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Background— The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). Methods and Results— Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow–derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; P =0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; P =0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group ( P Conclusions— Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs. Clinical Trial Registration— clinicaltrials.gov. Identifier: NCT00279175.

Standard electrocardiogram (ECG), His-bundle electrogram and biphasic thallium myocardial scanning was undertaken in 13 patients with histologically confirmed sarcoidosis (lung stages I--III). Changes in the standard ECG were present in five (sinus bradycardia, A-V nodal and intraventricular conduction disturbances, non-specific S-T--T changes). The His-bundle electrogram was abnormal in four of eleven patients in whom it was recorded (sick-sinus syndrome, supraventricular extrasystoles, damage to A-V node and supraventricular extrasystoles, damage to A-V node and intraventricular conduction disturbances). In seven of twelve patients who had thallium scans there was a definite irreversible defect, questionable abnormality in three others. Seven of ten patients who had all three tests had definite abnormalities in at least one of them. The electrophysiological findings and the abnormal scans point to cardiac involvement in sarcoidosis.

Two million units of urokinase were administered intravenously as a bolus, either before (group I, n = 40) or after hospital admission (group II, n = 38), to 66 men and 12 women (mean age 55 +/- 8 years) with typical symptoms of acute myocardial infarction of less than 4 hours' duration. Time elapsed between onset of symptoms and urokinase administration averaged 85 +/- 51 min for group I and 137 +/- 50 min for group II (P less than 0.005). The complication rate was low, both during the pre-hospital and the hospital phases, without any significant differences between the two groups. The rate of open infarct vessels (by angiography before discharge from hospital) was 61% for group I and 67% for group II (no significant difference). Global left ventricular function, regional wall motion in the infarct area and maximal creatinekinase values did not significantly differ between the two groups (ejection fraction 51 +/- 10% and 53 +/- 14%, respectively; creatinekinase 838 +/- 634 U/l and 924 +/- 595 U/l, respectively). The data indicate that thrombolytic pre-hospital treatment carried a low risk. The gain of 45 min, however, seems to be of secondary importance in any significant diminution of the acute infarction size.

Intravenous thrombolysis with urokinase (60,000 U/h) was undertaken in 15 patients with large thrombi in the left ventricle (demonstrated by echocardiography) after myocardial infarction. Complete lysis was achieved in ten, partial in four. None had post-thrombolysis signs of arterial emboli, two patients developed haematuria and one had partial separation of the thrombus which required operative removal. Four patients who had a mean ejection fraction of 37 +/- 12% had died a sudden cardiac death within six months of the thrombolysis. Nine patients survived for up to four years without recurrence of thrombi: seven of them had been treated with aspirin (acetylsalicylic acid), two with coumarin derivatives. Two patients could not be followed-up. These preliminary results suggest that large left-ventricular thrombi can be successfully lysed by intravenous thrombolysis without significant complications, probably without recurrent thrombi.

To examine whether the limitation in infarct size after effective thrombolytic therapy is time-dependent the relationship between left ventricular wall motion in the infarct region and the time interval between onset of symptoms and intracoronary streptokinase infusion was investigated. The relationship was significant: When intracoronary thrombolytic therapy was begun within 2 hours, wall motion was almost always within normal limits, whereas the probability of wall motion improvement fell to less than 50%, when treatment was begun later. As a further step a lysis procedure was examined which took account of these findings: the intravenous bolus injection of urokinase. Approximately one hour after bolus injection coronary patency could be demonstrated angiographically in 60% of the infarct patients. A clinically relevant limitation of the infarct size was found in those patients in whom lysis therapy could be begun within 2 hours. On the basis of these findings, a thrombolytic therapy seems to be indicated in all patients with acute myocardial infarction when lysis treatment can be begun within 2 hours. The intravenous urokinase therapy, by virtue of its simplicity, is an alternative to intravenous streptokinase therapy.

