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Biomedical subjects

W Flameng

Publications and source records attributed to W Flameng.

At least 109 records · Page 6Linked to original sources

Regional myocardial blood flow, glucose utilization and contractile function before and after revascularization and ultrastructural findings in patients with chronic coronary artery disease.

In patients with chronic coronary artery disease, follow-up measurements of myocardial blood flow, metabolism and function were correlated with histology. In 41 patients with chronic coronary artery disease and a severely stenosed left anterior descending coronary artery, a positron emission tomographic (PET) flow/metabolism study and nuclear angiography were performed immediately before and 3 months after bypass surgery. Biopsies were taken from the left ventricular anterior wall at the time of surgery. Control biopsies were taken from donor hearts for cardiac transplantation and from hearts of patients with a defect of the atrial septum. A significant improvement of flow (P<0.01) and regional contractile function (P<0.01) was observed in the mismatch group. Glucose utilization was significantly lower (P<0.001) as compared to preoperative values. The group with preserved flow and the PET match group revealed no significant changes in flow, metabolism or function. Control biopsies revealed significantly less myolytic cells as compared to biopsies taken from both match and mismatch groups (P<0.01) and less fibrosis as compared to biopsies taken from the match group (P<0.01). Postoperatively, linear relationships were found between flow and both % fibrosis (r = 0.71, P<0.001) and regional anterior ejection fraction (r = 0.7, P<0.001). Only mismatch areas revealed significant recovery of both flow and function after revascularization with a disappearance of enhanced glucose uptake. The better linear correlation between flow and % fibrosis after surgery as compared to preoperatively was probably due to improvement of flow values in the mismatch group.

Coronary Artery Bypass↗

Molecular changes of titin in left ventricular dysfunction as a result of chronic hibernation.

Cardiomyocytes of chronic hibernating myocardium are affected by partial to complete loss of sarcomeres, accumulation of glycogen, adaptations in size and shape of mitochondria, reorganisation of nuclear chromatin and depletion of sarcoplasmic reticulum. The nature of these changes, which from a purely morphologic viewpoint are akin to dedifferentiation, needed further clarification at the molecular level. For this purpose we have studied the expression and reorganization of titin, one of the earliest markers of cardiomyocytes differentiation. By use of monoclonal antibodies, recognizing different epitopes distributed over the whole length of the titin molecule, we were able to detect changes in its molecular organization as a result of chronic hibernation. The epitopes of the titin molecule attached to the Z-disc and those present close to the M-line remained detectable at all stages of hibernation, while epitopes at the A-I junction and parts of the myosin anchoring region of the molecule became masked or were lost. A fragmented or punctuated appearance of the titin staining pattern with antibodies to A-I junction related epitopes is found in cells which we consider to represent a more advanced stage of dedifferentiation. Changes in the distribution of the titin molecule or its molecular environment in hibernating myocardium resemble at least in part changes occurring during muscle cell differentiation, although in reversed order.

Animals↗

Acadesine: a new drug that may improve myocardial protection in coronary artery bypass grafting. Results of the first international multicenter study. Multinational Acadesine Study Group.

The effect of acadesine, an adenosine-regulating agent, on the incidence of myocardial infarction, all adverse cardiovascular outcomes (myocardial infarction, cardiac death, left ventricular dysfunction, life-threatening arrhythmia, or cerebrovascular accident) and mortality was assessed in 821 patients undergoing coronary artery bypass grafting. Patients were prospectively stratified to a high-risk group (age > 70 years, unstable angina, previous coronary bypass, unsuccessful angioplasty, or ejection fraction < 30%) or a non-high-risk group. They were randomized in a double-blind manner to placebo (n = 418) or acadesine (n = 403) by intravenous infusion over 7 hours (0.1 mg/kg per minute) and in the cardioplegic solution (placebo or acadesine; 5 micrograms/ml). Acadesine did not significantly affect the incidence of myocardial infarction in the overall study population, but it significantly reduced the incidence of Q-wave myocardial infarction in high-risk patients (placebo, 19.7%; acadesine, 10.0%; p = 0.032). The incidences of all adverse cardiovascular outcomes (placebo, 19.4%; acadesine, 18.4%) and overall mortality (placebo, 3.4%; acadesine, 2.7%) were similar between the two treatment groups. However, acadesine reduced the incidence of cardiac related events that contributed to deaths occurring during the first 3 postoperative days so that the incidence of death in this period was lower (placebo, 1.9%; acadesine, 0.2%; p = 0.038). No adverse events were related to acadesine treatment. Although overall there were no statistically significant between-group differences for the primary study end points, a secondary analysis in a prospectively defined high-risk subgroup suggests that acadesine may be beneficial in some patients.

