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Biomedical subjects

R M Ungerleider

Publications and source records attributed to R M Ungerleider.

At least 19 recordsLinked to original sources
PubMed2001

Cryopreserved homografts in the pulmonary position: determinants of durability.

BACKGROUND: The cryopreserved homograft has emerged as the pulmonary conduit of choice for the repair of many congenital heart defects. It is also used for pulmonary valve replacement in the Ross procedure. Because of a wide range of patient ages and diagnoses, the risk of homograft failure may vary. METHODS: We reviewed 185 consecutive pulmonary position implants performed between September 1985 and January 1999. We examined three age groups: patients less than 1 year of age (n = 53), patients 1 to 10 years of age (n = 46), and patients more than 10 years of age (n = 86). RESULTS: Five-year Kaplan-Meier homograft survival was 25%, 61%, and 81% for the groups, respectively (p < 0.02). Smaller homograft size, younger patient age, and truncus arteriosus were risk factors for homograft failure in univariate analysis (p < 0.05). Smaller homograft size was the only predictor for homograft failure in multivariate analysis (p < 0.001). Twenty of 99 implants in patients less than 10 years old underwent transcatheter intervention. The 3-year Kaplan-Meier implant survival of this group (79%) was not different from those who did not undergo intervention (77%, p = 0.84). Survival of aortic and pulmonary homografts in patients less than 10 years of age was not different (p = 0.35). Ross procedure implants appear to have optimal survival (94%) at 5 years. Non-Ross implants in patients more than 10 years of age have 76% 5-year Kaplan-Meier survival, which is not different from Ross patients (p = 0.33). CONCLUSIONS: Small homografts have limited durability. Aortic homografts perform as well as pulmonary homografts in young patients. Once patients receive an "adult-size" homograft, at approximately 10 years of age, risk for implant failure approximates that of patients undergoing the Ross procedure. Transcatheter interventions, when indicated, may prolong homograft life.

Adolescent↗
PubMed2001

Intraoperative stents to rehabilitate severely stenotic pulmonary vessels.

BACKGROUND: Patch enlargement of severe branch pulmonary artery stenosis (PAS) or pulmonary vein ostial stenosis (PVS) can be technically challenging. Recurrences are common and exposure may require long periods of cardiopulmonary bypass (CPB). METHODS: Since 1993, we performed 31 procedures on 27 patients with endovascular stents placed intraoperatively under direct surgical vision: 22 patients with tight PAS and 5 patients with PVS. Selection for intraoperative (vs catheterization laboratory) stent placement was prompted by: (1) the need for a concomitant cardiac surgical procedure (16 cases); (2) limited vascular access for catheterization laboratory stent placement (11 cases); or (3) "rescue" of patients with complications after attempted placement of stents (4 cases). RESULTS: In this group of very complex and challenging patients there were 5 hospital deaths (hospital survival, 81%). Follow-up of survivors has ranged from 1 month to 7 years (mean 2.8 +/- 1.7 years). There have been 3 late deaths (late "series" survival, 70%). No complication or death was related to stent placement. Surviving patients have had significant clinical improvement. Mean pulmonary gradient (postoperative vs preoperative echo) has fallen in all survivors and has decreased from a mean of 66 mm Hg preoperatively to 28 mm Hg postoperatively (p = 0.01). All pulmonary arteries are appreciably enlarged and will be easier to deal with at a later date if necessary. One patient (DORV, HLHS ) with pulmonary vein stents has gone on to a successful Glenn procedure. The other two surviving patients with PV stents have occlusion of their proximal PVs on follow-up catheterization; thus only 1 of 5 patients with stents for PVS has had a successful outcome. Four patients have had repeat surgery. Stents have produced no impediment to subsequent surgical procedures, and the pulmonary arteries were easy to work with. CONCLUSIONS: Intraoperative stenting provides an attractive option for "rehabilitation" of pulmonary vessels. Direct vision insertion on CPB is extremely quick and immediately effective, limiting the CPB exposure required to treat this problem. Once stented, vessels remain open and are amenable to future surgical intervention as necessary. Outcome is better for patients with PAS versus those with PVS.

