Global and regional cerebral blood flow in neonatal piglets undergoing pulsatile cardiopulmonary bypass with continuous perfusion at 25 degrees C and circulatory arrest at 18 degrees C.

To investigate the influence of hypothermic cardiopulmonary bypass (HCPB) at 25 degrees C and circulatory arrest at 18 degrees C on the global and regional cerebral blood flow (CBF) during pulsatile perfusion, we performed the following studies in a neonatal piglet model. Using a pediatric physiologic pulsatile pump, we subjected six piglets to deep hypothermic circulatory arrest (DHCA) and six other piglets to HCPB. The DHCA group underwent hypothermia for 25 min, DHCA for 60min, cold reperfusion for 10 min, and rewarming for 40 min. The HCPB group underwent 15 min of cooling, followed by 60 min of HCPB, 10min of cold reperfusion, and 30 min of rewarming. The following variables remained constant in both groups: pump flow (150 ml/kg/min), pump rate (150 bpm), and stroke volume (1 ml/kg). During the 60-min aortic crossclamp period, the temperature was kept at 18 degrees C for DHCA and at 25 degrees C for HCPB. The global and regional CBF (ml/100g/min) was assessed with radiolabeled microspheres. The CBF was 48% lower during deep hypothermia at 18degrees C (before DHCA) than during hypothermia at 25 degrees C (55.2 +/- 14.3ml/100g/min vs 106.4 +/- 19.7 ml/100 g/min; p < 0.05). After rewarming, the global CBF was 45% lower in the DHCA group than in the HCPB group 48.3 +/- 18.1 ml/100g/min vs (87 +/- 35.9ml/100g/min; p < 0.05). Fifteen minutes after the termination of CPB, the global CBF was only 25% lower in the DHCA group than in the HCPB group (42.2 +/- 20.7 ml/100 g/min vs 56.4 +/- 25.8ml/100g/min; p = NS). In the right and left hemispheres, cerebellum, basal ganglia, and brain stem, blood flow resembled the global CBF. In conclusion, both HCPB and DHCA significantly decrease the regional and global CBF during CPB. Unlike HCPB, DHCA has a continued negative impact on the CBF after rewarming. However, 15 min after the end of CPB, there are no significant intergroup differences in the CBF.

Monitoring regional cerebral oxygen saturation using near-infrared spectroscopy during pulsatile hypothermic cardiopulmonary bypass in a neonatal piglet model.

Impairment of cerebral oxygenation in neonates and infants after hypothermic nonpulsatile cardiopulmonary bypass (CPB) support is well documented. The objectives of this study were: 1) using a neonatal piglet model to continuously monitor the regional cerebral oxygen saturation (rSO2) by near-infrared spectroscopy during pulsatile hypothermic CPB; and 2) to quantify the pulsatile flow in terms of energy equivalent pressure (EEP). After initiation of CPB, all piglets (n = 5) were subjected to 15 minutes of core cooling, reducing the rectal temperature to 25 degrees C, followed by 60 minutes of hypothermic CPB, then 10 minutes of cold reperfusion, and 30 minutes of rewarming. During CPB, mean arterial pressures (MAPs) and pump flow rates were maintained at 40-45 mm Hg and 150 ml/kg/min, respectively. During normothermic CPB, the rSO2 was significantly increased, compared with the pre-CPB level (56.8 +/- 5.2% vs. 41.8 +/- 5.5%, p < 0.01). At the end of cooling, the rSO2 level was 76.8 +/- 8.6% (p < 0.001 vs. pre-CPB). After 60 minutes of hypothermic CPB and 30 minutes of rewarming, the rSO2 level was decreased to 38.6 +/- 4.2%, which was not significantly different compared with the pre-CPB level. The average increase in pressure (from MAP to EEP) was 5 +/- 1%, and the average increase in extracorporeal circuit pressure (from ECCP to EEP) was 13 +/- 2%. This extra pressure may help to provide better regional cerebral oxygen saturation. During pulsatile CPB, there was no rSO2 deficiency in this high flow model. Near-infrared spectroscopy responded well to changes in rSO2 during different stages of these experiments and might be a helpful tool for intraoperative monitoring.

