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Biomedical subjects

Thomas R Porter

Publications and source records attributed to Thomas R Porter.

At least 19 recordsLinked to original sources
PubMed2007

Interaction of transthoracic ultrasound and intravenous microbubbles with cardiac mechanoreceptors.

The purpose of this study was to examine the effect of transthoracic ultrasound (TTU) and intravenous microbubbles (MB) on cardiac mechanoreceptors. In 16 rabbits (eight normal and eight chronic heart failure), renal sympathetic nerve activity (RSNA), heart rate and mean arterial pressure were examined before, during and after 1 MHz TTU at different peak negative pressures (0.12 to 0.43 MPa) and duty cycles in the presence and absence of perfluorocarbon MB. TTU applications were for 10 s, and the overall duration of MB infusion was approximately 60 s for each setting. TTU without MB had no effect on any parameter. During the microbubble infusion, however, TTU at higher peak negative pressures (> or =0.27 MPa) and 100% duty cycle resulted in a consistent decrease in RSNA(-41 +/- 41% p < 0.001). This was accompanied by brief reflex reductions in mean arterial pressure and heart rate. The changes in RSNA induced by TTU and MB in all rabbits were abolished by vagotomy. TTU, in the presence of MB, stimulates mechanoreceptors in the heart reflexively to reduce RSNA.

Animals↗
PubMed2006

The role of complement in the adherence of microbubbles to dysfunctional arterial endothelium and atherosclerotic plaque.

OBJECTIVE: To determine whether serum complement C3 mediates adherence of albumin-encapsulated microbubbles to vascular endothelium in the development of atherosclerotic plaques. METHODS: Adherence of microbubbles to aortic endothelium was examined with scanning electron microscopy following intravenous injection of 20% intralipid in wild-type mice, genetic complement-deficient mice (C3-/-), and in pharmacologic C3-depleted wild-type mice. In a second experimental model, atherosclerostic plaque was induced in apolipoprotein E-deficient mice (apoE-/-), and adherence of microbubbles to atherosclerotic plaques was evaluated using fluorescent microscopy of fluorescein isothiocynate-conjugated microbubbles. Finally, imaging of aortas was performed in eight rats (four JCR:LA-cp atherosclerosis-prone rats on high cholesterol diets; four controls) following intravenous albumin microbubble injections (PESDA) to determine whether microbubble adherence to the endothelium could be detected with low mechanical index pulse sequence schemes. RESULTS: Scanning electron microscopy confirmed the adherence of microbubbles to the endothelial cells of the aorta in wild-type mice following induction of hypertriglyceridemia but not in C3-depleted mice. Microbubble adherence to the endothelial surface of atherosclerotic plaque was confirmed in all apoE-/- mice (median 172 microbubbles/field; compared to a median of 3 microbubbles/field in cobra venom factor-treated apoE-/- mice; p < 0.001). Low mechanical index ultrasound imaging detected microbubble adherence in all JCR atherosclerosis prone rats even in the absence of vasomotor or phenotypical evidence of endothelial dysfunction. The numbers of adherent microbubbles correlated with serum triglyceride levels, and were seen in conjunction with increased endothelial nitric oxide synthase activity. CONCLUSIONS: Complement C3 binds to albumin-encapsulated microbubbles and mediates microbubble adherence to vascular endothelium both early and late in the atherosclerotic process.

Albumins↗
PubMed2006

Myocardial contrast echocardiography evolving as a clinically feasible technique for accurate, rapid, and safe assessment of myocardial perfusion: the evidence so far.

Intravenous myocardial contrast echocardiography (MCE) is a recently developed technique for assessment of myocardial perfusion. Up to now, many studies have demonstrated that the sensitivity and specificity of qualitative assessment of myocardial perfusion by MCE in patients with acute and chronic ischemic heart disease are comparable with other techniques such as cardiac scintigraphy and dobutamine stress echocardiography. Furthermore, quantitative parameters of myocardial perfusion derived from MCE correlate well with the current clinical standard for this purpose, positron emission tomography. Myocardial contrast echocardiography provides a promising and valuable tool for assessment of myocardial perfusion. Although MCE has been primarily performed for medical research, its implementation in routine clinical care is evolving. This article is intended to give an overview of the current status of MCE.

