Proof of concept of an accelerometer as a trigger for unilateral diaphragmatic pacing: a porcine model.

BACKGROUND: Unilateral diaphragmatic paralysis in patients with univentricular heart is a known complication after pediatric cardiac surgery. Because diaphragmatic excursion has a significant influence on perfusion of the pulmonary arteries and hemodynamics in these patients, unilateral loss of function leads to multiple complications. The current treatment of choice, diaphragmatic plication, does not lead to a full return of function. A unilateral diaphragmatic pacemaker has shown potential as a new treatment option. In this study, we investigated an accelerometer as a trigger for a unilateral diaphragm pacemaker (closed-loop system). METHODS: Seven pigs (mean weight 20.7 ± 2.25 kg) each were implanted with a customized accelerometer on the right diaphragmatic dome. Accelerometer recordings (mV) of the diaphragmatic excursion of the right diaphragm were compared with findings using established methods (fluoroscopy [mm]; ultrasound, M-mode [cm]). For detection of the amplitude of diaphragmatic excursions, the diaphragm was stimulated with increasing amperage by a cuff electrode implanted around the right phrenic nerve. RESULTS: Results with the different techniques for measuring diaphragmatic excursions showed correlations between accelerometer and fluoroscopy values (correlation coefficient 0.800, P < 0.001), accelerometer and ultrasound values (0.883, P < 0.001), and fluoroscopy and ultrasound values (0.816, P < 0.001). CONCLUSION: The accelerometer is a valid method for detecting diaphragmatic excursion and can be used as a trigger for a unilateral diaphragmatic pacemaker.

Dobutamine Versus Vasopressin After Mesenteric Ischemia.

BACKGROUND: Gastrointestinal blood flow may be compromised during and after vasopressor support. Endothelin expression may lead to microcirculatory dysfunction. The aim of this study was to analyze the effect of vasopressin and dobutamine after mesenteric ischemia on the gastrointestinal mucosal microcirculation, endothelin expression, and morphologic injury. MATERIALS AND METHODS: Pigs were studied in four groups (six pigs in each group): 1, sham; 2-4 ischemia (1 h superior mesenteric artery occlusion with 30 min reperfusion and 30 min of vehicle [2], dobutamine [3], or vasopressin [4] administration, followed by 30-min break and thiopental-induced hypotension [3, 4]). Blood flow of the gastric, jejunal, and rectosigmoidal mucosa was measured. At the end of the experiment, the mucosal expression of endothelin-1 (ET-1) and its receptor subtypes A (ETA) and B were determined by polymerase chain reaction. Mucosal injury, apoptotic cell death, and leukocytic infiltration were determined by histology and immunohistochemical analysis of cleaved caspase-3 and myeloperoxidase. RESULTS: Mesenteric ischemia increased jejunal mucosal ET-1 gene expression, arterial ET-1, intestinal fatty acid binding protein, and jejunal mucosal injury compared with sham. Dobutamine increased arteriovenous shunting at the cost of the jejunal mucosal blood perfusion. This was associated with an increased expression of ET-1 and ETA and mucosal leukocytic infiltration. In contrast, vasopressin increased postischemic capillary density and tissue blood flow. This was associated with a lower ET-1 gene expression. Vasopressin did not induce jejunal mucosal leukocytic infiltration. CONCLUSIONS: Vasopressin reduces mesenteric ischemia-associated alterations of the microcirculation and tissue integrity, whereas dobutamine does not.

First follow-up of a breakable stent for implantation in infants dedicated for a life-long stay.

