A Multicenter Experience With a New Fenestrated-Branched Device for Endovascular Repair of Thoracoabdominal Aortic Aneurysms.

PURPOSE: To investigate the outcomes of patients who were treated for thoracoabdominal aortic aneurysms (TAAAs) using custom-made fenestrated-branched stent-grafts. METHODS: A consecutive series of 108 patients (mean age 73.5 years; 73 men) with TAAA were treated with E-xtra Design Engineering customized fenestrated-branched stent-grafts between November 2011 and January 2017. Data on baseline characteristics, procedures, and clinical follow-up were collected from 6 regional European surgical centers for retrospective analysis of endoleaks, reinterventions, and target vessel patency. The median aneurysm diameter was 6.75 cm (range 5.5-13). The distribution of the TAAA according to the modified Crawford classification of extent was 25 (24%) type I, 19 (17%) type II, 20 (18%) type III, 29 (27%) type IV, and 15 (14%) type V. RESULTS: Technical success was achieved in 95% (103/108) of cases. Major early perioperative complications occurred in 40 (37%) patients. The 30-day mortality was 9.2% (10/108), and perioperative spinal cord ischemia was observed in 6 (5.5%) patients [2 (1.8%) permanent]. During the mean follow-up of 17.6 months (range 3-52), 28 (26%) patients required late reintervention. Two patients died due to aneurysm- or procedure-related causes. The estimated survival rates at 1, 2, and 4 years were 87%, 84%, and 51%, respectively. The estimated target vessel patency rates at the same time points were 95%, 91%, and 90%, respectively. The freedom from reintervention estimates were 84% and 73% at 1 and 4 years, respectively. CONCLUSION: Endovascular repair of TAAA using Jotec customized fenestrated-branched stent-grafts appears to be safe and effective in the early to midterm. The considerable rate of secondary interventions indicates that further improvements, graft surveillance, and follow-up are required.

Adjunct Perfusion Branch for Reduction of Spinal Cord Ischemia in the Endovascular Repair of Thoracoabdominal Aortic Aneurysms.

BACKGROUND: To analyze utilization of a perfusion branch for temporary sac perfusion to reduce the spinal cord ischemia (SCI) in the endovascular repair of thoracoabdominal aortic aneurysms (TAAAs). METHODS: Between January 2012 and August 2016, 30 patients (18, men; median age 72 years) were treated for TAAAs with total endovascular repair using customized branched/fenestrated endografts in our institution. The median aneurysm size was 6.6 cm. Types of TAAA were: type I, 9 (30%), type II, 5 (16.6%), type III, 4 (13.3%), type IV, 6 (20%), and type V, 6 (20%). Ten patients received a perfusion branch to create an intentional endoleak, which was occluded with vascular plugs in mean interval time of 8.2 weeks (range: 6-10). Staged procedure and automated cerebrospinal fluid drainage were used in 23 (77%) and 24 (80%) patients, respectively. RESULTS: The technical success was 97%; 107 renovisceral target vessels were revascularized (32 fenestrations, 75 branches). At the time of the planned reinterventions, the mean arterial pressure (MAP) gradients were measured between the temporarily perfused aneurysm sac and the aortic endografts, and they were significantly higher (mean gradients 42.5 ± 10 mm Hg; range: 30-60) within the aortic grafts. The in-hospital and 30-day mortality was 3.3%. The incidence of postoperative SCI was 3/20 (15%) in the standard group and 0% in the group of the perfusion branch (p = 0.28). The mean follow-up was 12 months (range: 2-51). CONCLUSION: We experience that the use of a dedicated perfusion branch is feasible and may serve as protective adjunct to reduce the risk of SCI in endovascular treatment of TAAA. The risk of rupture in interval appears to be low. Larger series and multicenter studies are warranted to corroborate these results.

Three-Dimensional Analysis of Component Stability of the Nellix Endovascular Aneurysm Sealing System After Treatment of Infrarenal Abdominal Aortic Aneurysms.

