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Métodos Terapéuticos y Terapias MTCI
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1.
Cardiovasc Res ; 32(6): 1008-15, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9015403

RESUMEN

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.


Asunto(s)
Emulsiones Grasas Intravenosas/uso terapéutico , Contracción Miocárdica/efectos de los fármacos , Aturdimiento Miocárdico/tratamiento farmacológico , Triglicéridos/uso terapéutico , Animales , Perros , Ácidos Grasos no Esterificados/metabolismo , Femenino , Glicina/análogos & derivados , Glicina/farmacología , Masculino , Reperfusión Miocárdica , Aturdimiento Miocárdico/metabolismo , Miocardio/metabolismo , Oxidación-Reducción , Función Ventricular Izquierda/efectos de los fármacos
2.
J Am Coll Cardiol ; 23(6): 1499-504, 1994 May.
Artículo en Inglés | MEDLINE | ID: mdl-8176113

RESUMEN

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.


Asunto(s)
Circulación Colateral/efectos de los fármacos , Trombosis Coronaria/tratamiento farmacológico , Metoprolol/administración & dosificación , Terapia Recuperativa/métodos , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Animales , Trombosis Coronaria/fisiopatología , Modelos Animales de Enfermedad , Perros , Evaluación Preclínica de Medicamentos , Femenino , Hemodinámica/efectos de los fármacos , Infusiones Intravenosas , Masculino , Distribución Aleatoria , Proteínas Recombinantes/uso terapéutico , Factores de Tiempo
3.
Basic Res Cardiol ; 89(1): 50-60, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-8010935

RESUMEN

31P-NMR spectroscopy has become the major tool for studying myocardial high energy phosphates. Conflicting results concerning NMR visibility of ATP in ischaemic myocardium were reported. A detailed study was undertaken to resolve this controversy. After cardioplegic arrest, canine hearts were excised and preserved for 24 h at 1 degree C (group 1) or for 6h at 23 degrees C (group 2). ATP breakdown was followed by 31P-NMR spectroscopy in a transmural piece of the anterior wall introduced in the NMR magnet, and by HPLC analysis using serial transmural biopsies from the rest of the anterior wall. At both temperatures, identical relative ATP decay curves were obtained, whether measured by NMR or by HPLC. Absolute quantification of ATP was carried out after varying periods of ischaemia at 1 degree C. The NMR-measured ATP concentration was 106 +/- 8% of the ATP concentration determined by HPLC. From our experiments, we conclude that ATP visibility for 31P-NMR spectroscopy is complete and constant during prolonged periods of hypothermic ischaemia in canine hearts.


Asunto(s)
Adenosina Trifosfato/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Isquemia Miocárdica/metabolismo , Miocardio/metabolismo , Animales , Cromatografía Líquida de Alta Presión/métodos , Perros , Femenino , Cinética , Masculino , Isquemia Miocárdica/patología , Miocardio/patología , Fósforo , Factores de Tiempo
4.
Circulation ; 82(5 Suppl): IV264-8, 1990 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-2225414

RESUMEN

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.


Asunto(s)
Adenosina Trifosfato/metabolismo , Corazón , Miocardio/metabolismo , Preservación de Órganos , Animales , Soluciones Cardiopléjicas , Frío , Paro Cardíaco Inducido , Trasplante de Corazón , Hipotermia Inducida , Papio , Factores de Tiempo
5.
Circulation ; 75(4): 830-6, 1987 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-3103951

RESUMEN

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)


Asunto(s)
Enfermedad Coronaria/tratamiento farmacológico , Trombosis Coronaria/tratamiento farmacológico , Metoprolol/uso terapéutico , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Sístole/efectos de los fármacos , Activador de Tejido Plasminógeno/uso terapéutico , Animales , Trombosis Coronaria/mortalidad , Trombosis Coronaria/fisiopatología , Perros , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Hemodinámica/efectos de los fármacos , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Proteínas Recombinantes/uso terapéutico , Factores de Tiempo
6.
Acta Chir Belg ; 86(2): 118-22, 1986.
Artículo en Inglés | MEDLINE | ID: mdl-3716720

