Aprotinin does not Impair Vascular Function in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Bleeding is a major complication in coronary artery bypass graft surgery. Antifibrinolytic agents like serine protease inhibitor aprotinin can decrease postoperative bleeding and complications of cardiac surgery. However, the effects of aprotinin on vascular function are not completely elucidated. We compared the ex vivo vascular function of left internal mammary arteries from patients undergoing coronary artery bypass graft surgery with and without intraoperative application of aprotinin using a Mulvany Myograph. Human internal mammary arteries were treated with aprotinin ex vivo and tested for changes in vascular function. We analyzed the impact of aprotinin on vascular function in rat aortic rings. Finally, impact of aprotinin on expression and activity of endothelial nitric oxide synthase was tested in human endothelial cells. Intraoperative application of aprotinin did not impair ex vivo vascular function of internal mammary arteries of patients undergoing coronary artery bypass graft surgery. Endothelium-dependent and -independent relaxations were not different in patients with or without aprotinin after nitric oxide synthase blockade. A maximum vasorelaxation of 94.5%±11.4vs. 96.1%±5.5% indicated a similar vascular smooth muscle function in both patient groups (n=13 each). Long-term application of aprotinin under physiological condition preserved vascular function of the rat aorta. In vitro application of increasing concentrations of aprotinin on human endothelial cells resulted in a similar expression and activity of endothelial nitric oxide synthase. In conclusion, intraoperative and ex vivo application of aprotinin does not impair the endothelial function in human internal mammary arteries and experimental models.

Half-dose enoxaparin vs. full-dose enoxaparin for postoperative bridging therapy in patients after cardiac surgery: which dose regimen should be preferred?

BACKGROUND: Patients who require oral anticoagulation (OAC) after cardiac surgery due to an increased risk for thromboembolic events should receive bridging therapy with heparin until the INR is in a therapeutic range. For this purpose, unfractionated heparin (UFH) or low molecular weight heparin (LMWH) can be used. Recently published studies have demonstrated the safety and efficiency of therapeutic dose LMWH as bridging anticoagulant in cardiac surgery. The present study compares a full-therapeutic dose regimen with a half-therapeutic dose regimen of LMWH looking for safety and efficiency. PATIENTS AND METHODS: This study represents a retrospective, single-center cohort study. In a period of 19 months all patients in whom a postoperative bridging therapy after cardiac surgery was necessary (atrial fibrillation, mechanical heart valve replacement, tricuspid valve repair, intracardiac patch implantation, excision of intracardiac tumors) were selected. In the first part of the study, patients received full-dose (FD = 1 mg/kg bodyweight twice daily) LMWH (Enoxaparin). Analogously, patients in the second part of the study were treated with half-dose (HD = 0.5 mg/kg bodyweight twice daily) LMWH. In case of renal insufficiency (GFR <30 ml/min) the dose was adjusted to one daily application. The duration of follow-up was the patients' entire stay in hospital. Main outcome parameters were bleeding, thromboembolic events, and death. The first dose of LMWH was given on the morning of the first postoperative day, considered that the bleeding risk was acceptable. OAC (Phenprocoumon) was started on the evening of the first postoperative day. RESULTS: Altogether 402 out of 3133 patients met the inclusion criteria (201 patients in each group). Despite a reduced renal function in the HD-group (p = 0.002) both groups were well matched. Mortality was significantly higher in the HD-group than in the FD-group (5.5% vs. 0.5%, p = 0.003) but not related to the anticoagulation regimen. We observed more bleeding events in the FD-group (11 vs. 5, p = 0.126) but vice versa more thromboembolic events in the HD-group (9 vs. 5, p = 0.277). In the HD-group postoperative dialysis was required more often (29 vs. 12, p = 0.011) and there was a higher incidence of patients who were psychic disorientated (42 vs. 26, p = 0.033). The hospital stay was longer in the FD-group (FD: 15.1 ± 9.3 days, HD 12.5 ± 8.1 days, p = 0.003). CONCLUSION: This study shows that a bridging therapy with LMWH is feasible and safe no matter which dose-regimen is used. The differences observed seem not to be related to the anticoagulation. The decision of using a full-dose or half-dose LMWH bridging regimen should be determined by the individual risk of the patient and the general bleeding risk of the procedure.

Effects of donor pre-treatment with dopamine on survival after heart transplantation: a cohort study of heart transplant recipients nested in a randomized controlled multicenter trial.