PURPOSE: To assess short-term stability and conformational changes of the Nellix EndoVascular Aneurysm Sealing (EVAS) System using 3-dimensional (3D) analysis. METHODS: Postoperative computed tomography (CT) scans obtained at 0, 3, and 12 months in 24 patients (mean age 75±7 years; 22 men) who underwent EVAS between December 2013 and December 2014 for intact abdominal aortic aneurysm (within the instructions for use) were evaluated for stent-graft deviation in multiple planes using dedicated 3D analysis software. In addition, 2D analysis using an anatomically fixed reference landmark was performed to assess craniocaudal migration. Clinical and follow-up data of the patients were recorded and matched with results of the imaging analysis. RESULTS: Overall stability of the Nellix endografts was promising. Relevant conformational changes in the majority of cases were limited to the iliac graft segment and were clinically benign in all cases. Conversely, the only deviation of the proximal stent-graft segment was found in a patient with type Ia endoleak. Additional 2D analysis found relevant (≥5 mm) caudal migration of the Nellix stent-graft in 6 patients, including the one with the type Ia endoleak. In 3 patients, 3D analysis demonstrated the absence of relevant conformational changes of the endografts despite caudal migration. CONCLUSION: Overall stability of the separate EVAS stent-grafts is promising in the short term. Relevant conformational changes (stent-graft deviation) in the majority of cases were benign and confined to the iliac segment.

Endovascular Aneurysm Sealing (EVAS) and Chimney EVAS in the Treatment of Failed Endovascular Aneurysm Repairs.

PURPOSE: To assess the technical success and clinical outcome of reinterventions using the Nellix Endovascular Aneurysm Sealing (EVAS) System to treat complications after endovascular aneurysm repair (EVAR). METHODS: Fifteen consecutive patients (mean age 79 years; 14 men) with prior EVAR were treated with EVAS between March 2014 and December 2015 at 2 institutions. The failed prior EVARs included 13 bifurcated endografts, 1 bifurcated graft plus fenestrated cuff, and 1 tube endograft. Endoleaks were the predominant indications: type Ia in 10 and type III in 5 (3 type IIIa and 2 type IIIb). All patients presented with progressive aortic aneurysms (median 7.85-cm diameter; range 6.5-11). Eight patients were treated on an urgent or emergency basis (6 symptomatic aneurysms and 2 contained ruptures). All patients underwent Nellix relining of the failed stent-graft; 10 had chimney (Ch) procedures in combination with EVAS (chEVAS) because the proximal landing zones were inadequate. RESULTS: Technical success was 100%. All endoleaks were successfully sealed, and no additional intervention was required. No further endoleak after EVAS or chEVAS was recorded. Endobag protrusion occurred in 1 case without sequelae. One elderly patient with ruptured aneurysm died from multiple organ failure 2 months postoperatively. One renal artery guidewire injury led to nephrectomy because of active bleeding. No reinterventions, aneurysm-related mortalities, graft thrombosis, endoleaks, or chimney graft occlusions were observed during a median follow-up of 8 months (range 3-24). CONCLUSION: The present preliminary experience demonstrates that the use of EVAS/chEVAS is feasible for treatment of failed EVAR. This technique may be used as bailout or an alternative treatment when other established methods are infeasible or not available.

Initial Experience in the Treatment of Extensive Iliac Artery Aneurysms With the Nellix Aneurysm Sealing System.

