Biomedical subjects

W Flameng

Publications and source records attributed to W Flameng.

At least 127 records · Page 7Linked to original sources

PubMed1994

Effects of unloaded reperfusion on mitochondrial function in the postischemic myocardium.

The effect of mechanical unloading on recovery of postischemic myocardial performance, high energy phosphate content, and mitochondrial function was tested in an isolated working rabbit heart model. After 30 min of global ischemia, prolonged unloaded reperfusion could prevent complete loss of contractility, deterioration of mitochondrial function, and depletion of the ATP pool as was found when only short-term unloading was performed. Aortic flow recovered to 21% of preischemic control, and left ventricular dP/dt max to 46% (p < 0.05 vs. short-term unloading). OPR and ADP/O stabilized at 42 and 72%, respectively (p < 0.05 vs. short-term unloading), and ATP at 33% of control (p < 0.05 vs. short-term unloading). These results show the beneficial effect of prolonged unloading in postischemic hearts.

Adenosine Triphosphate↗

PubMed1994

Resting and action potentials of nonischemic and chronically ischemic human ventricular muscle.

INTRODUCTION: The effect of chronic ischemia on the electrical properties of human cardiac tissue is not well understood. METHODS AND RESULTS: Membrane potentials were studied using microelectrode techniques in isolated human ventricular tissues obtained from nonischemic (n = 17) or chronically ischemic (n = 7) myocardium. In normal Tyrode's solution, resting potential (Vr) was lower in ischemic (-70.1 +/- 2.12 mV) than in nonischemic muscles (-77.6 +/- 0.93 mV; mean +/- SEM; P < 0.05). In high [K]o (> 10 mM) media, Vr was of similar magnitude in both types of tissue (in 21.6 mM [K]o, Vr was -53.1 +/- 2.24 mV in nonischemic and -49.6 +/- 2.03 mV in ischemic preparations; n = 7 each; P > 0.05). Lowering [K]o caused persistent hyperpolarization in nonischemic muscles, but caused depolarization in chronically ischemic preparations (in 2.7 mM [K]o, Vr was -84.9 +/- 2.74 mV and -61.7 +/- 7.72 mV, respectively; n = 7; P < 0.05). Pinacidil (100 microM) normalized the response of chronically ischemic preparations to [K]o. Action potentials (APs) from nonischemic tissues varied in shape and could show aberrations. Epinephrine (1.5 microM) and 4-aminopyridine (3 mM) increased the AP duration, while butanedione monoxime (20 mM) and tetrodotoxin (1 microM) shortened it. In chronically ischemic muscles, the AP was characterized by the absence of a plateau and the presence of a slow phase of final repolarization. CONCLUSION: The differential effect of low [K]o on the resting membrane potential of nonischemic and chronically ischemic tissues suggests a change in the properties or the regulation of background K+ channels during chronic ischemia.

4-Aminopyridine↗

PubMed1994

Use of left-ventricular assist with the Hemopump in cardiac surgery.

From July 1989 to May 1992 16 patients received circulatory support with a Hemopump assist device in the Department of Cardiac Surgery of the Katholieke Universiteit Leuven. The mean age of those patients was 56 +/- 13 years (ranging from 23 to 72 years). The mean time of assisted circulation was 60 +/- 46 h (ranging from 2 to 168 h). Group I consists of 13 patients who received the device after postcardiotomy cardiac failure (survival 38%). Group II includes 1 patient who received the pump prior to repair of a large postinfarction ventricular septal defect (survival 10%). Group III consists of 2 patients for whom the Hemopump was used as a bridge to cardiac retransplantation. Both are still alive (survival 100%). If the 21-F Hemopump is implanted following a critical indication it can be used rather successfully for mechanical circulatory support.

Adult↗

PubMed1994

New Na(+)-H+ exchange inhibitor HOE 694 improves postischemic function and high-energy phosphate resynthesis and reduces Ca2+ overload in isolated perfused rabbit heart.

