.1 mL; p = 0.0004). Left atrial volume was an independent risk factor for POAF (OR 10.03; 95% CI 10.01 to 10.05; p = 0.01), along with postoperative bleeding with hemoglobin levels below 8 g/dL (OR 20.84; 95% CI 10.12 to 70.19; p = 0.03) and preoperative left ventricular ejection fraction below 40% (OR 10.08; 95% CI 10.01 to 10.15; p = 0.02). Conversely, preoperative statin therapy exerted a protective role (OR 0.30; 95% CI 0.12 to 0.74; p = 0.009). Conclusion: Preoperative echocardiographic evaluation of patients with isolated CABG demonstrated that left atrium volume measurements were independently correlated to the occurrence of POAF. Further investigations should focus on the opportunity to target prophylactic antiarrhythmic treatments to patients with large left atrial volumes. (J Card Surg 2012;27:128–135)

Acute cardiac failure caused by myocardial infarction or inadequate cardioprotection during heart surgery is associated with increased mortality and morbidity. Levosimendan is a new drug used in heart failure though it is limited by the systemic hypotension, which develops with intravenous administration. Intracoronary (IC) administration however should affect systemic circulation less while maintaining the beneficial cardiac effects of the drug. We herewith report the results from the first such clinical series. Levosimendan was administered IC in 33 consecutive patients who developed cardiogenic shock during heart surgery and were unable to wean off cardiopulmonary bypass despite maximal support. Preadministration/postadministration coronary graft flows, hemodynamic parameters, left ventricular function, and metabolic requirements were measured and compared. Levosimendan significantly increased graft flows and improved hemodynamic parameters. Systolic blood pressure (93 ± 26.4 vs. 106 ± 18.2 mm Hg, P < 0.05) and cardiac index (2.0 ± 0.5 vs. 3.1 ± 0.2, P < 0.001) were increased, whereas systemic vascular resistance (1470.7 ± 114 vs. 1195.8 ± 112, P < 0.01) was reduced. Better myocardial perfusion improved metabolic requirements, with myocardial oxygen extraction and glucose uptake increasing by 72% and 74%, respectively, whereas lactate production was reduced by 64%. Echocardiography demonstrated additional ventricular segment recruitment. Therefore, IC Levosimendan administration in acute heart failure is safe and efficacious producing improved cardiac function without significant detrimental hypotension.

Objective:Levosimendanhasbeenreportedtoexertcardioprotection.In thisstudy, wehaveexaminedthecardiaceffectsofdifferentdosesof intracoronary levosimendan on ischemia/reperfusion injuries, and the involvement of KATP channels and nitric oxide (NO). Methods: The experiments were performed in a total of 56 anesthetized pigs. In 21 pigs, 1.5, 5 and 12 mg min � 1 levosimendan was infused over 15 min into the coronary artery at the onset of 1 h reperfusion following 2-h ischemia and the effects on cardiac function, infarcted area, and on apoptosis/ autophagy were examined. In addition, the activation of Akt and extracellular receptor kinase (ERK) was analyzed. The findings were compared withthoseobtainedinafurther14pigswherethehighestdoselevosimendanwasinfusedafterglibenclamideand L-nitro-argininemethylester(LNAME). Results: Intracoronary 1.5, 5 and 12 mg min � 1 levosimendan caused an increase of segmental shortening, dP/dtmax and cardiac output of 7.8%, 22.6%, and 31.6%; 7.6%, 16.9%, and 21.6%; 2.8%, 5.9%, and 6.2%, respectively, from values measured at the end of ischemia. The beneficial effects elicited by levosimendan were still evident at the end of reperfusion when the increase of segmental shortening, dP/dtmax and cardiac output caused by the three doses of levosimendan amounted to 3.7%, 13.3%, and 16.5%; 1.5%, 9.4%, and 11%; 1.4%, 2.7%, and 3.9%, respectively. When doses of 5 and 12 mg min � 1 levosimendan were used, a reduction of infarcted area to about 69% and 67% of area at risk was observed, and was significantly different from that of about 79% measured in control animals. In addition, after intracoronary levosimendan, the inhibition of apoptosis and activation of autophagy and a dose-related increase of the level of phosphorylation of ERK and Akt were observed. These responses were completely prevented by glibenclamide and significantly reduced by L-NAME. Conclusions:The results of this study show that intracoronary levosimendan reduces cell death induced by ischemia/reperfusion in a dose-dependent manner and activates survival signaling through KATP channel opening and NO. These findings support interesting implications for cardioprotection in interventional cardiology and cardiac surgery. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Levosimendan exerts cardioprotection through mitochondrial K(ATP) (mitoK(ATP)) channels opening. In addition, intracoronary levosimendan was found to modulate programmed forms of cell death by nitric oxide (NO) involvement. The aim of this study was to examine the role of mitoK(ATP) channels and NO in the effects of levosimendan on apoptosis/autophagy. In H9c2 cells treated with hydrogen peroxide apoptosis/autophagy, survival signaling, cell viability, mitochondrial membrane potential, and permeability transition pore opening were analyzed through Western blot and colorimetric and fluorescence assays. Pretreatment of H9c2 cells with levosimendan was able to counteract the oxidative injuries caused by hydrogen peroxide. The effects of levosimendan were potentiated by diazoxide and were similar to those elicited by the autophagic activator rapamycin. The autophagic inhibitor 3-methyladenine reduced the effects of levosimendan, whereas after the pan-caspases inhibitor N-Acetyl-Asp-Glu-Val-Asp-al (Z-VAD.FMK), cell survival and autophagy in response to levosimendan increased. Both the mitoK(ATP) channels inhibition and the NO synthase blocking attenuated the cardioprotection elicited by levosimendan. The results have shown that levosimendan protects H9c2 cells against oxidative injuries through the modulation of the interplay between autophagy and apoptosis and the activation of survival signaling. The mitoK(ATP) channels and NO may be involved in such cardioprotection through interference with mitochondrial functioning.

