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Biomedical subjects

D R Holmes

Publications and source records attributed to D R Holmes.

At least 163 records · Page 9Linked to original sources

Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia.

Coronary arteries contain a network of vasa vasorum in the adventitia. The three-dimensional anatomy of the vasa vasorum in early coronary atherosclerosis is unknown. This study was designed to visualize and quantitate the three-dimensional spatial pattern of vasa vasorum in normal and experimental hypercholesterolemic porcine coronary arteries, using a novel computed tomography technique. Animals were killed after being fed either a high cholesterol diet (n = 4) or a control diet (n = 4) for 12 wk. The proximal left anterior descending coronary artery was removed from the heart, scanned, and reconstructed, and quantitation of vasa vasorum density was performed. Two different types of vasa vasorum were defined: first-order vasa vasorum ran longitudinally parallel to the vessel and second-order originated from first-order vasa circumferentially around the vessel wall. Compared with controls in hypercholesterolemic coronary arteries, there was a significant increase in the area of the vessel wall (3.86+/-0.22 vs. 8.07+/-0.45 mm2, respectively, P < 0.01) and in the density of vasa vasorum (1. 84+/-0.05/mm2 vs. 4.73+/-0.24/mm2; respectively, P = 0.0001). This occurred especially by an increase of second-order vasa vasorum and disorientation of normal vasa vasorum spatial pattern. This study suggests that adventitial neovascularization of vasa vasorum occurs in experimental hypercholesterolemic coronary arteries and may be a part of the early atherosclerotic remodeling process.

Animals↗

Frequency of adverse clinical events in the 12 months following successful intracoronary stent placement in patients treated with aspirin and ticlopidine (without warfarin).

Little is known about the frequency of adverse events in the year following stent placement in patients treated with aspirin and ticlopidine, without warfarin. We analyzed the first such 234 consecutive patients treated at our hospital between October 1994 and December 1995. Their mean age was 62+/-12 years; 40% had had a prior myocardial infarction, 22% had undergone coronary artery bypass surgery, and 65% had multivessel disease. The indication for stent placement was dissection or abrupt closure in 24% of patients and suboptimal balloon angioplasty results in 14%; placement was elective in 62% of patients. Three hundred forty-five coronary segments were treated in the 234 patients; 305 stents (1.3 stents/patient) were placed. Palmaz-Schatz coronary stents (75%), Gianturco-Roubin stents (21%), and Johnson & Johnson biliary stents (4%) were used. Mean nominal stent size was 3.4+/-0.4 mm. High-pressure inflations (> or = 14 atm, mean 17+/-2) were performed in all patients. The mean residual stenosis was 3+/-5% by visual estimate. Intravascular ultrasound was utilized to facilitate stent placement in 53% of patients. Mean follow-up was 1.6+/-0.5 years. There were no deaths, Q-wave myocardial infarctions, coronary artery bypass operations, or repeat angioplasty procedures required during the remainder of the hospitalization or in 30 days after stent placement; stent thrombosis did not occur. Kaplan-Meier analysis of adverse events in the 6 months following the procedure revealed a mortality rate of 0.9%; the rate of myocardial infarction (Q-wave or non-Q-wave) was 1.3%. Bypass surgery was performed in 0.9% and angioplasty for in-stent restenosis was performed in 9.5% of patients. Any 1 of these events occurred in 11.7% of patients in the 6 months after the procedure. The corresponding event rates at 1 year were 1.3%, 2.2%, 3.5%, and 12.2%, respectively; any 1 of these events occurred in 16.5% of patients. In patients receiving intracoronary stents of varying designs followed by high-pressure postdeployment inflations in whom an excellent visual angiographic result is achieved, antithrombotic therapy with aspirin and ticlopidine is associated with a very low frequency of adverse cardiovascular events in the 12 months following the procedure regardless of the indication for stent placement.

Adult↗

Percutaneous balloon mitral valvuloplasty by the Inoue balloon technique: the procedure of choice for treatment of mitral stenosis.