[New antithrombotic therapy approaches in coronary heart disease--prospects for gene therapy]. / Neue antithrombotische Therapieansätze bei koronarer Herzerkrankung--Perspektiven einer Gentherapie.

Despite considerable progress, pharmacological therapies have not provided a complete solution for common cardiovascular problems, including recurrent thrombosis, restenosis, and vein graft deterioration. Optimal drug dosage, reproducing plasma concentrations achieved in animal studies establishing proof-of-principle, would often be too toxic to administer. Local gene therapy aims at overexpressing proteins that regulate the cell cycle of vascular smooth muscle cells, inhibit vascular smooth muscle cell migration, endow the endothelium with enhanced vasoprotective properties. Alternatively, some approaches tend to suppress gene expression of proteins believed to promote vascular smooth muscle cell proliferation and migration. In sharp contrast to drug treatments, local gene therapy limits expression of the beneficial agent to the injured vascular site, where it can extend the presence of this agent to weeks and, with some gene vectors, to many months. This review summarizes and discusses antithrombotic gene therapy approaches for the prevention of restenosis and late thrombosis after catheter-based revascularizations.

Simultaneous carotid and coronary artery surgery: indications and perioperative outcome.

BACKGROUND: A significant number of patients with coronary artery disease is diagnosed with additional carotid artery disease. This subset of patients has been identified as a high-risk group for cardiac and cerebral complications following surgical intervention. METHODS: In a retrospective analysis we investigated the perioperative outcome of combined single-stage carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in 63 patients operated between January 1989 and August 1998. In all of these patients, CEA was performed prior to CABG and before initiation of cardiopulmonary bypass. RESULTS: Perioperative mortality rate was 7.9% (5/63) for simultaneous CEA and CABG and was due to cardiac complications in all patients. Postoperative unilateral neurological symptoms were diagnosed in 1 patient (1.7%) and were completely reversible. No neurologic events suggestive for permanent cerebral damage were observed during the 30 d postoperative period. CONCLUSIONS: In our study combined single-stage CEA and CABG was associated with low cerebral morbidity and patient outcome was mainly determined by cardiac complications. In this subset of patients, simultaneous CEA and CABG appears to be a safe method.

Atrial fibrillatory electrogram measurement allows atrial lead placement in patients who develop atrial fibrillation during permanent dual chamber pacemaker implantation.

The benefit of DDD(R) pacing is proven even in patients with intermittent atrial fibrillation. Atrial fibrillation developing during dual chamber pacemaker implantation creates a difficult problem. Maneuvers to reestablish a stable atrial rhythm often are required if atrial fibrillation sets in. This study was performed to determine if atrial lead placement can be performed with acceptable long-term results in the presence of atrial fibrillation. Twenty-one patients in whom atrial fibrillation developed during permanent pacemaker implantation were included in this study. In 12 patients, episodes of intermittent atrial fibrillation had been documented before the procedure. Screw-in leads were used in 15 patients and J-shaped passive fixation leads in 6 patients. All leads were bipolar. The intraoperative atrial fibrillation electrogram amplitudes ranged from 0.9 to 3.2 mV (mean 1.8 +/- 0.6 mV). One patient required lead revision due to a high atrial pacing threshold after conversion to SR. One patient remained in atrial fibrillation at 3-month follow-up. The other 20 patients converted to SR, 11 of whom had intermittent atrial fibrillation with successful mode switch activation. P wave amplitudes were 2.8 +/- .6 mV (range 1.4 to 4.0 mV) after conversion to SR. The mean atrial pacing threshold was 1.1 +/- 0.5 V (range 0.5 to 3.5 V). Placement of atrial leads in patients who develop atrial fibrillation during pacemaker implantation is feasible; fibrillatory electrogram amplitudes showed a good correlation with the atrial signal after conversion to an organized atrial rhythm (r = 0.698). Acceptable atrial pacing thresholds can be expected as well.

