Apoptosis: A New Mechanism of Lethal Myocardial “Reperfusion Injury”?

Journal of Thrombosis and Thrombolysis -     

Percutaneous coronary intervention versus coronary bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: The VA AWESOME multicenter registry: comparison with the randomized clinical trial.

OBJECTIVES: This study was designed to compare the three-year survival after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) in physician-directed and patient-choice registries with the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial results. BACKGROUND: The AWESOME multicenter randomized trial and registry compared the long-term survival after PCI and CABG for the treatment of patients with medically refractory myocardial ischemia and at least one additional risk factor for adverse outcome with CABG. The randomized trial demonstrated comparable three-year survival. METHODS: Over a five-year period (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior heart surgery, myocardial infarction within seven days, left ventricular ejection fraction <0.35, age >70 years, intra-aortic balloon required to stabilize) were identified. By physician consensus, 1,650 patients formed a physician-directed registry assigned to CABG (692), PCI (651) or further medical therapy (307), and 781 were angiographically eligible for random allocation; 454 of these patients constitute the randomized trial, and the remaining 327 constitute a patient choice registry. Survival for CABG and PCI was compared using Kaplan-Meier curves and log-rank tests. RESULTS: The CABG and PCI 36-month survival rates for randomized patients were 79% and 80%, respectively. The CABG and PCI 36-month survival rates were both 76% for the physician-directed subgroup; comparable survival rates for the patient-choice subgroup were 80% and 89%, respectively. None of the global log-rank tests for survival demonstrated significant differences. CONCLUSIONS: Both registries support the randomized trial conclusion: PCI is an alternative to CABG for some medically refractory high-risk patients.     

The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle

BACKGROUND: Inadequate dietary protein intake results in loss of skeletal muscle mass. Some shorter-term nitrogen balance studies suggest that the Recommended Dietary Allowance (RDA) of protein may not be adequate for older people. The aim of this study was to assess the adequacy of the RDA of protein for older people by examining longer-term responses in urinary nitrogen excretion, whole-body protein metabolism, whole-body composition, and mid-thigh muscle area. METHODS: This was a 14-week precisely controlled diet study. Ten healthy, ambulatory men and women, aged 55 to 77 years, were provided eucaloric diets that contained 0.8 g protein.kg(-1).day(-1). The study was conducted at a General Clinical Research Center using an outpatient setting for 11 weeks and an inpatient setting for 3 weeks. The main outcome measures included urinary nitrogen excretion, postabsorptive and postprandial whole-body leucine kinetics via infusion of L-[1-(13)C]-leucine, whole-body density via hydrostatic weighing, total body water via deuterium oxide dilution, and mid-thigh muscle area via computed tomography scans. RESULTS: Mean urinary nitrogen excretion decreased over time from Weeks 2 to 8 to 14 (p =.025). At Week 14, compared with Week 2, there were no changes in postabsorptive or postprandial leucine kinetics (turnover, oxidation, incorporation into protein via synthesis, release via breakdown, or balance). Whole-body composition (% body fat, fat-free mass, and protein + mineral mass) did not change over time in these weight-stable subjects. Mid-thigh muscle area was decreased by -1.7 +/- 0.6 cm(2) (p =.019) at Week 14 compared with Week 2. The loss of mid-thigh muscle area was associated with the decrease in urinary nitrogen excretion (Spearman r =.83, p =.010). CONCLUSIONS: The maintenance of whole-body leucine metabolism and whole-body composition is generally consistent with a successful adaptation to the RDA for protein. However, the decrease in mid-thigh muscle area and the association with decreased urinary nitrogen excretion are consistent with a metabolic accommodation. These results suggest that the RDA for protein may not be adequate to completely meet the metabolic and physiological needs of virtually all older people.     