OBJECTIVES: We determined the outcome of cardiac allografts from multiorgan donors enrolled in a randomized trial of donor pre-treatment with dopamine. BACKGROUND: Treatment of the brain-dead donor with low-dose dopamine improves immediate graft function after kidney transplantation. METHODS: A cohort study of 93 heart transplants from 21 European centers was undertaken between March 2004 and August 2007. We assessed post-transplant left ventricular function (LVF), requirement of a left ventricular assist device (LVAD) or biventricular assist device (BVAD), need for hemofiltration, acute rejection, and survival of recipients of a dopamine-treated versus untreated graft. RESULTS: Donor dopamine was associated with improved survival 3 years after transplantation (87.0% vs. 67.8%, p = 0.03). Fewer recipients of a pre-treated graft required hemofiltration after transplant (21.7% vs. 40.4%, p = 0.05). Impaired LVF (15.2% vs. 21.3%, p = 0.59), requirement of a LVAD (4.4% vs. 10.6%, p = 0.44), and biopsy-proven acute rejection (19.6% vs. 14.9%, p = 0.59) were not statistically different between groups. Post-transplant impaired LVF (hazard ratio [HR]: 4.95; 95% confidence interval [CI]: 2.08 to 11.79; p < 0.001), requirement of LVAD (HR: 6.65; 95% CI: 2.40 to 18.45; p < 0.001), and hemofiltration (HR: 2.83; 95% CI: 1.20 to 6.69; p = 0.02) were predictive of death. The survival benefit remained (HR: 0.33; 95% CI: 0.12 to 0.89; p = 0.03) after adjustment for various risks affecting mortality, including pre-transplant LVAD/BVAD, inotropic support, and impaired kidney function. CONCLUSIONS: Treatment of brain-dead donors with dopamine of 4 µg/kg/min will not harm cardiac allografts but appears to improve the clinical course of the heart allograft recipient. (Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation; NCT00115115).

Reconstruction of chronic aseptic sternal pseudoarthrosis after median sternotomy: initial experience with the Ley prosthesis.

It has previously been reported that the Ley prosthesis, a 0.5-mm-thick titanium alloy plate designed for reconstruction and stabilization of the unstable sternotomy, leads to shorter hospital stay and reduces the need for further surgical procedures in patients with postoperative mediastinitis after open heart surgery. We report our initial experience with the Ley prosthesis in patients with chronic aseptic sternotomy dehiscence. The study included 6 male patients (age 42-80 years) with opiate-derivate-dependent intractable pain and significantly reduced quality of life caused by noninfected sternal pseudoarthrosis and unstable sternotomy with large sternal bone tissue deficit. Four of the patients had undergone various surgical fixation procedures 8 days to 12 months after the primary operation. The patients were treated with reconstruction and stabilization of the sternum with the Ley prosthesis 10 to 40 months after the primary operation. In 1 patient bone transplantation was used. No immediate peri- or postoperative complications were observed, and all patients were discharged 4 to 11 days after surgery. One patient who received a bone transplant developed wound infection, and the prosthesis was removed 5 weeks after implantation. At 6-month follow-up all sternotomies were found stable, and patients reported that pain had decreased and quality of life was significantly improved. Our results demonstrate that the Ley prosthesis can be safely and efficiently used for the reconstruction and stabilization of the sternum in patients with intractable pain caused by noninfected postoperative sternal dehiscence and large sternal bone tissue deficit.

Microwave ablation of permanent atrial fibrillation during isolated bypass grafting and isolated mitral valve surgery.

BACKGROUND: This study was designed to compare the rate of restoration to sinus rhythm in patients with permanent atrial fibrillation (pAF) undergoing endocardial microwave ablation during isolated coronary artery bypass grafting (CABG) or isolated mitral valve surgery. METHODS: A total of 42 patients who underwent isolated CABG (age, 70.1 +/- 5.8 years) and 68 patients (age, 64.4 +/- 8.7 years) who underwent isolated mitral valve surgery were included in the registry. During the operation, all patients received endocardial microwave ablation. Follow-up examinations were performed 1, 3, 6, and 12 months after discharge. RESULTS: A 1-year follow up was obtained for all patients. In the CABG and the mitral valve surgery groups, sinus rhythm, as determined by a 24-h Holter electrocardiograph, was observed in 72% and 63% of the patients, respectively. CONCLUSIONS: The difference in sinus rhythm restoration in the CABG and mitral valve surgery groups did not reach statistical significance. Microwave ablation in combination with CABG or mitral valve surgery can be performed with comparable and acceptable success rates.

Normothermic beating heart surgery with assistance of miniaturized bypass systems: the effects on intraoperative hemodynamics and inflammatory response.

