Biomedical subjects

E R Schwarz

Publications and source records attributed to E R Schwarz.

At least 19 recordsLinked to original sources

PubMed2000

Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat--angiogenesis and angioma formation.

OBJECTIVES: The effects of direct intramyocardial injection of the plasmid encoding vascular endothelial growth factor (phVEGF165) in the border zone of myocardial infarct tissue in rat hearts were investigated. BACKGROUND: Controversy exists concerning the ability of VEGF to induce angiogenesis and enhance coronary flow in the myocardium. METHODS: Sprague-Dawley rats received a ligation of the left coronary artery to induce myocardial infarction (MI). At 33.1 +/- 6.5 days, the rats were injected with phVEGF165 at one location and control plasmid at a second location (500 microg DNA, n = 24) or saline (n = 16). After 33.1 +/- 5.7 days, the hearts were excised for macroscopic and histologic analysis. Regional blood flow ratios were measured in 18 rats by radioactive microspheres. RESULTS: phVEGF165-treated sites showed macroscopic angioma-like structures at the injection site while control DNA and saline injection sites did not. By histology, 21/24 phVEGF165-treated hearts showed increased focal epicardial blood vessel density and angioma-like formation. Quantitative morphometric evaluation in 20 phVEGF165-treated hearts revealed 44.4 +/- 10.5 vascular structures per field in phVEGF165-treated hearts versus 21.4 +/- 4.7 in control DNA injection sites (p < 0.05). Regional myocardial blood flow ratios between the injection site and noninfarcted area did not demonstrate any difference between phVEGF,165-treated hearts (0.9 +/- 0.2) and saline-treated hearts (0.7 +/- 0.1). CONCLUSIONS: Injection of DNA for VEGF in the border zone of MI in rat hearts induced angiogenesis. Angioma formation at the injection sites did not appear to contribute to regional myocardial blood flow, which may be a limitation of gene therapy for this application.

Animals↗

PubMed2000

A new model of ventricular plication: a suturing technique to decrease left ventricular dimensions, improve contractility, and attenuate ventricular remodeling after myocardial infarction in the rat heart.

BACKGROUND: The Batista procedure (cardio-reduction) is a surgical technique in patients with dilated cardiomyopathy that results in improvement of ventricular function. The purpose of this study was to test a new suturing technique without resection for cardio-reduction of myocardial infarct scars in rats. METHODS AND RESULTS: Myocardial infarction (MI) was induced by occluding the left coronary artery 4 weeks before enrollment. Animals then were randomized to a control (n = 11) or treatment group (n = 11). A pursestring suture was placed within the border zones of the infarcted area and was either tightened (treated) or not (controls). Echocardiography was used to measure left ventricular diameters before, 1 hour, and 6 to 7 weeks after plication. Acutely after plication, end-diastolic length (EDL) decreased from 0.70 +/- 0.03 cm to 0.53 +/- 0.02 cm, P < .001; end-systolic length (ESL) decreased from 0.51 +/- 0.03 cm to 0.23 +/- 0.02 cm, P < .001; and fractional shortening (FS) increased from 27.6 +/- 1.5% to 57.6 +/- 2.3%, P < .001, whereas controls were unchanged. In control rats EDL increased from baseline at 0.73 +/- 0.02 cm to 0.82 +/- 0.04 cm at 6 weeks postsurgery, P < .05; ESL increased from 0.54 +/- 0.02 cm to 0.66 +/- 0.04 cm, P < .005; and FS decreased from 26.9 +/- 1.1% to 19.2 +/- 1.2% at 6 weeks, P < .05. In contrast, at 6 weeks in plicated animals, EDL was significantly less than controls at 0.64 +/- 0.02 cm, P < .005; ESL was significantly less than controls at 0.39 +/- 0.03 cm, P < .005, and FS was significantly better than controls at 40.5 +/- 2.2%, P < .005. CONCLUSION: The progressive LV enlargement between 4 and 10 weeks after MI reflects late ventricular remodeling. Plication by suturing infarcted tissue acutely decreases diameters and improves function. At 6 weeks, function remains improved over untreated animals.

