RESUMO
BACKGROUND: Children with advanced heart failure, particularly those with elevated pulmonary vascular resistance, pose a difficult management problem because the normal donor right ventricle cannot cope with the high pulmonary resistance and because of the relative shortage of donor organs of an appropriate size for this age group. METHODS: In an attempt to address these issues and evaluate the role of heterotopic transplantation in this context, we operated on 12 children, six boys and six girls, in the period between January 1, 1991, and March 31, 1996. Their ages ranged from 11 months to 15.2 years (mean 81.6 +/- 62.8 months) and their mean weight was 23.3 kg (range 7.6 to 56.8 kg). Eight patients (66.6%) had significant elevation of pulmonary artery pressure (pulmonary artery systolic pressure = 66 +/- 9.4 mm Hg, mean transpulmonary gradient = 22.3 +/- 3.4 mm Hg). In all patients the donor pulmonary artery was anastomosed to the recipient right atrium without the use of any prosthetic material. Ischemic times varied between 135 and 255 minutes (mean 182.1 +/- 30.7 minutes). The immunosuppression regimen included cyclosporine and azathioprine. Steroids were not routinely used. RESULTS: One patient died in the hospital of acute rejection on postoperative day 16. Three patients had lobe collapse within 1 week and all were treated successfully. Two late deaths (18.2%) occurred as a result of cardiac rejection 3 months and 2 years after the operations. Nine survivors (75%) are alive, active, and growing normally at a mean follow-up of 2.2 years (range 11 months to 4.75 years). Repeated cardiac catheterization performed in seven patients with preoperative pulmonary hypertension showed a slow progressive drop in mean pulmonary artery pressure. No significant change was observed in the function of the recipient hearts. CONCLUSION: We conclude that heterotopic heart transplantation is feasible for a selected group of children with good medium-term results, notably regression of pulmonary artery pressure, normal growth, and lack of long-term chest complications.
Assuntos
Cardiomiopatia Dilatada/cirurgia , Cardiomiopatia Restritiva/cirurgia , Transplante de Coração , Transplante Heterotópico , Adolescente , Anastomose Cirúrgica , Pressão Sanguínea , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Lactente , Masculino , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/cirurgia , Estudos Retrospectivos , Volume Sistólico , Resultado do TratamentoRESUMO
Endothelium-mediated relaxation and smooth muscle function in large coronary arteries are resistant to prolonged global ischemia. We used a small-vessel myograph to test the hypothesis that small intramyocardial artery endothelium and smooth muscle function have greater sensitivity to ischemic injury than large artery endothelium and smooth muscle. Normothermic global ischemia was induced in 15 porcine hearts. Intramyocardial arterial ring segments were assessed at 0, 30, 60, 90, and 120 minutes of ischemia in vitro with a small-vessel myograph. Potassium determined smooth muscle contraction, bradykinin endothelium-mediated relaxation, and sodium nitroprusside direct smooth muscle relaxation. Endothelium-mediated relaxation after 30 minutes of ischemia was similar to control (56% versus 66%) but was impaired at 60, 90, and 120 minutes of ischemia (32%, 11%, and 6%). Smooth muscle contraction was unchanged at 30 and 60 minutes compared with control (56 and 53 versus 63 mm Hg) but was significantly decreased at 90 and 120 minutes (33 and 13 mm Hg). Direct smooth muscle relaxation was significantly decreased at 120 minutes of ischemia compared with control (58% versus 95%). In a previous study, epicardial coronary artery endothelium-mediated smooth muscle vasodilation and direct smooth muscle vasodilation were preserved until 160 minutes of ischemia. After 160 minutes of ischemia, endothelium-mediated relaxation was lost and only direct smooth muscle vasodilation was preserved. In contrast to vasodilation, vasoconstriction was significantly reduced at 140 minutes of ischemia. These data indicate a greater and earlier adverse effect of ischemia on intramyocardial arterial endothelium-mediated relaxation than smooth muscle contraction or relaxation. These data support the hypothesis that there is an early functional endothelial cell injury associated with global ischemia. Relaxation that is endothelium-dependent in intramyocardial arteries is more sensitive to ischemic injury than in epicardial arteries. Unique to this study was the evaluation of small intramyocardial arteries (281 +/- 29 microns) that are the primary sites of coronary vascular resistance. Microvascular endothelial dysfunction after ischemia, therefore, may contribute to the "no-reflow phenomenon" seen during reperfusion injury.
