摘要:

Background We previously identified in piglet cardiac allografts an immunoinflammatory response in coronary arteries in which increased fibronectin regulated by interleukin-1 beta was associated with early evidence of intimal thickening. In the present study, we used rabbits to assess whether acute neointimal formation after cardiac transplantation was reduced by blockade of tumor necrosis factor (TNF)- alpha, which modulates interleukin-1 beta, or by cyclosporine A.Methods and Results Sixteen rabbits underwent heterotopic cardiac transplantation and were given saline, TNF-soluble receptor (sr), or cyclosporine A. In host hearts from saline- or TNFsr-treated groups, few coronary arteries ((approximately) 13% to 16%) had intimal thickening, whereas values were higher in the cyclosporine A-treated group ((approximately) 30%). In donor hearts from the saline-treated group, however, (approximately) 68% of vessels had intimal thickening versus (approximately) 32% in TNFsr- and (approximately) 30% in cyclosporine A-treated groups (P<.01 for both). Severity of intimal thickening assessed quantitatively as percent vessel area was (approximately) 38% in the saline-treated group but reduced in TNFsr- and cyclosporine A-treated groups to (approximately) 22% and 18%, respectively (P<.01 for each). Immunohistochemistry revealed increased staining for major histocompatibility complex II, T cells, interleukin-1 beta, TNF- alpha, and fibronectin in donor coronary arteries from saline-treated animals when compared with TNFsr- and cyclosporine A-treated animals. Grade 3 myocardial rejection was observed in both saline- and TNFsr-treated groups, but only grade 1 was apparent in the cyclosporine A-treated group.Conclusions In vivo blockade of TNF- alpha suppresses the acute development of neointimal formation by selectively reducing the vascular immunoinflammatory reaction and accumulation of fibronectin, whereas cyclosporine A suppresses both the myocardial and the vascular immune reaction. (Circulation. 1994;89:2768-2779.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Recent studies suggest that both endocardial endothelium and coronary vascular endothelium influence myocardial contraction, but the mediators responsible and their mechanisms of action are not well defined.Methods and Results We investigated the effects of cultured endocardial endothelial and vascular endothelial cell superfusate on contraction and intracellular calcium transients of isolated rat cardiac myocytes. Endothelial cell superfusate induced a potent negative inotropic effect, with a rapid reversible decrease in myocyte twitch amplitude, earlier twitch relaxation, and a significant increase in diastolic length. This effect was not associated with significant changes in intracellular calcium or pH; was not attributable to nitric oxide, prostanoids, cGMP, or protein kinase C activation; and did not involve pertussis toxin-sensitive G proteins. The activity was stable at 37 degrees C for several hours, was not destroyed by protease treatment, and was found in low-molecular-weight (<<1 kD) superfusate fractions.Conclusions These data suggest the tonic release by endothelial cells of a novel, stable factor that acts predominantly by reducing the response of cardiac myofilaments to calcium (ie, "desensitizes" them). This "desensitizing factor" could rapidly modulate cardiac contraction-relaxation coupling and diastolic tonus and exert distant effects because of its stability. (Circulation. 1994;89:2492-2497.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background This study was designed to demonstrate the development of biochemical tolerance to organic nitrates by measuring levels of exhaled gaseous nitric oxide (NO) in lambs given intravenous (IV) nitroglycerin or sodium nitroprusside.Methods and Results IV injections of nitroglycerin or sodium nitroprusside produced dose-dependent and sustained increases in the exhaled levels of nitric oxide measured by chemiluminescence in awake lambs with tracheostomies. After a 6-hour IV infusion of 25 micrograms x kg sup -1 x min sup -1 nitroglycerin, peak exhaled NO levels were significantly reduced (-53.6+-4.9%, mean+-SEM, P<.001) and systemic hypotensive responses were attenuated (-52.6+-5.9%, P<.001) after an IV challenge of nitroglycerin but not sodium nitroprusside. After a subsequent 12-hour nitroglycerin-free period, there was complete recovery of NO excretion in exhaled breath and a return to baseline of systemic hypotensive changes on administration of IV nitroglycerin boluses. For IV sodium nitroprusside challenges, pulmonary NO excretion and systemic hypotensive responses remained constant throughout the study. Challenges with IV nitroglycerin but not sodium nitroprusside during a 12-hour nitroglycerin-free period resulted in delayed biochemical recovery with various exhaled NO levels and systemic hypotensive responses to challenges with IV nitroglycerin.Conclusions Measurements of exhaled NO provide in vivo, noninvasive evidence for the development of biochemical tolerance to nitroglycerin. There was reduced NO release into exhaled gas from the pulmonary vasculature concomitant with evidence of tolerance to nitroglycerin vasodilation in the systemic circulation. (Circulation. 1994;89:2498-2502.