Animals↗

PubMed1999

Clinical effects of ischemic preconditioning.

A variety of experimental studies have confirmed that preconditioning the myocardium by brief periods of ischemia represents a powerful cardioprotective effect resulting in a reduction of infarct size. After 15 years of research in the experimental laboratory, some evidence shows the existence of preconditioning in human patients with coronary artery disease: repeated balloon inflations before coronary angioplasty induce preconditioning-like effects; moreover, some studies demonstrate better clinical outcome in patients with angina before acute myocardial infarction, resembling a preconditioning effect. So far, a few drugs have been identified as potential mediators of preconditioning, e.g., adenosine, adenosine receptor agonists, and adenosine triphosphate-sensitive potassium channel openers. Before coronary angioplasty and heart surgery, these preconditioning mimetics might be used to protect myocardial tissue by means of preconditioning. Further research is required before preconditioning mimetics could be used for therapy in patients with chronic myocardial ischemia. Possible antipreconditioning effects of several drugs, e.g., sulfonylurea drugs have to be considered in the treatment of patients with coronary artery disease.

Cardiovascular Agents↗

PubMed1999

Therapeutic dissolution of an intracoronary thrombus by prolonged intravenous platelet glycoprotein IIb/IIIa antagonism.

This case report describes the therapeutic dissolution of an intracoronary thrombus in a patient with ectatic coronary arteries post-myocardial infarction by prolonged intravenous glycoprotein (GP) IIb/IIIa antagonist administration. The report emphasizes the potential thrombotic complications in patients with ectatic coronary arteries and the beneficial use of GP IIb/IIIa receptor antagonists as direct thrombolytic agents even in partially organized thrombus formation. In addition to the well-documented effects of GP IIb/IIIa blockade in the scenario of percutaneous interventions, unstable angina, and non-Q wave infarction, the use of this new class of drugs in acute myocardial infarction seems to be promising and might also be considered in the setting of persistent thrombotic material within the coronary vasculature.

Abciximab↗

PubMed1998

[Cardiomyocyte transplantation--a cell replacement for repair of myocardial infarction?].

Cardiomyocytes lose the ability to proliferate after birth. Subsequently, irreversible cellular damage, e.g., during myocardial infarction, causes loss of functional properties and cell replacement by fibrotic tissue. It is, therefore, not surprising that cell replacement strategies such as cardiomyocyte transplantation in damaged myocardium or scar tissue has gained widespread interest. In other species such as mice, rats, and dogs, the technical feasibility of skeletal myoblast-, satellite cell-, and fetal cardiomyocyte engraftment into normal and diseased myocardium has been demonstrated by simple injection methods. Repeatedly, it has been shown that transplanted cells may survive for weeks within host myocardium and build intercellular connections such as gap junctions and desmosomes. In contrast, grafthost connections have not, as yet, been convincingly demonstrated. Hypothetically, cell transplants might exhibit the following functional properties: stabilization of diseased tissue to prevent structural remodeling; carrier for recombinant proteins, growth factors or drugs to induce molecular alterations of host myocardium; and improvement of regional and global myocardial function due to active contractility. However, clear evidence of coordinated contractility of transplanted cells, and, thus, of a clinically relevant therapeutical use of cardiomyocyte transplantation as a replacement strategy for damaged host cardiac cells, remains to be demonstrated.

Animals↗

PubMed1998

Evaluation of cardiac structures and function in small experimental animals: transthoracic, transesophageal, and intraventricular echocardiography to assess contractile function in rat heart.