BACKGROUND: Experiments were carried out using the new Na(+)-H+ exchange inhibitor (3-methylsulfonyl-4-piperidinobenzoyl)guanidine methanesulfonate (HOE 694) to assess the role of Na(+)-H+ exchange in myocardial ischemic and reperfusion injury. METHODS AND RESULTS: Three groups of rabbit hearts (n = 5 in each) were perfused with blood and were subjected to 45 minutes of global normothermic (37 degrees C) ischemia, followed by 1 hour of reperfusion. Group 1 was the control group (vehicle only); in group 2, HOE 694 (1 mumol/L) was administered before ischemia (pretreatment group); and in group 3, HOE 694 was given only during reperfusion to separate actions exerted during ischemia from those specifically obtained during reperfusion. End-diastolic pressure rise at 1 hour of reperfusion was reduced by administration of HOE 694 starting before ischemia (from 52.2 +/- 8.5 mm Hg in group 1 to 17.6 +/- 4.5 mm Hg in group 2, P < .01) or starting on reperfusion (28.8 +/- 5.4 mm Hg in group 3, P < .05 versus group 1). Left ventricular developed pressure (LVDP) and its derivative (dP/dt) recovered better in HOE 694-pretreated hearts (LVDP, 79 +/- 9.9 mm Hg in group 2 versus 24.8 +/- 10 mm Hg in group 1; dP/dt, 1580 +/- 198 mm Hg/s versus 340 +/- 221 mm Hg/s, P < .01). In hearts treated only on reperfusion, some improvement was observed, which, however, did not reach statistical significance. Coronary flow on reperfusion was higher in groups 2 and 3 compared with controls, and no "no-reflow" was observed. Two additional groups of hearts were perfused with phosphate-free Krebs-Henseleit solution to enable studies with 31P nuclear magnetic resonance (NMR). ATP was better preserved in HOE 694-pretreated (62 +/- 4.9% of preischemic value) than in control hearts (44 +/- 3.3%) at the end of 30 minutes of reperfusion, and phosphocreatine resynthesis was higher (109 +/- 3.7% versus 86 +/- 5.4%). HOE 694 did not affect the time course of intracellular acidosis during ischemia but suppressed a small alkaline overshoot occurring early in reperfusion (pH 6.96 +/- 0.02 in HOE 694-pretreated hearts versus 7.14 +/- 0.05 in control hearts). Electron microscopy with Ca2+ staining of the blood-perfused hearts showed that clumping of Ca2+ aggregates in mitochondria was prevented by HOE 694. CONCLUSIONS: Postischemic dysfunction was associated with a rise in end-diastolic pressure. This rise was effectively blocked by HOE 694. The drug was most effective when hearts were treated before ischemia, although partial protection was observed when administration was started on reperfusion. The action of HOE 694 strengthens the idea that Na(+)-H+ exchange during both ischemia and reperfusion contributes to contractile dysfunction.

Adenosine Triphosphate↗

PubMed1994

Histological alterations in chronically hypoperfused myocardium. Correlation with PET findings.

BACKGROUND: In patients with chronic coronary artery disease (CAD) and left ventricular dysfunction, flow/metabolic studies of the myocardium with positron emission tomography (PET) are able to distinguish viable but dysfunctional myocardium from irreversible ischemic injury and scar tissue. In this study, PET findings of blood flow and metabolism in chronically hypoperfused myocardium were correlated with histology. METHODS AND RESULTS: We studied 33 patients suffering from CAD. In each patient, myocardial blood flow and metabolism were measured with PET 1 or 2 days before revascularization. During surgery, transmural biopsies were taken from the left ventricular anterior wall and planimetrically scored for the degree of myolysis (sarcomere loss). The amount of connective tissue was calculated using morphometric techniques. Contrast ventriculography demonstrated abnormal wall motion in 23 patients. Fourteen patients with a mismatch pattern (decreased flow with preserved metabolism) in the biopsy region after quantitative analysis of the PET data showed 11 +/- 6 vol% fibrosis and 25 +/- 13% cells with sarcomere loss. The space formerly occupied by sarcomeres was mainly replaced by glycogen and mitochondria. A significant wall motion improvement was noted 3 months after surgery. Nine patients showed a match pattern (concordant flow/metabolism defects). The biopsies revealed 35 +/- 25% fibrosis and 24 +/- 15% glycogen-storing cells. The biopsies of the 10 patients with normal anterior wall motion showed 8 +/- 4% fibrosis and 12 +/- 8% glycogen-accumulating cells. CONCLUSIONS: It can be concluded that areas with impaired wall motion and a PET match pattern show extensive fibrosis. Regions with reduced flow and preserved FDG metabolism, however, contain predominantly viable cells. In these regions, significant recovery of wall motion is found after revascularization. Regions with normal wall motion contain predominantly viable cells. Cells with reduced contractile material and increased glycogen content are mainly found in areas with wall motion impairment but are also present in areas with normal wall motion and a severe stenosis of the coronary vessel.

