Isoflurane preconditions myocardium against infarction via release of free radicals

BACKGROUND: Isoflurane exerts cardioprotective effects that mimic the ischemic preconditioning phenomenon. Generation of free radicals is implicated in ischemic preconditioning. The authors investigated whether isoflurane-induced preconditioning may involve release of free radicals. METHODS: Sixty-one alpha-chloralose-anesthetized rabbits were instrumented for measurement of left ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe), and myocardial infarct size (triphenyltetrazolium staining). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits of all six groups underwent a treatment period consisting of either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane inhalation (1 minimum alveolar concentration end-tidal concentration) followed by a 10-min washout period (isoflurane group, n = 12). Four additional groups received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg. kg-1.min-1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100 microg.kg-1.min-1) during the treatment period with (isoflurane + MPG; n = 11; isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11; MnTBAP, n = 7). RESULTS: Hemodynamic baseline values were not significantly different between groups (LV pressure, 97 +/- 17 mmHg [mean +/- SD]; cardiac output, 228 +/- 61 ml/min). During coronary artery occlusion, LV pressure was reduced to 91 +/- 17% of baseline and cardiac output to 94 +/- 21%. After 2 h of reperfusion, recovery of LV pressure and cardiac output was not significantly different between groups (LV pressure, 83 +/- 20%; cardiac output, 86 +/- 23% of baseline). Infarct size was reduced from 49 +/- 17% of the area at risk in controls to 29 +/- 19% in the isoflurane group (P = 0.04). MPG and MnTBAP themselves had no effect on infarct size (MPG, 50 +/- 14%; MnTBAP, 56 +/- 15%), but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50 +/- 24%, P = 0.02; isoflurane + MnTBAP, 55 +/- 10%, P = 0.001). CONCLUSION: Isoflurane-induced preconditioning depends on the release of free radicals.     

Factors influencing intensive care unit length of stay after surgery for acute aortic dissection type A

BACKGROUND: Operative mortality after acute aortic dissection type A is still high, and prolonged stay at the intensive care unit is common. Little has been documented about factors influencing the intensive care unit length of stay. The aim of this study was to determine such variables. METHODS: During a 10-year period, 67 patients (47 male, 20 female) were operated on for acute aortic dissection type A. In 42 patients (63%), an ascending aortic replacement was performed, 23 patients (34%) underwent a Bentall procedure, and 2 patients (3%) received a valve-sparing David type of operation. In 14 of these cases (20%), an additional partial or total arch replacement was performed. RESULTS: Hospital mortality was 9 of 67 (14%). Median postoperative intensive care unit length of stay was 5 days (range, 1 to 72 days). Intensive care unit stay was in univariate analysis significantly influenced by the following factors: age (p = 0.008), body mass index (p = 0.039), cardiopulmonary bypass time (p = 0.018), aortic cross-clamp time (p = 0.031), postoperative low cardiac output syndrome (p < 0.001), and postoperative lactate levels (p = 0.01). By multivariate analysis, age (p = 0.012), cardiopulmonary bypass time (p = 0.037), and the presence of a postoperative low cardiac output syndrome (p < 0.001) significantly influenced intensive care unit stay. CONCLUSIONS: Stay in the intensive care unit after operation for acute aortic dissection type A seems to be determined by age, cardiopulmonary bypass time, and the postoperative presence of a low cardiac output syndrome.     

Celsior versus custodiol: early postischemic recovery after cardioplegia and ischemia at 5 degrees C

BACKGROUND: The aim of this experimental study was to compare the protective efficacy of the cardioplegic solutions Celsior and Custodiol. Canine hearts were examined with regard to energy metabolism and early postischemic recovery after 8 or 12 hours of ischemia at 5 degrees C. METHODS: Canine hearts were preserved with Celsior or Custodiol (each n = 19). Five hearts of each group were used to determine myocardial content of energy-rich phosphates immediately after preservation and after 8 and 12 hours of ischemia at 5 degrees C; the remainder were reperfused after 8 and 12 hours of ischemia. Control variables during reperfusion were myocardial content of energy-rich phosphates, myocardial K+ uptake, left ventricular dP/dtmax and dP/dtmin, and incidence of arrhythmias in percentage of heart rate. RESULTS: Custodiol-preserved hearts contained more ATP than Celsior-preserved hearts after 8 and 12 hours of ischemia (8 hours p = ns, 12 hours, p < 0.05). During reperfusion after 8 hours of ischemia, dP/dtmax and dP/dtmin showed the same values for both solutions, after 12 hours values were significantly higher in Custodiol-preserved hearts (p < 0.005). The incidence of reperfusion arrhythmias was higher in hearts of the Celsior group (8 hours p < 0.01, 12 hours p = ns). Myocardial K+ uptake during reperfusion after 8 and 12 hours of ischemia was about twice as high in Celsior-preserved compared to Custodiol-preserved hearts (p < 0.005). CONCLUSIONS: In the Langendorff model of the canine heart, cardioplegia with Celsior showed no advantage over cardioplegia with Custodiol. Differences were observed, however, which may be clinically important, especially in the case of long cold-storage times.     

