Early leaf senescence is associated with an altered cellular redox balance in Arabidopsis cpr5/old1 mutants.

Reactive oxygen species (ROS) are the inevitable by-products of essential cellular metabolic and physiological activities. Plants have developed sophisticated gene networks of ROS generation and scavenging systems. However, ROS regulation is still poorly understood. Here, we report that mutations in the Arabidopsis CPR5/OLD1 gene may cause early senescence through deregulation of the cellular redox balance. Genetic analysis showed that blocking stress-related hormonal signalling pathways, such as ethylene, salicylic acid, jasmonic acid, abscisic acid and sugar, did not affect premature cell death and leaf senescence. We took a bioinformatics approach and analysed publicly available transcriptome data of presymptomatic cpr5/old1 mutants. The results demonstrate that many genes in the ROS gene network show at least fivefold increases in transcripts in comparison with those of wild-type plants, suggesting that presymptomatic cpr5/old1 mutants are in a state of high-cellular oxidative stress. This was further confirmed by a comparative, relative quantitative proteomics study of Arabidopsis wild-type and cpr5/old1 mutant plants, which demonstrated that several Phi family members of glutathione s-transferases significantly increased in abundance. In summary, our genetic, transcriptomic and relative quantitative proteomics analyses indicate that CPR5 plays a central role in regulating redox balance in Arabidopsis.

Clinical benefits of continuous leukocyte filtration during cardiopulmonary bypass in patients undergoing valvular repair or replacement.

Valve operations in the form of repair or replacement make up a significant population of patients undergoing surgical procedures in the USA annually with the use of cardiopulmonary bypass. These patients experience a wide range of complications that are considered to be mediated by activation of complement and leukocytes. The extracorporeal perfusion circuit consists of multiple synthetic artificial surfaces. The biocompatibility of the blood contact surfaces is a variable that predisposes patients to an increased risk of complement mediation and activation. This can result in an inflammatory process, causing leukocytes to proliferate and sequester in the major organ systems. The purpose of this study was to determine whether filtration of activated leukocytes improved clinical outcomes following surgical intervention for valve repair or replacement. In this paper, we report a retrospective matched cohort study of 700 patients who underwent valve procedures from June 1999 to December 2002. The control group (CG) consisted of patients who had a conventional arterial line filter. In the study group (SG), patients had a conventional arterial line filter and a leukocyte arterial line filter (Pall Medical, NY). In the SG, blood diverted to the cardioplegia system was also leukocyte depleted to enhance myocardial preservation by adapting this device to the outflow port on the filter. Patient characteristics were similar for the SG and the CG, including 228 males and 122 females, mean age (62.4 versus 64.2 years), cardiopulmonary bypass time (127+/-64 versus 116+/-53 min), and aortic crossclamp time (84+/-23 versus 81+/-23 min). Our results demonstrate that the SG achieved statistically significant reduction in the time to extubation (p =0.03) and the number of patients with prolonged intubation in excess of 24 hours (p <0.04), in addition to improved postoperative oxygenation (p=0.01), and decreased length of hospital stay (p =0.03). We believe that leukocyte filters are clinically beneficial, as demonstrated by the results presented in this study.

Prospective analysis of endoscopic vein harvesting.

BACKGROUND: Utilization of bridging vein harvesting (BVH) of saphenous vein grafts (SVG) for coronary artery bypass grafting (CABG) results in large wounds with great potential for pain and infection. Endoscopic vein harvesting (EVH) may significantly reduce the morbidity associated with SVG harvesting. METHODS: A prospective database of 200 matched patients receiving EVH and BVH was compared. The patients all underwent CABG done over a period of 4 months (April to August 2000). Patients were excluded if they had prior vein harvesting. RESULTS: The EVH and BVH group included 100 patients each with similar demographics. The patients in the EVH group had significantly fewer wound complications, mean days to ambulation, and total length of stay (P <0.05). There was no difference in harvest time or vein injuries. CONCLUSION: Endoscopic vein harvesting results in significantly fewer wound complications, decrease in days to ambulation, and the total length of stay. EVH is superior to BVH in patients undergoing CABG.

Comparison of age, gender, number of aortic valve cusps, concomitant coronary artery bypass grafting, and magnitude of left ventricular-systemic arterial peak systolic gradient in adults having aortic valve replacement for isolated aortic valve stenosis.

Correlation of the structure of the operatively excised aortic valve with various clinical variables has received relatively little attention. This report describes certain observations in 115 patients aged >30 years (mean age 70) who had aortic valve replacement for aortic valve stenosis unassociated with mitral valve dysfunction. The operatively excised aortic valve was congenitally unicuspid in 3 patients (3%), congenitally bicuspid in 54 patients (47%), tricuspid in 57 patients (50%), and of uncertain structure in 1. Of the 87 patients (76%) aged > or =65 years (Medicare population), 36 (41%) had congenitally malformed valves (bicuspid in each), and of the 28 patients (24%) aged <65 years, 21 (75%) had congenitally malformed valves. A higher percentage of patients with congenitally malformed valves had peak systolic pressure gradients across the valve >50 mm Hg than did patients with tricuspid valves (57% vs 43%). Concomitant coronary artery bypass grafting (CABG) was performed in 52 patients (45%) (34 men and 18 women), and they had average peak systolic pressure gradients across the valve significantly lower than patients without coronary bypass (46 vs 64 mm Hg): 39% of the 57 patients with congenitally malformed valves and 53% of the 57 patients with tricuspid valves had concomitant coronary bypass (insignificant difference). Thus, in a relatively older population of 115 patients having aortic valve replacement for isolated aortic valve stenosis, with or without associated aortic regurgitation, one half had congenitally malformed valves (either unicuspid or bicuspid valves) and one half had tricuspid valves. Patients having concomitant CABG had significantly smaller gradients across the stenotic valves than those who had no CABG.

