Jack G. Copeland

Implications of preoperative administration of aspirin in patients undergoing coronary artery bypass grafting

The perioperative consequences of preoperative aspirin administration were assessed in a large prospective cooperative study of 772 patients undergoing coronary artery bypass grafting. The 772 patients were randomized to receive either aspirin (325 mg once a day), aspirin (325 mg three times a day), aspirin plus dipyridamole (325 and 75 mg together three times a day) (aspirin group), sulfinpyrazone (267 mg three times a day) or placebo (nonaspirin group). The therapy, except in the aspirin group, was started 48 h before the operation. In all aspirin subgroups, one 325 mg aspirin dose was given 12 h before surgery and maintained thereafter according to the assigned regimen. Patients in the aspirin group had significantly more postoperative bleeding and received more packed blood cells and blood products than did patients in the nonaspirin group. Although total operative duration and cardiopulmonary bypass duration were not different, the interval between completion of cardiopulmonary bypass and wound closure was significantly longer (p = 0.035) in the aspirin group. Thirty-one (6.6%) of 471 patients in the aspirin group and 5 (1.7%) of 301 patients in the nonaspirin group also required reoperation for control of postoperative bleeding (p = 0.002). The site of bleeding found at reoperation was not different between the two groups. There was no difference in operative mortality rates, incidence of other bleeding complications or occurrence of other post-operative complications between the two groups. Thus, antiplatelet regimens involving preoperative initiation of aspirin therapy, which has been shown to improve graft patency, increase the risk of abnormal postoperative bleeding and the need for reoperation.(ABSTRACT TRUNCATED AT 250 WORDS)

Starting aspirin therapy after operation. Effects on early graft patency. Department of Veterans Affairs Cooperative Study Group.

BackgroundAlthough aspirin therapy started before operation improves vein graft patency after coronary artery bypass grafting, it also causes bleeding. The objective of this prospective, centrally directed, randomized, double-blind, placebo-controlled trial was to compare the effects of aspirin therapy started before operation with aspirin started 6 hours after operation on early (7–10-day) graft patency. Methods and ResultsPatients were randomized to receive either aspirin 325 mg or placebo the night before surgery; after operation, all patients received aspirin 325 mg daily, with the first dose administered through the nasogastric tube 6 hours after operation. Angiography was performed in 72% of the analyzed patients an average of 8 days after operation, and the primary end point was saphenous vein graft patency in 351 patients. Internal mammary artery graft patency was also assessed in 246 patients because many individuals received both internal mammary artery and vein grafts. In the patients given preoperative aspirin, the vein graft occlusion rate was 7.4 ± 1.3% compared with 7.8 ± 1.5% in those who received preoperative placebo (p =0.871). In the subgroup of patients receiving Y grafts, 0.0% of the grafts were occluded in the preoperative aspirin group compared with 7.0 ± 3.6% in the preoperative placebo group (p =0.066). The internal mammary artery occlusion rate was 0.0% (0 of 131) in the aspirin group compared with 2.4 ± 1.4% (three of 125) in the placebo group (p =0.081). Patients in the aspirin group received more transfusions than those in the placebo group (median, 900 versus 725 ml,p=0.006). The reoperation rate for bleeding in the aspirin group was 6.3% compared with 2.4% in the placebo group (p =0.036). Median chest tube drainage within the first 6 hours after operation was 500 ml in the aspirin group compared with 448 ml in the placebo group (p =0.011). Conclisions. Thus, preoperative aspirin is associated with increased bleeding complications and offers no additional benefit in early vein graft patency compared with starting aspirin therapy 6 hours after operation. There was a trend, although not significant, toward improved early patency for Y grafts and internal mammary artery grafts with preoperative aspirin.

Aprotinin for Primary Coronary Artery Bypass Grafting: A Multicenter Trial of Three Dose Regimens

BACKGROUND High-dose aprotinin reduces transfusion requirements in patients undergoing coronary artery bypass grafting, but the safety and effectiveness of smaller doses is unclear. Furthermore, patient selection criteria for optimal use of the drug are not well defined. METHODS Seven hundred and four first-time coronary artery bypass grafting patients were randomized to receive one of three doses of aprotinin (high, low, and pump-prime-only) or placebo. The patients were stratified as to risk of excessive bleeding. RESULTS All three aprotinin doses were highly effective in reducing bleeding and transfusion requirements. Consistent efficacy was not, however, demonstrated in the subgroup of patients at low risk for bleeding. There were no differences in mortality or the incidences of renal failure, strokes, or definite myocardial infarctions between the groups, although the pump-prime-only dose was associated with a small increase in definite, probable, or possible myocardial infarctions (p = 0.045). CONCLUSIONS Low-dose and pump-prime-only aprotinin regimens provide reductions in bleeding and transfusion requirements that are similar to those of high-dose regimens. Although safe, aprotinin is not routinely indicated for the first-time coronary artery bypass grafting patient who is at low risk for postoperative bleeding. The pump-prime-only dose is not currently recommended because of a possible association with more frequent myocardial infarctions.