The Inoue technique of percutaneous balloon mitral valvuloplasty, introduced in 1984, is a truly startling advance in cardiology in modern times. It is time to reeducate our colleagues that when they hear the opening snap in patients with mitral stenosis, they should automatically open these stenotic mitral valves with an Inoue balloon catheter rather than submit these patients to surgical correction.

Aged↗

Balloon angioplasty versus new device intervention: clinical outcomes. A comparison of the NHLBI PTCA and NACI registries.

OBJECTIVES: We sought to compare outcomes of patients treated in the National Heart, Lung, and Blood Institute (NHLBI) Percutaneous Transluminal Coronary Angioplasty (PTCA) and New Approaches to Coronary Intervention (NACI) registries. BACKGROUND: Coronary angioplasty has numerous shortcomings. New devices for performing coronary interventions have been introduced in an effort to improve clinical outcomes. METHODS: Under the sponsorship of the NHLBI, a registry of consecutive patients treated with PTCA during 1985 to 1986 was established. In 1990, the NHLBI funded a second registry, the NACI. The two registries used the same data coordinating center to collect detailed baseline and follow-up information. RESULTS: Patients enrolled in the NACI registry were older, had undergone more previous bypass surgery procedures and had more stenoses located in bypass grafts than patients in the NHLBI PTCA registry. Procedural success was achieved in 72.1% and 82.6% of patients in the PTCA and NACI registries, respectively; however, in-hospital and 1-year mortality rates were 1.0% versus 1.8% and 3.1% versus 5.9% for the PTCA versus NACI registries, respectively. After risk adjustment, there was no difference in 1-year mortality. Rates of target lesion revascularization (TLR) were 21.5% for the PTCA registry and 24.2% for the NACI registry. NACI registry patients had a higher risk for TLR and the composite end point of death, myocardial infarction or revascularization (relative risk 1.28 and 1.23, respectively). However, the NACI registry patients who received stents tended to have a lower adjusted TLR rate. CONCLUSIONS: This comparative study found no overall superiority of these newer devices in terms of patient survival or freedom from TLR after adjustment for baseline risk profiles. Although technologic improvements (especially improved stenting) continue, these observations highlight the importance of careful assessment of clinical results in the broad population of patients in whom interventions are used.

Angioplasty, Balloon, Coronary↗

Summary of the Mayo Clinic experience with direct left ventricular puncture.

Hemodynamic assessment of patients with prosthetic valves can be challenging. Noninvasive techniques may be limited by interference from the prosthetic material, whereas access to the left ventricle for direct pressure measurements often is not possible using common methods. The technique of direct, percutaneous left ventricular puncture has been proven to be a safe method that often provides needed data to help manage difficult clinical situations. We report our 8-yr experience with this technique for assessment of patients with valvular prostheses. Direct left ventricular puncture is a safe technique in patients with prior cardiac surgery and provided significant diagnostic information in the set of patients with multiple valvular prostheses.

Aortic Valve↗

Cine film replacement: digital archival requirements and remaining obstacles.

The acceptance of the Digital Imaging and Communication in Medicine (DICOM) standard and the Compact Disk-Recordable (CD-R) as the interchange medium have been critical developments for laboratories that need to move forward on the cine replacement front, while at the same time retain a means to communicate with other centers. One remaining essential component which has not been satisfactorily addressed is the issue of how digital image data should be archived within an institution. Every laboratory must consider the diverse issues which affect the choice of a digital archiving system. These factors include technical and economic issues, along with the clinical routines prevailing in their laboratory. A complete understanding of the issues will lead to the formulation of multiple options which may prove acceptable and will help to overcome the last obstacle which remains for the complete replacement of cine film in the cardiac catheterization laboratory.

Archives↗

Effect of basal epicardial tone on endothelium-independent coronary flow reserve measurement.