Myocardial protection by pressure- and volume-controlled continuous hypothermic coronary perfusion in combination with Esmolol and nitroglycerine for correction of congenital heart defects in pediatric risk patients.

OBJECTIVE: This study assesses the technical applicability and the clinical value of the continuous coronary perfusion with oxygenated blood as a method for myocardial protection used for congenital heart surgery in pediatric risk patients. METHODS: Thirty non-consecutive pediatric risk patients aged from 1 month to 16 years (mean 3.9 years; 11/30 patients aged <6 months) underwent open heart procedures on the beating heart for simple and complex cardiac malformations using a self designed perfusion system with pressure- and volume-controlled continuous hypothermic coronary perfusion (PVC-CONTHY-CAP) in combination with ultra-short beta1-receptor blockade (Esmolol) and nitroglycerine for myocardial protection. The following procedures were done: VSD patch closure (n = 6), repair of total a-v canal with 'double patch' (n = 4), total repair of tetralogy of Fallot (n = 7), correction of truncus arteriosus communis type IV (n = 1), mitral valve reconstruction (n = 4), total cavo-pulmonary connection (n = 4), and Rastelli procedure (n = 4). RESULTS: The mean cardio-pulmonary bypass time was 131.5 min (range: 44-245 min), the mean coronary perfusion time: 90.1 min (range: 13-202 min). The weaning off extracorporeal circulation was uneventful in all patients, in 21 patients with low-dose and in nine patients with moderate catecholamine support: the mean weaning time was 25 min (range: 7 58 min). The post-operative mean peak creatine kinase (CK-MB) value was 58 U/l, (range: 14-202 U/l). The mean ICU stay in the cardiac surgery unit was 2.9 days, (range: 1-10 days). The mean post-operative mechanical ventilatory support was 2 days (range: 6 h-9 days). Six patients developed thrombocytopenia with values <40 tsd/microl, four patients renal dysfunction, two patients ascites, five patients heart rhythm disturbances, one patient neurological deficits. In three patients (VSD closure: n = 2; age: 1 and 2 months; total a-v-canal: n = 1; age: 3 months) re-do procedures for significant intraventricular shunt had to be done, in one patient implantation of a permanent pacemaker system was necessary. One patient died due to multiple organ failure after uneventful surgery (total cavo-pulmonary connection for single ventricle). CONCLUSIONS: PVC-CONTHY-CAP can be successfully used for repair of simple and complex congenital cardiac malformations. However, in children less than 3 months of age, the transatrial repair of intraventricular defects is technically much more demanding and challenging than under conventional cardioplegic arrest and is possibly accompanied by an increased incidence of residual or recurring intraventricular shunts.

Dynamic training of skeletal muscle ventricles. A method to increase muscular power for cardiac assistance.

BACKGROUND: Skeletal muscle can be used for cardiac assistance after electrical stimulation over a period of several weeks. This will adapt it to do chronic work with no resulting fatigue. The result of this procedure, however, is a reduction of 80% in muscle power, > 60% in muscle mass, and approximately 85% in contractile speed. To minimize these disadvantages, the following study was done to develop and test a method to dynamically train skeletal muscle ventricles (SMVs). METHODS AND RESULTS: Barrel-shaped SMVs were tested in 15 Jersey calves. They were made from the latissimus dorsi muscle, which was wrapped around an elastic silicone training device. Six SMVs were used extrathoracically in a single layer and nine intrathoracically in a double layer. With dynamic training preserving contractile speed, the output increased to approximately 5 L/min, the systolic pressure increased to > 200 mm Hg, and power developed to approximately 10 W after 3 months of dynamic training. The contractile speed of dynamically trained SMVs was between 250 and 700 mm/s. The diameter of the latissimus dorsi muscle increased to three times that of the corresponding contralateral muscle. CONCLUSIONS: The combination of electrical conditioning with dynamic training of the SMVs resulted in a strong muscle pump that did not develop fatigue. Dynamic training for skeletal muscle represents a new and promising method for providing powerful autologous cardiac assist.