Acute Disease↗
PubMed2006

Carcinoid crisis and reversible right ventricular dysfunction after embolization in untreated carcinoid syndrome.

A 59-year-old white male with carcinoid tumor and hepatic metastases underwent hepatic artery embolization. The patient developed carcinoid crisis and a subsequent transthoracic echocardiogram showed classic findings of carcinoid heart disease along with a dilated hypertrophied right ventricle and severely depressed right ventricular ejection fraction. After treatment with octreotide the patient's clinical condition improved and a repeat transthoracic echocardiogram showed a significant improvement and normalization of right ventricular systolic function. Serotonin levels showed a progressive decline that correlated well with the patient's improved clinical condition. These findings suggest that the acute right ventricular dysfunction was secondary to acute carcinoid crisis and resolution resulted in a significant improvement of both right ventricular systolic function and clinical condition.

Acute Disease↗
PubMed2006

Value of dobutamine stress myocardial contrast perfusion echocardiography in patients with advanced liver disease.

Although dobutamine stress echocardiography has been used for the preoperative evaluation of patients with advanced liver disease (ALD), no data exist regarding the value of myocardial perfusion imaging (MPI) with real-time myocardial contrast echocardiography (RTMCE) in this patient population. We sought to determine the value of MPI during dobutamine stress RTMCE for predicting prognosis in patients with ALD. We examined both wall motion and MPI in 230 patients with ALD who underwent dobutamine stress RTMCE using intravenous commercially available contrast agents (Optison, GE-Amersham, Princeton, NJ; or Definity, Bristol-Myers Squibb Medical Imaging, North Billerica, MA). The prognostic value of clinical variables, including the Model for End-Stage Liver Disease (MELD) score, and echocardiographic data were examined using a Cox Hazard model. The primary endpoint was mortality of all causes. Among the 85 patients who underwent orthotopic liver transplantation, 4 had abnormal MPI and 81 had normal perfusion. The hospital mortality rate was 50% (2/4) in patients with abnormal MPI and 2% (2/81) in patients with normal MPI (P = 0.01). Among patients with abnormal MPI, 1 died from myocardial infarction in the first postoperative day and the second 1 from hemorrhagic shock. During a median follow-up of 15 months, 53 (23%) patients died. The independent predictors of death were an age of > or = 65 yr (RR = 2.2; 95% confidence interval (CI) = 1.1-4.4; P = 0.03), MELD score of > or = 25 (RR = 3.2; 95% CI = 1.8-5.5; P < 0.0001), and abnormal MPI (RR = 2.4; 95% CI = 1.1-5.2; P = 0.02). The 2-yr mortality was 24% for patients with normal MPI and 45% for those with inducible MPI abnormalities (P = 0.003). In conclusion, MPI obtained by RTMCE appears to be a useful tool in predicting mortality in patients with ALD. Further studies are required to verify its independent value.

Adrenergic beta-Agonists↗
PubMed2006

Efficacy of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation at 6 months: a randomized controlled trial.

BACKGROUND: Electrical cardioversion in patients with atrial fibrillation (AF) is associated with an increased risk of stroke. We compared a transesophageal echocardiography (TEE)-guided strategy with a conventional strategy in patients with AF > 2 days' duration undergoing electrical cardioversion over a 6-month follow-up. METHODS: The ACUTE study was a multicenter, randomized, clinical trial, with 1222 patients. Six-month follow-up was available in 1034 patients (85%), 525 in the TEE group and 509 in the conventional group. The primary composite end points were cerebrovascular accident, transient ischemic attack, and peripheral embolism at 6 months, which was a prespecified time point. Secondary end points were hemorrhage, mortality, and sinus rhythm. RESULTS: At 6 months, there was no difference in composite embolic events between the TEE group and the conventional group (10 [2%] vs 4 [0.8%]; risk ratio (RR) 2.47, 95% CI 0.78-7.88; P = .11). However, the hemorrhagic rate was significantly lower in the TEE group (23 [4.4%] vs 38 [7.5%]; RR 0.58, 96% CI 0.35-0.97; P = .04). There was no difference between the 2 treatment groups in all-cause mortality (21 [4%] vs 14 [2.8%]; RR 1.48, 95% CI 0.76-2.92; P = .25) and in the occurrence of normal sinus rhythm between the 2 groups (305 [62.2%] vs 280 [58.1%]; P = .51). Sinus rhythm at 6 months was more common in the TEE-guided group, in those patients who had direct current cardioversion (238 [62.5%] vs 151 [53.9%]; P = .03). CONCLUSION: The TEE-guided strategy may be considered a clinically effective alternative to a conventional anticoagulation strategy for patients with AF of > 2 days' duration undergoing electrical cardioversion over a 6-month period.