Aminoimidazole Carboxamide↗

Isolated right ventricular unloading for postcardiotomy right ventricular failure in a child.

Severe right ventricular (RV) failure after total correction of double outlet RV (DORV) with pulmonary atresia was completely reversed with extracorporeal mechanical RV unloading in a 2.5-year-old child. The patient could be weaned after 168 h of RV assist device (RVAD) support using a centrifugal Bio-Medicus pump and was discharged from the hospital without adverse effects. This experience of isolated RV unloading in a child encourages further application of RVAD in pediatric patients.

Cardiopulmonary Bypass↗

Left-ventricular unloading with a new pulsatile assist device: the HIA-VAD system and its influence on myocardial stunning.

To assess the mechanical unloading properties of a new pneumatic cardiac assist device (60 ml Medos HIA-VAD) and its possible influence on recovery from myocardial stunning we performed a study in 12 anaesthetized sheep. After left thoracotomy measuring transducers were placed and the assist device connected between the left-atrial appendage and the descending thoracic aorta. Global hemodynamics were measured before and after unloading was performed. Myocardial stunning was induced by transient occlusion of a coronary artery for 15 minutes and regional myocardial wall thickening was measured. A group without unloading served as controls (group I, n = 4). In a second group unloading was performed during the last ten minutes of ischemia (group II, n = 4) and in a third group unloading was performed for 30 minutes starting after ten minutes of reperfusion (group III, n = 4). After starting the Medos HIA-VAD, significant unloading could be demonstrated: left-ventricular dP/dtmax decreased significantly (p < 0.05) to 54% and 61% in groups II and III and left-atrial pressure to 50% and 71%, respectively. Systolic and mean arterial pressure did not change significantly (p > 0.05), while the diastolic pressure increased (p < 0.05) to 134% and 138% in groups II and III. After mechanical unloading whether during ischemia or during reperfusion systolic wall thickening in the postischemic area recovered to 103% and 92% of preischemic control in groups II and III, respectively. Recovery was incomplete in the non-unloaded controls (76%) (p < 0.05 versus groups II and III). Post-ejection thickening, a diastolic measure of stunning, diminished significantly after unloading in both protocols (p < 0.05 for groups II and III versus group I). We conclude that mechanical unloading with the 60 ml Medos HIA-VAD significantly improves recovery from myocardial stunning.

Animals↗

New strategies for intraoperative myocardial protection.

In the past, most strategies for intraoperative myocardial protection were developed in models using nondiseased adult hearts from various animal species. In the clinical setting, however, myocardial status in cardiac patients may be quite different and there is a need to adapt our current protective strategies to the actual pathophysiological status of the heart. In the immature heart as well as in the senescent heart, current protective techniques have been shown to be deficient and further research is required. New insights have been gained into the pathophysiological processes underlying chronic ischemic left ventricular dysfunction in the "hibernating" myocardium. It has been shown that viability in these hearts is associated with subcellular alterations related to dedifferentiation of the myocytes. This finding explains the delayed recovery in function of these hearts after revascularization and the need for intraoperative protective strategies focusing on the prevention of stunning in the nonhibernating segments. Tepid continuous retrograde blood cardioplegia is suggested as the optimal technique. Unraveling the mechanisms of preconditioning in the heart and understanding endogenous myocardial protection may provide clues for novel cardioprotective techniques. Adenosine itself may be used as an adjunct to cardioplegia, and treatment with adenosine regulating agents or nucleoside transport inhibitors shows promising results. Like adenosine, other hyperpolarizing agents (potassium-channel openers) are suggested for arrest of the heart instead of the depolarizing agents commonly used in cardioplegia. Finally, the role of Na(+)-H+ exchange in the development of ischemic and postischemic injury has become more clear. By the use of a new selective Na(+)-H+ exchange inhibitor, postischemic contracture can be dramatically reduced and contractility improved. This opens prospective approaches in emergency coronary bypass surgery for evolving myocardial infarction.

