Ernesto Greco

Bridging regenerative medicine based therapies into the 21st Century: solo or symphony?

Clinical translation in the field of regenerative medicine means manufacturing a safe, reproducible and effective clinical product for the benefit of patients. This represents the ultimate goal of applied research, but beyond researchers and clinicians, multiple intermediate players are involved, including other researchers, reviewers, funding agencies, scientific societies, guideline authors, and policy regulators. Consequently, bridging translational research and regenerative medicine therapies into the 21 st Century requires a resolute effort. We envisage that strategic and synergistic efforts in seven key areas will facilitate the mainstream adoption and implementation of regenerative medicine based therapies.

Nitric oxide release during hypothermic versus normothermic cardiopulmonary bypass

Cardiopulmonary bypass (CPB) produces hemodynamic and inflammatory disorders involving changes in vascular permeability and regional blood flow and alterations of coagulation and complement systems. It has been reported that an abnormal release of vasoactive substances during CPB, like bradykinin or nitric oxide, could play a role. The aim of this study was to investigate the changes in nitric oxide (NO) release occurring in patients undergoing CPB, under both hypothermic and normothermic conditions. Forty patients (mean age 61.4 +/- 8.4 years) undergoing coronary bypass surgery were studied. In 20 patients (group A) systemic hypothermic CPB and antegrade cold intermittent crystalloid cardioplegia were used. The remaining 20 cases (group B) underwent surgery under systemic normothermic CPB and with antegrade warm blood intermittent cardioplegia. Nitric oxide was measured as the nitrite plasma level (NPL) by the Gries reaction. The time course of changes in NPL were obtained by collecting five whole blood samples: before CPB, 10 and 30 min after the start of CPB, and 10 and 60 min after the end of CPB. Although there were no significant variations of NPL shortly after the start of CPB (10 min after), values measured 30 min after CPB commencement and 10 min after the end of CPB showed a significant increase (P < 0.0001) in both groups. Considering the two groups separately, NPL changes seemed to be similar, so independent of temperature; however, in group B higher values of NPL were measured during (30 min) and after (60 min) CPB (P < 0.0001). In conclusion, during CPB there is a progressive increase, independent of temperature in NO release.

Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study

PurposeVentricular–arterial (V–A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV).MethodsAfter at least 24xa0h of hemodynamic optimization, 45 septic shock patients, with an HRxa0≥95xa0bpm and requiring norepinephrine to maintain mean arterial pressure (MAP)xa0≥65xa0mmHg, received a titrated esmolol infusion to maintain HR between 80 and 94xa0bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis, and norepinephrine requirements, were obtained at baseline and at 4xa0h after commencing esmolol.ResultsEsmolol reduced HR in all patients and this was associated with a decrease in Ea (2.19xa0±xa00.77 vs. 1.72xa0±xa00.52xa0mmHgxa0l−1), arterial dP/dtmax (1.08xa0±xa00.32 vs. 0.89xa0±xa00.29xa0mmHgxa0ms−1), and a parallel increase in SV (48xa0±xa014 vs. 59xa0±xa018xa0ml), all pxa0<xa00.05. Cardiac output and ejection fraction remained unchanged, whereas norepinephrine requirements were reduced (0.7xa0±xa00.7 to 0.58xa0±xa00.5xa0µgxa0kg−1xa0min−1, pxa0<xa00.05).ConclusionsHR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V–A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock.

Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells

Β-blockers (BB) are a primary treatment for chronic heart disease (CHD), resulting in prognostic and symptomatic benefits. Cardiac cell therapy represents a promising regenerative treatment and, for autologous cell therapy, the patients clinical history may correlate with the biology of resident progenitors and the quality of the final cell product. This study aimed at uncovering correlations between clinical records of biopsy-donor CHD patients undergoing cardiac surgery and the corresponding yield and phenotype of cardiospheres (CSs) and CS-derived cells (CDCs), which are a clinically relevant population for cell therapy, containing progenitors. We describe a statistically significant association between BB therapy and improved CSs yield and CDCs phenotype. We show that BB-CDCs have a reduced fibrotic-like CD90u2009+u2009subpopulation, with reduced expression of collagen-I and increased expression of cardiac genes, compared to CDCs from non-BB donors. Moreover BB-CDCs had a distinctive microRNA expression profile, consistent with reduced fibrotic features (miR-21, miR-29a/b/c downregulation), and enhanced regenerative potential (miR-1, miR-133, miR-101 upregulation) compared to non-BB. In vitro adrenergic pharmacological treatments confirmed cytoprotective and anti-fibrotic effects of β1-blocker on CDCs. This study shows anti-fibrotic and pro-commitment effects of BB treatment on endogenous cardiac reparative cells, and suggests adjuvant roles of β-blockers in cell therapy applications.

