RESUMO
OBJECTIVE: Our objectives are 2-fold: (1) to serially measure the release of endothelin and graft-conduit endothelin sensitivity during and after coronary artery bypass grafting and (2) to define potential relationships of changes in endothelin levels to perioperative parameters. METHODS: Endothelin plasma content was measured in patients (n = 105) undergoing bypass grafting from select vascular compartments before operations and at specific intervals up to 24 hours postoperatively. Endothelin sensitivity was determined in isolated internal thoracic artery segments. RESULTS: Systemic arterial and pulmonary arterial endothelin levels were increased by approximately 50% immediately after bypass grafting and increased by another 85% during the first 24 hours postoperatively. Endothelin levels were highest in patients with prolonged ventilatory requirements and extended stays in the intensive care unit (10.2 +/- 0.8 vs 13.2 +/- 1.1 fmol/mL, P =.02, and 9.8 +/- 0.7 vs 13.9 +/- 1.2 fmol/mL, P =.01, respectively. Endothelin sensitivity of the internal thoracic artery was increased in patients requiring prolonged vasodilator support with nitroglycerin. CONCLUSIONS: Systemic and pulmonary arterial endothelin levels remained increased for at least 24 hours postoperatively. Prolonged pharmacologic management and increased intensive care unit stay were associated with increased systemic endothelin release and heightened graft-conduit sensitivity to endothelin.
Assuntos
Ponte Cardiopulmonar , Circulação Coronária , Endotelina-1/sangue , Análise de Variância , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Nitroglicerina/uso terapêutico , Respiração Artificial , Veia Safena/metabolismo , Artérias Torácicas/metabolismo , Vasodilatadores/uso terapêuticoRESUMO
BACKGROUND: A number of cellular and molecular events can be induced after cardiac procedures requiring cardiopulmonary bypass (CPB). The matrix metalloproteinases (MMPs) are a recently discovered family of enzymes that degrade the extracellular matrix, but expression during and after CPB is unknown. METHODS: Systemic plasma MMP levels were measured in patients (n = 28, 63 +/- 1 years) undergoing elective coronary revascularization requiring CPB at baseline, termination of CPB, and 30 minutes, 6 and 24 hours after CPB. Representative classes of MMP species known to degrade matrix and basement membrane components were selected for study. Specifically, the interstitial collagenases MMP-8 and MMP-13, and the gelatinases MMP-2 and MMP-9 were determined by internally validated enzyme-linked immunosorbent assay. RESULTS: The MMP-8 levels increased by fourfold at separation from CPB, and returned to within normal values within 30 minutes after CPB. The proenzyme forms of MMP-13 and MMP-9 increased by more than twofold at cross-clamp release and returned within normal limits within 6 hours after CPB. The proform of MMP-2 increased from baseline values at 6 and 24 hours postoperatively; likely indicative of de novo synthesis. CONCLUSIONS: A specific portfolio of MMPs are released and synthesized during and after CPB. Because MMPs can degrade extracellular proteins essential for maintaining normal cellular architecture and function, enhanced MMP release and activation may contribute to alterations in tissue homeostasis in the early postoperative period.
Assuntos
Ponte Cardiopulmonar , Ponte de Artéria Coronária , Metaloproteinases da Matriz/sangue , Idoso , Indução Enzimática/fisiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine endothelin levels in arterial, pulmonary, and myocardial vascular compartments in patients undergoing coronary artery bypass graft surgery and to examine the influence of endothelin on postoperative recovery. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Fifty patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Endothelin plasma content (fmol/mL) was measured in 50 patients undergoing coronary revascularization from various vascular compartments before surgery and at specific intervals up to 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Myocardial endothelin gradient (coronary sinus - aorta) was calculated before cardiopulmonary bypass (CPB), at release of the aortic cross-clamp, immediately after CPB, and 0.5 hour after CPB. The requirement for inotropic therapy and duration of patient stay in the intensive care unit were determined. Systemic and pulmonary endothelin levels were increased by >80% immediately after CPB when compared with preoperative values and increased again by approximately 60% during the first 24 hours postoperatively (p < 0.05). The myocardial endothelin gradient was reversed after CPB, indicating myocardial production of endothelin (pre-CPB, -0.72+/-0.39 fmol/mL v 0.5 hour post-CPB, 0.60+/-0.49 fmol/mL; p < 0.05). Longer intensive care unit times (>28 hours) were associated with higher systemic endothelin levels when compared with shorter times (<18 hours) (16.30+/-1.33 fmol/mL v 9.81+/-1.67 fmol/mL; p < 0.05). Patients with higher endothelin levels 6 hours postoperatively had greater inotropic requirements during the intensive care unit period. CONCLUSION: Endothelin levels after CPB remained persistently increased for at least 24 hours after surgery and were associated with increased myocardial production of endothelin. These results suggest that the increased endothelin observed in the early postoperative period may contribute to a complex recovery from coronary artery bypass graft surgery.
