Impact of route of access and stenosis subtype on outcome after transcatheter aortic valve replacement.

Introduction: Previous analyses have reported the outcomes of transcatheter aortic valve replacement (TAVR) for patients with low-flow, low-gradient (LFLG) aortic stenosis (AS), without stratifying according to the route of access. Differences in mortality rates among access routes have been established for high-gradient (HG) patients and hypothesized to be even more pronounced in LFLG AS patients. This study aims to compare the outcomes of patients with LFLG or HG AS following transfemoral (TF) or transapical (TA) TAVR. Methods: A total of 910 patients, who underwent either TF or TA TAVR with a median follow-up of 2.22 (IQR: 1.22-4.03) years, were included in this multicenter cohort study. In total, 146 patients (16.04%) suffered from LFLG AS. The patients with HG and LFLG AS were stratified according to the route of access and compared statistically. Results: The operative mortality rates of patients with HG and LFLG were found to be comparable following TF access. The operative mortality rate was significantly increased for patients who underwent TA access [odds ratio (OR): 2.91 (1.54-5.48), p = 0.001] and patients with LFLG AS [OR: 2.27 (1.13-4.56), p = 0.02], which could be corroborated in a propensity score-matched subanalysis. The observed increase in the risk of operative mortality demonstrated an additive effect [OR for TA LFLG: 5.45 (2.35-12.62), p < 0.001]. LFLG patients who underwent TA access had significantly higher operative mortality rates (17.78%) compared with TF LFLG (3.96%, p = 0.016) and TA HG patients (6.36%, p = 0.024). Conclusions: HG patients experienced a twofold increase in operative mortality rates following TA compared with TF access, while LFLG patients had a fivefold increase in operative mortality rates. TA TAVR appears suboptimal for patients with LFLG AS. Prospective studies should be conducted to evaluate alternative options in cases where TF is not possible.

Different calcification patterns of tricuspid and bicuspid aortic valves and their clinical impact.

OBJECTIVES: Mechanical strain plays a major role in the development of aortic calcification. We hypothesized that (i) valvular calcifications are most pronounced at the localizations subjected to the highest mechanical strain and (ii) calcification patterns are different in patients with bicuspid and tricuspid aortic valves. METHODS: Multislice computed tomography scans of 101 patients with severe aortic stenosis were analysed using a 3-dimensional post-processing software to quantify calcification of tricuspid aortic valves (n = 51) and bicuspid aortic valves (n = 50) after matching. RESULTS: Bicuspid aortic valves exhibited higher calcification volumes and increased calcification of the non-coronary cusp with significantly higher calcification of the free leaflet edge. The non-coronary cusp showed the highest calcium load compared to the other leaflets. Patients with annular calcification above the median had an impaired survival compared to patients with low annular calcification, whereas patients with calcification of the free leaflet edge above the median did not (P = 0.53). CONCLUSIONS: Calcification patterns are different in patients with aortic stenosis with bicuspid and tricuspid aortic valves. Patients with high annular calcification might have an impaired prognosis.

Surgery out of office hours for type A aortic dissection: does night-time and weekend surgery worsen outcome?

OBJECTIVES: Immediate surgical repair for type A aortic dissection is gold standard and at most centres is performed by the surgeon on call during night-time and weekends. The objective was to evaluate whether emergency surgery during night-time or weekends has an influence on 30-day mortality. METHODS: In 319 patients undergoing surgery for type A aortic dissection, skin incision was documented. Patients were divided into 2 groups according to the time point of skin incision (05:00 a.m. to 07:00 p.m. = daytime group; 07:01 p.m. to 04:59 a.m. = night-time group). We also noted whether their surgeries were started on weekdays (Monday 00:00 to Friday 23:59) or weekends (Saturday 00:00 to Sunday 23:59). RESULTS: The median age was 61 years (interquartile range 49-70) and 69.6% (n = 222) were male. Almost 50% (n = 149) of patients presented in a critical preoperative state. Forty-one percent of patients (n = 131) underwent night-time surgery. There were no differences in baseline data, time from onset of symptoms to surgery or surgical treatment between groups, except from preferred femoral access for arterial cannulation during night-time. Advanced age [odds ratio 1.042, 95% confidence interval (CI) 1.014-1.070], preoperative malperfusion syndrome (odds ratio 2.542, 95% CI 1.279-5.051) and preoperative tamponade (odds ratio 2.562, 95% CI 1.215-5.404) emerged as risk factors for 30-day mortality. Night-time or weekend surgery did not have any impact on 30-day mortality when covariates were considered. CONCLUSIONS: Based on the natural course of the disease and our results, surgery for type A aortic dissection should be performed as an emergency surgery regardless of time and day.