Adenosine↗

Severe liver rupture and tricuspid valve rupture in a patient with multiple trauma.

A patient with a severe liver injury and an acute cardiac failure due to a traumatic tricuspid valve failure is presented. During liver surgery, massive venous bleeding was caused by regurgitation of blood through the insufficient tricuspid valve. Right ventricular failure, leading to persistent hemodynamic instability, and caused by massive posttraumatic tricuspid regurgitation, has been treated with biological valve replacement. Diagnosis and management of posttraumatic tricuspid insufficiency are discussed.

Accidents, Traffic↗

Mechanical unloading with a miniaturized axial flow pump (hemopump): an experimental study.

A family of miniaturized axial flow pumps has been developed, including the Hemopump, the 14-F, and the 21-F HP, which were especially designed for cardiological use. We designed an experimental set-up to study the unloading properties of these devices in a model of regional stunning in an anesthetized, open thorax preparation in sheep. Stunning was caused by 15-min occlusion of the diagonal branch of the left anterior descending coronary artery with subsequent 90 min of reperfusion. Regional myocardial function was assessed by sonomicrometry. A control group was compared with 2 groups with either mechanical unloading during part of ischemia (Group 2) or the early phase of reperfusion (Group 3). In either unloading protocol, both Hemopumps were used. It was shown that recovery from asynchrony was significantly faster in Groups 2 and 3 if unloading was performed with the 21-F HP compared with control Group 1 and the groups using the 14-F HP (p > 0.05). Thus, mechanical unloading with the 21-F Hemopump enhances recovery from stunning whereas unloading with the 14-F HP has only minor effects on hemodynamics and no effects on recovery.

Animals↗

Hemolysis with the F21 hemopump.

The aim of this study was to determine the influence of mechanical factors on free hemoglobin using an F21 hemopump cannula. These factors (flow, rotary speed, reduction of the cross section area of the silicone tube and foreign material on the screw) were tested in a mock circulation with ox blood. Irrelevant increase in free hemoglobin were induced by foreign bodies either in the inlet or on the screw. The hemopump flow was easily affected and almost suppressed by small amounts of foreign bodies on the screw. Other reasons for elevated concentrations of plasma free hemoglobin may imply a general disorder of the pump, anticoagulation, renal function, red cells or a combination of these factors.

Animals↗

Mechanical unloading properties of axial flow pumps and their effect on myocardial stunning.

Postischemic myocardial dysfunction affects morbidity and mortality in patients with coronary artery disease. It is known that mechanical unloading of the left heart ventricle can positively influence postischemic myocardial dysfunction. In this respect we tested two miniaturised axial flow pumps, i.e. the 14-F and the 21-F Hemopump. An experimental study was carried out on 30 open chest sheep where regional myocardial wall motion was followed using sonomicrometry in a preparation of transient coronary artery occlusion. Only the larger 21-F Hemopump showed hemodynamically significant unloading of the left ventricle. Furthermore, as far as stunning is concerned, systolic wall thickening recovered better when this type of pump was used during reperfusion. Also postejection thickening, which is an indication of diastolic postischemic dysfunction, is reduced significantly in the postischemic area (ANOVA, p < 0.05). Thus, the 21F Hemopump, but not the 14F Hemopump, provides adequate mechanical unloading in order to beneficially influence myocardial stunning.

Analysis of Variance↗

ALCAPA syndrome: an example of chronic myocardial hypoperfusion?

