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Biomedical subjects

William F Armstrong

Publications and source records attributed to William F Armstrong.

At least 19 recordsLinked to original sources
PubMed2006

Microvascular permeabilization and cardiomyocyte injury provoked by myocardial contrast echocardiography in a canine model.

OBJECTIVES: The aim of this research was to evaluate the potential for myocardial contrast echocardiography (MCE) to provoke microscale bioeffects in a canine model. BACKGROUND: Myocardial contrast echocardiography induces bioeffects in rat hearts, but translation of such results to larger animal models is uncertain. METHODS: Dogs were anesthetized and prepared for open- (n = 22) or closed- (n = 6) chest MCE. Evans blue dye was injected intravenously as an indicator of microvascular leakage, and propidium iodide was used to stain for irreversibly injured myocytes in frozen sections. The contrast agent (Definity, Bristol-Myers Squibb Medical Imaging Inc., North Billerica, Massachusetts) was diluted in saline and infused intravenously at 2 microl/kg/min. Myocardial contrast echocardiography in a short-axis (open-chest) or modified four-chamber view (closed-chest) with 1:4 end systolic electrocardiogram triggering was performed at 1.5 MHz for 10 min in a single imaging plane. RESULTS: Petechiae and leakage of Evans blue were observed in the ultrasound scan plane within the anterior left ventricle. For 1.2 MPa and 2.2 MPa, open- or closed-chest MCE, Evans blue content in tissue within the scan plane was significantly greater than in tissue outside this plane. Counts of propidium-iodide-stained nuclei for 2.2 MPa open-chest MCE were also significantly greater inside than outside the scan plane. CONCLUSIONS: In a canine model, MCE induces myocardial injury comparable to that seen in the rodent model.

Animals↗
PubMed2005

Stress echocardiography: current methodology and clinical applications.

Stress echocardiography is commonly employed for the clinical management of known or suspected coronary artery disease. This review discusses the accuracy of the technique, which is equivalent to that of competing imaging techniques, as well as its overall role in patient management. The utilization of stress echocardiographic modalities in clinical presentations, such as chest pain, congestive heart failure, and valvular heart disease, and preoperative risk assessment, as well as determining myocardial viability, are discussed.

Cell Survival↗
PubMed2005

The influence of agent delivery mode on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

Myocardial contrast echocardiography (MCE) can induce bioeffects in rat hearts by local activation of the contrast agent gas bodies. This study was designed to examine the influence of agent delivery mode on the magnitude of cardiomyocyte injury. A total of 69 hairless rats were anesthetized and mounted vertically in a water bath. Evans blue dye was injected as vital stain for cardiomyocyte injury. Definity contrast agent was diluted in saline and injected via tail vein at 20 or 80 microL/kg in bolus or infusion mode. In 12 rats, 0.57 mg/kg dipyridamole was given to simulate a stress test. MCE in a short axis view with 1:4 or 1:16 ECG triggering was performed at 1.5 MHz for 5 or 20 min. The peak rarefactional pressure amplitude was set to 1.1 or 2.0 MPa. Premature beats were counted from the ECG record. Evans blue fluorescent cells were counted on frozen sections from the center of the scan plane of heart samples obtained 24 h postMCE. Infusion of the contrast agent led to more cardiomyocyte injury than did bolus injection. Dipyridamole stress also increased the effect. Varying the infusion rate or trigger interval was less important than the overall dosage during scanning. Exposure at 1.1 MPa and 80 microL/kg yielded significant cell killing relative to shams. Premature beats generally followed the same trends as cell injury, except that lower infusion rates tended to increase this effect. Contrast agent delivery mode, as well as dose and peak rarefactional pressure amplitude, has a significant influence on the bioeffects potential of MCE.

Animals↗
PubMed2005

Histological characterization of microlesions induced by myocardial contrast echocardiography.