Adolescent↗
PubMed2001

Use of ECMO without the oxygenator to provide ventricular support after Norwood Stage I procedures.

Extracorporeal membrane oxygenation (ECMO) has been found effective in supporting infants with severe cardiac dysfunction following open heart surgery. Centers using this mode of support can also, in instances of single ventricle morphology, consider the option of eliminating the oxygenator from the standard ECMO set-up and thereby provide roller pump ventricular assist. In these cases, the infant's own lungs can provide excellent oxygenation simply by leaving the aortopulmonary shunt open. Since ventricular support ensures maintenance of normal cardiac output, manipulation of pulmonary versus systemic flows is not necessary. This configuration retains the safety features of the ECMO system and is easily staffed by the ECMO support personnel. There may be several benefits to employing this type of management.

Cardiopulmonary Bypass↗
PubMed2000

Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection.

The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation. Thymic transplantation was done without immunosuppression, using postnatal HLA-unmatched cultured allogeneic thymus tissue. Patients were immunized every 6 months with the neoantigen keyhole limpet hemocyanin (KLH) and the recall antigen tetanus toxoid (TT). T cell phenotype and function and T cell receptor rearrangement excision circles (TRECs) were assessed. Thymic allografts were biopsied at 2 months. Six HIV-infected patients completed the study. Four patients received cultured allogeneic postnatal thymic grafts, two others were controls. CD4+ T cell counts increased and T cell-proliferative responses to Candida antigen and TT normalized in all patients. Proliferative responses to KLH developed in three of four transplant recipients and one of two controls. Patients responding to KLH after secondary immunization had greater TREC increases compared with the patients who did not respond. All thymic allografts were rejected within 2 months. In summary, four of six patients developed T cell-proliferative responses to the neoantigen KLH over the first 2 years of HAART. The transplanted thymus tissue, however, was rejected. There was no clear difference in restoration of T cell function in the transplant recipients compared with the controls. Increases in TRECs after initiation of HAART may correlate with improved immune function.

Adult↗
PubMed2000

Soluble complement receptor-1 protects heart, lung, and cardiac myofilament function from cardiopulmonary bypass damage.

BACKGROUND: Host defense system activation occurs with cardiopulmonary bypass (CPB) and is thought to contribute to the pathophysiological consequences of CPB. Complement inhibition effects on the post-CPB syndrome were tested with soluble complement receptor-1 (sCR1). METHODS AND RESULTS: Twenty neonatal pigs (weight 1.8 to 2.8 kg) were randomized to control and sCR1-treated groups. LV pressure and volume, left atrial pressure, pulmonary artery pressure and flow, and respiratory system compliance and resistance were measured. Preload recruitable stroke work, isovolumic diastolic relaxation time constant (tau), and pulmonary vascular resistance were determined. Pre-CPB measures were not statistically significantly different between the 2 groups. After CPB, preload recruitable stroke work was significantly higher in the sCR1 group (n=5, 46.8+/-3.2x10(3) vs n=6, 34.3+/-3.7x10(3) erg/cm(3), P=0.042); tau was significantly lower in the sCR1 group (26.4+/-1.5, 42.4+/-6. 6 ms, P=0.003); pulmonary vascular resistance was significantly lower in the sCR1 group (5860+/-1360 vs 12 170+/-1200 dyn. s/cm(5), P=0.009); arterial PO(2) in 100% FIO(2) was significantly higher in the sCR1 group (406+/-63 vs 148+/-33 mm Hg, P=0.01); lung compliance and airway resistance did not differ significantly. The post-CPB Hill coefficient of atrial myocardium was higher in the sCR1 group (2.88+/-0.29 vs 1.88+/-0.16, P=0.023). CONCLUSIONS: sCR1 meaningfully moderates the post-CPB syndrome, supporting the hypothesis that complement activation contributes to this syndrome.