OBJECTIVES: The purpose of this study was to evaluate functional variables and morphologic correlates of chronically hypoperfused myocardium before and after revascularization. BACKGROUND: Neonates with congenital anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA syndrome) develop some myocardial necrosis shortly after birth. The survivors of this event are left with a localized infarction and an almost entirely collateral circulation-dependent perfusion of the left ventricle that results in poor global left ventricular function. Survival beyond infancy is uncommon because of severe left heart failure. Revascularization, however, brings about functional recovery with good clinical outcome. The ALCAPA syndrome is thus characterized by chronic collateral circulation-dependent low perfusion, low contraction matching and potential revivability. METHODS: Five patients with ALCAPA syndrome are presented, with preoperative and postoperative clinical findings and histologic data obtained from intraoperative transmural biopsy specimens. RESULTS: The angiographically assessed preoperative ejection fraction was 33 +/- 19% (mean +/- SD). Postoperative echocardiographic follow-up revealed normal left ventricular function in all patients. Histologic study of the biopsy specimens taken from the region perfused by the anomalous artery showed a variable degree of fibrosis (51 +/- 32%). The ultrastructure of the remaining myocytes revealed viable characteristics, but a substantial percent (46 +/- 26%) showed a markedly reduced fraction of contractile material. CONCLUSIONS: These ultrastructural studies suggest delayed subcellular adaptive responses in the chronically hypoperfused myocardium of patients with ALCAPA syndrome.

Adolescent↗

Effects of oral pretreatment with metoprolol on left ventricular wall motion, infarct size, hemodynamics, and regional myocardial blood flow in anesthetized dogs during thrombotic coronary artery occlusion and reperfusion.

OBJECTIVES: To study the effects of oral pretreatment with metoprolol over 3 days on hemodynamics, left ventricular function, regional myocardial blood flow, and infarct size in an anesthetized dog model of thrombotic occlusion of the anterior descending coronary artery treated with thrombolysis. METHODS: Ten dogs received 200 mg metoprolol (Selozok) orally and 8 dogs received placebo for 3 days twice daily and 1 hour before the experiment. Under general anesthesia, thrombotic occlusion was provoked by the copper-coil technique. Intracardiac pressures and their derivatives, cardiac output (thermodilution method), regional coronary blood flow (microspheres), global and regional left ventricular function (ventriculography), and infarct size (triphenyltetrazolium staining) were measured. Measurements were performed during control, after 60 minutes of occlusion, and after 30 and 90 minutes of reperfusion. Thrombolysis was performed in all dogs 60 minutes after occlusion by intravenous infusion of 10 micrograms/kg/min of rt-PA for 30 minutes. RESULTS: During control cardiac output was lower, total peripheral resistance higher, and Tau and the left ventricular isovolumic relaxation time greater in the metoprolol group. During occlusion and after reperfusion, there were no significant hemodynamic differences between both groups. Blood flow to the area at risk and circumflex territory during occlusion were, respectively, 12.8 +/- 5.80 ml/100 g/min versus 9.65 +/- 8.35 ml/100 g/min (p > 0.05) and 42.58 +/- 7.86 ml/100 g/min versus 61.52 +/- 20.43 ml/100 g/min (p = 0.01) in the metoprolol- and placebo-treated dogs. The ratios of flow area at risk/circumflex territories in the epicardial, midmyocardial, and endocardial layers were, respectively, 0.44 +/- 0.20, 0.19 +/- 0.09, and 0.20 +/- 0.13 in the metoprolol- versus 0.24 +/- 0.16, 0.08 +/- 0.06, and 0.06 +/- 0.07 (p > or = 0.04) in the placebo-treated dogs. The ratio of flow endocardium/epicardium was higher (p > or = 0.02) in the active treatment group during the control period, both in the area at risk and circumflex territory; this was also the case in the circumflex territory at the end of the experiment (p = 0.003). Thirty minutes after occlusion, blood flow to the three layers of the area at risk rose to 2-3 times control values in both groups; a significant increase above control values also occurred in the circumflex territory. After 90 minutes reperfusion, blood flow to both territories was similar in both groups but was comparable to the control; however, in necrotic tissue of the subendocardial layer of both groups, flow fell below control values (p < 0.05). End-systolic volume rose from 21.2 +/- 7.4 ml to 36.1 +/- 11.5 ml (p < 0.05), end-diastolic volume remained constant (46.0 +/- 13.8 vs. 47.9 +/- 12.1 ml; p > 0.05), and ejection fraction fell from 53.9 +/- 8.3% to 25.8 +/- 10.2% (p < 0.05) at the end of the experiment in the metoprolol group. Respective figures for the placebo group were 19.4 +/- 7.9 versus 27.9 +/- 10.9 (p < 0.05), 38.5 +/- 13.0 versus 42.1 +/- 11.0 (p > 0.05), and 50.6 +/- 5.7 versus 35.5 +/- 11.7 (p < 0.05). Fractional shortening of the chords analyzed was similar in both groups during the control period; it fell significantly at the end of the experiment in three chords of the metoprolol group and in five chords of the placebo group. The apical chord in the placebo, but not in the metoprolol, dogs was dyskinetic: fractional shortening was -0.86 +/- 9.7 versus 7.5 +/- 13.5% (p > 0.05). The area at risk was 41.6 +/- 10.6 cm2 in metoprolol- and 40.5 +/- 7.2 cm2 in placebo-treated dogs (p > 0.05); the infarct size, expressed as a percentage of the area at risk, was 29.0 +/- 22.5% and 45.3 +/- 23.6% (p = 0.02), respectively. CONCLUSIONS: Oral pretreatment with metoprolol limited infarct size and improved regional left ventricular function, probably due to its negative chronotropic and inotropic effects, and also due to an enhancement of collateral flow fr

