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W Flameng

Publications and source records attributed to W Flameng.

At least 181 records · Page 10Linked to original sources
PubMed1990

Long-term preservation of baboon hearts. Effects of hypothermic ischemic and cardioplegic arrest on high-energy phosphate content.

Baboon hearts were preserved ex vivo after hypothermic ischemic or cardioplegic arrest and were stored cold (0.5 degrees C) for 24 hours. Ischemic arrest was induced on cardiopulmonary bypass after general cooling to 25 degrees C. Cardioplegic arrest was induced using either a hyperkalemic standard cardioplegic solution National Institutes of Health [( NIH] solution) or the recently developed University of Wisconsin (UW) organ preservation solution. ATP and catabolites were assessed in serial transmural biopsies. Cardioplegia significantly delayed the breakdown of ATP during storage. After infusion of the adenosine-supplemented UW solution, myocardial content of adenosine was high as compared with that in NIH-arrested hearts (9.12 versus 0.01 mumol.g-1 dry wt). During cold storage, however, adenosine converted to inosine in spite of profound hypothermia. This renders unlikely the potential of fast resynthesis of ATP out of the supplemented nucleoside pool after reoxygenation.

Adenosine Triphosphate↗
PubMed1990

[Catabolism of high-energy phosphates during the long-term preservation of explanted donor hearts in a dog model].

The catabolism of high-energy phosphates (HEP) during long-term preservation of donor hearts was investigated in mongrel dogs. Hearts were explanted after being randomly assigned to one of the following groups. Group I: normothermic ischaemic arrest (n = 6), group II: hypothermic ischaemic arrest (n = 6), group III: cardioplegic arrest with NIH cardioplegia (n = 6) and group IV: cardioplegic arrest with UW solution (n = 6). After explantation all hearts were stored cold for 24 hours, achieving a myocardial temperature of 0,5 degrees C. HEP content (ATP and creatine phosphate) and catabolites were determined from serial left ventricular biopsies taken before explantation and during cold storage. A significant decrease of HEP content was found in all groups. In group I and II a significant decrease of HEP was found after one hour of cold storage. After 4 and 8 hours cold storage ATP content was significantly higher in group II. Cardioplegic arrest of dog hearts resulted in a significantly delay of HEP depletion. In group III a significant decrease of ATP was only seen after 12 hours and in group IV already after 6 hours of cold storage. Hearts preserved with the newly developed UW solution showed significantly lower ATP values after 10, 12 and 24 hours than NIH preserved hearts. It is concluded that UW solution is less advantageous than NIH solution in terms of HEP preservation.

Adenosine Triphosphate↗
PubMed1989

Metabolic and haemodynamic changes in the heart during the early phase of cardiopulmonary bypass: I. Clinical observations.

Knowledge of the effects of cardiopulmonary bypass on the myocardium and on cardiac function is limited. We therefore studied changes in haemodynamics and myocardial metabolism during the initial phase of cardiopulmonary bypass in two patient groups. In one group "normothermia" (34 degrees C) was used while on bypass, with an empty beating heart; in the other group hypothermia (range 27-33 degrees C) with ventricular fibrillation was used. Mean aortic pressure and myocardial oxygen consumption decreased significantly in both groups after instalment of CPB. The arterial-coronary sinus differences in lactate changed to negative values within 5 min of the start of bypass, indicating release instead of uptake of lactate. This release was maintained during the observation period and increased significantly in the hypothermic patient group when the ventricles were fibrillating. Therefore in patients undergoing aorto-coronary bypass surgery, detrimental changes in the myocardium must be anticipated during the initial phase of cardiopulmonary bypass prior to aortic cross clamping.

Aorta↗
PubMed1989

Limitation of experimental infarct size by drugs.

Testing drugs on their efficacy in limiting infarct size is difficult in the experimental setting because of the considerable variation in the sizes of infarcts produced in control animals, mainly in dogs. This variation in infarct size in the canine model is theoretically related to variations in the size of the ischemic bed or area at risk, in pre-existing collateral blood flow, and in myocardial metabolic demand. In this study, we identified the determinants of infarct size after different periods of coronary artery occlusion in unconscious dogs and constructed a mathematical model based on these determinants using stepwise logistic regression analysis. Eighty-nine percent of the variability in infarct size is accounted for by variations in the size of the ischemic bed and coronary collateral blood flow. Using this model, we were able to predict infarct size and to make valid comparisons between treated and control groups.

