Biomedical subjects

Mark R Adams

Publications and source records attributed to Mark R Adams.

11 recordsLinked to original sources

PubMed2006

Endothelial dysfunction and restenosis following percutaneous coronary intervention.

BACKGROUND: Restenosis remains an important limitation of PCI. Although local factors such as small vessel diameter and systemic factors such as diabetes explain some of its incidence, it nevertheless also occurs in low-risk patients. We hypothesize that endothelial dysfunction may be an independent risk factor in some of these cases. METHODS: 20 patients who had previously undergone PCI were studied at cardiac catheterization (10 with restenotic lesions were matched to 10 without restenosis). Infusion of multiple concentrations of acetylcholine (ACh) and nitroglycerine (GTN) were made via a 3F infusion catheter into the target artery. Following infusion, changes in diameter of segments proximal and distal to the PCI site were measured. RESULTS: There was a significant impairment in endothelium-dependent dilatation at the maximal dose of acetylcholine in those with restenosis compared to those without restenosis, both proximal and distal to the stented area (proximal; 11.5+/-7.0% versus -20.9+/-9.0% p<0.001, distal; 12.0+/-3.1% versus -17.8+/-8.1% p<0.001), but there was no difference in the response to GTN. There was a significant correlation between the endothelium-dependent dilatation response and the percent restenosis (r=-0.65, p=0.003). CONCLUSIONS: Coronary endothelium-dependent dilatation is reduced in subjects with restenosis in arterial segments separate from the stented lesion. This supports a hypothesis that endothelial dysfunction contributes to the development of restenosis, following percutaneous coronary intervention.

Acetylcholine↗

PubMed2006

Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging.

Oxidative stress is implicated in atherogenesis, yet most clinical trials with antioxidants, particularly vitamin E, have failed to protect against atherosclerotic diseases. A striking exception is probucol, which retards atherosclerosis in carotid arteries and restenosis of coronary arteries after angioplasty. Because probucol has in vitro cellular-protective effects independent of inhibiting lipid oxidation, we investigated the mode of action of probucol in vivo. We used three models of vascular disease: apolipoprotein E-deficient mice, a model of atherosclerosis; rabbit aortic balloon injury, a model of restenosis; and carotid injury in obese Zucker rats, a model of type 2 diabetes. Unexpectedly, we observed that the phenol moieties of probucol were insufficient, whereas its sulphur atoms were required for protection. Probucol and its sulphur-containing metabolite, but not a sulphur-free phenolic analogue, protected via cell-specific effects on inhibiting macrophage accumulation, stimulating reendothelialization, and inhibiting vascular smooth muscle cell proliferation. These processes were mediated via induction of heme oxygenase-1 (HO-1), an activity not shared by vitamin E. Our findings identify HO-1 as the molecular target of probucol. They indicate 2-electron rather than radical (1-electron) oxidants as important contributors to atherogenesis, and point to novel lead compounds for therapeutic intervention against atherosclerotic diseases.

Animals↗

PubMed2006

Predictors of long-term outcome following percutaneous coronary intervention in patients with type 2 diabetes mellitus.

OBJECTIVES: Diabetes has a major impact on the long-term outcome following percutaneous coronary intervention, being a major risk factor for restenosis. We aimed at assessing the clinical, hemodynamic and angiographic factors that predict outcome in this high-risk group. METHODS: Diabetic patients who underwent percutaneous coronary intervention during the period 1996-2000 were identified retrospectively, and their medical records, hemodynamic data and angiograms studied at the time of their procedure. Angiographic data were analyzed to determine procedural factors, quantitative angiographic results of their percutaneous coronary intervention and severity and extent scores of coronary artery disease. Clinical follow-up was obtained in 99.7% to a mean time of 782+/-153 days after percutaneous coronary intervention. RESULTS: A total of 327 consecutive diabetic patients underwent percutaneous coronary intervention on 389 lesions. The overall procedural success rate was 96.2%; however, during follow-up, 40.2% of patients had an adverse cardiac event. The strongest independent predictors of adverse outcome were presence of renal disease, need for medical diabetic treatment, and the extent of coronary artery disease as assessed by the extent score, but not the duration of diabetes or glycemic control. Other factors, which are often predictive of short-term outcome in a general population, such as vessel diameter, lesion length, and severity of coronary artery disease, were not predictive of outcome. CONCLUSIONS: In patients with type 2 diabetes mellitus, the extent of the coronary arteries involved with atheroma as well as systemic factors such as renal involvement are the best predictors of long-term outcome following percutaneous coronary intervention.

Aged↗

PubMed2005

Safety of coronary angioplasty to chronic total occlusions.

Percutaneous transluminal coronary angioplasty (PTCA) of chronic total occlusions (CTO) is not performed routinely in some centres due to concerns of low procedural success rates and high rates of short-term complications. This retrospective study examines the safety of PTCA to CTO in 100 consecutive cases compared to 100 matched controls. Success rate was 79% for CTO versus 98% for controls (p<0.001), however 5% of CTO patients had a cardiac enzyme rise compared to 13% of controls (p<0.05) and 0% of CTO patients compared to 6% of controls had a significant enzyme rise (p=0.03). These results suggest that PTCA to CTO can be carried out successfully in the majority of patients with only a relatively small risk of myocardial necrosis.