Increased basal epicardial tone may attenuate the coronary flow reserve (CFR) by causing vasodilatation of resistance vessels. We examined the effect of basal epicardial tone on the endothelium-independent CFR measurements in subjects with nonobstructive coronary disease. Patients underwent evaluation of endothelium-independent CFR using adenosine (18-36 microg) and endothelium-dependent CFR using acetylcholine (10(-6) M-10(-4) M), both administered intracoronary. CFR to adenosine, presented as the ratio of Doppler flow velocities post- and pre-adenosine, was measured at baseline and after intracoronary nitroglycerin (200 microg). Nitroglycerin increased the coronary artery diameter by 19.7 +/- 2.5%, and decreased the coronary vascular resistance from 3.0 +/- 0.2 mm Hg/ml/min to 1.8 +/- 0.1 mm Hg/ml/min (p < 0.0001). The response to adenosine at baseline and after nitroglycerin was similar (CFR ratio of 2.52 +/- 0.09 and 2.57 +/- 0.10, respectively, p = NS). The effect of nitroglycerin on the response to adenosine did not correlate with coronary endothelial function (r2 = 0.06, p = 0.13). The basal epicardial tone does not affect CFR measurements in patients with angina and nonobstructive coronary disease.

Acetylcholine↗

Variability of radiation output dynamic range in modern cardiac catheterization imaging systems.

Automatic exposure control (AEC) is one of the most important characteristics for optimizing cardiac catheterization imaging; this allows the X-ray system to provide sufficient radiation output under a variety of clinical conditions so that a satisfactory image is obtained. AEC was assessed in 97 cardiac catheterization laboratories using a standard set of phantoms. Three different copper attenuators were used to simulate three patient sizes. As magnification increased, many systems had limited dynamic range and were unable to increase radiation output. With increasing atttenuator thickness, the problem worsened. With the thickest attenuator and largest magnification (4.5"-5.0" FOV), 60% of systems could not achieve the typical 70% increase in exposure while 20% were unable to increase radiation output at all.

Body Burden↗

Neointimal response following rotational atherectomy compared to balloon angioplasty in a porcine model of coronary in-stent restenosis.

In-stent restenosis remains a clinical therapeutic challenge. Rotational atherectomy (RA) is an attractive treatment option as it may cause less vascular injury than balloon angioplasty (BA) and, therefore, limit further neointimal response. In an animal model of coronary in-stent restenosis, thermal injury and stenting created neointima (old NI). The treatment of in-stent restenosis with either BA (n = 9) or RA (n = 11) also generated neointima (new NI). The average areas (mm2) of old NI in the BA and RA groups were similar (3.77 +/- 0.40 vs. 3.67 +/- 0.53; P = 0.32). However, new NI formed after treatment of in-stent restenosis was significantly less in the RA as compared to the BA group (0.33 +/- 0.12 vs. 0.73 +/- 36, P < 0.01). In this porcine coronary artery model of in-stent restenosis, treatment with rotational atherectomy resulted in significantly less recurrent neointimal hyperplasia than balloon angioplasty. This animal study, thus, provides a rationale for the clinical use of rotablation in the treatment of in-stent restenosis.

Angioplasty, Balloon, Coronary↗

Prevalence of spontaneous reperfusion and associated myocardial salvage in patients with acute myocardial infarction.

This study sought to determine the prevalence of spontaneous reperfusion of an infarct-related artery (IRA) and associated myocardial salvage in the absence of thrombolysis or angioplasty. Twenty-one patients with acute myocardial infarction received only heparin and aspirin. At a median of 18 hours after presentation, 12 patients (57%) had angiographic patency of the IRA. Technetium-99m sestamibi was injected acutely on presentation and again at hospital discharge. Acute and final perfusion defect sizes were measured. Their difference, myocardial salvage, was calculated along with salvage index (myocardial salvage/acute defect). Comparing patients with a patent versus occluded IRA, myocardium at risk was similar (16% +/- 12% vs 12% +/- 9% left ventricle, p = NS); however, myocardial salvage (9% +/- 9% vs -2% +/- 7% left ventricle, p = 0.01), and salvage index (0.62 +/- 0.37 vs 0.19 +/- 0.33, p = 0.01) were greater in patients with spontaneous reperfusion. Resolution of chest pain was greater in patients with a patent IRA (100% vs 55%, p = 0.003). Spontaneous reperfusion of the IRA occurs frequently in patients with acute myocardial infarction and is associated with significant myocardial salvage.