Effects of intravenous glucose on whole body leucine dynamics, studied with 1-13C-leucine, in healthy young and elderly adults

We examined whole body leucine metabolism in healthy young and elderly adults while in the postabsorptive state and during an intravenous glucose administration at two rates. Leucine flux, incorporation into whole body protein, and oxidation were estimated from a continuous intravenous infusion of L-[1-13C]leucine and determination of 13C enrichment in plasma leucine and expired air. Per unit of body weight, leucine flux and rates of incorporation into protein were similar in young and old men. Old women showed lower rates compared with young women. Rates were similar for both age groups when expressed per unit of total body water and/or of muscle protein mass. Intravenous glucose infusion (4 mg . kg-1 . min-1) reduced plasma leucine levels and flux similarly in both age groups. Thus, age-related differences in muscle mass and sensitivity of peripheral tissues to insulin-mediated glucose uptake and metabolism are not paralleled by alterations in whole body leucine kinetics in the postabsorptive state.     

Early clinical results of long coronary arteriotomy, endarterectomy and reconstruction combined with multiple bypass grafting for severe coronary artery disease

Within a 2.5-year period between 1985 and 1988, long coronary arteriotomy, endarterectomy and reconstruction (principally left anterior descending artery) and multiple bypass grafting (mean graft rate was 9) were performed in 130 of 329 patients (40%) with severe diffuse coronary artery disease to ensure complete myocardial revascularization. Ninety-two percent of the patients who underwent exercise testing had abnormal (greater than 1 mm ST) depression and/or positive results on scintigraphy. Long coronary arteriotomy (5 to 12 cm), endarterectomy and reconstruction of the left anterior descending artery and its branches, were performed in 121 patients; of the left circumflex artery and its branches in 13 patients; and of the right coronary artery and its branches beyond the crux in 18 patients. Single endarterectomy and reconstruction was performed in 109 patients, double in 20 and triple in 1. The operative mortality was 2.3% and the perioperative infarction was 1.5%. Twenty-four patients (among them 38% who had undergone greater than 1 previous bypass operation) were randomly selected and studied within 20 days after surgery. This group comprised a total of 69 coronary conduits of which 68 (99%) were patent, and a total of 206 coronary anastomoses of which 202 (98%) were patent. Thirty-two of 33 conduits (97%) to endarterectomized and reconstructed arteries were patent. One hundred and twenty-six of 127 patients were followed up for a mean of 20 months; 120 of the 121 patients (99%) were in angina class I by Canadian Cardiovascular Society classification, and 63 of 71 patients (89%) had a normal treadmill exercise stress test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is intimal hyperplasia a marker of neuro-ophthalmic complications of giant cell arteritis?

Objective. The ischaemic complications of giant cell arteritis(GCA) such as blindness and stroke may result from luminal narrowingof the affected arteries. This study focuses on the associationbetween the severity of intimal proliferation on temporal arterybiopsy (TAB) histology and neuro-ophthalmic complications (NOCs)of GCA. Method. We identified 30 cases of biopsy-proven temporal arteritis.One histopathologist (blinded to the clinical details) evaluatedthe TAB specimens and categorized the degree of maximum stenosisdue to intimal hyperplasia into four grades: grade 1 is <50%luminal occlusion due to intimal hyperplasia, grade 2 is 50–75%,grade 3 is >75% and grade 4 is complete luminal occlusion.A second histopathologist (also blinded to the clinical details)independently evaluated the TAB specimens using the same gradingsystem. The NOCs in these patients were noted after a case recordreview. Results. Of the 30 patients, 12 had NOC-10 with eye complications(complete visual loss, anterior ischaemic neuropathy, visualfield defects), one patient had cerebral infarcts and one hadboth cerebral infarcts and vision loss. There was evidence fora statistically significant trend of NOC associated with higherintimal hyperplasia scores (P = 0.001). The scores of the histopathologistsagreed for 23 (77%) patients and differed by 1 category forthe remaining 7 (-statistic 0.88). Conclusions. Our study suggests that the degree of intimal hyperplasiaon TAB histology (routinely available to all hospital units)seems to be closely associated with NOCs of GCA. The study highlightsthe possible prognostic as well as diagnostic role of the biopsy.We feel that intimal hyperplasia noted in biopsy specimens mayhelp us in the risk stratification of GCA patients and targetingof appropriate and novel therapies. KEY WORDS: Intimal hyperplasia, Giant cell arteritis, Neuro-ophthalmic complications Submitted 1 June 2007; revised version accepted 7 January 2008.