BACKGROUND: Myocardial contrast echocardiography (MCE) has been shown to have a potential for apparently reversible side effects related to the interaction of ultrasound with the contrast microbubbles, including premature ventricular contractions and microvascular leakage. We investigated the potential for high-dose MCE to induce histologically definable microlesions. METHODS: Myocardial contrast echocardiography with 1:4 end-systolic triggering was performed at 1.5 MHz and 1.7 mechanical index in a short axis view of the left ventricle in rats. Two high doses (500 microl/kg) of Optison agent were given 5 minutes apart during 10 minutes of echocardiography. For histology, the hearts were perfused and fixed in 10% neutral-buffered formalin. Slides from rats sacrificed 1 day after MCE were scored blind by a pathologist, and, in addition, photomicrographs in the anterior half were evaluated by digital image analysis. RESULTS: In rats sacrificed 10 minutes after MCE, microvascular leakage and petechiae were highly significant. However, lesions displaying necrotic debris associated with inflammatory infiltrates were not histologically evident at this time. Heart samples 24 hours after MCE showed microlesions with inflammatory infiltrates scattered primarily over the anterior half of the sections. Pathologically, there was inflammatory cell infiltration in areas of 0.6 +/- 0.5% for shams and 3.6 +/- 3.6% for MCE (P < 0.01). Analysis of photographs from the anterior wall found microlesion areas of 0.5 +/- 0.8% for shams and 7.4 +/- 5.0% for MCE (P < 0.02). For rats sacrificed 1 week and 6 weeks after MCE, the microlesions healed to form small fibrous regions interspersed with normal myocytes. CONCLUSION: High-dose MCE has a potential for causing microscale lesions in the myocardium and the possibility of therapeutic applications.

Albumins↗
PubMed2005

Rate-dependent AV delay optimization in cardiac resynchronization therapy.

BACKGROUND: During cardiac resynchronization therapy (CRT), cardiac performance is dependent on an optimized atrioventricular delay (AVD). However, the optimal AVD at different heart rates has not been defined yet during CRT. METHOD: The effects of an increase in heart rate by pacing or physical exercise on optimal AVD were studied in 36 patients with biventricular pacemakers/defibrillators. The velocity time integral (VTI) in the left ventricular outflow tract (LVOT) was measured with pulsed Doppler either at three different paced heart rates in the supine position or in seated position before and after physical exercise. RESULTS: The baseline AVD was optimized to 99 +/- 19 ms in the supine and 84 +/- 22 ms in the seated position. When the heart rate was increased by DDD pacing, there was a positive linear relationship between an increase in heart rate, in AVD and in VTI (LVOT-VTI + 0.047 cm/s per 10 beats per minute (bpm) heart rate increase per 20 ms increase in AVD, P = 0.007). A similar but more pronounced relationship was found after physical exercise in the seated position (LVOT-VTI + 0.146 cm/s per 10 bpm heart rate increase per 20 ms increase of AVD, P = 0.013). This effect was observed in patients with and without AV block and mitral regurgitation. CONCLUSIONS: In conclusion, the systolic performance of the dilated ventricle, which depends on an elevated preload, is critically affected by the appropriate timing of the AVD during exercise. In contrast to normal pacemaker patients, in CRT the relatively short baseline AVD should be prolonged at increased heart rates. Further studies with other means of measuring exercise cardiac performance are needed to confirm these unexpected findings.

Atrioventricular Node↗
PubMed2005

Influence of contrast agent dose and ultrasound exposure on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

PURPOSE: To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. MATERIALS AND METHODS: All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. RESULTS: EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P < .02) and 2.0 MPa (P < .005) relative to the cell counts at sham myocardial contrast echocardiography. Premature heartbeats had a similar exposure-response relationship; however, number of premature heartbeats and EB-stained cell count did not appear to be directly related (coefficient of determination r2 = 0.03). The EB-stained cell counts at end-diastolic triggering were not significantly different from those at end-systolic triggering (P > .1). EB-stained cell counts increased with increasing contrast material dose, from 10 to 50 microL/kg, at 2.0 MPa. CONCLUSION: Cardiomyocyte injury was induced by the interaction of ultrasound pulses with contrast agent microbubbles during myocardial contrast echocardiography in rats, and the numbers of injured cells increased with increasing contrast agent dose and ultrasound exposure.