OBJECTIVE AND METHODS: The use of conventional metal stents in infants is severely limited by subsequent somatic growth. The use of a breakable balloon expandable stent (BS) designed for initial implant at small diameters but with properties that allow unlimited dilation in line with growth has potential advantages in this patient group. This study reports our experience with this stent between 2010 and 2014. A total of 17 BS were implanted in 14 infants (mean age 4.8 months). All but one stent was placed into the aorta to treat coarctation. RESULTS: All implantations were successful and initial gradients dropped from a mean of 25-6 mm Hg (range from 1-50 down to 0-24 mm Hg). Mean follow-up was 3.3 years (range 5 days to 7 years) with a total cumulative follow-up of 46.7 patient years. Stent redilation was performed a median of 2.5 times (range 0-5). Sixteen stents in 13 patients remain in place. Following redilation beyond 10 mm, circumferential integrity of the BS was lost in 10 patients. No further stent implantation or related surgery was necessary. A 3 mm dissection occurred in one patient after redilation. CONCLUSIONS: The BS performed well in terms of relief of stenosis and could be successfully dilated during the phase of the infants' most rapid growth. Mild intimal proliferation occurred in some patients early after implantation. In the course of the stepwise redilations and growth adjustments, both, planned longitudinal and transverse fractures occurred without allowing a collapse of the stented area.

Vasopressin aggravates cardiopulmonary bypass-induced gastric mucosal ischemia.

BACKGROUND/AIM: Upper gastrointestinal bleeding (UGIB) is one of the most frequent gastrointestinal complications after cardiac surgery with cardiopulmonary bypass (CPB). Endothelin expression and microcirculatory dysfunction have been shown to be involved in UGIB. The aim of this study was to analyze the effect of vasopressin during CPB on the gastric mucosal microcirculation and the involvement of the endothelin system. METHODS: Eighteen pigs were randomized into three groups (n = 6 each): group I = sham, group II = CPB (1-hour CPB) and group III = CPB + vasopressin (1-hour CPB and vasopressin administration during CPB to maintain baseline arterial pressure). All animals were observed for a further 90 min after termination of CPB. Systemic hemodynamics as well as blood flow and oxygen saturation of the gastric mucosa were measured continuously. At the end of the experiment, the gastric mucosal expressions of endothelin-1 (ET-1) and its receptor subtypes A (ET(A)) and B (ET(B)) were determined by polymerase chain reaction. Gastric mucosal injury, apoptotic cell death and leukocytic infiltration were determined by histology and immunohistochemical analyses of cleaved caspase-3 and myeloperoxidase. RESULTS: CPB decreased gastric microvascular perfusion, which was associated with an increased expression of ET-1 and ET(A). Vasopressin aggravated the CPB-associated malperfusion, whereas it completely abrogated the upregulation of ET-1 and ET(A). Interestingly, vasopressin did not induce gastric mucosal morphologic injury, leukocytic infiltration or apoptotic cell death. CONCLUSION: Vasopressin aggravates CPB-associated microvascular malperfusion of the gastric mucosa but does not induce gastric mucosal injury.

In a porcine model of implantable pacemakers for pediatric unilateral diaphragm paralysis, the phrenic nerve is the best target.

BACKGROUND: A frequent complication of Fontan operations is unilateral diaphragmatic paresis, which leads to hemodynamic deterioration of the Fontan circulation. A potential new therapeutic option is the unilateral diaphragmatic pacemaker. In this study, we investigated the most effective stimulation location for a potential fully implantable system in a porcine model. METHODS: Five pigs (20.8 ± 0.95 kg) underwent implantation of a customized cuff electrode placed around the right phrenic nerve. A bipolar myocardial pacing electrode was sutured adjacent to the motor point and peripherally at the costophrenic angle (peripheral diaphragmatic muscle). The electrodes were stimulated 30 times per minute with a pulse duration of 200 µs and a stimulation time of 300 ms. Current intensity was the only variable changed during the experiment. RESULTS: Effective stimulation occurred at 0.26 ± 0.024 mA at the phrenic nerve and 7 ± 1.22 mA at the motor point, a significant difference in amperage (p = 0.005). Even with a maximum stimulation of 10 mA at the peripheral diaphragm muscle, however, no effective stimulation was observed. CONCLUSION: The phrenic nerve seems to be the best location for direct stimulation by a unilateral thoracic diaphragm pacemaker in terms of the required amperage level in a porcine model.