Aged↗

Aortocoronary bypass grafting with expanded polytetrafluoroethylene: 12-year patency.

Prosthetic coronary artery bypass conduits are rarely used because the rate of thrombosis is inherently higher than that with autologous conduits. The low medium-term patency rates of prosthetic grafts have restricted their use primarily to patients with inadequate autologous conduits or to selected emergencies. We describe a patient treated with expanded polytetrafluoroethylene who had documented patency 12 years after the operation.

Anastomosis, Surgical↗

Insulin and IGF-I attenuate the coronary vasoconstrictor effects of endothelin-1 but not of sarafotoxin 6c.

OBJECTIVE: To examine the hypothesis that insulin and insulin-like growth factor I (IGF-I) attenuate endothelin-induced contraction of porcine coronary epicardial arteries in vitro. BACKGROUND: Endothelin-induced coronary vasoconstriction is mediated by two types of receptors, A (ETA) and B (ETB), resulting in calcium influx. Both insulin and IGF-I attenuate endothelin-induced calcium influx into porcine coronary artery smooth muscle. METHODS: Epicardial arteries harvested from juvenile pigs were contracted with cumulative concentrations of endothelin-1 (ETA- and ETB-receptor agonist; 10(-10)-10(-6) M) or of sarafotoxin-6c (ETB-receptor agonist; 10(-11)-10(-7) M). In additional experiments, endothelin-1 or sarafotoxin-6c were added after incubation with 10(-8) M regular insulin or IGF-I. These experiments were repeated in vessels without endothelium. Contraction for each vessel was calculated relative to the response to 60 mM KCl. RESULTS: The maximal contractions to endothelin-1 in vessels with and without endothelium were 158 +/- 8 and 200 +/- 21%, respectively (p < 0.05 at 10(-8.5)-10(-6.5) M). Both insulin (at 10(-7)-10(-6) M) and IGF-I (at 10(-6.5)-10(-6) M) attenuated the contraction to endothelin-1 in vessels with intact endothelium, as well as in vessels without endothelium (at 10(-7) and 10(-6) M for insulin and 10(-7.5)-10(-6) M for IGF-I). The maximal contractions to sarafotoxin-6c in vessels with and without endothelium were 54 +/- 13 and 84 +/- 7%, respectively (p < 0.05 at 10(-9), 10(-8.5) and 10(-7) M). Insulin and IGF-I did not affect the response to sarafotoxin-6c in vessels with and without endothelium. CONCLUSION: Insulin and IGF-I attenuated ETA-receptor-mediated coronary contraction through an endothelium-independent mechanism. The IGF axis may serve as an endogenous modulator of endothelin-mediated vasoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Experimental hypercholesterolemia induces ultrastructural changes in the internal elastic lamina of porcine coronary arteries.

The internal elastic lamina (IEL) serves as a barrier for cells and macromolecules migration between the intima and the media in the vascular wall. Several investigators have reported internal elastic lamina ultrastructural changes in elastic arteries with atherosclerosis. However, no quantitative and qualitative assessment of the internal elastic lamina architecture in muscular arteries such as the coronary circulation during early atherosclerosis have been performed yet. In this study, we therefore evaluated the ultrastructural morphological changes of the IEL in the coronary circulation of pigs fed with high cholesterol diet. Animals were sacrificed after being fed either a high cholesterol diet for 10-12 weeks (n = 5, 12 coronary segments) or a control diet (n = 4, 15 coronary segments). Coronary arteries were analyzed by transmission and scanning electron microscopy. In addition, computerized digital analysis of the images obtained by confocal scanning microscopy was performed for the quantitation of the morphologic changes in the internal elastic lamina. Confocal microscopy and scanning electron microscopy revealed an altered pattern characterized by large oval fenestration formation in the internal elastic lamina of hypercholesterolemic animals. Computerized morphometric analysis of confocal microscopy images demonstrated that compared to controls, the IEL of cholesterol-fed animals was characterized by an increase in the minor diameter of the fenestrae (2.16 +/- 0.04 microm versus 3.32 +/- 0.06 microm, P = 0.003) and a decrease in the fenestrae density (22333 +/- 1334/mm2 versus 17552 +/- 931/mm2, P = 0.015) of the internal elastic lamina. The percentage of the IEL area covered by the fenestrae correlated with the intimal thickness (r = 0.79, P = 0.004). This study demonstrates that experimental hypercholesterolemia is characterized by ultrastructural changes of the internal elastic lamina in the coronary circulation. This study suggests that the IEL may play an important role in the development of structural changes which characterize the early phase of coronary atherosclerosis.

