Dipyridamole preserved platelets and reduced blood loss after cardiopulmonary bypass

Cardiopulmonary bypass activates and depletes platelets, which may contribute to postoperative bleeding. In addition, activated platelets may be deposited in the coronary vasculature after ischemia and cardioplegia, which may delay recovery of cardiac function and metabolism and may contribute to early bypass graft occlusion. The antiplatelet agent dipyridamole reduces platelet activation and depletion and may decrease postoperative bleeding and transfusion requirements. A prospective randomized trial was conducted in 58 patients undergoing elective coronary bypass operations to compare the effects of oral (19 patients) and intravenous (21 patients) dipyridamole to the results obtained in a control group (18 patients) who received no dipyridamole. Preoperative oral administration of dipyridamole resulted in lower plasma drug concentrations in the early postoperative period than perioperative intravenous administration (p = 0.0001 by analysis of variance). Postoperative arterial platelet counts were highest in the patients receiving intravenous dipyridamole, intermediate in those receiving oral dipyridamole, and lowest in the control group (p = 0.03 by analysis of variance). Postoperative blood loss and blood product transfusions were significantly reduced with both oral and intravenous dipyridamole (p = 0.04 by analysis of variance). Dipyridamole preserved platelets and reduced postoperative bleeding. Intravenous dipyridamole resulted in higher platelet counts than oral dipyridamole and may be required to reduce postoperative bleeding in high-risk patients.     

Decreased postoperative myocardial fatty acid oxidation

Myocardial substrate preferences following cardioplegic arrest for coronary bypass surgery have not been established. Fatty acids are believed to be the major fuel source for aerobic metabolism. Following cardioplegic arrest arterial fatty acid levels are elevated and myocardial fatty acid accumulation without oxidation may contribute to reperfusion injury. Perioperative fatty acid metabolism was evaluated in 18 patients undergoing elective coronary bypass surgery who were randomized to receive either blood (n = 11) or crystalloid (n = 7) cardioplegia. Palmitate labeled with 14carbon was infused perioperatively and arterial and coronary sinus blood samples were obtained to calculate myocardial fatty acid extraction and oxidation before and after cardioplegic arrest. Lactate and glycerol were released from the heart during both blood and crystalloid cardioplegia, suggesting ischemic glycolysis and lipolysis. Myocardial oxygen consumption was depressed and the myocardial consumptions of lactate, glucose, and fatty acids were minimal during the first 60 min after aortic clamp removal in both groups despite high arterial concentrations. Fatty acid oxidation was minimal after blood cardioplegia and was not found after crystalloid cardioplegia. Fatty acids were extracted by the heart, but were not aerobically metabolized following cardioplegic arrest. Myocardial fatty acid accumulation without oxidation may have been deleterious. The inability of the heart to oxidize exogenous fatty acids may reflect altered myocardial exogenous substrate preferences during reperfusion following coronary bypass surgery.     

Heart valve operations in patients with active infective endocarditis

Sixty-two consecutive patients underwent heart valve operation for active infective endocarditis. There were 42 men and 20 women whose mean age was 49 years (range, 21 to 79 years). The infection was in the aortic valve in 37 patients, the mitral valve in 18, the aortic and mitral valves in 5, and the tricuspid valve in 2. Twenty-four patients had prosthetic valve endocarditis. Staphylococcus and Streptococcus were responsible for 86% of the infections. Annular abscess was encountered in 33 patients. Complex valve procedures involving reconstruction of the left ventricular inflow or outflow tract or both were performed in 31 patients. There were three operative deaths (4.8%). Predictors of operative mortality were prosthetic valve endocarditis, preoperative shock, and annular abscess. Patients were followed for 1 month to 130 months (mean follow-up, 43 months). Only 1 patient required reoperation for persistent infection. There were ten late deaths. Most survivors (96%) are currently in New York Heart Association class I or II. The 5-year actuarial survival was 79% +/- 7%. These data demonstrate excellent results in patients with native valve endocarditis, and support the premise that patients with prosthetic valve endocarditis should have early surgical intervention.     