Assuntos
Ponte Cardiopulmonar , Circulação Coronária , Endotelinas/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Endotelinas/sangue , Humanos , Unidades de Terapia Intensiva , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Radial artery (RA) is being used for coronary artery bypass grafting (CABG) with greater frequency. However, RA is prone to post-CABG vasospasm, which may be neurohormonally mediated. Use of the calcium channel antagonist diltiazem has been advocated as a strategy to reduce post-CABG RA vasospasm. However, whether and to what degree different calcium channel antagonists influence neurohormonally induced RA vasoconstriction remains unknown. METHODS: RA segments were collected from patients undergoing elective CABG (n = 13), and isometric tension was examined in the presence of endothelin (10 nM) or norepinephrine (1 microM). In matched RA, endothelin- or norepinephrine-induced contractions were measured in the presence of diltiazem (277 nM), amlodipine (73 nM), or nifedipine (145 nM). These concentrations of calcium channel antagonists were based upon clinical plasma profiles. RESULTS: Endothelin and norepinephrine caused a significant increase in RA-developed tension (0.54+/-0.1 and 0.68+/-0.1 g/mg, respectively; p<0.05). Amlodipine or nifedipine significantly reduced RA vasoconstriction in the presence of endothelin (30+/-6% and 41+/-9%, respectively; p<0.05) or norepinephrine (27+/-8% and 53+/-9%, respectively; p<0.05), whereas diltiazem did not significantly reduce RA vasoconstriction. CONCLUSIONS: These results demonstrate that neurohormonal factors released post-CABG can cause RA vasoconstriction, and that calcium channel antagonists are not equally effective in abrogating that response. Both amlodipine and nifedipine, which have a higher degree of vascular selectivity, appear to be the most effective in reducing RA vasoconstriction.
Assuntos
Anlodipino/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Diltiazem/farmacologia , Nifedipino/farmacologia , Artéria Radial , Vasoconstrição/efeitos dos fármacos , Ponte de Artéria Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The efficacy of magnesium in the prevention of arrhythmias in pediatric patients after heart surgery remains unknown. Therefore we prospectively examined the effect of magnesium treatment on the incidence of postoperative arrhythmias in pediatric patients undergoing surgical repair of congenital heart defects. METHODS AND RESULTS: Twenty-eight pediatric patients undergoing heart surgery with cardiopulmonary bypass were prospectively, randomly assigned in a double-blind fashion to receive intravenous magnesium (magnesium group, n = 13; 30 mg/kg) or saline (placebo group, n = 15) immediately after cessation of cardiopulmonary bypass. Magnesium, potassium, and calcium levels were measured at defined intervals during surgery and 24 hours after surgery. Continuous electrocardiographic documentation by Holter monitor was performed for 24 hours after surgery. Magnesium levels were significantly decreased below the normal reference range for patients in the placebo group compared with the magnesium group on arrival in the intensive care unit and for 20 hours after surgery. Magnesium levels remained in the normal range for patients in the magnesium group after magnesium supplementation. In 4 patients in the placebo group (27%), junctional ectopic tachycardia developed within the initial 20 hours in the intensive care unit. No junctional ectopic tachycardia was observed in the magnesium group (P =.026). CONCLUSIONS: Although this study was originally targeted to include 100 patients, the protocol was terminated because of the unacceptable incidence of hemodynamically significant junctional ectopic tachycardia that was present in the placebo group. Thus low magnesium levels in pediatric patients undergoing heart surgery are associated with an increased incidence of junctional ectopic tachycardia in the immediate postoperative period.
Assuntos
Arritmias Cardíacas/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias Congênitas/cirurgia , Magnésio/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Arritmias Cardíacas/sangue , Arritmias Cardíacas/diagnóstico , Cálcio/sangue , Ponte Cardiopulmonar/efeitos adversos , Pré-Escolar , Digitalis/uso terapêutico , Método Duplo-Cego , Eletrocardiografia Ambulatorial/efeitos dos fármacos , Feminino , Cardiopatias Congênitas/tratamento farmacológico , Humanos , Infusões Intravenosas , Magnésio/sangue , Deficiência de Magnésio/sangue , Deficiência de Magnésio/diagnóstico , Deficiência de Magnésio/prevenção & controle , Masculino , Fitoterapia , Plantas Medicinais , Plantas Tóxicas , Complicações Pós-Operatórias/sangue , Potássio/sangue , Estudos Prospectivos , Taquicardia Ectópica de Junção/sangue , Taquicardia Ectópica de Junção/etiologia , Taquicardia Ectópica de Junção/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND: Pretreatment with potassium channel openers (PCOs) has been shown to provide protective effects in the setting of myocardial ischemia. The goal of the present study was to examine whether PCO pretreatment would provide protective effects on left ventricular (LV) and myocyte function after cardioplegic arrest. METHODS AND RESULTS: The first study quantified the effects of PCO pretreatment on LV myocyte contractility after simulated cardioplegic arrest. LV porcine myocytes were randomly assigned to 3 groups: (1) normothermic control: 37 degrees C x 2 hours (n = 116); (2) cardioplegia: K+ 24 mEq/L, 4 degrees C x 2 hours followed by reperfusion and rewarming (n = 62); and (3) PCO/cardioplegia: 5 minutes of PCO treatment (50 mumol/L, SR47063, 37 degrees C; n = 94) followed by cardioplegic arrest and rewarming. Myocyte contractility was measured after rewarming by videomicroscopy. The second study determined whether the effects of PCO pretreatment could be translated to an in vivo model of cardioplegic arrest. Pigs (weight 30 to 35 kg) were assigned to the following: (1) cardioplegia: institution of cardiopulmonary bypass (CPB) and cardioplegic arrest (K+ 24 mEq/L, 4 degrees C x 2 hours) followed by reperfusion and rewarming (n = 8); and (2) PCO/cardioplegia: institution of CPB, antegrade myocardial PCO perfusion without recirculation (500 mL of 50 mumol/L, SR47063, 37 degrees C), followed by cardioplegic arrest (n = 6). LV function was examined at baseline (pre-CPB) and at 0 to 30 minutes after separation from CPB by use of the preload-recruitable stroke work relation (PRSWR; x 10(5) dyne.cm/mm Hg). LV myocyte velocity of shortening was reduced after cardioplegic arrest and rewarming compared with normothermic control (37 +/- 3 vs 69 +/- 3 microns/s, P < 0.05) and was improved with 5 minutes of PCO treatment (58 +/- 3 microns/s). In the intact experiments, the slope of the PRSWR was depressed in the cardioplegia group compared with baseline with separation from CPB (1.07 +/- 0.15 vs 2.57 +/- 0.11, P < 0.05) and remained reduced for up to 30 minutes after CPB. In the PCO-pretreated animals, the PRSWR was higher after cessation of CPB when compared with the untreated cardioplegia group (1.72 +/- 0.07, P < 0.05). However, in the PCO pretreatment group, 50% developed refractory ventricular fibrillation by 5 minutes after CPB, which prevented further study. CONCLUSIONS: PCO pretreatment improved LV myocyte contractile function in an in vitro system of cardioplegic arrest. The in vivo translation of this improvement in contractile performance with PCO pretreatment was confounded by refractory arrhythmogenesis. Thus the application of PCO pretreatment as a protective strategy in the setting of cardiac surgery may be problematic.
Assuntos
Trifosfato de Adenosina/fisiologia , Parada Cardíaca Induzida , Canais de Potássio/metabolismo , Função Ventricular/fisiologia , Animais , Separação Celular , Cromanos/farmacologia , Coração/fisiologia , Contração Miocárdica/fisiologia , Miocárdio/citologia , Canais de Potássio/efeitos dos fármacos , Suínos , Fatores de TempoRESUMO
PURPOSE: Previous studies have not determined the correlation between dural puncture and postural headache in paediatric patients. Furthermore, no studies have evaluated the correlation between atypical headache and dural puncture in the paediatric population. Therefore, we prospectively analyzed the incidence of typical postdural puncture headache (PDPHA) and atypical headache in paediatric oncology patients following dural puncture. METHODS: The study population consisted of 66 paediatric patients undergoing 128 consecutive procedures, including 99 lumbar punctures and 29 bone marrow aspirations without concomitant lumbar puncture. Patients were prospectively randomized into four groups: Group I, preteens (< 13 yr) undergoing lumbar puncture, Group II, adolescents (13-21 yr) undergoing lumbar puncture, Group III, preteens undergoing bone marrow aspiration, and Group IV, adolescents undergoing bone marrow aspiration. The presence and description of headache was documented immediately after dural puncture or bone marrow aspiration, and on post-procedure days # 1, 3 and 5 by personnel blinded to the type of procedure. RESULTS: There was an increase in the incidence of headache (9.1%) after lumbar puncture in patients < 21 yr relative to patients undergoing bone marrow aspiration (P < 0.05). No difference was found between the incidence of typical PDPHA after dural puncture in preteens and adolescents. There was also no difference in the incidence of atypical headache after dural puncture or after bone marrow aspiration among preteens and adolescents. CONCLUSIONS: Paediatric patients experience an increased incidence of typical postdural puncture headache after dural puncture compared with age-matched patients undergoing bone marrow aspiration only. Atypical headache is relatively common in the paediatric population after dural puncture or bone marrow aspiration.
Assuntos
Cefaleia/etiologia , Punção Espinal/efeitos adversos , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Neoplasias/cirurgia , Estudos ProspectivosRESUMO
Transient elevations of the potent vasoconstrictive peptide endothelin have been reported to occur with the institution of cardiopulmonary bypass. We measured plasma endothelin levels in a 24-year-old gravid patient undergoing a mitral valve replacement operation. Plasma endothelin levels increased by more than 250% in the first 24 hours postoperatively and remained elevated above baseline values at 36 hours postoperatively.
Assuntos
Ponte Cardiopulmonar , Endotelinas/sangue , Implante de Prótese de Valva Cardíaca , Valva Mitral , Complicações Cardiovasculares na Gravidez/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Gravidez , Falha de Prótese , Reoperação , Trombose/cirurgiaRESUMO
BACKGROUND: Pharmacologic treatment using potassium-channel openers (PCOs) before cardioplegic arrest has been demonstrated to provide beneficial effects on left ventricular performance with subsequent reperfusion and rewarming. However, the PCO treatment interval necessary to provide protective effects during cardioplegic arrest remains to be defined. The present study was designed to determine the optimum period of PCO treatment that would impart beneficial effects on left ventricular myocyte contractility after simulated cardioplegic arrest. METHODS: Left ventricular porcine myocytes were assigned randomly to three groups: (1) normothermic control = 37 degrees C for 2 hours; (2) cardioplegia = K+ (24 mEq/L) at 4 degrees C for 2 hours followed by reperfusion and rewarming; and (3) PCO and cardioplegia = 1 to 15 minutes of treatment with the PCO aprikalim (100 micromol/L) at 37 degrees C followed by hypothermic (4 degrees C) cardioplegic arrest and subsequent rewarming. Myocyte contractility was measured after rewarming by videomicroscopy. A minimum of 50 myocytes were examined at each treatment and time point. RESULTS: Myocyte velocity of shortening was reduced after cardioplegic arrest and rewarming compared with normothermic controls (63+/-3 microm/s versus 32+/-2 microm/s, respectively; p < 0.05). With 3 minutes of PCO treatment, myocyte velocity of shortening was improved after cardioplegic arrest to values similar to those of normothermic controls (56+/-3 microm/s). Potassium channel opener treatment for less than 3 minutes did not impart a protective effect, and the protective effect was not improved further with more prolonged periods of PCO treatment. CONCLUSIONS: A brief interval of PCO treatment produced beneficial effects on left ventricular myocyte contractile function in a simulated model of cardioplegic arrest and rewarming. These results suggest that a brief period of PCO treatment may provide a strategy for myocardial protection during prolonged cardioplegic arrest in the setting of cardiac operation.