Long-term graft patency (3 years) after coronary artery surgery. Effects of aspirin: results of a VA Cooperative study.

BACKGROUND The long-term success of coronary bypass surgery is dependent on graft patency after surgery. This trial was designed to determine if aspirin improved saphenous vein graft or internal mammary artery (IMA) graft patency between 1 and 3 years after coronary artery bypass grafting (CABG). METHODS AND RESULTS After receiving aspirin 325 mg/d for 1 year after CABG and undergoing a 1-year postoperative cardiac catheterization, patients were randomized to receive either aspirin (325 mg) or placebo for 2 additional years. Angiography was performed 3 years after surgery to determine the primary end point-saphenous vein graft patency in 288 patients and IMA graft patency in 167 patients. At 3 years after CABG, the saphenous vein graft occlusion rate was 17.0% (62 of 365) for patients treated with aspirin compared with 19.7% (74 of 376) for those who received placebo (P = .404). For saphenous vein grafts that were patent at 1 year, the occlusion rate at 3 years was 4.8% (15 of 313) for patients treated with aspirin compared with 4.2% (13 of 310) for patients who received placebo (P = .757). At 3 years, the IMA graft occlusion rate was 10.3% (8 of 78) for patients treated with aspirin compared with 7.9% (7 of 89) for patients who received placebo (P = .594). For IMA grafts that were patent at 1 year, the occlusion rate was 4.3% (3 of 70) for patients treated with aspirin compared with 2.5% (2 of 81) for patients who received placebo (P = .541). CONCLUSIONS These data suggest that aspirin treatment does not improve saphenous vein graft or IMA graft patency between 1 and 3 years after CABG.

Multicenter experience with the thoratec ventricular assist device in children and adolescents

BACKGROUND Patient size is 1 determinant in selecting a mechanical circulatory support device. The current pulsatile ventricular assist devices (VADs) were designed primarily for average-sized adults. The flexibility of the Thoratec VAD, however, has encouraged physicians to use it in a significant number of intermediate-sized older children and adolescents. METHODS We conducted a retrospective study in 58 children and adolescents <18 years (41 boys, 17 girls) who had been supported with the Thoratec VAD in 27 centers worldwide as of December 1999. Mean patient age was 13.8 years (range, 7 to 17 years), and mean patient weight and body surface area were 51.6 kg (range, 17 to 93 kg) and 1.5 m(2) (range, 0.7 to 2.1 m(2)), respectively. RESULTS Thirty-five patients (60%) survived to transplantation and 6 (10%) to recovery of the native heart, respectively; 38 were discharged from the hospital (66%). In the transplanted group, post-transplantation survival was 97%. Patient age and size were not associated with significantly increased risk for death or adverse events. Fifteen patients (27%) had 18 neurologic events during support, and 6 of these were fatal. Left atrial cannulation proved a risk factor for neurologic complications. CONCLUSIONS The Thoratec VAD has successfully been used in a large number of children and adolescents with similar morbidity and mortality results as with adults. The risk of neurologic complications may be increased, particularly in patients cannulated in the left atria.

Experience with more than 100 total artificial heart implants.

OBJECTIVE The SynCardia Total Artificial Heart (SynCardia Systems Inc, Tucson, Ariz) has been used as a bridge to cardiac transplantation in 930 patients worldwide and in 101 patients in our program. Our experience with SynCardia Total Artificial Heart implantation documents its indications, safety, and efficacy. METHODS Data regarding preoperative condition, mortality, and morbidity have been reviewed and analyzed. RESULTS From January 1993 to December 2009, 101 patients had bridge to transplant procedures with the SynCardia Total Artificial Heart. Ninety-one percent of cases were Interagency Registry for Mechanically Assisted Circulatory Support profile 1, and the remaining 9% of cases were failing medical therapy on multiple inotropic medications. The mean support time was 87 days (median, 53 days; range, 1-441 days). Pump outputs during support were 7 to 9 L/min. Adverse events included strokes in 7.9% of cases and take-back for hemorrhage in 24.7% of cases. Survival to transplantation was 68.3%. Causes of death of 32 patients on device support included multiple organ failure (13), pulmonary failure (6), and neurologic injury (4). Survival after transplantation at 1, 5, and 10 years was 76.8%, 60.5%, and 41.2%, respectively. The longest-term survivor is currently alive 16.4 years postimplantation. CONCLUSIONS These patients were not candidates for left ventricular assist device therapy and were expected to die. The SynCardia Total Artificial Heart offers a real alternative for survival with a reasonable complication rate in appropriate candidates who otherwise might have been assigned to hospice care.

