Hartmuth B. Bittner

Laparoscopic Nissen fundoplication: operative results and short-term follow-up.

The operative results, outcome, and short-term follow-up after laparoscopic exploration for Nissen fundoplication were evaluated in 35 patients with symptomatic gastroesophageal reflux and reflux-induced pulmonary disease. There were 19 female and 16 male patients, ranging in age from 17 to 72 years (mean: 42 years, SD: 11.6 years). In 20 patients, the symptoms were predominantly of regurgitation and heartburn; the remaining 15 patients had mixed regurgitation/heartburn and pulmonary symptoms. All patients underwent 24-hour pH monitoring, upper endoscopy, and manometry. The indication for surgery was medical failure or the need for long-term medical management with omeprazole. The operation, which was performed laparoscopically, is identical to the conventional Nissen fundoplication. There was a mortality rate of 0% and a morbidity rate of 25.7%. Five patients required conversion to open Nissen fundoplication, which was due to hemodynamic instability secondary to presumed pneumothorax in three patients and colotomy and a distal esophageal perforation in the other two patients. Thirty patients underwent laparoscopic Nissen fundoplication. Three patients developed early dysphagia, and one patient experienced a perforation of the piriform sinus due to nasogastric tube manipulation under anesthesia. All these patients had an uncomplicated postoperative course, and there was no long-term disability. The total surgical time of laparoscopic Nissen fundoplication was on average 107 minutes (SD: 35.3 minutes). Discharge usually occurred on the evening of postoperative day 2 (mean: 3.3 days; SD: 1.5 days). Twenty-six of the 30 patients who underwent laparoscopic Nissen fundoplication described the outcome as excellent and good (87%); however, 4 patients (13%) were unsatisfied. Fifteen patients (50%) had difficulty belching or vomiting, and moderate dysphagia was described by 7 patients (24%) in follow-up. Regurgitation and heartburn were cured in 96%, whereas reflux-induced pulmonary disease was cured in 50%. The results of laparoscopic Nissen fundoplication compare favorably with those of conventional Nissen fundoplication with respect to mortality, complications, and outcome.

Milrinone Improves Pulmonary Hemodynamics and Right Ventricular Function in Chronic Pulmonary Hypertension

BACKGROUND Right ventricular failure after cardiac transplantation is commonly related to preexisting recipient pulmonary hypertension. This study was designed to investigate the effects of intravenous milrinone on pulmonary hemodynamic indices and right ventricular function in a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. METHODS Eight mongrel dogs underwent pulmonary artery catheterization to measure right-sided hemodynamic indices before and 6 weeks after a right atrial injection of monocrotaline pyrrole. Six weeks after injection, all hearts were instrumented with a pulmonary artery flow probe, ultrasonic dimension transducers, and micromanometers. Data were collected at baseline and after milrinone infusion. RESULTS Six weeks after monocrotaline pyrrole injection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed. Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling. CONCLUSIONS This investigation demonstrates the well-known hemodynamic and inotropic effects of milrinone which, in the setting of monocrotaline pyrrole-induced pulmonary hypertension, were also associated with significant increases in pulmonary blood flow and left ventricular filling.

Current Trends in Implantable Left Ventricular Assist Devices

The shortage of appropriate donor organs and the expanding pool of patients waiting for heart transplantation have led to growing interest in alternative strategies, particularly in mechanical circulatory support. Improved results and the increased applicability and durability with left ventricular assist devices (LVADs) have enhanced this treatment option available for end-stage heart failure patients. Moreover, outcome with newer pumps have evolved to destination therapy for such patients. Currently, results using nonpulsatile continuous flow pumps document the evolution in outcomes following destination therapy achieved subsequent to the landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure Trial (REMATCH), as well as the outcome of pulsatile designed second-generation LVADs. This review describes the currently available types of LVADs, their clinical use and outcomes, and focuses on the patient selection process.

Pharmacological Strategies for Improving Diastolic Dysfunction in the Setting of Chronic Pulmonary Hypertension