OBJECTIVES: The efficacy of three different echocardiographic techniques to assess cardiac structures and function in the rat heart was studied. BACKGROUND: With increasing costs for large animal studies there is need for improved assessment of ventricular function in small animal models. METHODS: Transthoracic, transesophageal, or intracavitary echocardiography was performed in 138 rats using either a pediatric or an intravascular ultrasound transducer in control, infarcted, and obese rats. Left ventricular dimensions and wall thickness were measured. RESULTS: Transthoracic echocardiography allows qualitative and quantitative estimation of cardiac dimensions and ventricular function. End-diastolic and end-systolic diameters were 0.53 +/- 0.08 and 0.26 +/- 0.05 cm in controls, 0.63 +/- 0.08 and 0.41 +/- 0.07 cm in infarcted (p < 0.001 vs controls), and 0.66 +/- 0.1 and 0.21 +/- 0.07 cm in obese rats (p < 0.01 vs controls). Fractional shortening was 52 +/- 6% in controls, 36 +/- 5% in infarcted (p < 0.001), and 68 +/- 9% in obese rats (p < 0.001). Wall thickness was increased in obese rats. Transesophageal echocardiography allows a qualitative rather than quantitative assessment. Intracavitary ultrasound enabled visualization of the endocardium. Following coronary occlusion, fractional shortening and ejection fraction were decreased (30.8 +/- 4.5 vs 44.4 +/- 4.7%, p < 0.005, and 46.7 +/- 8.5 vs 63.4 +/- 5.4%, p < 0.005, respectively). CONCLUSIONS: Transthoracic echocardiography is a non-invasive technique to sufficiently provide information about cardiac structures and function, while transesophageal echocardiography allows rather a qualitative estimation of the rat heart. Intracavitary ultrasound can be used to assess the endocardium, ventricular function, and dimensions in open-chest studies in rats.

Animals↗

PubMed1998

A small animal model of non-ischemic cardiomyopathy and its evaluation by transthoracic echocardiography.

BACKGROUND: Costs for large animal studies have escalated. Therefore there is a need to develop small animal models of non-ischemic cardiac failure and accurate non-invasive techniques that will allow serial quantitation of left ventricular function. OBJECTIVES: The purpose of our study was to determine the efficacy and reliability of adriamycin for inducing cardiomyopathy in rats. We hypothesized that high frequency transthoracic 2-dimensional and M-mode echocardiography would allow for serial testing of cardiac function in this small animal model. METHODS: Adriamycin was administered at a dose of 2.5 mg/kg intravenously once a week for 10 weeks in 54 rats. Transthoracic echocardiography by use of a 7.5 MHz transducer was performed in 19 rats at baseline and additionally at 12 weeks after beginning of adriamycin therapy to measure left ventricular dimensions and calculate fractional shortening. RESULTS: The mortality rate during the treatment period was 11%, but increased to 52% at 13 weeks. Transthoracic echocardiography provided adequate visualization of left ventricular dimensions and cardiac function in a parasternal short axis view. In follow-up echocardiography, pericardial effusion was detected in 8/19 rats (42%). Compared to baseline, end-diastolic diameters increased from 0.56 +/- 0.06 to 0.64 +/- 0.08 mm (p < 0.001), end-systolic diameters increased from 0.27 +/- 0.03 to 0.42 +/- 0.08 mm (p < 0.001), and fractional shortening decreased from 52.8 +/- 4.0 to 34.3 +/- 7.1% (p < 0.001) at 12 weeks. Electron microscopy in a subset of rats revealed cardiomyocyte degeneration, mitochondrial and sarcoplasmatic reticular edema, numerous intracellular vacuoles and 'onion-ring' shaped mitochondrial cristae, characteristic for adriamycin cardiotoxicity in human patients. CONCLUSION: Adriamycin at an intravenous dose of 2.5 mg/kg over 10 weeks can be used to create a reliable model of non-ischemic dilated cardiomyopathy with a high success rate. For in-vivo diagnostic purposes, transthoracic echocardiography provides a reliable technique to non-invasively assess cardiac function quantitatively and qualitatively in follow-up studies in rat cardiomyopathy. This small animal model can easily be used for testing new therapeutic strategies in cardiac failure.

Animals↗

PubMed1998

Prolonged myocardial hibernation exacerbates cardiomyocyte degeneration and impairs recovery of function after revascularization.