Desmopressin acetate following cardiopulmonary bypass: evaluation of coagulation parameters.

Desmopressin acetate (DDAVP) has been advocated as efficacious in reducing mediastinal bleeding following cardiopulmonary bypass (CPB), and has been shown to ameliorate platelet dysfunction; however, this has not been evaluated during routine coronary artery bypass grafting (CABG). In the present study, this therapy was evaluated utilizing the thromboelastograph (TEG), a rapid, on-line means of diagnosing a coagulopathy. During elective CABG, 20 patients received either DDAVP, 0.3 microgram/kg, intravenously, following heparin reversal after CPB, or a placebo infusion, in a randomized, double-blind fashion. Hemostasis was monitored with both the TEG and conventional coagulation tests. No significant differences between the two groups were found at induction, postprotamine, post-"study infusion," or 2 hours postoperatively, with the exception of the postoperative PTT (31.1 +/- 3.2 v 36.5 +/- 5.9 seconds for DDAVP v placebo, P = 0.03). Total blood products transfused intraoperatively, and in the first 8, 16, 24, or 48 postoperative hours, were also similar between the groups. No manifestations of hypercoagulability were seen, but hypotension during the infusion was noted in four patients receiving DDAVP, and in none of the controls. It is concluded that the expense and potential complications of DDAVP therapy do not justify its routine use in CABG.

Simplified technique for open placement and removal of intraaortic balloon.

A rapid simplified technique for removal of a surgically placed intraaortic balloon is described.

Treatment of moderate mitral regurgitation and coronary disease by coronary bypass alone.

We have favored treatment of moderate mitral regurgitation and coronary disease with coronary bypass alone because of the high operative mortality of combined mitral valve replacement and coronary bypass. Between 1977 and 1983, coronary bypass alone was performed on 58 patients (mean age 63 +/- 8 years). Preoperatively, 90% had Canadian Cardiovascular Society class III or IV angina, and 10% had class III or IV congestive heart failure. In 72% mitral regurgitation had been caused by coronary disease. Hospital mortality was 3.4% (2/58). At follow-up (100% complete, mean 4.3 years) 66% of survivors were functional classes I and II (compared with 7% preoperatively, p less than 0.0001). Of those patients who worked preoperatively, 84% returned to work. There were no reoperations. The 5-year survival was 77%. In the same period combined mitral valve replacement and coronary bypass was required in 20 unmatched patients with moderate mitral regurgitation and coronary disease. Indications for valve replacement included congestive heart failure (10 cases), high left atrial pressure (three cases), and mitral stenosis (four cases). In these patients with more advanced symptoms the hospital mortality was 25%, and the 5-year survival was 31%. Treatment of moderate mitral regurgitation and coronary disease by coronary bypass alone achieved excellent hospital survival and long-term functional stability without a subsequent valve operation.

Effect of selective thromboxane synthetase inhibitor on vein grafts.

We evaluated the effect of a selective thromboxane synthetase inhibitor (TSI) on the patency of autogenous vein grafts in dogs. Treatment involved oral dosing (10 mg/kg bid) of TSI or placebo, combined with local treatment of the graft with TSI or placebo (papavarine) at the time of implantation. At harvest, two animals, one from each oral dosing group, had an occluded graft; both grafts had been locally treated with papavarine. We found no significant histopathologic difference between graft treatment groups. Attempts to estimate the effect of TSI dosing on the prostacyclin/thromboxane balance through radioimmunoassay analysis of graft perfusates were unsuccessful. As measured by in vitro platelet aggregation, oral TSI was found to alter platelet function, though not in a dose-dependent fashion, and the animals rebounded toward normal at 12 hours.

The management of splenic injury.

Increased concern over the potential immunologic consequences of splenectomy has prompted surgeons to attempt salvage of traumatized spleens. We report a retrospective study of 172 consecutive patients with documented splenic injury treated over a 2-year period: 107 patients underwent splenectomy; 65 were managed without total splenectomy; 32 were not explored. The overall mortality rate was 27%; the overall complications were 30%, including a 13% incidence of post-splenectomy subphrenic abscess. The incidence of infectious complications after splenectomy was 36%, while the incidence in nonsplenectomized patients was 9%. The Injury Severity Scores (ISS) in the two groups were significantly different (p less than or equal to 0.05). When the group whose spleens were salvaged was compared to an equivalent group matched for ISS, age, and sex, there was no significant difference in sepsis rates (23% vs. 10.7%; 0.10 greater than or equal to p greater than or equal to 0.05). Survival in those with postinjury infectious complications was significantly improved in patients with a remaining spleen (p less than or equal to 0.01). Abdominal computerized tomography was used successfully as a method of following injured and repaired spleens in order to predict return to full activity.