BACKGROUND Right ventricular (RV) hypertrophy is an adaptive process that occurs in the setting of chronic pulmonary hypertension (CPH) and can lead to alterations in normal RV diastolic properties. This study was designed to investigate the effects of NO and milrinone on RV diastolic dysfunction in the setting of CPH and RV hypertrophy by use of a canine model of monocrotaline pyrrole (MCTP)-induced CPH. METHODS AND RESULTS Sixteen mongrel dogs (22 to 24 kg) were used. Animals underwent percutaneous pulmonary artery (PA) catheterization to measure pulmonary hemodynamics before and 8 weeks after injection of 3 mg/kg MCTP (n=8) or placebo (control, n=8). Eight weeks after injection, all hearts were instrumented with a PA flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and after both NO and milrinone administration. Diastolic properties were quantified by use of the end-diastolic pressure-volume relationship and the time constant of ventricular isovolumic relaxation. Eight weeks after injection, significant increases in the PA pressure and pulmonary vascular resistance were observed in MCTP dogs. Significant worsening of RV diastolic function occurred in association with significant increases in the ratio of RV dry weight to LV+septal dry weight. NO and milrinone administration both led to significant improvements in RV diastolic properties. CONCLUSIONS In the setting of MCTP-induced CPH, significant worsening of RV diastolic function was observed in association with significant increases in the ratio of RV dry weight to LV+septal dry weight, suggesting that these changes are partially due to RV hypertrophy. The significant improvement in RV diastolic properties after both NO and milrinone administration suggests that these agents may be effective forms of pharmacological therapy for improving RV diastolic dysfunction in the setting of CPH.

Pharmacodynamics of T-cell function for monitoring immunosuppression

Abstract.  Objectives: Recent studies show that measuring pharmacodynamic (PD) effects offers a unique possibility to predict immunosuppression. Thus, in this study we have monitored the PD properties of immunosuppressants on diverse T‐cell functions in heart transplant (HTx) recipients. Materials: PDs and blood concentrations (PK) of three different basis‐immunosuppressive drugs were studied: cyclosporin A (CsA); tacrolimus (TRL) and sirolimus (SRL). T‐cell function was analysed by expression of proliferating cell nuclear antigen (PCNA) labelling, expression of cytokines (IL‐2, IFN‐γ) and surface antigen (for example, CD25) by FACS analysis. Results: In group I, at time points C0 and C2, increased CsA‐PK significantly inhibited expression of IL‐2, IFN‐γ, PCNA and CD25 (P < 0.05). Correlations (r2) at C2 between inhibition of T‐cell functions (PD) with PK and with drug doses were: CsA‐PK: 0.71–0.91 and CsA‐dose: 0.73–0.87. In group II, increased TRL‐PK over time did not further inhibit expression of CD25, but inhibited PCNA expression more on day 3, and IL‐2 and IFN‐γ expression was significantly higher on days 2 and 3 compared to PD effects of CsA (P < 0.05). Blood SRL concentrations in C0 group III, increased on day 1 and remained stable at days 3 and 4. Expression of PCNA was not altered in the SRL‐PK category, whereas expression of CD25 was higher and expression of cytokines was lower than PD effects of CsA. Conclusions: Our results show that PD effects on T‐cell function can be used to monitor immunosuppression bringing potential to increase the efficacy and safety of immunosuppressive therapy after HTx.

Physiologic Effects Of Extracellular Superoxide Dismutase Transgene Overexpression On Myocardial Function After Ischemia And Reperfusion Injury

OBJECTIVE Myocardial injury after ischemia and reperfusion may be mediated, in part, by oxygen-derived free radicals. In this study the protective effects of extracellular superoxide dismutase overexpression were directly assessed in the hearts of transgenic mice, after ischemia and reperfusion injury, using an isolated work-performing murine heart preparation and computerized analysis of functional data. METHODS A blinded study was performed to compare cardiac function in the hearts of both transgenic mice with a 3.5-fold overexpression of myocardial extracellular superoxide dismutase (n = 6, 22 to 26 gm) and littermate controls (n = 8, 22 to 26 gm). Preload-dependent cardiac output, contractility, heart rate, stroke work, and stroke volume were evaluated in the two groups before and after a 6-minute period of normothermic ischemia. RESULTS No differences were found between extracellular superoxide dismutase hearts and control hearts in any parameter of myocardial function before ischemia. After ischemia, decreases in cardiac output occurred in both groups; however, this decrease was larger in control mice compared with extracellular superoxide dismutase mice. A higher percentage of recovery was also observed in the contractility, heart rate, stroke work, and stroke volume of extracellular superoxide dismutase hearts compared with control hearts. CONCLUSION After global normothermic ischemia and subsequent reperfusion, decreases in cardiac function occurred in both extracellular superoxide dismutase and control mice; however, a higher percentage of recovery was observed in the extracellular superoxide dismutase overexpressed hearts. These data suggest that extracellular superoxide dismutase transgene overexpression significantly improves preservation of myocardial function after ischemia and reperfusion injury.