PURPOSE: To assess the feasibility and effectiveness of the Nellix prosthesis in the treatment of common iliac artery aneurysms. METHODS: Between May 2013 and June 2015, 230 patients underwent implantation of the Nellix device at 2 institutions. Fifty of these patients (mean age 76 years; 35 men) were identified as having 60 common iliac artery aneurysms (CIAAs) with a median diameter of 4 cm (range 3.5-7). The majority of patients had aortoiliac aneurysms (5, 70%), 10 (20%) had isolated CIAAs, and 5 (10%) had iliac anastomotic aneurysms after aortoiliac bypass. In 20 patients, the iliac aneurysm was the indication for the intervention; in the other 30 patients, the endovascular iliac repair was an adjunct procedure to endovascular aneurysm sealing (EVAS). An iliac branch device (IBD) was used when feasible to preserve flow to the internal iliac artery. RESULTS: Seventeen (34%) patients underwent elective implantation of the Nellix graft in combination with an IBD, 33 (66%) patients underwent Nellix sealing of the CIAA using 1 (n=5), 2 (n=22), or 3 Nellix grafts (2 bilateral grafts and 1 graft as an extension to the external iliac artery in 6 patients). The technical success rate was 100%, and no graft-related complications were reported postoperatively. No buttock claudication, reinterventions, graft thrombosis, or endoleaks were observed during a mean follow-up of 12 months. CONCLUSION: Our initial experience demonstrates that Nellix grafts are feasible and safe for the treatment of extensive iliac artery aneurysms. The long-term durability of these grafts should be validated in larger patient cohorts before this promising alternative endovascular technique can gain widespread acceptance.

Impact of previous cardiovascular surgery on postoperative morbidity and mortality after major pulmonary resection for non-small cell lung cancer.

PURPOSE: The aim of this study was to evaluate the impact of previous cardiovascular surgery on the postoperative morbidity and mortality following major pulmonary resection for non-small cell lung cancer (NSCLC). METHODS: Medical records of 227 patients, who underwent major pulmonary resection for NSCLC from 2003 to 2012 at our department, were reviewed retrospectively. Thirty-one patients with a mean age of 65.8 years had previous cardiovascular surgery (group A) including coronary artery revascularization in 11 patients, peripheral arterial revascularization in 6 patients, carotis endarterectomy in 9 patients, and combined coronary artery revascularization and carotis endarterectomy in 5 patients, whereas 167 patients (mean age = 62.0 years) had no cardiovascular comorbidity (group B). Twenty-nine patients with nonsurgically treated cardiovascular comorbidity were excluded from this study. RESULTS: There were no significant differences in overall postoperative morbidity (22.6 % in group A vs. 19.2 % in group B) and mortality (no mortality in group A vs. 2.4 % in group B) between both groups. CONCLUSIONS: Major pulmonary resections for NSCLC can be performed safely in patients with previous cardiovascular surgical history who are fulfilling the common cardiopulmonary criteria of operability. Operative risk in this subpopulation is comparable to that in patients without cardiovascular comorbidity.

A minimally invasive approach for aortobifemoral bypass procedure.

Surgical aortobifemoral bypass procedure for aortoiliac occlusive disease remains the gold standard treatment despite rapidly expanding range of indications for endovascular repair. Besides several disadvantages such as dysparaesthesias, hernias, and unpleasant outcome, transperitoneal exposure of the aorta is also associated with operative autonomic nerve injury. In five male patients, infrarenal aorta was exposed through a small (8 cm) supraumbilical midline incision. Incision of the posterior peritoneum above the infrarenal aorta was limited to 3 cm. A 1 cm infraumbilical incision allowed transperitoneal placement of the distal aortic clamp outside of the operative field. Four centimeters transverse incisions were made over the femoral bifurcations and implantation of the aortobifemoral graft followed. Extubation was performed after an operating time of 200 to 150 minutes with 30 to 20 minutes aortic clamping time. Nonopioids or nonsteroidal anti-inflammatory drugs were intermittently administered during 12 hours of intermediate care unit monitoring. Oral alimentation started 6 hours and complete mobilization at 48 hours postoperatively. Hospital discharge followed on the fourth to tenth postoperative day. This minimally invasive technique allows a precise and controlled open performance of all vascular anastomoses minimizing intraoperative and postoperative complications and significantly decreasing patient discomfort related to standard abdominal surgery.

Liver transplantation and combined liver-heart transplantation in patients with familial amyloid polyneuropathy: a single-center experience.