Immediate Surgery in Acute Type A Dissection and Neurologic Dysfunction: Fighting the Inevitable?

BACKGROUND: Neurologic dysfunction remains an ongoing challenge in the diagnosis of type A aortic dissection (AAD). Our study analyzed the impact of preoperative neurologic dysfunction (PND) on outcome and assessed a potential link between PND and specific patterns of postoperative neurologic injury. METHODS: Medical records of 338 patients (70.1% men; mean age, 59.3 ± 13.7 years) undergoing surgical repair for AAD were screened for the presence of PND. Preoperative characteristics, surgical treatment, and hospital and neurologic outcomes were analyzed according to patients with PND (PND+) and without PND (PND-) RESULTS: There were 50 patients (14.8%) admitted with PND. PND+ patients showed significantly higher rates of postoperative neurologic injury (44.4%) than PND- patients (14.3%; P < .001) with a specific pattern of ischemic lesions in accordance with preoperative neurologic status. While PND+ patients suffered mainly from right hemispheric strokes (66.7% vs 32.4% in PND- patients, P = .024), PND- patients more frequently presented with bilateral cerebral ischemia (56.8% vs 13.3% in PND+ patients, P = .004). Multivariable analysis identified presence of PND (odds ratio, 2.977; 95% confidence interval, 1.357-6.545) as an independent predictor for new postoperative neurologic injury. PND was associated with impaired survival (P = .005). CONCLUSIONS: This study identified an association of preoperative neurologic status and specific stroke patterns after surgical repair of AAD. Irrespective of timing of surgery and reperfusion strategies, preoperative neurologic dysfunction is strongly associated with impaired neurologic outcome.

Dataset on the prognostic value of cardiac biomarkers used in clinical routine in patients with severe aortic stenosis undergoing valve replacement.

Hereby, the supplemental data of the research article "Long-Term Prognostic Value of High-Sensitivity Troponin T added to N-Terminal Pro Brain Natriuretic Peptide Plasma Levels before Valve Replacement for Severe Aortic Stenosis" are presented [1]. It offers enhanced input on the predictive value of these biomarkers considering the influence of the presence of concomitant coronary artery disease (CAD) in various severities as well as an additional cox proportional hazard model on cardiovascular mortality. Furthermore, the receiver operating characteristic (ROC) curves are shown as figures. The material described increases therefore the understanding of the predictive value of these already routinely available biomarkers and reduces the risk of potential bias due to possible confounding factors. It also underlines the urge for a multi-factorial approach in diagnostics to detect the optimal point for referral to valve replacement other than just symptomatic status, an observed reduction in left ventricular ejection fraction or the presence of CAD with the necessity for coronary artery bypass grafting (CABG) [2]. The data of the 3595 patients were gathered retrospectively at a consortium of four university hospital centers in Austria and combined with prospectively collected data on cardiovascular and all-cause mortality.

Long-Term Prognostic Value of High-Sensitivity Troponin T Added to N-Terminal Pro Brain Natriuretic Peptide Plasma Levels Before Valve Replacement for Severe Aortic Stenosis.