Myocardial β-Adrenergic Receptor Function and High-Energy Phosphates in Brain Death– Related Cardiac Dysfunction

BACKGROUND Cardiac failure remains an important problem after heart transplantation and may be associated with events that occur during brain death (BD) before transplantation. In this study, cardiac function is studied after BD, and biochemical evaluation of myocardial high-energy phosphates and the beta-adrenergic receptor system is presented. METHODS AND RESULTS The hearts of 17 mongrel dogs (23 to 31 kg) were instrumented with flow probes, micromanometers, and ultrasonic dimension transducers to measure ventricular pressure and volume relationships. In a validated canine BD model, systolic right and left ventricular (RV/LV) function was analyzed by load-insensitive measurements during caval occlusion (preload-recruitable stroke work, PRSW). The beta-adrenergic receptor (BAR) density, adenylate cyclase (AC) activity, and myocardial ATP and creatine phosphate (CP) were measured before and 6 to 7 hours after BD. Results are expressed as mean +/- SEM (*P < .05 versus baseline, paired two-tailed Students t test). Myocardial function deteriorated significantly from baseline PRSW (RV, 22 +/- 1 erg x 10(3); LV, 75 +/- 4 erg x 10(3)) by 37 +/- 10% for the RV (P < .001) and 22 +/- 7% for the LV (P < .001). BAR density increased from 282 +/- 42 to 568 +/- 173 fmol/mg for the RV and from 291 +/- 64 to 353 +/- 56 fmol/mg for the LV. Isoproterenol-stimulated AC activity was also significantly enhanced after BD. ATP and CP, however, remained unchanged after BD compared with baseline values before BD. CONCLUSIONS BD causes significant systolic biventricular dysfunction. The loss of ventricular function after BD was more prominent in the right ventricle and may contribute to early postoperative RV failure in the recipient. These injuries occurred despite BAR system upregulation after BD. Global myocardial ischemia is unlikely, since ATP and CP remained normal before and after BD.

Right ventricular dysfunction after cardiac transplantation: primarily related to status of donor heart

BACKGROUND It is unclear whether right ventricular dysfunction after transplantation is due to donor brain death-related myocardial injury or recipient pulmonary hypertension. METHODS A canine donor model of brain death and a monocrotaline pyrrole-induced chronic pulmonary hypertension recipient model were established, and used for 30 orthotopic bicaval cardiac transplantations divided into three groups: Controls (group A, normal donor/recipient), group B (brain-dead donors/normal recipient), and group C (normal donor/recipients with pulmonary hypertension). Right ventricular function was measured before transplant and brain death, 4 hours after brain death, and after transplant (1 hour off bypass) by load-independent means plotting stroke work versus end-diastolic volume during caval occlusion. Right ventricular total power and pulmonary vascular impedance were determined by Fourier analysis. RESULTS In comparison to the control group right ventricular preload-recruitable stroke work and total power decreased significantly after brain death and transplant in group B (from 22.7 x 10(3) erg (+/-1.2) at baseline to 15.6 x 10(3) (+/-0.9) after brain death and to 11.3 x 10(3) (+/-0.9) after transplant). In group C there was a significant increase in pulmonary artery pressure, impedance, right ventricular preload-recruitable stroke work, total power after transplant. CONCLUSIONS Normal donor hearts adapt acutely to the recipients elevated pulmonary vascular resistance by increasing right ventricular power output and contractility. Brain death caused significant right ventricular dysfunction and power loss, which further deteriorated after graft preservation and transplantation. The effects of donor brain death on myocardial function contribute to right ventricular dysfunction after cardiac transplantation.

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).

Outcome of Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation and Graft Recovery

BACKGROUND Indications for extracorporeal membrane oxygenation (ECMO) use in lung transplantation are (1) temporary assistance as a bridge to transplantation, (2) stabilization of hemodynamics during transplantation in place of cardiopulmonary bypass, and (3) treatment of severe lung dysfunction and primary graft failure after transplantation. This study compares the survival of lung transplant recipients requiring ECMO support with survival of patients without ECMO. METHODS A retrospective database review was performed for 108 consecutive patients who underwent single-lung or bilateral-lung transplantation at our center between 2002 and 2009. RESULTS Of 108 transplant recipients, 27 (25%) required venoarterial ECMO compared with 81 patients who did not. Nine patients required ECMO preoperatively (87±102 hours), and ECMO was continued for 5 patients during the lung transplant operation. Seven additional patients received ECMO during transplantation. Six patients required early (<7 days) and 5 patients delayed (≥7 days) postoperative ECMO for treatment of allograft dysfunction. The subgroup with support showed the most favorable patient discharge rate (66.7%). ECMO support was a significant risk factor for death (p<0.001). Survival was significantly reduced with the use of ECMO: 30-day, 90-day, 1-year, and 5-year survival was 97%, 91%, 83%, and 58% in the patients without ECMO compared with 63%, 44%, 33%, and 21% in those with ECMO, respectively. CONCLUSIONS Survival after lung transplantation was significantly reduced with ECMO. However, patients who survived the first year showed similar long-term survival as those patients who did not need perioperative ECMO support.