Lamotrigine attenuates cortical glutamate release during global cerebral ischemia in pigs on cardiopulmonary bypass. (1/1874)

BACKGROUND: The dose-response effects of pretreatment with lamotrigine (a phenyltriazine derivative that inhibits neuronal glutamate release) in a porcine cerebral ischemia model during cardiopulmonary bypass were studied. METHODS: Sagittal sinus catheters and cortical microdialysis catheters were inserted into anesthetized pigs. Animals undergoing normothermic cardiopulmonary bypass were pretreated with lamotrigine 0, 10, 25, or 50 mg/kg (n = 10 per group). Fifteen minutes of global cerebral ischemia was produced, followed by 40 min of reperfusion and discontinuation of cardiopulmonary bypass. Cerebral oxygen metabolism was calculated using cerebral blood flow (radioactive microspheres) and arterial-venous oxygen content gradients. Concentrations of microdialysate glutamate and aspartate were quantified; electroencephalographic signals were recorded. After cardiopulmonary bypass, blood and cerebrospinal fluid were sampled for S-100B protein, and a biopsy was performed on the cerebral cortex for metabolic profile. RESULTS: Lamotrigine caused dose-dependent reductions in systemic vascular resistance so that additional fluid was required to maintain venous return. Concentrations of glutamate and aspartate did not change during reperfusion after 50 mg/kg lamotrigine in contrast to fivefold and twofold increases, respectively, with lower doses. There were no intergroup differences in cerebral metabolism, electroencephalographic scores, cortical metabolites, brain lactate, or S-100B protein concentrations in the cerebrospinal fluid and blood. CONCLUSIONS: Lamotrigine 50 mg/kg significantly attenuated excitatory neurotransmitter release during normothermic cerebral ischemia during cardiopulmonary bypass without improving other neurologic parameters. Lamotrigine caused arterial and venous dilation, which limits its clinical usefulness.  (+info)

Biventricular repair approach in ducto-dependent neonates with hypoplastic but morphologically normal left ventricle. (2/1874)

OBJECTIVES: Increased afterload and multilevel LV obstruction is constant. We assumed that restoration of normal loading conditions by relief of LV obstructions promotes its growth, provided that part of the cardiac output was preoperatively supported by the LV, whatever the echocardiographic indexes. BACKGROUND: Whether to perform uni- or biventricular repair in ducto dependent neonates with hypoplastic but morphologically normal LV (hypoplastic left heart syndrome classes II & III) remains unanswered. Echocardiographic criteria have been proposed for surgical decision. METHODS: Twenty ducto dependent neonates presented with this anomaly. All had aortic coarctation associated to multilevel LV obstruction. Preoperative echocardiographic assessment showed: mean EDLW of 12.4 +/- 3.03 ml/m2 and mean Rhodes score of -1.73 +/-0.8. Surgery consisted in relief of LV outflow tract obstruction by coarctation repair in all associated to aortic commissurotomy in one and ASD closure in 2. RESULTS: There were 3 early and 2 late deaths. Failure of biventricular repair and LV growth was obvious in patients with severe anatomic mitral stenosis. The other demonstrated growth of the left heart. At hospital discharge the EDLVV was 19.4+/-3.12 ml/m2 (p = 0.0001) and the Rhodes score was -0.38+/-1.01 (p = 0.0003). Actuarial survival and freedom from reoperation rates at 5 years were 72.5% and 46%, respectively. CONCLUSIONS: Biventricular repair can be proposed to ducto dependent neonates with hypoplastic but morphologically normal LV provided that all anatomical causes of LV obstruction can be relieved. Secondary growth of the left heart then occurs; however, the reoperation rate is high.  (+info)

Coronary sinus adrenomedullin rises in response to myocardial injury. (3/1874)

