Gautam Sreeram

β2-Adrenergic and Several Other G Protein–Coupled Receptors in Human Atrial Membranes Activate Both Gs and Gi

Cardiac G protein–coupled receptors that couple to G&agr;s and stimulate cAMP formation (eg, &bgr;-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cells have revealed that one of these receptors, the &bgr;2-adrenergic receptor (AR), also couples to the inhibitory G protein G&agr;i (activation of which inhibits cAMP formation). If &bgr;2ARs could be shown to couple to G&agr;i in the human heart, it would have important ramifications, because levels of G&agr;i increase with age and in failing human heart. Therefore, we investigated whether &bgr;2ARs in the human heart activate G&agr;i. By photoaffinity labeling human atrial membranes with [32P]azidoanilido-GTP, followed by immunoprecipitation with antibodies specific for G&agr;i, we found that G&agr;i is activated by stimulation of &bgr;2ARs but not of &bgr;1ARs. In addition, we found that other G&agr;s-coupled receptors also couple to G&agr;i, including histamine, serotonin, and glucagon. When coupling of these receptors to G&agr;i is disrupted by pertussis toxin, their ability to stimulate adenylyl cyclase is enhanced. These data provide the first evidence that &bgr;2AR and many other G&agr;s-coupled receptors in human atrium also couple to G&agr;i and that abolishing the coupling of these receptors to G&agr;i increases the receptor-mediated adenylyl cyclase activity.

Transfusion and hematologic variables after fibrinogen or platelet transfusion in valve replacement surgery: preliminary data of purified lyophilized human fibrinogen concentrate versus conventional transfusion.

Platelet (PLT) and plasma transfusion remain the mainstay hemostatic therapy for perioperative bleeding. Several studies have indicated that acquired fibrinogen (FIB) deficiency can be the primary cause of bleeding after cardiac surgery. The aim of this study was to compare hematologic and transfusion profiles between the first‐line FIB replacement and PLT transfusion in post–cardiac surgical bleeding.

Anaesthetic considerations for a child with combined Prader-Willi syndrome and mitochondrial myopathy.

We report the anaesthetic management of a child with Prader–Willi syndrome and mitochondrial myopathy for open heart surgery. We used ketamine, fentanyl, rocuronium and caudal morphine together with a propofol infusion with no untoward effects. The implications of both conditions for anaesthesia are discussed.

Leukocyte-reduced blood transfusions: perioperative indications, adverse effects, and cost analysis.

I n recent years, interest in leukocyte-reduced blood products has increased as accumulating evidence suggests that cancer recurrence, graft-versus-host disease (GVHD), and postoperative infections are mediated by leukocyte contamination of blood components (Table 1). Herzig et al. (1) in the mid-1970s stimulated interest in leukocyte depletion by showing that leukocyte reduction of platelet components improved posttransfusion platelet counts in patients with human-leukocyte-associated (HLA) antigen incompatibilities. Further studies by Eernisse and Brand (2) demonstrated that leukocyte contamination of platelet concentrates was responsible for HLA antibody formation. These findings led to growing use of leukocyte-reduced platelet transfusions. However, debate continues as to how low the leukocyte count must be to prevent leukocyte-mediated alloimmunization. In the last decade, great strides have been made in developing more efficient leukocyte filters, and the administration of leukocyte-reduced blood products has become routine. This review focuses on evidence that leukocyte-reduced blood products may decrease adverse effects associated with blood transfusion.

Association of leukocyte-depleted blood transfusions with infectious complications after cardiac surgery.

BACKGROUND To test the hypothesis that leukocyte-mediated immunosuppression may contribute to postoperative infections after blood transfusions, we compared the incidence of postoperative infections in patients undergoing elective coronary artery bypass graft (CABG) surgery who received either leukocyte-depleted (LD-RBCC) or non-LD transfusions of red blood cell concentrates (RBCC) within 48 h of surgery. MATERIALS AND METHODS Data for all primary elective CABG patients between 1995 and 1998 who received allogeneic RBCC transfusions in the first 48 h after surgery were collected. Patients were divided into two groups (group LD: LD-RBCC transfusions only; group non-LD: non-LD-RBCC transfusions only were excluded). Patients who received a combination of LD and non-LD-RBCC transfusions, or any blood products other than RBCC were excluded. Infectious complications recorded included pneumonia, acute respiratory distress syndrome, mediastinitis, leg wound/sternal wound infection, nosocomial infection, catheter-related infection, urinary tract infection, decubitus ulcers, and bacteremia/fungemia. RESULTS One hundred forty-two patients received only LD-RBCC transfusions, and 1,765 patients received only non-LD-RBCC transfusions. Power analysis demonstrated that the sample size attained 80% power to detect an odds ratio of 2.1 at a significance level of p < 0.05. Infection rates were not significantly different between the non-LD and LD groups (7.57% vs. 9.52%, p = 0.40). Leukocyte depletion status of RBCC transfusions was not a predictor of infectious complications (p = 0.73). However, total units of RBCC received was highly associated with increased infection (p = 0.0001). CONCLUSIONS No association between postoperative infections and the use of leukocyte-depleted blood was identified. However, an increased incidence of postoperative infections was observed to be associated with blood transfusions in general.

Elevated factor VIII enhances thrombin generation in the presence of factor VIII-deficiency, factor XI-deficiency or fondaparinux.

BACKGROUND Increased levels of factor VIII occur as a response to vascular injury and/or inflammation, and may increase thrombotic risks. In contrast, factor VIII deficiency poses a major hemostatic challenge. The role of factor VIII in modulating hemostasis/thrombosis was investigated in plasma models of hypocoagulable and hypercoagulable state using thrombin generation (TG) assay. METHODS TG was performed in undiluted/diluted control, FVIII-deficient, FVIII-deficient with low antithrombin (AT activity, ~59%), and factor XI-deficient plasma samples using relipidated tissue factor (TF, 2 pM) or dilute Actin as activators. The impact of elevated FVIII on TG was simulated by adding Humate-P (0 to 3 U/ml) to the above plasma samples. In fondaparinux (1 μg/ml) treated plasma with normal or lower AT activity effects of Humate-P vs. 60 nM of recombinant activated factor VII (rFVIIa) were also evaluated. RESULTS Humate-P increased TG concentration dependently in undiluted and diluted control plasma with TF activation. With Actin activation, only the concentration dependent shortening of lag time, but no change in peak thrombin was observed. In FVIII-deficient, FVIII-deficient with low AT, and FXI-deficient samples, 3 U/ml of Humate-P increased TG, and decreased its onset with either activator. The reduced peak thrombin due to fondaparinux was reversed with Humate-P (3 U/ml) more than with rFVIIa. Elevated FVIII levels seem to favor intrinsic tenase formation and antagonize fondaparinux because anti-FIXa aptamer added to fondaparinux effectively attenuated TG. CONCLUSION Elevated FVIII supports the propagation of TG via intrinsic tenase formation under low TF condition, factor XI deficiency or in the presence of fondaparinux.