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Biomedical subjects

R C Leinbach

Publications and source records attributed to R C Leinbach.

At least 19 recordsLinked to original sources
PubMed1992

Antithrombotic effect of a monoclonal antibody against tissue factor in a rabbit model of platelet-mediated arterial thrombosis.

Activation of the coagulation system by contact of circulating blood with tissue factor, a component of the extrinsic blood coagulation pathway that is produced in the vessel wall, may represent a pathway for the initiation of thrombosis in atherosclerotic vessels. This hypothesis was tested in vivo in a rabbit femoral artery eversion (inside-out) graft model, in which the adventitia, with its tissue factor, was exposed to circulating blood. Intra-arterial infusion of a neutralizing monoclonal antibody against tissue factor (D3) at a rate of 12 mg/kg over 15 minutes prevented thrombosis of a 7-8-mm eversion graft within a 2-hour observation period in four of five rabbits, whereas with a control antibody infusion (MA-15C5), occlusion occurred within 2 hours in five of six rabbits. In vitro immersion before reinsertion of the arterial segment in a solution containing 2 mg/ml of the control antibody for 30 minutes was associated with occlusion in all six rabbits, whereas pretreatment with D3 was associated with persistent patency in three of nine rabbits. Stepwise logistic-regression analysis of the results with perfusion status as the dependent variable and type of antibody (D3 or MA-15C5), application method (infusion versus immersion), and graft segment length as independent variables yielded a significant difference in frequency of occlusion with the two antibodies (p = 0.016). It is concluded that exposure of tissue factor to flowing blood may constitute a trigger mechanism for platelet-mediated arterial thrombosis.

Animals↗
PubMed1991

Bleeding time prolongation and bleeding during infusion of recombinant tissue-type plasminogen activator in dogs: potentiation by aspirin and reversal with aprotinin.

Thrombolytic therapy is associated with a bleeding tendency that may be exacerbated by adjunctive antiplatelet agents. The effect of recombinant tissue-type plasminogen activator (rt-PA) alone or in combination with aspirin on serial measurements of template bleeding time, ex vivo platelet aggregation and coagulation factors and the frequency of bleeding was studied in dogs. During infusion of rt-PA (15, 30 or 60 micrograms/kg per min for 90 min), a dose-related increase in bleeding time was observed. In a randomized blinded study of 25 dogs, the baseline bleeding time (mean +/- SD) was 3.5 +/- 1 min in control animals and 4 +/- 2 min after oral aspirin (15 mg/kg body weight). Infusion of rt-PA (15 micrograms/kg per min for 90 min) prolonged the bleeding time to a maximum of 15 +/- 12 min. In contrast, combined aspirin and rt-PA therapy produced an increase to greater than 30 min during infusion, reverting to 13 +/- 10 min within 2 h after cessation of infusion. Recurrent continuous bleeding from incision sites occurred in one of six dogs given aspirin alone, two of seven given rt-PA alone and all six dogs given both aspirin and rt-PA (p = 0.02). Bleeding time greater than 9 min correlated significantly with bleeding frequency (p less than 0.0001), with a sensitivity of 100% and a specificity of 87%. Intravenous bolus injection of aprotinin (20,000 kallikrein inhibitor units/kg body weight) in six dogs given both rt-PA and aspirin produced a decrease in bleeding time from greater than 30 min to 9.5 +/- 9 min and resulted in cessation of bleeding. Thus, bleeding and bleeding time prolongation in this canine model are potentiated by a marked interactive effect of rt-PA and aspirin that is rapidly reversible. Template bleeding times may provide a useful quantitative index for monitoring the bleeding tendency associated with thrombolytic therapy.

Animals↗
PubMed1991

Kistrin, a polypeptide platelet GPIIb/IIIa receptor antagonist, enhances and sustains coronary arterial thrombolysis with recombinant tissue-type plasminogen activator in a canine preparation.