A porcine model of postoperative hemi-diaphragmatic paresis to evaluate a unilateral diaphragmatic pacemaker.

Unilateral phrenic nerve damage is a dreaded complication in congenital heart surgery. It has deleterious effects in neonates and children with uni-ventricular circulation. Diaphragmatic palsy, caused by phrenic nerve damage, impairs respiratory function, especially in new-borns, because their respiration depends on diaphragmatic contractions. Furthermore, Fontan patients with passive pulmonary perfusion are seriously affected by phrenic nerve injury, because diaphragmatic contraction augments pulmonary blood flow. Diaphragmatic plication is currently employed to ameliorate the negative effects of diaphragmatic palsy on pulmonary perfusion and respiratory mechanics. This procedure attenuates pulmonary compression by the abdominal contents. However, there is no contraction of the plicated diaphragm and consequently no contribution to the pulmonary blood flow. Hence, we developed a porcine model of unilateral diaphragmatic palsy in order to evaluate a diaphragmatic pacemaker. Our illustrated step-by-step description of the model generation enables others to replicate and use our model for future studies. Thereby, it might contribute to investigation and advancement of potential improvements for these patients.

Continuous regional myocardial blood flow measurement: validation of a near-infrared laser Doppler device in a porcine model.

OBJECTIVE: RMBF measurement is a major concern in various clinical and experimental settings, but no validated device for RMBF is currently available. METHODS: An LVP-triggered laser Doppler to measure RMBF was validated by simultaneous fluorescent MS RMBF in a porcine LAD flow reduction model (n = 10 pigs). The laser probe was positioned on the left ventricle's anterior wall. LAD blood flow reduction was achieved by a shaft-driven occluder positioned proximal to the transit-time flow meter measuring coronary blood flow. RMBF was measured at baseline; after the reduction of LAD blood flow to 70% and 30% of baseline; at 20 and 120 minutes of reperfusion; and, finally, 15 minutes after LAD occlusion. RESULTS: Laser Doppler RMBF (LDU) correlated strongly with MS RMBF under all tested conditions: baseline (epicardial 194.7 ± 41.9, endocardial 130.2 ± 29.2); 70% baseline-flow (epicardial 160.4 ± 27.7, endocardial 112.1 ± 15.1); 30% baseline-flow (epicardial 44.3 ± 5.5, endocardial 32.9 ± 9); 20 minutes reperfusion (epicardial 175.8 ± 33.6, endocardial 126.5 ± 30); 120 minutes reperfusion (epicardial 146.3 ± 31.1, endocardial 107.1 ± 29.7); and complete LAD occlusion (epicardial 10.5 ± 5.8 endocardial 1.4 ± 0.3) (r = 0.986-0.962, p < 0.001). CONCLUSIONS: This new blood pressure waveform-triggered laser Doppler probe is able to measure RMBF at different depths online in the beating heart.

Perioperative Cefazolin Prophylaxis in Pediatric Cardiac Surgery: A Prospective, Cohort Study.

BACKGROUND: This study's objective was to determine the effect of age, prolonged bypass, and hypothermia on serum cefazolin concentrations in children undergoing cardiac surgery. METHODS: A prospective, single-center, observational study was conducted, examining children undergoing cardiac surgery. Participants received cefazolin intravenously approximately 1 hour before skin incision, 3 hourly intraoperatively, and 8 hourly postoperatively. Blood samples were collected at 6 to 8 time points intraoperatively and at 6 time points in the first 24 hours postoperatively. Target unbound serum cefazolin concentrations were 2 mg/L. RESULTS: Sixty-eight patients were enrolled in the study, and 64 were included in the analysis. All maintained concentrations ≥ 2 mg/L throughout the operation. Nineteen patients (30%) did not maintain concentrations ≥ 2 mg/L in the first 24 hours after surgery. Older, larger children (P < .0001) were significantly less likely to achieve target unbound serum cefazolin concentrations. CONCLUSIONS: Intraoperative cefazolin concentrations reached the target concentration in all pediatric cardiac surgical cases. Postoperative cefazolin dosing appears to be insufficient to achieve minimum inhibitory concentrations in many patients.