Animals↗
PubMed1989

[Long-term preservation of the heart in view of its transplantation. An experimental study].

Actually the maximum preservation time for donor hearts is limited to 4 hours. The aim of this experimental study in dogs was to develop techniques allowing an extension of this period up to 24 hours. In the first part of the study the influence of diastolic arrest on the preservation of high energy phosphates was studied: The following methods of cardioplegic arrest were used: 1. hyperkalemic arrest 2. hyperkalemic arrest plus high magnesium 3. low sodium and calcium-free cardioplegia. In all experiments cardioplegic arrest was followed by cold storage (0.5 degrees C). Single dose K+ plus Mg2+ cardioplegia offered the least protection. The other two types of cardioplegia were better but the ATP content was still below 50% after 24 hrs preservation. Reperfusion after cardiac transplantation induced irreversible injury and function did not recover after transplantation. In the second part of the study continuous hypothermic perfusion with low sodium and calcium-free cardioplegia was studied. With this technique HEP content, myocardial structure and functional recovery were 100% after transplantation.

Adenosine Triphosphate↗
PubMed1988

Optimal storage temperature and benefit of hypothermic cardioplegic arrest for long-term preservation of donor hearts: a study in the dog.

Currently, for practical clinical purposes, the preservation of donor hearts is limited to about 4 h. Transplantation must be finished within this period to assure complete functional recovery upon reperfusion. From the clinical setting it is well known that hypothermia results in a better myocardial preservation during ischemia. During ischemia, rapid catabolism of high-energy phosphates (e.g., ATP and creatine phosphate) occurs. The purpose of this study was to investigate the influence of temperature during a 24-h preservation period on the rate of catabolism of ATP and on the rate of accumulation of breakdown products (ADP, AMP, adenosine, inosine, hypoxanthine, and xanthine). For this purpose, hearts were excised and stored for 24 h at 0.5 degrees, 12 degrees, or 18 degrees C. In addition, the effect of initial cardioplegic arrest was compared with simple normothermic excision of the heart followed by 24 h in cold storage. It was found that the higher the storage temperature, the higher the rate of catabolism of high-energy phosphates and, hence, after 24 h, the lower the final ATP level and the higher the level of breakdown products, mainly nucleosides. It was also found that the initial cardioplegic arrest strongly benefits the preservation of high-energy phosphates as a result of the ATP-sparing effect.

Adenosine Triphosphate↗
PubMed1988

Energy state of the myocardium during long-term cold storage and subsequent reperfusion.

Long-term preservation of dog hearts was performed over 24 h using Bretschneider-HTK cardioplegia and cold storage. Preservation was assessed in terms of conservation of myocardial tissue levels of high-energy phosphates (HEP) and functional outcome after cardiac transplantation. Serial left ventricular biopsies were taken and analysed for ATP, ADP, AMP, adenosine, inosine, hypoxanthine, xanthine and creatine phosphate. Myocardial structure was studied by electron microscopical examination of a similar biopsy specimen. Cardiac performance was measured before and after cardiac transplantation. Several techniques of cardioplegic arrest were studied: single dose cardioplegia, multidose cardioplegia and continuous perfusion with the cardioplegic solution. In all groups, the hearts were stored at 0.5 degree C for 24 h. In the group of single dose Bretschneider-HTK cardioplegia, myocardial ATP content after 24 h of cold storage was only 25% of control. The total sum of nucleotides at that time interval was however 65% of the control value. Reperfusion of these hearts using a support dog (whole blood reperfusion) did not result in any recovery of ATP. Creatinine phosphate however showed an overshoot. Accumulated nucleosides were washed out. The hearts showed electrical activity but were severely arrhythmic. Contractility was poor. In the group of multidose Bretschneider-HTK cardioplegia, HEP preservation was better than after single dose cardioplegia. ATP content was about 50% of control. The total sum of nucleotides was 85% of control. Ultrastructural assessment of the myocytes revealed only slight ischaemic damage to the mitochondria. Reperfusion on cardiopulmonary bypass after cardiac transplantation did not show any restoration of ATP, but a steady catabolism of HEP. The nucleosides adenosine and inosine were not washed out upon reperfusion. After cardiac transplantation, none of these hearts could be weaned from cardiopulmonary bypass due to irreversible low cardiac output. Histological examination demonstrated irreversible myocardial tissue damage. In the group of continuous cold Bretschneider cardioplegia, HEP content was completely preserved throughout the 24 h of perfusion. Ultrastructure of the myocytes was normal. Reperfusion of the transplanted hearts showed a mild breakdown of ATP to 70% of control values accompanied by a slight accumulation of nucleosides. Haemodynamic recovery however was perfect and none of the hearts needed positive inotropic support. Myocytes after reperfusion had a normal subcellular appearance.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1988