Animals↗

Echocardiography in the invasive laboratory: utility of two-dimensional echocardiography in performing transseptal catheterization.

OBJECTIVE: To evaluate the potential utility of transthoracic two-dimensional echocardiography as an aid in the technique of transseptal catheterization. DESIGN: We performed a prospective study of 58 patients (29 men and 29 women; mean age, 64.2 years) referred for cardiac catheterization, in whom a systematic approach was used with selective application of two-dimensional echocardiography. MATERIAL AND METHODS: The study group of 58 patients had the following diagnoses: mitral stenosis in 17, hypertrophic cardiomyopathy in 13, dilated cardiomyopathy in 13, aortic stenosis in 13, and prosthetic valve dysfunction and pulmonary hypertension in 1 each. With use of only fluoroscopic guidance, initial gentle pressure on the dilator alone was attempted for left atrial access. If the catheter resisted entry into the left atrium, two-dimensional echocardiography was performed to assess the catheter's position relative to the atrial septum, and adjustments were made accordingly. Transseptal puncture with a Brockenbrough needle was performed only after confirmation of the catheter position at the region of the fossa ovalis with two-dimensional echocardiography. RESULTS: The catheterization procedure was performed without complication in all 58 patients; the mean time to catheter placement was 5.6 +/- 3.5 minutes (range, 3 to 20). Two-dimensional echocardiography was used in 33 patients (57%) when left atrial access was not obtained. On the basis of echocardiographic images, the transseptal catheter had to be repositioned in 16 of these 33 patients (48%). CONCLUSION: Two-dimensional echocardiography offers value in demonstrating catheter position during transseptal catheterization and may be used in some patients to ensure transseptal puncture at the region of the fossa ovalis.

Adult↗

Fibrin-film stenting in a porcine coronary injury model: efficacy and safety compared with uncoated stents.

OBJECTIVES: This study was designed to test the efficacy and safety of a fibrin-film-covered stent compared with that of a bare metal stent in the porcine coronary injury model. BACKGROUND: Biodegradable stents are a potential method of achieving total lesion coverage and delivering local, lesion-specific drug therapy. METHODS: Two coronary arteries in each pig were randomly assigned to deployment of either a fibrin-film or a bare tantalum wire-coil stent. An oversized balloon injury, 1.15 to 1.30 times the reference vessel diameter, was induced in each coronary segment before stenting to simulate angioplasty injury. Thirty pigs were studied: group 1 for 28 days (15 pigs); group 2 for 90 days (5 pigs); group 3 for 6 months (5 pigs); group 4 for 1 year (5 pigs). RESULTS: Two pigs died of occlusion of the bare stent and one of occlusion of the fibrin stent (p > 0.99). There were no significant differences between the fibrin-stented and bare-stented coronary segments with regard to arterial injury. In group 1 (28 days, 14 pigs), the mean neointimal thicknesses in the fibrin-stented and bare-stented groups were 0.57+/-0.31 and 0.57+/-0.27 mm, respectively (p=0.89). In groups 2 to 4 (90 days, four pigs; 6 months, four pigs; 1 year, five pigs), the mean neointimal thicknesses for fibrin- and bare-stented coronary segments at the times studied were 0.48+/-0.26 versus 0.50+/-0.22 mm at 90 days; 035+/-0.04 versus 0.35+/-0.16 mm at 6 months; and 0.33+/-0.14 versus 0.30+/-0.14 mm at 1 year (p=0.98). CONCLUSIONS: Fibrin-film stents appear to be an excellent candidate for local drug delivery because they can completely and safely cover the stented coronary segment while degrading slowly over 1 to 3 months. This result is important when compared with the poor results of previous studies of synthetic polymer stents.