Background Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction. Methods In a multicenter trial, we randomly assigned 204 patients with acute myocardial infarction to receive an intracoronary infusion of progenitor cells derived from bone marrow (BMC) or placebo medium into the infarct artery 3 to 7 days after successful reperfusion therapy. Results At 4 months, the absolute improvement in the global left ventricular ejection fraction (LVEF) was significantly greater in the BMC group than in the placebo group (mean [±SD] increase, 5.5±7.3% vs. 3.0±6.5%; P = 0.01). Patients with a baseline LVEF at or below the median value of 48.9% derived the most benefit (absolute improvement in LVEF, 5.0%; 95% confidence interval, 2.0 to 8.1). At 1 year, intracoronary infusion of BMC was associated with a reduction in the prespecified combined clinical end point of death, recurrence of myocardial infarction, and any revascularization procedure (P = 0.01). Conclusions Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infarction. Largescale studies are warranted to examine the potential effects of progenitor-cell administration on morbidity and mortality. (ClinicalTrials.gov number, NCT00279175.)

Objective: The complement system has been suggested to play a role in reperfusion injury which may result from an enhanced destruction of myocardial tissue or from an impairment of reflow. We investigated the influence of the C5b-9 complement complex on infarct size, reflow and arrhythmogenesis. Methods: Twenty-eight C6-competent rabbits and 18 rabbits with congenital C6 deficiency were subjected to either 30 min or 2 h of coronary artery occlusion followed by reperfusion. C6 deficiency was confirmed by the complement titration test and immunohistology. The triphenyl tetrazolium chloride method was used to delineate infarct size. Reflow into infarcted areas was evaluated histologically after an in vivo injection of propidium iodide which served as an early fluorescence microscopic marker of damaged myocardium subjected to reflow. Continuous ECG monitoring allowed the recording of arrhythmias. Results: After 30 min of coronary artery occlusion infarct size was significantly smaller in C6-deficient rabbits (5.0 ± 2% of the risk region) as compared to C6-competent rabbits (28.4 ± 8.5%, P = 0.0371). The extent of reflow into damaged myocardium was nearly the same in both animal groups at this time (38 ± 9 vs. 39 ± 7% of the risk region). After 2 h of coronary artery occlusion, infarct size was not different between both animal groups, but the extent of reflow into damaged myocardium was significantly smaller in C6-competent rabbits than in C6-deficient rabbits (25 ± 4 vs. 40 ± 4%; P = 0.0185). Two of the 18 C6-deficient rabbits had ventricular arrhythmias (Lown II–IV), none of which was fatal. Eleven of the 28 C6-competent animals had major ventricular arrhythmmias which were fatal in 6 rabbits. Conclusions: These results suggest that the lytic C5b-9 complement complex leads to reperfusion injury in the early phase (30 min) of ischaemia, resulting in a larger infarct. After 2 h of ischaemia, complement activation enhances the no-reflow phenomenon but does not affect infarct size. Finally, the C6 status seems to influence the susceptibility to ventricular arrhythmias after coronary artery occlusion, independent of reperfusion.

As part of a prospective randomized double-blind trial (PRIMI) to study the early patency rate of the infarct-related artery after saruplase (INN for recombinant unglycosylated full-length human single-chain urokinase-type plasminogen activator) vs streptokinase in a subgroup of patients, left ventricular function was compared between both treatment groups at 90 min and 24 h after thrombolysis and at discharge, and ventricular function was related to the coronary perfusion grade. Despite a higher patency rate in the saruplase group 60 min after initiating thrombolysis, neither global ejection fraction nor hypokinesia at the infarct site were significantly different between the treatment groups at any of the three time points when function was measured. Hypokinesia at the infarct site remained almost equally severe throughout the study in patients with perfusion grade O, I, and II, and was consistently significantly milder in patients with perfusion grade III. In contrast, in patients with perfusion grade II there was a significant drop in hyperkinesia at the opposite wall at 24 h after thrombolysis and before discharge despite unchanged wall motion at the infarct site. Although patients treated with saruplase had a higher patency rate in the infarct related vessel shortly after the start of thrombolysis, no difference was found in left ventricular function compared to patients treated with streptokinase. Complete reperfusion (TIMI grade III) seems to be a prerequisite for left ventricular function recovery after thrombolysis, whereas only an occluded vessel (TIMI grade O and I) seems to be related to a longer lasting hyperkinesia at the opposite wall.