Natriuretic peptide plasma levels help to manage patients with severe aortic stenosis (AS). The role of troponin plasma levels in this patient cohort remains speculative. A consortium of 4 university hospital centers in Austria analyzed retrospectively 3,595 patients admitted for valve replacement because of severe AS since 2007. The aim was to compare the additive preprocedural value of high-sensitivity troponin T (hsTnT) to N-terminal pro brain natriuretic peptide (NT-proBNP) plasma levels in predicting postoperative long-term survival in a large cohort undergoing either surgical (57.8%) or transcatheter (42.2%) aortic valve replacement. During a median follow-up of 2.93 (1.91 to 4.92) years, 919 patients (25.6%) died, in them 556 (15.5%) due to cardiovascular causes. Both normal hsTnT (<14 ng/l) and NT-proBNP (within age- and sex-corrected normal range) plasma levels were found in 481 patients (14.3%, group 1). Normal hsTnT but elevated NT-proBNP plasma levels were found in 748 patients (22.3%, group 2). Elevated hsTnT but normal NT-proBNP plasma levels were found in 258 patients (7.7%, group 3). Both elevated hsTnT and elevated NT-proBNP plasma levels were found in 1,869 patients (55.7%, group 4). Using Log Rank tests for comparison there was a highly significant difference in both cardiovascular mortality (p <0.0001) and all-cause mortality (p <0.0001). All-cause mortality rates after 1, 3, and 5 years were 2.1%, 5.4%, 7.7% in group 1; 4.0%, 7.5%, 11.5% in group 2; 5.8%, 8.9%, 14.0% in group 3; and 12.3%, 22.6%, 28.4% in group 4. In conclusion, hsTnT adds additional impact to NT-proBNP as a routinely available biomarker for risk stratification concerning postoperative survival in patients with severe AS admitted for valve replacement. The present study supports the concept to integrate hsTnT plasma levels in the management of severe AS.

Stroke after emergent surgery for acute type A aortic dissection: predictors, outcome and neurological recovery.

OBJECTIVES: Despite improvement in operative and cerebral perfusion techniques, cerebral malperfusion and neurological injury remain a dreaded complication of acute type A aortic dissection. We aimed to identify predictors for postoperative stroke and analyse the impact on morbidity, neurological recovery and mid-term survival. METHODS: Between 2000 and 2017, 303 (71.9% men, mean age 58.9 ± 13.6 years) patients with acute type A aortic dissection underwent surgical repair. Clinical and imaging data were retrospectively evaluated. Patients were divided into 2 groups depending on the presence of postoperative stroke. RESULTS: Postoperative stroke was detected in 15.8% (n = 48) of the patients. Patients with postoperative stroke showed higher rates of preoperative cardiopulmonary resuscitation (stroke: 18.8% vs no stroke: 3.5%, P < 0.001) and malperfusion syndrome (stroke: 47.9% vs no stroke: 22.4%, P < 0.001). Multivariable analysis identified the presence of bovine aortic arch [odds ratio (OR) 2.33, 95% confidence interval (CI) 1.086-4.998; P = 0.030], preoperative cardiopulmonary resuscitation (OR 6.483, 95% CI 1.522-27.616; P = 0.011) and preoperative malperfusion (OR 2.536, 95% CI 1.238-5.194; P = 0.011) as independent predictors for postoperative stroke. Postoperative stroke had a strong impact on morbidity and was associated with higher rates of postoperative complications and a significantly longer hospital stay (stroke: 23 ± 16 days vs no stroke: 17 ± 18 days, P = 0.021). Postoperative stroke was not independently associated with in-hospital mortality (adjusted OR 1.382, 95% CI 0.518-3.687; P = 0.518). There was no difference in mid-term survival between patients with stroke and patients without stroke. CONCLUSIONS: This study identified independent preoperative predictors for postoperative stroke. Although postoperative stroke was associated with significant morbidity and postoperative complications, significant impairment in mid-term survival could not be confirmed by the data.

Comparison of Two Minimally Invasive Techniques and Median Sternotomy in Aortic Valve Replacement.

BACKGROUND: Propensity score-matched analysis of the anterolateral minithoracotomy and the partial upper hemisternotomy vs the median sternotomy approach has not been reported to date for isolated aortic valve replacement. METHODS: From 2005 to 2013, isolated aortic valve replacement was performed through a partial upper hemisternotomy in 315 patients (38.9%), through a median sternotomy in 328 patients (40.5%), and through an anterolateral minithoracotomy in 167 patients (20.6%). After propensity score-matched analysis, both minimally invasive techniques were independently compared with median sternotomy in 118 matched pairs. RESULTS: In the anterolateral group, conversion to median sternotomy was significantly higher (17 [14.4%]), a second pump run (6 [5.1%]) and second cross clamp (12 [10.2%]) were significantly more often necessary, the median cross-clamp time (94 minutes; range, 43 to 231 minutes) and median perfusion time (141 minutes; range, 77 to 456 minutes) were significantly longer, and more groin complications occurred (17 [14.4%]), all compared with the median sternotomy group. No difference in perioperative results was identified between the partial upper hemisternotomy and the median sternotomy group. There was no significant difference in 1-year survival among the three groups, although a trend of better survival was observed in the partial upper hemisternotomy group. CONCLUSIONS: In minimally invasive isolated aortic valve replacement, the partial upper hemisternotomy shows similar perioperative outcome as the median sternotomy, whereas, the anterolateral minithoracotomy is associated with more perioperative complications. Therefore, only the partial upper hemisternotomy should be the preferred surgical technique for minimally invasive aortic valve replacement in the daily routine for a broad spectrum of surgeons.