The Ethical Design of an AIDS Vaccine Trial in Africa

Proper conduct of an AIDS vaccine trial in Africa must be informed not only by the epidemiology and biology of HIV infection in African settings, but also by the ethical norms and cultural constraints prevailing in African settings.     

Focal spacing and near-field heating during pulsed high temperature ultrasound therapy

It has been proposed that high temperature short duration hyperthermia treatment would be perfusion insensitive and thus, significantly improved thermal exposure uniformity could be achieved. This study investigates the execution of such a treatment, which utilizes single spherically curved transducer and multiple sonications to cover the complete target volume. The spacing of neighboring pulses as a function of the transducer characteristics was studied utilizing computer simulations. In addition, the temperature elevation in front of the focal zone during multiple sonications was evaluated. It was found that significant delays (20 s or longer) between the sonications must be introduced in order to avoid unwanted tissue damage in front of the focal zone. In addition, decreasing the pulse duration and F-number reduced the temperature build-up in front of the focus. The results were verified in vivo in dog's thigh muscle. This study is important not only for hyperthermia but also for ultrasound surgery, and indicates that each sonication system must be carefully evaluated for potential thermal damage outside of the target volume prior to implementation in therapy.     

Pulse duration and peak intensity during focused ultrasound surgery: Theoretical and experimental effects in rabbit brain in vivo

The goal of this study was to establish the exposure parameters that will generate predictable thermally induced lesions in brain. In addition, the accuracy of a theoretical model for prediction of the lesion size was tested. To do this, 160 adult rabbits were sonicated (frequency 0.936 and 1.72 MHz) and then sacrificed at various intervals after the sonications. The results showed that predictable thermal lesions could be induced if the exposure durations were between 0.5 and 2 s. Dimensions of the necrosed tissue volume were roughly predictable by the theoretical calculations based on purely thermal effects. Shorter sonications required higher intensities (above 3700 W cm⁻² at 1.72 MHz) resulting in mechanical effects with extensive vascular damage. Lesion size varied more at longer exposures (5 and 10 s), perhaps due to the increased effect of tissue perfusion. As a conclusion, focused ultrasound can be used for destruction of tissues deep in brain without causing undesirable mechanical effects, if the exposure parameters are selected properly.     

Timing of referral of terminally Ill patients to an outpatient hospice

Objective: Since inordinately long or short lengths of stay at hospice can create problems for patients, providers, and payers, the author sought to identify predictors of timing of patient referral. Methods: A retrospective cohort of 405 hospice outpatients was analyzed with Cox regression to evaluate the effect on length of stay of patient age, gender, race, diagnosis, activity level, mental status, dyspnea, insurance, income, religion, and home support, and of referring physician specialty. Results: Median survival time at the hospice was 29 days; 15% of the patients died within seven days and 12% lived longer than 180 days. A one-unit increment in a six-unit activity-level scale was associated with a 19% reduction in the rate of death. Compared with reference groups, oriented patients and depressed patients had 57% and 35% lower death rates; patients with prostate cancer and cardiovascular disease had 50% and 58% lower death rates. There was no significant gender, race, religion, insurance, or income difference among the patient groups. Conclusions: Inappropriately early or late referral occurs in a substantial minority of patients referred to the hospice under study. Closer attention to accurate prognostication in different types of terminally ill patients and more timely referral to hospice might help to optimize the use of this health care resource from both patient and societal perspectives. Received from the Division of General Internal Medicine, Leonard Davis Institute of Health Economics, Department of Sociology, University of Pennsylvania, Philadelphia, Pennsylvania. Supported by the Robert Wood Johnson Foundation Clinical Scholars Program and by the Warren-Whitman-Richardson Fellowship from Harvard Medical School. Dr. Christakis is the recipient of a NRSA Fellowship from the Agency for Health Care Policy and Research. Computer facilities were provided by the Department of Sociology, University of Pennsylvania. The opinions and conclusions herein are the author’s and do not necessarily represent the views of the Robert Wood Johnson Foundation.