Atherosclerosis aggravates ischemia/reperfusion injury in the gut and remote damage in the liver and the lung.

OBJECTIVE: We investigated whether mesenteric ischemia/reperfusion (I/R)-associated gut injury and remote liver and lung damage are affected by prevalent atherosclerosis. METHODS: Mesenteric ischemia was induced in atherosclerotic ApoE-deficient (ApoE(-/-)) and control C57BL/6 mice by clamping the superior mesenteric artery for 30 min. Mesenteric microcirculatory dysfunction and leukocytic inflammation were studied in the terminal ileum by intravital fluorescence microscopy (IVM). Histological analyses included quantitative assessment of parenchymal injury in the terminal ileum, liver and lung. RESULTS: In the gut, IVM of the terminal ileum revealed aggravated postischemic microcirculatory dysfunction and absence of reactive hyperemia-induced vasodilation in atherosclerotic mice compared to controls. In addition, leukocyte-endothelial cell adhesive interactions, i.e. rolling and firm adhesion, were significantly increased in atherosclerotic animals. This was associated with enhanced mucosal tissue damage in ApoE(-/-) mice. Moreover, mesenteric I/R-provoked remote parenchymal injury in the liver was found to be significantly aggravated in atherosclerotic mice. This was accompanied by enhanced neutrophilic lung inflammation in ApoE(-/-) mice. CONCLUSION: Prevalent generalized atherosclerosis not only aggravates splanchnic microcirculatory dysfunction and leukocytic inflammation in response to mesenteric I/R, but also exacerbates mucosal tissue damage and remote injury in the liver and the lung.

Repair of Complex Transposition of Great Arteries: Up to 30 Years of Follow-up.

BACKGROUND: To characterize treatment of transposition of great arteries with ventricular septal defect and left ventricular outflow tract obstruction (LVOTO) in Germany and to analyze late outcomes. METHODS: German Registry for Congenital Heart Defects data were searched for transposition of great arteries with ventricular septal defect and LVOTO. One hundred thirty-nine patients were treated at 15 institutions between 1968 and 2016. Risk factor analyses were performed for the primary endpoints of death and reoperation/reintervention. RESULTS: Follow-up was 88% complete, with a mean follow-up of 16 ± 7 years (median, 15 years [range, 1-48]) and a cumulative follow-up comprising 1739 patient-years. Atrial switches were performed in 15%, Rastelli procedure in 48%, Nikaidoh procedure in 9%, réparation a l'étage ventriculair (REV) in 8%, and arterial switch in 20%. Actuarial survival at 30 years was 86% (range, 83%-90%), with no difference between repairs. Freedom from primary reoperation was 17% (range, 12%-21%) at 30 years. Freedom from reoperation for LVOTO at 30 years was 74% (range, 70%-78%). Recurrent LVOTO was found in 9%, with risk factor diffuse subvalvular LVOTO (odds ratio, 9.8; P = .04). Late freedom from first reoperations other than right ventricle-to-pulmonary artery conduit was 60% (range, 59%-61%), with predictors multiple ventricular septal defect (hazard ratio, 6; P = .03) and Rastelli procedure (hazard ratio, 12; P = .03). Absolute reoperation rates were lowest for REV procedure (16% at a mean of 12 years). CONCLUSIONS: Long-term survival is good without detectable differences between operations. Since the early 2000s increasing use of Nikaidoh and REV procedures was obvious, with REV performing particularly well. Surgery-specific and -unspecific reoperations are most common after the Rastelli technique.

Critical single proximal left arterial descending coronary artery stenosis to mimic chronic myocardial ischemia: a new model induced by minimal invasive technology.