The terminal, membrane-damaging complement complex C5b-9 accumulates in the infarcted myocardium. In experimental myocardial infarction, we investigated the time course of C5b-9 deposition and the influence of reperfusion. In a group of 17 rabbits (group 1), the circumflex coronary artery was occluded for different time periods ranging from 0.5 to 29 h without subsequent reperfusion. A second group of 23 rabbits (group 2) underwent coronary artery occlusion for periods ranging from 0.5 to 6 h followed by reperfusion. C5b-9 was determined in transmural myocardial biopsies by immunohistochemistry and by ELISA. In group 1, C5b-9 accumulation in the ischaemic myocardium was found only after 5 to 6 h of coronary artery occlusion. In group 2 (ischaemia and reperfusion), significant C5b-9 deposition was already observed after 30 min of myocardial ischaemia. We conclude that in the absence of reperfusion C5b-9 accumulation occurs as a late event when most of the jeopardized myocardium has probably already become necrotic. In the presence of reperfusion, however, the complement system is activated rapidly and this could play a role in the pathogenesis of reperfusion injury.

The prevalence of spontaneous recanalisation (SR) of the infarct-affected coronary artery and the subsequent effect on left ventricular and functional reserve was assessed in 50 patients 35 ± 10 days after acute myocardial infarction and compared to control patients without angiographic evidence of SR but with permanent coronary occlusion. The clinical characteristics of both groups were similar. None of the patients in either group received thrombolytic therapy. The prevalence of SR at the time of the study was 44% versus 56% permanent occlusion. The degree of residual stenosis in the SR group varied widely, from < 50% to subtotal. Neither radionuclide global left ventricular ejection fraction and left ventricular functional reserve nor cineangiographic analysis of wall motion abnormalities 35 ± 10 days post-infarction could significantly separate the SR group from patients with permanent coronary occlusion, comparable in variables such as age, history and site of infarction. Patients with inferior wall infarction, however, revealed a tendency to SR-related preservation of left ventricular function. In patients with anterior infarction no such trend was detectable. We conclude that SR occurs too late to salvage a significant amount of myocardium at risk and thus to limit infarct size when compared to permanent occlusion of the infarct-affected vessel.

To assess the efficacy of prophylactic lidocaine treatment in the prevention of ventricular tachyarrhythmias after recanalisation of an occluded coronary artery, 49 patients with acute myocardial infarction undergoing intra-coronary thrombolysis were studied. The patients were admitted to the hospital within 3 h of the onset of symptoms and were randomised into 2 groups: 23 patients received, after a loading dose of 200 mg, 2 mg min−1 intravenous lidocaine (group A), whereas the other 26 did not (group B). Reperfusion arrhythmias occurred in 16 of 20 successfully recanalised patients in Group A, and in 15 of 21 successfully recanalised patients in group B. There was no difference between the groups in the incidence of ventricular tachycardia and fibrillation. Regardless of lidocaine treatment, two types of ventricular tachycardia could be distinguished. The first, and most frequent, type was associated with electrophysiologic properties characteristic of enhanced automalicity, whereas the other type of tachycardia had characteristics suggesting re-entry or triggered activity as the underlying mechanism. Our findings indicate that intravenous lidocaine, in the dosage given here, is ineffective in preventing either type of reperfusion tachycardia or fibrillation in man.

