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Biomedical subjects

David R Holmes

Publications and source records attributed to David R Holmes.

At least 163 records · Page 9Linked to original sources
PubMed2002

Dendroaspis natriuretic peptide relaxes isolated human arteries and veins.

BACKGROUND: Dendroaspis natriuretic peptide (DNP) is the newest member of the natriuretic peptide family and is a circulating peptide in humans. The effects of DNP on the human vasculature are unknown. Since other natriuretic peptides are known to cause vasorelaxation, we determined the response to DNP on human blood vessels in vitro. We also investigated the mechanism of DNP mediated vasorelaxation. METHODS: Rings of human internal mammary artery and saphenous vein were suspended in an organ bath. The response to cumulative concentrations of DNP was obtained. Inhibiting agents were used to determine the mechanism of this vasorelaxation. RESULTS: DNP caused dose-dependent relaxation, with a greater effect on the internal mammary arteries (relaxation from 10(-7) mol/l DNP: 80.6+/-4.1%) than the saphenous veins (33.4+/-4.1%). At 10(-7) mol/l, DNP resulted in less arterial relaxation compared with atrial and C-type natriuretic peptides and similar relaxation to brain natriuretic peptide. In veins, DNP caused the greatest relaxation of the natriuretic peptides. DNP increased tissue cyclic guanosine monophosphate (cGMP) determined by radioimmunoassay by over 7-fold. Barium chloride and indomethacin attenuated DNP mediated vasorelaxation. However, glibenclamide, charydotoxin, apamin, tetraethyl-ammonium chloride and diisothiocyanato-stilbene-2,2'-disulfonic acid did not. DNP mediated vasorelaxation was mildly attenuated with removal of the endothelium. DNP immunoreactivity was identified in both arteries and veins. CONCLUSIONS: The current study demonstrates that DNP is an endogenous human natriuretic peptide that relaxes human arteries more than veins. Furthermore, DNP mediated vasorelaxation involves the inward rectifying potassium channels, prostaglandins, and cGMP. This newest member of the natriuretic peptide family may have an important physiologic role in the human vasculature.

Chloride Channels↗
PubMed2002

Rationale for on-site cardiac surgery for primary angioplasty: a time for reappraisal.

Since the early 1990s, with significant improvement in the procedural success of percutaneous coronary interventions (PCIs), there has been a concomitant reduction in the need for emergency coronary artery bypass graft surgery. This review article focuses on the need for on-site cardiac surgery in patients with acute myocardial infarction undergoing primary angioplasty at centers without on-site cardiac surgical backup. It gives an overview of the need for emergency bypass surgery in both the large trial setting and the community hospital setting. Special consideration is also given to the risks and benefits of primary angioplasty compared with thrombolytic therapy, transfer to an institution with an on-site cardiac surgical facility compared with primary PCI, the frequency and indications for emergency cardiac surgery related and unrelated to primary angioplasty and the requirements for primary angioplasty that must be met in hospitals without the capability of on-site cardiac surgery.

Angioplasty, Balloon, Coronary↗
PubMed2002

Comparison of patients undergoing enhanced external counterpulsation and percutaneous coronary intervention for stable angina pectoris.

Enhanced external counterpulsation (EECP) has recently emerged as a treatment option for angina in selected patients suitable for revascularization with percutaneous coronary intervention (PCI). We compared baseline characteristics and 1-year outcome in 2 cohorts of PCI candidates presenting with stable symptoms: 323 patients treated with EECP in the International EECP Patient Registry (IEPR), and 448 NHLBI Dynamic Registry patients treated with elective PCI. Compared with patients receiving PCI, IEPR patients had a higher prevalence of many risk factors including prior PCI (53.0% vs 33.3%, p <0.001), prior coronary artery bypass grafting (42.1% vs 18.6%, p <0.001), prior myocardial infarction (56.4% vs 27.8%, p <0.001), history of congestive heart failure (16.8% vs 9.2%, p <0.01), and history of diabetes (37.9% vs 23.5%, p <0.001). Left ventricular ejection fraction was lower among IEPR patients (mean 50.3% vs 59.2%, p <0.001). At 1 year, survival was comparable in the 2 cohorts (98.7% IEPR vs 96.8% PCI, p = NS), as were rates of coronary artery bypass grafting during follow-up (4.5% IEPR vs 5.7% PCI, p = NS). At 1 year, 43.7% of IEPR patients reported no anginal symptoms compared with 73.4% of Dynamic Registry patients (p <0.001). Rates of severe symptoms (Canadian Cardiovascular Society class III, IV, or unstable) at 1 year were 15.5% among IEPR patients and 9.5% in the Dynamic Registry (p = 0.02). PCI candidates suitable for and treated with EECP had 1-year major event rates comparable to patients receiving elective PCI. Although PCI was associated with substantially lower rates of 1-year symptoms, EECP may be a safe treatment option for selected patients with obstructive coronary disease.