BACKGROUND/AIMS: The present report examines a new pig model for progressive induction of high-grade stenosis, for the study of chronic myocardial ischemia and the dynamics of collateral vessel growth. METHODS: Thirty-nine Landrace pigs were instrumented with a novel experimental stent (GVD stent) in the left anterior descending coronary artery. Eight animals underwent transthoracic echocardiography at rest and under low-dose dobutamine. Seven animals were examined by nuclear PET and SPECT analysis. Epi-, mid- and endocardial fibrosis and the numbers of arterial vessels were examined by histology. RESULTS: Functional analysis showed a significant decrease in global left ventricular ejection fraction (24.5 +/- 1.6%) 3 weeks after implantation. There was a trend to increased left ventricular ejection fraction after low-dose dobutamine stress (36.0 +/- 6.6%) and a significant improvement of the impaired regional anterior wall motion. PET and SPECT imaging documented chronic hibernation. Myocardial fibrosis increased significantly in the ischemic area with a gradient from epi- to endocardial. The number of arterial vessels in the ischemic area increased and coronary angiography showed abundant collateral vessels of Rentrop class 1. CONCLUSION: The presented experimental model mimics the clinical situation of chronic myocardial ischemia secondary to 1-vessel coronary disease.

Aortic stenosis of the neonate: A single-center experience.

OBJECTIVES: Because data for neonates are limited, optimal management of critical aortic stenosis remains controversial (balloon valvotomy [BV] or open valvoplasty [OV]). In a center with balanced experience in both methods, we hypothesized that OV can provide a better individualized approach than blunt BV and better serve long-term outcomes. METHODS: A retrospective review of data and follow-up (survival, freedom from operation/replacement) of all neonates, suitable for biventricular repair, undergoing aortic valve procedure (1989-2015), was performed. RESULTS: One hundred three patients were concomitantly treated (BV [n = 51], OV [n = 52). Median age was 8 days, median aortic annulus Z-score was -1.3 for BV (range, -3.9 to 2.0) and OV (-3.9 to 3.2) groups. Operative mortality after BV or OV was 8% (n = 4) and 4% (n = 2), respectively. With a 13-year median follow-up, 10-year freedom from operation was 36% and 66% after BV or OV, respectively. Valve replacement was ultimately required in 32 patients (n = 20 [39%] in the BV group; n = 12 [23%] in the OV group) within a 5.9-year median time. After OV, tricuspid arrangement of the repaired aortic valve provided a 10-year freedom from operation and replacement of 87% and 95%, respectively. In multivariate analysis, associated left heart malformations, BV, nontricuspid geometry, and inadequate post procedural result were predictive of operation and replacement. CONCLUSIONS: In neonates with critical aortic stenosis, both methods (BV and OV) offer excellent survival benefit. OV significantly minimizes the need for operation, whereas BV did not postpone age of replacement. Clearly superior results are achieved with OV when a post repair tricuspid arrangement is obtained.

Emboli formation rather than inflammatory mediators are responsible for increased cerebral water content after conventional and assisted beating-heart myocardial revascularization in a porcine model.

BACKGROUND AND PURPOSE: Emboli and proinflammatory mediators are suspected of generating cerebral edema after coronary surgery. In contrast to cardiopulmonary bypass (CPB), off-pump coronary artery bypass surgery (OPCAB) reduces microemboli count and proinflammatory mediator release but carries the risk of hemodynamic instability. A microaxial blood pump can augment cardiac output. METHODS: Coronary bypasses were constructed in pigs with CPB and cardioplegia (n=9), OPCAB (n=9), or blood-pump support CAB (n=9). Nine animals underwent sham operation. Embolus count was monitored and regional cerebral blood flow was assessed with microspheres in 21 brain specimens per animal (n=189 per group). Interleukins 6 and 8 and tumor necrosis factor-alpha concentrations were determined. These variables were studied before, during, and for 4 hours after surgery. Finally, cerebral water content was determined. RESULTS: During CPB and blood-pump CAB, a significant number of emboli were counted in contrast to OPCAB and controls (P<0.05). During CPB, regional cerebral blood flow was affected (32 of 189) and showed reactive hyperemia except in 10 specimens after aortic cross-clamp release. This impairment persisted in 20 specimens. During and after OPCAB, regional cerebral blood flow remained nearly unchanged but showed low flow during (58 of 189) and after (35 of 189) the blood-pump run. A significant increase in proinflammatory mediators was observed only in the CPB group. CPB and blood-pump CAB significantly increased cerebral water content (P<0.05). A strong correlation between embolic load and cerebral water content was observed in all groups. No correlation between proinflammatory mediator release and cerebral water content was detected. CONCLUSIONS: Emboli formation rather than inflammatory mediators are responsible for increased cerebral water content after conventional and assisted beating-heart myocardial revascularization.

