Effect of amlodipine on cardiopulmonary performance in volunteers.

1. In order to exclude a significant effect of the calcium channel antagonist amlodipine on cardiopulmonary performance in normal subjects, we performed a double-blind cross-over study of amlodipine (10 mg daily for 2 weeks) on oxygen uptake and catecholamine responses during exercise in eight volunteers. 2. Despite a therapeutic plasma concentration of amlodipine (22.8+/-9 ng/mL), there was no change in resting heart rate or blood pressure. Amlodipine did not cause significant change in oxygen uptake at the anaerobic threshold or at maximum exercise and there was also no change in heart rate or catecholamine responses. 3. Although there was an awareness of peripheral vasodilation and reports of lethargy during the active treatment period, the volunteers had no objective evidence of a decrease in cardiopulmonary performance. We suggest that use of amlodipine as a vasodilator in the perioperative period would not add to the myocardial depressant effects of general anaesthesia in patients with normal cardiac function.

Renal xenografts from triple-transgenic pigs are not hyperacutely rejected but cause coagulopathy in non-immunosuppressed baboons.

BACKGROUND: The genetic modification of pigs is a powerful strategy that may ultimately enable successful xenotransplantation of porcine organs into humans. METHODS: Transgenic pigs were produced by microinjection of gene constructs for human complement regulatory proteins CD55 and CD59 and the enzyme alpha1,2-fucosyltransferase (H-transferase, HT), which reduces expression of the major xenoepitope galactose-alpha1,3-galactose (alphaGal). Kidneys from CD55/HT and CD55/CD59/HT transgenic pigs were transplanted into nephrectomised, nonimmunosuppressed adult baboons. RESULTS: In several lines of transgenic pigs, CD55 and CD59 were expressed strongly in all tissues examined, whereas HT expression was relatively weak and did not significantly reduce alphaGal. Control nontransgenic kidneys (n=4) grafted into baboons were hyperacutely rejected within 1 hr. In contrast, kidneys from CD55/HT pigs (n=2) were rejected after 30 hr, although kidneys from CD55/CD59/HT pigs (n=6) maintained function for up to 5 days. In the latter grafts, infiltration by macrophages, T cells, and B cells was observed at days 3 and 5 posttransplantation. The recipients developed thrombocytopenia and abnormalities in coagulation, manifested in increased clotting times and an elevation in the plasma level of the fibrin degradation product D-dimer, within 2 days of transplantation. Treatment with low molecular weight heparin prevented profound thrombocytopenia but not the other aspects of coagulopathy. CONCLUSIONS: Strong expression of CD55 and CD59 completely protected porcine kidneys from hyperacute rejection and allowed a detailed analysis of xenograft rejection in the absence of immunosuppression. Coagulopathy appears to be a common feature of pig-to-baboon renal transplantation and represents yet another major barrier to its clinical application.

Patient-controlled epidural versus intravenous pethidine to supplement epidural bupivacaine after abdominal aortic surgery.

In a double-blind, randomized, crossover study of 25 patients after abdominal aortic surgery, we compared patient-controlled analgesia (PCA) with epidural versus intravenous pethidine. All patients received continuous epidural infusions of 0.125% bupivacaine adjusted to maintain appropriate sensory levels. The 48 hour study period commenced 36 to 48 hours after surgery and covered postoperative days 2 and 3. There was a crossover in PCA mode (epidural or intravenous) after 24 hours. Plasma pethidine concentration at the end of each 24 hour period and the total 24 hour pethidine dose did not change significantly between postoperative days 2 and 3. Pethidine plasma concentration was lower after 24 hours epidural than after intravenous PCA [125 (SD 108) ng/ml versus 171 (SD 107) ng/ml, P = 0.03], although pethidine dose did not differ significantly [mean 147 (SD 124) mg/24 h]. Visual analog pain scores (VAS) did not differ significantly between postoperative days 2 and 3, or at rest between epidural and i.v. groups. However, VAS with coughing and with abdominal palpation were lower in the epidural PCA group (P = 0.05, 0.008). With a background epidural infusion of 0.125% bupivacaine, PCA with epidural pethidine provided better pain control than PCA intravenous pethidine and this was achieved at lower plasma pethidine concentrations.