Liver transplantation (LT) is the only curative option for patients with familial amyloid polyneuropathy (FAP) at present. Twenty patients with FAP underwent LT between May 1998 and June 2007. Transthyretin mutations included predominantly the Val30Met mutation but also 10 other mutations. Seven patients received a pacemaker prior to LT, and because of impairment of mechanical cardiac function, 4 combined heart-liver transplants were performed, 1 simultaneously and 3 sequentially. The first patient, who underwent simultaneous transplantation, died. Seven patients died after LT, with 5 dying within the first year after transplantation. The causes of death were cardiac complications (4 patients), infections (2 patients), and malnutrition (1 patient). One-year survival was 75.0%, and 5-year survival was 64.2%. Gly47Glu and Leu12Pro mutations showed an aggressive clinical manifestation: 2 patients with the Gly47Glu mutation, the youngest patients of all the non-Val30Met patients, suffered from severe cardiac symptoms leading to death despite LT. Two siblings with the Leu12Pro mutation, who presented only with grand mal seizures, died after LT because of sepsis. In conclusion, the clinical course in patients with FAP is very variable. Cardiac symptoms occurred predominantly in patients with non-Val30Met mutations and prompted combined heart-liver transplantation in 4 patients. Although early LT in Val30Met is indicated in order to halt the typical symptoms of polyneuropathy, additional complications occurring predominantly with other mutations may prevail and lead to life-threatening complications or a fatal outcome. Combined heart-liver transplantation should be considered in patients with restrictive cardiomyopathy.

Increased Lymphangiogenesis and Lymphangiogenic Growth Factor Expression in Perivascular Adipose Tissue of Patients with Coronary Artery Disease.

Experimental and human autopsy studies have associated adventitial lymphangiogenesis with atherosclerosis. An analysis of perivascular lymphangiogenesis in patients with coronary artery disease is lacking. Here, we examined lymphangiogenesis and its potential regulators in perivascular adipose tissue (PVAT) surrounding the heart (C-PVAT) and compared it with PVAT of the internal mammary artery (IMA-PVAT). Forty-six patients undergoing coronary artery bypass graft surgery were included. Perioperatively collected C-PVAT and IMA-PVAT were analyzed using histology, immunohistochemistry, real time PCR, and PVAT-conditioned medium using cytokine arrays. C-PVAT exhibited increased PECAM-1 (platelet endothelial cell adhesion molecule 1)-positive vessel density. The number of lymphatic vessels expressing lymphatic vessel endothelial hyaluronan receptor-1 or podoplanin was also elevated in C-PVAT and associated with higher inflammatory cell numbers, increased intercellular adhesion molecule 1 (ICAM1) expression, and fibrosis. Significantly higher expression of regulators of lymphangiogenesis such as vascular endothelial growth factor (VEGF)-C, VEGF-D, and VEGF receptor-3 was observed in C-PVAT compared to IMA-PVAT. Cytokine arrays identified angiopoietin-2 as more highly expressed in C-PVAT vs. IMA-PVAT. Findings were confirmed histologically and at the mRNA level. Stimulation of human lymphatic endothelial cells with recombinant angiopoietin-2 in combination with VEGF-C enhanced sprout formation. Our study shows that PVAT surrounding atherosclerotic arteries exhibits more extensive lymphangiogenesis, inflammation, and fibrosis compared to PVAT surrounding a non-diseased vessel, possibly due to local angiopoietin-2, VEGF-C, and VEGF-D overexpression.

Effects of aprotinin on gene expression and protein synthesis after ischemia and reperfusion in rats.