Animals↗

Time to therapy and salvage in myocardial infarction.

OBJECTIVES: This study sought to examine the influence of time to reperfusion on myocardial salvage. BACKGROUND: Major trials of reperfusion therapy for myocardial infarction (MI) have demonstrated improved outcome for patients achieving earlier reperfusion. However, some patients experience significant benefit despite delayed reperfusion. METHODS: Fifty-five patients with a first anterior MI underwent successful reperfusion therapy (angioplasty or thrombolysis). Technetium-99m (Tc-99m) sestamibi was injected before reperfusion therapy and again at hospital discharge to determine the myocardial salvage index for each patient. Residual flow to the infarct territory was assessed by the nadir of the Tc-99m sestamibi count-profile curve. RESULTS: The salvage index showed wide variability (range -0.04 to 1.0), and extreme values were seen in 34.5% of the group (<0.10 in 9%, >0.90 in 25%). A high salvage index was associated with reperfusion therapy before 2 h (p=0.02) or good residual blood flow (p < 0.01). For the 10 patients who received reperfusion therapy within 2 h, residual blood flow was not correlated with salvage (p=0.12). For the 45 patients treated after 2 h, residual blood flow correlated significantly with salvage (r=0.57, p < 0.0001). There was a significant interaction (p < 0.05) between residual blood flow and time to therapy, indicating that the effect of each variable on salvage depended on the value of the other. Multiple historic and hemodynamic variables were examined, but none demonstrated any association with residual flow or myocardial salvage. CONCLUSIONS: In patients with acute MI, successful reperfusion therapy within 2 h is associated with the greatest degree of myocardial salvage. For patients treated after 2 h, residual blood flow to the infarct-related territory appears to be the most important determinant of myocardial salvage.

Adult↗

Rescue angioplasty after failed thrombolysis: technical and clinical outcomes in a large thrombolysis trial. GUSTO-1 Angiographic Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: We sought to assess the angiographic outcome, complication rates and clinical features of percutaneous transluminal coronary angioplasty (PTCA) after failed thrombolysis for acute myocardial infarction. BACKGROUND: "Rescue angioplasty" refers to mechanical reopening of an occluded infarct-related artery (IRA) after failed intravenous thrombolysis. Although the procedure is commonly performed, data describing its technical and clinical outcome are sparse. Early reports suggested that rescue PTCA is less often successful and produces more complications than primary PTCA. Other reports have described beneficial effects of successful rescue PTCA but adverse outcomes when PTCA is unsuccessful. METHODS: Using data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) angiographic substudy, we compared clinical and angiographic outcomes of 198 patients selected for a rescue PTCA attempt with those of 266 patients with failed thrombolysis but managed conservatively and, for reference, with those of 1,058 patients with successful thrombolysis. RESULTS: Patients offered rescue PTCA had more impaired left ventricular function than those in whom closed vessels were managed conservatively. Rescue successfully opened 88.4% of closed arteries, with 68% attaining Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. The interventions did not increase catheterization laboratory or postprocedural complication rates. Multivariate analysis identified severe heart failure to be a determinant of a failed rescue attempt. Successful rescue PTCA resulted in superior left ventricular function and 30-day mortality outcomes, comparable to outcomes in patients with closed IRAs managed conservatively, but less favorable than in patients in whom thrombolytic therapy was initially successful. The mortality rate after a failed rescue attempt was 30.4%; however, five of the seven patients who died after failed rescue PTCA were in cardiogenic shock before the procedure. CONCLUSIONS: Rescue PTCA tends to be selected for patients with clinical predictors of a poor outcome. It is effective in restoring patency. Patients who die after a failed rescue attempt are often already in extremis before the angioplasty attempt.

Aged↗