Actin Cytoskeleton↗
PubMed2000

Extracorporeal membrane oxygenation for infant postcardiotomy support: significance of shunt management.

BACKGROUND: After repair of complex congenital heart defects in infants and children, postcardiotomy cardiac failure requiring temporary circulatory support can occur. This is usually accomplished with the use of extracorporeal membrane oxygenation (ECMO). ECMO management of patients with single-ventricle physiology and aorto-pulmonary shunts can be particularly challenging. We retrospectively reviewed our experience with postcardiotomy support with particular attention to those children with single-ventricle palliation. METHODS: Thirty-five consecutive children (age 1 to 820 days, median 19 days) out of 1,020 patients (3.4%) required mechanical support (ECMO) after repair of congenital cardiac lesions from February 1994 to April 1999. Twenty-five patients underwent two ventricle repairs and 10 patients had single-ventricle palliation. Various parameters analyzed included strategies of shunt management, presence of presupport cardiac arrest, and timing of support initiation. RESULTS: Overall hospital survival for these 35 patients was 61%. There were four additional late deaths. Hospital survival was the same for those patients in whom support was initiated for failure to wean from cardiopulmonary bypass in the operating room versus those patients in whom support was initiated after successful separation from cardiopulmonary bypass (6 of 10 vs 15 of 25 or 60% survival). In those patients with shunt-dependent pulmonary circulation, survival was significantly improved in those patients in which the aorto-pulmonary shunt was left open (4 of 5 with open shunt vs 0 of 4 with occluded shunt (p = 0.048). CONCLUSIONS: The ability to readily implement postcardiotomy support is vital to the management of children with complex congenital cardiac disease. Overall survival can be quite satisfactory if support is employed in a rational and expedient manner. In patients with single-ventricle physiology and aorto-pulmonary shunts, leaving the shunt open during the period of support can result in markedly improved outcomes.

Cardiac Surgical Procedures↗
PubMed2000

Congenital Heart Surgery Nomenclature and Database Project: pulmonary venous anomalies.

The extant nomenclature for pulmonary venous anomalies is reviewed for the purpose of establishing a unified reporting system. The subject was debated and reviewed by members of the STS-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. All efforts were made to include all relevant nomenclature categories using synonyms where appropriate. The basis for classification are the prenatal errors of embryologic development. The major categories include: partially anomalous pulmonary venous connection, totally anomalous pulmonary venous connection, atresia of the common pulmonary vein, cor triatriatum, and stenosis or abnormal number of pulmonary veins. A comprehensive database set is presented that is based on a hierarchical scheme. Data are entered at various levels of complexity and detail that can be determined by the clinician. These data can lay the foundation for comprehensive risk stratification analyses. A minimum database set is also presented that will allow for data sharing and would lend itself to basic interpretation of trends. Potential diagnostic-related risk factors are presented.

Databases, Factual↗
PubMed2000

Congenital Heart Surgery Nomenclature and Database Project: transposition of the great arteries.

The extant nomenclature for transposition of the great arteries (TGA) is reviewed for the purposes of establishing a unified reporting system. The subject was debated and reviewed by members of the STS-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. All efforts were made to include relevant nomenclature categories including synonyms where appropriate. The general categories of TGA are: TGA with intact ventricular septum, TGA with ventricular septal defect (VSD) and TGA with VSD and left ventricular outflow tract obstruction (LVOTO). A comprehensive database set is presented which is based on a hierarchical scheme. Data are entered at various levels of complexity and detail that can be determined by the clinician. A detailed hierarchical system is described herein for classification of the coronary artery anatomy associated with TGA. These data can lay the foundation for comprehensive risk stratification analyses. A minimum database set is also presented which will allow for data sharing and would lend itself to basic interpretation of trends.

Databases, Factual↗
PubMed2000

The free radical spin trap alpha-phenyl-tert-butyl nitrone attenuates the cerebral response to deep hypothermic ischemia.

