摘要:

BackgroundRepetitive, brief periods of ischemia and reperfusion (“preconditioning”) increase the resistance of myocardial tissue to subsequent prolonged ischemic episodes and limit infarct size. We investigated whether preconditioning also protects against coronary endothelial dysfunction induced by ischemia and reperfusion.Methods and ResultsExperiments were performed in four groups of rats (n=8 in each group): group 1 rats underwent sham surgery, group 2 rats were subjected to 20 minutes of left coronary artery occlusion without reperfusion, group 3 rats underwent 20 minutes of occlusion followed by 1 hour of reperfusion, and group 4 rats (preconditioning group) underwent the same protocol as group 3 rats, preceded by three cycles of 5 minutes of ischemia and 5 minutes of reperfusion. At the end of the experiments, coronary segments (internal diameter, 250 to 300 μm) were removed distal to the occlusion site and mounted in wire myographs for isometric tension recording. Relaxations induced by increasing concentrations of acetylcholine, the calcium ionophore A23187, or the nitric oxide (NO) donor SIN-1 were determined in arteries precontracted by serotonin. Basal NO release was estimated by measuring contractions to NG-nitro L-arginine methyl ester (L-NAME). In addition, we determined the effect of preconditioning on infarct size in two additional groups that were subjected to the same protocols as those of groups 3 and 4. In those animals, area at risk (India ink injection) and infarct size (triphenyltetrazolium stain) were determined by computerized analysis of enlarged sections after video acquisition. Preconditioning markedly limited infarct size (percent of area at risk: controls, 57±2; preconditioning, 2.2±0.6;P< .01). Ischemia (without or with reperfusion) or preconditioning did not affect the coronary responses to L-NAME, serotonin, A23187, or SIN-1. Ischemia without reperfusion did not modify the relaxations to acetylcholine (maximal relaxation: sham, 58±4%; ischemia, 56±7%;P= NS). In contrast, ischemia followed by reperfusion markedly impaired the response to acetylcholine (26±6%;P< .01 versus sham). This impaired response was restored by preconditioning (maximal relaxation: 59±9%;P= NS versus sham;P< .01 versus ischemia/reperfusion).ConclusionsIn addition to protecting myocardial cells, preconditioning also protects coronary endothelial cells against ischemia/reperfusion injury.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundBalloon angioplasty of atherosclerotic arteries results in activation of the coagulation cascade. Several coagulation factors, including factor Xa and thrombin, are mitogenic for vascular smooth muscle cells in vitro and thus may play a role in restenosis after balloon angioplasty. Specific inhibition of factor Xa can be achieved with recombinant antistasin (rATS) or tick anticoagulant peptide (rTAP). We hypothesized that inhibition of Xa would limit restenosis after balloon angioplasty in an atherosclerotic rabbit model.Methods and ResultsFocal femoral atherosclerosis was induced by air desiccation injury and a high-cholesterol diet in 38 New Zealand White rabbits. Recombinant antistasin (n=20 arteries) or rTAP (n= 14 arteries) was administered by intravenous bolus at the time of balloon angioplasty and followed by a 2-hour infusion; controls (n=21 arteries) received bolus heparin alone (150 U/kg). Therapeutic prolongation of the activated partial thromboplastin time occurred, and antithrombotic drug levels were achieved in all animals. Luminal diameter in millimeters by quantitative angiography did not differ between treatment groups before (1.1±0.2 for controls, 1.1±0.2 for rATS, and 1.1±0.3 for rTAP) or after balloon angioplasty (1.5±0.3 for controls, 1.4±0.2 for rATS, and 1.4±0.2 for rTAP). At 28 days, treatment with factor Xa inhibitors tended to result in arteries with larger luminal diameter than controls (1.2±0.3 for rATS, 1.2±0.3 for rTAP versus 1.0±0.3 for control,P= .09 by one-way ANOVA). Restenosis, defined as reduction in angiographic luminal diameter (in mm) from 2 hours after angioplasty to 28 days after angioplasty was less in the rATS group than in controls (−0.2±0.1 versus −0.5±0.4,P< .001) and tended to be less in the rTAP group (−0.3 ±0.2 versus −0.5 +0.4,P= .07). Quantitative histopathological analysis showed less percent crosssectional area narrowing by plaque in both rATS- and rTAPtreated arteries compared with controls (42±21%, 47±18%, and 63±14%, respectively;P< .01 by one-way ANOVA).ConclusionsWe conclude that a 2-hour infusion of rATS or rTAP reduced angiographic restenosis and resulted in less luminal cross-sectional narrowing by plaque compared with controls.