Robert C. Leinbach

Coronary thrombolysis with recombinant human tissue-type plasminogen activator: a prospective, randomized, placebo-controlled trial.

Forty-five patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were prospectively randomized, two for one, to treatment of acute coronary thrombosis with intravenous recombinant human tissue-type plasminogen activator (rt-PA) or placebo. Each of five additional consecutive patients was treated with a high dose of rt-PA for 2 hr. Twenty-five of 33 patients (75%) receiving 0.5 to 0.75 mg/kg of rt-PA over 30 to 120 min had angiographically proven recanalization within 90 min of initiation of therapy. Only one of 14 patients given placebo had spontaneous recanalization within 45 min (p less than .001). Thirteen placebo-treated patients were crossed over to the intracoronary rt-PA group. Nine (69%) exhibited subsequent recanalization within 45 min. Levels of circulating fibrinogen decreased after treatment with rt-PA by an average of only 8% of baseline values. None of the patients manifested a depletion of fibrinogen level to below 100 mg/dl. Six patients who were completely unresponsive to rt-PA were subsequently treated with intracoronary streptokinase and none responded. Thus, either intravenous or intracoronary rt-PA induced coronary thrombolysis without eliciting clinically significant fibrinogenolysis in patients with evolving myocardial infarction due to thrombotic coronary occlusion.

Comparison Between the Effects of Nitroprusside and Nitroglycerin on Ischemic Injury during Acute Myocardial Infarction

SUMMARY This clinical and experimental investigation was designed to delineate and compare the relative effects of sodium nitroprusside (NP) and nitroglycerin (TNG) on electrocardiographic ischemic injury following acute myocardial infarction in patients and following coronary artery occlusion in dogs. Accordingy, in ten patients with anterior acute myocardial infarction and ST-segment elevation stable for 60 min, the effects ofNP (average 95 4g/min i.v.) and TNG (average 0.48 mg sublingually) were studied. The hemodynamic actions of NP and TNG were directionally similar. However, NP increased average ST-segment elevation (ST) by 2.0 ± 0.2 mm, while TNG reduced ST by 1.4 ± 0.4 mm. In order to clarify this disparity, coronary artery occlusions were carried out in 14 open-chest dogs. During control, NP and TNG time periods, epicardial electrograms were recorded and regional myocardial blood flow (RMBF) determined by the microsphe te N side increased ST-egment elevation from 4.6 ± 0.6 to 5.7 ± 0.6 mV (P < 0.05) and reduced RMBF from 35± 3 to 27 ± 2 mI/uul/100 g (P < 0.01) in the ischemic zones. In contrs, TNG reced; STsegment elevation from 4.9 ± 0.7 to 3.0 ± 0.7 mV (P < 0.05), Wle increasing RMBF to 43 ± 4 ml/mi/100 g (P < 0.05) and the endo/ epicardial ratio from 0.57 ± 0.06 to 0.69 ± 0.07 (P < 0.01). Although TNG and NP exhibit similar hemodynamic effects, TNG reduced electrocardiographic ischemic injury, at least in part, by increasing perfusion of the ischemic areas and redistriutng it favorably, while NP increased electrocardiographic iscbemic injury, at least in part, by reducing perfusion. Therefore, TNG seems preferable to NP for reducing preload and afterload in ts during the early phase of acute myocardial infarction.

Unstable angina pectoris: National cooperative study group to compare surgical and medical therapy: II. In-Hospital experience and initial follow-up results in patients with one, two and three vessel disease

Abstract A prospective randomized study comparing intensive medical therapy with urgent coronary bypass surgery for the acute management of patients with unstable angina pectoris was carried out by nine cooperating medical centers under the auspices of the National Heart, Lung, and Blood Institute. Between 1972 and 1976, a total of 288 patients were entered into the study. All patients had transient S-T or T wave changes, or both, in the electrocardiogram during pain; 90 percent had pain at rest in the hospital, and 76 percent had multivessel coronary disease. The medically and surgically treated patients were comparable with respect to clinical, electrocardiographic and angiographic characteristics and left ventricular function. During the total study period, the hospital mortality rate was 5 percent in the surgical group and 3 percent in the medical group (difference not significant). The rate of in-hospital myocardial infarction was 17 and 8 percent in the respective groups (P In the 1st year after hospital discharge class III or IV angina (New York Heart Association criteria) was more common in medically than in surgically treated patients with one vessel disease (22 percent versus 3 percent, P The results indicate that patients with unstable angina pectoris can be managed acutely with intensive medical therapy, including the administration of propranolol and long-acting nitrates in pharmacologic doses, with adequate control of pain in most patients and no increase in early mortality or myocardial infarction rates. Later, elective surgery can be performed with a low risk and good clinical results if the patients angina fails to respond to intensive medical therapy.