Resistance of the internal mammary artery to restenosis: a histomorphologic study of various porcine arteries.

BACKGROUND/AIMS: Restenosis after percutaneous transluminal angioplasty (PTA) of the internal mammary artery (IMA) grafts is much less pronounced than in other arteries and venous grafts. The aim of the study was to test whether various arteries respond differently to dilatation. METHODS: PTA of the IMA, carotid, renal and circumflex coronary (RCx) arteries was performed in 9 pigs (balloon to artery ratio of 1:1.5). After 8 weeks, angiography was repeated and vessels prepared for histological analysis. Immunohistochemical staining was done to examine proliferative activity (Ki67) and to identify the vasa vasorum of the adventitia (F VIII-RA). RESULTS: The intima-media ratio after PTA was lowest in the IMA (0.06), followed by the carotid (0.27) and renal arteries (0.49) and the RCx (0.69). Proliferation of the intima was seen at 287 degrees of the vessel circumference in the RCx, at 286 degrees in the renal and at 166 degrees in the carotid artery. No proliferative activity was seen in the IMA. The intima-adventitia ratio was lower in the IMA than in the RCx and renal arteries (p < 0.05). CONCLUSION: Intima proliferation after PTA varies between the different vessels, with best results seen in the IMA. There are differences in remodeling after PTA between muscular, muscular/elastic and elastic arteries.

Promising Outcome of Anatomic Correction of Corrected Transposition of the Great Arteries.

BACKGROUND: Anatomic correction of corrected transposition of the great arteries with associated lesions, utilizing the morphologic left ventricle as a systemic pumping chamber, is the preferred method in many centers. The purpose of this study was to analyze functional outcome after anatomic correction. METHODS: Between Jan 1997 and May 2016, 63 patients with corrected transposition of the great arteries and associated lesions underwent anatomic correction. Forty-two patients (67%) underwent palliation before correction, including 14 patients (22%) who required training of systemic ventricle. The double switch procedure was performed in 37 patients; 25 patients underwent the Senning-Rastelli operation, and 1 patient underwent the Senning-Nikaidoh procedure. The median age at correction was 1.6 ± 3.7(SD) years (range, 0.2 to 17.8 years). RESULTS: The survival and freedom from any event was 95% and 71%, respectively, at 15-year follow-up. The combined freedom from death, failure of systemic ventricle, or heart transplant was 93% at 15-year follow-up regardless of procedure type. Sinus rhythm was present in 49 patients, with 14 patients requiring pacemaker (22%)-8 preoperatively, 4 early postoperatively, and 2 late postoperatively. Neurological development is normal in all patients. Fifty-four percent of the patients are not on medication. CONCLUSIONS: Anatomic correction of corrected transposition of the great arteries is a safe procedure that provides encouraging survival and functional benefits. Ninety-three percent preservation of morphological left ventricle function in 15 years of follow-up supports the concept of anatomic correction. Longer follow-up is needed to confirm superiority of this approach over other management strategies.

Contemporary results of aortic valve repair for congenital disease: lessons for management and staged strategy.