The use of miniaturized cardiopulmonary bypass (CPB) circuits and avoidance of cardioplegic arrest are attempts to reduce the inflammatory response to cardiac surgery. We studied the effects of beating heart surgery (BHS) with assistance of simplified bypass systems (SBS) on global hemodynamics, myocardial function and the inflammatory response to CPB. We hypothesized that the use of SBS was associated with less hemodynamic instability after CPB resulting from attenuation of the inflammatory response when compared with surgery performed with a conventional CPB (cCPB) circuit. Forty-five patients undergoing coronary artery bypass grafting were prospectively studied. Fifteen patients were randomized to the use of a cCPB circuit, cold crystalloid cardioplegia, and moderate hypothermia. Two groups of 15 patients underwent BHS during normothermia with assistance of two different SBS consisting of only blood pump and oxygenator. Hemodynamic variables were assessed with transpulmonary thermodilution and transesophageal echocardiography. Plasma levels of proinflammatory and antiinflammatory mediators were measured perioperatively. After CPB, variables of global hemodynamics and systolic ventricular function did not differ among groups. Left ventricular diastolic function was impaired after CPB equally in all groups (P < 0.01 versus pre-CPB). At the end of surgery, there was more need for vasopressor (norepinephrine) support in both SBS groups than in the cCPB group (P < 0.01). After CPB, the release of interleukin (IL)-6 did not differ significantly among groups, whereas plasma levels of IL-10 were higher in the cCPB group (P < 0.01 versus SBS). The extent of myocardial necrosis (Troponin T) was comparable in all groups. We conclude that in our study, miniaturizing bypass systems and avoidance of cardioplegic arrest were not effective in improving hemodynamic performance and in attenuating the proinflammatory immune response after CPB.

Temperature-independent Inhibition of L-type calcium currents by halothane and sevoflurane in human atrial cardiomyocytes.

BACKGROUND: Cardiac L-type calcium currents (ICa,L) are affected by volatile anesthetics, possibly contributing to their side effects. Actions of anesthetics on ion channels are usually studied in vitro at room temperature. However, the solubility of anesthetic gases as well as ICa,L are markedly sensitive to the study temperature. Therefore, temperature-dependent effects of halothane and sevoflurane on cardiac ICa,L were analyzed. METHODS: ICa,L were studied at 21 degrees C and 36 degrees C with the patch clamp technique in isolated human atrial cardiomyocytes. Concentrations of anesthetics brought into solution by gassing at both temperatures were determined with gas chromatography. RESULTS: The aqueous concentrations of halothane and sevoflurane were linearly related to their concentration in the gas phase (1 to 3 minimum alveolar concentration [MAC]). At 21 degrees C, the slope of this relation was 0.52 and 0.12 mm/vol % for halothane and sevoflurane, respectively, and decreased at 36 degrees C to 0.29 and 0.09 mm/vol %, respectively. ICa,L displayed significantly higher current amplitudes at 36 degrees C than at 21 degrees C and significantly accelerated time-dependent inactivation. Halothane (1-2 MAC) and sevoflurane (1-3 MAC) evoked stronger inhibitions of ICa,L at 21 degrees C than at 36 degrees C. In spite of different temperature-dependent current amplitudes, the fractional (percent) inhibition of ICa,L showed the same linear relationship to the concentrations of halothane and sevoflurane in the bath medium at both temperatures, as revealed from present and previous experiments. CONCLUSIONS: Inhibition of ICa,L by halothane and sevoflurane is determined by the aqueous concentration of the anesthetics, independently of the temperature. Increased solubility may explain the stronger effects of the anesthetics at lower temperatures.

A new right ventricular assist device for right ventricular support.

Right ventricular support by mechanical devices for postcardiotomy right heart failure is still associated with a high mortality. We report on the first use of a new paracardiac microaxial blood pump for postcardiotomy right heart failure in two patients undergoing emergency coronary artery bypass grafting (the first patient for a myocardial infarction complicated by a left ventricular wall rupture, the second patient for a dissection of the right coronary artery after an interventional procedure).

[Surgical therapy of end-stage heart failure]. / Chirurgische Therapie der chronischen Herzinsuffizienz]

Heart failure is still associated with a poor prognosis despite great advances in drug therapy, so that surgical procedures are necessary in patients with end-stage cardiac failure. Cardiac transplantation was the therapy of choice during the last decades, but due to its disadvantages and the increasing scarcity of donor organs other surgical procedures were developed. Multisite pacing improves quality of life, but a longterm survival benefit remains to be proved. Coronary artery bypass grafting and valve surgery demonstrated to improve quality of life and to increase long-term survival. Ventricular assist devices are effective in bridging up to 70% of patients to cardiac transplantation, but the number of complications must be reduced. Partial left ventriculectomy may be performed with results similar to those obtained of cardiac transplantation, but long-term results are not yet available. Dynamic cardiomyoplasty and Myosplint implantation were not successful, but it must be awaited, if passive cardiomyoplasty leads to better results. Xenotransplantation is under intense investigation, but cannot be used clinically until now due to the hurdles of rejection and transfer of infectious diseases. This work provides a summary of today's knowledge about surgical procedures for end-stage heart failure.