Acute coronary reocclusion after thrombolysis with recombinant human tissue-type plasminogen activator: prevention by a maintenance infusion.

Twenty-nine patients with acute myocardial infarction were treated with recombinant human tissue-type plasminogen activator (rt-PA). The incidence of acute coronary reocclusion and its prevention by a maintenance infusion of rt-PA were studied. Intravenous rt-PA was given at a rate of 0.4 to 0.75 mg/kg over 60 to 120 min after angiographic documentation of complete coronary occlusion. Reperfusion was accomplished within 1 hr in 24 of 29 patients (83%) and was associated with a decrease of the plasma fibrinogen level by 20%. In a first group of 13 patients, 11 of whom were successfully reperfused, prevention of reocclusion was attempted with heparin anticoagulation. However, acute reocclusion within 1 hr after cessation of rt-PA was demonstrated angiographically in five of these patients (45%). Quantitative angiographic analysis indicated that acute reocclusion only occurred in patients with 80% or greater residual stenosis. In patients with less than 80% residual stenosis, heparin anticoagulation was sufficient to maintain patency during the hospital stay in four of five patients. In a second group of patients (n = 16), 13 of whom underwent reperfusion with intravenous rt-PA, seven demonstrated a residual stenosis of 80% or greater. These patients were given heparin and, in addition, 10 mg of rt-PA per hour for 4 hr. None developed acute angiographic reocclusion or clinical signs of reocclusion during the hospital stay. Repeat angiography at 10 to 14 days confirmed persistent patency in six of the seven patients. The maintenance infusion resulted in only a moderate additional drop in fibrinogen, while a steady-state plasma rt-PA level of 750 +/- 250 ng/ml was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. A possible explanation for resistance to coronary thrombolysis.

Acute myocardial infarction is triggered by coronary artery occlusion that may be recanalized by thrombolytic therapy with a success rate of up to 75% only. The resistance of coronary artery occlusion to thrombolysis may either be due to obstruction of the lumen by a nonthrombotic mechanism or by intrinsic resistance of thrombus to dissolution. Coronary arterial thrombi are composed of platelet-rich and erythrocyte-rich material in variable proportions. To evaluate the relative sensitivity of these thrombus components to thrombolysis, we have used two femoral arterial thrombosis models in the rabbit, consisting of erythrocyte-rich clot produced by injecting whole blood and thrombin in an isolated segment and of platelet-rich thrombus spontaneously formed on an everted (inside out) femoral arterial segment. Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) at a rate of 30 micrograms/kg/min consistently reperfused arteries occluded with erythrocyte-rich clot (six of six animals compared with zero of six placebo-treated animals, p = 0.002), whereas infusion of 30 or 100 micrograms/kg/min was significantly less efficient for reperfusion of everted segments occluded with platelet-rich material (only four of 12 animals, p = 0.01). Intra-arterial infusion proximal to the occlusion, at a rate of 20 micrograms/kg/min reperfused six of seven rabbits with erythrocyte-rich clots but only one of seven rabbits with occluded everted segments (p = 0.03). A dose of 100 micrograms/kg/min was necessary to reperfuse platelet-rich occlusions in five of six rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular septal rupture: a review of clinical and physiologic features and an analysis of survival.

Forty-one patients with postinfarction ventricular septal rupture were cared for in our hospital during 1971–1975. Cardiogenic shock developed after septal rupture in 55% of these patients. Shock was unrelated to site of infarction, extent of coronary artery disease, left ventricular ejection fraction, or pulmonaryto-systemic flow ratio, but mean pulmonary artery pressure was lower in shock than in nonshock patients. These observations suggest that shock was produced mainly by right ventricular impairment. Perioperative survival was much higher in patients who did not have shock preoperatively (14 of 17 [82%]) than in those who did (three of 11 [27%]). Magnitude of shunt, left ventricular ejection fraction, extent of coronary artery disease, and performance of aortocoronary bypass grafting were not distinctly correlated with perioperative survival. After a minimum 4-year follow-up, 76% of the perioperative survivors are alive, and none suffer more than New York Heart Association functional class II disability. All 13 unoperated patients (11 in shock) died within 3 months.