Assuntos
Vasos Coronários/fisiopatologia , Microcirculação/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Animais , Bradicinina/farmacologia , Endotélio Vascular/fisiopatologia , Técnicas In Vitro , Músculo Liso Vascular/fisiopatologia , Nitroprussiato/farmacologia , Suínos , Sistema Vasomotor/fisiopatologiaRESUMO
We tested the hypothesis that dynamic cardiomyoplasty produces beneficial changes in the functional mechanics of the dilated, failing left ventricle. Chronic dilated cardiomyopathy was induced in seven mongrel dogs by rapid ventricular pacing (260 beats/min) for 3 to 4 weeks. After completion of the induction period, dynamic cardiomyoplasty was performed with the left latissimus dorsi muscle, paced synchronously with the R waves of the electrocardiogram (Medtronic SP1005). Instruments included an aortic flow probe, a left ventricular Millar pressure catheter, and piezoelectric sonomicrometric crystals on the left ventricle for measurements of wall thickness and minor and major axis dimensions. Data were obtained with the stimulator off and on. Statistical comparisons were made with Student's t test for paired data. Dynamic cardiomyoplasty increased the cardiac output of the failing heart (966 +/- 124 versus 1166 +/- 112 ml/min; p less than 0.01). Systolic shortening of both minor and major axis dimensions increased (3.1 +/- 0.3 versus 4.7 +/- 0.3 mm, p less than 0.01, and 4.6 +/- 0.3 versus 7.3 +/- 0.9 mm, p less than 0.05, respectively). Left ventricular end-diastolic pressure decreased by 16% (18 +/- 1 versus 15 +/- 1 mm Hg, p less than 0.01). Although skeletal muscle contraction increased the pressure development in the left ventricular chamber, mean systolic wall stress was diminished by concomitant changes in left ventricular dimensions (116,144 +/- 11,530 versus 101,268 +/- 7464 dynes/cm2, p less than 0.05). At end-systole, wall thickness increased (11.8 +/- 1.1 versus 12.7 +/- 1.1 mm, p less than 0.01), minor axis dimension decreased (51.3 +/- 1.4 versus 49.2 +/- 1.8 mm, p less than 0.01), and major axis dimension also decreased (85.6 +/- 3.3 versus 79.0 +/- 2.3 mm, p less than 0.05). Our detailed evaluation of left ventricular chamber mechanics suggests that dynamic cardiomyoplasty may have a role in ameliorating the functional and mechanical derangements associated with progression of dilated cardiomyopathy both by augmenting cardiac performance and by diminishing determinants of myocardial oxygen consumption. (All values are expressed as mean +/- standard error of the mean.)
Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiomiopatia Dilatada/cirurgia , Coração/fisiopatologia , Músculos/transplante , Animais , Débito Cardíaco , Procedimentos Cirúrgicos Cardíacos/métodos , Cardiomiopatia Dilatada/fisiopatologia , Cães , Contração Miocárdica , Pressão , Retalhos Cirúrgicos , Função Ventricular EsquerdaRESUMO
The gastroepiploic artery is an alternate conduit for coronary artery bypass grafting. To test the hypothesis that its vasoreactive properties are different from those of the internal mammary artery, we obtained gastroepiploic artery segments from human gastrectomy specimens. Trimmed internal mammary artery segments were obtained during coronary artery bypass. Ring segments were mounted on a strain gauge and stretched to optimum resting length (90% of the internal circumference at 100 mm Hg). Potassium chloride, serotonin, and norepinephrine were chosen to simulate physiologic vasospasm induced by depolarization, platelet aggregation, or adrenergic stimulation, respectively. Contractions to potassium and a concentration-response curve to serotonin or norepinephrine were obtained. Sodium nitroprusside was used to assess relaxation. Gastroepiploic artery segments had stronger contractions to the depolarizing agent (potassium chloride), adrenergic stimulation (norepinephrine), and product of platelet aggregation (serotonin). The gastroepiploic and internal mammary arteries showed equal sensitivity, measured by concentration causing half-maximal contraction to norepinephrine and serotonin. There was no difference in relaxation to sodium nitroprusside. These data suggest that prevention of platelet-, adrenergic-, or potassium-induced contraction may be more important when the gastroepiploic artery is used as an alternate conduit for coronary artery bypass, reinforcing consideration of nitrovasodilators and platelet inhibitors in the perioperative interval.