The release of gastrointestinal hormones has been reported to modulate reflex cardiovascular responses caused by gastric distension, although the role played by gastrin 17 is as yet unknown. The present study was therefore planned to determine the primary in vivo effect of gastrin 17 on coronary blood flow and cardiac function and the involvement of autonomic nervous system, CCK1/2 receptors, and nitric oxide (NO). In 40 anesthetized pigs, gastrin 17 was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure. In 35 of the 40 pigs, the mechanisms of the observed hemodynamic responses were analyzed by repeating gastrin 17 infusion after autonomic nervous system and NO blockade, and after specific CCK receptors agonists/antagonists administration. Intracoronary gastrin 17 administration caused dose-related increases of both coronary blood flow and cardiac function. The intracoronary co-administration of CCK33/pentagastrin and gastrin 17 potentiated the coronary effects observed when the above agents were given alone ( P

Background Mitral valve prolapse (MVP) is the most frequent cause of chronic, pure, and isolated mitral regurgitation, and is estimated to affect more than 144 million individuals worldwide. This short review focuses in particular on the structural and cellular aspects of MVP in humans. The key microscopic change in MVP appears to occur in the fibrosa, on which the structural integrity of the entire valve depends. Recent discoveries showed that proteoglycans may play an active role in both MVP initiation and/or progression together with valvular interstitial cells. A full understanding of the cellular basis of MVP goes beyond a mere mechanicistic description of the disease, involving the transformation of resting fibroblasts into activated myofibroblasts. Conclusions Mitral valve could represent therefore an ideal environment to study early transformation phases of fibroblasts toward a protomyofibroblast phenotype.

Background: In endothelial cells urocortin II has recently been found to activate nitric oxide synthase through cAMP-dependent and Ca2+-related pathway. Aim: The present study was therefore planned to determine the mechanisms of urocortin II effect on Ca2+ movements. Methods. In Fura-2 loaded porcine aortic endothelial cells (PAE), the effects of urocortin II on [Ca2+]c were analyzed and compared with those of various K+ channels agonists/antagonists. Results: In Fura-2 loaded PAE, urocortin II promoted a transient increase of [Ca2+]c mainly originating from an intracellular pool sensitive to thapsigargin and slightly from the extracellular space. In addition, urocortin II caused the hyperpolarization of plasma membrane through the opening of K+ channels, which contributed to the increased [Ca2+]c. These effects were abolished by the corticotropin releasing factor receptors (CRFR2) blocker, the adenylyl cyclase and Ca2+-calmodulin-kinase (CaMKII) inhibitors and by blockers of K+ channels. In addition, in PAE cultured in Na+-free medium or loaded with the plasma-membrane Ca2+ pump inhibitor the urocortin II-evoked Ca2+ transient was slower. Conclusion: The results obtained show that urocortin II affects intracellular Ca2+ homeostasis in PAE by both promoting a discharge of intracellular pool and by interfering with the operation of store-dependent channels through CRFR2-cAMP-CaMKII related signalling and K+ channels opening.