OBJECTIVE: The aim of this study was to assess the role of reactive oxygen species in the impairment of cerebral recovery that follows deep hypothermic circulatory arrest. METHODS: Twelve 1-week-old piglets were randomized to placebo (control group; n = 6) or 100 mg x kg(-1) intravenous alpha-phenyl-tert -butyl nitrone, a free radical spin trap (PBN group; n = 6). All piglets underwent cardiopulmonary bypass, cooling to 18 degrees C, 60 minutes of circulatory arrest followed by 60 minutes of reperfusion, and rewarming. Cerebral blood flow and metabolism were determined at baseline before deep hypothermic circulatory arrest and after 60 minutes of reperfusion. RESULTS: In control animals, mean global cerebral blood flow (+/- 1 standard error) before circulatory arrest was 48.4 +/- 3.6 mL x 100 g(-1) x min(-1) and fell to 25.1 +/- 3.6 mL x 100 g(-1) x min(-1) after circulatory arrest (P =.001). Global cerebral metabolism fell from 3.5 +/- 0.2 mL x 100 g(-1) x min(-1) before arrest to 2.2 +/- 0.2 mL x 100 g(-1) x min(-1) after circulatory arrest (P =.0002). In the PBN group after circulatory arrest, the mean global cerebral blood flow and metabolism of 37.2 +/- 4.9 and 3.6 +/- 0.5 mL. 100 g(-1). min(-1), respectively, were significantly higher than in the control group (P <.05). Recovery of cerebral blood flow in the PBN group was 78% of pre-arrest level compared with 52% in the control group (P =.002). Global cerebral metabolism after circulatory arrest was 100% of the pre-arrest value compared with 61% in the control group (P =.01). Regional recovery of cerebral metabolism in the cerebellum, brain stem, and basal ganglia was 131%, 130%, and 115%, respectively, of pre-arrest values in the PBN group compared with 85%, 78%, and 70% in the control group (P <.04). CONCLUSIONS: Reactive oxygen species contribute to the impairment of cerebral recovery that follows deep hypothermic circulatory arrest. The use of alpha-phenyl-tert -butyl nitrone before the arrest period attenuates the normal response to ischemia and improves recovery by affording protection from free radical-mediated damage.

Animals↗
PubMed2000

Radiofrequency catheter ablation of supraventricular tachycardia substrates after mustard and senning operations for d-transposition of the great arteries.

OBJECTIVES: The purpose of this study was to determine the efficacy and risks of radiofrequency ablation of various forms of supraventricular tachycardia after Mustard and Senning operations for d-transposition of the great arteries. BACKGROUND: In this patient group, the reported success rate of catheter ablation of intraatrial reentry tachycardia is about 70% with a negligible complication rate. There are no reports of the use of radiofrequency ablation to treat other types of supraventricular tachycardia. METHODS: Standard diagnostic criteria were used to determine supraventricular tachycardia type. Appropriate sites for attempted ablation included 1) intraatrial reentry tachycardia: presence of concealed entrainment with a postpacing interval similar to tachycardia cycle length; 2) focal atrial tachycardia: a P-A interval < or =-20 ms; and 3) typical variety of atrioventricular (AV) node reentry tachycardia: combined electrographic and radiographic features. RESULTS: Nine Mustard and two Senning patients underwent 13 studies to successfully ablate all supraventricular tachycardia substrates in eight (73%) patients. Eight of eleven (73%) patients having intraatrial reentry tachycardia, 3/3 having typical AV node reentry tachycardia, and 2/2 having focal atrial reentry tachycardia were successfully ablated. Among five patients having intraatrial reentry tachycardia (IART) and not having ventriculoatrial (V-A) conduction, two suffered high-grade AV block when ablation of the systemic venous portion of the medial tricuspid valve/inferior vena cava isthmus was attempted. CONCLUSIONS: Radiofrequency catheter ablation can be effectively and safely performed for certain supraventricular tachycardia types in addition to intraatrial reentry. A novel catheter course is required for slow pathway modification. High-grade AV block is a potential risk of lesions placed in the systemic venous medial isthmus.