232 consecutive patients with acute myocardial infarction were treated either with 2 x 10(6) IU urokinase as an intravenous bolus injection, or 250,000 IU streptokinase intracoronary, or 60 mg recombinant tissue-type plasminogen activator (rt-PA) over 90 min. All patients enrolled had chest pain for more than 30 min and less than 3 h before admission and a typical electrocardiogram. Contra-indications to thrombolytic treatment were absent. All bleeding complications occurring within 24 h after admission were assumed to be due to thrombolytic therapy. Bleeding complications occurred in 14 patients (6.5%). Only seven patients received a blood transfusion (3%). No correlation was evident between previous hypertension, diabetes mellitus, smoking, sex, age, fibrinogen level before and 24 h after thrombolytic therapy and bleeding complications. The risk of bleeding was not significantly different between the different thrombolytic regimens despite marked differences in the fall of the fibrinogen level. The decrease of fibrinogen following thrombolytic therapy did not influence the patency rate of the infarct vessel. Thrombolytic therapy in acute myocardial infarction is a safe treatment even among patients advanced in years and with medically controlled hypertension and diabetes mellitus, irrespective of the kind of thrombolytic treatment.

Clinical, angiographic, and necropsy data of 16 patients who died 1–18 days after streptokinase treatment for acute coronary occlusion are presented. In 8 cases prompt recanalisation was documented clinically by angiography. At post-mortem angiography, thrombolysis was documented in one patient. In the remaining 7 patients the occluded vessel had not been recanalised. All 16 patients had a transmural acute myocardial infarction. In 7 patients with unsuccessful thrombolytic therapy the infarct was anaemic. In the 9 successfully recanalised patients, 3 cases of anaemic infarction and 6 cases of haemorrhagic infarction were observed. Two of the latter also had minor anaemic infarctions. The mean period of time preceding successful recanalisation was significantly shorter in patients having anaemic infarcts (1·9 h) than in those having haemorrhagic infarcts {3·2 h) (P

A contraction abnormality of the left ventricle has previously been described in patients with systolic click-late systolic murmur syndrome. To determine if the contraction abnormality is present in the preprolapse period, LV dimensions and the instantaneous velocity of circumferential fiber shortening (VCF) were studied in 18 patients with the mitral valve prolapse and 16 normal subjects using computer analysis of echocardiograms. VCF attained its maximum (max VCF) during the preprolapse period an average of 94 msec before the mid-systolic click. Max VCF was significantly reduced in patients with mitral valve prolapse (2.06 vs 2.55 circ/sec in normal subjects, P less than 0.001). Despite the reduction in max VCF, no difference in the extent and percentage of diameter shortening was found between patients and normal subjects. This discrepancy is explained by a sustained rate of mid-to-late systolic diameter shortening in the presence of mitral valve prolapse as manifested by a typical VCF profile (P less than 0.001) and a longer duration of diameter shortening (353 vs 306 msec in normal subjects, P less than 0.01). The decrease of max VCF in patients with mitral valve prolapse suggests a reduction in LV contractility. Since the abnormality is present in the preprolapse period, it is unrelated to a direct mechanical effect of the prolapse itself. Additional fiber shortening in mid-to-late systole indicates that the sudden displacement of the mitral leaflets may have an unloading effect on the left ventricle.

To evalulate the relation between ventricular endocardial potentials (QRS amplitude) and ventricular dimensions, left and right ventricular endocardial potentials were recorded with hook electrodes in anaesthetised open-chest dogs during transfusion and withdrawal of blood. Left ventricular end-diastolic diameter was measured by ultrasonic crystals, and end-diastolic volume was determined by thermodilution. In each dog, left ventricular endocardial potentials, whether recorded from anterior or posterolateral walls, decreased linearly as left ventricular end-diastolic diameter or volume increased, and vice versa. With an average increase in left ventricular end-diastolic diameter from 40.1 +/- 1.7 to 44.6 +/- 1.8 mm, left ventricular endocardial potentials decreased from 32.8 +/- 2.5 to 23.5 +/- 2.3 mV (P less than 0.001); and for an increase in left ventricular end-diastolic volume from 1.36 "/- 1.25 to 3.43 +/- 0.58 ml/kg left ventricular endocardial potentials decreased from 36.2 +/- 6.6 to 14.9 +/- 4.3 mV (P less than 0.001). Changes in right ventricular endocardial potentials paralleled the changes in left ventricular endocardial potentials. These findings indicate that acute changes in ventricular dimensions influence endocardial potentials considerably, and suggest a potential clinical application for detecting acute changes in ventricular volume.