OBJECTIVES: We sought to define the effects of time on contractile function, morphology and functional recovery after coronary revascularization in patients with dysfunctional but viable (hibernating) myocardium. BACKGROUND: Functional recovery after coronary artery bypass graft surgery in patients with chronic myocardial hibernation is incomplete or delayed. The proposed cause is a progressive temporal degeneration of cardiomyocytes. METHODS: In 32 patients with multivessel coronary disease, regional wall motion analysis was performed in hypoperfused but metabolically active areas before and 6 months after bypass surgery. During bypass surgery, transmural biopsy samples were obtained from the center of the hypokinetic zone for light and electron microscopic analyses. The proposed duration of myocardial hibernation was retrospectively assessed. RESULTS: Patients with a subacute hibernating condition (<50 days) demonstrated a higher preoperative ejection fraction (EF, 50+/-8%), and a better preserved wall motion (WM) in the supraapical wall (-1.4+/-0.4) than did patients with intermediate-term (>50 days, EF 37+/-9%, p < 0.05; WM -2.4+/-1.5, p = 0.08) or chronic (>6 months, EF 40+/-14%, WM -2.7+/-0.9, p < 0.005) ischemia. Structural degeneration correlated with the duration of ischemia (r = 0.56, p < 0.05). Postoperative recovery of function was enhanced in patients with a short history of hibernation compared with patients with an intermediate-term or chronic condition (EF 60+/-10% vs. 40+/-10%, p < 0.001, and vs. 47+/-14%, p < 0.05). CONCLUSIONS: Hibernating myocardium exhibits time-dependent deterioration due to progressive structural degeneration with enhanced fibrosis. Early revascularization should be attempted to salvage the jeopardized tissue and improve postoperative outcome.

Aged↗

PubMed1998

Myocardial ischaemia in a case of a solitary coronary ostium in the right aortic sinus with retroaortic course of the left coronary artery: documentation of the underlying pathophysiological mechanisms of ischaemia by intracoronary Doppler and pressure measurements.

Only a few cases of a single coronary ostium and retroaortic course of the coronary artery have been described. Almost all cases reported so far had additional coronary artery or valvar disease. However, myocardial ischaemia may be caused by the coronary malformation alone. A 40 year old woman with severe myocardial ischaemia in the absence of clinically relevant coronary atherosclerosis is described. To clarify the origin and mechanisms of ischaemia, intracoronary Doppler, pressure and ultrasound studies were performed using microtransducers. In its outer portion along the course behind the ascending aorta, coronary blood flow velocities were increased, there was an external elliptical compression, and distal coronary flow reserve was reduced. Furthermore, an overshoot in diastolic pressure above aortic pressure was detectable within this portion. Dobutamine stimulation exaggerated the observed intracoronary haemodynamics and induced myocardial ischaemia. The intracoronary diagnostic procedures performed were helpful in clarifying the pathophysiological mechanisms of functional coronary obstruction and ischaemia in this malformation. Bypass surgery was successfully performed with symptomatic improvement.

Adult↗

PubMed1997

Disturbed intracoronary hemodynamics in myocardial bridging: early normalization by intracoronary stent placement.

BACKGROUND: The purpose of this study was to evaluate the hemodynamic mechanisms leading to myocardial ischemia in patients with myocardial bridging. Myocardial bridging is known to induce angina and even severe myocardial ischemia. METHODS AND RESULTS: In 12 symptomatic patients with myocardial bridges, quantitative coronary angiography was performed to obtain systolic/diastolic vessel diameters within the bridged segments. Coronary flow velocities, flow reserve, and pressures were determined with a 0.014-in Doppler and a 0.014-in pressure microtransducer. In 3 symptomatic patients, coronary stents were implanted and hemodynamic measurements were repeated immediately and after 7 weeks. An in vitro validation of the pressure measurements was performed. Angiography revealed a systolic diameter reduction of 80.6+/-9.2% and a persistent diastolic reduction of 35.3+/-11% within the bridged segment. Diastolic flow velocities (cm/s) were increased (31.5+/-14.3 within versus 17.3+/-5.7 proximal and 15.2+/-6.3 distal, P<.001). Coronary flow reserve distal to the bridge was 2.5+/-0.5. There was an increased peak systolic pressure within the bridged segment (171+/-48 versus 113+/-10 mm Hg proximal, P<.001). Stent placement abolished the phasic lumen compression, the diastolic flow abnormalities, the intracoronary peak systolic pressure, and clinical symptoms. Coronary flow reserve improved to 3.8+/-0.3. CONCLUSIONS: Coronary hemodynamics in myocardial bridges are characterized by a phasic systolic vessel compression with a localized peak pressure, persistent diastolic diameter reduction, increased blood flow velocities, retrograde flow, and a reduced flow reserve. These alterations may explain the occurrence of symptoms and ischemia in these patients. Intracoronary stent placement abolished all hemodynamic abnormalities and may improve clinical symptoms in otherwise unsuccessfully treated patients with myocardial bridges.