Adolescent↗
PubMed2000

Preoperative high dose methylprednisolone attenuates the cerebral response to deep hypothermic circulatory arrest.

OBJECTIVE: The aim of this study was to assess the effects of preoperative high dose methylprednisolone on cerebral recovery following a period of deep hypothermic circulatory arrest (DHCA). METHODS: Sixteen 1-week-old piglets were randomized to placebo (n=8), or 30 mg/kg intramuscular methylprednisolone sodium succinate (MPRED) given at 8 and 2 h before induction of anaesthesia. All piglets underwent cardiopulmonary bypass, cooling to 18 degrees C, 60 min of circulatory arrest followed by 60 min of reperfusion and rewarming. The radiolabelled microsphere method was used to determine the global and regional cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) at baseline before DHCA and after 60 min of reperfusion. RESULTS: In controls, mean global CBF (+/-1 standard error) before DHCA was 53.7+/-2.4 ml/100 g per min and fell to 23.8+/-1.2 ml/100 g per min following DHCA (P<0.0001). This represents a post-DHCA recovery to 45.1+/-3.3% of the pre-DHCA value. In the MPRED group recovery of global CBF post-DHCA was significantly higher at 63.6+/-5.2% of the pre-DHCA value (P=0.009). The regional recovery of CBF in the cerebellum, brainstem and basal ganglia was 80, 75 and 69% of pre-DHCA values in the MPRED group respectively compared to 66, 60 and 55% in controls (P<0.05). Global CMRO(2) in controls fell from 3.9+/-0.2 ml/100 g per min before to 2. 3+/-0.2 ml/100 g per min after DHCA (P=0.0001). This represents a post-DHCA recovery to 58.6+/-4.4% of the pre-DHCA value. In the MPRED group, however, recovery of global CMRO(2) post-DHCA was significantly higher at 77.9+/-7.1% of the pre-DHCA value (P=0.04). CONCLUSIONS: Treatment with high dose methylprednisolone at 8 and 2 h preoperatively attenuates the normal cerebral response to a period of deep hypothermic ischaemia. This technique may therefore offer a safe and inexpensive strategy for cerebral protection during repair of congenital heart defects with the use of DHCA.

Animals↗
PubMed2000

The effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest.

OBJECTIVE: The purpose of this study was to determine the effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest. METHODS: Sixteen 1-week-old piglets underwent cardiopulmonary bypass, were cooled to 18 degrees C, and underwent 60 minutes of circulatory arrest, followed by 60 minutes of reperfusion and rewarming. Global and regional cerebral blood flow, cerebral oxygen metabolism, and renal blood flow were determined before cardiopulmonary bypass, after the institution of cardiopulmonary bypass, and at 1 hour of deep hypothermic circulatory arrest. In the study group (n = 8 piglets), a leukocyte-depleting arterial blood filter was placed in the arterial side of the cardiopulmonary bypass circuit. RESULTS: With cardiopulmonary bypass, no detectable change occurred in the cerebral blood flow, cerebral oxygen metabolism, and renal blood flow in either group, compared with before cardiopulmonary bypass. In control animals, after deep hypothermic circulatory arrest, blood flow was reduced to all regions of the brain (P <.004) and the kidneys (P =.02), compared with before deep hypothermic circulatory arrest. Cerebral oxygen metabolism was also significantly reduced to 60.1% +/- 11.3% of the value before deep hypothermic circulatory arrest (P =.001). In the leukocyte-depleting filter group, the regional cerebral blood flow after deep hypothermic circulatory arrest was reduced, compared with the value before deep hypothermic circulatory arrest (P <.01). Percentage recovery of cerebral blood flow was higher in the leukocyte filter group than in the control animals in all regions but not significantly so (P >.1). The cerebral oxygen metabolism fell to 66.0% +/- 22.3% of the level before deep hypothermic circulatory arrest, which was greater than the recovery in the control animals but not significantly so (P =.5). After deep hypothermic circulatory arrest, the renal blood flow fell to 81.0% +/- 29.5% of the value before deep hypothermic circulatory arrest (P =.06). Improvement in renal blood flow in the leukocyte filter group was not significantly greater than the recovery to 70.2% +/- 26.3% in control animals (P =.47). CONCLUSIONS: After a period of deep hypothermic circulatory arrest, there is a significant reduction in cerebral blood flow, cerebral oxygen metabolism, and renal blood flow. Leukocyte depletion with an in-line arterial filter does not appear to significantly improve these findings in the neonatal piglet.