Total Adiponectin Is Inversely Associated with Platelet Activation and CHA2DS2-VASc Score in Anticoagulated Patients with Atrial Fibrillation

Background. Adiponectin (APN) possesses anti-inflammatory and antiatherogenic effects. Atrial fibrillation (AF) is burdened by enhanced systemic inflammation and platelet activation, as documented by increased blood levels of soluble CD40L (sCD40L). The interplay between APN and platelet activation in AF is still undefined. Materials and Methods. Circulating levels of APN and sCD40L were measured in 257 anticoagulated nonvalvular AF patients. Exclusion criteria were as follows: prosthetic heart valves, cardiac revascularization in the previous year, severe cognitive impairment, chronic infectious or autoimmune diseases, and active cancer. Results. Mean age was 72.9 (±8.7) years and 41.6% were female. Serum APN and plasmatic sCD40L were inversely correlated (R −0.626, P < 0.001). A progressive increase of sCD40L across tertiles of CHA2DS2-VASc score was observed (rS 0.473, P < 0.001), whilst APN was inversely correlated (rS −0.463,u2009u2009P < 0.001). A multivariable linear regression analysis showed that CHA2DS2-VASc score (B −0.227, P < 0.001) and sCD40L (B −0.524, P < 0.001) correlated to APN. Conclusions. AF patients at high risk of stroke disclose low and high levels of APN and sCD40L, respectively, suggesting a role for APN if it favors platelet activation in vivo in this clinical setting. Enhancing APN levels may be a future goal to reduce the risk of vascular outcomes in AF patients.

Ivabradine: a preliminary observation for a new terapeutic role in patients with multiple organ dysfunction syndrome.

Sirs: Severe sepsis is a major cause of mortality and morbidity worldwide. Septic patients often develop multiple organ dysfunction syndrome (MODS) that is characterized by an acute functional impairment of two or more organs so that homeostasis cannot be maintained without intervention [1]. Patients with MODS typically present with an elevated heart rate (HR) that accompanies a highly impaired autonomic dysfunction with depressed parasympathetic control of the heart. An elevated heart rate was found to increase the incidence of major cardiac events in critically ill patients [2–4]. Furthermore, an elevated heart rate in the early phase of MODS was found to be an independent

«Mold-like» calcification of the left atrium and of the pulmonary veins. Total endoatriectomy in a patient undergoing mitral valve replacement

Mold-like left atrial calcification is a rare aspect of rheumatic mitral valvular disease. Its interest lies in the difficulty of surgical technique during interventions for valvular substitution. This is a case report in which the total excision of the calcified mold by a wide endoatriectomy was necessary in order to substitute the stenotic mitral valve.

Port Access (Thru-Port System) video-assisted mitral valve surgery

The aim of this review is to focus the attention on the state of the art of port-access and video-assisted mitral valve surgery appraising the results compared to the traditional approach, describing different technical strategies and analyzing how to avoid and manage its related complications concomitantly elucidating which procedure is associated with the most favorable risk-benefit and cost-benefit profile. Our default strategy is to use the minimally invasive approach combining video-assisted right mini-thoracotomy with endo-cardiopulmonary bypass and endo-aortic balloon occlusion (EBO) whenever possible. This choice is supported by the evidence that, after an initial learning curve, it is a safe and effective approach in terms of short- and long-term results, mainly for redo operations and even for elderly patients with moderately elevated peri-operative risk.

Emergency Cardiac Surgery for Irreversible MitraClip Delivery System Entrapment

itraClip (Abbott Vascular, Santa Clara, CA) imThis unique case of entire MitraClip delivery system entrapment requiring emergency surgery, in which all Mplantationwas attempted in a 72-year-old gentleman with severe mitral regurgitation [1]. However, after clip closure it was impossible to detach the distal anchoring tip, and the whole system remained entrapped with the clip anchored to mitral leaflets. The procedure was thus converted to emergency surgery. After patient and entire delivery system mobilization to the operating room (Fig 1), standard median sternotomy and bicaval cannulation were performed. The exposure was challenging due to the

An International Survey on Taking Up a Career in Cardiovascular Research: Opportunities and Biases toward Would-Be Physician-Scientists.

Background Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular research training with an international survey. Methods and Results We administered a 20-closed-question survey to mentors and mentees belonging to different international institutions. A total of 247 (12%) surveys were available (out of 2,000 invitations). Overall, mentees and mentors were reasonably satisfied with the educational and research resources. Significant differences were found analyzing results according to gender, geographic area, training and full-time researcher status. Specifically, women proved significantly less satisfied than men, disclosed access to fewer resources and less support from mentors (all P<0.05). People working in institutions not located in North America or Northern/Central Europe were significantly less satisfied and disclosed much less support (both P<0.05). Those in training reported limited opportunities for collaboration (P = 0.009), and non-full-time researchers disclosed more limited access to tutors and formal grant writing training (both P<0.05). Conclusions Several potential biases appear to be present in the way training in cardiovascular research is provided worldwide, including one against women. If confirmed, these data require proactive measures to decrease discriminations and improve the cardiovascular research training quality.