Percutaneous transluminal coronary angioplasty (PTCA) was complicated by acute coronary artery occlusion associated with ST elevation and severe chest pain in three patients. Within 10 minutes, the occluded artery was reopened by an intracoronary (i.c.) infusion of streptokinase, resulting in the disappearance of chest pain and normalization of ST segments. To keep the artery patent, i.c. streptokinase had to be continued until emergency bypass surgery was performed. In two patients, no myocardial infarction occurred, as shown by a normal postoperative left ventricular angiogram. ECG and thallium-201 scintigram. In the other patient, who was admitted with an inferior infarction and underwent PTCA after i.c. lysis, no infarct extension was observed. These results show that i.c. streptokinase rapidly opens an acute coronary artery occlusion complicating PTCA, preventing myocardial infarction.

The kinetics of the activity of total creatine kinase (CK) and creatine phosphokinase isoenzyme muscle-brain were investigated in 48 patients with acute myocardial infarction after successful intracoronary thrombolysis, and compared to the enzyme activities in 17 patients in whom thrombolysis failed. CK activity peaked significantly earlier after a successful thrombolysis than after an unsuccessful attempt: in patients with successful thrombolysis, CKmax = 10.5 +/- 3.7 h and in patients with an unsuccessful attempt, CKmax = 19.3 +/- 5.9 h; p less than or equal to 0.05. The area under the activity time curve after successful thrombolysis was significantly smaller than after unsuccessful thrombolysis: in patients with successful thrombolysis, CK area = 25,255 U/l per day and in patients with an unsuccessful attempt, CK area = 32,602 U/l per day; p = 0.015. There was a negative correlation between the area under the CK serum curve after successful thrombolysis, and the change of regional wall motion at the site of the acute infarct (p less than or equal to 0.05). From the smaller area under the CK curve in patients after successful thrombolysis, and the significant negative correlation of this measurement with regional left ventricular wall motion, we conclude that myocardial salvage after intracoronary thrombolysis can be assessed by serial CK measurements.

Thirty-one patients with acute myocardial infarction underwent intracoronary thrombolysis. Intracoronary thallium scintigrams were obtained before and after thrombolysis. In 16 of the 31 patients intracoronary technetium pyrophosphate scintigraphy was performed simultaneously after thrombolysis. The scintigraphic results were compared with changes in regional ejection fraction in the area of infarction. Two patients had a normal left ventricular cine angiogram initially with no significant ventricular thallium defect before thrombolysis. In 8 patients regional ejection fraction normalized, all showed substantial new thallium uptake after thrombolysis. In 5 patients regional ejection fraction improved, 3 of these had new thallium uptake with a large residual defect after thrombolysis. Nine patients had no significant change in regional ejection fraction despite thrombolysis, and the initial thallium defect remained unchanged in 7. Four patients had a technetium pyrophosphate accumulation in the area of new thallium uptake. In these 4 patients regional wall motion did not change to an extent which was expected from the thallium scintigram.

To analyze the relationships between left ventricular function, catecholamine concentrations in plasma and myocardium, and morphological alterations, 20 patients were studied. Fifteen patients had idiopathic dilated cardiomyopathy, and 5 had normal left ventricular function. All patients underwent right ventricular endomyocardial biopsy to determine muscle fibre thickness, percent volume fraction of interstitium, and myocardial catecholamine content. Blood was sampled to measure plasma catecholamine concentrations, and left ventricular cineangiography was performed to determine global ejection fraction. In a simple correlation analysis a significant correlation was found between left ventricular ejection fraction and myocardial norepinephrine content (r = 0.80, P less than 0.001). Left ventricular ejection fraction was negatively correlated with plasma epinephrine concentration (r- = 0.53, P less than 0.02), and with muscle fibre thickness (r = -0.50, P less than 0.03). Myocardial norepinephrine concentration was negatively correlated with plasma epinephrine (r = -0.62, P less than 0.01). Multiple linear regression analysis revealed a strong correlation between myocardial norepinephrine depletion and left ventricular dysfunction, which was independent of all other variables. These data suggest that myocardial norepinephrine depletion determined from right ventricular endomyocardial biopsies strongly correlates with left ventricular dysfunction in idiopathic dilated cardiomyopathy, and seems to be independent of the degree of muscle fibre hypertrophy, volume fraction of interstitium, and of the increased sympathetic tone.