Administration, Oral↗

Coronary reserve and contractile reserve in crystalloid- and blood-perfused rabbit hearts.

Coronary reserve and contractile reserve were compared between crystalloid-perfused and blood-perfused rabbit hearts at various perfusion pressures (40-110 mmHg). Contractile function of the crystalloid-perfused hearts was dependent on the perfusion pressure, according to Gregg's phenomenon. Developed left ventricular pressure (LVP) increased from 67 +/- 6 mmHg to 121 +/- 5 mmHg and positive dP/dt maximum (dP/dt max) from 1,083 +/- 75 to 2,233 +/- 126 mmHg/s at perfusion pressures between the lowest and highest perfusion pressure. In the blood-perfused hearts, the perfusion pressure-induced changes were less pronounced: developed LVP changed from 107 +/- 11 mmHg to 138 +/- 8 mmHg and dP/dt max from 1,517 +/- 181 to 2,008 +/- 187 mmHg/s. The blood-perfused hearts showed better cardiac function, especially negative dP/dt minimum (dP/dt min), compared to the crystalloid-perfused hearts. Contractile reserve estimated by paired pacing technique was quite independent of the perfusion pressure in the blood-perfused hearts but not in the crystalloid-perfused hearts, and was significantly better in the blood-perfused hearts (e.g., 81% increase of developed LVP with blood perfusion, and 26% increase with crystalloid perfusion at a perfusion pressure of 80 mmHg). Coronary reserve, estimated by reactive hyperemia, was independent of the perfusion pressure in both groups. Coronary reserve was small in the crystalloid-perfused hearts (< 23%) and more than double the control value in the blood-perfused hearts. It is proposed that blood-perfused hearts are more suitable for physiological and pathophysiological studies.

Animals↗

Early intravenous administration of metoprolol enhances myocardial salvage by thrombolysis with recombinant tissue-type plasminogen activator after thrombotic coronary artery occlusion in the dog by improvement of the collateral blood flow to the area at risk.