Adult↗
PubMed2006

Noninvasive diagnosis of coronary artery bypass graft disease by dobutamine stress real-time myocardial contrast perfusion imaging.

BACKGROUND: The aim of this study was to assess the accuracy of real-time myocardial contrast perfusion imaging (MCPI) during dobutamine stress echocardiography, for the diagnosis of coronary artery bypass graft disease. METHODS: MCPI was performed using commercially available ultrasound contrast agents (Optison or Definity) at rest and at peak dobutamine-atropine stress in 64 patients with previous coronary artery bypass graft. Significant disease was defined as 70% or greater stenosis in one or more grafts or a native nongrafted coronary artery. MCPI was considered diagnostic in the presence of reversible perfusion abnormalities (RPA). RESULTS: Significant stenosis (>or=70% by quantitative angiography) in one or more grafts was detected in 49 patients (77%). RPA were detected in 44 of these patients (sensitivity 90%, confidence interval [CI] 81-98). Significant stenosis was detected in 74 of the 176 bypass grafts (42%). RPA were detected in the distribution of 55 diseased grafts and 21 nondiseased grafts (regional sensitivity 74%, CI 64-84; specificity 79%, CI 71-87; and accuracy 77%, CI 71-84). RPA were detected in two or more vascular distributions in 25 of 33 patients with multivessel stenotic lesions and in 4 of 31 patients without (sensitivity 76%, CI 61-90; specificity 87%, CI 75-99; and accuracy 81%, CI 72-91). CONCLUSION: Dobutamine stress MCPI is a useful technique for the evaluation of coronary artery bypass graft disease.

Coronary Artery Bypass↗
PubMed2006

Treatment of deeply located acute intravascular thrombi with therapeutic ultrasound guided by diagnostic ultrasound and intravenous microbubbles.

OBJECTIVE: We sought to determine the added value of simultaneous imaging of intravenously infused microbubbles that are being used to dissolve an intravascular thrombus with therapeutic ultrasound (TUS). METHODS: In a chronic canine arteriovenous graft occluded by a thrombus, TUS (1 MHz) was applied through a 6-cm-thick tissue-mimicking phantom (measured mean +/- SD peak negative pressure through the phantom, 958 +/- 104 kPa) during an intravenous infusion of either saline (n = 6 occlusions) or lipid-encapsulated microbubbles (ImaRx Therapeutics, Inc, Tucson, AZ). Therapeutic ultrasound was intermittently applied during the microbubble infusion either at set time intervals (n = 6 occlusions) or when simultaneous diagnostic ultrasound (DUS) indicated a sustained presence of microbubbles (n = 12 occlusions). Success was defined as return of rapid flow within the graft (grade 3 flow). RESULTS: Diagnostic ultrasound showed microbubbles moving through small channels within the thrombus before angiographic evidence of flow in the graft. This guided the timing of TUS application better than using set time intervals. Angiographic clearance of the thrombus and restoration of grade 3 flow at 45 minutes of treatment were seen in 33% of deeply located thrombosed grafts treated with TUS at set time intervals and 92% of grafts treated with TUS guided by DUS (P < .001 compared with set time intervals). CONCLUSIONS: The use of TUS with intravenous microbubbles has a high success rate in recanalizing deeply located thrombosed arteriovenous grafts when performed with DUS guidance.

Angiography↗
PubMed2005

Association of myocardial ischemia with mortality and implantable cardioverter-defibrillator therapy in patients with coronary artery disease at risk of arrhythmic death.