BACKGROUND: Kistrin is a 68-amino acid polypeptide from the venom of the Malayan pit viper Agkistrodon rhodostoma, which inhibits the platelet GPIIb/IIIa receptor. Its effect on thrombolysis, reocclusion, and bleeding associated with administration of recombinant tissue-type plasminogen activator (rt-PA) was studied in a canine model of coronary artery thrombosis. METHODS AND RESULTS: Coronary patency was monitored for 2 hours by ultrasonic flow probe and repeated coronary angiography. The rt-PA was given as 0.45-mg/kg bolus injections at 15-minute intervals until recanalization or to a maximum of four boluses. Four groups of four or five dogs were studied: a control group that received intravenous heparin (4,000-unit bolus and 1,000 units each hour) and three groups that received heparin and 0.48, 0.24, or 0.12 mg/kg kistrin, administered as a 10% bolus injection and an infusion during a 60-minute period. In the control group, reflow occurred in four of five dogs within 37 +/- 47 minutes but was followed by cyclic reflow and reocclusion. Kistrin at a dose of 0.48 and 0.24 mg/kg reduced the time to reflow to 6 +/- 5 and 10 +/- 3 minutes, respectively, and abolished reocclusion. With 0.12 mg/kg kistrin, reflow occurred in all four animals, within 27 +/- 23 minutes, and reocclusion occurred in two animals. Kistrin induced a dose-related prolongation of the template bleeding time: with 0.48 mg/kg kistrin, the bleeding time was prolonged from 3.8 +/- 1.3 minutes before infusion to 29 +/- 2 minutes during infusion, but it was shortened to 8.3 +/- 2.6 minutes at 90 minutes after the end of infusion. Kistrin also caused a dose-related inhibition of platelet aggregation with ADP and collagen: with 0.48 mg/kg kistrin, platelet aggregation was abolished during the infusion but had partially recovered toward the end of the observation period. Pathological examination of recanalized coronary arterial segments of dogs given 0.48 or 0.24 mg/kg kistrin revealed widely patent arteries with some platelets layered on the damaged intimal surface. CONCLUSIONS: Kistrin increases the rate and extent of thrombolysis with a reduced dose of rt-PA, and it prevents reocclusion. At an effective dose, it is associated with a transient prolongation of the bleeding time and inhibition of platelet aggregation. Kistrin may offer promise as adjunctive treatment to thrombolytic agents in patients with acute myocardial infarction.

Animals↗
PubMed1991

Animal models for arterial thrombolysis and prevention of reocclusion. Erythrocyte-rich versus platelet-rich thrombus.

Experimental animal models for erythrocyte-rich (ER) and platelet-rich (PR) arterial thrombosis were developed in dogs and rabbits and used for the evaluation of the effect of antithrombin and antiplatelet agents on thrombolysis with recombinant tissue-type plasminogen activators (rt-PA). The canine models consist of a whole blood clot produced in the left anterior descending coronary artery (ER thrombus) or a 1-cm everted (inside-out) segment graft in the circumflex coronary artery that predisposes to occlusion with PR material (PR thrombus). The rabbit models consist of a femoral arterial whole blood clot (ER thrombus) or a femoral arterial eversion graft (PR thrombus). The whole blood clot models are sensitive to recanalization with rt-PA but are consistently associated with reocclusion, notwithstanding the concomitant use of heparin and/or aspirin. Clot lysis is accelerated and reocclusion is prevented by the administration of F(ab')2 fragments of a monoclonal antibody 7E3 directed against the platelet glycoprotein IIb/IIIa receptor; of Argatroban, a synthetic thrombin inhibitor; or of kistrin, a glycoprotein IIb/IIIa-blocking polypeptide from the Malayan pit viper venom. The PR thrombus models are very resistant to recanalization with rt-PA, but this resistance can be overcome by the concomitant use of the platelet glycoprotein IIb/IIIa-blocking antibody. Thus, selective platelet glycoprotein IIb/IIIa inhibitors are more effective than aspirin, heparin, or both in accelerating arterial thrombolysis with rt-PA; in preventing reocclusion after clot lysis; and in overcoming the resistance of PR thrombus to dispersion with rt-PA. These experimental animal models may be useful in the development of improved thrombolytic strategies using plasminogen activators in conjunction with specifically targeted antiplatelet and anticoagulant agents.

Animals↗
PubMed1990

Quantitation of acute myocardial infarct size by nuclear magnetic resonance imaging.