Assuntos
Ponte de Artéria Coronária/métodos , Artéria Torácica Interna/fisiologia , Omento/irrigação sanguínea , Estômago/irrigação sanguínea , Artérias/efeitos dos fármacos , Artérias/fisiologia , Humanos , Artéria Torácica Interna/efeitos dos fármacos , Nitroprussiato/farmacologia , Norepinefrina/farmacologia , Cloreto de Potássio/farmacologia , Serotonina/farmacologia , Estresse Mecânico , Vasoconstrição/fisiologia , Vasodilatação/fisiologiaRESUMO
The marked edema observed in neonatal cardiopulmonary bypass is thought to result from pathologic increases in capillary permeability. Pentafraction is a subfraction of hydroxyethyl starch that is thought to be of appropriate size and shape to be retained by leaking capillaries and seal endothelial gaps in capillary basement membranes. To test the hypothesis that pentafraction would reduce edema in neonatal cardiopulmonary bypass, we established a model of edema formation in neonatal bypass in which neonatal piglets underwent 2 hours of normothermic cardiopulmonary bypass with crystalloid prime and no myocardial ischemia. Before initiation of bypass, experimental animals (n = 11) received intravenous pentafraction, 3 gm/kg. Control animals (n = 10) received an equivalent volume of saline. Hemodynamic parameters, animal weight, fluid redistribution, and percent tissue water of individual organs were assessed during and after bypass. Pentafraction treatment resulted in significant differences in (1) lowered percent body weight gain from baseline (11% versus 48%), (2) lowered volume requirement to maintain venous reservoir during cardiopulmonary bypass (148 ml/kg versus 581 ml/kg), (3) less fluid loss from the peritoneum (11 ml/kg versus 115 ml/kg), and (4) lowered percent tissue water of kidney, pancreas, stomach, jejunum, colon, and skeletal muscle (p less than 0.05 by unpaired t test). Pentafraction had no effect on hemodynamic parameters during bypass nor in percent tissue water of heart, lung, liver, spleen, skin, or brain. In summary, pentafraction lessened weight gain and fluid requirements during cardiopulmonary bypass, favorably influencing the percent tissue water of certain organs. If pentafraction functions as proposed, it may have wide applicability not only in cardiopulmonary bypass (or extracorporeal membrane oxygenation) but also in other clinical scenarios with altered capillary permeability.
Assuntos
Ponte Cardiopulmonar , Edema/prevenção & controle , Derivados de Hidroxietil Amido/administração & dosagem , Animais , Animais Recém-Nascidos , Água Corporal , Edema/fisiopatologia , Hemodinâmica , Peso Molecular , Monitorização Fisiológica , Suínos , Aumento de PesoRESUMO
Internal mammary arteries (IMAs) from women and the elderly have been postulated to be smaller and more reactive than IMAs from men and younger patients and, therefore, not as reliable for coronary artery bypass grafting in the short term. This study tests the physiologic basis for that hypothesis. Trimmed IMA segments were obtained from patients aged 50 to 76 years at coronary artery bypass grafting. Eighteen ring segments from 12 women and 35 ring segments from 17 men were mounted on a strain-gauge apparatus, and internal diameter at a transmural pressure of 100 mm Hg was determined from length-tension curves. Contractions to potassium chloride and a dose-response curve to norepinephrine or serotonin were obtained to simulate physiologic vasospasm. Sodium nitroprusside determined arterial relaxation. Linear regression was used to determine correlation of these parameters with age. Internal mammary arteries from women and men were of equal size. They had equal strength of contraction to potassium chloride and norepinephrine, but female IMAs had greater strength of contraction to serotonin. Female IMAs had weaker contraction to norepinephrine as a percent of maximum contraction to potassium chloride than IMAs from men. Internal mammary arteries from women had equal relaxation to sodium nitroprusside compared with IMAs from men. There was no correlation between age and arterial reactivity to vasoconstrictors, relaxation to sodium nitroprusside, or size. These data suggest that IMAs from women and the elderly are not more susceptible to reduction in flow due to smaller size. Postoperatively, it may be important that women be kept on platelet inhibitors because of their greater absolute contraction to serotonin and men on nitrovasodilators because of their greater relative contraction to norepinephrine.