Assuntos
Trifosfato de Adenosina/fisiologia , Cardiotônicos/uso terapêutico , Parada Cardíaca Induzida , Contração Miocárdica/fisiologia , Picolinas/uso terapêutico , Canais de Potássio/fisiologia , Piranos/uso terapêutico , Agonistas Adrenérgicos beta/uso terapêutico , Animais , Soluções Cardioplégicas/uso terapêutico , Células Cultivadas , Modelos Animais de Doenças , Glibureto/uso terapêutico , Hipotermia Induzida , Processamento de Imagem Assistida por Computador , Isoproterenol/uso terapêutico , Soluções Isotônicas/uso terapêutico , Microscopia de Vídeo , Contração Miocárdica/efeitos dos fármacos , Reperfusão Miocárdica , Miocárdio/citologia , Potássio/uso terapêutico , Bloqueadores dos Canais de Potássio , Canais de Potássio/efeitos dos fármacos , Distribuição Aleatória , Reaquecimento , Solução de Ringer , Suínos , Fatores de Tempo , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
BACKGROUND: An increased number of patients with preexisting left ventricular (LV) dysfunction and congestive heart failure (CHF) are undergoing cardiac surgery with a higher risk for decreased LV contractility after hyperkalemic cardioplegic arrest. Activation of adenosine triphosphate-sensitive potassium channels by potassium channel openers (PCO) within the myocyte appears to confer a protective effect in the setting of ischemia. Accordingly, the present study was designed to determine whether PCO supplementation during hyperkalemic cardioplegic arrest would provide protective effects on myocyte contractile function, particularly in the setting of CHF. METHODS AND RESULTS: LV myocytes were isolated from control pigs (n=7) and pigs with CHF (rapid pacing, 240 beats per minute; n=7) and then assigned to the following treatment groups: normothermia (cell culture media, 2 hours, 37 degrees C); cardioplegia (24 mEq/L K+, 2 hours, 4 degrees C; then 10 minutes of reperfusion); or PCO/cardioplegia (cardioplegia supplemented with 100 micromol/L of the PCO aprikalim). Myocyte velocity of shortening was reduced in both control (66+/-2 versus 33+/-1 microm/s) and CHFmyocytes (32+/-1 versus 22+/-1 microm/s) after hyperkalemic cardioplegic arrest (P<.05). Contractility after PCO cardioplegia was similar to normothermic values in control (57+/-2 microm/s) and CHF (33+/-1 microm/s) myocytes (P<.05). Intracellular free Ca2+ increased from normothermia during hyperkalemic cardioplegia in control (81+/-4 to 145+/-7 nmol/L) and CHF (262+/-30 to 823+/-55 nmol/L) myocytes (P<.05). PCO cardioplegia attenuated the intracellular increase in free Ca2+ during the cardioplegic interval in control (110+/-6 nmol/L) and CHF (383+22 nmol/L) myocytes (P<.05). CONCLUSIONS: PCO-augmented cardioplegic arrest preserved myocyte contractility and reduced the intracellular free Ca2+ release, which therefore may be of particular benefit in the setting of preexisting LV dysfunction.