Animals↗
PubMed2000

Right ventricular injury in young swine: effects of catecholamines on right ventricular function and pulmonary vascular mechanics.

Acute right ventricular (RV) injury is commonly encountered in infants and children after cardiac surgery. Empiric medical therapy for these patients results from a paucity of data on which to base medical management and the absence of animal models that allow rigorous laboratory testing. Specifically, exogenous catecholamines have unclear effects on the injured right ventricle and pulmonary vasculature in the young. Ten anesthetized piglets (9-12 kg) were instrumented with epicardial transducers, micromanometers, and a pulmonary artery flow probe. RV injury was induced with a cryoablation probe. Dopamine at 10 microg/kg/min, dobutamine at 10 microg/kg/min, and epinephrine (EP) at 0.1 microg/kg/min were infused in a random order. RV contractility was evaluated using preload recruitable stroke work. Diastolic function was described by the end-diastolic pressure-volume relation, peak negative derivative of the pressure waveform, and peak filling rate. In addition to routine hemodynamic measurements, Fourier transformation of the pressure and flow waveforms allowed calculation of input resistance, characteristic impedance, RV total hydraulic power, and transpulmonary vascular efficiency. Cryoablation led to a stable reproducible injury, decreased preload recruitable stroke work, and impaired diastolic function as measured by all three indices. Infusion of each catecholamine improved preload recruitable stroke work and peak negative derivative of the pressure waveform. Dobutamine and EP both decreased indices of pulmonary vascular impedance, whereas EP was the only inotrope that significantly improved transpulmonary vascular efficiency. Although all three inotropes improved systolic and diastolic RV function, only EP decreased input resistance, decreased pulmonary vascular resistance, and increased transpulmonary vascular efficiency.

Animals↗
PubMed1999

Effects of ischemia on pulmonary dysfunction after cardiopulmonary bypass.

BACKGROUND: Pulmonary hypertension and lung injury secondary to cardiopulmonary bypass (CPB) are probably caused by a combination of ischemia and inflammation. This study was undertaken to investigate the potential ischemic effects of cessation of pulmonary arterial flow during CPB on pulmonary injury. METHODS: Twenty neonatal piglets (2.5 to 3.1 kg) were randomly assigned to two groups. Group A (n = 10) underwent 90 minutes of CPB at full flow (100 mL x kg(-1) x min(-1)) and clamping of the main pulmonary artery (PA). Group B (n = 10) underwent 90 minutes of partial CPB (66 mL x kg(-1) x min(-1)) with continued mechanical ventilation and without clamping of the PA. All hearts were instrumented with micromanometers and a PA ultrasonic flow probe. Endothelial function was assessed by measuring endothelial-dependent relaxation (measured by change in pulmonary vascular resistance after PA infusion of acetylcholine) and endothelial-independent relaxation (measured by change in pulmonary vascular resistance after ventilator infusion of nitric oxide and PA infusion of sodium nitroprusside). RESULTS: All groups exhibited signs of pulmonary injury after CPB as evidenced by significantly increased pulmonary vascular resistance, increased alveolar-arterial O2 gradients, and decreased pulmonary compliance (p<0.05); however, pulmonary injury was significantly worse in group A (p<0.05). CONCLUSIONS: This study suggests that although exposure to CPB alone is enough to cause pulmonary injury, cessation of PA flow during CPB contributes significantly to this pulmonary dysfunction.

