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Biomedical subjects

W Flameng

Publications and source records attributed to W Flameng.

At least 19 recordsLinked to original sources
PubMed1997

Assessment of myocardial viability in chronic coronary artery disease using technetium-99m sestamibi SPECT. Correlation with histologic and positron emission tomographic studies and functional follow-up.

OBJECTIVES: The value of 99mTc-sestamibi (2-methoxy-isobutyl isonitrile [MIBI]) as a viability tracer was investigated in patients undergoing coronary artery bypass graft surgery. BACKGROUND: Initial studies claim that rest MIBI single-photon emission computed tomographic (SPECT) studies can be used to assess myocardial viability. METHODS: Thirty patients with a severely stenosed left anterior descending coronary artery and wall motion abnormalities were prospectively included. The patients underwent a MIBI rest study, a positron emission tomographic (PET) flow (13NH3) and metabolism (18F-deoxyglucose) study and nuclear angiography before undergoing bypass surgery. A preoperative transmural biopsy specimen was taken from the left ventricular anterior wall. Morphometry was performed to assess percent fibrosis. After 3 months, radionuclide angiography was repeated. RESULTS: Statistically significant higher MIBI values were found in the group with myocardial viability as assessed by PET than in the group with PET-assessed nonviability (p < 0.01). Significantly higher MIBI values were found in the group with enhanced contractility at 3 months (76 +/- 13% vs. 53 +/- 22%, p < 0.01). A linear relation was found between MIBI uptake and percent fibrosis in the biopsy specimen (r = 0.78, p < 0.00001). When maximizing the threshold for assessment of viability with MIBI by using functional improvement as the reference standard, a cutoff value of 50% was found, with positive and negative predictive values of 82% and 78%, respectively. CONCLUSIONS: 99mTc MIBI uptake was significantly higher in PET-assessed viable areas and in regions with enhanced contractility at 3 months. A linear relation was found between percent fibrosis and MIBI uptake. An optimal threshold of 50% was found for prediction of functional recovery.

Ammonia↗
PubMed1996

Changes in organ perfusion after brain death in the rat and its relation to circulating catecholamines.

Brain death can have an impact on donor organ function. This is often attributed to an altered hormonal, mainly thyroidal, status after brain death. A second possible explanation is that during the brain death process, blood flow is redistributed, causing ischemic damage in underperfused organs or regions. We investigated blood flow redistribution with colored microspheres in the rat early and late after brain death, induced by inflation of an intracranial balloon, and correlated this with the global hemodynamic situation and plasma catecholamine concentrations. Brain death was proven by the demonstration of lasting absence of brain perfusion in all animals. Myocardial blood flow closely followed the myocardial oxygen need as estimated by the rate-pressure product. The abdominal organs showed intense vasoconstriction early after brain death, which led to significantly decreased perfusion of these organs despite the highly increased perfusion pressure, followed by significant vasodilation. Total plasma catecholamine concentration was 57 times higher at 30 sec after brain death as compared with basal levels. Plasma noradrenaline concentration fell significantly below basal levels late after brain death. We conclude that brain death importantly alters regional perfusion, with possible implications for donor organ function. These changes are probably due to the tremendous alterations in the activity of the sympathetic nervous system.

Animals↗
PubMed1996

Only hibernating myocardium invariably shows early recovery after coronary revascularization.

BACKGROUND: The aims of this study were to identify hibernating myocardium (hypocontractile, hypoperfused viable myocardium that regains contractility after revascularization) in the clinical setting and to predict functional outcome in patients with coronary artery disease after coronary revascularization. METHODS AND RESULTS: Preoperative data related to the anterior free wall of the left ventricle were collected in 50 coronary bypass surgery candidates (positron emission tomography [PET], [13N]NH3 for flow, and [18F]FDG for metabolism [MET]; equilibrium-gated nuclear angiography [EGNA] for regional ejection fraction [REF]; and histological data from myocardial biopsies for percentage fibrosis and viable myocytes). Three months after surgery, the patients had follow-up PET and EGNA investigations. A principal-components analysis identified four patient clusters. Cluster 1 (n = 9) had normal viable myocardium. Cluster 2 (n = 18) had viable hypocontractile myocardium (REF, 39 +/- 12%) showing a PET mismatch pattern. Cluster 3 (n = 16) had viable hypocontractile myocardium associated with morphological myocyte injury showing a matched moderate decrease in flow (66 +/- 11%) and MET (70 +/- 11%). Cluster 4 (n = 7) had hypocontractile myocardium with mainly scar tissue (fibrosis, 74 +/- 12%). After surgery, only cluster 2, with hibernating myocardium, showed significant improvement in REF (from 39 +/- 12% to 50 +/- 13%, P < .05). Cluster 3, with sites of morphological myocyte injury, showed no recovery. The stepwise logistic regression showed a combination of low preoperative REF and high MET to be the best predictor of functional recovery (P < .008). CONCLUSIONS: Multivariate analysis identifies hibernating myocardium showing early postrevascularization recovery, as opposed to viable but myolytic myocardium with no early recovery. Postrevascularization recovery can be predicted (combination of low REF and high MET) by noninvasive techniques.