Age Factors↗
PubMed2002

Improved outcomes for women undergoing contemporary percutaneous coronary intervention: a report from the National Heart, Lung, and Blood Institute Dynamic registry.

OBJECTIVES: The goal of this study was to determine whether women undergoing contemporary percutaneous coronary intervention (PCI) remain at increased risk in comparison with men and whether the outcomes in women have improved. BACKGROUND: Previous studies have shown that women treated with coronary angioplasty have a higher incidence of procedural morbidity and mortality than men. METHODS: Gender differences in wave 1 of the National Heart, Lung and Blood Institute (NHLBI) Dynamic registry were evaluated. Baseline characteristics and outcomes in women in the Dynamic registry were compared with those in women in the 1985-1986 and 1993-1994 NHLBI Percutaneous Transluminal Coronary Angioplasty (PTCA) registries. RESULTS: Women were older with a higher prevalence of diabetes mellitus, hypertension, congestive heart failure, unstable angina and single vessel disease in comparison with men. Although procedural success and in-hospital death (2.2% vs. 1.3%), myocardial infarction (MI) (2.3% vs. 3.0%) and coronary artery bypass graft surgery (CABG) (1.3% vs. 1.4%) were similar in women and men, respectively, one-year mortality (6.5% vs. 4.3%, p = 0.02) and combined end point of death/MI/CABG (18.3% vs. 14.4%, p = 0.03) were higher in women than in men. After controlling for other factors, gender was not a significant predictor of death or death plus MI at one year. Despite a higher risk profile in women in the Dynamic registry in comparison with women in the 1985-1986 NHLBI PTCA registry, in-hospital death/MI/CABG was lower (6.0% vs. 11.6%, p < 0.001). CONCLUSIONS: Despite persistent high-risk characteristics in women, gender differences in outcomes in patients undergoing contemporary PCI have decreased, and outcomes in women have improved.

Aged↗
PubMed2002

Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI) in the modern era, the incidence and prognostic implications of acute renal failure (ARF) are unknown. METHODS AND RESULTS: With a retrospective analysis of the Mayo Clinic PCI registry, we determined the incidence of, risk factors for, and prognostic implications of ARF (defined as an increase in serum creatinine [Cr] >0.5 mg/dL from baseline) after PCI. Of 7586 patients, 254 (3.3%) experienced ARF. Among patients with baseline Cr <2.0, the risk of ARF was higher among diabetic than nondiabetic patients, whereas among those with a baseline Cr >2.0, all had a significant risk of ARF. In multivariate analysis, ARF was associated with baseline serum Cr, acute myocardial infarction, shock, and volume of contrast medium administered. Twenty-two percent of patients with ARF died during the index hospitalization compared with only 1.4% of patients without ARF (P<0.0001). After adjustment, ARF remained strongly associated with death. Among hospital survivors with ARF, 1- and 5-year estimated mortality rates were 12.1% and 44.6%, respectively, much greater than the 3.7% and 14.5% mortality rates in patients without ARF (P<0.0001). CONCLUSIONS: The overall incidence of ARF after PCI is low. Diabetic patients with baseline Cr values <2.0 mg/dL are at higher risk than nondiabetic patients, whereas all patients with a serum Cr >2.0 are at high risk for ARF. ARF was highly correlated with death during the index hospitalization and after dismissal.