BACKGROUND: Reperfusion injury of ischemic myocardium has been attributed to neutrophil infiltration, inflammatory activation and cardiac necrosis/apoptosis. Serine protease inhibition with aprotinin is cardioprotective, but the mechanism is unknown. METHODS AND RESULTS: We studied aprotinin in a rat model of myocardial ischemia for 20 minutes and reperfusion for 20 minutes, 8 hours or 24 hours. Aprotinin (20,000 IU/kg) given 5 minutes before reperfusion significantly reduced leukocyte accumulation (P<0.01), myocardial injury (determined by CK depletion, P<0.01) and myocyte apoptosis (P<0.05) compared with vehicle treated rats. Differential gene expression analysis showed myocardial ischemia plus reperfusion increased expression of proinflammatory genes like P-selectin, E-selectin, intercellular adhesion molecule, tumor necrosis factor-alpha, tumor necrosis factor-alpha receptor, interleukin-6, monocyte chemoattractant protein-1, p53, and Fas (CD59). Aprotinin before reperfusion suppressed expression of these inflammatory genes. Finally, differential protein expression analysis demonstrated increased intercellular adhesion molecule-1, tumor necrosis factor-alpha, and p53 after myocardial ischemia plus reperfusion, and this effect was diminished by aprotinin. CONCLUSIONS: We demonstrated myocardial ischemia plus reperfusion induced leukocyte accumulation, inflammation, gene expression, protein expression and finally tissue injury and showed aprotinin limiting reperfusion injury through each of these stages, even after 24 hours of reperfusion. This effect seems partly attributable to suppression of proinflammatory genes and leukocyte accumulation. This work casts further light on the complex signaling of ischemia and reperfusion.

Poly(ADP-Ribose) polymerase inhibition reduces reperfusion injury after heart transplantation.

The aim of the present study was to investigate the effects of the novel poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide) on myocardial and endothelial function after hypothermic ischemia and reperfusion in a heterotopic rat heart transplantation model. After a 1-hour ischemic preservation, reperfusion was started either after application of placebo or PJ34 (3 mg/kg). The assessment of left ventricular pressure-volume relations, total coronary blood flow, endothelial function, myocardial high energy phosphates, and histological analysis were performed at 1 and 24 hours of reperfusion. After 1 hour, myocardial contractility and relaxation, coronary blood flow, and endothelial function were significantly improved and myocardial high energy phosphate content was preserved in the PJ34-treated animals. Improved transplant function was also seen with treatment with another, structurally different PARP inhibitor, 5-aminoisoquinoline. The PARP inhibitors did not affect baseline cardiac function. Immunohistological staining confirmed that PJ34 prevented the activation of PARP in the transplanted hearts. The activation of P-selectin and ICAM-1 was significantly elevated in the vehicle-treated heart transplantation group. Thus, pharmacological PARP inhibition reduces reperfusion injury after heart transplantation due to prevention of energy depletion and downregulation of adhesion molecules and exerts a beneficial effect against reperfusion-induced graft coronary endothelial dysfunction.

Treating iliac aneurysm using the Nellix Endovascular Sac Sealing System.

As endovascular treatment of abdominal aortic aneurysms has become established, there has been growing focus on treatment of the aneurysmal iliac artery. Isolated, large iliac aneurysms >30 mm pose a risk of rupture, but, in addition, 20% to 30% of abdominal aortic aneurysms are associated with iliac aneurysmal dilatation, which can compromise long-term outcomes. Endovascular solutions are evolving and until recently have utilized standard stent graft technology. The endovascular aortic sealing system was introduced as a new, effective method for the treatment of infrarenal aortic aneurysms. In this article, we present our recent extended use of the Nellix system, with or without a combination of adjuvant endovascular techniques, in the treatment of 84 common iliac artery aneurysms. The results support the use of endovascular aortic sealing system in endovascular therapy for aneurysmal iliac pathologies. Different endovascular sealing techniques for the treatment of common iliac artery aneurysms, re-interventions, and extended follow-up are also discussed.

Mortality in patients with acute aortic dissection type A: analysis of pre- and intraoperative risk factors from the German Registry for Acute Aortic Dissection Type A (GERAADA).