Does continuous mucosal partial carbon dioxide pressure measurement predict leakage of intrathoracic esophagogastrostomy?

BACKGROUND: Gastroplasty after esophagectomy is associated with relevant morbidity due to anastomotic leakage of the esophagogastrostomy. The aim of this study was to find out whether continuous partial carbon dioxide pressure (pCO2) measurement of the gastric mucosa is an adequate method of monitoring the gastric tube during the postoperative course and of detecting patients with an anastomotic leakage. METHODS: Forty-seven patients with esophageal cancer underwent esophagectomy and gastric tube formation with intrathoracic esophagogastrostomy. Postoperatively, mucosal pCO2 of the gastric tube (pCO2i) was measured using continuous tonometry (TONOCAP, Datex Ohmeda). pCO2i was related to the arterial pCO2 (delta pCO2 = pCO2i - pCO2a). RESULTS: A total of 4,338 delta pCO2 measurements were recorded. On average, the pCO2i of each patient was monitored over a period of 92 hours. In 5 patients an anastomotic leakage of the esophagogastrostomy developed. The mean delta pCO2 of this group was 31.7 mm Hg (+/-19.3 SD) and significantly higher (p < 0.0001) than that of patients without anastomotic leakage (20.7 mm Hg +/- 12.8 SD). With a delta pCO2 cut-off point of 56 mm Hg measured for 5 hours, the sensitivity was 0.8, the specificity 0.9, and the positive predictive value 0.5. In patients with anastomotic leakage, the peak delta pCO2 preceded clinical symptoms. False positive delta pCO2 measurements (n = 4) were mainly due to severe pneumonia with long-term ventilation. CONCLUSIONS: Mucosal pCO2 measurement of the gastric tube can be used as an early indicator of a complicated postoperative course predicting anastomotic leakage of the esophagogastrostomy.     

Valve-sparing aortic root reconstruction in patients with significant aortic insufficiency

BACKGROUND: To assess the feasibility and outcome of the valve-sparing aortic root reimplantation technique in patients with severe preoperative aortic insufficiency (AI). METHODS: Within 8 years we have operated on 158 patients with aneurysms of the ascending aorta using the reimplantation technique. We identified 83 patients with AI grade 3 or 4 (mean 3.1 +/- 0.4) preoperatively (study group). This cohort was compared with 71 patients with AI grade 2 or less (mean 1.3 +/- 0.9; control group) with regard to mortality, operative variables, complications, need for reoperation, postoperative AI, and clinical presentation during follow-up. RESULTS: Patient demographics were comparable in both groups. However, Marfan's syndrome (32% versus 13%, p = 0.006) and acute type A aortic dissection (20% versus 8.4%, p = 0.059) were more frequent in the control group. In addition, bypass (177 +/- 60 minutes versus 160 +/- 36 minutes, p = 0.022) and cross clamp times (133 +/- 34 minutes versus 124 +/- 27 minutes, p = 0.049) were significantly longer in controls. Mortality was low in the study group and comparable with controls (30-day, 3.6% versus 4.2%; during follow-up, 3.8% versus 5.9%; p = not significant [NS]). Reoperation rate was almost identical in both groups (3.8% versus 4.4%, p = NS). Mean grade of AI was significantly higher in the study group early postoperatively (0.31 +/- 0.46 versus 0.18 +/- 0.42, p = 0.049) but comparable at the last visit (0.43 +/- 0.58 versus 0.42 +/- 0.62, p = NS). During follow-up neither thromboembolic complications nor bleeding events were noted in either group. Clinical performance at the last visit revealed no significant difference between the groups. CONCLUSIONS: Preoperative severe aortic insufficiency does not impair the excellent outcome seen after a mean of 3 years of follow-up in patients undergoing the reimplantation technique for valve-sparing aortic root reconstruction.     