Acute Kidney Injury↗
PubMed2002

Chronic endothelin receptor antagonism prevents coronary vasa vasorum neovascularization in experimental hypercholesterolemia.

OBJECTIVES: The purpose of this study was to test the hypothesis that endothelin (ET) receptor antagonism reduces coronary vasa vasorum neovascularization in experimental hypercholesterolemia. BACKGROUND: Experimental hypercholesterolemia is associated with increased expression of ET-1, an endothelium-derived peptide with vasoconstricting, mitogenic and angiogenic properties, in the coronary arterial wall as well as with vasa vasorum neovascularization. A pathomechanistic role of the endogenous ET system in vasa vasorum neovascularization in hypercholesterolemia has, however, remained uncertain so far. METHODS: Female domestic pigs were placed on a normal diet (N; n = 7) or on a hypercholesterolemic diet without (HC; n = 6) or with ET-A receptor antagonism (ABT-627, 4 mg/kg/day; HC + ET-A; n = 6). After 12 weeks, coronary vasa vasorum structure was assessed by three-dimensional microscopic computed tomography, expression of vascular endothelial growth factor (VEGF) within the coronary arterial wall by Western blotting and immunostaining. RESULTS: Compared with the N group, plasma concentrations of low-density lipoprotein cholesterol were higher in both the HC and HC + ET-A groups (36 +/- 3 mg/dl vs. 312 +/- 153 mg/dl and 303 +/- 113 mg/dl, p < 0.01). Vasa vasorum density was higher in the HC group compared with the N group (4.7 +/- 1.8 per mm(2) vs. 2.5 +/- 1.5 per mm(2); p < 0.05) and was preserved in the HC + ET-A group (3.2 +/- 0.7 per mm(2)). In parallel, increase in VEGF expression in the coronary arterial wall in the HC group was preserved in the HC + ET-A group. CONCLUSIONS: The current study demonstrates that chronic endothelin receptor antagonism prevents the increase in VEGF expression and vasa vasorum density of coronary arteries in experimental hypercholesterolemia. These findings support a role for the endogenous ET system in vasa vasorum neovascularization in early coronary atherosclerosis.

Animals↗
PubMed2002

Differential influence of diabetes mellitus on increased jeopardized myocardium after initial angioplasty or bypass surgery: bypass angioplasty revascularization investigation.

BACKGROUND: Data are absent that compare midterm angiographic outcome between patients with and without diabetes after initial percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG). Importantly, diabetes mellitus may differentially influence long-term survival after PTCA or CABG. METHODS AND RESULTS: Patients with multivessel coronary disease who were previously enrolled in the Bypass Angiopathy Revascularization Investigation to compare initial PTCA versus CABG (n=1829) and who had a reduction in jeopardized myocardium after initial revascularization and at least 1 angiogram during 5-year follow-up were analyzed (n=897). This included 369 CABG-treated patients (16% with diabetes) and 528 PTCA-treated patients (18% with diabetes). The influence of diabetes on angiographic increase in percentage of jeopardized myocardium after initial revascularization with either PTCA or CABG was investigated. Among PTCA patients, the mean percentage increase in total jeopardized myocardium was significantly greater in those with diabetes than in those without at 1-year protocol-directed angiography (42% versus 24%, P=0.05) and on the first clinically performed (unscheduled) angiogram within 30 months (63% versus 50%, P=0.01) but not at 5-year protocol-directed angiography (34% versus 26%, P=0.33). This excess midterm risk associated with diabetes persisted after statistical adjustment. In contrast, among CABG patients, diabetes was not associated with percentage increase in jeopardized myocardium at any angiographic follow-up interval. CONCLUSIONS: Presence of diabetes differentially influences worsening of jeopardized myocardium after initial PTCA compared with CABG. This differential effect occurs irrespective of whether follow-up angiography is undertaken for clinical or nonclinical purposes.

Aged↗
PubMed2002

The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions.