Adult↗

PubMed1997

Angiotensin II receptor antagonist EXP 3174 reduces infarct size comparable with enalaprilat and augments preconditioning in the pig heart.

There is no agreement on the effect of angiotensin II receptor blockade in the setting of ischemic reperfusion. Our aim was to assess the acute effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin II AT1-subtype receptor blockade in pig heart. Five groups of open-chest pigs received 1 hour of left anterior descending (LAD) coronary artery occlusion and 2 hours of reperfusion. Left ventricular pressure was monitored by an intraventricular catheter, and regional segment shortening (%SS) in the LAD-supplied territory was measured by ultrasonic crystals implanted in the subendocardium. Group 1 (n = 6) served as the control; groups 2 (n = 6) and 3 (n = 6) received the angiotensin II receptor blocker, EXP 3174 (C22H21Cl1N6O2), and the ACE inhibitor, enalaprilat, respectively, prior to LAD occlusion; group 4 (n = 6) was preconditioned with two cycles of 10 minutes of coronary occlusion and 30 minutes of reperfusion; and group 5 (n = 6) underwent preconditioning with additional administration of EXP 3174 prior to the 60-minute occlusion period. Infarct sizes were measured by p-nitrobluetetrazolium staining and were expressed in percent of the ischemic area of risk. The angiotensin II receptor blocker EXP 3174 and enalaprilat reduced infarct sizes significantly (35.3 +/- 17.1% and 40.1 +/- 15.1%, respectively) compared with controls (71.2 +/- 12.8%, P < 0.05), and EXP 3174 augmented the infarct size-limiting effects of preconditioning by ischemia (10.5 +/- 6% vs. 28.6 +/- 5.3%, P < 0.05). Regional contractile dysfunction during reperfusion demonstrated no changes after angiotensin II receptor blockade. Angiotensin II receptor blockade reduced infarct size comparable with that obtained with angiotensin converting-enzyme inhibition. The infarct size-limiting effects of ischemic preconditioning were augmented by administration of the angiotensin II receptor antagonist EXP 3174. These data support the concept that blockade or inhibition of angiotensin II before coronary occlusion is protective in a swine model of acute ischemia and reperfusion.

Angiotensin Receptor Antagonists↗

PubMed1997

Functional characteristics of myocardial bridging. A combined angiographic and intracoronary Doppler flow study.

AIMS: Combined quantitative coronary angiography and intracoronary Doppler flow velocity measurements were performed to study the underlying haemodynamic mechanisms leading to myocardial ischaemia in patients with myocardial bridging in the absence of coronary artery disease. METHODS AND RESULTS: In 42 symptomatic patients with myocardial bridging of the left anterior descending coronary artery, quantitative coronary angiography was used to measure absolute and relative vessel diameters during systole and diastole. In 14 patients, serial frame-by-frame diameter quantification during a complete cardiac cycle was performed. Intracoronary blood flow velocities were determined using a 0.014 inch Doppler flow guide wire proximal, within, and distal to myocardial bridges, and coronary flow reserve was calculated. Quantitative coronary angiography revealed a maximal systolic lumen diameter reduction of 71 +/- 16% with a persistent diameter reduction of 35 +/- 13% during mid-diastole. Flow velocities revealed increased average diastolic peak flow velocities within myocardial bridges of 38.6 +/- 19 cm.s-1 vs 22.4 +/- 7.7 cm.s-1 proximal and 18.6 +/- 4.6 cm.s-1 distal (P < 0.001), which increased during rapid pacing (64.7 +/- 25 cm.s-1, P < 0.001 vs baseline). Coronary flow reserve distal to myocardial bridges was 2.3 +/- 0.9 (vs 2.9 +/- 0.9 proximal, P < 0.05). There was a characteristic Doppler flow profile within myocardial bridges with an early diastolic overshoot, which was further augmented during rapid pacing. CONCLUSION: Myocardial bridging is characterized by a delay in diastolic lumen gain and a concomitant increase in diastolic intracoronary Doppler flow velocities, which are enhanced by rapid pacing. In combination with a reduced coronary flow reserve and anginal symptoms these findings support the concept of a haemodynamically significant obstruction to coronary flow due to myocardial bridging in a selected subset of patients.