Use of Sublingual Nitroglycerin in Congestive Failure following Acute Myocardial Infarction

The effect of 0.3 mg sublingual nitroglycerin (NTG) was evaluated by hemodynamic measurements and precordial S-T-segment mapping in 17 patients following acute myocardial infarction.In all cases NTG produced a prompt reduction in mean pulmonary capillary wedge pressure (PCW) from an average of 19 ± 2 to 14 ± 1 mm Hg associated with a small fall in mean arterial pressure from a mean of 85 ± 4 to 82 ± 4 mm Hg. No significant change in heart rate occurred.In patients without left ventricular failure (PCW 3-12 mm Hg) cardiac output (CO) fell 9%. By contrast, in patients with moderate left ventricular failure (PCW 13-22 mm Hg) CO rose 18%. In three patients with refractory left ventricular failure (PCW 25-31 mm Hg) CO rose 25%. Two of these patients were treated with repetitive NTG doses in addition to previously ineffective diuretic therapy with resolution of resistant pulmonary edema. No significant changes in the magnitude of S-T-segment elevations were noted.NTG may have a special role in the management of acutely ill patients with myocardial infarction in whom pulmonary edema does not respond to conventional therapy.

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.

Clinical and Hemodynamic Results of Intraaortic Balloon Pumping and Surgery for Cardiogenic Shock

The AVCO balloon pump has been employed in treating 40 patients with cardiogenic shock from acute myocardial infarction (CS-MI). All patients were given a trial of medical therapy with hemodynamic monitoring. The time from the development of shock to institution of intraaortic balloon pumping (IABP) was less than 24 hours in all but nine patients. Prior to IABP the mean hemodynamic values were: cardiac index (CI) 1.7 liters/min/m2; mean arterial pressure (MAP) 66 mm Hg; pulmonary artery wedge pressure (PAW) 22 mm Hg. After 24-48 hours of IABP the CI and MAP had increased 0.8 liters/min/m2 and 8 mm Hg, respectively, and the PAW had decreased 4.8 mm Hg. During IABP the shock syndrome was reversed in 31 patients. Four of 25 patients treated with IABP alone survived to be discharged, but two have died from subsequent infarctions. Because of the persistent high mortality, 15 patients judged unable to survive off IABP have undergone emergency surgical procedures with IABP continuing during preoperative angiography and postoperatively. Six were long-term survivors. It is concluded: (1) IABP is a safe, effective means of supporting the circulation in CS-MI; (2) IABP alone will improve survival in some patients; (3) IABP can provide circulatory support during angiography and the perioperative period in patients requiring revascularization for survival; and (4) some patients with CS-MI have myocardial necrosis too extensive to permit survival without permanent circulatory assistance or total cardiac replacement.

Scintigraphic quantification of myocardial necrosis in patients after intravenous injection of myosin-specific antibody.

The Fab fragments of antimyosin antibodies, labeled with 99mTc, were used in the scintigraphic examination of 30 patients with myocardial infarction. The ability to detect necrosis and determine its extent from the antimyosin scan were compared with the results of quantitative regional wall motion analysis by contrast ventriculography at 10 to 14 days and 99mTc-pyrophosphate imaging. Antimyosin images recorded by planar and single photon-emission computed tomography (SPECT) delineated areas of myocardial necrosis in 27 of 30 patients (90%) compared with a 91% sensitivity of pyrophosphate in 21 of 23 patients. Infarct size was determined by both antimyosin and pyrophosphate SPECT images. Results by both techniques showed a significant correlation with computer-derived hypokinetic segment length (r = .79 for both, p = .002) and peak creatine kinase (r = .9 for both, p less than .01). Although sensitivity for and correlations with markers of necrosis were similar with both techniques, infarct size by pyrophosphate SPECT was 1.7 times larger than infarct size by antimyosin SPECT (p less than .01). Certain zones in the infarct area were differentially labeled; the nature and irreversibility of injury within these zones remains to be clarified.