OBJECTIVES: Any aortic valve (AoV) operation in children (repair, Ross or mechanical replacement) is a palliation and reinterventions are frequent. AoV repair is a temporary solution primarily aimed at allowing the patient to grow to an age when more definitive solutions are available. We retrospectively analysed AoV repair effectiveness across the whole age spectrum of children, excluding neonates and AoV disease secondary to congenital heart disease. METHODS: From 2003 to 2015, 193 consecutive patients were included. The mean age was 9.2 ± 6.9 years (22% <1 year); 86 (45%) had a preceding balloon valvuloplasty. The indications for the procedure were stenotic (n = 123; 64%), regurgitant (n = 63; 33%) or combined (n = 7; 4%) disease. The procedures performed were commissurotomy shaving (n = 74; 38%), leaflet replacement (n = 78; 40%), leaflet extension (n = 21; 11%) and neocommissure creation (n = 21; 11%). Post-repair geometry was tricuspid in 137 (71%) patients. RESULTS: The 10-year survival rate was 97.1%. Freedom from reoperation and replacement at 7 years was, respectively, 57% (95% confidence interval, 47-66) and 68% (95% confidence interval, 59-76). In multivariate analysis, balloon dilatation before 6 months, the absence of a developed commissure, a non-tricuspid post-repair geometry and cross-clamp duration were predictors for reoperation and replacement. After a mean follow-up period of 5.1 ± 3.0 years, 145 (75%) patients had a preserved native valve, with undisturbed valve function (peak gradient <40 mmHg, regurgitation ≤mild) in 113 (58%). CONCLUSIONS: Aortic valve repair in children is safe and effective in delaying the timing for more definitive solution. Surgical strategy should be individualized according to the age of the patient. Avoidance of early balloon dilatation and aiming for a tricuspid post-repair arrangement may improve outcomes.

Potent low dose platelet inhibitory effects of clopidogrel and aspirin on coronary thrombus formation in an animal model of acute unstable angina.

Application of clopidogrel before percutaneous coronary intervention in patients with acute coronary syndrome reduces the risk of cardiac events. Clopidogrel administration before surgery increases bleeding complications after CABG. Therefore,the antithrombotic effect of the low-dose combination of clopidogrel and aspirin was investigated in an in vivo pig model of coronary artery thrombus formation with cyclic flow reductions. The platelet inhibitory effect was determined by platelet aggregation and CFR, according to the methodology described by Folts. CFR were initiated by endothelial damage and placement of a constrictor around the LAD. 30 min after CFR were established, clopidogrel (0. I mg/kg or 5 mg/kg), aspirin (I mg/kg or 7 mg/kg) or LDC (0. I mg/kg clopidogrel and I mg/kg aspirin) were administered orally. CFR-frequency was determined for further 240 min.CFR-frequency (CFR/30 min) was significantly reduced at 60 min in response to aspirin (7 mg/kg, -48%, p<0.05), and at 120 min in response to clopidogrel (5 mg/kg,-65%, p<0.05) but not at low doses of either compound. In contrast, LDC of clopidogrel (0. I mg/kg) plus aspirin (I mg/kg) resulted in a complete and rapid abrogation of CFR at 90 min (-70%, p<0.05 y. Furthermore, LDC led to reduction of platelet aggregation when CFR-frequency was already significantly decreased. In contrast, high dose groups presented a significant reduction of platelet aggregation prior to CFR-frequency decrease. Low dose combination of clopidogrel plus aspirin demonstrates a potent over additive anti-thrombotic effect in vivo with a significant reduction in thrombus formation early after drug application. The effect occurs before inhibition of platelet aggregation is detectable.

Expanding the Limits of Posterior Aortic Translocation: Biventricular Correction of Complex Transposition With Complete Atrioventricular Septal Defect and Heterotaxy.

This case report describes successful repair of d-transposition of the great arteries with severe left ventricular outflow tract obstruction and complete atrioventricular septal defect associated with heterotaxy by the use of posterior aortic translocation combined with repair of the atrioventricular septal defect and systemic venous anomalies.

Current mid-term outcome with an integrated surgical strategy for correction of d-transposition of the great arteries with ventricular septal defect and left ventricular outflow tract obstruction.