Adult↗
PubMed1996

Nuclear lamin expression in chronic hibernating myocardium in man.

Cardiomyocytes of chronic hibernating myocardium are known to undergo structural changes, indicative of dedifferentiation. Amongst these are changes in nuclear shape and chromatin distribution. Nuclear A-type lamins are known to be expressed in a differentiation-related fashion and to contribute to nuclear integrity and chromatin organization. Lamin expression was investigated with immunocytochemical staining procedures in biopsies from patients with chronic hibernating myocardium. The expression of A-type (lamin A and C) were shown to be downregulated during hibernation, while lamin B2 remained present in hibernating cardiomyocytes in a way similar to embryonic muscle cells. All heart muscle cells were shown to be negative for lamin B1. The absence of A-type lamins in chronic hibernating cardiomyocytes could be taken as an additional argument for the dedifferentiation state of these cells. The absence of A-type lamins was accompanied by dispersion of the nuclear heterochromatin, in a way similar to nuclei of embryonic cardiomyocytes.

Biopsy↗
PubMed1996

Paramagnetic metalloporphyrins: infarct avid contrast agents for diagnosis of acute myocardial infarction by MRI.

In previous experiments in tumors we demonstrated that metalloporphyrins are particularly avid for nonviable tumor components. This study was performed to find out whether these agents can be used as MRI contrast agents for the visualization of acute myocardial infarction (MI). A total of 44 rats, 6 normal controls and 38 with occlusive MI (2-24 h old), were used. Gadolinium mesoporphyrin (Gd-MP) or manganese tetraphenylporphyrin (Mn-TPP) was intravenously injected at doses of 0.1, 0.05, and 0.01 mmol/kg. Three to 24 h after injection, axial and coronal T1-weighted (TR/TE 300/15 ms) spin-echo MR images were obtained before and after killing the animals and correlated with triphenyl tetrazolium chloride (TTC) histochemical preparations. The Gd-MP content in infarcted and noninfarcted myocardium was measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). MRI without contrast media could not discern the MI. However, 3-24 h after injection of either Gd-MP or Mn-TPP, the infarcted area was positively stained on MR images. This area matched well with the negatively TTC-stained area on the heart slices (r = 0.97). The contrast ratios between the infarcted necrotic myocardium and the noninfarcted regions varied from 150 to 300% depending on the type of agents and doses used. Neither false-positive nor false-negative findings were encountered. The metalloporphyrin concentration was more than 10 times higher in the infarcted than in the noninfarcted heart. Metalloporphyrins appear to be promising MRI contrast agents for detection and quantification of necrosis in MI. These preclinical results may open new perspectives in cardiac imaging.

Animals↗
PubMed1996

Long-chain triglycerides improve recovery from myocardial stunning in conscious dogs.

OBJECTIVES: Free fatty acid (FFA) oxidation is depressed in the postischaemic stunned myocardium and recovers in parallel with the normalization of contractile performance. Assuming a causal role for this metabolic disturbance in the pathogenesis of stunning, we questioned whether exogenous administration of high dose triglycerides during reperfusion of postischaemic myocardium, could improve its functional recovery. METHODS: Thirteen dogs were chronically instrumented to measure global and regional haemodynamics and to produce a 10 min episode of regional myocardial ischaemia. In 7 dogs, Intralipid 20% was administered i.v. during the reperfusion phase. Contractile recovery of stunned myocardium was compared with control saline treatments. The series were repeated in another 6 animals, but oxfenicine (CPT I inhibitor) preceeded Intralipid during reperfusion. RESULTS: Contractile recovery of stunned myocardium was faster and more extensive when Intralipid was administered during reperfusion than with saline treatment (wall thickening fraction 86 +/- 6% of preischaemic controls versus 52 +/- 11% at 90 min post-reperfusion; P < 0.05). Oxfenicine pretreatment completely abolished this beneficial effect. CONCLUSIONS: Exogenous administration of triglycerides during reperfusion of postischaemic myocardium improves functional recovery from stunning. This beneficial effect most likely operates through enhanced FFA availability and/or oxidation since it could be abolished by selective inhibition of the carnitine palmitoyl I enzyme.

