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The intra-aortic balloon pump (IABP) is frequently used to support severely compromised ventricles in critically ill patients. Its relatively affordability and ease of insertion has cemented its position as the first line of treatment for hemodynamic support in cardiogenic shock. Accordingly, the current ACC/AHA recommendations maintain a Class 2A for the use of IABP in shock. However, a review of the current literature suggests that the evidence supporting the American College of Cardiology and American Heart Association (ACC/AHA) guidelines are equivocal. Alternative uses for IABP such as perioperative support during high-risk cardiac surgery, treatment of left ventricular distention on extracorporeal membrane oxygenation, and as bridge to transplant have been proposed. The effectiveness of the IABP in these clinical situations remains largely unproven, due to the paucity of available data.

Objective: The aim of the present study was to construct a new drug delivery system for milrinone using microparticles. This novel technology enhances drug bioavailability and decreases toxicity, with future implications for the treatment of end-stage heart failure., Methods: Polylactic-co-glycolic acid microparticles (PLGA-MPs) loaded with milrinone were prepared using a double emulsion-solvent evaporation technique. In vitro release kinetics was evaluated at physiologic conditions. A total of 24 female Lewis rats underwent left coronary artery ligation. One week after ligation, all rats were randomized to 1 of 3 groups (n=8 per group). Group I received an intravenous injection of PLGA-MPs alone; group II, a bolus intravenous injection of milrinone; and group III an intravenous injection of milrinone-PLGA-MPs. All injections were administrated slowly by way of the tail vein over 10 minutes. Transthoracic echocardiography, noninvasive heart rate monitoring, and blood pressure measurements were performed at different predetermined intervals before and for 24 hours after the injection. All rats survived for 24 hours and were then killed by euthanasia. Serum plasma was taken for cytokine assays and determination of milrinone levels using high-performance liquid chromatography., Results: Group III had a significantly greater left ventricular ejection fraction at 90 minutes and 3, 6, and 12 hours after treatment compared with the other groups. The milrinone plasma level was significantly greater in group III than in the other groups (group I, 0 ng/mL; group II, 1.7±2.4 ng/mL; group III, 9.1±2.2 ng/mL; P<.05). The intercellular adhesion molecule and cytokine-induced neutrophil chemoattractant-1 levels were significantly lower in group III than in the other 2 groups (P<.05)., Conclusions: Drug encapsulation using microparticles can prolong the effects of milrinone. We propose a new strategy for future drug delivery in patients with end-stage heart failure., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Previous regenerative studies have demonstrated massive cell losses after intramyocardial cellular delivery. Therefore, efforts at reducing mechanical losses may prove more successful in optimising cellular therapy. In this study, we hypothesized that escalating mesenchymal stem cells (MSCs) dose will not produce corresponding improvement in cardiac function due to washout of the small cells in microcirculation. Using microspheres similar in size to MSCs, that are encapsulated in alginate-poly-l-lysine-alginate (APA), we tested the hypothesis that size is an important factor in early losses., Methods: In experiment I, five groups of rats (n=9 each) underwent coronary ligation; group I had no treatment; the other groups received escalating 0.5 × 10(6), 1.5 × 10(6), 3 × 10(6) and 5 × 10(6) of MSCs each. Echocardiogram was performed at baseline, 2 days and 7 weeks after surgery. In experiment II, cell-sized microspheres (10 μm) were encapsulated in APA microcapsules. In group I (n=16), rats received bare microspheres, group II (n=16) microspheres within 200 μm microcapsules and in group III (n=16), microspheres within 400 μm microcapsules. After 20 min, hearts were quantified for the amount retained., Results: Myocardial function did not improve further with escalating cell doses beyond an initial response at 1.5 × 10(6) cells. Encapsulated microspheres in 200 μm and 400 μm microcapsules demonstrated a fourfold increase in retention rate compared with 10 μm microspheres., Conclusion: We concluded that suboptimal functional improvement in this animal model starts at 1.5 × 10(6) cells and does not respond to escalating cell doses. Improving mechanical retention is possible by increasing the size of the injectate. Microencapsulation could be used to encapsulate donor cells and facilitate functional improvement in cellular heart failure therapy., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Transvenous coronary sinus lead placement is currently the standard approach for left ventricular pacing. The aim of this study is to assess whether a mini-thoracotomy approach would be feasible and safe when used for cases in which transvenous procedures were ineffective or judged unlikely to succeed. Biventricular pacing was performed in 138 consecutive patients with 47 patients undergoing a mini-thoracotomy procedure. NYHA status, quality of life, electrical and echocardiographic data were assessed in the two groups over a follow-up period of 17.6+/-4.2 weeks. There was no significant difference in the preoperative characteristics in both groups other than a greater prevalence of renal failure and previous cardiac surgery among the surgical patients. The mean procedure time was significantly longer in the transvenous group. No significant differences were noted in the immediate or long-term pacing parameters. Two mortalities were observed in the surgical group >2 weeks following the procedure. During the follow-up period, we noted a comparable improvement in the echocardiographic parameters, QRS duration and NYHA status with both approaches. Our results suggest that even when performed on high-risk patients, epicardial lead placement through a mini-thoracotomy is beneficial and feasible as a 'rescue' procedure after a failed transvenous approach.