OBJECTIVES: The optimal surgical treatment strategy for transposition of the great arteries (TGA) associated with ventricular septal defect (VSD) and left ventricular outflow tract obstruction (LVOTO) leading to the best long-term outcome has not been established yet. The wide range of anatomical variability has led to the development of different surgical treatment options. In a retrospective single-centre review, we aimed to report the long-term outcome in patients who underwent biventricular repair. METHODS: Between 1992 and 2015, 49 patients underwent biventricular repair for TGA with VSD and LVOTO. On the basis of anatomical substrate, the type of repair was chosen. According to the type of repair, the patients were divided into two groups. Group A (n = 30 patients) includes all patients who underwent intraventricular rerouting (Rastelli, n = 22; réparation à l'étage ventriculaire, n = 8); Group B patients (n = 14) had repair on an arterial level (arterial switch operation + VSD closure + LVOTO resection, n = 10; Bex-Nikaidoh, n = 4). RESULTS: The follow-up was completed in 90% with a median follow-up of 12.3 years (17.1-17.7 years). There was no difference in survival (Group A: 97% at 5, 10 and 15 years; Group B: 92% at 5, 10 and 15 years) and functional outcome between the groups. All patients were in New York Heart Association class I, having sinus rhythm and normal left ventricular (LV) function. Neurological and educational development was adequate for age in all but one who suffered from attention-deficit hyperactivity disorder. Group A exhibited significantly less freedom from right ventricular outflow tract (RVOT) reoperations/reintervention (79, 48 and 21% at 5, 10 and 15 years) (P = 0.008) due to RVOT dysfunction and endocarditis. Event-free LVOTO survival in Group A at 5, 10 and 15 years amounted to 96, 91 and 91% and was similar to Group B with event-free LVOTO survival at 5, 10 and 15 years of 100, 88 and 88%, respectively. CONCLUSIONS: LV function is well preserved irrespective of the type of procedure. Patients who had undergone intraventricular rerouting (Group A) suffered from recurrent RVOT interventions due to RVOT dysfunction and endocarditis. The neurological outcome and the educational level were adequate for age in both groups. Executing the appropriate type of surgery for the individual patient's anatomy provides excellent functional and event-free outcome.

Off-pump coronary artery bypass prevents visceral organ damage.

OBJECTIVES: Visceral malperfusion after coronary artery bypass grafting (CABG) results in high morbidity and mortality. This study was designed to evaluate the effect of CABG performed by surgical techniques on visceral perfusion and function. METHODS: Pigs (n = 28) were studied in four groups: I. Sham; II. Off-pump coronary artery bypass grafting (OPCAB): 1 h stabilizer with 40 min intracoronary shunt; III. Extracorporeal circulation (ECC): 1 h ECC with 40 min aortic cross-clamping and cardioplegic arrest; IV. Impella: 1 h left ventricular blood-pump support and stabilizer with 40 min intracoronary shunt. A left internal mammary to left anterior descending coronary artery bypass was performed in Groups II-IV. All animals were observed for a further 240 min. During the experiment haemodynamics, creatinine clearance, intestinal fatty acid binding protein (iFABP), pancreatic (lipase and amylase) and liver enzymes (α-glutathione s-transferase, glutamate-oxaloacetate transaminase (GOT), gamma-glutamyl transferase (GGT), glutamate dehydrogenase and glutamate-pyruvate transaminase (GPT)) were measured. Visceral perfusion (VP) was assessed in both kidneys, intestine, pancreas, liver and spleen with 15 µm fluorescent microspheres. RESULTS: During OPCAB surgery, VP decreased slightly. Renal functional parameters, iFABP, pancreatic and liver enzymes remained unchanged. ECC and Impella led to significantly reduced renal, pancreatic and intestinal blood flow (P < 0.05). Creatinine clearance, pancreatic and liver (GPT, GGT) enzymes were significantly decreased only after ECC (P < 0.05). ECC and Impella resulted in a significantly increased iFABP level (P < 0.05). GOT was elevated significantly after surgery in Groups II, III and IV (P < 0.05). CONCLUSIONS: CABG with ECC or Impella leads to impaired visceral blood flow and function. OPCAB minimizes these procedure associated alterations.