Shock Wave Treatment Protects From Neuronal Degeneration via a Toll-Like Receptor 3 Dependent Mechanism: Implications of a First-Ever Causal Treatment for Ischemic Spinal Cord Injury.

BACKGROUND: Paraplegia following spinal cord ischemia represents a devastating complication of both aortic surgery and endovascular aortic repair. Shock wave treatment was shown to induce angiogenesis and regeneration in ischemic tissue by modulation of early inflammatory response via Toll-like receptor (TLR) 3 signaling. In preclinical and clinical studies, shock wave treatment had a favorable effect on ischemic myocardium. We hypothesized that shock wave treatment also may have a beneficial effect on spinal cord ischemia. METHODS AND RESULTS: A spinal cord ischemia model in mice and spinal slice cultures ex vivo were performed. Treatment groups received immediate shock wave therapy, which resulted in decreased neuronal degeneration and improved motor function. In spinal slice cultures, the activation of TLR3 could be observed. Shock wave effects were abolished in spinal slice cultures from TLR3(-/-) mice, whereas the effect was still present in TLR4(-/-) mice. TLR4 protein was found to be downregulated parallel to TLR3 signaling. Shock wave-treated animals showed significantly better functional outcome and survival. The protective effect on neurons could be reproduced in human spinal slices. CONCLUSIONS: Shock wave treatment protects from neuronal degeneration via TLR3 signaling and subsequent TLR4 downregulation. Consequently, it represents a promising treatment option for the devastating complication of spinal cord ischemia after aortic repair.

Comparison of Anterolateral Minithoracotomy Versus Partial Upper Hemisternotomy in Aortic Valve Replacement.

BACKGROUND: In aortic valve replacement, a comparison between the anterolateral minithoracotomy and the partial upper hemisternotomy approach has not been reported to date. METHODS: From 2006 to 2012, isolated aortic valve replacement was performed in 1,118 consecutive patients. Aortic valve replacement was performed through a anterolateral minithoracotomy in 166 patients (14.9%) and through a partial upper hemisternotomy in 245 patients (21.9%). A propensity score-matched analysis was performed in 160 matched pairs. RESULTS: Conversion to median sternotomy was significantly higher in the anterolateral group (n = 22, 13.1%) than in the hemisternotomy group (n = 7, 4.4%) (p = 0.004). A second cross-clamp was significantly more often necessary in the anterolateral group (n = 14, 8.8%) than in the hemisternotomy group (n =2, 1.3%) (p = 0.003). The median cross-clamp time was significantly longer in the anterolateral group, 93 minutes (range, 43 to 231 minutes) than in the hemisternotomy group, 75 minutes (range, 46 to 137 minutes) (p < 0.0001). The median perfusion time was significantly longer in the anterolateral group, 137 minutes (range, 81 to 456 minutes) than in the hemisternotomy group, 113 minutes (range, 66 to 257 minutes) (p < 0.0001). Significantly more groin adverse events occurred in the anterolateral group (n = 17, 10.8%) than in the hemisternotomy group (n = 0, 0%) (p < 0.0001). No significant difference in 90-day mortality was seen in the anterolateral group (n = 6, 3.8%) than in the hemisternotomy group (n = 2, 1.3%) (p = 0.16). CONCLUSIONS: The anterolateral minithoracotomy is associated with more perioperative adverse events. The partial upper hemisternotomy is an excellent surgical technique for minimally invasive aortic valve replacement in the daily routine for every staff surgeon.

Bovine aortic arch: predictor of entry site and risk factor for neurologic injury in acute type a dissection.