Animals↗
PubMed1996

Effects of failure of the right side of the heart and increased pulmonary resistance on mechanical circulatory support with use of the miniaturized HIA-VAD displacement pump system.

This experimental study was designed to assess the influence of failure of the right side of the heart or pulmonary hypertension, or both, on the performance of a novel miniaturized left ventricular assist device. In small-sized dogs (n = 50) ischemic global left ventricular failure was induced and support was provided by the HIA-VAD displacement pump (stroke volume 10 or 25 ml) installed as a left ventricular assist device. In three groups of animals (n = 10 each) pulmonary hypertension was created before induction of global left ventricular failure. During left ventricular assist device support temporary ischemic failure of the right side of the heart was induced in four groups of animals (n = 10 each). In the group subjected to left ventricular failure, support with the left ventricular assist device, and right ventricular failure during left ventricular assist, left atrial pressure and cardiac index were significantly lower than in the group subjected to left ventricular failure and left ventricular assist alone (2 +/- 6 versus 11 +/- 6 mm Hg and 1.6 +/- 0.4 versus 1.0 +/- 0.4 L/(min/m2), respectively, p < 0.05). In the group subjected to pulmonary hypertension, left ventricular failure, and left ventricular support, left atrial pressure dropped to values near zero but cardiac index remained unaltered as compared with results with the same regimen without pulmonary hypertension. However, when right ventricular failure was added (that is, pulmonary hypertension, left ventricular failure, left ventricular support, and right ventricular failure during support with the left ventricular assist device) left atrial pressure dropped to negative values (p < 0.05) and cardiac index progressively deteriorated. When, in an additional group of dogs, biventricular support was installed in the latter regimen, circulation was initially well supported but oxygenation deteriorated in 60% of cases. We conclude that (1) adequate right ventricular function was indispensable during support with the left ventricular assist device, (2) the combination of pulmonary hypertension and right ventricular failure led to the "low left ventricular assist device output syndrome," and (3) biventricular mechanical support in the presence of pulmonary hypertension may be complicated by the alveolar leakage syndrome.

Animals↗
PubMed1996

Rhythm disturbances after mitral valve surgery: comparison between left atrial and extended trans-septal approach.

This study was undertaken to determine the incidence of postoperative arrhythmias in mitral valve surgery through the left atrium as compared with the extended trans-septal approach. All patients undergoing mitral valve surgery for acquired valve disease between 1 January 1991 and 31 December 1993 were reviewed. Only patients with preoperative normal sinus rhythm were included in this study. End-points for analysis were: 'any supraventricular arrhythmia'; 'atrial fibrillation of flutter'; and 'ectopic atrial or junctional rhythm'. All predictive factors with a P-value < 0.10 in univariate analysis were entered into the multivariate proportional hazard model of Cox. Some 72 patients were included for analysis. No variables were independently predictive of 'any supraventricular arrhythmia'. Age is an independent predictor of 'atrial fibrillation or flutter' and surgical approach of 'ectopic atrial or junctional rhythm'.

Adult↗
PubMed1996

Interaction of heart rate and hypothermia on global myocardial contraction of the isolated rabbit heart.

We studied the effects of mild hypothermia on cardiac contractility in isolated rabbit hearts perfused with Krebs-Henseleit solution according to the technique of Langendorff. Isovolumetric left ventricular pressure (LVP) was measured with a fluid-filled balloon. Hearts were paced after induction of atrioventricular block. At low heart rates ( < 30 bpm) mild hypothermia (cooling to 30 degrees C) induced a 32% increase in LVp (146.5 +/- 10 mm Hg at 30 degrees C vs 110.7 +/- 13 mm Hg at 37 degrees C) but this positive inotropic response was progressively lost by increasing heart rate. At pacing rates > or = 90 bpm, lower systolic LVP, higher diastolic LVP, and lower positive and negative LV dP/dt were obtained in hypothermic (93 +/- 12 mm Hg, 55 +/- 18 mm Hg, 584 +/- 137 mm Hg/s, and 323 +/- 57 mm Hg/s at 210 bpm, respectively) compared to normothermic hearts (123 +/- 4 mm Hg, 10 +/- 4 mm Hg, 1705 +/- 145.5 mm Hg/s, and 1155 +/- 78 mm Hg/s at 210 bpm, respectively.) The duration of mechanical diastole was reduced or suppressed in these hearts. Exposure to the beta-adrenoreceptor agonist, isoproterenol, improved this diastolic dysfunction during hypothermia and pacing at high rates, suggesting that the sarcoplasmic reticulum Ca2+ uptake might be involved. Our data are also consistent with an increase in myofilament Ca2+ sensitivity that is opposed by isoproterenol during hypothermia.