Preservation of myocardial energy-rich phosphates by retrograde application of Bretschneider cardioplegia during aortocoronary bypass surgery.

The efficacy of myocardial protection obtained by antegrade application of a cardioplegic solution was compared with that obtained by retrograde application via the coronary sinus. Myocardial preservation was assessed using biochemical parameters, i.e. tissue content of lactate, creatine phosphate, nucleotides, nucleosides and hypoxanthine. Nineteen patients undergoing routine aortocoronary bypass surgery were randomly allocated to a study group. During cardiac arrest induced by antegrade Bretschneider cardioplegia, myocardial tissue content of creatine phosphate dropped to 52% of its pre-ischemic value and degradation of nucleotides occurred, characterized mainly by an accumulation of adenosine. Retrograde cardioplegia prevented this catabolism of energy-rich phosphates completely during ischemic cardiac arrest and is therefore considered to be superior to antegrade cardioplegia.

Adenosine↗
PubMed1988

Histology of the postischaemic myocardium and its relation to left ventricular function.

The relation between the histology of the myocardium and left ventricular function was studied in 23 dogs submitted to 90 min of coronary artery occlusion followed by reperfusion for up to 1 week. It was shown that 32% of the perfusion area of the occluded coronary artery was irreversibly damaged. There was, however, no significant correlation between the decrease in left ventricular function (ejection fraction assessed by angiography) and the extent of myocardial necrosis. Upon reperfusion, salvage of 68% of the perfusion area of the occluded vessel was obtained. Viability of the myocardium in this area was demonstrated by electron microscopy. However, postischaemic regional function was completely lost in the first 24 h, in spite of this considerable amount of viable tissue. Nevertheless, regional function recovered after 1 week of reperfusion, which suggests a stunned myocardium in the early postischaemic phase. These results show that histological examination of postischaemic tissue has prognostic value in terms of recovery of function, but a direct correlation between structure and function does not exist in the early reperfusion phase.

Actin Cytoskeleton↗
PubMed1988

Long term spontaneous evolution of left ventricular function after experimental acute coronary occlusion.

In a canine model of acute occlusion of the left anterior descending artery (LAD), left ventriculography was performed before and immediately after occlusion and also one and three weeks later. Regional left ventricular function was evaluated by the centreline method. Global and regional left ventricular function were significantly depressed immediately after occlusion and showed no significant recovery after one and three weeks, except for a decrease in the paradoxical motion of the LAD territory, which was probably due to stiffening of the infarct area.

Angiocardiography↗
PubMed1987

Relation between coronary artery stenosis and myocardial purine metabolism, histology and regional function in humans.

