The critical role of aprotinin in controlling haemostasis in conjunction with non-pharmacological blood-saving strategies during routine coronary artery bypass surgery.

OBJECTIVE: Aprotinin, a non-specific serine protease inhibitor, has been confirmed to be safe and effective in reducing intra- and postoperative blood drainage, transfusion requirements, and perioperative morbidity and mortality during coronary artery bypass surgery. It is the only one of the currently available haemo-static agents that is approved by the U.S. Food and Drug Administration (FDA) for use in cardiac surgery. However, one major weakness of currently available trials is the lack of information regarding the concomitant usage of aprotinin with blood-saving strategies that have been used more frequently in recent years. METHODS: Patients undergoing elective first-time coronary artery bypass grafting (n = 172) who were given systemic high-dose aprotinin (n = 85), combined systemic high-dose aprotinin and topical aprotinin (n = 27), or no aprotinin (n = 60) were reviewed retrospectively. The use of all blood-saving procedures was systematically taken in account. RESULTS: Postoperative blood drainage was significantly less in patients treated with aprotinin than controls (P < 0.0001). Concomitant use of topical aprotinin was accompanied by a postoperative blood loss reduction of 35% compared to systemic aprotinin use alone (P < 0.003). The intra- and postoperative donor blood requirements were dramatically reduced in both aprotinin-treated groups compared to controls, although patients received different blood saving strategies as appropriate (P < 0.0001). A trend of up to 20% lower postoperative blood drainage was noted in patients in whom intraoperative haemodilution and autologuos blood transfusions were used (P > 0.05). CONCLUSIONS: The present analysis demonstrates that the local and systemic administration of aprotinin is safe and effective in reducing intra- and postoperative blood drainage and transfusion requirements. In elective CABG procedures, aprotinin should still be used even if blood-saving strategies are employed.

European multi-centre comparison of thallium 201 and technetium 99m methoxyisobutylisonitrile in ischaemic heart disease.

Fifty-six patients in Europe were entered into a multi-centre study to compare the accuracy of technetium 99m methoxyisobutylisonitrile (99mTc-MIBI) for the detection of coronary artery disease (CAD) with thallium 201 (201Tl) chloride perfusion scanning. The results showed a high degree of concordance between the two radiopharmaceuticals. Some 81% (678/840) of myocardial segments showed the same result (normal, infarct or ischaemia), and 80% (45/56) of patients had the same diagnosis. Overall detection of CAD in patients was 98% for 201T1 and 96% for 99mTc-MIBI. Detection of CAD in total arteries was 68% for both agents. In this study 99mTc-MIBI was as accurate as 201Tl for the detection of coronary artery stenoses.

99mTc hexakis-t-butyl isonitrile (TBI): an agent for the diagnosis of coronary artery diseases.

Basic and clinical studies were undertaken to determine pharmacokinetic mechanisms, blood flow-related characteristics and potential clinical utility of the 99mTc hexakis-t-butyl isonitrile (TBI) in the non-invasive diagnosis of ischemic heart diseases. Pharmacokinetic studies with TBI in animals demonstrated a high initial lung, heart and liver uptake. The lung clears at a relatively faster rate, the activity in the heart remained constant with a buildup of activity in the liver. These pharmacokinetic characteristics allowed for a myocardial imaging at 30-45 min post-injection at rest. The regional myocardial distribution of TBI was shown to be linearly related to microsphere-determined regional myocardial blood flow with a redistribution potential in transient ischemic myocardium (i.e., mimics 201Tl). The first pass extraction fraction (in vitro) for TBI was shown to be nearly 100% and independent on flow levels. In general, the slow tissue clearance rate or the lack of it might be due to the high degree of lipophilicity with the complete lack of any hepatic or extrahepatic metabolism to a less lipophilic metabolite. The complex demonstrated a high degree of cardiac membrane association. The net extraction in isolated heart slices was shown to be dependent on pH and temperature, independent of energy. The clinical studies demonstrated a similar pharmacokinetic pattern to the animal studies and documented the perfusion and ventricular function utility of TBI in the diagnosis of ischemic heart diseases.