ObjectivesThis study sought to evaluate the impact of chronic kidney disease (CKD) on coronary atherosclerotic plaque composition, morphology, and outcomes in patients with acute coronary syndromes (ACS).BackgroundCKD patients presenting with ACS are at increased risk for adverse events. Whether or not this increased risk reflects differences in coronary plaque composition remains unknown.MethodsIn the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, patients presenting with ACS in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and radiofrequency intravascular ultrasound imaging. Lesions were prospectively characterized, and patients were followed for a median of 3.4 years. We conducted a patient-level and lesion-level analysis of study participants by comparing intravascular ultrasound parameters of untreated nonculprit lesions in patients with and without CKD.ResultsPatients with CKD (n = 73, 11.3%) were older, more often female and diabetic compared to those without CKD (n = 573). Nonculprit lesions in patients with (n = 280) versus without (n = 2,390) CKD were more likely to have plaque burden ≥70% (11.8% vs. 8.5%, p = 0.05) and minimal luminal area ≤4.0 mm2 (25.9% vs. 19.2%, p = 0.005). The percentage of plaque comprised of necrotic core (15.0% vs. 13.0%, p = 0.0001) and dense calcium (8.2% vs. 6.4%, p < 0.0001) was higher while fibrous tissue (57.7% vs. 59.8%, p < 0.0001) was lower in CKD versus non-CKD lesions. The 3-year composite rate of cardiac death, cardiac arrest, or myocardial infarction (15.1% vs. 3.3%, p < 0.0001) was significantly higher in patients with than in those without CKD, although there were no differences in the rates of events adjudicated to nonculprit lesions.ConclusionsFollowing percutaneous coronary intervention of all culprit lesions in ACS, patients with versus without CKD have more extensive and severe atherosclerosis remaining in their coronary tree with plaque composed of greater necrotic core and less fibrous tissue. These influences resulted in nonsignificantly different rates of non-culprit lesion–related adverse events, although cardiac death, arrest, or myocardial infarction were more common in patients with CKD.

Based on the relation between the impedance to right ventricular ejection and ejection fraction of the right ventricle (RVEF) we tested the hypothesis that radionuclide RVEF correlates inversely with pulmonary artery pressure and allows the noninvasive prediction of pulmonary hypertension. A recently developed improved equilibrium right ventricular blood pool imaging technique using ultrashort-lived krypton-81m and simultaneous right heart catheterization were combined for assessment of right ventricular systolic performance in relation to right ventricular loading in a heterogeneous group of cardiopulmonary disorders. The study group included 9 patients with pulmonary artery hypertension secondary to left ventricular dysfunction, 5 with primary pulmonary hypertension, 5 with corrected tetralogy of Fallot, and 10 normal subjects. Linear regression analysis between radionuclide RVEF and simultaneously recorded hemodynamic measurements of right ventricular loading revealed a significant inverse correlation with mean PA pressure (r = -0.87; P less than 0.001), with total pulmonary resistance index (r = -0.81; P less than 0.001) and with pulmonary vascular resistance index (r = -0.78, P less than 0.01). The sensitivity and specificity of a resting RVEF less than 40% to indicate pulmonary hypertension (mean PA pressure greater than 20 mmHg) were 71% and 100%, respectively; positive and negative predictive values were 100% and 80%, respectively. Thus, radionuclide RVEF as a parameter of right ventricular systolic performance is predominantly dependent on right ventricular afterload and has the potential for the noninvasive prediction of pulmonary hypertension in a heterogeneous group of cardiopulmonary disorders.