OBJECTIVES: Acute aortic dissection type A (AADA) is an emergency with excessive mortality if surgery is delayed. Knowledge about independent predictors of mortality on surgically treated AADA patients is scarce. Therefore, this study was conducted to identify pre- and intraoperative risk factors for death. METHODS: Between July 2006 and June 2010, 2137 surgically treated patients with AADA were enrolled in a multicentre, prospective German Registry for Acute Aortic Dissection type A (GERAADA), presenting perioperative status, operative strategies, postoperative outcomes and AADA-related risk factors for death. Multiple logistic regression analysis was performed to identify the influence of different parameters on 30-day mortality. RESULTS: Overall 30-day mortality (16.9%) increased with age [adjusted odds ratio (OR) = 1.121] and among patients who were comatose (adjusted OR = 3.501) or those who underwent cardiopulmonary resuscitation (adjusted OR = 3.751; all P < 0.0001). The higher the number of organs that were malperfused, the risk for death was (adjusted OR for one organ = 1.651, two organs = 2.440, three organs or more = 3.393, P < 0.0001). Mortality increased with longer operating times (total, cardiopulmonary bypass, cardiac ischaemia and circulatory arrest; all P < 0.02). Arterial cannulation site for extracorporeal circulation, operative techniques and arch interventions had no significant impact on 30-day mortality (all P > 0.1). No significant risk factors, but relevant increases in mortality, were determined in patients suffering from hemiparesis pre- and postoperatively (each P < 0.01), and in patients experiencing paraparesis after surgery (P < 0.02). CONCLUSIONS: GERAADA could detect significant disease- and surgery-related risk factors for death in AADA, influencing the outcome of surgically treated AADA patients. Comatose and resuscitated patients have the poorest outcome. Cannulation sites and operative techniques did not seem to affect mortality. Short operative times are associated with better outcomes.

Nitric oxide-sensitive soluble guanylyl cyclase activity is preserved in internal mammary artery of type 2 diabetic patients.

Vascular reactivity to nitric oxide (NO) is mediated by NO-sensitive soluble guanylyl cyclase (sGC). Since a diminished activity of vascular sGC has been reported in an animal model of type 2 diabetes, the sGC activity was assayed in vitro in internal mammary artery specimens obtained during bypass surgery from patients with and without type 2 diabetes. The sensitivity of sGC to NO, which is dependent on Fe(2+)-containing heme, was measured in vitro using stimulation with diethylamine NONOate (DEA/NO). In addition, the novel cyclic guanosine monophosphate-elevating compound HMR-1766 was used to test the stimulation of the oxidized heme-Fe(3+)-containing form of sGC. Basal activity of sGC and its sensitivity to stimulation by DEA/NO and HMR-1766 were not different between control and type 2 diabetic patients: maximum stimulation by DEA/NO amounted to 475 +/- 67 and 418 +/- 59 pmol. mg(-1). min(-1) in control and type 2 diabetic patients, respectively. The maximum effects of HMR-1766 were 95 +/- 18 (control subjects) and 83 +/- 11 pmol. mg(-1). min(-1) (type 2 diabetic patients). Hypertension, hyperlipidemia, drug treatment with statins, ACE inhibitors, or nitrates had no effect on sGC activity. In conclusion, the present findings do not support the hypothesis that desensitization of sGC contributes to the pathogenesis of diabetic vascular dysfunction in humans.

Brain death impairs coronary endothelial function.

BACKGROUND: To characterize the impact of brain death (BD) on endothelial dysfunction after cardiac transplantation we investigated coronary circulation and vasomotor function in a canine model. METHODS: Left ventricular pressure-volume data (conductance catheter) and coronary blood flow (CBF) were monitored continuously. Endothelium-dependent vasodilatation after acetylcholine and endothelium-independent vasodilation after sodium nitroprusside were assessed before and 3 hr after BD induction (inflation of a subdural balloon). RESULTS: BD led to an initial hyperdynamic reaction with significant (P<0.05) increase of CBF. After 3 hr, CBF decreased significantly (P<0.05). Although before BD, application of acetylcholine led to a monophasic vasodilatative response, after BD a short mild vasodilatation was followed by a longer vasoconstriction. Endothelium-independent vasodilatation remained unchanged. CONCLUSIONS: BD affects coronary circulation by two means: (1) impairment of CBF to decrease in parallel in afterload with consecutive hemodynamic deterioration and (2) severe endothelial dysfunction that may be a contributing factor to posttransplant outcome.