Nuclear magnetic resonance (NMR) imaging has shown potential in the detection and characterization of acute myocardial infarction in humans. This study was performed to evaluate the capability of NMR imaging in the measurement of infarct size in patients with recent myocardial infarction. Electrocardiographic (ECG)-gated spin-echo NMR imaging was performed in 26 patients a mean of 9 +/- 3 days (range 5 to 20) after infarction. The imaging technique used provided single-slice, spin-echo (time to echo [TE] = 60 ms) images of the left ventricle in its true short axis, allowing direct correlation of NMR infarct location and size with the region of severe hypokinesia on left ventriculography. In all 20 patients with complete NMR studies, infarct location was correctly identified by using specific, objective criteria. The correlation between the mean infarct volume (29 +/- 11 ml) and the quantitated left ventricular hypokinetic segment (7.5 +/- 4.0 cm) was good (r = 0.84, p = 0.0002), suggesting that NMR imaging of the heart may have a role in the noninvasive assessment of myocardial infarct size in patients.

Electrocardiography↗
PubMed1990

Lysis of plasminogen activator-resistant platelet-rich coronary artery thrombus with combined bolus injection of recombinant tissue-type plasminogen activator and antiplatelet GPIIb/IIIa antibody.

Resistance of coronary occlusive thrombus to thrombolytic therapy, found in some patients with acute myocardial infarction, may be due to the presence of platelet-rich coronary clot. Reperfusion therapy in such patients may require the development and evaluation of alternative strategies in animal models. Therefore, platelet-rich coronary artery thrombus was developed by excision, eversion (inside out) and reanastomosis of a 1 cm segment of the left circumflex coronary artery in anesthetized dogs maintained on heparin antiocoagulation. Blood flow was restored in 25 of 27 dogs. Thrombotic occlusion of the everted segment graft with primarily platelet-rich thrombus or thrombus containing platelet-rich and erythrocyte-rich zones, persisting for at least 30 min, occurred within 4.5 +/- 3.5 min (mean +/- SD) in 20 of these 25 dogs. In 5 of these 20 dogs (group I, control), stable occlusion, as monitored with an ultrasound flow probe and coronary angiography, was maintained during a 2 h observation period. In group II (n = 5), intravenous bolus injections of recombinant tissue-type plasminogen activator (rt-PA) at a dose of 0.45 mg/kg body weight at four 15 min intervals did not cause reperfusion in four dogs and produced cyclic reperfusion and reocclusion in one dog. In group III (n = 5), a single intravenous bolus injection of 0.8 mg/kg of the F(ab')2 fragment of a murine monoclonal antibody (7E3) against the human platelet GPIIb/IIIa receptor [7E3-F(ab')2] produced stable reperfusion in two of the five dogs, whereas occlusion persisted in the other three. In group IV (n = 5), injection of 7E3-F(ab')2 (0.8 mg/kg) followed by rt-PA (0.45 mg/kg) caused stable reperfusion without reocclusion in all dogs (p less than 0.05 versus rt-PA alone and p less than 0.01 versus control). This study confirms that platelet-rich occlusive coronary thrombus is very resistant to lysis with intravenous rt-PA. However, this resistance may be overcome by the combined use of a reduced dose of rt-PA and the antiplatelet GPIIb/IIIa receptor antibody 7E3. The results indicate that platelet-rich thrombus resistant to thrombolytic agents may be dispersed pharmacologically without resort to mechanical recanalization. The present dog model may be useful in investigating specific strategies for the dispersion of resistant platelet-rich coronary thrombus.

Animals↗
PubMed1990

Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet glycoprotein IIb/IIIa antibody on coronary artery reperfusion, reocclusion and bleeding with recombinant tissue-type plasminogen activator in a canine preparation.

The comparative effects of intravenous aspirin, the synthetic thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (Argatroban) and F(ab')2 fragments of monoclonal antibody 7E3 against platelet glycoprotein IIb/IIIa (7E3-F[ab']2) on thrombolysis, reocclusion and bleeding associated with 0.45 mg/kg body weight bolus injections of recombinant tissue-type plasminogen activator (rt-PA) were studied in a canine coronary artery thrombosis model. Coronary patency was monitored for 2 h both by flow probe and by coronary angiography. Four groups were studied: Group I = pretreated with 17 mg/kg intravenous aspirin (n = 6), Group II = pretreated with 200 micrograms/kg per min intravenous Argatroban for 60 min (n = 5), Group III = pretreated with aspirin and Argatroban (n = 5) and Group IV = pretreated with 0.8 mg/kg intravenous 7E3-F(ab')2 (n = 5). In Group I, reflow occurred in four of six dogs, but did not persist; reflow was induced in Group II in four of five dogs, persisting in one; in Group III, reflow occurred in all five dogs, persisting in four; in Group IV reflow was achieved in four of five dogs, persisting in two. The frequency of persistent reflow in Group III was significantly higher than in the combined Groups I and II (p = 0.012), whereas the time to reflow was significantly shorter in the groups receiving Argatroban than in the aspirin group (median 25 versus 55 min, p = 0.04). There were no significant differences between Groups III and IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Serial evaluation of right ventricular dysfunction associated with acute inferior myocardial infarction.