Assuntos
Parada Cardíaca Induzida , Contração Miocárdica/efeitos dos fármacos , Picolinas/farmacologia , Canais de Potássio/efeitos dos fármacos , Piranos/farmacologia , Disfunção Ventricular Esquerda/fisiopatologia , Animais , Cálcio/metabolismo , Doença Crônica , Insuficiência Cardíaca/fisiopatologia , Reperfusão Miocárdica , SuínosRESUMO
BACKGROUND: Left ventricular (LV) dysfunction can occur after hyperkalemic cardioplegic arrest and subsequent reperfusion and rewarming. Activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels within the myocyte sarcolemma has been shown to be cardioprotective for myocardial reperfusion injury and ischemia and may play a contributory role in preconditioning for cardioplegic arrest. Accordingly, the present study tested the hypothesis that cardioplegic arrest and activation of KATP channels by a potassium channel opener (PCO) would attenuate alterations in ionic homeostasis and improve myocyte contractile function. METHODS AND RESULTS: Porcine LV myocytes were isolated and randomly assigned to the following treatment groups: normothermic control, incubation in cell culture media for 2 hours at 37 degrees C (n=60); hyperkalemic cardioplegia, incubation for 2 hours in hypothermic hyperkalemic cardioplegic solution (n=60); or PCO/cardioplegia, incubation in cardioplegic solution containing 100 micromol/L of the PCO aprikalim (n=60). Hyperkalemic cardioplegia and rewarming caused a significant reduction in myocyte velocity of shortening compared with normothermic control values (33+/-2 versus 66+/-2 microm/s, P<.05). Cardioplegic arrest with PCO supplementation significantly improved indices of myocyte contractile function when compared with hyperkalemic cardioplegia (58+/-4 microm/s, P<.05). Myocyte intracellular calcium increased during hyperkalemic cardioplegic arrest compared with baseline values (147+/-2 versus 85+/-2 nmol/L, P<.05). The increase in intracellular calcium was significantly reduced in myocytes exposed to the PCO-supplemented cardioplegic solution (109+/-4 nmol/L, P<.05). CONCLUSIONS: Cardioplegic arrest with simultaneous activation of KATP channels preserves myocyte contractile processes and attenuates the accumulation of intracellular calcium. These findings suggest that changes in intracellular calcium play a role in myocyte contractile dysfunction associated with cardioplegic arrest. Moreover, alternative strategies may exist for preservation of myocyte contractile function during cardioplegic arrest.
Assuntos
Soluções Cardioplégicas , Parada Cardíaca Induzida , Coração/fisiopatologia , Contração Miocárdica/efeitos dos fármacos , Picolinas/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização , Canais de Potássio/fisiologia , Piranos/farmacologia , Vasodilatadores/farmacologia , Animais , Cálcio/metabolismo , Células Cultivadas , Coração/efeitos dos fármacos , Coração/fisiologia , Temperatura Alta , Isoproterenol/farmacologia , Cinética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/citologia , Potássio/farmacologia , Canais de Potássio/efeitos dos fármacos , Suínos , Fatores de TempoRESUMO
BACKGROUND: Although propofol (2-6 di-isopropylphenol) is commonly used to induce and maintain anesthesia and sedation for surgery, systematic hypotension and reduced cardiac output can occur in patients with or without intrinsic cardiac disease. The effect of propofol on myocyte contractility after the development of congestive heart failure (CHF) remains unknown. This study tested the hypothesis that propofol would have direct effects on myocyte contractile function in both healthy and CHF cardiac myocyte preparations. METHODS: Isolated left ventricular (LV) myocyte contractile function (shortening velocity, micron/s) was examined in myocytes from five control pigs and in five pigs with pacing-induced CHF (240 beats/min, for 3 weeks) in the presence of propofol concentrations ranging from 1-6 micrograms/ml. In addition, myocyte contractility in response to beta-adrenergic receptor stimulation (isoproterenol, 10-50 nM) in the presence of propofol (3 micrograms/ml) was examined. RESULTS: Three weeks of pacing caused LV dysfunction consistent with CHF as evidenced by increased LV end-diastolic diameter (control 3.3 +/- 0.1 cm vs. CHF 5.6 +/- 0.2 cm; P < 0.05) and reduced LV fractional shortening (control 34 +/- 3% vs. CHF 12 +/- 2%, P < 0.05). Propofol (6 micrograms/ml) caused a concentration-dependent negative effect on velocity of shortening from baseline in both control (67 +/- 2 microns/s vs. 27 +/- 3 microns/s; P < 0.05) and CHF myocytes (29 +/- 1 microns/s vs. 15 +/- 1 microns/s; P < 0.05). Importantly, CHF myocytes were more sensitive than control myocytes to the negative effects of propofol on velocity of shortening at the lower concentration (1 microgram/ml). beta-adrenergic responsiveness was reduced by propofol (3 micrograms/ml) in control myocytes only. CONCLUSIONS: Propofol has a direct and negative effect on basal myocyte contractile processes in the setting of CHF, which is more pronounced than that on healthy myocytes at reduced propofol concentrations.
Assuntos
Anestésicos Intravenosos/farmacologia , Anestésicos Intravenosos/toxicidade , Insuficiência Cardíaca/fisiopatologia , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/toxicidade , Contração Miocárdica/efeitos dos fármacos , Propofol/farmacologia , Propofol/toxicidade , Agonistas Adrenérgicos beta/farmacologia , Animais , Estimulação Cardíaca Artificial , Cardiotônicos/farmacologia , Células Cultivadas , Ventrículos do Coração/citologia , Ventrículos do Coração/fisiopatologia , Isoproterenol/farmacologia , Miocárdio/citologia , Receptores Adrenérgicos beta/fisiologia , Sensibilidade e Especificidade , Suínos , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
UNLABELLED: Perioperative bleeding following coronary artery bypass grafting (CABG) is associated with increased blood product usage. Although aprotonin is effective in reducing perioperative blood loss, excessive cost prohibits routine utilization. Epsilon aminocaproic acid (EACA) and tranexamic acid (TA) are inexpensive antifibrinolytic agents, which, when given prophylactically, may reduce blood loss. The present study was undertaken to compare the efficacy of TA and EACA in reducing perioperative blood loss. METHODS: The study population consisted of first-time CABG patients. Patients were allocated in a prospective double-blind fashion: (1) group EACA (loading dose 15 mg/kg, continuous infusion 10 mg/kg per hour for 6 hours, N = 20); (2) group TA (loading dose 15 mg/kg, continuous infusion 1 mg/kg per hour for 6 hours, N = 20); (3) control group (infusion of normal saline for 6 hours, N = 19). RESULTS: Treatment groups were similar preoperatively. No significant difference in intraoperative blood loss or perioperative use of blood products was noted. D-dimer concentration was elevated in the control group compared to the EACA and TA groups (p < 0.05). Group TA had less postoperative blood loss than the EACA and control groups at 6 and 12 hours postoperatively (p < 0.05). TA had reduced total blood loss (600 +/- 49 mL) postoperatively compared to EACA (961 +/- 148 mL) and control (1060 +/- 127 mL, p < 0.05). CONCLUSION: TA and EACA effectively inhibited fibrinolytic activity intraoperatively and throughout the first 24 hours postoperatively. TA was more effective in reducing blood loss postoperatively following CABG. This suggests that TA may be beneficial as an effective and inexpensive antifibrinolytic in first-time CABG patients.