Biopsy↗

PubMed1994

Cardiac transplantation in giant cell myocarditis. A case report.

The present report describes a 15-year-old boy who underwent an urgent cardiac transplantation for giant cell myocarditis because of fulminant progressive heart failure, complicated by ventricular tachycardia, unresponsive to classical inotropic medical treatment. The physiopathology and the treatment are discussed.

Adolescent↗

PubMed1994

Importance of the coronary collateral circulation for the distribution of anterograde and retrograde delivered cardioplegic solution in aortocoronary bypass surgery: a haemodynamic study.

The importance of coronary collateral circulation for homogeneous distribution of anterograde and retrograde delivery of cardioplegia was evaluated in 36 patients undergoing myocardial revascularization. All patients had three-vessel coronary artery disease, with a stenosis of the right coronary artery of at least 80%. The patients were randomized into two groups: group A (n = 19) received anterograde delivered cardioplegic solution and group B (n = 17) received retrograde. Both groups were further subdivided depending on the pathology of the right coronary artery, as evaluated on preoperative coronary angiography. In group A1 (n = 8) and group B1 (n = 7) there was no visualization of collateral circulation from the left to the right coronary artery system, whereas in group A2 (n = 11) and group B2 (n = 10) there was retrograde filling of the right coronary artery by collateral circulation. Right atrial pressure increased significantly (P < 0.05) in group A1 and was elevated in group A2, but not significantly (P = 0.07). By contrast, right arterial pressure decreased in groups B1 and B2. Analysis of the individual differences in the right atrial filling pressure showed a statistical significance between the two subgroups (group B1-1.0(0.5) versus group B2-1.8(1.1), P < 0.05), although the individual decrease of the right ventricular stroke work index was not significant. It is concluded that collateral circulation is important for an adequate distribution of anterogradely delivered cardioplegia and is also beneficial in cases of retrograde delivery.

Adult↗

PubMed1994

Global and regional haemodynamic effects of urapidil in conscious dogs with chronic coronary artery occlusion.

The haemodynamic effects of urapidil, an alpha 1-antagonist with central serotoninergic properties, were studied in an experimental canine model of chronic ischaemic heart disease. Global and regional haemodynamic recordings were made in conscious dogs with ameroid-induced single vessel coronary artery occlusion. Three intravenous bolus-infusion doses of urapidil (0.1 mg kg-1 + 0.3 mg min-1; 0.5 mg kg-1 + 1.5 mg min-1; 2.5 mg kg-1 + 7.5 mg min-1) were given on separate occasions in 12 animals. Regional blood flows were measured with radioactively labelled tracer microspheres. The effects of urapidil and dipyridamole, a powerful arteriolar vasodilator, on regional myocardial blood flow distribution to normal and collateral-dependent myocardium were compared. Urapidil caused a dose-dependent reduction of arterial blood pressure. There was moderate tachycardia and decreased left atrial filling pressures at the higher doses. Urapidil was a much weaker coronary vasodilator than dipyridamole. Dipyridamole caused maldistribution of intercoronary and transmural flows (endo-to-epicardial flow ratio in collateral-dependent regions from 1.35 +/- 0.07 to 0.7 +/- 0.13 and flow ratio between collateral-dependent and normal regions from 1.09 +/- 0.03 to 0.57 +/- 0.14). Urapidil preserved blood flow to both regions. Urapidil did not affect systolic wall thickening fraction in normal or ischaemic regions of the heart. Renal (+16%) and splanchnic perfusion (+45%) increased during urapidil infusion. Urapidil preserves myocardial function and perfusion and increases renal and intestinal blood flow in dogs with chronically ischaemic hearts.