Right ventricular (RV) function was evaluated serially by multigated blood pool imaging in 18 patients with RV dysfunction associated with acute inferior myocardial infarction. Radionuclide ventriculograms were performed on all patients within 18 hours of chest pain and again at 10 days. In addition, 15 of 18 patients had rest and exercise radionuclide ventriculograms at 3 months. The mean resting right ventricular ejection fractions (RVEF) at admission, 10 days, and 3 months in these patients was 31.8 +/- 12.6% (SD), 46.9 +/- 11.2% (p less than 0.05), and 44.5 +/- 10.2% (p less than 0.05), while the left ventricular ejection fractions were 55.9 +/- 10.6%, 57.9 +/- 13.3%, and 53.1 +/- 11.2% (p = ns). The 3-month exercise radionuclide ventriculogram demonstrated an increase in RVEF greater than 5% in 6 of 15 patients. In eight catheterized patients, neither the location nor the severity of coronary artery narrowing nor the presence of collaterals correlated with the RV exercise response. Improvement in RV function over a 10-day interval following acute inferior myocardial infarction suggests the presence of significant reversible right ventricular dysfunction during the acute phase.

Cardiac Catheterization↗
PubMed1990

Prevention of platelet-rich arterial thrombosis by selective thrombin inhibition.

The effect of heparin and of the synthetic competitive thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfon yl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (argatroban) on platelet-rich arterial thrombosis was studied in a rabbit model, consisting of a 4-6-mm everted ("inside-out") femoral arterial segment. Intravenous injection of heparin (200 units/kg) failed to prevent occlusion within 60 minutes in all 10 rabbits, whereas intravenous argatroban infusion at a rate of 100 or 200 micrograms/kg/min for 60 minutes, which prolonged the thrombin time more than fourfold, prevented thrombosis in nine of 13 rabbits (p = 0.002 vs. i.v. heparin). Intra-arterial infusion of 200 units/kg heparin over 60 minutes prevented occlusion in six of nine rabbits (p = 0.003 vs. i.v. heparin), whereas intra-arterial argatroban at a rate of 100 micrograms/kg/min for 60 minutes prevented thrombosis in all 10 rabbits (p = 0.00001 vs. i.v. heparin). Patency of femoral arterial segments was maintained after the end of the intra-arterial heparin and intravenous or intra-arterial argatroban infusion for up to 3 hours despite normalization of the thrombin time and partial thromboplastin time. Pathologic examination of the graft revealed that the inverted adventitial surface was covered by layers of platelets without platelet aggregation or fibrin deposition. These findings indicate that thrombin plays an important role in platelet-rich arterial thrombosis, and that the thrombogenic stimulus is rapidly attenuated by short-term infusion of the synthetic thrombin inhibitor. Selective thrombin inhibition can constitute an alternative approach to the prevention of arterial occlusion after angioplasty or thrombolytic therapy in patients with unstable coronary syndromes.

Animals↗
PubMed1990

In vivo thrombin inhibition enhances and sustains arterial recanalization with recombinant tissue-type plasminogen activator.