In seven patients thermodilution coronary sinus flow (TD-CSF) was higher (164 +/- 21 ml/min) during ventricular pacing than during atrial pacing (119 +/- 21 ml/min, P less than 0.005) at identical heart rate, without an increase in the determinants of myocardial oxygen consumption. To assess the possibility of right atrial admixture in coronary sinus blood during ventricular pacing we compared electromagnetic coronary arterial blood flow (CBF) with TD-CSF in nine dogs during interventions that increased right atrial pressure. During ventricular pacing, rapid atrial pacing, pulmonary artery constriction and increased intrathoracic pressure, right atrial pressure increased and electromagnetic CBF was significantly less (41-166%) than TD-CSF. Marked reflux from the right atrium to the coronary sinus was also demonstrated by bolus injection of cold saline into the right atrium and continuous infusion of contrast material into coronary sinus. Caution needs to be exercised in interpreting TD-CSF in the presence of changing right atrial pressure.

In 24 patients (pts)(mean age 54.2 ± 12.1 years) with acute myocardial infarction (onset of symptoms Thus, intravenous application of 80 mg PUK is more effective than 40 mg PUK with low incidence of systemic side effects.

Reinfarction in the first days after successful thrombolysis occurs in 10 to 20% of patients (1, 2). Percutaneous transluminal coronary angioplasty (3) or bypass surgery (4) have been shown to prevent reinfarction in selected patients (3,4). Because of a certain risk involved, these methods should only be applied in those patients in whom a clinically relevant limitation of infarct size could be achieved. Therefore, myocardial salavage should be assessed immediately after thrombolysis.

Intracoronary lysis (ICL) was carried out in 108 patients with acute coronary artery thrombosis. In 79 subjects, recanalization of the occluded vessel was achieved, while 29 patients were unresponsive to the method. Thirty patients required early aorto-coronary bypass (ACB) surgery after successful ICL, while 49 patients with successful lysis were treated medically as well as the 29 patients with unsuccessful lysis. Mortality was 20% among the patients unresponsive to ICL, 12% among the 49 patients with successful lysis treated on a medical regimen thereafter, and 3.3% among the 30 patients undergoing early surgery after successful lysis. Early aorto-coronary surgery, however, was felt to be indicated only when the myocardium supplied by the occluded vessel was still viable. Beside LV angiography and ECG studies, intracoronary Thallium-scintigraphy was most helpful in assessing the viability of the heart muscle.

Recombinant unglycosylated pro-urokinase (recombinant single chain urokinase-type plasminogen activator, CG4509) was given to twelve patients (pts.) with acute myocardial infarction as a 20 mg bolus followed by a 60 mg intravenous infusion (iv.inf.) over 1 hour and to twelve pts. as a 10 mg bolus followed by a 30 mg iv.inf. over 1 hour. Reperfusion was angiographically confirmed in 9/12 pts. with the higher dose and in 6/12 pts. who obtained the lower dose. Different parameters of hemostasis were determined before administration, 30 min after the beginning of inf.,at the end of inf., 60 min thereafter and 6-12 hours afterwards .The most significant systemic changes were observed 60 min after the end of inf. when the following mean values ± SEM were determined (pre-inf. values in brackets):Fibrinolytic activity in plasma determined on fibrin plates was highest in both groups 30 min after the beginning of inf. and hardly measurable 60 min after the end of inf. No bleeding complications were observed. Based on these results,a randomized double-blind multicenter trial was started to study the effects of 80 mg CG 4509 versus 1.5 million U streptokinase iv.