Assuntos
Artéria Torácica Interna/fisiologia , Fatores Etários , Idoso , Ponte de Artéria Coronária , Relação Dose-Resposta a Droga , Feminino , Humanos , Técnicas In Vitro , Masculino , Artéria Torácica Interna/anatomia & histologia , Artéria Torácica Interna/efeitos dos fármacos , Artéria Torácica Interna/transplante , Pessoa de Meia-Idade , Músculo Liso Vascular/efeitos dos fármacos , Nitroprussiato/farmacologia , Norepinefrina/farmacologia , Cloreto de Potássio , Análise de Regressão , Serotonina/farmacologia , Fatores Sexuais , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
We describe a patient who sustained a traumatic rupture of an aberrant right subclavian artery. An interposition graft was used to restore continuity of the artery to the descending thoracic aorta.
Assuntos
Artéria Subclávia/anormalidades , Artéria Subclávia/lesões , Adulto , Aorta Torácica/cirurgia , Aortografia , Implante de Prótese Vascular , Humanos , Masculino , Ruptura , Artéria Subclávia/cirurgiaRESUMO
Hypothyroidism is associated with profound left ventricular dysfunction. Brain-dead organ donors and patients undergoing cardiopulmonary bypass are chemically hypothyroid with significantly reduced circulating free triiodothyronine (T3). To test the hypothesis that T3 enhances left ventricular function in a hormonally deficient environment, a total of 36 healthy New Zealand White rabbit hearts were studied using a modified Langendorff preparation with Krebs-Henseleit perfusate and intra-ventricular balloon. In 9 normal rabbit hearts a cumulative dose-response curve with logarithmically increasing doses of T3 was obtained. The vehicle solution for T3 dissolution served as control (n = 9). Left ventricular function was assessed from peak developed pressure at baseline and after T3 administration. Triiodothyronine had no effect in normal hearts on peak developed pressure or end-diastolic pressure. In 18 rabbits, the acute effect of T3 administration after ischemia was investigated. Preischemic left ventricular function was measured to serve as baseline, and hearts were subjected to 37 degrees C global ischemia. Triiodothyronine (n = 9) or vehicle (n = 9) was infused during reperfusion, and left ventricular peak developed pressure was measured at 30 and 60 minutes of reperfusion. Recovery of function (expressed as percent return of left ventricular peak developed pressure) was significantly improved within 15 minutes of reperfusion (65.0% +/- 2.1% versus 80.2% +/- 4.1%) and remained significantly improved throughout the reperfusion period (p less than 0.05 by analysis of variance). These data suggest that although T3 possesses no inotropic properties, it significantly improves postischemic left ventricular function. The rapidity of the functional improvement suggests that these effects may be due to plasma membrane-mediated mechanisms.
Assuntos
Doença das Coronárias/fisiopatologia , Tri-Iodotironina/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Hemodinâmica/efeitos dos fármacos , Coelhos , Valores de ReferênciaRESUMO
Cardiopulmonary bypass causes a "euthyroid-sick" state characterized by low levels of circulating triiodothyronine. Triiodothyronine supplementation in this setting has been postulated to improve postischemic left ventricular function by increasing the availability of myocardial high-energy phosphates. These postulates have not been substantiated, however, using load-independent parameters of left ventricular function and analysis of high-energy phosphate metabolism. To test these hypotheses, 14 healthy pigs (30 to 40 kg) were placed on cardiopulmonary bypass and instrumented with left ventricular minor-axis ultrasonic crystals and micromanometer-tipped pressure catheters. Hearts were subjected to 30 minutes of global, normothermic ischemia. Triiodothyronine (0.1 mg/kg; n = 7) or placebo (n = 7) was administered in a random, investigator-blinded fashion at the removal of the aortic cross-clamp and after 60 minutes of reperfusion. Hemodynamic, metabolic, and ultrastructural data were obtained before ischemia and after 30, 60, 90, and 120 minutes of reperfusion. By 90 minutes of reperfusion left ventricular contractility had returned to preischemic levels in hearts supplemented with triiodothyronine, despite postischemic myocardial adenosine triphosphate levels of 50% to 60% of baseline in both groups. Ultrastructurally, the sarcoplasmic reticulum and mitochondria were significantly better preserved in the group treated with triiodothyronine. This study suggests that triiodothyronine supplementation significantly enhances postischemic left ventricular functional recovery and that this recovery is due to mechanisms other than enhanced availability of myocardial high-energy phosphates.