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Implantable cardioverter/defibrillators (ICDs) have conventionally been implanted in the operating room by surgeons. However, technological developments have reduced size and increased simplicity, bringing the procedure into the realm of the electrophysiologist. The purpose of this study was to evaluate the safety and efficacy of implantation of the entire ICD system by electrophysiologists in an electrophysiology laboratory.Methods and Results Between July 1993 and February 1994, 23 patients (21 men; age, 64+-11 years) underwent transvenous ICD implantation by electrophysiologists working alone, entirely in the electrophysiology laboratory. Indications for ICD were sudden death in 10 patients, uncontrolled life-threatening ventricular tachycardia in 12, and syncope with cardiomyopathy and familial sudden death in 1. Seventeen patients had coronary artery disease and a past history of acute myocardial infarction. Four patients had idiopathic dilated cardiomyopathy, 1 had coronary ectasia and poor left ventricular function, and another had poor left ventricular function related to valvular dysfunction. The mean left ventricular ejection fraction was 34+-10% (range, 20% to 50%). General anesthesia was administered in 22 cases, and deep sedation was used in 1 elderly patient. After positioning of transvenous leads and subcutaneous patch/array lead positioning, defibrillation testing was performed. After transvenous and subcutaneous lead tunneling, all generators were placed subcutaneously in an abdominal pocket. The mean total time in the electrophysiology laboratory was 254+-68 minutes (range, 150 to 375 minutes), with 104+-42 minutes for anesthetic and other preparation, 159+-45 minutes for implantation, and 8.7+-5 minutes (range, 3 to 25 minutes) of fluoroscopy required for positioning of transvenous and subcutaneous lead systems. Implant times showed a significant improvement when the first 10 cases (188+-44 minutes) were compared with the last 10 in the series (124+-44 minutes, P<.01). The mean defibrillation threshold was 17+-5 J (range, 5 to 25 J). There were 5 complications (22%): 1 patch-site hematoma, 1 pneumothorax related to subclavian venous puncture, 1 pulmonary embolism, and 2 patients requiring overnight ventilation after hemodynamic deterioration following defibrillation testing. There were no deaths, and there were no infections. The mean time to hospital discharge after the implant was 5.1+-3.5 days. After 11.6+-9 weeks of follow-up, all devices were functioning satisfactorily, all patients had successfully defibrillated at postimplant predischarge checkup with 29+-5 J, and there had been no late complications.Conclusions This is the first report to show that nonthoracotomy ICD implantation may be successfully carried out by electrophysiologists working alone in the electrophysiology laboratory, with a high rate of success and few complications, even in high-risk patients. This high rate of success and safety probably relates to the availability of high-quality fluoroscopy and familiarity with electrophysiology laboratory equipment and personnel. (Circulation. 1994;89:2503-2508.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Transesophageal echocardiography (TEE) has been used recently to detect atrial thrombi before cardioversion of atrial arrhythmias. It has been assumed that embolic events after cardioversion result from embolism of preexisting atrial thrombi that are accurately detected by TEE. This study examined the clinical and echocardiographic findings in patients with embolism after cardioversion of atrial fibrillation despite exclusion of atrial thrombi by TEE.Methods and Results Clinical and echocardiographic data in 17 patients with embolic events after TEE-guided electrical (n=16) or pharmacological (n=1) cardioversion were analyzed. All 17 patients had nonvalvular atrial fibrillation, including four patients with lone atrial fibrillation. TEE before cardioversion showed left atrial spontaneous echo contrast in five patients and did not show atrial thrombus in any patient. Cardioversion resulted in return to sinus rhythm without immediate complication in all patients. Thirteen patients had cerebral embolic events and four patients had peripheral embolism occurring 2 hours to 7 days after cardioversion. None of the patients were therapeutically anticoagulated at the time of embolism. New or increased left atrial spontaneous echo contrast was detected in four of the five patients undergoing repeat TEE after cardioversion including one patient with a new left atrial appendage thrombus.Conclusions Embolism may occur after cardioversion of atrial fibrillation in inadequately anticoagulated patients despite apparent exclusion of preexisting atrial thrombus by TEE. These findings suggest de novo atrial thrombosis after cardioversion or imperfect sensitivity of TEE for atrial thrombi and suggest that screening by TEE does not obviate the requirement for anticoagulant therapy at the time of and after cardioversion. A randomized clinical trial is needed to compare conventional anticoagulant management with a TEE-guided strategy including anticoagulation after cardioversion. (Circulation. 1994;89:2509-2513.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Profound reduction in antegrade epicardial coronary flow with concomitant ischemia is seen occasionally during percutaneous coronary intervention despite the absence of evident vessel dissection, obstruction, or distal vessel embolic cutoff. In a prior small series of cases, this "no-reflow" phenomenon appeared to be promptly reversed by the intracoronary administration of verapamil.Methods and Results To further understand the prevalence of this syndrome and its responsiveness to the proposed therapy, we reviewed 1919 percutaneous interventions performed between January 1991 and April 1993. During the study period, 39 patients (2.0%) met our criteria for no reflow, 37 of whom were treated with intracoronary nitroglycerin followed by intracoronary verapamil and 2 of whom received intracoronary nitroglycerin alone. An additional 16 patients (0.8%) were given verapamil as part of the management of a flow-limiting dissection or distal embolus (mechanical obstruction). Intracoronary verapamil (50 to 900 micrograms, total dose) improved TIMI flow grade in 89% of no-reflow patients and markedly reduced the number of cineframes between contrast injection and opacification of a selected distal landmark (from 91+-56 to 38+-21 frames, P<.001). By contrast, only 19% of patients with epicardial mechanical obstruction showed improvement in TIMI flow grade after verapamil, with minimal reduction in frames to opacification (from 107+-42 to 101+-69, P=.73).Conclusions The no-reflow phenomenon--reduction in distal flow without apparent dissection or distal embolization--occurs in 2% of coronary interventions. It generally responds promptly to intracoronary verapamil administration, suggesting that distal microvascular spasm may be its etiology. (Circulation. 1994;89:2514-2518.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID