[Individualized use of levosimendan in cardiac surgery]. / Individualisierter Einsatz von Levosimendan in der Herzchirurgie.

BACKGROUND: Levosimendan is a cardiac inotrope that augments myocardial contractility without increasing myocyte oxygen consumption. Additionally, levosimendan has been shown to exhibit anti-inflammatory, antioxidative, and other cardioprotective properties and is approved for treatment of heart failure. Recent studies indicated that these beneficial effects can be achieved with doses lower than the standard dose of 12.5 mg. Patients with preoperatively diagnosed left ventricular ejection fraction (LVEF) ≤40% received 1.25 mg levosimendan after induction of anesthesia. After surgery, administration of low-dose levosimendan was repeated until cardiovascular stability was achieved. OBJECTIVE: This study aimed to evaluate if pharmacological preconditioning with 1.25 mg levosimendan in patients with LVEF ≤40% altered the postoperative need for inotropic agents, the incidence of newly occurring atrial fibrillation, renal replacement therapy, mechanical circulatory support and 30-day mortality. The cumulative dosage of levosimendan was recorded to assess the required dosage in the context of individualized treatment. MATERIAL AND METHODS: This retrospective study included patients with preoperatively diagnosed LVEF ≤40% who underwent cardiac surgery at this institution between January 2015 and December 2018 and who received 1.25 mg levosimendan after induction of anesthesia to prevent postoperative low cardiac output syndrome. Based on echocardiography results, invasive hemodynamic monitoring, and central venous or mixed venous oxygen saturation and lactate clearance, repetitive doses of levosimendan in 1.25 mg increments could be postoperatively administered until cardiovascular stability was achieved. The results were compared to the current literature. RESULTS: We identified 183 patients with LVEF <40% who received pharmacological preconditioning with 1.25 mg levosimendan. Maximum doses of epinephrine, incidence of atrial fibrillation, need for renal replacement therapy and 30-day mortality were found to be below the published rates of comparable patient collectives. In 73.2% of patients, a cumulative dosage of 5 mg levosimendan or less was considered sufficient. CONCLUSION: The presented concept of pharmacological preconditioning with 1.25 mg levosimendan followed by individualized additional dosing in cardiac surgery patients with preoperative LVEF ≤40% suggests that this concept is safe, with possible advantages regarding the need of inotropic agents, renal replacement therapy, and 30-day mortality, compared to the current literature. Individualized treatment with levosimendan to support hemodynamics and a timely reduction of inotropic agents needs further confirmation in randomized trials.

Continuous graft perfusion: optimizing the quality of saphenous vein grafts.

BACKGROUND: Healthy unaltered vascular endothelium in graft material is a prerequisite for a successful CABG operation. Damage done to the endothelium during vein harvest is responsible for an early graft occlusion rate of 20% in the first year after operation. Minimally invasive vein harvesting is regarded to minimize the damage done to the Endothelium. We compared minimally invasive vein harvesting with conventional vein harvesting and studied the influence of a continuous perfusion of the veins with patient autologous blood on their endothelial integrity. METHODS: 80 patients were randomly split into 4 groups: Group 1: Conventional vein harvest and storage of the vein in a crystalloid solution before usage. Group 2: Endoscopic vein harvest and storage in cristallloid solution. Group 3: Conventional harvest under continuous perfusion of the vein with 100 ml blood via the heart lung machine. Group 4: Endoscopic vein harvest under continuous perfusion. Immediately prior to the first peripheral anastomosis a sample was taken from each graft and evaluated by scanning electron microscopy. The endothelial integrity was rated in 5 categories (from "completely confluent endothelium" (1) to "no endothelium" (5)). RESULTS: Group 1: 2.7+/-1.13 Group 2: 2.2+/-1.06 Group 3: 1.6+/-0.68 Group 4: 1.6+/-0.69 CONCLUSION: In regard to the endothelial integrity endoscopic vein harvesting is superior to conventional vein harvest. If the grafts are harvested while continuously perfused with blood there is no more difference between the groups. Considering the well known additional benefits such as reduction in wound healing disorders endoscopic vein harvesting appears to be the preferable technique.

Autologous endothelialized vein allograft: a solution in the search for small-caliber grafts in coronary artery bypass graft operations.