Assuntos
Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Tri-Iodotironina/farmacologia , Nucleotídeos de Adenina/metabolismo , Animais , Ponte Cardiopulmonar , Hemodinâmica/efeitos dos fármacos , Isquemia Miocárdica/metabolismo , Reperfusão Miocárdica , Miocárdio/metabolismo , Miocárdio/ultraestrutura , Suínos , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Orotic acid accelerates compensatory myocardial hypertrophy after regional ischemia and improves left ventricular function acutely after global ischemia. In this study, the effect of orotic acid on left ventricular function was investigated 4 days after global ischemia (75 minutes, 21 degrees C) using heterotopically transplanted rabbit hearts (n = 18). Experimental animals received daily 100-mg/kg doses of intraperitoneally administered orotic acid, starting 1 day before transplantation, and showed a threefold increase in the serum level of orotic acid by 4 days. After 1 hour of reperfusion, the developed pressure was equally depressed in both the control and experimental groups; however, 4 days later, the developed pressure in control animals was decreased by 3 +/- 3 mm Hg (versus the developed pressure measured at 1 hour) while the developed pressure in experimental animals was significantly increased by 25 +/- 8 mm Hg. Heterotopically transplanted hearts manifested diminished systolic function (stemming from ischemia and unloading) as well as decreased expression of adult myosin. Because orotic acid has been observed to produce an increase in protein synthesis in other models, we investigated whether this improvement in systolic function resulted from an orotic acid-mediated augmentation (or preservation) or normal adult myosin expression. Both orotic acid-treated and untreated hearts manifested decreased expression of the beta-myosin heavy chain protein and steady-state messenger RNA levels. Because function improved with decreased beta-myosin heavy chain expression, an alternate mechanism underlying orotic acid-mediated improvement in function is implicated. Nevertheless, orotic acid may be a therapeutic agent facilitating long-term recovery from global ischemia.
Assuntos
Transplante de Coração , Ácido Orótico/farmacologia , Transplante Heterotópico/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Animais Endogâmicos , Eletroforese em Gel de Poliacrilamida , Rejeição de Enxerto/patologia , Miocárdio/metabolismo , Miosinas/análise , Ácido Orótico/sangue , RNA Mensageiro/análise , CoelhosRESUMO
Right ventricular (RV) failure is commonly treated with intravascular volume expansion to increase the RV-left atrial pressure gradient and improve left-sided filling. As RV pressure rises, chamber distention occurs and wall tension increases. These studies were designed to determine if increased wall tension might impede RV myocardial blood flow in the normal canine right ventricle and thus contribute to RV failure. Hemodynamic data, the septal-RV free wall dimension, and RV myocardial blood flow were obtained at low and high levels of preload and in both the autoregulated and vasodilated (adenosine, 2 mg per kilogram of body weight per minute) states. Elevated filling pressure decreased RV myocardial blood flow in both the autoregulated (0.85 +/- 0.18 to 0.67 +/- 0.15 ml/min/gm; p less than .05) and vasodilated (2.25 +/- 0.50 to 0.85 +/- 0.25 ml/min/gm; p less than .05) states but did not change the transmural distribution of blood flow to the right ventricle. Vasodilator reserve was markedly impaired in the high-preload state. These observations suggest that preload is an important determinant of RV myocardial blood flow. Volume loading to treat RV dysfunction may be limited by impairment of RV myocardial blood flow.
Assuntos
Circulação Coronária , Coração/fisiologia , Animais , Pressão Sanguínea , Ponte Cardiopulmonar , Vasos Coronários/fisiologia , Cães , Microesferas , Radioisótopos , Volume Sistólico , Vasodilatação , Função VentricularRESUMO
We hypothesized that coronary artery endothelial cell function and smooth muscle function are modified by global myocardial ischemia and used bradykinin-induced secretion of endothelium-derived relaxing factor as a marker of endothelial cell function. Bradykinin and sodium nitroprusside together determined maximum smooth muscle relaxation. Potassium chloride-induced contraction determined smooth muscle contractility. Endothelium-mediated smooth muscle relaxation expressed as a ratio of total coronary smooth muscle relaxation before and after ischemia quantified endothelial cell function. The effect of global normothermic ischemia on in situ coronary arteries from 7 swine hearts was studied. Coronary arterial rings taken from 0 to 220 minutes of ischemia at 20-minute intervals were studied in vitro. The data revealed unexpected tolerance of endothelium-mediated relaxation to ischemia. Endothelium-derived relaxing factor function was maintained to 160 minutes and smooth muscle function, to 120 minutes of ischemia. Coronary artery dysfunction seen in other studies after less ischemia may be the result of injury introduced during reperfusion, may be the consequence of myocardial injury, or may be due to events operative at the level of small arterioles.