Selection of patients for cardiac transplantation.

Selection of potential cardiac recipients is not a simple process. Identification of patients who are declining from end-stage cardiac disease and may be expected to die within 12 months or less and deciding which of a number of cardiac invalids are reasonable candidates for cardiac transplantation involves prognostication as well as a working knowledge of the expected benefits and survival rates in cardiac transplantation. Screening by means of the currently accepted contraindications for cardiac transplantation is somewhat more difficult in 1986 than it was 10 years ago when these contraindications were changing less rapidly. However, for optimal use of the limited supply of donor organs and maintenance of reasonable survival rates such screening is absolutely necessary. A second area of restriction that is less approachable by the physician is that of financial limitations. It would appear that the working poor and lower middle class may be deprived of the opportunity for cardiac transplantation much as they are deprived of the opportunity for optimal medical care in our society today.

DIURESIS WITH CONTINUOUS INFUSION OF FUROSEMIDE AFTER CARDIAC SURGERY

We prospectively evaluated the diuretic effect of furosemide administered by bolus injection and by continuous infusion in 18 cardiac surgery patients. Nine patients were randomly assigned to receive 0.3 mg/kg of furosemide as a bolus injection at time 0 and again 6 hours later (nine patients) or 0.05 mg/kg per hour of furosemide as a constant infusion for 12 hours (nine patients). There were no significant differences between groups with respect to age, weight, creatinine clearance, changes in serum sodium and potassium levels, total urinary concentrations of sodium and potassium, or total urine volume for 12 hours. Diuresis during continuous infusion of furosemide was less variable from hour to hour than after bolus injection of furosemide and was sustained throughout the infusion period. Although the continuous infusion of furosemide will not provide the rapid and vigorous diuresis that is necessary in some clinical situations, it may be useful whenever a gentle, sustained diuresis is desired.

Cyclosporine inhibits prolactin induction of ornithine decarboxylase in rat tissues

Cyclosporine (CyA), formerly cyclosporin A, significantly inhibited the ability of prolactin (PRL) to elevate ornithine decarboxylase (ODC) activity in a variety of rat tissues. Administration of PRL to hypophysectomized rats also resulted in an induction of ODC activity which was inhibited markedly in all tissues studied in the presence of CyA. Transglutaminase ( TGase ) activity was not affected in any significant manner by PRL or CyA in most tissues studied. However, it was elevated in the adrenal by 10(-8) M PRL. Bromocryptine, which selectively antagonizes pituitary PRL release, decreased the kidney ODC basal levels to 30% of vehicle control and serum PRL level to 4.3 +/- 1.4 compared to 28 +/- 10 in controls, suggestive of PRL maintenance of steady-state ODC activity in the kidney. CyA administration did not affect the action of glucagon, a known cyclic AMP-mediated hormone, or 8-bromo-cyclic AMP on kidney ODC activity. The elevation of rat kidney ODC activity by dexamethasone and triiodothyronine (T3), compounds which elevated serum prolactin levels in all cases, was also blocked by administration of CyA. Epidermal growth factor (EGF), which did not induce rat kidney ODC activity by itself, was capable of producing a small increment in ODC activity in the presence of CyA. The marked effect of CyA to selectively block ODC induction by PRL may be due to the ability of CyA to interact with receptor-required phospholipids in membranes and thus to antagonize hormone-receptor interaction.

Ultrasonic imaging of the coronary arteries in open-chest humans: evaluation of coronary atherosclerotic lesions during cardiac surgery.

We explored techniques that would allow the surgeon to localize coronary artery lesions demonstrated angiographically or to supplement angiographic information in patients who are undergoing coronary artery bypass procedures by intraoperative scanning of the coronary arteries using ultrasound. A 9-MHz electronically focused water-path ultrasound scanner was first used to image the coronary arteries in three anesthetized, open-chest sheep. In a subsequent study, 10 human subjects undergoing cardiac surgery for valve replacement who had normal coronary angiograms were scanned during heart surgery to provide images of normal coronary arteries. The ultrasoundprobe was sterilized with gas and placed directly on the beating heart by the surgeon. In the third phase of this study, 21 patients with coronary artery disease were scanned and the ultrasonic appearance of their imaged coronary lesions was compared to independently interpreted angiographic estimates of percent obstruction, with close correlation (r = 0.91). The ultrasound scan could be used to identify lesions in vessels beyond proximal occlusions, which are not visualized well angiographically, and could localize thesite of lesions to determine placement of saphenous vein bypass grafts. This new technique may provide a method of evaluating coronary atheroscleroticlesions during coronary artery surgery and aid decisions regarding placement of saphenous vein grafts.