OBJECTIVES: We sought to determine the effect of varying degrees of renal insufficiency on death and cardiac events during and after a percutaneous coronary intervention (PCI). BACKGROUND: Patients with end-stage renal disease have a high mortality from coronary artery disease. Little is known about the impact of mild and moderate renal insufficiency on clinical outcomes after PCI. METHODS: Cardiac mortality and all-cause mortality were determined for 5,327 patients undergoing PCI from January 1, 1994, to August 31, 1999, at the Mayo Clinic, based on the estimated creatinine clearance or whether the patient was on dialysis. RESULTS: In-hospital mortality was significantly associated with renal insufficiency (p = 0.001). Even after successful PCI, one-year mortality was 1.5% when the creatinine clearance was > or =70 ml/min (n = 2,558), 3.6% when it was 50 to 69 ml/min (n = 1,458), 7.8% when it was 30 to 49 ml/min (n = 828) and 18.3% when it was < 30 ml/min (n = 141). The 18.3% mortality rate for the group with < 30 ml/min creatinine clearance was similar to the 19.9% mortality rate in patients on dialysis (n = 46). The mortality risk was largely independent of all other factors. CONCLUSIONS: Renal insufficiency is a strong predictor of death and subsequent cardiac events in a dose-dependent fashion during and after PCI. Patients with renal insufficiency have more baseline cardiovascular risk factors, but renal insufficiency is associated with an increased risk of death and other adverse cardiovascular events, independent of all other measured variables.

Aged↗
PubMed2002

Strain rate imaging for assessment of regional myocardial function: results from a clinical model of septal ablation.

BACKGROUND: Regional myocardial function assessment is essential in the management of coronary artery disease (CAD). Tissue Doppler imaging (TDI) by depicting local myocardial motion can potentially quantify regional myocardial function. Strain rate imaging (SRI) that depicts regional deformation is less susceptible to cardiac translation and tethering and may be superior to TDI for regional function analysis. We examined regional myocardial function using TDI and SRI in a unique clinical model of a small, discrete myocardial infarction. METHODS AND RESULTS: Ten patients with severely symptomatic septal hypertrophy underwent basal septal ablation via intracoronary alcohol injection and had TDI and SRI pre- and postablation. Invasive hemodynamics showed no appreciable change in global function. Peak systolic strain rate was significantly lower postablation versus preablation (-0.5 versus -1.2 s(-1), P<0.001) and when comparing infarct and noninfarct areas (-0.5 versus -1.5 s(-1), P<0.001). In contrast, peak systolic tissue velocities were similar pre- and postablation (3.9 versus 2.9 cm/s, P=0.16) and between infarct and noninfarct areas (2.9 versus 2.2 cm/s, P=0.13). SRI analysis demonstrated reduced systolic function in the peri-infarct zone and preserved systolic function in the remote nonischemic zone. CONCLUSION: In the clinical setting of a small, discrete infarct unaccompanied by changes in global function, SRI accurately depicted changes in regional function. These data suggest that SRI may be the optimal method for objective, quantitative assessment of regional myocardial dysfunction.

Cardiac Catheterization↗
PubMed2002

Pulse transmission coefficient: a novel nonhyperemic parameter for assessing the physiological significance of coronary artery stenoses.

OBJECTIVES: We sought to test the hypothesis that the pulse transmission coefficient (PTC) can serve as a nonhyperemic physiologic marker for the severity of coronary artery stenosis in humans. BACKGROUND: Coronary lesions may impair the transmission of pressure waves across a stenosis, potentially acting as a low-pass filter. The PTC is a novel nonhyperemic parameter that calculates the transmission of high-frequency components of the pressure signal through a stenosis. Thus, it may reflect the severity of the coronary artery stenosis. This study was designed to examine the correlation between PTC and fractional flow reserve (FFR) in patients with coronary artery disease. METHODS: Pressure signals were obtained by pressure guidewire in 56 lesions (49 patients) in the nonhyperemic state and were analyzed with a new algorithm that identifies the high-frequency components in the pressure signal. The PTC was calculated as the ratio between the distal and proximal high-frequency components of the pressure waveform across the lesion. The FFR measurements were assessed with intracoronary adenosine. RESULTS: There was a significant correlation between PTC and FFR (r = 0.81, p < 0.001). By using a receiver operating characteristic analysis, we identified a PTC < 0.60 (sensitivity 100%, specificity 98%) to be the optimal cutoff value for predicting an FFR < 0.75. CONCLUSIONS: Pulse transmission coefficient is a novel nonhyperemic parameter for the physiologic assessment of coronary artery stenoses. It correlates significantly with FFR and may predict an FFR < 0.75 with high accuracy. Pulse transmission coefficient may be useful as an adjunct measurement to FFR, especially in patients with microcirculatory disease and impaired maximal hyperemia.