Modulation of catecholamine responsiveness and beta-adrenergic receptor/adenylyl cyclase pathway during cardiac allograft rejection1 2.

BACKGROUND: This study investigated the changes of catecholamine responsiveness and beta-adrenergic receptor/adenylyl cyclase pathway during acute cardiac transplant rejection. METHODS: Isogeneic Lewis to Lewis and allogeneic Dark Agouti (DA) to Lewis rat cardiac transplants were studied 3 and 5 days after heterotopic intraabdominal transplantation (n=6/group). Myocardial blood flow (MBF), left ventricular systolic pressure (LVSP), maximum pressure development (+dP/dt), and end-diastolic pressure (LVEDP) were measured using an intraventricular balloon. Contractile response to dobutamine (5 microg/kg/min) was also assessed. In separate groups beta-adrenergic receptor density and adenylyl cyclase activity were measured in the grafts, in the recipients' native hearts and in native hearts of sham-operated controls. RESULTS: During mild to moderate rejection cardiac function indices remained unchanged, although MBF and contractile response to dobutamine decreased significantly (P<0.05) in the allogeneic group. The beta-adrenergic receptor density was significantly (P<0.05) increased in both isografts and allografts and in the native hearts of allografted recipients in comparison to native hearts of controls. Adenylyl cyclase activity showed a significant decrease (P<0.05) only in allografts. During severe rejection, LVSP and +dP/dt decreased and LVEDP increased in allografts in comparison to isografts (P<0.05). This was accompanied by a significant decrease in MBF, contractile response to dobutamine, beta-adrenergic receptor density, and adenylyl cyclase activity (P<0.05). CONCLUSIONS: Both microcirculatory disturbances and primary alteration in adenylyl cyclase activity may contribute to decreased contractile reserve in mild to moderate cardiac allograft rejection, whereas beta-adrenergic receptor density seems to be also influenced by cardiac denervation. Severe rejection leads to systolic and diastolic heart failure with complex dysregulation of the beta-adrenergic receptor/adenylyl cyclase pathway and impaired microcirculation.

INO-1001 a novel poly(ADP-ribose) polymerase (PARP) inhibitor improves cardiac and pulmonary function after crystalloid cardioplegia and extracorporal circulation.

Poly(ADP-ribose) polymerase (PARP) activation plays a key role in free radical-induced injury in the context of systemic inflammation and ischemia/reperfusion. In the present preclinical study, we investigated the effects of INO-1001, a novel PARP inhibitor, on cardiac and pulmonary function during reperfusion in an experimental model of cardioplegic arrest and extracorporal circulation. Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or INO-1001 (1 mg/kg), a potent PARP inhibitor (n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow and vasodilative responses to acetylcholine and sodium nitroprusside as well as pulmonary gas exchange were also determined. The administration of INO-1001 led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 min of reperfusion. Coronary blood flow was also significantly higher in the INO-1001 group (P < 0.05). Although the vasodilative response to sodium nitroprusside was similar in both groups, acetylcholine resulted in a significantly greater increase in coronary and pulmonary blood flow in the INO-1001 group (P < 0.05). Pulmonary function in terms of alveolar arterial oxygen difference was better preserved in the INO-1001-treated group (P < 0.05). Thus, PARP inhibition improves the recovery of myocardial and endothelial function after hypothermic cardiac arrest and reduces pulmonary injury associated with extracorporal circulation.

Ventricular energetics after the Fontan operation: contractility-afterload mismatch.