OBJECTIVES: We sought to assess the relation between myocardial ischemia during stress echocardiography and major events in patients with implantable cardioverter-defibrillator (ICD). BACKGROUND: The association of myocardial ischemia with subsequent ICD therapy and mortality is unknown. METHODS: We studied 90 patients (age 65 +/- 13 years, 27 women) with history of coronary heart disease who received ICD for primary (53 patients) or secondary (37 patients) prevention of sudden cardiac death. Sixty-five (72%) patients had a previous coronary artery bypass surgery. Patients underwent exercise treadmill or dobutamine stress echocardiography. Ischemia was defined as new or worsening wall motion abnormalities. End points were death and appropriate ICD therapy. RESULTS: Mean ejection fraction was 34 +/- 12%. During a mean follow-up of 2.8 +/- 1.5 years, 5 patients died and 19 patients had ICD therapy. Ischemia was detected in 20 of 24 patients with subsequent events and in 24 of 66 patients without (83% vs. 36%, p < 0.001). Events occurred in 17 of the 32 patients (53%) with both ischemia and inducible ventricular tachycardia (VT) on electrophysiologic (EP) studies. None of the 16 patients without ischemia or inducible VT on EP studies had events. In a Cox multivariate analysis model, independent predictors of events were a history of spontaneous sustained VT (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.3 to 3.8), inducible VT on EP studies (HR 1.7, 95% CI 1.2 to 4.5), and ischemia (HR 2.1, 95% CI 1.2 to 3.5). CONCLUSIONS: Ischemia during stress echocardiography is an independent predictor of death and ICD therapy in patients with coronary heart disease at high risk of arrhythmic death. Patients without inducible ischemia or VT on a previous EP study have a very low risk of events. A combination of ischemia and a positive EP study is associated with a very high risk of events.

Aged↗
PubMed2005

Prognostic value of dobutamine stress myocardial contrast perfusion echocardiography.

BACKGROUND: Myocardial perfusion (MP) imaging with real-time contrast echocardiography (RTCE) improves the sensitivity of dobutamine stress echocardiography for detecting coronary artery disease. Its prognostic value is unknown. We sought to determine the value of MP and wall motion (WM) analysis during dobutamine stress echocardiography in predicting the outcome of patients with known or suspected coronary artery disease. METHODS AND RESULTS: We retrospectively studied 788 patients with RTCE during dobutamine stress echocardiography using intravenous commercially available contrast agents. The incremental prognostic value of MP imaging over clinical risk factors and other echocardiographic data was examined through the use of a log-likelihood test (Cox model). During a median follow-up of 20 months, 75 events (9.6%) occurred (58 deaths, 17 nonfatal myocardial infarctions). Abnormal MP had significant incremental value over clinical factors, resting ejection fraction, and WM responses in predicting events (P<0.001). By multivariate analysis, the independent predictors of death and nonfatal myocardial infarction were resting left ventricular ejection fraction <50% (relative risk [RR], 1.9; 95% CI, 1.2 to 3.2; P=0.01), hypercholesterolemia (RR, 0.5; 95% CI, 0.3 to 0.9; P=0.01), and abnormal MP (RR, 5.2; 95% CI, 3.0 to 9.0; P<0.0001). The 3-year event free survival was 95% for patients with normal WM and MP, 82% for normal WM and abnormal MP, and 68% for abnormal WM and MP. CONCLUSIONS: MP imaging during dobutamine stress RTCE provides incremental prognostic information in patients with known or suspected coronary artery disease. Patients with normal MP have a better outcome than patients with normal WM.

Aged↗
PubMed2005

Comparison of dobutamine stress echocardiography with and without real-time perfusion imaging for detection of coronary artery disease.

In a pilot study of 27 patients, those who presented with chest pain underwent 2 dobutamine stress echocardiographic studies, 1 with high mechanical index harmonic imaging to analyze wall motion without contrast and 1 with real-time low mechanical index perfusion imaging with intravenous Optison to assess myocardial perfusion and wall motion. All patients then underwent quantitative coronary angiography. Two independent reviewers demonstrated an improvement in sensitivity when analyzing myocardial perfusion. In the 21 patients who had significant coronary stenoses, 14 had abnormal myocardial perfusion detected at peak stress and 7 had abnormal wall motion detected by standard dobutamine stress echocardiography. There was decreased specificity with perfusion imaging by 1 reviewer. The addition of real-time perfusion imaging after intravenous contrast during dobutamine stress echocardiography has the potential to improve detection of coronary artery disease.