Adult↗
PubMed2002

A tissue-engineered stent for cell-based vascular gene transfer.

Cell-based gene transfer using a stent platform would provide a significant advantage in terms of site-specific gene expression in the vasculature. The current study presents a novel stent design that allows stable in vivo transgene expression over a 4-week period in the vasculature. A mesh-stent coated with fibronectin provided an excellent platform for adherent porcine smooth muscle cells (SMC). Autologous porcine SMC were stably transduced with a plasmid encoding green fluorescence protein (GFP), seeded at high density in the mesh-stent, and deployed in the porcine coronary artery. Stable in vivo GFP expression within the mesh-stent (5.2 x 10(5) GFP-positive cells/cm(2) mesh) was demonstrated 1 month after implantation in the porcine coronary artery by fluorescence microscopy and flow cytometry. No significant change in GFP positive cell number within the stent occurred over a 1-month period in vivo when compared to preinsertion. Angiographic and histologic analysis revealed mild neointimal proliferation and no inflammatory infiltrate in the stented segment. This study has implications for treatment of cardiovascular and other diseases where long-term cell-based delivery of transgene is a desirable therapeutic option.

Animals↗
PubMed2002

Simvastatin preserves the structure of coronary adventitial vasa vasorum in experimental hypercholesterolemia independent of lipid lowering.

BACKGROUND: Previous studies have demonstrated that experimental hypercholesterolemia leads to neovascularization in the coronary artery vasa vasorum (VV). Recent evidence suggests that HMG-CoA reductase inhibitors (statins) have beneficial effects independent of lipid lowering. We aimed to determine the effect of simvastatin on coronary VV neovascularization, in the absence of cholesterol lowering. METHODS AND RESULTS: Pigs were randomized to 3 groups fed a normal (N), high cholesterol (HC), or HC+simvastatin (HC+S) diet for 12 weeks. The proximal left anterior descending artery was isolated, scanned with micro-CT, and reconstructed. Quantification of the VV density in serial cross-sections along the vessel was then performed. LDL cholesterol was similarly increased in HC and HC+S compared with N. There was an increase in both VV density (4.7+/-0.3 versus 2.7+/-0.2 n/mm(2); P<0.05) and vessel wall area (3.1+/-0.2 versus 1.8+/-0.1 mm(2); P<0.05) in HC compared with N. The VV density in HC+S was preserved compared with HC (3.0+/-0.2 n/mm(2); P<0.05), despite similar increase in vessel wall area compared with N (2.5+/-0.1 mm(2); P<0.05). Coronary artery tissue expression of VEGF was increased in HC but not in HC+S compared with N. In parallel, immunoreactivity for HIF-1alpha, VEGF, MMP-2, and MMP-9 was accentuated in the outer media in HC but not in HC+S compared with N. CONCLUSIONS: This study demonstrates that simvastatin attenuates hypoxia in the coronary artery wall and VV neovascularization in experimental hypercholesterolemia, despite no change in plasma lipids. These data are consistent with an additional mechanism for the vascular effects of the statins, independent of cholesterol lowering.

Animals↗
PubMed2002

Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting.