Assuntos
Ácido Aminocaproico/uso terapêutico , Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica , Ponte Cardiopulmonar/efeitos adversos , Hemorragia Pós-Operatória/tratamento farmacológico , Hemorragia Pós-Operatória/etiologia , Ácido Tranexâmico/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Volume Sanguíneo , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
The placement of pointed cranial pins into the periosteum is a recognized acute noxious stimulation during intracranial surgery which can result in sudden increases in blood pressure and heart rate, causing increases in intracranial pressure. A skull block (blockade of the nerves that innervate the scalp, including the greater and lesser occipital nerves, the supraorbital and supratrochlear nerves, the auriculotemporal nerves, and the greater auricular nerves) may be effective in reducing hypertension and tachycardia. Twenty-one patients were allocated in a prospective, double-blind fashion to a control group or a bupivacaine group. After a standardized induction and 5 min prior to head pinning, a skull block was performed. Patients in the control group received a skull block of normal saline, while the bupivacaine group received a skull block with 0.5% bupivacaine. Systolic (SAP), diastolic (DAP), mean arterial pressure (MAP), heart rate (HR), and end-tidal isoflurane were recorded at the following times: 5 min after the induction of anesthesia, during performance of the skull block, during head pinning, and 5 min after head pinning. Significant increases in SAP of 40 +/- 6 mm Hg, DAP of 30 +/- 5 mm Hg, MAP of 32 +/- 6 mm Hg, and HR of 22 +/- 5 bpm occurred during head pinning in the control group, while remaining unchanged in the bupivacaine group. These results demonstrate that a skull block using 0.5% bupivacaine successfully blunts the hemodynamic response to head pinning.
Assuntos
Bupivacaína/administração & dosagem , Craniotomia , Bloqueio Nervoso , Couro Cabeludo/inervação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Inalatórios/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Pinos Ortopédicos , Craniotomia/instrumentação , Método Duplo-Cego , Orelha Externa/inervação , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/prevenção & controle , Pressão Intracraniana/efeitos dos fármacos , Isoflurano/administração & dosagem , Pessoa de Meia-Idade , Osso Occipital/inervação , Órbita/inervação , Periósteo/cirurgia , Estudos Prospectivos , Taquicardia/prevenção & controle , Osso Temporal/inervação , Volume de Ventilação Pulmonar , Nervo Troclear/efeitos dos fármacosRESUMO
BACKGROUND: Preconditioning protects the myocardium from ischemia and may be a potent means of endogenous cardioprotection during cardioplegic arrest and rewarming. However, fundamental mechanisms that potentially contribute to the beneficial effects of preconditioning during cardioplegic arrest and rewarming remain unclear. Accordingly, the overall goal of the present study was to examine the potential mechanisms by which preconditioning protects myocyte contractile function during simulated cardioplegic arrest and rewarming. METHODS AND RESULTS: Left ventricular isolated porcine myocyte contractile function was examined with the use of videomicroscopy under three conditions: (1) normothermia, maintained in cell medium (37 degrees C) for 2 hours; (2) simulated cardioplegic arrest and rewarming, incubated in crystalloid cardioplegic solution (24 mEq/L K+, 4 degrees C) for 2 hours followed by normothermic reperfusion; and (3) preconditioning/cardioplegic arrest and rewarming, hypoxia (20 minutes) and reoxygenation (20 minutes) followed by simulated cardioplegic arrest and rewarming. Cardioplegic arrest and rewarming caused a decline in steady-state myocyte shortening velocity compared with normothermic controls (22.0 +/- 1.6 versus 57.2 +/- 2.6 microns/s, respectively, P < .05), which was significantly improved with preconditioning (36.1 1.7 microns/s, P < .05). In the next series of experiments, the influence of nonmyocyte cell populations with respect to preconditioning and cardioplegic arrest was examined. Endothelial or smooth muscle cell cultures were subjected to a period of hypoxia (20 minutes) and reoxygenation (20 minutes) and the eluent incubated with naive myocytes, which were then subjected to simulated cardioplegic arrest and rewarming. Pretreatment with the eluent from endothelial cultures followed by cardioplegic arrest and rewarming improved myocyte function compared with cardioplegia-alone values (31.7 +/- 2.2 versus 24.7 +/- 1.6 microns/s, respectively, P < .05), whereas smooth muscle culture eluent pretreatment resulted in no change (23.7 +/- 4.0 microns/s, P = .81). Molecular mechanisms for the protective effects of preconditioning on myocyte contractile processes with cardioplegic arrest and rewarming were examined in a final series of experiments. Adenosine-mediated pathways or ATP-sensitive potassium channels were activated by augmenting cardioplegic solutions with adenosine (200 mumol/L) or the potassium channel opener aprikalim (100 mumol/L), respectively. Both adenosine and aprikalim augmentation significantly improved myocyte function compared with cardioplegia-alone values (53.5 +/- 1.7, 57.6 +/- 2.0 versus 25.7 +/- 1.4 microns/s, respectively, P < .05). CONCLUSIONS: The unique findings from the present study demonstrated that preconditioning provides protective effects on myocyte contractile processes independent of nonmyocyte cell populations and that these effects are mediated in part through the activation of adenosine pathways or ATP-sensitive potassium channels. Thus, preconditioning adjuvant to cardioplegia may provide a novel means of protecting myocardial function after cardioplegic arrest and rewarming.