Adrenergic alpha-Antagonists↗

PubMed1994

Energetic state of the postischemic myocardium and its relation to contractile failure.

We used the isolated working rabbit heart preparation as a model to study the relationship between postischemic myocardial dysfunction and the energetic state of the heart in terms of mitochondrial function and myocardial high energy phosphate (HEP) contents. Normothermic global myocardial ischemia (10, 20 and 30 min) was induced. Cardiac function, mitochondrial function and myocardial HEP contents were measured. Viability of the postischemic myocardium was assessed by electron microscopy. Myocardial tissue was found to be intact up to 20 min of ischemia plus reperfusion. Areas of irreversibly damaged myocardium were found after 30 min of ischemia. Myocardial contractile function was significantly depressed after 10 and 20 min of ischemia and severely depressed after 30 min of ischemia. Postischemic myocardial dysfunction was associated with normal mitochondrial function and HEP content after 10 min of ischemia, with near-normal mitochondrial function and HEP content after 20 min of ischemia and with pathologic values after 30 min of ischemia. It is concluded that postischemic myocardial stunning is not associated with a disturbance of the energy producing processes. More severe ischemia however leads to progressive deterioration of mitochondrial function which may contribute to complete deterioration of myocardial contractile function upon reperfusion.

Adenosine Triphosphate↗

PubMed1994

Mitral valve surgery combined with coronary bypass grafting: multivariate analysis of factors predicting early and late results.

Total of 123 patients (mean age: 63.8 +/- 7.3 years, (male/female 65/35 percent) underwent mitral valve surgery combined with coronary artery bypass grafting during a seven year period. Preoperatively 12% of them belonged to NYHA functional class II, 54% to class III, 29% to class IV and 3% was operated under emergency conditions. The mitral valve lesion was most frequently either ischaemic (45%) or rheumatic (33%) in origin. Left ventricle function was moderately decreased in 18% and severely damaged in 3% of the patients as documented by preoperative ventriculography. Coronary surgery was performed in all cases with an average number of distal anastomosis of 2.2 +/- 1.1 per patient. The hospital mortality was 13%. Risk factors for early and late mortality were determined by univariate and multivariate analysis. Advanced preoperative functional class and decreased left ventricular function or ischaemic etiology were identified as significant risk factors for early mortality. The patients were followed for an average of 33 +/- 25 months. The majority of them experienced significant functional improvement postoperatively with 69% belonging to NYHA class I or II. The late survival for the 107 hospital survivors was 94.7% at one year, and 84.7% at five years, respectively. Late survival was independently determined by preoperative functional class or previous myocardial infarction. Freedom from ischemic and valve related complications at five years was 95% and 71.2% respectively. 58.2% of the hospital survivors were in functional class I or II and free of any valve related or ischemic complications at the end of the fifth follow up year.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Aortic and mitral valve replacement with the Carpentier-Edwards pericardial bioprosthesis: mid-term clinical results.

Between May 1st 1985 and December 31st 1992, 283 Carpentier-Edwards pericardial valves were implanted in 260 patients in the aortic (n = 196), mitral (n = 41) and both aortic and mitral (n = 23) positions at the Gasthuisberg University Hospital in Leuven, Belgium. Patients undergoing tricuspid valve replacement or mixed replacement with another type of prosthesis were excluded from this study. The mean age was 70 +/- 7 years, there were 121 males and 139 females. The mean follow up was 40.55 months, the total follow up experience 10543 months (878.6 patients years). Hospital mortality was 10.4%, and was not significantly related to the position of the valve: 17.3% +/- 7.88% (n = 23) for double valve replacement, 10.2% +/- 2.16% (n = 196) for aortic valve replacement and 7.3% +/- 4.06% (n = 41) for mitral valve replacement. Hospital mortality was 14.1% +/- 3.27% for those with and 7.48% +/- 2.5% for those without concomitant coronary surgery (p = NS). Survival at 92 months was 63% +/- 6% and was not significantly related to the position of the valve. Not a single patient needed to be reoperated because of primary tissue failure. We conclude that the mid-term durability of this valve is excellent and consider the Carpentier-Edwards pericardial valve as the stented bioprosthesis of choice both in the aortic and mitral positions for the elderly. Because of the older age of our study population and the medium term length of follow up, we were unable to draw any conclusions concerning the incidence of calcific degeneration of this valve.