BACKGROUND: Early graft failure after the use of less satisfactory autologous grafts (30% of all vein grafts) is caused primarily by the following problems: (1) suitable autologous transplants are limited; (2) biotechnology has not yet been able to produce reliable graft substitutes that are legally and ethically approved; and (3) current prosthetic materials are prothrombotic. To overcome these problems, we developed an easily accessible, quality-controlled graft. METHODS AND RESULTS: Human autologous venous endothelial cells (HAVECs) were isolated from short segments of peripheral veins unsuitable for bypass grafting. After mechanical deendothelialization of cryopreserved allograft veins (CAVs) and precoating with recipient autologous serum, these homologous cells were seeded by use of a rotating device. Growth of a confluent HAVEC layer within 1 week in a special incubator was observed. After histological and mechanical tests, 12 patients received 15 grafts in total. Bypass operation was followed by clinical and angiographic follow-up. Production period was 22+/-8 days. HAVEC-coated CAVs showed normal connective tissue wall structure and a tight endothelial monolayer (burst pressure >2000 mm Hg). To date, 12 CABG patients lacking suitable autologous graft material have been treated. One patient died of a cause unrelated to the grafts, which were found morphologically normal and patent during autopsy. Of 15 grafts, 2 were occluded at the first angiographic follow-up. The oldest graft has now been in place for approximately 3 years. Immune suppression was not administered. CONCLUSIONS: At present, autologous endothelialized CAVs present good alternative small-caliber grafts for patients lacking suitable autologous vessels.

The harmonic scalpel: optimizing the quality of mammary artery bypass grafts.

BACKGROUND: The damage done to the endothelium during the preparation of a graft used in an aortocoronary procedure is a risk factor for early graft failure. We compared the effect on the endothelium of the mammary arteries when the harvest was done either by the harmonic scalpel (HS) or the high-frequency electrocauter (HF). METHODS: Twenty-four mammary arteries were harvested and divided into two groups depending on the use of the HS or the HF. The endothelial damage was analyzed with a scanning electron microscope. The groups were compared in regard to the size of the internal mammary artery (IMA) pedicle. RESULTS: The endothelial damage of the IMAs taken down with the HS was significantly less than when taken down with the HF if the IMA pedicle size was less than 0.5 cm. CONCLUSIONS: The HS has a positive effect on the endothelial preservation, especially when the preparation is done closely to the IMA. The HS is profitable in minimally invasive procedures, particularly when it is difficult to keep a wide enough distance from the IMA.

An inward rectifier and a voltage-dependent K+ current in single, cultured pericytes from bovine heart.

OBJECTIVE: The purpose of this study was to describe passive electrical properties and major membrane currents in coronary pericytes. METHODS: 78 single, cultured bovine pericytes were studied with the patch-clamp technique in the whole-cell mode. RESULTS: The membrane potential of the cells was -48.9+/-9.6 mV (mean+/-S.D.) with 5 mM and -23.2+/-2.2 mV with 60 mM extracellular K+. The membrane capacitance was 150.2+/-123.2 pF. The current-voltage relation of the pericytes was dominated by an inward current at hyperpolarized potentials and an outward current at depolarized potentials. Increasing extracellular K+ from 5 to 60 mM led to an increase of the inward current and to a shift of this current to more depolarized potentials. The inward current was very sensitive to extracellular barium (50 microM). The maximum slope conductance of the cells at hyperpolarized potentials was 2.9+/-2.8 nS. Inward rectification of whole-cell currents was steep (slope factor = 6.8 mV). With elevated external K+ the outward current reversed near the potassium equilibrium potential. Onset of the outward current was sigmoid and inactivation of this current was monoexponential, slow (time constant = 12.8 s) and incomplete. Voltage-dependence of outward current steady-state activation was steep (slope factor = 4.6 mV). The outward current was very sensitive to 4-aminopyridine (dissociation constant = 0.1 mM). The maximum slope conductance at depolarized potentials was 16.6+/-15.6 nS. CONCLUSION: We report for the first time, patch-clamp recordings from coronary pericytes. An inward rectifier and a voltage-dependent K+ current were identified and characterized. Regulation of these currents may influence coronary blood flow.