In 54 patients undergoing elective or emergency aortocoronary bypass grafting, angiographic and electrocardiographic changes were studied. Five patients with unstable angina and five patients with evolving myocardial infarction were included. High energy phosphate metabolism and the histologic appearance of the myocardium were analyzed in transmural biopsy specimens acquired at the time of surgery. In patients without anterior infarction on the electrocardiogram, severe stenosis of the left anterior descending coronary artery resulted in a reduction of anterior wall motion that was associated with a partial depletion of the adenylate pool. Mitochondrial function, however, remained intact: the adenosine diphosphate/adenosine triphosphate ratio, the energy charge and the creatine phosphate/adenosine triphosphate ratio were in the normal range. Histologic assessment demonstrated viable myocardium with a high incidence of atrophic cells. In evolving myocardial infarction, 170 minutes of acute coronary artery obstruction resulted in anterior wall akinesia associated with a decrease of the sum of the adenylates to 52% and of creatine phosphate to 16% of their normal value (p less than 0.05). The nucleosides accumulated; their major fraction (91%) was inosine. The adenosine diphosphate/adenosine triphosphate ratio increased from 0.14 +/- 0.04 to 0.49 +/- 0.20 (p less than 0.01) and the energy charge decreased from 0.924 +/- 0.021 to 0.660 +/- 0.169 (p less than 0.01). Ultrastructure examination revealed irreversible cell damage in at least the subendocardial layer. These results suggest that the energetic base of reduced contractility due to severe coronary artery stenosis is different from that in acute coronary obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

The value of ejection fraction as a predictor of early and late survival following aortocoronary bypass surgery in patients with moderate to severe depression of the left ventricular function.

Predictability analysis of early and late survival of coronary bypass patients with reduced left ventricular function was performed using stepwise logistic regression based on preoperative and operative data. The total perioperative mortality was 3.4% and the total actuarial survival of the whole group at 42 months was 87.7%. Thirty preoperative and operative parameters of 149 patients were entered into a first mathematical model. Four parameters were selected as a consequence: ejection fraction, anginal class, obesity, septal infarct. A prediction model based on these parameters, gave a correct prediction of the operative outcome in 99.3% of the patients. However due to the only five perioperative deaths, this model should be interpreted with caution. The accuracy of ejection fraction alone was 97.3%, the sensitivity was 100% but the specificity was only 20%. The same parameters of 97 patients were entered into a second mathematical model. Four parameters were selected in this case: ejection fraction, NYHA functional classification, septal infarct, anterior infarct. A second prediction model, based on these parameters, gave a correct prediction of the late outcome at 24 months in 93.8% of the patients. The accuracy of the discrimination on the basis of ejection fraction alone was 89.7%, its sensitivity was 96.5% but its specificity was only 41.7%. Ejection fraction was the best predictor out of the studied variables but due to its low specificity not good enough as a sole parameter.

Adult↗
PubMed1987

Reduction in infarct size and enhanced recovery of systolic function after coronary thrombolysis with tissue-type plasminogen activator combined with beta-adrenergic blockade with metoprolol.

The effect of beta-adrenergic blockade on the salvage and functional recovery of reperfused myocardium was investigated in anesthetized dogs. Immediately after thrombotic occlusion of the left anterior descending coronary artery, the cardioselective beta-blocking agent metoprolol was given intravenously at a dose of 0.5 mg/kg infused over 10 min. One hour after the onset of occlusion, recanalization was initiated by intravenous infusion of recombinant human tissue-type plasminogen activator (rt-PA, 10 micrograms/kg/min for 30 min). Anatomic infarct size expressed as percent of the left ventricular mass (I/LV), global ejection fraction, and mean systolic shortening of the segmental radii (SS) of the infarcted area were measured either after 24 hr or 1 week in six groups of six dogs each: group I (rt-PA + metoprolol, evaluated at 24 hr), group II (rt-PA + metoprolol, evaluated at 1 week, group III (rt-PA alone, evaluated at 24 hr), group IV (rt-PA alone, evaluated at 1 week), group V (persistent occlusion, evaluated at 24 hr), and group VI (persistent occlusion, evaluated at 1 week). The smallest infarcts were found in reperfused dogs given metoprolol, but the differences from dogs receiving rt-PA alone were not statistically significant (I/LV, expressed as mean +/- SEM: 5.5 +/- 0.9% in group I, 6.7 +/- 1.9% in group II, 15.4 +/- 5.0% in group III, 11.4 +/- 3.5% in group IV, 23.6 +/- 2.5% in group V, and 26.9 +/- 2.3% in group VI).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