OBJECTIVE: Fontan-type operations offer the opportunity to create pulmonary and systemic circulation in series with a single pumping chamber. The effectiveness of such a circulatory pattern determines resting and exercise hemodynamics in these patients. The present study investigated cardiac performance after the Fontan operation by using ventricular-vascular coupling framework analysis. METHODS: In 12 anesthetized open-chest dogs, Fontan circulation was established by using a cavopulmonary anastomosis. Left ventricular hemodynamic variables were measured by using a combined pressure-volume-conductance catheter. Additionally, aortic flow and pressure were recorded continuously. Ventricular contractility was quantified by using the load-independent slope of the end-systolic pressure-volume relationship. Arterial system properties were quantified by using the end-systolic pressure/stroke volume ratio. The coupling between the left ventricle and arterial system was expressed by using the ratio of end-systolic pressure/stroke volume to slope of the end-systolic pressure-volume relationship. Additionally, external stroke work, total mechanical energy and mechanical efficiency (Mechanical efficiency = Stroke work/Total mechanical energy) were calculated. Impedance spectra were determined by means of Fourier analysis. RESULTS: During Fontan circulation, the slope of the end-systolic pressure-volume relationship (5.3 +/- 0.6 vs 7.5 +/- 0.6 mm Hg/mL, P <.05) decreased, and the end-systolic pressure-stroke volume relationship (4.2 +/- 0.7 vs 3.3 +/- 0.5 mm Hg/mL, P =.23) increased with parallel increased characteristic impedance. Furthermore, the end-systolic pressure-stroke volume/slope of the end-systolic pressure-volume relationship ratio increased significantly (0.76 +/- 0.04 vs 0.42 +/- 0.03, P <.005). Simultaneously, stroke work (1846 +/- 146 vs 1389 +/- 60 mm Hg/mL, P <.05) and mechanical efficiency (0.82 +/- 0.09 vs 0.56 +/- 0.05, P <.05) were significantly reduced. CONCLUSIONS: Fontan circulation leads to contractility-afterload mismatch by means of increased impedance caused by additional connection of the pulmonary vascular bed to the systemic vasculature and by means of deterioration of myocardial contractility. The increased ventriculoarterial coupling ratio and reduced mechanical efficiency predict limited cardiac functional reserve after the Fontan operation.

In vivo validation of cardiac spiral computed tomography using retrospective gating.

BACKGROUND: Cardiac functional assessment represents the basis for diagnostics and cardiac operation planning. Spiral computed tomography (CT) combines the advantages of three-dimensional imaging and high temporal resolution when using gating techniques. However, in vivo validation data of this novel imaging technology are lacking. The purpose of this study was to validate in vivo the new imaging method using retrospective gating and to evaluate the clinical usefulness of the achieved temporal resolution. METHODS: In domestic pigs (n = 10, weight 35 to 40 kg) a flowmeter was placed surgically on the ascending aorta. Flow velocity integrated over systole served as the gold standard for left ventricular (LV) stroke volume (LVSV-FM). CT signal, projection data, pacemaker signal, and flow velocity were recorded simultaneously at constant heart rate (pacemaker, 90 beats per minute). End-systolic and end-diastolic frames were calculated by retrospective gating. LV volumes were traced, the difference representing CT stroke volume (LVSV-CT). Image data were three-dimensionally reconstructed using ray-tracing. RESULTS: Temporal resolution was 170 ms. Correlation of stroke volumes was high (r = 0.94, mean difference 1.75 mL). Intraobserver (0.49 mL for LVEDV, 0.31 for LVESV) and interobserver variability (p = 0.21 and p = 0.06, respectively) were low. Postprocessing resulted in four-dimensional beating-heart models useful for operation planning. CONCLUSIONS: Spiral CT using retrospective gating was validated in vivo. Clinically acceptable temporal resolution and accuracy in determining cardiac stroke volumes were found. As a true volumetric imaging modality the method may now play an important role in computer-assisted diagnostics and surgery.