We determined the mechanical and metabolic effects of graded myocardial ischemia in 23 open-chest, anesthetized pigs. By connecting the midportion of the left anterior descending artery (LAD) to the carotid artery via a constant volume, calibrated pump, we reduced the flow in the LAD to 0, 25, 50, and 75% of control rates for periods of 1 h. Flows of 100% and 150% were also examined. Using pairs of ultrasonic crystals to measure segment dimensions, we calculated segment shortening and thickening, and total and systolic stroke work in the ischemic and normally perfused segments. Blood gases, pH, and lactate and inosine balances were determined from the regional coronary venous blood. At coronary blood flows of 0, 25, 50, and 75% of normal resting flow, total segment work was 8 +/- 8, 25 +/- 4, 51 +/- 5, and 80 +/- 6% of control, respectively, while systolic segment work was -2 +/- 5, -10 +/- 5, 40 +/- 5, and 86 +/- 7% of control, respectively (means +/- SE). Thus, the decrease in total segment stroke work is proportional to the decrease in flow over the range 0-100%. However, no useful work (i.e., systolic work) is done until flow exceeds 25%. Segment shortening and thickening are significantly depressed with flows diminished by only 25%. Segmental inosine production correlates with lactate production and parallels decreased mechanical performance.

The aim of coronary reperfusion by thrombolysis in acute myocardial infarction (AMI) is the improvement of left ventricular function and of survival as a result of the reduction of infarct size. Although most of data presented in the literature are from non-randomized trials the following conclusions seem to be justified: 1. The immediate results in terms of reopening rate, decrease of infarct size, improvement of regional wall motion in the infarct area and early (hospital) mortality depend on a.) the time delay between AMI and the application of the thrombolytic agent, which is linked to b.) the reperfusion rate (successful reopening), c.) the size of the occluded vessel, which determines in combination with the degree of collateralization the initial infarct size and - at least partially - the initial hemodynamic state, d.) the age. 2. Among these, the time up to reperfusion is the single factor to be influenced by therapy. In 80% of the patients, successfully treated within 2.0 hours, the initial infarct size was reduced and regional wall motion improved. 3. After achieving a favourable immediate result for the longterm course it is of major importance to maintain a sufficient antegrade coronary flow by avoiding reocclusion. Whether aortocoronary bypass-surgery, percutaneous coronary angioplasty, alterations in the dosage and/or duration of the thrombolytic compound or some type of effective anticoagulation or a combination of these measures will be the follow-up therapy of choice has to be clarified by further investigations.

From experimental studies it is known that after 40 min of coronary artery occlusion only 60% of ischemic myocardium can be salvaged by reperfusion; after a 3-h coronary artery ligation myocardial infarction had developed completely [6]. A similar relationship between myocardial salvage and the time interval from symptom onset to start of thrombolytic therapy could be found in patients with acute myocardial infarction [4]. For estimation of myocardial salvage after thrombolysis in this study, regional wall motion in the infarct region was measured 2 – 3 weeks after the acute infarct. A normal or only slightly depressed wall motion was interpreted as a significant limitation of infarct size due to thrombolytic therapy, an abnormal wall motion, in contrast, as irreversible myocardial damage.

The interest in calculating acute infarct mass following occlusion of a coronary artery originates mainly from two sources: 1. Acute infarct mass is related not only to the short-term (hospital) prognosis, but also to the long-term course, since pump failure and severe cardiac arrhythmias develop, depending on the size of the infarction [1, 2]. 2. The quantification of an acute infarction may offer the possibility to evaluate the effect of therapeutic measures like thrombolysis, angioplasty, aortocoro-nary bypass surgery, or others.

It has been shown repeatedly that hydralazine’s peripheral arteriolar dilating effect raises cardiac output (Fig. 1) in patients with chronic left heart insufficiency by up to 100%, the mean being 50% (1, 2). While there have been cases of tachyphylaxis reported with treatment involving prazosin, the hemodynamic effect of hydralazine during long-term therapy does not diminish. These observations were confirmed by Chatterjee et al., who determined after 3 months hydralazine treatment a 65% increase in the cardiac index compared to an increase of 56% following an acute hydralazine dose (3).