OBJECTIVES: We sought to determine whether clopidogrel is at least as efficacious as ticlopidine. BACKGROUND: Several trials have supported the enhanced safety and tolerability of clopidogrel compared with ticlopidine after coronary stent deployment. However, none of these individual trials were powered to detect possible differences in the efficacy for reducing ischemic end points. METHODS: Published data from trials and registries that compared clopidogrel with ticlopidine in patients receiving coronary stents were pooled, and a formal meta-analysis was performed. The rate of 30-day major adverse cardiac events (MACE), as defined in each trial, was used as the primary end point. RESULTS: There were a total of 13,955 patients. The pooled rate of major adverse cardiac events was 2.10% in the clopidogrel group and 4.04% in the ticlopidine group. After adjustment for heterogeneity in the trials, the odds ratio (OR) of having an ischemic event with clopidogrel, as compared with ticlopidine, was 0.72 (95% confidence interval [CI] 0.59 to 0.89, p = 0.002). Mortality was also lower in the clopidogrel group compared with the ticlopidine group-0.48% versus 1.09% (OR 0.55, 95% CI 0.37 to 0.82; p = 0.003). CONCLUSIONS: Based on all available evidence from randomized clinical trials or registries, clopidogrel, in addition to better tolerability and fewer side effects, is at least as efficacious as ticlopidine in reducing MACE. This finding may be due to the more rapid onset of an antiplatelet effect seen with the loading dose of clopidogrel, which was used in most of these studies, or to better patient compliance with clopidogrel therapy. Therefore, clopidogrel plus aspirin should replace ticlopidine plus aspirin as the standard antiplatelet regimen after stent deployment.

Aspirin↗
PubMed2002

Unrestricted availability of intracoronary stents is associated with decreased abrupt vascular closure rates and improved early clinical outcomes.

The purpose of this study was to determine whether the unrestricted availability of intracoronary stents is affecting abrupt vascular closure rates and early clinical outcomes. Intracoronary stents have improved procedural outcome despite their application in more complex lesions, but the impact of unrestricted availability of stents on abrupt closure and early clinical outcomes is unknown. Two cohorts were identified retrospectively from a coronary intervention registry: patients treated between 1988 and 1992 (n = 3,617) when stents were not generally available, and patients treated between 1994 and 1997 (n = 4,518) when stents were freely available. The late cohort patients consisted of more females; it also had greater comorbidity and more complex presentation. However, there was a significant reduction in the abrupt closure rates between the two time periods (7% vs. 4%, P < 0.0001). After adjusting for female gender, thrombus, and lesion angulation, the late cohort remained significantly associated with decreased odds of abrupt closure (odds ratio [OR] = 0.62, 95% upper and lower confidence intervals [CI] = 0.52-0.75, P = 0.0001). The late cohort also had decreased in-hospital mortality (OR = 0.91, CI = 0.86-0.95, P = 0.0002) and major adverse clinical event (OR = 0.93, CI = 0.91-0.96, P = 0.0001). Unrestricted availability of intracoronary stents is associated with reduced abrupt closure rates and improved early clinical outcomes among patients undergoing coronary intervention despite treatment of high-risk patients.

Acute Disease↗
PubMed2002

Rheolytic thrombectomy with Angiojet in thrombus-containing lesions.

The AngioJet thrombectomy device removes thrombus by creating a negative pressure and causing fragmentation of the thrombus. The objective was to study the safety and efficacy of this thrombectomy device during coronary interventions and to report the results of our experience. We studied 72 patients (mean age, 64.9 +/- 12.6 years; 79% males) who had an AngioJet procedure during coronary intervention; 33 (46%) had vein graft intervention. All patients had angiographic thrombus. Most patients presented either with unstable angina (54%) or acute myocardial infarction (32%) within 24 hr. The procedural success was high with AngioJet (93%). TIMI grade 3 flow was achieved in 79% of lesions treated with AngioJet. In-hospital mortality was 1.4%, death/Q-wave myocardial infarction was 4.2%, and the composite endpoint of death and Q-wave myocardial infarction/revascularization was 5.6% for patients undergoing AngioJet. Subgroup analysis of patients with vein graft intervention demonstrated high procedural success in those undergoing AngioJet (91%). At 1-year follow-up of the successful percutaneous interventions with AngioJet, the mortality, death/Q-myocardial infarction, and composite endpoint rates were 10%, 13.3%, and 35.5%, respectively. Long-term event-free survival was worse in vein graft interventions. The incidence of death, death/myocardial infarction, or composite endpoints at 1 year was 16%, 19%, and 46%, respectively. High procedural success can be achieved with the AngioJet thrombectomy device in lesions containing thrombus. It is effective in both native coronary arteries and vein graft interventions. However, the long-term outcome of patients with vein graft intervention was worse.

Aged↗