OBJECTIVES: We studied the effects of beta 1-adrenergic blockade preceding thrombolysis on hemodynamic variables, myocardial blood flow and infarct size in a canine model of thrombotic occlusion of the left anterior descending coronary artery. BACKGROUND: Previous work suggested a reduction in infarct size and improvement in left ventricular function by intravenous beta-blockade preceding thrombolysis. METHODS: Experiments were conducted in 34 anesthetized dogs; 17 received 0.975 mg/kg body weight of metoprolol intravenously starting 15 min after occlusion, and thrombolysis was initiated 60 min after occlusion. Seventeen dogs received saline solution followed by thrombolysis. Coronary blood flow was measured by radioactive microspheres, infarct size by a dye method, hemodynamic variables by catheter-tipped pressure transducers and cardiac output by the thermodilution method. RESULTS: Infarct size in metoprolol- and placebo-treated dogs was 23.62 +/- 18.04% and 41.50 +/- 16.03% of area at risk, respectively (p < 0.01). Before occlusion, myocardial blood flow and hemodynamic variables were similar. Sixty minutes after occlusion, cardiac output (1.94 +/- 0.41 vs. 2.32 +/- 0.68 liters/min, p < 0.01) was lower in the metoprolol-treated dogs. Collateral flow to the area at risk (17.27 +/- 7.44 vs. 10.25 +/- 5.33) and to its epicardial (21.68 +/- 8.04 vs. 11.5 +/- 6.10), midmyocardial (14.30 +/- 8.63 vs. 7.35 +/- 4.94) and endocardial (13.18 +/- 8.21 vs. 6.26 +/- 5.34 cm3/min per 100 g) layers was higher (p < or = 0.05) in the metoprolol-treated dogs. The ratio of epicardial flow area at risk/circumflex territory was inversely correlated to infarct size (r = -0.69, p < 0.01). After 5 min of occlusion, collateral flow was comparable in the five dogs of each group; over the next 55 min it remained constant in the metoprolol group but decreased in the placebo dogs. CONCLUSIONS: Intravenous metoprolol, administered before thrombolysis, enhances infarct size limitation, partly by improvement of collateral flow to area at risk.

Animals↗

Combined valve and coronary artery bypass surgery: early and late results.

Determinants of early, late and event-free survival of combined valve and coronary artery bypass graft (CABG) surgery were studied in 420 patients using multivariate analysis. It was found that the risk of hospital death increases 5 times when the preoperative NYHA class was > or = IV, 3 times when left ventricular (LV) function is significantly impaired and is double when mitral regurgitation is present. The survival probability of hospital survivors was 91% (87.3-94.5%) at 5 years. Late mortality was determined by advanced preoperative NYHA class ( > or = IV) and the presence of mitral regurgitation. The event-free survival probability of hospital survivors, i.e. total events including death, valve-related complications, ischemic complications and recurrent NYHA class > or = IV, was 73.0% (66.7-79.5%) at 5 years. Postoperative events were determined by the presence of preoperative NYHA class > or = IV, impaired ventricular function, mitral regurgitation and non-sinus rhythm. It is concluded that these parameters can be considered as the most important predictors of clinical outcome after combined valve and CABG surgery.

Adult↗

Intravenous metoprolol preceding thrombolysis in acute thrombotic myocardial infarction in the dog; effects on infarct size, myocardial blood flow, and left ventricular function.

Intravenous (i.v.) metoprolol preceding thrombolysis in an anesthetized dog model of thrombotic occlusion of the anterior descending coronary artery helps limit infarct size (IS). We wished to determine whether these effects are caused at least in part by enhancement of collateral blood flow to the area at risk (AAR). Thrombotic occlusion was provoked by a copper-coil technique. We measured intracardiac pressures and their derivatives by catheter-tip micromanometers, cardiac output (CO) by thermodilution method, regional myocardial blood flow (RMBF) by radioactive microspheres technique, global and regional left ventricular (LV) function by ventriculography, and IS with triphenyltetrazolium at the end of the experiment. Measurements were performed before and after 60-min occlusion and after 30- and 90-min reperfusion. Received fifteen minutes after occlusion, 12 dogs metoprolol 0.3 mg/kg i.v. followed by 0.3 mg/kg/h; 12 received saline. Thrombolysis was performed in all dogs after 60-min occlusion with recombinant tissue-type plasminogen activator (rt-PA) 10 micrograms/kg/min for 30 min. Hemodynamic findings were similar in both groups. During occlusion, collateral flow to total AAR (18.6 +/- 7.5 vs. 11.0 +/- 6.1 ml/min/100 g), to its subepicardial (22.1 +/- 8.1 vs. 12.2 +/- 7.2 ml/min/100 g), midmyocardial (16.0 +/- 8.9 vs. 8.0 +/- 5.5 ml/min/100 g), and endocardial (14.1 +/- 8.1 vs. 7.3 +/- 6.0 ml/min/100 g) layers was higher (p < or = 0.03) in metoprolol than in placebo-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