Albumins↗
PubMed2005

Safety of dobutamine stress real-time myocardial contrast echocardiography.

OBJECTIVES: The aim of this study was to determine the safety of dobutamine stress myocardial perfusion imaging (MPI) obtained by real-time contrast echocardiography (RTCE) and intravenous ultrasound contrast in a large cohort of patients with suspected coronary artery disease (CAD). BACKGROUND: Despite the increasing number of studies showing the potential clinical utility of myocardial contrast perfusion imaging with commercially available contrast agents, the safety of this technique in a clinical setting has not been demonstrated. METHODS: Over a four-year period, 1,486 patients underwent dobutamine stress RTCE with low mechanical index pulse sequence schemes after intravenous injections of commercially available contrast agents (35% Definity, Bristol Myers Squibb Medical Imaging Inc., North Billerica, Massachusetts; 65% Optison, GE-Amersham, Princeton, New Jersey). The hemodynamic and adverse effects of RTCE were compared with 1,012 patients who underwent conventional dobutamine stress echocardiography (DSE) without contrast. The feasibility of image analysis was defined as the ability to analyze MPI in at least two of the three standard segments in each left ventricular wall. RESULTS: No myocardial infarction or death occurred during dobutamine stress. There was no difference in the incidence of nonsustained ventricular tachycardia, sustained ventricular tachycardia, or supraventricular tachycardia during dobutamine infusion between RTCE and DSE. Myocardial perfusion imaging was considered feasible for analysis in 94% of the walls at baseline and 95% at peak stress. The anterior, lateral, and posterior walls were the most common regions in which MPI was not feasible. Myocardial perfusion imaging with RTCE had a higher accuracy for detecting patients with angiographically significant CAD than the analysis of wall motion (84% vs. 66%, respectively; p < 0.001). CONCLUSIONS: Dobutamine stress RTCE appears to be a safe and feasible technique for evaluating patients with known or suspected CAD.

Cardiotonic Agents↗
PubMed2005

Comparison of low-mechanical index pulse sequence schemes for detecting myocardial perfusion abnormalities during vasodilator stress echocardiography.

Myocardial contrast echocardiography has the potential to accurately detect functionally significant coronary artery disease during pharmacologic stress testing. Different low-mechanical index modalities, including triggering replenishment imaging (TRI) and real-time imaging (RTI), are currently used to identify myocardial perfusion defects. We compared the ability of TRI with that of RTI for detecting and localizing perfusion abnormalities. Thirty-six patients (62 +/- 14 years old, 15 men) underwent single-photon emission computed tomography (SPECT) with technetium-99m sestamibi and myocardial contrast echocardiography at baseline and after infusion of 0.56 mg/kg of dipyridamole. Sixteen of these patients also underwent quantitative angiography. Contrast-enhanced images were obtained in 4-, 3-, and 2-chamber views after intravenous bolus injections of lipid-encapsulated microbubbles (0.1 ml of Definity). A myocardial perfusion defect was defined by myocardial contrast echocardiography as a delay of >2 seconds in contrast replenishment after high-mechanical index flash impulse. The myocardial segments were divided into 3 major coronary territories. There was agreement in detecting perfusion defects between SPECT and TRI in 26 patients (72%, kappa = 0.46) and between SPECT and RTI in 27 patients (75%, kappa = 0.50). Agreements between myocardial contrast echocardiography and SPECT for localizing coronary territories with perfusion defects were 81% for TRI (kappa = 0.43) and 85% for RTI (kappa = 0.61). Accuracy of RTI for detecting >50% diameter stenoses by quantitative angiography was 79%, that of TRI was 71%, and that of SPECT was 65%. These data indicate that the different low-mechanical index imaging schemes are equivalent to radionuclide SPECT in accurately detecting diseased coronary artery territories during vasodilator stress.

Coronary Angiography↗
PubMed2005

Novel site-specific systemic delivery of Rapamycin with perfluorobutane gas microbubble carrier reduced neointimal formation in a porcine coronary restenosis model.