Systemic intermedin (IMD)1–47 administration has been reported to result in vasodilation and marked hypotension through calcitonin-related receptor complexes. However, its effects on the coronary circulation and the heart have not been examined in vivo. The present study was therefore planned to determine the primary in vivo effect of IMD1–47 on coronary blood flow and cardiac function and the involvement of the autonomic nervous system and nitric oxide (NO). In 35 anesthetized pigs, IMD1–47, infused into the left anterior descending coronary artery at doses of 87.2 pmol/min, at constant heart rate and arterial blood pressure, augmented coronary blood flow and cardiac function. These responses were graded in a further five pigs by increasing the infused dose of IMD1–47 between 0.81 and 204.1 pmol/min. In the 35 pigs, the blockade of cholinergic receptors (intravenous atropine, 5 pigs), α-adrenoceptors (intravenous phentolamine, 5 pigs), and β1-adrenoceptors (intravenous atenolol, 5 pigs) did not abolish the cardiac response to IMD1–47, the effects of which were prevented by blockade of β2-adrenoceptors (intravenous butoxamine, 5 pigs), NO synthase (intracoronary Nω-nitro-l-arginine methyl ester, 5 pigs), and calcitonin-related receptors (intracoronary CGRP8–37/AM22–52, 10 pigs). In porcine coronary endothelial cells, IMD1–47 induced the phosphorylation of endothelial NO synthase and NO production through cAMP signaling leading to ERK, Akt, and p38 activation, which was prevented by the inhibition of β2-adrenoceptors, calcitonin-related receptor complexes, and K+ channels. In conclusion, IMD1–47 primarily augmented coronary blood flow and cardiac function through the involvement of calcitonin-related receptor complexes and β2-adrenoreceptor-mediated NO release. The intracellular signaling involved cAMP-dependent activation of kinases and the opening of K+ channels.

Background: Urocortin II has previously been shown in anesthetized pigs to increase coronary blood flow through activation of the endothelial nitric oxide synthase (eNOS) pathway and involvement of the subtype 2 of corticotropin releasing factor receptors (CRFR2). However, little information has been available regarding the intracellular signalling through these receptors and leading to the release of nitric oxide (NO). Aim: The present study was therefore planned to determine the mechanism involved in such signalling. Methods: In porcine aortic endothelial cells (PAE) the effects of urocortin II on NO production and ERK, Akt, p38 and eNOS phosphorylation were examined in absence or presence of the adenylyl cyclase agonist forskolin and antagonist 2’5’ dideoxyadenosine, the Ca2+ ionophore A23187, the Ca2+-calmodulin-kinase inhibitor KN93, the CRFR2 blocker astressin 2B and of the protein kinases specific inhibitors UO126, wortmannin and SB203580. Results: Urocortin II caused a significant increase of NO production, which was amplified by forskolin and A23187 (P 2+-related phoshorylation of ERK, Akt and p38 leading to eNOS activation.