There is a very limited published material about experience with long-term pediatric mechanical circulatory support as a bridge to heart transplant. We report on a 2-year-old, 12 kg boy admitted with 2-week history of low-grade fever, ear pain, pulmonary edema, and congestive heart failure. Trans-thoracic echocardiography confirmed severe myocardial dysfunction with a left ventricular ejection fraction of 0.20 and percentage shortening of 13. After 2 days of ventilatory and inotropic support, the patient continued to deteriorate and subsequently required femoro-femoral extracorporeal life support (ECLS). This was later complicated by a progressive coagulopathy and massive bleeding. On day 17, a pulsatile pediatric paracorporeal biventricular assist device (VAD) (Berlin Heart) was implanted. The patient's condition improved significantly with all coagulopathies corrected, and the patient was extubated 21 days later. After 109 days of bi-VAD support, the patient was successfully transplanted and discharged home 45 days post transplant. Our early experience with initial ECLS bridge to VAD and subsequently to transplant was encouraging. It allowed for additional time to select the ideal organ donor and optimize the recipient's comorbid condition and multiorgan failure. VAD provides an additional armamentarium of circulatory support in pediatric patients with severe heart failure.

Congestive heart failure, a prominent cardiovascular disease results primarily from myocardial infarction or ischemia. Milrinone (MRN), a widely used clinical drug for heart failure, improves myocardial contractility and cardiac function through its inotropic and vasodilatory effects. However, lacking target specificity, it exhibits low bioavailability and lower body retention time. Therefore, in this study, angiotensin II (AT1) peptide conjugated human serum albumin nanoparticles (AT1-HSA-MRN-NPs) have been synthesized for targeted delivery of MRN to the myocardium, overexpressing AT1 receptors under heart failure. The NPs were surface functionalized through a covalent conjugation reaction between HSA and AT1. Nanoparticle size was 215.2±4.7 nm and zeta potential -28.8±2.7 mV and cumulative release of MRN was ~72% over 24 hrs. The intracellular uptake of nanoparticles and cell viability was studied in H9c2 cells treated with AT1-MRN-HSA-NPs vs the control non-targeted drug, MRN Lactate under normal, hypoxic and hypertrophic conditions. The uptake of AT1-HSA-MRN-NPs in H9c2 cells was significantly higher as compared to non-targeted nanoparticles, and the viability of H9c2 cells treated with AT1-MRN-HSA-NPs vs MRN Lactate was 73.4±1.4% vs 44.9±1.4%, respectively. Therefore, AT1-HSA-MRN-NPs are safe for in vivo use and exhibit superior targeting and drug delivery characteristics for treatment of heart failure. [ABSTRACT FROM AUTHOR]

Congestive heart failure is a fatal cardiovascular disease resulting in tissue necrosis and loss of cardiac contractile function. Inotropic drugs such as milrinone are commonly used to improve the myocardial contractility and heart function. However, milrinone is associated with severe side effects and lower circulation time. In this article, a novel protein nanoparticle formulation for heart-targeted delivery of milrinone has been designed and tested. The formulation was prepared using albumin protein conjugated with the targeting ligand, angiotensin II peptide to form nanoparticles following the ethanol desolvation method. The formulation was characterized for size, charge, and morphology and tested in a rat model of congestive heart failure to study pharmacokinetics, biodistribution, and efficacy. The overall cardiac output parameters were evaluated comparing the formulation with the control non-targeted drug, milrinone lactate. This formulation exhibited improved pharmacokinetics with a mean retention time of 123.7 min, half-life of 101.3 min, and clearance rate of 0.24 L/(kg*h). The targeted formulation also significantly improved ejection fraction and fractional shortening parameters thus improving cardiac function. This study demonstrates a new approach in delivering inotropic drugs such as milrinone for superior treatment of congestive heart failure. [ABSTRACT FROM AUTHOR]