Earlier studies demonstrated that perfluorobutane gas microbubble carrier (PGMC) adheres to injured arteries and enhances the drug uptake specifically into the cells of the denuded vessel segment. The purpose of this study was to investigate the effect of PGMC-based systemic delivery of Rapamycin on expression of p27 in vascular tissue and restenosis in porcine coronary arteries after stent implantation. Eight pigs underwent coronary stent implantation (three stents per animal). Five pigs were treated with i.v. injection of PGMC with 2 mg of Rapamycin and three animals served as control. Four hours postprocedure, three pigs were sacrificed and stented segments were analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, five pigs (15 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion-fixed. HPLC of the treated arteries demonstrated high drug concentration in the vessel tissue, and Western blot analysis showed elevated expression of p27 at 4 hr postprocedure. Histomorphometry revealed significantly reduced (by 40%) neointimal formation in the PGMC/Rapamycin group compared with controls (1.84 +/- 0.84 vs. 4.77 +/- 1.71 mm2, respectively; P < 0.001). In the porcine coronary model, site-specific systemic delivery of Rapamycin utilizing PGMC resulted in overexpression of p27 and a significant reduction of neointimal formation within the stented segments.

Animals↗
PubMed2005

Effectiveness of lipid microbubbles and ultrasound in declotting thrombosis.

The objectives of this study were to determine the effectiveness of lipid-encapsulated microbubbles and ultrasound (US) in recanalizing arteriovenous graft thrombi and the effect that tissue attenuation has on the success rate. A total of 55 thrombotic occlusions were created in four canines. The thrombosed grafts were randomly treated with two different 1-MHz US intensities, low (0.4 to 0.6 W/cm(2)) and high (10 W/cm(2)). Intragraft microbubbles were compared with intragraft saline and with the same dose of microbubbles given IV. IV microbubbles were also given both in the presence and absence of a tissue-mimicking phantom. High-intensity US (10 W/cm(2)) with intragraft microbubbles produced significantly higher patency and flow scores than did US with saline (p < 0.01). US with IV microbubbles had higher success rates in recanalizing thrombosed grafts than did US alone at all intensities. Attenuation reduced the rate at which successful recanalization occurred at both low and high intensities. US and microbubbles are capable of recanalizing acute arteriovenous graft thromboses. Higher intensities may be needed in the presence of tissue attenuation.

Acute Disease↗
PubMed2005

Intravenous myocardial contrast echocardiography for the diagnosis of coronary artery disease.

PURPOSE OF REVIEW: Myocardial contrast echocardiography is a recently developed technique that permits the noninvasive assessment of myocardial perfusion. Myocardial contrast enhancement from microbubbles characteristically reflects the myocardial blood volume. The analysis of microbubble kinetics using quantitative myocardial contrast echocardiography permits the evaluation of myocardial blood flow both at rest and during pharmacological stress. RECENT FINDINGS: Myocardial contrast echocardiography has been shown to have good concordance with single photon emission computed tomography for the localization of perfusion abnormalities. As a result of its better spatial resolution and the fact that it tracks myocardial blood flow changes, it seems to have higher sensitivity for the detection of angiographically significant coronary artery disease, while maintaining similar specificity to single photon emission computed tomography. Low mechanical index imaging techniques (real-time myocardial contrast echocardiography) have the advantage of permitting simultaneous analysis of wall motion and perfusion, which is particularly important during dobutamine stress. Myocardial perfusion analysis using real-time myocardial contrast echocardiography has been shown to have higher sensitivity and diagnostic accuracy than wall motion analysis for the detection of coronary artery disease. Quantitative myocardial contrast echocardiography seems to overcome the expertise requirements for appropriate interpretation of myocardial perfusion images, and may have been demonstrated to be an accurate supplemental technique for estimating the severity of coronary artery disease. SUMMARY: Recent technological advances have positioned myocardial contrast echocardiography as a safe and feasible technique for the evaluation of myocardial perfusion. The analysis of myocardial perfusion using myocardial contrast echocardiography has higher diagnostic accuracy than wall motion analysis for detecting coronary artery disease.

Contrast Media↗