Adult↗

PubMed1993

R56865, a Na(+)- and Ca(2+)-overload inhibitor, reduces myocardial ischemia-reperfusion injury in blood-perfused rabbit hearts.

The cardioprotective effects of R56865 were studied in isolated rabbit hearts, blood-perfused with a support rabbit system. The effect on ischemic injury was evaluated by comparing myocardial contracture and contents of ATP catabolites and of lactate during 60 min of normothermic ischemia in untreated hearts (group I) and in hearts treated with 0.63 mg/kg of R56865 starting 20 min before ischemia (group II; n = 5 in each group). R56865 delayed the onset, and decreased the extent of ischemic contracture, but had no effect on the myocardial content of ATP, of its catabolites of lactate. The effect on reperfusion injury was studied by monitoring left ventricular function during 80-min reperfusion after the 60-min ischemia in three groups (n = 6 in each): an untreated group (group I) and two groups treated with R56865 given either before (group II) or after ischemia (group III). Ultrastructural changes and cellular calcium distribution after reperfusion were also studied. R56865 improved the recovery of function and prevented contracture during reperfusion. Left ventricular end-diastolic pressure was 13.2 +/- 2.8 mmHg in group II and 31.3 +/- 8.1 mmHg in group III vs 45.0 +/- 2.6 mmHg in group I (P < 0.0001 for II vs I; P > 0.05 for III vs I). Left ventricular developed pressure, maximum dP/dt and minimum dP/dt recovered to 71.0 +/- 5.4%, 98.9 +/- 6.1%, 85.3 +/- 4.8% of baseline values, respectively, in group II, to 64.5 +/- 3.0% (P > 0.05), 76.8 +/- 3.0%, 70.2 +/- 4.0% in group III, vs 52.0 +/- 6.5%, 58.9 +/- 6.9% and 53.6 +/- 5.8% in untreated hearts (P < 0.05 for II or III vs I). Coronary flow was 24.5 +/- 2.2 ml/min and 19.8 +/- 1.8 ml/min in groups II and III vs 14.8 +/- 0.7 ml/min (P < 0.05) in the untreated group. On histology the myocardium in hearts treated either before or after ischemia was well protected and calcium distribution was almost normal after reperfusion, while in untreated hearts, most of the myocardium displayed irreversible damage accompanied by massive intracellular calcium accumulation. We conclude that R56865 could attenuate Ca(2+)-overload, thereby reducing myocardial ischemia-reperfusion injury after an extended period of ischemia.

Animals↗

PubMed1993

Distribution of calcium in a subset of chronic hibernating myocardium in man.

The structural correlates of 'chronic hibernating myocardium' in man consist of myocardial cells which transformed from a functional state (rich in contractile material) to a surviving state (poor in contractile material, rich in glycogen). Since the calcium-handling organelles such as SR, sarcolemma and mitochondria underwent structural changes in cells so affected, the distribution of calcium was investigated in biopsies obtained from 'hibernating' areas. The material was processed for microscopic localization of total calcium (laser microprobe mass analysis, LAMMA) and of exchangeable calcium (phosphate-pyroantimonate precipitation method, PPA). Subcellular distribution of total calcium as assessed by LAMMA revealed that in the structurally affected cells the areas in which sarcomeres were replaced by glycogen contained significantly more calcium than all other areas probed such as mitochondria, remaining sarcomeres at the cell periphery and subcellular areas of normally structured cells. Calcium precipitate, obtained after PPA assessment, was localized at the sarcolemma but was virtually absent in the mitochondria of affected cells. The high calcium content in the myolytic areas of affected cells most probably belongs to a pool of bound calcium. The observations that calcium is retained at the sarcolemma and that mitochondria are devoid of precipitate favour the hypothesis that cells structurally affected as such are not ischaemic and are still able to regulate their calcium homeostasis.

Calcium↗

PubMed1993

Effect of inflation on adenosine triphosphate catabolism and lactate production during normothermic lung ischemia.

Although few biochemical data comparing adenosine triphosphate (ATP) catabolism or lactate production in isolated deflated versus inflated lung tissue are available, most transplant centers preserve their donor lungs inflated. We measured ATP level (using high-performance liquid chromatography), energy charge, and lactate level during 2 hours of normothermic ischemia in deflated lung tissue (n = 6), in lung tissue inflated with room air (n = 6), and in lung tissue inflated with 100% oxygen (n = 6). To determine the onset of anaerobic metabolism in lung tissue inflated with 100% O2, ATP and lactate levels were measured in another group (n = 6) during 8 hours of normothermic ischemia. Rabbit lungs were flushed in situ with a modified Krebs-Henseleit solution (60 mL/kg). They were isolated and immersed in 0.9% NaCl at 37 degrees C. In deflated lung tissue, ATP level (control value, 9.4 +/- 0.58 mumol/g dry wt) decreased and lactate level (control value, 5.6 +/- 1.16 mumol/g dry wt) increased after 15 minutes of ischemia (ATP, 5.2 +/- 0.86 mumol/g dry wt; lactate, 13.3 +/- 1.58 mumol/g dry wt). When the lung was stored inflated with room air, ATP breakdown and increase of lactate concentration only occurred after 90 minutes of normothermic ischemia (at 60 minutes: ATP, 8.0 +/- 0.58 mumol/g dry wt; lactate, 6.3 +/- 1.1 mumol/g dry wt). In lungs stored inflated with 100% O2, ATP breakdown and lactate accumulation only occurred after 5 hours of normothermic ischemia (at 4 hours: ATP, 8.1 +/- 0.74 mumol/g dry wt; lactate, 5.9 +/- 1.28 mumol/g dry wt).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1993

Surgery for cardiac myxoma. A 20-year experience with long-term follow-up.

Data on 32 consecutive patients undergoing resection of a cardiac myxoma over a 20-year period (1971-1991) was analyzed. The mean age of the patients was 57 +/- 11 years (range 36 to 78). All myxomas were located in the left atrium except one right ventricular tumor. Ten of the atrial resections were performed with only an endocardial cuff while a full thickness atrial septum cuff was removed in 21 cases. One patient, operated under emergency conditions, died 11 days later as a result of cardiac and pulmonary failure (hospital mortality 3.1%). Late follow-up (mean 6.4 +/- 4.4 years) shows excellent results. All patients are alive and well. No recurrences have been found. In this series, good long-term results were obtained by simple excision of cardiac myxomas. This finding supports the theory that recurrence is mainly confined to patients with familial presentation and/or myxoma complex.

Adult↗

PubMed1993

Muscarinic receptor stimulation by carbachol improves functional recovery in isolated, blood perfused rabbit heart.

OBJECTIVE: The aim was to test whether, besides adenosine A1 receptors, other receptors coupled to the "inhibitory" GTP binding protein Gi confer protection against ischaemic and reperfusion injury. METHODS: Isolated hearts were Langendorff perfused at 37 degrees C with blood and were divided into five groups, all subjected to 45 min zero flow normothermic ischaemia, followed by 1 h reperfusion. Group 1 consisted of control untreated hearts (n = 5). Group 2 consisted of hearts treated with the muscarinic agonist carbachol (CCh, 10 microM; n = 5). In group 3 (CCh+atropine, n = 5) 5 microM atropine was given as well as CCh. Groups 1, 2, and 3 were paced at 3 Hz except during ischaemia. Groups 4 (n = 5) and 5 (n = 6) were similar to groups 1 and 2, except that pacing was continued throughout ischaemia. RESULTS: In group 1, left ventricular end diastolic pressure increased during ischaemia, from 7.2(SEM 1.2) mm Hg to 57(5.6) mm Hg, and remained increased during reperfusion, whereas in group 2, it increased moderately during ischaemia, from 9.2(0.9) mm Hg to 21.6(4.9) mm Hg and returned to preischaemic levels during reperfusion. In hearts paced during ischaemia, contracture developed faster than in unpaced hearts, but CCh still delayed contracture. Postischaemic recovery of isovolumetric left ventricular pressure or its first derivative (dP/dt) and reactive hyperaemia were significantly greater in CCh treated hearts [left ventricular pressure = 69.8(4.9)% of preischaemic value after 60 min reperfusion] than in control hearts [29.3(6.8)%]. Recovery of left ventricular pressure and dP/dt was worsened by pacing, but CCh still improved this recovery [left ventricular pressure = 13.1(8.4)% in control, 46.7(5.3)% in CCh treated hearts]. The CCh effect could be prevented by atropine. ATP breakdown and lactate accumulation during the first minute of ischaemia were lower in non-paced CCh treated hearts than in controls. ATP recovered better at the end of reperfusion in both non-paced [7.1(0.72) mumol.g-1] and paced [4.4(0.77) mumol.g-1] CCh treated hearts, as compared with non-paced [1.8(0.58) mumol.g-1] and paced [1.2(0.39) mumol.g-1] control hearts. In paced hearts, less creatine kinase and lactate dehydrogenase were released in the CCh treated group throughout the reperfusion phase. CONCLUSIONS: Carbachol improves functional recovery and confers cellular protection, and this protection depends mainly but not entirely on its bradycardic effect.