The impact of spinal angiography on the neurological outcome after surgery on the descending thoracic and thoracoabdominal aorta

BACKGROUND: Neurologic complications remain one of the major concerns in surgery on the descending thoracic and thoracoabdominal aorta. The impact of preoperative spinal angiography on postoperative neurologic outcome was assessed. METHODS: Between September 1993 and December 1999, 109 patients (mean age, 58.2 years; range, 24 to 77) underwent preoperative spinal angiography: 50 (45.9%) for aneurysm and 59 (54.1%) for chronic dissection. Sixty-one patients (56.0%) underwent replacement of the descending thoracic aorta whereas the thoracoabdominal aorta was replaced in 48 (44.0%) patients. All intercostal or lumbar arteries that had previously been visualized as the origin of the great radicular artery (GRA) were preserved. RESULTS: The origin of the GRA was located by spinal angiography in 65 of the 109 patients (59.6%). It was found between level T-5 and L-3 and on the left side in 75.4% (49 of 65) patients. In patients with aneurysms, it was identified less frequently (48%) compared with patients with chronic dissection (69.5%, p = 0.02). The overall operative mortality rate was 5.5% (6 of 109 patients). There were 7 patients (6.4%) with postoperative paraplegia. In 3 of them the origin of the GRA had been reimplanted. CONCLUSIONS: Even in patients with an identified and subsequently reimplanted GRA, postoperative paraplegia could not always be prevented. Spinal angiography has no impact on the neurologic outcome of thoracic and thoracoabdominal aortic replacement.     

Selective removal of circulating immune complexes from patient plasma

The principle of a patient-specific immunoadsorber (PsIA) is demonstrated. Studies with model systems (HSA/anti-HSA) on immobilization, stability, and leakage form the basis for the presented fast-performance liquid chromatography (FPLC) and batch experiments, which were conducted using two different protein A adsorbers and autologous and heterologous PsIA systems. Experiments to determine the binding capacity of protein A adsorbers and PsIAs are described. In all experiments, the adsorption of plasma IgG, total protein, and C1q and C3d circulating immune complexes were measured. Plasma of patients with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus) was investigated. Analysis was performed in both the initial plasma and the flow-through or supernatant. Results of the investigations using FPLC and batch experiments were compared. Autologous PsIA systems are suitable for the selective removal of elevated levels of circulating immune complexes in the plasma.     

Changes in lymphocytic cluster distribution during extracorporeal immunoadsorption

The success of apheresis treatment is often measured as a decrease in the detected antibodies and an improvement in different disease-related scores. Sometimes, however, the seriousness of the disease does not correlate with the antibody level. During a period of 8 years, 15 patients (3 myasthenia gravis, 1 multiple sclerosis, 2 systemic lupus erythematosus, 3 alloimmunized kidney transplant, 6 rheumatoid arthritis) were treated by protein A immunoadsorption. Lymphocyte subpopulations (activated T cells, cytolytic T cells, B cells, natural killer cells) and inflammatory proteins (ferritin, C-reactive protein, alpha1-antitrypsin, alpha2-macroglobulin) were analyzed. After observing clinical outcomes, the patients could be divided into 2 groups, respectively: Group 1, responding patients with remission of disease; and Group 2, delayed-responding patients, who required chronic treatment. Group 1 patients characteristically showed a greater increase in activated T and cytolytic T cells which correlated with a greater decrease of B cells. It might be possible that protein A immunoadsorption induced immunomodulation. Further immunological investigation is required to verify these findings.     

Development of cellulose-DNA immunoadsorbent

The aim of this study was to prepare a DNA immunoadsorbent for the specific, extracorporeal removal of anti-DNA antibodies from the blood of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Two kinds of cellulose beads were applied as a carrier. Calf thymus DNA was covalently coupled to the carrier using the epichlorohydrin method. Efforts were focused on optimization of conditions for activation and coupling, trying to couple as much DNA as possible to a certain amount of carrier. It was found that the activation level increased with the increase of NaOH concentration and the amount of epichlorohydrin used. The mole of epichlorohydrin must be in excess of that of NaOH because excess NaOH could react further with the epoxy groups in the beads resulting in a decrease of activation level. High activation level could be obtained in a medium of 3.0 M NaOH. The DNA coupling was found to be mainly temperature and pH dependent. Using 0.1 M Tris-HCl buffer, pH 8 at a temperature of 50-90 degrees C, more than 3 mg of DNA could be coupled to 1 ml of wet beads. Prolonging the coupling reaction under 50 degrees C to 72 h resulted in the same coupling capacity as that obtained under 90 degrees C. To evaluate the adsorption ability for anti-DNA of this immunoadsorbent, batch and circulation tests were applied using SLE patient plasma. The immunoadsorbents showed excellent adsorption capacity, especially the cellulose with smaller size (200-300 microm). The incubation of 20 ml of patient's plasma with 1 ml of adsorbent resulted in an 80% decline in the anti-DNA antibody level. In the circulation tests, 30 ml of plasma was circulated through a column containing 3 ml of adsorbent. The maximum decline in anti-DNA level, 80%, was obtained after 60 min. Such high adsorption capacity and high adsorption rate suggest this immunoadsorbent may be used for treatment. For comparison, 1,4-butanediol diglycidyl ether activation method and other DNA sources were tested with the same protocol.