Background and purpose: Levosimendan acts as a vasodilator through the opening of ATP-sensitive K+ channels (KATP) channels. Moreover, the coronary vasodilatation caused by levosimendan in anaesthetized pigs has recently been found to be abolished by the nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester, indicating that nitric oxide (NO) has a role in the vascular effects of levosimendan. However, the intracellular pathway leading to NO production caused by levosimendan has not yet been investigated. Thus, the purpose of the present study was to examine the effects of levosimendan on NO production and to evaluate the intracellular signalling pathway involved. Experimental approach: In porcine coronary endothelial cells (CEC), the release of NO in response to levosimendan was examined in the presence and absence of Nω-nitro-L-arginine methyl ester, an adenylyl cyclase inhibitor, KATP channel agonists and antagonists, and inhibitors of intracellular protein kinases. In addition, the role of Akt, ERK, p38 and eNOS was investigated through Western blot analysis. Key results: Levosimendan caused a concentration-dependent and K+-related increase of NO production. This effect was amplified by the mitochondrial KATP channel agonist, but not by the selective plasma membrane KATP channel agonist. The response of CEC to levosimendan was prevented by the KATP channel blockers, the adenylyl cyclase inhibitor and the Akt, ERK, p38 inhibitors. Western blot analysis showed that phosphorylation of the above kinases lead to eNOS activation. Conclusions and implications: In CEC levosimendan induced eNOS-dependent NO production through Akt, ERK and p38. This intracellular pathway is associated with the opening of mitochondrial KATP channels and involves cAMP.

Objective: To evaluate the possible protective effects of fenoldopam on renal function in patients undergoing cardiopulmonary bypass. Design: Prospective, randomized trial. Setting: University teaching hospital. Participants: One hundred sixty consecutive patients with serum creatinine >1.5 mg/dL who underwent uncomplicated moderate hypothermic cardiopulmonary bypass for cardiac surgery. Interventions: A random group of 80 patients was managed conventionally (group A), whereas another random group of 80 patients received continuous intravenous administration of low-dose fenoldopam (0.1–0.3 μg/kg/min) during cardiopulmonary bypass and in the early postoperative period (group B). Measurements and main results: An improvement of postoperative renal parameters were observed only in group B: preoperative serum creatinine 1.82 ± 0.2 versus 1.43 ± 0.73 postoperatively (p Conclusions: In this study, fenoldopam was an effective agent in the prevention of renal dysfunction after cardiopulmonary bypass.

Presentation of the inferior epigastric artery as conduit for coronary artery bypass grafting (CABG): harvesting, use and results.

We present a novel postinfarction ventricular septal defect repair, through a single ventriculotomy, using a biseptal double patch and gelatin-resorcinol-formaldehyde glue. This technique reduces the postoperative recurrence of ventricular septal defects by reducing the tension on the patch sutures and by preventing blood from infiltrating into the suture lines within the ventricular septal defect cavity.

Yersinia enterocolitica is an unusual cause of septicaemia, usually occurring in immunocompromised hosts. Endocardial involvement is rare and generally presents as acute endocarditis. We describe the case of a 73-y-old woman, apparently without risk factors for endocarditis, admitted to hospital for persistent fever of unknown origin, arthralgia, and weight loss. Y. enterocolitica was isolated from blood and urine cultures, and echocardiography showed a pedunculated vegetation attached to the non-coronary cusp of the aortic valve. Symptoms and fever resolved after 3 days of intravenous cefotaxime plus amikacin, which were continued for the 2 weeks of her hospital stay; this treatment was followed by intravenous ceftriaxone after discharge. We hypothesized that a chemotherapy course administered 2 months previously for breast cancer might have been a predisposing factor for the Y. enterocolitica valvular infection and that immune system recovery contributed to mitigate the clinical presentation as subacute endocarditis.

Background The endocannabinoid system reportedly plays a role in the pathogenesis of cardiovascular diseases. This system is expressed also in adipose tissue, which could thus be involved in cardiac disorders through modulation of metabolically triggered inflammation. The current study aims to determine the relevance of the endocannabinoid system in epicardial adipose tissue in heart disease. Methods Expression of the endocannabinoid receptors CB1 and CB2, and of the endocannabinoid-degrading enzyme, fatty acid amidohydrolase, and activation of protein kinase A (PKA), phospholipase C (PLC), protein kinase C (PKC), endothelial nitric oxide synthase (eNOS) and inducible (i)NOS, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (a member of the reperfusion-injury salvage kinase pathway), were analyzed by Western blot in patients after coronary artery bypass surgery (ischemics; N=18) or valve surgery (nonischemics; N=15) and in preadipocytes isolated from epicardial adipose tissue. Results In ischemics, the CB1-to-CB2 expression ratio shifted toward CB1 and was accompanied by higher PKA activation. In contrast, in nonischemics, CB2, fatty acid amidohydrolase, PLC and PKC, and ERK1/2 were upregulated. Moreover, NO production and iNOS-to-eNOS ratios were higher in preadipocytes from ischemics. Conclusions These results show a different modulation and functioning of the endocannabinoid system in ischemics compared with nonischemics. Hence, while CB2, PLC and PKC, ERK1/2, and eNOS are more strongly expressed in patients without ischemic heart disease, high CB1 and PKA expression is associated with low survival intracellular pathway activation and high iNOS activation in ischemic heart disease patients. The changes in the endocannabinoid system in ischemics may contribute to cardiac dysfunction and therefore represents a potential therapeutic target.