BACKGROUND: The aim of this study was to evaluate if the presence of a bovine aortic arch (BAA)- the most common aortic arch anomaly-influences the location of the primary entry tear, the surgical procedure, and the outcome of patients undergoing operation for type A acute aortic dissection (AAD). METHODS: A total of 157 patients underwent emergency operations because of AAD (71% men, mean age 59.5 ± 13 years). Preoperative computed tomographic scans were screened for the presence of BAA. Patients were separated into 2 groups: presenting with BAA (BAA+, n = 22) or not (BAA-, n = 135). Location of the primary tear, surgical treatment, outcome, and risk factors for postoperative neurologic injury and in-hospital mortality were analyzed. RESULTS: Fourteen percent (22 of 157) of all patients operated on for AAD had a concomitant BAA. Location of the primary entry tear was predominantly in the aortic arch in patients with BAA (BAA+, 59.1% versus BAA-, 13.3%; p < 0.001). Multivariate analysis revealed the presence of a BAA to be an independent risk factor for having the primary tear in the aortic arch (odds ratio [OR], 14.79; 95% confidence interval [CI] 4.54-48.13; p < 0.001) but not for in-hospital mortality. Patients with BAA had a higher rate of postoperative neurologic injury (BAA+, 35% versus BAA-, 7.9%; p = 0.004). Multivariate analysis identified the presence of BAA as an independent risk factor for postoperative neurologic injury (OR, 4.9; 95% CI, 1.635-14.734; p = 0.005). CONCLUSIONS: In type A AAD, the presence of a BAA predicts the location of the primary entry site in the aortic arch and is an independent risk factor for a poor neurologic outcome.

Bilirubin rinse of the graft ameliorates ischemia reperfusion injury in heart transplantation.

Ischemia and reperfusion contribute to substantial organ damage in transplantation. Clinically feasible measures for the prevention thereof are scarce. We tested whether rinsing rodent hearts with the antioxidant bilirubin ameliorates ischemia reperfusion injury (IRI). Left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDevP), rate per pressure product (RPP), coronary flow, maximum (+dP/dt) and minimum (-dP/dt) rate of contraction were analyzed in Lewis rat hearts rinsed with bilirubin prior to reperfusion on a Langendorff apparatus after 12 h of cold ischemia. In vivo, isogenic C57Bl/6 mouse hearts rinsed with bilirubin were transplanted after 12 h of cold ischemia. Cardiac function and apoptosis were assessed 24 h after reperfusion. Heart lysates recovered 15 min after reperfusion were probed for the total and the phosphorylated forms of extracellular signal-related protein kinases (ERK), JNK, p38-MAPK, and Akt. In isolated perfused hearts, bilirubin rinse resulted in significantly lower LVEDP and improved LVDevP, RPP, coronary flow, +dP/dt and -dP/dt. In vivo, after reperfusion, all mitogen-activated protein kinases (MAPKs) were suppressed significantly by bilirubin pretreatment. Bilirubin rinse improved cardiac scores (3.4 ± 0.5 vs. 2.0 ± 1.0 in controls, P < 0.05) and significantly suppressed apoptosis. Ex vivo administration of bilirubin to heart grafts prior reperfusion ameliorates IRI and provides a simple and effective tool to ameliorate outcome in heart transplantation.

The angiogenic factor secretoneurin induces coronary angiogenesis in a model of myocardial infarction by stimulation of vascular endothelial growth factor signaling in endothelial cells.