Actin Cytoskeleton↗
PubMed1996

Aortic and mitral valve disease induced by ergotamine therapy for migraine: a case report and review of the literature.

A case of aortic and mitral valve disease associated with ergotamine abuse is reported. A 34-year-old woman presented with dyspnea after a long standing history of peripheral vascular pathology associated with ergotamine abuse. Cardiac dysfunction was rapidly progressive. At surgery, nodular thickening of both valves and fusion of the posterior leaflet of the mitral valve were seen. Microscopy revealed proliferation of myofibroblasts with little destruction of normal valvular elements. The similarity to lesions in carcinoid heart disease and in methysergide-associated valvular disease suggests direct stimulation of myofibroblast growth by serotonin agonist effect.

Adult↗
PubMed1996

The heart-Hemopump interaction: a study of Hemopump flow as a function of cardiac activity.

The Hemopump is a useful left ventricular assist device. Because it is a rotary blood pump, the pump performance is not constant and is dependent on the cardiac cycle. We measured the static flow delivered by the pump at varying pressure heads (delta P) in a mock circulation. These data are compared to the pump performance in vivo. On the basis of these results, 5 sheep were instrumented for continuous Hemopump flow measurement as well as left ventricular and aortic pressure measurements. The Hemopump flow was relayed instantaneously to the pressure head. Low filling and ventricular failing (through intravenous administration of a beta-blocker) conditions were applied. The in vivo measured flows also are pressure head dependent, but the flow curve shows hysteresis resulting in a loop during each cardiac cycle. The in vivo peak flows (delta P = 0) are similar to the in vitro data. The in vivo means flows (delta = 50 mm Hg) are similar to the in vitro data for the lower pump speeds but are less than that at the higher pump speeds (3.74 +/- 0.55 L/min in vivo at Speed 7 versus 4.6 L/min in vitro). Low filling interrupts the delta P-flow loop and reduces flow. In the failing ventricle, delta P increases and flow is reduced. The cannula leaks and results in aortic insufficiency (0.36 +/- 0.05 L/min) when the pump is turned off. Several conclusions have been drawn from these tests: Cardiac activity is beneficial for the pump performance as well as when the aortic pressure curve is nonpulsatile; the longer the systolic phase, the higher the pump flow; the pump should never be turned off in clinical use, and filling is important for the pump's performance.

Animals↗
PubMed1996

Hemodynamic system analysis of intraarterial microaxial pumps in vitro and in vivo.

Because of the lack of a sophisticated pump management system, the performance of the Hemopump in patients cannot assessed successfully. To clarify the interrelationship between an intravascular nonpulsatile pump and a pulsating ventricle, an in vitro study was set up under controlled conditions. Before these in vitro experiments, a series of in vivo experiments were performed in sheep using Hp31 cannulae. As anticipated, the resulting pulsatile pump flow was a function of the momentary pressure difference across the pump. This varying pump flow showed a significant flow loop hysteresis, indicating that the pressure difference across the pump is not the only parameter governing momentary pump flow of a rotary pump operating at constant speed in a pulsatile environment. Furthermore, flow in the Hp31 was significantly influenced by the inflow situation, blood supply, size of the ventricular cavity, and shape and position of the inflow cannula within the ventricle. Pulsatile flow conditions with good as well as impaired inflow into the pump were accordingly simulated in vitro to verify the in vivo measurements, to characterize the various inflow conditions, and to discuss methods of improved pump management. As a result of the in vivo and in vitro experiments, one can rely on the measurement of nonpulsatile in vitro flow and pressure differences across the pump to characterize the momentary pump flow for good inflow conditions into the pump. For these situations, the flow hysteresis produced, caused by fluid inertia within the pump and cannula, can be neglected. In contrast, for an impaired inflow situation, the calculated pump flow based on pressure difference measurements can be misleading. Consequently, an improved pump management system is required to adjust the pump speed, the pump performance, to any kind of impaired inflow.

Animals↗