Blood Flow Velocity↗

PubMed1997

Effect of myocardial viability assessed by technetium-99m-sestamibi SPECT and fluorine-18-FDG PET on clinical outcome in coronary artery disease.

UNLABELLED: PET imaging of myocardial perfusion and metabolism identifies regional viability as well as patients at high risk for future cardiac events. This study evaluated a combined "hybrid" imaging approach using 99mTc-sestamibi SPECT and [18F]fluoro-2-deoxy-D-glucose (FDG) PET with regard to reversibility of regional dysfunction and to patient clinical outcome during a 2-yr follow-up. METHODS: In this study, 161 consecutive patients underwent baseline viability imaging. All had regional wall motion (RWM) abnormalities and 88% had a history of previous myocardial infarction. Regions were classified by semiquantitative analysis of sestamibi and FDG uptake as normal, mild match, mismatch or scar. For clinical outcome, patients were divided into three groups: predominantly scar tissue (Group A, n = 90), mild match (Group B, n = 26) and mismatch (Group C, n = 45). Treatment was performed with the knowledge of nuclear results. Cardiac events during follow-up were defined as death, myocardial infarction, unstable angina requiring revascularization, heart transplantation and survived resuscitation. RESULTS: Patients were followed for 29 +/- 6 mo. Revascularization rate was 30% in Group A, 81% in Group B and 80% in Group C, whereas the other patients were treated by medication. Only Group C demonstrated a significant reduction of cardiac events after revascularization, whereas, particularly in Group A, revascularization did not influence the frequency of events. Subjective assessment of angina pectoris and heart failure revealed more patients with improvement after revascularization as compared with conservative treatment. Of the 84 revascularized patients, 61 underwent follow-up angiography at 5 +/- 2 mo with RWM analysis using the centerline method. RWM improved only in mismatch regions from -2.2 +/- 1.0 s.d. to -1.0 +/- 1.4 s.d. (p < 0.01), whereas regions with a mild match or scar did not change. CONCLUSION: Nuclear imaging using 99mTc-sestamibi SPECT and [18F]FDG PET allows diagnosis of viability in regions with reduced perfusion and function with prognostic implications for functional outcome as well as for identification of patients who benefit most from revascularization.

Angioplasty, Balloon, Coronary↗

PubMed1997

Ischemic preconditioning.

It has been shown that repeated brief coronary occlusions increase myocardial resistance towards prolonged episodes of ischemia. This phenomenon, which renders the heart more tolerant to ischemia with subsequent limitation of infarct size, has been termed ischemic preconditioning and has been described in a variety of species. Preconditioning may also protect the heart against postischemic dysfunction and ventricular arrhythmias. Although the beneficial effects seem to be transient, they re-appear at 24 hours, representing a "second window of protection." Ischemia-induced activation of adenosine receptors and opening of ATP-sensitive potassium channels appear to play a role in the acute cardioprotection. For the late protection, stress protein synthesis may play a role. There is experimental and clinical evidence that preconditioning effects may also exist in the human heart. If so, the mechanisms of ischemic preconditioning might be applied to future therapy.

Adenosine Triphosphate↗

PubMed1996

Synaptogenesis and Fos expression in the motor cortex of the adult rat after motor skill learning.