BACKGROUND: Secretoneurin is a neuropeptide located in nerve fibers along blood vessels, is upregulated by hypoxia, and induces angiogenesis. We tested the hypothesis that secretoneurin gene therapy exerts beneficial effects in a rat model of myocardial infarction and evaluated the mechanism of action on coronary endothelial cells. METHODS AND RESULTS: In vivo secretoneurin improved left ventricular function, inhibited remodeling, and reduced scar formation. In the infarct border zone, secretoneurin induced coronary angiogenesis, as shown by increased density of capillaries and arteries. In vitro secretoneurin induced capillary tubes, stimulated proliferation, inhibited apoptosis, and activated Akt and extracellular signal-regulated kinase in coronary endothelial cells. Effects were abrogated by a vascular endothelial growth factor (VEGF) antibody, and secretoneurin stimulated VEGF receptors in these cells. Secretoneurin furthermore increased binding of VEGF to endothelial cells, and binding was blocked by heparinase, indicating that secretoneurin stimulates binding of VEGF to heparan sulfate proteoglycan binding sites. Additionally, secretoneurin increased binding of VEGF to its coreceptor neuropilin-1. In endothelial cells, secretoneurin also stimulated fibroblast growth factor receptor-3 and insulin-like growth factor-1 receptor, and in coronary vascular smooth muscle cells, we observed stimulation of VEGF receptor-1 and fibroblast growth factor receptor-3. Exposure of cardiac myocytes to hypoxia and ischemic heart after myocardial infarction revealed increased secretoneurin messenger RNA and protein. CONCLUSIONS: Our data show that secretoneurin acts as an endogenous stimulator of VEGF signaling in coronary endothelial cells by enhancing binding of VEGF to low-affinity binding sites and neuropilin-1 and stimulates further growth factor receptors like fibroblast growth factor receptor-3. Our in vivo findings indicate that secretoneurin may be a promising therapeutic tool in ischemic heart disease.

The impact of distension pressure on acute endothelial cell loss and neointimal proliferation in saphenous vein grafts.

OBJECTIVES: We aimed to determine the extent of acute endothelial cell loss and neointimal proliferation in the long-term in saphenous vein grafts (SVGs) exposed to defined distension pressures. METHODS: During routine competence testing of SVGs for coronary artery bypass grafting (CABG), blinded peak pressure measurements were performed in 10 patients. In an experimental set-up, distension pressure-related endothelial damage was studied in the SVGs of 20 patients. In a subgroup (n = 10), each patient's SVG was divided into segments and subjected to four constant pressures (50, 100, 150 and 300 mmHg) for 30 min each. In another subgroup (n = 10), SVGs were exposed to a short phase of high pressure (low pressure followed by 300 mmHg for 5 min). Acute endothelial cell loss was quantified by CD31-immunostaining. After 2 weeks of organ culture, the neointimal proliferation was evaluated using histomorphometry. Pressure-related damage was compared with damage at baseline (0 mmHg). RESULTS: During routine competence testing for CABG, we revealed a median peak pressure of 355 mmHg (range: 240-639 mmHg). In the experimental set-up, significant acute endothelial cell loss occurred at all tested distension pressures: at 50 mmHg, the median endothelial cell loss was 29% (range: 20-51%, P = 0.015), at 100 mmHg 54% (range: 37-69%, P < 0.001), at 150 mmHg 75% (range: 41-88%, P < 0.001), at 300 mmHg 91% (range: 63-100%, P < 0.001) and at short high-pressure exposure 65% (range: 49-82%, P < 0.001) in comparison with 20% (range: 0-44%) at baseline. Significant neointimal proliferation occurred when a distension pressure of 50 mmHg was exceeded: at 50 mmHg, median neointimal proliferation was 97 µm (range: 60-380 µm, P = 0.176), at 100 mmHg 168 µm (range: 100-600 µm, P = 0.001), at 150 mmHg 183 µm (range: 160-440 µm, P < 0.001) at 300 mmHg 347 µm (range: 190-590 µm, P < 0.001) and at short high-pressure exposure 130 µm (range: 60-410 µm, P = 0.02) in comparison with 90 µm (range: 60-170 µm) at baseline. CONCLUSIONS: In vitro exposure of SVGs to low distension pressure ranges causes significant acute endothelial cell loss and crucial long-term damage, namely neointimal proliferation.

Perivascular administration of drugs and genes as a means of reducing vein graft failure.

Coronary artery bypass surgery is a highly effective and durable therapy of coronary artery disease. Together with internal mammary arteries the saphenous vein grafts are the most important conduits for coronary surgery. We reviewed the topic of local pharmacologic and gene therapeutic treatment approaches to prevent neointimal hyperplasia in vein grafts. Perivascular therapy of veins before arterialization would be a simple approach that avoids systemic side effects of medications. The current data available show that there are promising experimental approaches (in vitro models, animal in vivo models) for pharmacological and gene therapeutic treatment of vein graft failure.

Graft function after heterotopic rat heart transplant with an isolated reperfused working heart: a methodic consideration.