Human adrenomedullin (ADM), a peptide comprising 52 amino acids, is a circulating hormone with vasodilator properties. We have evaluated its release by the heart following ischaemic myocardial damage, as indicated by elevated levels of the cardiospecific protein troponin-T (Tn-T) during cardiopulmonary bypass. ADM (pg/ml) and Tn-T (ng/ml) were measured in coronary sinus blood before and after aortic cross-clamp and in venous blood 6 h after surgery in 22 coronary-bypass patients. Based on the pre- and post-clamp Tn-T levels in the coronary sinus, the patients were divided into group I (no change; n=10) and group II (two times increase; n=12). Baseline ADM (362.7+/-106.2 and 303+/-58.7 pg/ml in groups I and II respectively; means+/-S.D.) and Tn-T (0.66+/-0.14 and 0.57+/-0.13 ng/ml respectively) levels were similar in both groups. In group I, the post-clamp ADM (317.6+/-80.8 pg/ml) and Tn-T (0.68+/-0.15 ng/ml) levels did not change significantly. In group II, the post-clamp ADM levels rose significantly above the baseline, mimicking the change in Tn-T (ADM, 541.4+/-89.4 pg/ml; Tn-T, 1.37+/-0.31 ng/ml; P=0.009). After 6 h, the systemic Tn-T levels were similar in both groups (2. 09+/-0.44 and 1.95+/-0.52 ng/ml in groups I and II respectively). We suggest that: (1) minor degrees of myocardial ischaemic damage result in release of ADM by the heart, and (2) ADM may play a protective role in the myocardium during an ischaemic insult. This suggests a possible therapeutic role for ADM in the management of intra-operative myocardial ischaemia.  (+info)

Transitory cerebral microvascular blockade after cardiopulmonary bypass. (4/1874)

Dogs were submitted to cardiopulmonary bypass (CPB) carried out under conditions calculated to generate large numbers of microbubbles and microemboli. On the day following the procedure the dogs showed evidence of neurological damage including impaired consciousness and ataxia. These abnormalities largely cleared within a week. When the animals were sacrificed at intervals after the procedure, the cerebral microvasculature was demonstrated by injecting a suspension a lamp black into the carotid artery. This revealed that multiple filling defects were present in the microcirculation of the brain immmediately after CPB and for two days thereafter. However, by seven days the microvascular blockade had disappeared, and the vascular blockade had disappeared, and the vascular pattern of the brain had returned to normal. Neuropathological findings were sparse and restricted to the cerebellum. This study suggests that the transient neurological syndromes that sometimes follow cardiopulmonary bypass for heart surgery may be due to a transient microvascular blockade, perhaps by microbubbles and microparticles.  (+info)

A single dose of milrinone facilitates separation from cardiopulmonary bypass in patients with pre-existing left ventricular dysfunction. (5/1874)

Milrinone is used during cardiac surgery to facilitate separation from cardiopulmonary bypass (CPB) and/or to treat myocardial dysfunction in the post-bypass period. We have demonstrated, in patients with preoperative depression of systolic function undergoing aorto-coronary artery bypass surgery, sustained improvement in cardiac function after a single loading dose of milrinone 50 micrograms kg-1, administered at the end of bypass, thus significantly decreasing the need for beta-agonist therapy.  (+info)

Effect of cardiopulmonary bypass and heparin on plasma levels of Lp(a) and Apo(a) fragments. (6/1874)

Fragments of apolipoprotein(a) [apo(a)], the distinctive glycoprotein of lipoprotein(a) [Lp(a)], are present in human plasma and urine and have been implicated in the development of atherosclerosis. The mechanism responsible for the generation of apo(a) fragments in vivo is poorly understood. In this study, we examined the plasma levels of Lp(a) and apo(a) fragments [or free apo(a)] and urinary apo(a) in 15 subjects who underwent cardiac surgery necessitating cardiopulmonary bypass. We also measured the plasma concentration and activity of polymorphonuclear elastase, an Lp(a)-cleaving enzyme in vitro, and plasma levels of C-reactive protein. Despite a marked activation of polymorphonuclear cells and a pronounced inflammatory response, as documented by an 8-fold and a 35-fold increase in plasma levels of polymorphonuclear elastase and C-reactive protein, respectively, the proportion of plasma free apo(a) to Lp(a) and urinary excretion of apo(a) remained unchanged over a 7-day period after surgery, and polymorphonuclear elastase activity remained undetectable in plasma. No fragmentation of apo(a) was observed ex vivo in plasma samples collected before and after surgery. These data indicate that in this model, apo(a) is not fragmented in plasma and are consistent with the hypothesis that apo(a) fragments result from a constitutively active tissue mechanism that is not modified by cardiac surgery with cardiopulmonary bypass.  (+info)