Assuntos
Vasos Coronários/fisiopatologia , Endotélio Vascular/fisiopatologia , Músculo Liso Vascular/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Vasoconstrição , Vasodilatação , Animais , Bradicinina/farmacologia , Circulação Coronária , Óxido Nítrico/fisiologia , Nitroprussiato/farmacologia , Suínos , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
We tested the hypothesis that 3,4,5,-trihydroxybenzamidoxime (VF 233), a demonstrated hydroxyl radical scavenger and an effective Fe3+ chelator, attenuates reperfusion injury and improves isovolumic left ventricular function. Eighteen isolated, perfused rabbit hearts with intracavitary balloons were subjected to normothermic, global ischemia until the initiation of ischemic contracture. Effects on the adenine nucleotide pool metabolites were determined by high-pressure liquid chromatography from right ventricular biopsy specimens before ischemia and at 15-minute intervals throughout reperfusion. In the experimental group (n = 9), a 5-mL bolus of 1 mol/L VF 233 was given immediately before reperfusion and followed by a continuous infusion (0.125 mumol/min). The control group (n = 9) received the vehicle solution at identical times. Rabbits treated with VF 233 had significant improvement in left ventricular function (expressed as percent return of left ventricular peak developed pressure) within 15 minutes of reperfusion (55.0 +/- 3.0 versus 66.2 +/- 4.1; p less than 0.05 by analysis of variance) after global ischemia and remained significantly improved throughout the reperfusion period. Myocardial adenine nucleotide pool intermediates were not significantly different between groups. These results demonstrate that administration of VF 233 significantly improves ventricular function but does not affect adenine nucleotide metabolism after ischemia and reperfusion.
Assuntos
Benzamidinas/uso terapêutico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Nucleotídeos de Adenina/metabolismo , Animais , Técnicas In Vitro , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Coelhos , Função Ventricular EsquerdaRESUMO
Inotropic support for the dilated, failing ventricle results in complex hemodynamic changes affecting preload, afterload, contractility, and heart rate, each of which affects myocardial oxygen consumption. Appreciation of a hierarchy of hemodynamic determinants of myocardial oxygen consumption may be helpful to the clinician trying to balance oxygen demands and hemodynamic performance. We tested the hypothesis that epinephrine alters the hierarchy of hemodynamic determinants of myocardial oxygen consumption in a canine model of dilated cardiomyopathy created by rapid ventricular pacing. Dogs (n = 10) were instrumented to record left ventricular pressure and dimension, and a modified right heart bypass preparation was used to control left ventricular workload. Coronary sinus effluent was quantitatively collected and analyzed for oxygen content and used to calculate myocardial oxygen consumption. Epinephrine administration significantly increased myocardial oxygen consumption in the empty, beating heart; however, when the relationships of multiple determinants of left ventricular work and load were compared before and after epinephrine administration, no oxygen wasting effect was observed. Using multivariate linear regression analysis, a hierarchy of hemodynamic determinants of myocardial oxygen consumption was created. In the untreated heart, stroke work and cardiac output were the primary hemodynamic determinants of oxygen consumption; epinephrine significantly altered the determinants such that wall stress became the dominant hemodynamic determinant of myocardial oxygen consumption. Focused manipulation of wall stress in the treated, failing heart may limit the potentially deleterious effects of inotropic stimulation in this setting.