Powerful mediators of programmed cell death, such as apoptosis and autophagy, can contribute to myocyte cell loss during pathological cardiac conditions. Levosimendan has been shown to exert beneficial hemodynamic effects in presence of global myocardial ischemia and heart failure through vasodilatation and increase of cardiac contractility. Recently, the intracoronary administration of a bolus levosimendan was found to exert favourable cardiac anti-stunning effects without lowering arterial pressure, which limits the use of levosimendan mainly in coronary artery disease. Here we tested whether the intracoronary administration of levosimendan can beneficially modulate programmed cell death in acute regional myocardial ischemia. Acute regional myocardial ischemia was induced in 20 anaesthetized pigs and intracoronary levosimendan 15 min bolus administration was started 4 h afterwards. The effects of levosimendan on coronary blood flow and cardiac function were evaluated and myocardial biopsies were examined for criteria of autophagy and apoptosis. The administration of levosimendan caused a significant increase of coronary blood flow (p

Background The circumference of the aortic annulus adjusts proportionally with changes in left ventricular volume. These dimensional changes in the aortic annulus improve the left ventricular outflow tract (LVOT) hemodynamics and enhance the anterior mitral valve leaflet (AML) movement. In this study, we investigated the impact of circumferential and partial circumference prosthetic mitral rings on aortomitral apparatus function. Methods Forty patients who underwent coronary artery bypass graft surgery and restrictive annuloplasty of the mitral valve annulus through either a partial circumference flexible ring (group A=20 patients) or a circumferential rigid ring (group B=20 patients) were evaluated using cardiac magnetic resonance imaging. Imaging was performed at the end of a 2-year follow-up period. Variations in LVOT diameter, transmitral valve gradient, and effective mitral valve area were measured and compared. Results Mean variation in LVOT diameter was significantly higher in group A compared with group B (12.7% ± 4% versus 3.6% ± 5%, p = 0.0005). Transmitral valve gradient was higher in group B than in group A (6.2 ± 3 mm Hg versus 4.6 ± 2 mm Hg, p = 0.007), whereas effective mitral valve area was larger in group A than group B (3.9 ± 4 cm 2 versus 3.1 ± 6 cm 2 , p = 0.009). The long-axis cardiac magnetic resonance imaging of patients in group B demonstrated that movement at the base of the AML was hindered with the AML pivotal point appearing to shift posteriorly. Conclusions This study demonstrated that the use of circumferential annular rings significantly impairs overall aortomitral apparatus function by reducing outflow diameter and AML movement.

Various studies have suggested that the phytoestrogen genistein has beneficial cardioprotective and vascular effects. However, there has been scarce information regarding the primary effect of genistein on coronary blood flow and its mechanisms including estrogen receptors, autonomic nervous system, and nitric oxide (NO). The present study was planned to determine the primary effect of genistein on coronary blood flow and the mechanisms involved. In anesthetized pigs, changes in left anterior descending coronary artery caused by intracoronary infusion of genistein at constant heart rate and arterial pressure were assessed using ultrasound flowmeters. In 25 pigs, genistein infused at 0.075 mg/min increased coronary blood flow by about 16.3%. This response was graded in a further five pigs by increasing the infused dose of the genistein between 0.007 and 0.147 mg/min. In the 25 pigs, blockade of cholinergic receptors (iv atropine; five pigs) and alpha-adrenergic receptors (iv phentolamine; five pigs) did not abolish the coronary response to genistein, whose effects were prevented by blockade of beta(2)-adrenergic receptors (iv butoxamine; five pigs), nitric oxide synthase (intracoronary N(omega)-nitro-L-arginine methyl ester; five pigs) and estrogenic receptors (ERs; ERalpha/ERbeta; intracoronary fulvestrant; five pigs). In porcine aortic endothelial cells, genistein induced the phosphorylation of endothelial nitric oxide synthase and NO production through ERK 1/2, Akt, and p38 MAPK pathways, which was prevented by the concomitant treatment by butoxamine and fulvestrant. In conclusion, genistein primarily caused coronary vasodilation the mechanism of which involved ERalpha/ERbeta and the release of NO through vasodilatory beta(2)-adrenoreceptor effects.