Recent work has suggested that changes in synapse number as well as changes in the expression of the Fos protein may occur within the motor cortex in association with motor learning. The number of synapses per neuron and the percentage of Fos-positive neurons within layer II/III of the rat motor cortex was measured after training on a complex motor learning task. Adult female rats were allocated randomly to either an acrobatic condition (AC), a motor control condition (MC), or an inactive control condition (IC). AC animals were trained to traverse a complex series of obstacles, and each AC animal was pair matched with an MC animal that traversed an obstacle-free runway. IC animals received no motor training. Animals from each condition were killed at various points during training, and unbiased stereological techniques were used to estimate the number of synapses per neuron and the percentage of Fos-positive cells within layer II/III of the motor cortex. AC animals exhibited an overall increase in the number of synapses per neuron in comparison to MC and IC animals at later stages of training. AC animals also had a significantly higher overall percentage of Fos-positive cells in comparison to both controls, with a trend for the increase to be greater during the acquisition versus the maintenance phase. These data suggest that Fos may be involved in the biochemical processes underlying skill acquisition and that motor learning, as opposed to motor activity, leads to increases in synapse number in the motor cortex.

Animals↗

PubMed1996

Myocyte degeneration and cell death in hibernating human myocardium.

OBJECTIVES: The aim of this study was to analyze the morphologic characteristics of myocyte degeneration leading to replacement fibrosis in hibernating myocardium by use of electron microscopy and immunohistochemical techniques. BACKGROUND: Data on the ultrastructure and the cytoskeleton of cardiomyocytes in myocardial hibernation are scarce. Incomplete or delayed functional recovery might be due to variable degree of cardiomyocyte degeneration in hibernating myocardium. METHODS: In 24 patients, regional wall motion abnormalities were analyzed by use of the centerline method before and 6 +/- 1 months after coronary artery bypass surgery. Preoperative technetium-99m sestamibi uptake was measured by single-photon emission computed tomography for assessing regional perfusion. Fluorine-18 fluorodeoxyglucose uptake was measured by positron emission tomography to assess glucose metabolism. Transmural biopsy specimens were taken during coronary artery bypass surgery from the center of the hypocontractile area of the anterior wall. RESULTS: The myocytes showed varying signs of mild-to-severe degenerative changes and an increased degree of fibrosis. Immunohistochemical analysis demonstrated disruption of the cytoskeletal proteins titin and alpha-actinin. Electron microscopy of the cell organelles and immunohistochemical analysis of the cytoskeleton showed a similarity in the degree of degenerative alterations. Group 1 (n = 11) represented patients with only minor structural alterations, whereas group 2 (n = 13) showed severe morphologic degenerative changes. Wall motion abnormalities showed postoperative improvements, and nuclear imaging revealed a perfusion-metabolism mismatch without significant differences between the groups. CONCLUSIONS: Long-term hypoperfusion causes different degrees of morphologic alterations leading to degeneration. Preoperative analysis of regional contractility and perfusion-metabolism imaging does not distinguish the severity of morphologic alterations nor the functional outcome after revascularization. The insufficient act of self-preservation in hibernating myocardium may lead to a progressive structural degeneration with an incomplete and delayed recovery of function after restoration of blood flow.

Adult↗

PubMed1996

Functional, angiographic and intracoronary Doppler flow characteristics in symptomatic patients with myocardial bridging: effect of short-term intravenous beta-blocker medication.