Assuntos
Cardiomiopatia Dilatada/metabolismo , Epinefrina/farmacologia , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Consumo de Oxigênio , Nucleotídeos de Adenina/metabolismo , Animais , Estimulação Cardíaca Artificial , Cardiomiopatia Dilatada/fisiopatologia , Cães , Hemodinâmica/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Estimulação Química , Volume Sistólico/efeitos dos fármacosRESUMO
BACKGROUND: The platelet GP IIb/IIIa inhibitor eptifibatide improves outcomes in patients with acute coronary syndromes. Patients requiring emergent coronary artery bypass grafting, however, may be at increased risk for bleeding if exposed to eptifibatide. Data from the PURSUIT trial were reviewed to assess this risk in patients undergoing coronary surgery immediately after exposure to eptifibatide. METHODS: In PURSUIT, 10,948 patients who presented with non-ST segment elevation acute coronary syndromes were prospectively randomized to receive eptifibatide (180 microg/kg bolus plus 2 microg/kg/min infusion) or placebo. A total of 78 patients underwent immediate coronary artery bypass surgery within 2 hours of cessation of study drug (placebo, n = 46; eptifibatide, n = 32). Clinical outcome, bleeding, and transfusion requirements within this subset were examined. RESULTS: Major bleeding was not different between groups, occurring in 64% of patients receiving placebo and 63% of patients receiving eptifibatide. The incidence of blood transfusion was similar as well (57% vs 59%). Postoperative thrombocytopenia occurred less often after eptifibatide exposure. Perioperative myocardial infarction was significantly reduced in patients who received eptifibatide (46% vs 22%, p < 0.05). There was no difference in perioperative stroke (2.2% vs 6.3%) or mortality (6.3% vs 6.5%). CONCLUSIONS: Patients may safely undergo coronary artery bypass surgery within 2 hours of discontinuation of eptifibatide. Eptifibatide infusion in the immediate preoperative period had no adverse clinical effects, but did significantly decrease the incidence of perioperative myocardial infarction. Additionally, platelet counts after surgery were higher in the group of patients who received eptifibatide, perhaps indicative of a platelet-sparing effect during cardiopulmonary bypass.
Assuntos
Ponte de Artéria Coronária/métodos , Peptídeos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Adulto , Idoso , Angina Instável/tratamento farmacológico , Transfusão de Sangue , Método Duplo-Cego , Eptifibatida , Feminino , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Peptídeos/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Contagem de Plaquetas , Complicações Pós-Operatórias , Estudos ProspectivosRESUMO
BACKGROUND: Abciximab (ReoPro; Eli Lilly and Co, Indianapolis, IN) is a monoclonal antibody that binds to the platelet glycoprotein IIb/IIIa receptor and produces powerful inhibition of platelet function. Clinical trials of abciximab in patients undergoing coronary angioplasty have demonstrated a reduction in thrombotic complications and have encouraged the widespread use of this agent. We have observed a substantial incidence of excessive bleeding among patients who receive abciximab and subsequently require emergency cardiac operations. METHODS: The records of 11 consecutive patients who required emergency cardiac operations after administration of abciximab and failed angioplasty or stent placement were reviewed. RESULTS: The interval from the cessation of abciximab administration to operation was critical in determining the degree of coagulopathy after cardiopulmonary bypass. The median values for postoperative chest drainage (1,300 versus 400 mL; p < 0.01), packed red blood cells transfused (6 versus 0 U; p = 0.02), platelets transfused (20 versus 0 packs; p = 0.02), and maximum activated clotting time (800 versus 528 seconds; p = 0.01) all were significantly greater in the early group (cardiac operation < 12 hours after abciximab administration; n = 6) compared with the late (cardiac operation >12 hours after abciximab administration; n = 5) group. CONCLUSIONS: This report suggests that the antiplatelet agent abciximab is associated with substantial bleeding when it is administered within 12 hours of operation.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Perda Sanguínea Cirúrgica , Procedimentos Cirúrgicos Cardíacos , Tratamento de Emergência , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia Pós-Operatória/induzido quimicamente , Abciximab , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagemRESUMO
OBJECTIVE: Although airway problems after lung and heart-lung transplantation have been greatly reduced due to changes in surgical technique, excessive granulation tissue at the anastomosis may threaten airway patency. Treatment options include electrocautery, dilation, laser coagulation and stent placement however, recurrence remains a problem. Cryotherapy, the controlled application of extreme cold, is effective at causing cell lysis in granulation tissue and may therefore be effective after lung transplantation for airway problems arising from granulation stenosis. Our objective was to review our experience with cryotherapy as a first-line treatment for airways compromised by granulation tissue after lung and heart-lung transplantation. METHODS: A retrospective analysis of patient records after lung and heart-lung transplantation was performed. A total of 696 patients were identified who received lung or heart-lung transplants, 64 of whom were found to have granulation tissue at the site of airway anastomosis (8.9% of 721 airways at risk). When the granulation tissue was found to narrow the lumen by > or = 50% and affect lung function. RESULTS: The trachea was involved in 5 patients and the main stem bronchus in 16. Each patient required a mean of 2.6 +/- 2.0 cryoapplications. Anatomical results of cryotherapy were judged excellent to good in 15 patients and fair in 6 patients. Eight patients required endobronchial stenting as part of a multimodality treatment. Overall, the post-treatment FEV1 and FVC increased by 34 +/- 36% and 25 +/- 27% from pre-treatment values respectively (P < 0.001). In 13 patients in whom cryotherapy and dilation alone were effective, the FEV1 increased by 41 +/- 43% (range -11 +/- 138%) and the FVC by 28 +/- 29% (range -4 +/- 96%). These changes were also significant (P < 0.001). Changes in these two parameters were positively and significantly correlated (P < 0.01). Acturial survival at 3 and at 5 years were 57 and 43%, respectively (NS compared to total cohort), and median survival was 978 days (range 365-1862). Six patients are alive at a median follow-up of 5.75 years (range 0.6-8.3). CONCLUSIONS: We conclude that cryotherapy is a safe, effective treatment for excessive granulation tissue after lung and heart lung transplantation and may reduce the need for endobronchial stenting and limit recurrence.
Assuntos
Crioterapia , Transplante de Coração , Transplante de Coração-Pulmão , Complicações Pós-Operatórias/terapia , Adulto , Broncopatias/etiologia , Broncopatias/terapia , Criança , Feminino , Tecido de Granulação , Humanos , Masculino , Pessoa de Meia-Idade , Estenose Traqueal/etiologia , Estenose Traqueal/terapia , Resultado do TratamentoRESUMO
Platelet-mediated coronary thrombosis is the primary pathophysiologic mechanism of acute coronary syndromes (ACS) and acute ischemic complications of percutaneous coronary intervention (PCI). The final common pathway of platelet aggregation that leads to thrombotic occlusion of coronary arteries involves cross-linking of receptor glycoprotein (GP) IIb-IIIa on adjacent platelets by adhesive plasma proteins, primarily fibrinogen. Clinical trials of several GP IIb-IIIa inhibitors have demonstrated an unequivocal clinical benefit of this potent antithrombotic therapy in patients with ACS as well as in those undergoing PCI. Nevertheless, a significant number of patients with ischemic heart disease may still be expected to require elective or emergency coronary artery bypass graft (CABG) after treatment with GP IIb-IIIa inhibitors. In the emergency CABG setting, complications and platelet blockade with GP IIb-IIIa inhibitors may further enhance the already heightened risk of bleeding as compared with elective procedures. This issue became apparent in the first large clinical trial of the GP IIb-IIIa inhibitor abciximab (c7E3 Fab, ReoPro((R)); Centocor, Malvern, Pa, and Eli Lilly and Co, Indianapolis, Ind) in patients undergoing high-risk PCI. In this study, mortality rates and bleeding complications were increased among patients undergoing emergency CABG after treatment with a bolus plus infusion of abciximab. Subsequent clinical experience also suggests that the potential for bleeding complications related to emergency CABG may be increased in patients treated with abciximab, particularly if the drug is discontinued within 6 hours of the operation. Higher bleeding risk with abciximab is a result of its prolonged antiplatelet effect, which is in contrast to the readily reversible platelet blockade provided by more recently developed small-molecule GP IIb-IIIa inhibitors such as the peptide eptifibatide (Integrilin((R)); COR Therapeutics, South San Francisco, Calif, and Key Pharmaceuticals, Kenilworth, NJ) and the nonpeptide tirofiban HCl (MK-383, Aggrastat((R)); Merck & Co, Whitehouse Station, NJ). Therefore, among patients requiring CABG after treatment with GP IIb-IIIa inhibitors, eptifibatide and tirofiban may be associated with fewer bleeding episodes than is abciximab. With recent approval of eptifibatide for patients with ACS and those scheduled for PCI and of tirofiban for patients with ACS, the number of patients receiving GP IIb-IIIa inhibitor therapy who subsequently undergo CABG is expected to increase significantly. Strategies for improved management of bleeding complications in these patients, including the choice of a GP IIb-IIIa inhibitor, are clearly needed and are discussed in detail.