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D T Eitzman

Publications and source records attributed to D T Eitzman.

22 records · Page 2Linked to original sources
PubMed1994

Heparin neutralization by platelet-rich thrombi. Role of platelet factor 4.

BACKGROUND: Platelets contain several factors that inhibit heparin. This study was designed to assess the heparin-neutralizing activity present in acute, platelet-rich arterial thrombi formed at sites of arterial injury in animals. METHODS AND RESULTS: Platelet-rich thrombi (n = 3) were induced in pig coronary arteries by balloon catheter-mediated arterial injury. Soluble extracts were prepared from each thrombus and assayed for the capacity to inhibit heparin in an in vitro clotting assay (activated partial thromboplastin time). Mean heparin-neutralizing activity was 28 U of heparin neutralized per milliliter of thrombus, indicating that 1 vol of coronary thrombus completely inhibited the heparin present in 140 vols of therapeutically anticoagulated (0.2 U heparin/mL) plasma. In contrast, thrombus extracts had no effect on the anticoagulant activity of hirudin, a direct-acting thrombin inhibitor. The heparin-neutralizing activity present in coronary thrombi bound to heparin-agarose and was eluted from it by 1.4 mol/L NaCl, suggesting that platelet factor 4 mediated the antiheparin effect of thrombi. Consistent with this hypothesis, a murine monoclonal antibody to rabbit platelet factor 4 nearly completely inhibited the heparin-neutralizing activity present in rabbit thrombi (n = 3) generated by carotid artery injury. CONCLUSIONS: Extracts prepared from platelet-rich arterial thrombi significantly inhibit the in vitro anticoagulant potency of heparin but not of hirudin. This antiheparin effect appears to be mediated by platelet factor 4. These results are consistent with the hypothesis that localized inhibition of heparin at sites of platelet activation may reduce its antithrombotic efficacy. In addition, they suggest an additional mechanism for the apparent superiority of hirudin over heparin as a thrombin inhibitor at sites of arterial injury.

Animals↗
PubMed1994

Relation of regional function, perfusion, and metabolism in patients with advanced coronary artery disease undergoing surgical revascularization.

BACKGROUND: Imaging of myocardial glucose metabolism using [18F]fluorodeoxyglucose (FDG) with positron emission tomography (PET) has been proposed for identification of tissue viability in patients with advanced coronary artery disease. This study was designed to evaluate the predictive value of flow and metabolic imaging for functional recovery after revascularization in myocardial segments of varying degrees of dysfunction. METHODS AND RESULTS: Thirty-seven patients (mean age, 59 +/- 11 years) with coronary artery disease and impaired left ventricular function (ejection fraction, 34 +/- 10%) were studied with PET using FDG and [13N]ammonia before surgical coronary revascularization (3 +/- 1 grafts per patient). Tissue was scintigraphically characterized as normal, nonviable (concordant reduction of perfusion and FDG uptake), viable without discordance of perfusion and metabolism (mildly reduced perfusion and metabolism), or ischemically compromised (mismatch of reduced perfusion and maintained FDG uptake). Functional outcome was assessed by serial radionuclide ventriculography before and at 13 +/- 13 weeks (median interval of 8 weeks) after coronary revascularization. Preoperatively impaired regional wall motion improved significantly in ischemically compromised (mismatch) revascularized segments but not in nonviable myocardium or in viable myocardium without discordance of perfusion and metabolism. The negative predictive value of PET for functional recovery was 86%, whereas the positive predictive value in revascularized regions ranged from 48% to 86% depending on severity of baseline wall motion abnormalities. CONCLUSIONS: PET identifies metabolically active tissue, which benefits from revascularization. Although the negative predictive value of PET for recovery was high, functional improvement of viable but ischemically compromised tissue was less frequent than previously reported. The predictive value of PET was highest in left ventricular segments with severe dysfunction and a mismatch or reduced perfusion but preserved metabolism. Integration of PET, angiographic, and functional data is necessary for the optimal selection of patients with advanced coronary artery disease and impaired left ventricular function for revascularization.

Adult↗
PubMed1989

Nifedipine administered after reperfusion ablates systolic contractile dysfunction of postischemic "stunned" myocardium.

Recent evidence suggests that postischemic contractile dysfunction of viable myocardium salvaged by reperfusion ("stunned myocardium") may be a consequence of abnormal calcium flux within the previously ischemic cells. Calcium channel blocking agents have been shown to enhance contractile function of stunned postischemic tissue, but it is not certain whether these improvements in function are due to the profound hemodynamic and vasodilator effects of these agents or to a direct effect on calcium flux within the stunned myocytes. Therefore, the effects of 1) high doses of nifedipine, given intravenously at 30 min after reperfusion, and 2) minute doses of nifedipine, infused directly into the coronary circulation at 30 min after reflow, were assessed and compared in anesthetized open chest dogs subjected to 15 min of transient coronary artery occlusion. As anticipated, intravenous nifedipine significantly reduced arterial pressure and increased regional myocardial blood flow. In addition, intravenous nifedipine restored systolic contractile function of the stunned, previously ischemic tissue to essentially normal preocclusion values: segment shortening averaged 102 +/- 8% versus 26 +/- 11% of baseline at 2 h after treatment in treated versus control dogs, respectively (p less than 0.003). Low dose intracoronary infusion of nifedipine did not alter hemodynamic variables or myocardial blood flow, but did improve segment shortening (90 +/- 9% versus 37 +/- 10% of preocclusion values at 1 h after treatment versus 25 min after reperfusion [that is, pretreatment], respectively; p less than 0.03). These data indicate that the calcium channel blocking agent nifedipine, given 30 min after reperfusion, enhances systolic contractile function of postischemic stunned myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