raffinose and Coronary-Artery-Disease

We performed this study to determine the dose-response of hemoglobin raffimer administered in conjunction with intraoperative autologous donation in patients undergoing coronary artery bypass grafting surgery. A secondary objective was to evaluate hemoglobin raffimer for reducing the incidence of allogeneic red blood cell transfusions.. This was a phase II, single-blind, multicenter, placebo-controlled, open-label study. Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation were randomized to receive a single dose of hemoglobin raffimer or control (10% pentastarch). Patients were sequentially enrolled in a dose block of 250, 500, 750, and 1000 mL.. Sixty patients received hemoglobin raffimer (n = 30) or control (n = 30). Hemoglobin raffimer was well tolerated. Most (98%) adverse events were mild or moderate in severity. There was an expected dose-dependent increase in the incidence of blood pressure increases and jaundice in hemoglobin raffimer-treated patients. In a dose-pooled analysis of hemoglobin raffimer versus control, increased blood pressure (43% vs 17%), nausea (37% vs 33%), and atrial fibrillation (37% vs 17%) were the most frequently reported adverse events. All serious adverse events were considered unrelated or unlikely to be related to study drug. No hemoglobin raffimer-treated patient required an intraoperative allogeneic red blood cell transfusion, compared with 5 (17%) pentastarch-treated patients (P =.052). This advantage of hemoglobin raffimer was maintained at 24 hours after surgery (7% vs 37%; P =.010) and up to 5 days after surgery (10% vs 47%; P =.0034).. Hemoglobin raffimer was not associated with any serious adverse events in patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation in a dose-response study up to 1000 mL. Hemoglobin raffimer was effective in facilitating decreased exposure or avoidance of allogeneic red blood cell transfusions when used in conjunction with intraoperative autologous donation.

Topics: Adult; Aged; Analysis of Variance; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Dose-Response Relationship, Drug; Elective Surgical Procedures; Female; Follow-Up Studies; Hemoglobins; Humans; Intraoperative Period; Male; Maximum Tolerated Dose; Middle Aged; Probability; Raffinose; Reference Values; Risk Assessment; Severity of Illness Index; Single-Blind Method; Treatment Outcome

We aimed to study the effect of cariporide (CP) on protecting the saphenous vein and the role of acetaldehyde dehydrogenase 2 (ALDH2) in coronary artery bypass grafting (CABG).. The saphenous vein is the main graft material used in CABG. Recent studies suggested that CP is effective in protecting against various cardiovascular diseases.. Segments of a surgically removed saphenous vein were used to examine the vascular response to CP. The ALDH2 genotype and expression of related proteins were assessed by Western blotting and immunohistochemistry.. Among the conditions tested, the University of Wisconsin solution with CP (4°C, 5 min) treatment showed the best protective effect on the saphenous vein. The incidence of major adverse cardiac events was higher in the ALDH2-GA (heterozygous mutant) genotype population after CABG.. CP plays a role in reducing the production of reactive oxygen species and apoptosis by ALDH2-mediated mitochondrial function improvement. The ALDH2 mutant genotype might be one of the risk factors for coronary atherosclerotic heart disease.

Topics: Adenosine; Adult; Aldehyde Dehydrogenase, Mitochondrial; Allopurinol; Apoptosis; Coronary Artery Bypass; Coronary Artery Disease; Female; Genotype; Glutathione; Guanidines; Humans; Insulin; Male; Middle Aged; Organ Preservation Solutions; Raffinose; Reactive Oxygen Species; Saphenous Vein; Sulfones

The long-term success of cardiac transplantation is limited by graft atherosclerosis, also known as graft vascular disease (GVD). GVD is currently the leading cause of late allograft failure in cardiac transplant recipients. The aim of this study was to assess the effects of cold ischemic preservation time (CIPT) and degree of donor-recipient histocompatibility on GVD using a rat heterotopic cardiac transplantation model.. ACI-Lewis (n=9), Lewis-F344 (n=9), and Lewis-Lewis (n=9) donor-recipient rat strain combinations were subjected to variable durations of CIPT (0, 4, and 24 hours in University of Wisconsin solution at 4°C) prior to transplantation (n=81 total). The ACI-Lewis allografts differed in both major histocompatibility complex (MHC) class I and II antigens, the Lewis-F344 allograft combination differed in multiple non-MHC antigens, and the Lewis-Lewis isograft combination was syngeneic. Grafts were harvested at 90 days. Intimal area ratio (IAR), intimal thickness score (ITS), and rejection score (RS) were determined for each specimen.. The Lewis-Lewis transplant group had a significantly higher mean RS (P=.036) with 24 hours than with 0 hours of CIPT in this rat heterotopic transplantation model at 90 days. The Lewis-F344 group had a significantly higher IAR (P=.035), ITS (P=.030), and RS (P=.017) with 24 hours than with 0 hours of CIPT. The ACI-Lewis group had high levels of GVD with all durations of CIPT (0, 4, and 24 hours); as a consequence, there were no significant differences in the ITS, IAR, or RS. With 0 hours of CIPT, the ACI-Lewis transplantation group yielded a significantly higher mean IAR (P=.029), ITS (P=.003), and RS (P=5.02×10(-5)) than the Lewis-Lewis group. The Lewis-F344 group had a significantly higher mean RS (P=.003) than the Lewis-Lewis (syngeneic) group. The ACI-Lewis transplantation group had a significantly higher mean IAR (P=.035), and trended toward a higher ITS (P=.058) than the Lewis-F344 group.. Longer cold ischemic preservation time and less donor-recipient histocompatibility were associated with more advanced GVD in a rat heterotopic transplantation model, especially when there were multiple MHC mismatches as in ACI-Lewis allografts, but also occurred when there were differences in multiple non-MHC antigens as in the Lewis-F344 allografts. There was a lesser effect of longer cold ischemic time on GVD in the Lewis-Lewis syngeneic (isograft) group, suggesting that greater histocompatibility can mitigate the adverse effects of longer ischemic times.

Topics: Adenosine; Allopurinol; Animals; Cold Ischemia; Coronary Artery Disease; Glutathione; Graft Rejection; Heart Transplantation; Histocompatibility; Histocompatibility Antigens; Insulin; Male; Organ Preservation Solutions; Raffinose; Rats; Rats, Inbred ACI; Rats, Inbred F344; Rats, Inbred Lew; Risk Assessment; Risk Factors; Time Factors