OBJECTIVES: Assessment of graft function in experimental cardiac transplant has been underused by insufficient methods (echo-cardiography, magnetic resonance imaging). The isolated reperfused working-heart model is an excellent tool for hemodynamic evaluation of rodent hearts. So far, it has never been used in a cardiac transplant setting. Our study tries to combine the in vivo technique of a rat heart transplant model with the ex vivo method of an isolated working heart. MATERIALS AND METHODS: Heterotopic heart transplants have been performed in rats with a nonsuture cuff technique. After 8 hours of cold ischemia and 24 hours of reperfusion, grafts were mounted on the working heart. To assess graft function, cardiac output was measured with increasing levels of afterload pressure. Nontransplanted hearts were mounted directly to the working heart apparatus to serve as a control group. Each heart was assessed subjectively by the Stanford score before being mounted on the working-heart apparatus. RESULTS: The working-heart assessment detected significantly impaired graft function in the transplant group compared with control hearts. In contrast, functional assessment with the score-system could not detect any difference between transplanted and native hearts. CONCLUSIONS: The isolated working-heart model is an excellent tool for assessing graft function after experimental heart transplant in rodents.

Evidence for cosmetics as a source of mineral oil contamination in women.

BACKGROUND: There is strong evidence that mineral oil hydrocarbons are the greatest contaminant of the human body, amounting to approximately 1 g per person. Possible routes of contamination include air inhalation, food intake, and dermal absorption. The present study aims to identify the most relevant sources of mineral oil contamination. METHODS: One hundred forty-two women undergoing elective cesarean section were enrolled. A specimen of subcutaneous fat was removed prior to wound closure. On days 4 and 20 postpartum, milk samples were collected from the women. Fat and milk samples were analyzed for mineral oil saturated hydrocarbons (MOSH). All women completed a questionnaire on personal data, nutrition habits, and use of cosmetics. MOSH concentrations in fat tissue were compared with data from the questionnaire and with MOSH concentrations in corresponding milk samples. RESULTS: The predominant predictor for MOSH contamination of fat tissue was age (p<0.001). Furthermore, body mass index (p=0.001), country of main residence (p=0.03), number of previous childbirths (p=0.029), use of sun creams in the present pregnancy (p=0.002), and use of hand creams and lipsticks in daily life (p=0.011 and p=0.007, respectively) were significant independent determinants. No association was found with nutritional habits. A strong correlation was seen between MOSH concentration in fat tissue (median 52.5 mg/kg) and in the corresponding milk fat sample from day 4 (median 30 mg/kg) (p<0.001) and day 20 (median 10 mg/kg) (p=0.028). CONCLUSIONS: The increase in MOSH concentration in human fat tissue with age suggests an accumulation over time. Cosmetics might be a relevant source of the contamination.

Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart.

Heart failure is a consequence of progressive deterioration of cardiac performance. Little is known about the role of impaired oxidative phosphorylation in the progression of the disease, since previous studies of mitochondrial injuries are restricted to end-stage chronic heart failure. The present study aimed at evaluating the involvement of mitochondrial dysfunction in the development of human heart failure. We measured the control of oxidative phosphorylation with high-resolution respirometry in permeabilized myocardial fibres from donor hearts (controls), and patients with no or mild heart failure but presenting with heart disease, or chronic heart failure due to dilated or ischemic cardiomyopathy. The capacity of the phosphorylation system exerted a strong limitation on oxidative phosphorylation in the human heart, estimated at 121 pmol O(2)s(-1)mg(-1) in the healthy left ventricle. In heart disease, a specific defect of the phosphorylation system, Complex I-linked respiration, and mass-specific fatty acid oxidation were identified. These early defects were also significant in chronic heart failure, where the capacities of the oxidative phosphorylation and electron transfer systems per cardiac tissue mass were decreased with all tested substrate combinations, suggesting a decline of mitochondrial density. Oxidative phosphorylation and electron transfer system capacities were higher in ventricles compared to atria, but the impaired mitochondrial quality was identical in the four cardiac chambers of chronic heart failure patients. Coupling was preserved in heart disease and chronic heart failure, in contrast to the mitochondrial dysfunction observed after prolonged cold storage of cardiac tissue. Mitochondrial defects in the phosphorylation system, Complex I respiration and mass-specific fatty acid oxidation occurred early in the development of heart failure. Targeting these mitochondrial injuries with metabolic therapy may offer a promising approach to delay the progression of heart disease.