Systemic hypotension limits the intravenous use of levosimendan, particularly in coronary disease. Published reports show that the intracoronary administration of levosimendan in animal models causes an increase of coronary blood flow without systemic hypotension. In this case report, the intracoronary administration of levosimendan bolus in a 74-year-old man with postpericardiotomy heart failure elicited beneficial cardiac effects, increasing both systolic and diastolic functions and blood flow in all of the grafts. No changes of heart rate and systemic arterial blood pressure were observed.

In this study the hemodynamic effects of intracoronary injection of levosimendan in anesthetized pigs and the mechanisms involved were examined. In 12 anesthetized pigs instrumented for measurement of heart rate (HR), aortic blood pressure (ABP), central venous pressure (CVP), left ventricular end-diastolic blood pressure, left ventricular contractility and relaxation, and mean coronary blood flow (CBF), levosimendan has been injected into the left anterior descending coronary artery at doses corresponding to the ones commonly used in clinics as bolus administration but adapted to the measured CBF. In a further 9 pigs levosimendan has been administered after the blockade of alpha and beta adrenoceptors, muscarinic receptors, and coronary nitric oxide synthase (NOS) to investigate the action mechanism of the drug. The intracoronary bolus administration of doses of levosimendan corresponding to 12 and 24 microg/kg in 10 minutes exerted, respectively, CBF increases of 26.3% and 41.3% of the control values in the absence of changes in the other hemodynamic variables. The blockade of the autonomic nervous system did not prevent the coronary vasodilation, which was, however, abolished by the NOS inhibition. The intracoronary administration of levosimendan exerts positive effects on myocardial blood supply without changes in ABP, HR, CVP, or in myocardial kinetics. The coronary effects of levosimendan are related to NO production.

Two patients underwent combined heart and lung surgery performed through a limited left anterior thoracotomy. Good exposure of the left pulmonary hilum and the left anterior descending artery was obtained, allowing left upper lobectomy combined with off-pump coronary bypass grafting. This approach avoids potential complications due to sternotomy, staged operations, and cardiopulmonary bypass. These cases show that a limited thoracotomy allows safe and effective combined lung and cardiac surgery in carefully selected patients.

Objectives Mechanical complications of median sternotomy may cause significant morbidity and mortality in cardiac surgical patients. This study was aimed at assessing the role of Posthorax support vest (Epple, Inc., Vienna, Austria) in the prevention of sternal complications and the improvement of anatomical healing in patients at high risk for mechanical sternal dehiscence after cardiac surgery by mean of median sternotomy. Methods A prospective, randomized, study was performed and 310 patients with predisposing factors for sternal dehiscence after sternotomy for cardiac surgery were included. The patients were divided into two groups: patients who received the Posthorax support vest after surgery, and patients who did not. Primary variables assessed included the incidence of mechanical sternal complications, the quality of sternal healing, the rate of re-operation, the duration of hospitalization, rate and duration of hospital, re-admission for sternal complications. Secondary variables assessed were the post-operative pain, the number of requests for supplemental analgesia and the quality of life measured by means of the EQ-5D format. Results Patients using vest demonstrated a lower incidence of mechanical sternal complications, a better anatomical sternum healing, lower hospital stay, no re-operations for sternal dehiscence before discharge and lower re-admissions for mechanical sternal complication. In addition, patients using a vest reported a better quality of life with better freedom from limitations in mobility, self-care, and pain. Conclusions Our findings demonstrate that the use of the Posthorax vest reduces post-sternotomy mechanical complications and improves the healing of the sternotomy, the clinical course, and the post-operative quality of life.