Intraoperative cardiac troponin T release and lactate metabolism during coronary artery surgery: comparison of beating heart with conventional coronary artery surgery with cardiopulmonary bypass. (7/1874)

OBJECTIVE: To compare cardiac troponin T release and lactate metabolism in coronary sinus and arterial blood during uncomplicated coronary grafting on the beating heart with conventional coronary grafting using cardiopulmonary bypass. DESIGN: A prospective observational study with simultaneous sampling of coronary sinus and arterial blood: before and 1, 4, 10, and 20 minutes after reperfusion for analysis of cardiac troponin T and lactate. Cardiac troponin T was also analysed in venous samples taken 3, 6, 24, 48, and 72 hours after surgery. SETTING: Cardiac surgical unit in a tertiary referral centre. PATIENTS: 18 patients undergoing coronary grafting on the beating heart (10 single vessel and eight two-vessel grafting) and eight undergoing two-vessel grafting with cardiopulmonary bypass. RESULTS: Cardiac troponin T was detected in coronary sinus blood in all patients by 20 minutes after beating heart coronary artery surgery before arterial concentrations were consistently increased. Peak arterial and coronary sinus cardiac troponin T values on the beating heart during single (0.03 (0 to 0. 05) and 0.09 (0.07 to 0.16 microg/l, respectively) and two-vessel grafting (0.1 (0.07 to 0.11) and 0.19 (0.14 to 0.25) microg/l) were lower than the values obtained during cardiopulmonary bypass (0.64 (0.52 to 0.72) and 1.4 (0.9 to 2.0) microg/l) (p < 0.05). The area under the curve of venous cardiac troponin T over 72 hours for two-vessel grafting on the beating heart was less than with cardiopulmonary bypass (13 (10 to 16) v 68 (26 to 102) microg.h/l) (p < 0.001). Lactate extraction began within one minute of snare release during beating heart coronary surgery while lactate was still being produced 20 minutes after cross clamp release following cardiopulmonary bypass. CONCLUSIONS: Lower intraoperative and serial venous cardiac troponin T concentrations suggest a lesser degree of myocyte injury during beating heart coronary artery surgery than during cardiopulmonary bypass. Oxidative metabolism also recovers more rapidly with beating heart coronary artery surgery than with conventional coronary grafting. Coronary sinus cardiac troponin T concentrations increased earlier and were greater than arterial concentrations during beating heart surgery, suggesting that this may be a more sensitive method of intraoperative assessment of myocardial injury.  (+info)

Urgent homograft aortic root replacement for aortic root abscess in infants and children. (8/1874)

OBJECTIVE: To assess the results of early homograft aortic root replacement in infants and children with an aortic root abscess. DESIGN: Descriptive study of all patients with an aortic root abscess during 1987-97, identified by retrospective review of the echocardiographic and surgical registries. SETTING: A tertiary referral centre. PATIENTS: Five patients (age 0.6 to 13 years; two female) were identified with an aortic root abscess. Four had no known pre-existing congenital heart abnormality. Three had a misleading presentation and were referred to our hospital with non-cardiac diagnoses (fulminant hepatic failure; adult respiratory distress syndrome; cerebrovascular accident). The other two presented with septicaemia and a murmur, respectively. Blood cultures identified Staphylococcus aureus (n = 3) and Streptococcus pneumoniae (n = 2). Aortic root abscess was diagnosed by transthoracic echocardiography. INTERVENTIONS: Homograft aortic root replacement with coronary reimplantation was performed urgently (median one day after diagnosis). RESULTS: Four patients survived. The youngest died following multiorgan failure, multiple aortic fistulae, three valve involvement, and extensive tissue destruction preventing mitral valve replacement (S pneumoniae). Two of the four survivors have required further surgery: mitral valve replacement (0.3 years later), and pulmonary autograft replacement of the homograft (8.3 years later). All survivors remain in sinus rhythm and New York Heart Association functional class I. CONCLUSIONS: Infective endocarditis should be considered in any child with severe septicaemia or embolic phenomena. Echocardiographic diagnosis of an aortic root abscess indicates uncontrolled infection and impending haemodynamic collapse. Homograft aortic root replacement can be performed successfully in critically ill children with active infection.  (+info)