Animals↗
PubMed2004

Impact of myocardial contrast echocardiography on vascular permeability: comparison of three different contrast agents.

Microvascular permeabilization, petechial hemorrhage and premature ventricular contractions (PVCs) have been demonstrated in an in vivo rat model of myocardial contrast echocardiography (MCE). The purpose of this study was to compare these effects for three US Food and Drug Administration (FDA)-approved ultrasound (US) contrast agents (US CA): Optison, Definity and Imagent. Evans blue dye, an indicator of microvascular permeability, and a contrast agent were injected IV in anesthetized rats suspended in a water bath to mimic scanning depths seen in clinical echocardiology. Diagnostic US B-mode scans with 1:4 end-systolic triggering were performed at 1.7 MHz using a cardiac phased-array scanhead to provide a short axis view of the left ventricle. To elicit readily measurable effects for comparisons, relatively high doses of the agent were used (50 to 500 microL kg(-1) for Optison, 25 to 200 microL kg(-1) for Imagent, 10 to 100 microL kg(-1) for Definity). Microvascular leakage was characterized by the area of Evans blue dye coloration on the hearts and by extraction of the dye from tissue samples. The number of petechia were counted on the epicardial surface of excised hearts. PVCs were counted from ECG traces recorded with the MCE images. Neither evidence of capillary leakage nor PVCs were seen in sham animals. Based on volume dose, Definity MCE produced more microvascular leakage, but there was no apparent difference between the three agents' microvascular damage potential, which increased linearly with dose at low doses, when expressed in terms of the number of stabilized microbubbles. Definity MCE resulted in fewer PVCs than the other agents. The effects increased strongly with peak rarefactional pressure amplitude, with apparent thresholds for petechiae at 0.4 MPa and for PVCs at about 1.0 MPa. These results should be of value for minimizing adverse potential in diagnosis and optimizing efficacy in therapeutic applications.

Albumins↗
PubMed2004

The effect of time and of vasoactive drugs on capillary leakage induced during myocardial contrast echocardiography.

BACKGROUND: Premature ventricular contractions (PVC), capillary leakage, and petechial hemorrhage can occur during myocardial contrast echocardiography (MCE). The effects occur as a result of the interaction of contrast agent microbubbles and the ultrasound, but the detailed etiology of the effects is not yet clear. This study tested the hypothesis that the capillary leakage results from a physiological response to injury, which might be protracted and modulated by vasoactive drugs. METHODS: Hairless rats were anesthetized and transthoracically scanned with a diagnostic ultrasound system (GE Vingmed System V) at 1.7 MHz with 1:4 triggered frames at end systole. The scan head and rats were mounted in a 37 degrees C water bath to assure free-field conditions and placement of the heart at a similar focal distance as humans. A tail vein was cannulated for injections of Optison contrast agent, vasoactive medications, and Evans Blue dye (EB). EB was injected as a marker of capillary leakage before or after scanning. RESULTS: PVCs, petechia, and capillary leakage occurred during ultrasound exposure of microbubbles in myocardium, with no effects detected in shams. The influence of the vasoactive medications propranolol and isoproterenol on the effects did not support the hypothesis. Capillary leakage occurred during and postexposure, but diminished for EB injection 20 minutes after scanning with or without isoproterenol pretreatment. CONCLUSION: MCE induced PVCs, petechia, and capillary leakage, all of which ended immediately or within 20 minutes after the examination. Contrary to the hypothesis of a physiological mechanism, the capillary leakage appears to be primarily a mechanical effect rather than a physiological response.

Animals↗
PubMed2003

Impact of myocardial contrast echocardiography on vascular permeability: an in vivo dose response study of delivery mode, pressure amplitude and contrast dose.