RESUMEN

Between 1970 and 1984 the diagnosis of acute, massive lung embolism was made 30 times in our department. In 29 patients the clinical diagnosis was correct and a Trendelenburg operation under extra-corporeal circulation was performed. In 18 cases there was an operation in the immediate preoperative course. In 1 case there was a combination of operation and the use of contraceptives. 3 cases were immobilized by a plaster of Paris cast. In 4 cases the use of oral contraceptives and in 3 patients the history of chronic recurrent lung embolism were evident. The mean immobilisation time was 15 days. In 24 cases the diagnosis was made only on the base of the clinical anamnesis, and examination, E.C.G. and chest radiography. In 4 cases angiography and in 1 patient the scintigraphy confirmed the diagnosis. Preoperatively 28 patients were in severe shock. One patient was operated electively. 14 patients needed external cardiac massage. In all cases clots were found in the left pulmonary artery, 28 in the right pulmonary artery, in 3 cases clots in the right atrium, 3 in the right ventricle and three in the inferior caval vein. Nine De Weese caval vein clips were inserted and one Mobin-Uddin filter. Postoperatively 18 patients were alive and well without sequelae. Two patients developed a cerebro-vascular accident (CVA) with one complete recovery. Ten patients died. Postoperative treatment consisted of I.V. heparin administration immediately after surgery and 6 months of oral anticoagulants. Except for chronic recurrent lung embolism the pulmonary function tests were excellent postoperatively without recurrence of the disease.


Asunto(s)
Embolia Pulmonar/cirugía , Enfermedad Aguda , Adulto , Anticoagulantes/uso terapéutico , Reposo en Cama/efectos adversos , Anticonceptivos Orales/efectos adversos , Circulación Extracorporea , Femenino , Fracturas Óseas/complicaciones , Heparina/administración & dosificación , Heparina/uso terapéutico , Humanos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/cirugía , Embolia Pulmonar/etiología , Recurrencia
7.
Am Heart J ; 89(1): 51-9, 1975 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-1109552

RESUMEN

We studied the influence of controlled changes in perfusion pressure and heart rate on the regional distribution of myocardial flow in normal dogs and in dogs with multiple chronic coronary artery occlusions but without infarctions. Local myocardial blood flow was determined with the tracer microsphere technique. By stepwise altering of systemic blood pressure during maximal vasodilation classical pressure flow relations were obtained. One week after complete chronic occlusion a functionally and anatomically well-defined compartmentation of blood flow was found. The dilatory reserve is clearly compromised not only in the collateral-dependent myocardium but also in the apparently normal myocardium which delivers collateral flow. An "arterio-arterial shunting" mechanism is shown to exist. Several months after coronary occlusion, regional mycoardial flow is still nonhomogeneous. Although the coronary dilatory capacity of the collateralized myocardium is nearly normal, that of the normal myocardium is found to be higher than normal. Vessel growth in both areas is discussed as being responsible for this phenomenon. Right ventricular pacing during maximal vasodilation produces a flow decrease to the endocardial muscle layers in normal dogs, while the epicardial flow is unchanged. One week after complete chronic coronary occlusion pacing during maximal vasocilation reduces the dilatory capacity in the collateralized areas to such an extent that the supplementary increase in myocardial oxygen demand will induce ischemia because of the compromised oxygen supply.


Asunto(s)
Presión Sanguínea , Circulación Colateral , Circulación Coronaria , Enfermedad Coronaria/fisiopatología , Frecuencia Cardíaca , Animales , Isótopos de Cerio , Radioisótopos de Cromo , Enfermedad Coronaria/mortalidad , Perros , Endocardio , Femenino , Radioisótopos de Yodo , Masculino , Microesferas , Infarto del Miocardio/mortalidad , Miocardio , Niobio , Marcapaso Artificial , Radioisótopos , Radioisótopos de Estroncio
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