Acetylcholine↗
PubMed1999

Intermittent perfusion protects the brain during deep hypothermic circulatory arrest.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) has been shown to cause impairment in recovery of cerebral blood flow (CBF) and cerebral metabolism (CMRO2) proportional to the duration of the DHCA period. This effect on CMRO2 may be a marker for brain injury, because CMRO2 recovers normally after cardiopulmonary bypass (CPB) when DHCA is not used. The aim of this study was to investigate the effects of intermittent perfusion during DHCA on the recovery of CMRO2 after CPB and to correlate these findings with electron microscopy (EM) of the cerebral microcirculatory bed. METHODS: Fifteen neonatal piglets were placed on CPB and cooled to 18 degrees C. Each animal then underwent either: (1) 60 minute continuous CPB (control), (2) 60 minute uninterrupted DHCA (UI-DHCA), or (3) 60 minute DHCA with intermittent perfusion (1 minute every 15 minutes) (I-DHCA). All animals were then rewarmed and weaned from CPB. Measurements of CBF and CMRO2 were taken before and after CPB. A further 9 animals underwent CPB without DHCA (2 animals) or with DHCA (7 animals), under various conditions of arterial blood gas management, intermittent perfusion, and reperfusion time. RESULTS: UI-DHCA resulted in significant impairment to recovery of CMRO2 after CPB (p < 0.05). Regardless of the blood gas strategy used, the EM after UI-DHCA revealed extensive damage characterized by perivascular intracellular and organelle edema, and vascular collapse. I-DHCA, on the other hand, produced a pattern of normal CMRO2 recovery identical to controls, and the EM was normal for both these groups. CONCLUSIONS: Intermittent perfusion during DHCA is clinically practical and results in normal cerebral metabolic and ultrastructural recovery. Furthermore, the correlation between brain structure and CMRO2 suggests that monitoring CMRO2 during the operation may be an outstanding way to investigate new strategies for neuroprotection designed to reduce cerebral damage in children undergoing correction of congenital cardiac defects.

Animals↗
PubMed1999

Infant cardiopulmonary bypass: a procoagulant state.

BACKGROUND: Procoagulant activity after cardiopulmonary bypass (CPB) in infants may predispose to thrombotic and bleeding complications. The induction of tissue factor and prothrombinase activity on endothelial cell membranes is a primary step in the activation of the extrinsic clotting cascade. The purpose of this study is to characterize the fibrinolytic and endothelial procoagulant state in infants undergoing congenital cardiac repairs with and without CPB. METHODS: Fourteen infants (aged 1 to 12 weeks) underwent repair of congenital cardiac defects. Two patients had closed procedures (controls) and 12 had open cardiac procedures. Serum samples were taken before and after CPB, 1, 4, and 24 hours after CPB. Tissue plasminogen activator, plasminogen activator inhibitor-1, interleukin-1beta, interleukin-6, plasma tissue factor, and factor V levels were measured. Human umbilical vein endothelial cell cultures were incubated with serum taken from the above time points and assayed for induction of tissue factor and prothrombinase activity. RESULTS: Control patients had no change from preoperative values in any of the parameters examined. In experimental patients, tissue plasminogen activator levels peaked at 1 hour after CPB and then decreased to normal by 24 hours. Plasminogen activator inhibitor-1 levels peaked at 4 hours after CPB and returned to baseline by 24 hours. The plasma of all patients had no intrinsic tissue factor activity. Induction of tissue factor activity on umbilical vein endothelial cells peaked immediately and again at 24 hours, whereas prothrombinase activity peaked early and stayed elevated. Serum factor V levels were significantly reduced after CPB, but returned to near baseline levels by 24 hours. CONCLUSIONS: Cardiopulmonary bypass is associated with derangement of the coagulation and fibrinolytic systems in infants. The serum of these patients promotes the induction of endothelial procoagulant activity, suggesting that there may be a hypercoagulable state in the postbypass period.

Blood Coagulation Factors↗