Assuntos
Parada Cardíaca Induzida , Precondicionamento Isquêmico Miocárdico , Adenosina/farmacologia , Trifosfato de Adenosina/farmacologia , Animais , Contração Miocárdica , Picolinas/farmacologia , Canais de Potássio/efeitos dos fármacos , Piranos/farmacologia , SuínosRESUMO
Propofol is being used more often in cardiac surgery, particularly after hypothermic, hyperkalemic cardioplegic arrest (HHCA). The purpose of this study was to examine the effects of propofol on isolated myocyte contractile function under both normothermic conditions and after simulated HHCA and rewarming. Myocytes were isolated from the left ventricle of eight pigs. Myocyte contractile function was measured under both normothermic conditions and after simulated HHCA (incubation at 4 degrees C for 2 h in crystalloid cardioplegia; K+ = 24 mEq/L) using computer-assisted videomicroscopy in the presence of 2, 4, and 6 micrograms/mL propofol (11.2, 22.4, and 33.6 microM/L, respectively). Isoproterenol (25 nM) was then added and contractile function measurements repeated. Propofol caused significant dose-dependent reductions in myocyte velocity of shortening (baseline = 67 +/- 2 microns/s; propofol = 2 micrograms/mL, 45 +/- 4 microns/s; and propofol = 6 micrograms/mL, 27 +/- 3 microns/s; P < 0.05). HHCA and rewarming caused a significant reduction in myocyte velocity of shortening (29 +/- 0.9 microns/s, P < 0.05), with further significant dose-dependent reductions in contractile function after the addition of propofol. Propofol caused a decrease in beta-adrenergic responsiveness under normothermic conditions, but not after simulated HHCA. Results from the present study demonstrated for the first time that the reduction in isolated myocyte contractile function after simulated HHCA is further decreased by propofol administration.
Assuntos
Anestésicos Intravenosos/farmacologia , Parada Cardíaca Induzida , Coração/efeitos dos fármacos , Hipotermia Induzida , Contração Miocárdica/efeitos dos fármacos , Miocárdio/patologia , Propofol/farmacologia , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/farmacologia , Anestésicos Intravenosos/administração & dosagem , Animais , Soluções Cardioplégicas/administração & dosagem , Células Cultivadas , Soluções Cristaloides , Relação Dose-Resposta a Droga , Processamento de Imagem Assistida por Computador , Isoproterenol/farmacologia , Soluções Isotônicas , Microscopia de Vídeo , Substitutos do Plasma/administração & dosagem , Potássio/administração & dosagem , Propofol/administração & dosagem , Reaquecimento , Suínos , Função Ventricular EsquerdaRESUMO
UNLABELLED: The majority of myocardial protective techniques performed in the United States incorporate hypothermic, hyperkalemic blood or crystalloid cardioplegia. Oxygenated blood cardioplegia has not been compared with oxygenated crystalloid cardioplegia in an isolated myocyte model of hypothermic, hyperkalemic cardioplegic arrest in which direct measurements of contractile function and myocyte swelling can be made. Accordingly, isolated myocyte contractile function and myocyte profile surface area were examined after hypothermic arrest with oxygenated crystalloid or blood cardioplegia. METHODS: Isolated left ventricular pig myocytes were randomly assigned to undergo cardioplegic arrest for 2 hours at 4 degrees C. Either oxygenated crystalloid or blood cardioplegia was used. After 2 hours, myocytes were reperfused with standard cell medium at 37 degrees C and contractile function was examined. A control group of myocytes was maintained in cell medium at 37 degrees C for 2 hours. Myocyte velocity of shortening (micrometers per second) was examined at baseline and after beta-adrenergic stimulation (isoproterenol, 25 nmol/L). Velocity of shortening declined equally from baseline control values (65 +/- 2 micron n/sec) in the groups subjected to oxygenated crystalloid cardioplegia and blood cardioplegia (37 +/- 2 micron n/sec and 42 +/- 1 micron n/sec, respectively; p < 0.05). RESULTS: Although beta-adrenergic stimulation caused a significant increase in velocity of shortening in all myocyte groups, the increase was less pronounced in myocytes subjected to crystalloid cardioplegia (157 +/- 6 micron n/sec) and blood cardioplegia (159 +/- 6 micron n/sec) than in normothermic control myocytes (205 +/- microm/sec; p < 0.05). Myocyte profile surface area, an index of cell volume, was measured in all myocyte groups. Myocyte surface area increased equally after cardioplegic arrest and rewarming in both cardioplegia groups (crystalloid 4119 +/- 53 micron2; blood 3924 +/- 48 micron2); surface areas in both cardioplegia groups were significantly greater than in the normothermic control group (3158 +/- 39 micron2, p < 0.05). CONCLUSION: Equivalent effects of oxygenated crystalloid and blood cardioplegia were observed with respect to myocyte contractile function, inotropic responsiveness, and intracellular volume regulatory processes.