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThere is no doubt that high doses of nicotine have deleterious effects on cardiovascular function. However, the effects of lower and more clinically relevant doses of nicotine have received little attention, and the consequences of nicotine in the setting of ischemia/reperfusion are virtually unknown. The first objective of this study was to determine whether nicotine, given either before or after ischemia and at a dose mimicking that absorbed by humans during inhalation of one cigarette, exacerbated contractile dysfunction of canine myocardium “stunned” by brief transient ischemia. The second aim was to provide preliminary insight into the mechanism of action of nicotine on the stunned myocardium.Methods and ResultsAnesthetized open chest dogs underwent 15 minutes of left anterior descending coronary artery (LAD) occlusion and 3 hours of reperfusion. In protocol 1, each dog was randomized to receive nicotine at 30 minutes before LAD occlusion (80 gg/kg dissolved in 15 mL of saline, given IV over 10 minutes), nicotine at 1 hour after reperfusion (80μg/kg as above), or saline. Segment shortening (assessed by sonomicrometry) in both the LAD and circumflex beds, heart rate, arterial pressure, and coronary blood flow were monitored throughout the protocol, and regional myocardial blood flow (by injection of radiolabeled microspheres) was measured during LAD occlusion and at 5 minutes after nicotine/saline infusion. All groups were equally ischemic during LAD occlusion. As expected, segment shortening in the LAD bed of control animals was depressed after reperfusion, averaging 54±6% and 50±4% of baseline at 1 and 3 hours after reflow. Nicotine given before occlusion did not alter segment shortening before LAD occlusion and did not exacerbate dyskinesis during occlusion. However, segment short- ening in the LAD bed recovered to only 29±9% and 22±5% of baseline at 1 and 3 hours after reperfusion (P< .01 versus corresponding control values). Furthermore, nicotine given at 1 hour after reperfusion caused a significant deterioration in segment shortening, from 47±11% immediately before infusion (P= NS versus control at 1 hour after reflow) to 7±13% at 3 hours after reperfusion (P< .01 versus 1 hour after reperfusion;P< .01 versus control at 3 hours after reflow). This dose of nicotine did not alter heart rate, arterial pressure, or blood flow; did not cause myocyte necrosis; and did not impair contractile function in the normally perfused circumflex bed. In protocol 2, all dogs received a continuous infusion of the free radical scavenging agentN-2-mercaptopropionyl glycine (MPG; 50 mg ·kg−1.h−1) beginning 45 minutes after reperfusion and, at 1 hour after reflow, received either nicotine or saline as described in protocol 1. MPG given after reperfusion did not alter contractile function in control animals. However, MPG prevented the deterioration in postischemic function observed with nicotine in protocol 1; segment shortening averaged 54±11% and 56±9% of baseline at 1 and 3 hours after reperfusion (P= NS).ConclusionsNicotine, given before occlusion or after reflow, significantly exacerbated contractile dysfunction of postischemic stunned myocardium in this canine model. This exacerbated dysfunction was not a secondary consequence of unfavorable alterations in hemodynamics or coronary blood flow and may be mediated by free radicals acting on myocytes that had been reversibly injured by the brief ischemic insult.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundExposure to environmental tobacco smoke (ETS) has been epidemiologically linked to death from ischemic heart disease in nonsmokers. In this study, we evaluated the influence of 3 days, 3 weeks, and 6 weeks of ETS exposure on myocardial infarct size in a rat ischemia/reperfusion model.Methods and ResultsSprague-Dawley rats exposed to ETS four Marlboro cigarettes per 15 minutes, 6 hours per day, 5 days per week) for 3 days (n=24), 3 weeks (n=21), or 6 weeks (n= 12) and control rats (n=24, n=21, and n=12, respectively) were subjected to 35 minutes of left coronary artery occlusion and 2 hours of reperfusion. Infarct size and risk area were determined by triphenyltetrazolium chloride and phthalocyanine blue staining, respectively. Air nicotine, carbon monoxide, and total particulates were measured during ETS exposure. Serum lipids, plasma carbon monoxide hemoglobin COHb), nicotine, and cotinine concentrations were measured in additional groups (6 to 13 rats each) exposed to 3 days, 3 weeks, or 6 weeks of ETS and controls. Average air nicotine, carbon monoxide, and total particulate concentrations were 1103μg/m3, 92 ppm, and 60 mg/m3for the ETS-exposed rats. Infarct size (infarct mass/risk area ×100%) increased significantly in the ETS groups compared with the control groups in a dose-dependent manner (P= .023), with longer exposure associated with larger infarct size. Infarct size nearly doubled with 6 weeks of ETS exposure (61±5% versus 34±3% for control, mean+SEM). Plasma COHb, nicotine, and cotinine levels increased significantly in the ETS groups in a dosedependent manner (allP< .001).ConclusionsExposure to passive smoking increases myocardial infarct size in a rat model of ischemia and reperfusion. This increase of infarct size exhibited a dose-response relation. These results are consistent with epidemiological studies demonstrating that ETS increases the risk of heart death.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background99mTc-Q12 is a new Tc(III) perfusion imaging agent that permits prompt myocardial visualization in humans. We postulated that99mTc-Q12 myocardial activity is related to actual myocardial blood flow during conditions of myocardial ischemia and pharmacological coronary artery vasodilation and that99mTc-Q12 shows little or no myocardial redistribution as long as 4 hours after intravenous injection.Methods and ResultsIn seven anesthetized, open chest dogs, the left circumflex coronary artery was occluded, and dipyridamole (0.32 or 0.56 mg/kg) was infused into the right atrium, followed by 10 mCi of99mTc-Q12. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized, and a total of 315 myocardial samples were assayed in a well counter for99mTc activity. One week later, radiolabeled microsphere activity was determined, and myocardial blood flow was calculated.99mTc activity (y) was related to myocardial blood flow (x) from 0 to 2 mL· g−1· min−1by the relation y=0.64x+0.35 (r= .88,P= .0001). In 14 additional anesthetized, open chest dogs, an occluder was placed around the left circumflex coronary artery, and an ischemic level of circumflex blood flow was maintained constant over 4 hours as measured by an ultrasonic flowmeter. Dipyridamole (0.56 mg/kg) was infused intravenously beginning 15 minutes after coronary occlusion and then followed by 10 mCi of99mTc-Q12. Gamma camera images, hemodynamics, microsphere blood flow, and endocardial biopsies (latter in six dogs) were performed at 30, 60, 120, and 240 minutes after99mTc-Q12 injection. Myocardial blood flow in the distribution of the left anterior descending artery decreased by 29.6% from 30 to 240 minutes (P< .05), whereas left circumflex blood flow increased by 40.4% from 30 to 120 minutes (P< .05) as the dipyridamole hemodynamic effects dissipated. Nevertheless, the ratio of myocardial perfusion defect zone counts to normal myocardial zone counts remained constant over 4 hours, as did the technetium counts from the needle biopsy endocardial samples.ConclusionsOver a limited range of myocardial blood flows from 0 to approximately 2mL· g−1· min−199mTc-Q12 myocardial activity is related to actual myocardial flow at the time of tracer injection.99mTc-Q12 shows no evidence of myocardial redistribution.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundRadiofrequency catheter ablation requires precise positioning of the ablation electrode. Fluoroscopically guided catheter manipulation has limitations, and there are risks of radiation exposure. The purpose of this study was to examine the feasibility of guiding catheter ablation within the right atrium with catheter-based intracardiac echocardiography.Methods and ResultsA 10F, 10-MHz intracardiac imaging catheter was used to direct an ablation electrode at four or five anatomic landmarks in the right atrium. Thirty-eight radiofrequency energy applications were performed in nine anesthetized dogs, and 38 lesions were identified on pathological examination. Lesions were created a mean of 1.9±2.1 mm from the ultrasound-guided site. Twenty-six of 38 lesions (68%) were less than 2.2 mm from the imaged site. Intracardiac echocardiography also was used to confirm stable electrode- endocardial contact in 37 energy applications (97%) and identified catheter movement in 9 energy applications (24%). Discrete lesions, microcavitations, and thrombi were observed in 13 (34%), 23 (61%), and 19 (50%) of 38 energy applications, respectively. Microcavitations predicted the appearance of thrombus. Fluoroscopy time required to create four or five lesions decreased from 23 minutes in the first study to less than 2 minutes in the last five studies.ConclusionsCatheter-based intracardiac echocardiography can accurately guide catheter ablation directed at anatomic landmarks and potentially reduce ionizing radiation exposure. Intracardiac imaging can be used to confirm endocardial contact, identify electrode movement, and directly visualize lesions. Intracardiac echocardiography also can be used to identify microcavitations, which predict thrombus formation during radiofrequency energy applications.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundPrecise noninvasive evaluation of pulmonary artery (PA) morphology is extremely important for medical and surgical management of patients with cyanotic heart disease. In this study, the accuracy of two-dimensional echocardiography combined with color Doppler flow mapping to assess the size, stenosis, and atresia of the major PA branches was examined using a new parasternal approach.Methods and ResultsWith the use of right and left high parasternal windows, we visualized each of the major portions along the right (R-PA) and left (L-PA) pulmonary arteries in 45 of the 47 examinations (96%) in 38 patients with cyanotic heart disease. The patients were between 13 days and 20 years old (mean age, 2.9 years). The internal diameters of the major PA branches were measured at three points along the R-PA (the proximal, mid, and distal portions) and at the proximal and distal portions on the L-PA in systole by both twodimensional echocardiography and angiography. In addition, the diameter of the stenosis in the PA branch was measured. These PA values as determined by two-dimensional echocardiography correlated well with those obtained by angiography (r= .95 to .97). By two-dimensional echocardiography with color Doppler flow mapping, 17 of 19 lesions with stenoses or atresia of the major PA branches were predicted as defined by angiography (sensitivity, 89.5%; specificity, 100%). Differences between the distal parts of the L-PA and R-PA of >30% in diameter were determined by angiography in 15 examinations and by two-dimensional echocardiography in 12 examinations (sensitivity, 80%; specificity, 97.4%).ConclusionsOur technique permits noninvasive evaluation of the size, stenoses, and atresia of the major portions of the PA branches in patients with cyanotic heart disease both before and after surgery.

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