The effects of heparin and the synthetic competitive thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfon yl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (Argatroban) on thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) was studied in groups of six or seven rabbits with arterial thrombosis. The model consisted of a whole-blood clot produced in a 1-cm isolated femoral arterial segment with superimposed endothelial damage and distal high-grade stenosis. rt-PA was injected as an intravenous bolus of 0.45 mg/kg body wt at 15-minute intervals until recanalization, or up to a maximum of four boluses. In seven rabbits given an intravenous injection of 17 mg/kg aspirin, rt-PA induced transient reflow in only one animal. In seven rabbits that received intravenous heparin (200 units/kg over 60 minutes), rt-PA administration produced reflow in five animals, which was persistent in two rabbits. Combined administration of aspirin and heparin in seven rabbits was associated with similar rt-PA-induced recanalization. rt-PA administration in six rabbits given intravenous Argatroban (100 micrograms/kg/min for 60 minutes) caused recanalization in five, with persistent patency in three. In six rabbits given aspirin and Argatroban, rt-PA caused recanalization in all, with persistent patency in five animals. Reflow occurred significantly more rapidly with Argatroban (14 +/- 7 minutes) than with heparin (35 +/- 11 minutes), reflow was obtained with fewer boluses of rt-PA in combination with Argatroban (median value of one bolus) than with heparin (median value, three boluses), and reocclusion after reflow was less frequent with Argatroban (0 of 11 versus 5 of 10 rabbits). Furthermore, the degree of thrombolysis determined by pathological analysis was significantly more extensive with Argatroban than with heparin, and patency persisted during a 3-hour observation period, despite elimination of Argatroban from the circulation. Thus, Argatroban, relative to heparin, enhances and sustains thrombolysis with rt-PA. It may offer promise as an adjunctive agent for thrombolytic therapy of arterial thrombosis.

Animals↗
PubMed1979

Right ventricular infarction. Clinical diagnosis and differentiation from cardiac tamponade and pericardial constriction.

Twelve patients with a clinical diagnosis of right ventricular infarction are described. All had acute inferior wall myocardial infarction associated with the bedside findings of jugular venous distension, clear lungs on auscultation, and arterial hypotension. Hemodynamically, there was elevation of right-sided filling pressures not explained by normal or minimally elevated pulmonary wedge pressures. Four patients had an incorrect diagnosis of acute cardiac tamponade. However, a review of the data showed that the hemodynamic features of right ventricular infarction more closely resemble those of pericardial constriction, a point that may be helpful in distinguishing right ventricular infarction from cardiac tamponade. Invasive and noninvasive techniques that exclude the presence of pericardial fluid and suggest enlargement and abnormal contractility of the right ventricle were helpful in establishing the diagnosis of right ventricular infarction in several patients.

Aged↗
PubMed1979

Patterns of haemodynamic alteration during left ventricular ischaemia in man. Relation to angiographic extent of coronary artery disease.

Haemodynamic changes produced by rapid atrial pacing (60 patients, 52 of whom developed angina) or in association with spontaneous angina (32 patients) were measured in 92 patients with angiographic coronary artery disease. The extent of coronary artery disease was scored by the jeopardy score system (range 0 to 12). The haemodynamic changes induced by ischaemia occurred in 3 patterns: pattern I, no change in filling pressure or in mean systemic arterial pressure; pattern II, a rise in filling pressure and a rise in mean systemic arterial pressure; pattern III, a rise in filling pressure, but no significant change or a fall in mean systemic arterial pressure. In patients who had a pattern II or a pattern III response to ischaemia, the change in mean systemic arterial pressure was linearly related to the corresponding change in cardiac output. The likelihood of a patient showing a given pattern of ischaemia-induced haemodynamic change was related to the extent of coronary artery disease; of 22 patients with jeopardy scores of 2 or 4, 91% exhibited pattern I, 9% pattern II, and none pattern III; of 39 patients with jeopardy scores of 6 or 8, 40% exhibited pattern I, 22% pattern II, and 38% pattern III; of 31 patients with jeopardy scores of 10 or 12, 12% exhibited pattern I, 10% pattern II, and 78% pattern III (P less than 0.01). Among the 54 patients in whom serial cardiac output determinations were available, a decline of the left ventricular function curve during ischaemia was demonstrable in 8% of those with a pattern I response, in 54% of those with a pattern II response, and in 90% of those with a pattern III response (P less than 0.01). The pattern of response was unrelated to resting angiographic left ventricular ejection fraction, whether ST segments became elevated or depressed, or whether ischaemia was pacing-induced or spontaneous. These results suggest that the haemodynamic response to ischaemia is determined by the fraction of the left ventricle that becomes dysfunctional during ischaemia.

Blood Pressure↗
PubMed1979

Survival following mitral valve replacement for mitral regurgitation due to coronary artery disease.

Forty-six patients who underwent mitral valve replacement for mitral regurgitation due to coronary artery disease during 1970-1975 were identified. Forty patients underwent aortocoronary bypass procedures at the same operation. The survival rate at the fourth postoperative year was 73% in the 22 patients in whom the preoperative left ventricular ejection fraction exceeded 0.35, 38% in the 16 patients in whom the preoperative left ventricular ejection fraction was 35% or less, and 25% in the eight patients in whom aneurysmectomy was performed at the time of mitral valve replacement (p less than 0.05 for the former group compared to the latter two groups). Heart failure, present preoperatively in 41 patients, was improved in most of the long-term survivors. Neither the angiographic extent of coronary artery disease nor whether mitral valve replacement was performed in the acute (within 2 months in 13 patients) or chronic phase of myocardial infarction were distinctly correlated with survival.

Aged↗
PubMed1979

Safe early revascularization for continuing ischemia after acute myocardial infarction.

Early revascularization following myocardial infarction (MI) is reported to have a high risk of extension of and hemorrhage into infarction with resulting high mortality and morbidity. To evaluate this issue, 80 post-MI patients (aged 32-74 years) with unstable angina pectoris resistant to maximal medical therapy were reviewed. All patients underwent early uncomplicated angiography and subsequent revascularization; 55 (69%) were less than 10 days post-MI, and 25 (31%) were 10-30 days post-MI. Intraaortic balloon pumping was required in 72% for relief of intractable angina or hemodynamic instability. Of the 80 patients, 19% had single vessel disease (VD), 31% double VD, and 50% triple VD. The mortality rate from coronary bypass surgery was 7/80 (8.8%), with four cardiac and three noncardiac deaths. Two patients suffered a perioperative MI (2.5%). At a mean follow-up period of 33 months, there had been only one late death and one recurrent nonfatal MI; 96% of the patients had no significant angina. In patients with continuing ischemia immediately after MI, myocardial revascularization can be safely performed without further injury to the myocardium, and with excellent long-term results.

Adult↗
PubMed1978

Early intraaortic balloon pumping for anterior myocardial infarction without shock.

Eleven patients with anterior myocardial infarction less than six hours old underwent intraaortic balloon pumping (IABP) in an attempt to control injury. Direct hemodynamic measurements excluded shock. Response to therapy was judged individually by comparison to a one-hour pretreatment period. There was no parallel control group. Five patients responded with an 84% fall in ST elevation in one hour, with preservation of precordial R waves and good ventricular function. In contrast, six patients responded poorly, with a 40% fall in ST elevation in one hour, Q wave development and poorer residual left ventricular function. Coronary angiography demonstrated a significant correlation between response and presence or absence of complete left anterior descending coronary artery occlusion. Early use of IABP in anterior myocardial infarction may interrupt injury, though in this series only in cases with residual left anterior descending patency.

Adult↗
PubMed1978

Early imaging of experimental myocardial infarction by intracoronary administraion of 131I-labelled anticardiac myosin (Fab')2 fragments.

We examined the feasibility of early imaging of myocardial infarcts by intracoronary injection of 131I-labelled cardiac myosin-specific antibody (Fab')2. The left anterior descending coronary artery was occluded for 5 hours by a balloon catheter introduced through the carotid artery in 12 dogs. The catheter was withdrawn and 1 mCi 201Tl was injected intravenously and 500 muCi of 131I antibody were injected into the main left coronary artery. Six of these animals demonstrated evidence of myocardial infarction by ECG and subsequent triphenyl-tetrazolium chloride staining, while the others did not. In each of the infarcted animals, in vivo scintograms one-half hour after injection of isotope showed uptake of 131I in the anteroapical region of the heart corresponding to the region of absent 201Tl uptake. This relationship was confirmed in the excised hearts and in heart slices. In slices, 131I uptake corresponded to regions that did not stain with triphenyltetrazolium chloride. In the six animals that did not show evidence for infarction after coronary occlusion, uptake of 131I was not demonstrated, either in vivo or in excised specimens. In four additional dogs subjected to the same procedure, 125I-labelled (Fab')2 from nonimmune IgG was injected simultaneously into the left main coronary artery with 131I-labelled canine myosin-specific antibody (Fab')2. The ratio of uptake between infarct center and normal tissue was 34.3 +/- 1.5 (mean+/-SEM) for the specific antibody fragment as contrasted to 6.6+/-0.4 for the nonimmune IgG fragment, indicating that intracoronary injection does not favor nonspecific sequestration of protein in regions of infarction. Thus, the intracoronary administration of myosin-specific antibody fragments leads to early and specific one-half hour imaging of myocardial infarcts.

Animals↗