Assuntos
Sangue , Soluções Cardioplégicas/farmacologia , Parada Cardíaca Induzida , Contração Miocárdica , Miocárdio/citologia , Compostos de Potássio/farmacologia , Animais , Técnicas In Vitro , Oxigênio , SuínosRESUMO
BACKGROUND: Significant right ventricular (RV) dysfunction as measured by increased end-diastolic volume and reduced ejection fraction has been documented in the postoperative period after pulmonary resection. We hypothesized that changes in RV contractile state or afterload may contribute to this RV pump dysfunction. METHODS: In part one of the study, RV preload was altered on postoperative day 2 (n = 6) by rapid infusion of Hespan to a total of 250, 500, and 1,000 mL. The relationship between RV stroke work and end-diastolic volume was plotted using linear regression. This preload recruitable stroke work relation had been previously validated as a load-insensitive index of RV contractility. The slopes of the preoperative relation (n = 35) and postoperative relation were compared. In part two of the study, RV afterload was reduced by continuous infusion of prostaglandin E1 (n = 6) through postoperative day 2 and RV pump function was assessed. RESULTS: Comparison of the slopes of the preload recruitable stroke work relation plotted preoperatively and on postoperative day 2 revealed no significant difference, indicating no change in RV contractile state. Infusion of prostaglandin E1 in the postoperative period (n = 6) significantly reduced pulmonary vascular resistance (3.67 +/- 0.19 versus baseline 5.72 +/- 0.19 dyne . s . cm-5/ m2; p < 0.05). However, RV ejection fraction remained significantly reduced (0.34 +/- 0.01 versus baseline 0.42 +/- 0.01; p < 0.05) and end-diastolic volume significantly increased (105 +/- 5 versus baseline 93 +/- 2 mL/m2; p < 0.05). Heart rate was increased compared with baseline throughout the postoperative period. CONCLUSIONS: The present study suggests that RV dysfunction after pulmonary resection is not caused by primary alterations in contractility or immediate changes in afterload. Better control of heart rate with minimal effect on inotropy may enhance RV pump function.
Assuntos
Pneumonectomia , Complicações Pós-Operatórias/fisiopatologia , Disfunção Ventricular Direita/etiologia , Alprostadil/uso terapêutico , Frequência Cardíaca/fisiologia , Humanos , Derivados de Hidroxietil Amido/uso terapêutico , Neoplasias Pulmonares/cirurgia , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Volume Sistólico/fisiologia , Termodiluição , Disfunção Ventricular Direita/fisiopatologiaRESUMO
One proposed contributory mechanism for depressed ventricular performance after hypothermic, hyperkalemic cardioplegic arrest is a reduction in myocyte contractile function caused by alterations in intracellular calcium homeostasis. Because 2,3-butanedione monoxime decreases intracellular calcium transients, this study tested the hypothesis that 2,3-butanedione monoxime supplementation of the hyperkalemic cardioplegic solution could preserve isolated myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Myocytes were isolated from the left ventricles of six pigs. Magnitude and velocity of myocyte shortening were measured after 2 hours of incubation under normothermic conditions (37 degrees C, standard medium), hypothermic, hyperkalemic cardioplegic arrest (4 degrees C in Ringer's solution with 20 mEq potassium chloride and 20 mmol/L 2,3-butanedione monoxime). Because beta-adrenergic agonists are commonly employed after cardioplegic arrest, myocyte contractile function was examined in the presence of the beta-agonist isoproterenol (25 nmol/L). Hypothermic, hyperkalemic cardioplegic arrest and rewarming reduced the velocity (32%) and percentage of myocyte shortening (27%, p < 0.05). Supplementation with 2,3 butanedione monoxime normalized myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Although beta-adrenergic stimulation significantly increased myocyte contractile function under normothermic conditions and after hypothermic, hyperkalemic cardioplegic arrest, contractile function of myocytes exposed to beta-agonist after hypothermic, hyperkalemic cardioplegic arrest remained significantly reduced relative to the normothermic control group. Supplementation with 2,3-butanedione monoxime restored beta-adrenergic responsiveness of myocytes after hypothermic, hyperkalemic cardioplegic arrest. Thus, supplementation of a hyperkalemic cardioplegic solution with 2,3-butanedione monoxime had direct and beneficial effects on myocyte contractile function and beta-adrenergic responsiveness after cardioplegic arrest. A potential mechanism for the effects of 2,3-butanedione monoxime includes modulation of intracellular calcium transients or alterations in sensitivity to calcium. Supplementation with 2,3-butanedione monoxime may have clinical utility in improving myocardial contractile function after hypothermic, hyperkalemic cardioplegic arrest.