Calculation-assisted regioselective functionalization of the imidazo[1,2-]pyrazine scaffold zinc and magnesium organometallic intermediates.

Straightforward calculations such as determinations of p values and N-basicities have allowed the development of a set of organometallic reactions for the regioselective functionalization of the underexplored fused N-heterocycle imidazo[1,2-]pyrazine. Thus, regioselective metalations of 6-chloroimidazo[1,2-]pyrazine using TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) such as TMPMgCl·LiCl and TMPZn·2MgCl·2LiCl provided Zn- and Mg-intermediates, that after quenching with various electrophiles gave access to polyfunctionalized imidazopyrazine heterocycles. Additionally, the use of TMPZn·2MgCl·2LiCl as base for the first metalation allowed an alternative regioselective metalation.

Regioselective Magnesiations of Fluorinated Arenes and Heteroarenes Using Magnesium-bis-Diisopropylamide (MBDA) in Hydrocarbons.

We report a convenient preparation of a new and storable magnesium amide (iPr N) Mg (magnesium-bis-diisopropylamide; MBDA) which proved to be especially suitable for the non-cryogenic magnesiation of fluoro-substituted arenes and heteroarenes providing arylmagnesium amides (ArMgDA) or bis-heteroaryl magnesiums (HetAr) Mg in hydrocarbons. Further reactions with electrophiles (aldehydes, ketones, allylic bromides, aryl halides (Negishi cross-coupling)) furnished a range of polyfunctional fluoro-substituted unsaturated building blocks. Several postfunctionalizations were described as well as NMR-studies confirming the dimeric structure of the base.

Preparation of Polyfunctionalized Aromatic Nitriles from Aryl Oxazolines.

A selective ortho,ortho'-functionalization of readily available aryl oxazolines by two successive magnesiations with sBu Mg in toluene followed by trapping reactions with electrophiles, such as (hetero)aryl iodides or bromides, iodine, tosyl cyanide, ethyl cyanoformate or allylic bromides (39 examples, 62-99 % yield) is reported. Treatment of these aryl oxazolines with excess oxalyl chloride and catalytic amounts of DMF (50 °C, 4 h) provided the corresponding nitriles (36 examples, 73-99 % yield). Conversions of these nitriles to valuable heterocycles are reported, and a tentative mechanism is proposed.

Implantation technique of the 50-cm3 SynCardia Total Artificial Heart: does size make a difference?

Despite downsizing, implantation technique of the 50-cm(3) SynCardia Total Artificial Heart and settings of the Companion driver remain unchanged. Owing to the absence of de-airing nipples, de-airing procedure is even more crucial and has to be performed carefully.

Expanding Applicability of Total Artificial Heart Therapy: The 50-cc SynCardia Total Artificial Heart.

The 50-cc SynCardia total artificial heart is designed to facilitate orthotopic replacement of the native ventricles in patients with a body surface area below 1.7 m(2) in need of long-term circulatory support as a result of end-stage biventricular heart failure. We describe the implementation of this technology in a female patient with irreversible cardiogenic shock on the grounds of acute myocardial infarction and chronic ischemic cardiomyopathy.

Percutaneous dilatational tracheostomy following total artificial heart implantation.

Coagulation disorders and an immune-altered state are common among total artificial heart patients. In this context, we sought to evaluate the safety of percutaneous dilatational tracheostomy in cases of prolonged need for mechanical ventilatory support. We retrospectively analysed the charts of 11 total artificial heart patients who received percutaneous dilatational tracheostomy.

System overview of the fully implantable destination therapy--ReinHeart-total artificial heart.

Objectives: Owing to the lack of suitable allografts, the demand for long-term mechanical circulatory support in patients with biventricular end-stage heart failure is rising. Currently available Total Artificial Heart (TAH) systems consist of pump units with only limited durability, percutaneous tubes and bulky external equipment that limit the quality of life. Therefore we are focusing on the development of a fully implantable, highly durable destination therapy total artificial heart.

A monitoring and physiological control system for determining aortic valve closing with a ventricular assist device.

Objectives: Real-time monitoring of the aortic valve function and the loading state of the left ventricle (LV) during mechanical circulatory support is essential. Therefore, we developed a system that determines accurately the aortic valve closing moment based on integrals derived from the pump inlet pressure and the pump power [pressure-power area (PPA)].

Methods: A Deltastream diagonal pump was implanted in 10 healthy Rhoen sheep.

Repair of left ventricular driveline tear in a SynCardia-total artificial heart patient.

We report the case of a 64-year old Caucasian male patient with a tear of the left ventricular driveline just above the driveline-air tube junction. We describe the repair technique and the necessary set of tools.

Veno-venous extracorporeal membrane oxygenation with a bicaval dual-lumen catheter in a SynCardia total artificial heart patient.

We report the case of a 55 years old caucasian male patient with cardiogenic shock due to an extended myocardial infarction who underwent SynCardia Total Artificial Heart implantation and veno-venous extracorporeal membrane oxygenation with a bicaval dual-lumen cannula for the treatment of adult respiratory distress syndrome.

Beneficial aspects of real time flow measurements for the management of acute right ventricular heart failure following continuous flow ventricular assist device implantation.

Background: Optimal management of acute right heart failure following the implantation of a left ventricular assist device requires a reliable estimation of left ventricular preload and contractility. This is possible by real-time pump blood flow measurements.

Clinical Case: We performed implantation of a continuous flow left ventricular assist device in a 66 years old female patient with an end-stage heart failure on the grounds of a dilated cardiomyopathy.