Adenosine Triphosphate↗

PubMed1993

Left ventricular assistance using a catheter-mounted coaxial flow pump (Hemopump) in a canine model of regional myocardial ischaemia.

The global and regional effects of left ventricular circulatory assistance were examined in dogs during acute myocardial infarction using a new coaxial flow device (Hemopump). In 12 dogs the left anterior descending coronary artery was occluded for 4 h and subsequently reperfused for 12 h. In six dogs, left ventricular assistance was started 90 min after coronary artery occlusion and maintained for several hours; six control animals received no circulatory support. Survival rate in the animals receiving mechanical support was 100% vs 0% in the control group. The Hemopump reduced left ventricular stroke work up to 80% and maintained blood flows to the brain, kidneys, liver and intestine throughout the experiment. Infarct size, expressed as a percentage of the left ventricle, however, was not modified (12% in supported animals vs 13% in control dogs). Side effects of the coaxial flow pump were thrombocytopaenia, occurring in all six dogs, and haemolysis, which was demonstrated in one animal. It was concluded that the Hemopump provides effective global and regional circulatory support in a canine model of severe cardiogenic shock. However, the value of left ventricular support to modify infarct size could not be demonstrated in this experimental model.

Animals↗

PubMed1993

Mechanisms underlying myocardial stunning.

The effect of myocardial stunning on mitochondrial function was examined in rabbit hearts. After global normothermic ischemia followed by reperfusion, we previously found that mitochondrial high energy phosphate content was not significantly diminished. To determine whether myocardial stunning results from altered excitation-contraction coupling, we examined function and calcium uptake by sarcoplasmic reticulum (SR). Hearts were subjected to global ischemia under normothermic conditions. Ischemic hearts had significantly lower velocity of Ca2+ uptake by the SR (Vmax 36.3 +/- 1.94 nmol/min per mg vs 49.3 +/- 2.54 nmol/min per mg control) but velocity was restored by reperfusion. Similarly, myocardial ATP content was decreased during ischemia (4.5 +/- 1.23 mumol/g dry weight vs 13.6 +/- 0.98 mumol/g control) but returned to normal during reperfusion. Incubation of homogenates with 610 microM ryanodine did not alter the difference in Vmax between control, ischemic, or reperfused hearts, suggesting that ischemia affects SR Ca2+ pumping without affecting Ca2+ release. Recovery of calcium uptake during reperfusion also indicates that SR Ca2+ ATPase function is not the major cause of myocardial stunning. Potentiated contractions were studied in a Langendorff heart model, revealing that postrest potentiation (PRP) and peak paired-pulse potentiation (PPP) increase as a result of ischemia. On reperfusion, PPP also increased, but there was a decrease in PRP of left ventricular pressure (LVP) and LV dP/dt (PRP LV dP/dt = 127% preischemia vs 112% at 2 min postischemia), indicating than an impairment of an SR function other than Ca2+ ATPase occurs during myocardial stunning.

Adenosine Triphosphate↗