An in vivo rat model of myocardial contrast echocardiography (MCE) was defined and used to examine the dose range response of microvascular permeabilization and premature ventricular contractions (PVCs) with respect to method of imaging, peak rarefactional pressure amplitude (PRPA) and agent dose. A left ventricular short axis view was obtained on anesthetized rats at 1.7 MHz using a diagnostic ultrasound system with simultaneous ECG recording. Evans blue dye, a marker for microvascular leakage, and a bolus of Optison were injected i.v. Counts of PVCs were made from video tape during the 3 min of MCE. Hearts were excised 5 min after imaging and petechial hemorrhages, Evans blue colored area and Evans blue content were determined. No PVCs or microvascular leakage were seen in rats imaged without contrast agent followed by contrast agent injection without imaging. When PVCs were detected during MCE, petechial hemorrhages and Evans blue leakage were also found in the myocardium. Triggering 1:4 at end-systole produced the most PVCs per frame and most microvascular leakage, followed by end-systole 1:1, continuous scanning and end-diastole triggering 1:1. All effects increased with increasing Optison dosage in the range 25 to 500 microL kg(-1). Ultrasound PRPA was important, with apparent thresholds for PVCs at 1.0 MPa and for petechiae at 0.54 MPa. PVCs, petechial hemorrhages and microvascular leakage in the myocardium occur as a result of MCE in rats.

Albumins↗
PubMed2003

Feasibility of transesophageal echocardiography with a ten-French monoplane probe.

OBJECTIVES: We examined the feasibility of transesophageal echocardiography (TEE) using a 10F monoplane probe developed for intracardiac ultrasound (AcuNav, Acuson/Siemens, Mountain View, Calif). BACKGROUND: Traditional TEE uses a 10- to 12-mm-diameter probe, and conscious sedation is customary to minimize patient discomfort. Because of its small size (3.2-mm diameter), the 10F monoplane probe can be inserted into the esophagus using only topical anesthesia. This provides the potential for a more easily tolerated examination. METHODS: A total of 20 patients underwent a comprehensive TEE using an adult multiplane probe. Immediately afterward, the 10F monoplane probe was inserted into the esophagus and a targeted examination completed. The 10F monoplane studies were blindly reviewed by 3 observers for the study indication and for 16 diagnostic elements. These were graded against an expert's review of standard TEE. RESULTS: The 10F monoplane probe was well tolerated in all patients. Observers A, B, and C answered the clinical question in 80%, 85%, and 100%, respectively, with the 10F probe. The percentage of clinical elements deemed evaluable was 71%, 78%, and 80%, respectively. Limitations included incomplete visualization of the mitral valve and a systematic underestimation of the severity of valve regurgitation. CONCLUSIONS: The 10F monoplane probe is safe, well-tolerated, and capable of evaluating many clinical questions. Because of its small size, conscious sedation may not be necessary. It may be useful for targeted evaluations, for monitoring invasive procedures, or for intermediate or long-term monitoring in an intensive care department.

Anesthesia, Local↗
PubMed2002

Acute type A aortic dissection in the elderly: clinical characteristics, management, and outcomes in the current era.

OBJECTIVES: We sought to evaluate the clinical characteristics, management, and outcomes of elderly patients with acute type A aortic dissection. BACKGROUND: Few data exist on the clinical manifestations and outcomes of acute type A aortic dissection in an elderly patient cohort. METHODS: We categorized 550 patients with type A aortic dissection enrolled in the International Registry of Acute Aortic Dissection into two age strata (<70 and >or=70 years) and compared their clinical features, management, and in-hospital events. RESULTS: Thirty-two percent of patients with type A dissection were aged >or=70 years. Marfan syndrome was exclusively associated with dissection in the young, whereas hypertension, atherosclerosis and iatrogenic dissection predominated in older patients. Typical symptoms (abrupt onset of chest or back pain) and signs (aortic regurgitation murmur or pulse deficits) of dissection were less common among the elderly. Fewer elderly patients were managed surgically than younger patients (64% vs. 86%, p < 0.0001). Hypotension occurred more frequently (46% vs. 32%, p = 0.002) and focal neurologic deficits less frequently (18% vs. 26%, p = 0.04) among the elderly. In-hospital mortality was higher among older patients (43% vs. 28%, p = 0.0006). Logistic regression analysis identified age >or=70 years as an independent predictor of hospital death for acute type A aortic dissection (odds ratio 1.7, 95% confidence interval 1.1-2.8; p = 0.03). CONCLUSIONS: Our study shows significant differences between older (age >or=70 years) and younger (age <70 years) patients with acute type A aortic dissection in their clinical characteristics, management, and hospital outcomes. Future research should evaluate strategies to improve outcomes in this high-risk elderly cohort.