OBJECTIVES: We sought to define the effects of short-term beta-adrenergic blocking medication on intracoronary flow characteristics, clinical symptoms and angiographic diameter changes in patients with severe myocardial bridging of the left anterior descending coronary artery. BACKGROUND: Controversy exists regarding the pathophysiology, clinical relevance and optimal therapy in symptomatic patients with myocardial bridges because antianginal drugs have not been systematically tested. METHODS: In 15 symptomatic patients with myocardial bridging of the left anterior descending coronary artery, maximal lumen diameter reductions were evaluated by quantitative coronary angiography. There were no angiographic signs of coronary artery disease. Coronary blood flow velocities (using a 0.014-in. [0.035 cm] Doppler guide wire) were measured at rest, during atrial pacing and during intravenous administration of a short-acting beta-blocker (esmolol, 50 to 500 micrograms/kg body weight per min) with continuous atrial pacing. RESULTS: The maximal angiographic systolic lumen diameter reduction within the myocardial bridges was 83 +/- 9% at rest, with a persistent diastolic diameter reduction of 41 +/- 11% (mean +/- SD). Short-term intravenous beta-blocker therapy decreased the diameter reduction during both systole (from 83 +/- 9% to 62 +/- 11%) and diastole (from 41 +/- 11% to 30 +/- 9%, both p < 0.001). The average diastolic peak flow velocity was higher within the myocardial bridges (33 +/- 13 cm/s) than the proximal (26 +/- 13 cm/s) and distal bridges (17 +/- 4 cm/s, both p < 0.001). During tachypacing, average diastolic peak flow velocity increased within the bridged segments to 63 +/- 21 cm/s versus 29 +/- 12 cm/s in the proximal and 20 +/- 4 cm/s in the distal bridges (both p < 0.001). Beta-receptor blockade produced a return to baseline values (average diastolic peak flow velocity within bridge 35 +/- 16 cm/s, p < 0.001). ST segment changes and symptoms were abolished with beta-blocker administration. CONCLUSIONS: In patients with myocardial bridges, administration of short-acting beta-blockers during atrial pacing alleviates anginal symptoms and signs of ischemia. This effect was mediated by a reduction of vascular compression and maximal flow velocities within the bridged coronary artery segment.

Adrenergic beta-Antagonists↗

PubMed1996

[Effect of myocardial viability and coronary revascularization on clinical outcome and prognosis: a follow-up study of 161 patients with coronary heart disease].

One hundred and sixty-one consecutive patients (144 male, 57 +/- 9 years) with stable coronary artery disease underwent nuclear imaging for assessment of myocardial viability using Tc-99m sestamibi single-photon emission computed tomography (SPECT) and F-18 fluoro-deoxy-glucose (FDG) positron emission tomography (PET). 88% had a history of chronic myocardial infarction and all had angiographically proven regional wall motion (RWM) abnormalities in the distribution territory of a stenosed or occluded coronary artery. Patients were followed for 29 +/- 6 (22-44) months with 84/161 patients (52%) receiving elective revascularization by either bypass surgery or angioplasty. 61/84 patients underwent follow-up angiography after 5 +/- 2 months for quantitative assessment of RWM changes using serial analysis with the centerline method in 45 pts with technically suitable paired angiograms. Myocardial regions were classified according to semiquantitative analysis of regional sestamibi and FDG uptake as either normal, regions with evidence for maintained viability but no mismatch ("mild match"), regions with a perfusion/metabolism "mismatch," or scar. RWM improved in "mismatch" regions from -2.2 +/- 1.0 SD to -1.0 +/- 1.4 SD (p < 0.01) compared to the mean of a normal reference population. In contrast, in regions with a "mild match" or those classified as scar, RWM analysis revealed no functional changes at follow-up. For the assessment of clinical outcome, patients were divided into three groups depending on the result of viability imaging. Those with predominantly scar tissue in the target region for viability assessment (group A, n = 90), those with a "mild match" (B, n = 26), and group C (n = 45) consisting of patients with a "mismatch" pattern. Subsequent treatment was not blinded to nuclear imaging results and revascularization was performed in 30% of group A (group A2), 81% of group B, and 80% of group C, while the other patients were treated medically only. Cardiac events during follow-up were defined as cardiac death, myocardial infarction, unstable angina with subsequent revascularization, cardiac transplantation, and survived resuscitation without evidence for myocardial infarction. Group C demonstrated a significant reduction of cardiac events from 22% to 0% following revascularization, whereas in group A coronary revascularization did not influence the frequency of events. Subjective assessment of angina pectoris and heart failure symptoms revealed more patients with improvement following revascularization as compared to those treated medically. Thus, combined nuclear imaging using sestamibi SPECT and FDG PET with quantitative tracer uptake analysis allows detection of absent or preserved myocardial viability in regions with reduced perfusion and function with prognostic implication for regional myocardial functional outcome as well as for identification of patients who benefit most from coronary revascularization.

Adult↗