RESUMEN
BACKGROUND: Inhibition of the Na (+)/H (+) exchanger (NHE) is cardioprotective, but dosage and timing of NHE-inhibitors are critical for their efficacy. We studied the effect of a new dosing regime of the NHE-inhibitor cariporide on myocardial function and damage after cardioplegic arrest (CPA) and determined its myocardial and serum concentrations. METHODS: 3 pigs received a bolus of 180 mg cariporide intravenously (i. v.) and were sacrificed shortly thereafter to allow measurement of the myocardial concentrations of cariporide. Subsequently, 10 pigs were randomized to receive either i. v. cariporide (bolus followed by an infusion of 40 mg/h) or placebo. Cardiopulmonary bypass was initiated, and the heart was arrested for 60 minutes by infusion of St. Thomas Hospital solution. Left ventricular (LV) function was studied using microsonometry. Myocardial damage was assessed by troponin T. Serum concentrations of cariporide were measured throughout the study, and myocardial concentrations were measured before the end of CPA and 180 minutes thereafter. RESULTS: Cariporide was present in all myocardial specimens (median: 1.4 ng/mg) studied previously. In the main study, LV function or myocardial damage did not differ significantly between the groups at any time point. Stable serum cariporide concentrations were achieved (3.4 +/- 0.5 microg/ml). Cariporide was detectable in only one of the myocardial biopsies obtained before the end of CPA, but 180 minutes thereafter, the myocardial cariporide concentration was 2.5 +/- 0.3 ng/mg. CONCLUSION: We observed no effect of i. v. cariporide on LV function or myocardial damage after cardioplegic arrest. Our data suggest that cariporide is washed out of the myocardium by repeated application of crystalloid cardioplegia. Thus, the mode of delivery also appears to be critical for cardioprotection with NHE-inhibitors.
Asunto(s)
Antiarrítmicos/sangre , Guanidinas/sangre , Miocardio/metabolismo , Compuestos de Potasio/administración & dosificación , Intercambiadores de Sodio-Hidrógeno/sangre , Intercambiadores de Sodio-Hidrógeno/efectos de los fármacos , Sulfonas/sangre , Análisis de Varianza , Animales , Antiarrítmicos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Puente Cardiopulmonar , Circulación Coronaria/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Guanidinas/administración & dosificación , Paro Cardíaco Inducido , Frecuencia Cardíaca/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Isquemia Miocárdica/sangre , Isquemia Miocárdica/etiología , Isquemia Miocárdica/fisiopatología , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Proyectos de Investigación , Volumen Sistólico/efectos de los fármacos , Sulfonas/administración & dosificación , Porcinos , Troponina T/sangre , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Endoaneurysmorrhaphy (EAR) has become an important therapeutic option in the treatment of patients with left ventricular (LV) aneurysm and congestive heart failure. Today, more and more patients are referred for EAR with a dilated akinetic LV rather than a classic dyskinetic LV aneurysm. Little is known about the contribution of the extent of akinesis to perioperative mortality. We reviewed the data of 147 patients with anterior left ventricular aneurysms undergoing EAR. Seventy percent of the patients were male; mean age was 62+/-9 years. Demographic, hemodynamic, angiographic and surgical variables were analyzed using univariate statistic tests in order to determine risk factors for in-hospital mortality.Eighty-two percent of the LV aneurysms had at least some dyskinesia, but 70% were mainly akinetic. 133 patients had additional bypass surgery, one had additional mitral valve replacement. In-hospital mortality was 4.1% (n=6). Risk factors for in-hospital mortality were the total extent of akinetic myocardium (p=0.027) in the 30 degrees RAO view and the duration of cardiopulmonary bypass (CPB, p=0.0068) which was itself dependent on the LV ejection fraction (p=0.001), the number of stenosed coronary arteries (p=0.004), and the extent of akinesis (p=0.023). The extent of dyskinesia was not associated with either perioperative mortality (p=0.36) or CPB duration. EAR can be performed with acceptable perioperative results. Because akinesis increases in many patients with time, and because the duration of ECC was dependent on variables reflecting the severity of the underlying heart disease, our findings underscore the importance of optimal timing for the surgical intervention.