Acute Disease↗
PubMed2002

Consensus conference report: maximizing use of organs recovered from the cadaver donor: cardiac recommendations, March 28-29, 2001, Crystal City, Va.

The shortage of available donor hearts continues to limit cardiac transplantation. For this reason, strict criteria have limited the number of patients placed on the US waiting list to approximately 6000 to 8000 per year. Because the number of available donor hearts has not increased beyond approximately 2500 per year, the transplant waiting list mortality rate remains substantial. Suboptimal and variable utilization of donor hearts has compounded the problem in the United States. In 1999, the average donor yield from 55 US regions was 39%, ranging from 19% to 62%. This report provides the detailed cardiac recommendations from the conference on "Maximizing Use of Organs Recovered From the Cadaver Donor" held March 28 to 29, 2001, in Crystal City, Va. The specific objective of the report is to provide recommendations to improve the evaluation and successful utilization of potential cardiac donors. The report describes the accuracy of current techniques such as echocardiography in the assessment of donor heart function before recovery and the impact of these data on donor yield. The rationale for and specific details of a donor-management pathway that uses pulmonary artery catheterization and hormonal resuscitation are provided. Administrative recommendations such as enhanced communication strategies among transplant centers and organ-procurement organizations, financial incentives for organ recovery, and expansion of donor database fields for research are also described.

Cadaver↗
PubMed2002

Predicting death in patients with acute type a aortic dissection.

BACKGROUND: Given the high mortality rates in patients with type A aortic dissection, predictive tools to identify patients at increased risk of death are needed to assist clinicians for optimal treatment. METHODS AND RESULTS: Accordingly, we evaluated 547 patients with this diagnosis enrolled in the International Registry of Acute Aortic Dissection (IRAD) between January 1996 and December 1999. Univariate testing followed by multivariate logistic regression analysis was performed to identify independent predictors of death. In-hospital mortality rate was 32.5% in type A dissection patients. In-hospital complications (neurological deficits, altered mental status, myocardial or mesenteric ischemia, kidney failure, hypotension, cardiac tamponade, and limb ischemia) were increased in patients who died compared with survivors (P<0.05 for all). Logistic regression identified the following presenting variables as predictors of death: age > or =70 years (OR, 1.70; 95% CI, 1.05 to 2.77; P=0.03), abrupt onset of chest pain (OR 2.60; 95% CI, 1.22 to 5.54; P=0.01), hypotension/shock/tamponade (OR, 2.97; 95% CI, 1.83 to 4.81; P<0.0001), kidney failure (OR, 4.77; 95% CI, 1.80 to 12.6; P=0.002), pulse deficit (OR, 2.03; 95% CI, 1.25 to 3.29, P=0.004), and abnormal ECG (OR, 1.77; 95% CI, 1.06 to 2.95; P=0.03) (area under receiver operating curve, 0.74; Hosmer-Lemeshow statistic, P=0.75). CONCLUSIONS: The in-hospital mortality rate in acute type A aortic dissection is high and can be predicted with the use of a clinical model incorporated in a simple risk prediction tool. This tool can be used to educate patients with dissection about their predicted risk and in clinical research for risk adjustment while comparing outcomes of different therapies.

Aged↗