Angioplasty, Balloon, Coronary↗

PubMed2005

Endothelial dysfunction occurs in peripheral circulation patients with acute and stable coronary artery disease.

Atherosclerosis is a diffuse, systemic process. In addition, acute coronary syndromes (ACS) are associated with inflammatory marker elevations that are hypothesized to affect the function of nonculprit coronary as well as peripheral vessels. We investigated whether femoral vascular reactivity and/or fibrinolytic capacity are impaired in ACS patients over and above any dysfunction associated with stable coronary artery disease. Patients undergoing diagnostic coronary angiography (n = 42 total, 14 patients/group) were recruited into three groups as follows: 1) stable coronary syndromes (SAP group), 2) ACS as defined by rest angina with ECG changes and troponin rise (ACS group), and 3) angiographically normal coronary arteries (control group). After diagnostic coronary angiography, femoral artery endothelial and smooth muscle function were assessed by infusing acetylcholine (ACh) and nitroglycerin (GTN), and tissue-type plasminogen activator (t-PA) release across the femoral circulation was measured as the difference between arterial and venous concentrations before and after ACh and GTN stimulation. There were no significant differences between groups in relevant baseline characteristics apart from significantly higher C-reactive protein levels and reduced net t-PA release in the ACS group at baseline (P < 0.05). The ACS and SAP groups had equivalent angiographic severity of coronary artery disease. Endothelium-dependent dilatation was significantly higher in control individuals (14.9 +/- 9.1%; P < 0.001) compared with either stable patients (2.3 +/- 8.1%) or those with unstable syndromes (2.6 +/- 8.9%, who were similar to each other; P = not significant). Although baseline t-PA release was impaired in the ACS patients (0.09 +/- 0.06 compared with 0.39 +/- 0.33 and 0.49 +/- 0.56 ng/ml; P = 0.03), stimulation of t-PA release by ACh and GTN occurred only in the control subjects and not in the ACS or SAP patients. Coronary artery disease is associated with impaired endothelium-dependent dilatation and impaired stimulation of t-PA release in the systemic circulation. These aspects of endothelial dysfunction, however, were equally severe in acute and chronic coronary syndrome patients.

Acetylcholine↗

PubMed2003

Endothelial dysfunction as a predictor of acute coronary syndromes.

Endothelial dysfunction is a key early event in atherogenesis and is integral in the onset of acute coronary syndromes. Disruption of the normal endothelial functions leads to loss of vasomotor control, reduced production of nitric oxide, formation of a procoagulant surface, and promotion of inflammation. These events may lead to destabilization of atherosclerotic plaques and the onset of acute coronary syndromes. There are several direct and indirect ways of assessing endothelial dysfunction in vivo. Several of these measures of endothelial dysfunction have been shown to correlate with increased risk of adverse cardiovascular outcomes.

Acute Disease↗

PubMed2002

Stent deployment within a guide catheter aids removal of a fractured buddy wire.

We report a case of fractured buddy wire that was successfully removed by deploying a stent within the guide catheter, trapping the fractured segment of wire between stent and endoluminal surface of the guide catheter. This technique provides an alternative to either percutaneous snare or surgical intervention.

Angioplasty, Balloon, Coronary↗

PubMed2002

Rescue percutaneous coronary intervention following coronary artery bypass graft--a descriptive analysis of the changing interface between interventional cardiologist and cardiac surgeon.

BACKGROUND: Despite decreasing rates of acute and subacute complications of percutaneous coronary intervention (PCI), these procedures are generally only performed in centers where it is possible for failed PCI to be treated by rescue coronary artery bypass graft (CABG). Case reports and case series have documented successful PCI following failed CABG. We sought to confirm this decrease in the need for rescue CABG following failed PCI and to examine trends in the utilization of rescue PCI following failed CABG. HYPOTHESIS: The interface between interventional cardiologist and cardiac surgeon is characterized by changing practice patterns and resource utilization. METHODS: We examined the medical records of all patients admitted to the Brigham and Women's Hospital over a 7-year period and identified 169 patients who required both PCI and CABG during the same hospital admission. We describe and compare three predetermined groups of patients defined by the sequence of, and indication for, the relevant myocardial revascularization procedures. RESULTS: In all, 100 patients required CABG for failed PCI, 46 patients had planned hybrid procedures involving both CABG and PCI, and 23 patients required PCI following failed CABG. There was a decrease in the need for rescue CABG following failed PCI, both in total numbers and as a percentage of total cases (2.5% in 1994 and 0.22% in 1999). There was a simultaneous increase in the utilization of rescue PCI following failed CABG (0% in 1994 and 1.6% in 2000). Hybrid procedures were identified as a source of innovative solutions to a variety of challenging clinical problems. CONCLUSIONS: Changing patterns of resource utilization should be considered when planning hospital facilities and patient triage, and these patients undergoing percutaneous or surgical revascularization may benefit from close cooperation between the cardiac surgeon and the interventional cardiologist.

Aged↗

PubMed2002

Clopidogrel inhibits shear-induced platelet function.

We enrolled 17 healthy adult volunteers and measured platelet hemostasis time (PHT) and collagen-induced thrombus formation (CITF) before and after the oral administration of 300 mg of clopidogrel utilizing the Xylum Clot Signature Analyzer. We documented a statistically significant 30% prolongation of the PHT from 291+/-13 (SE) seconds to 376+/-31 (SE) s (P=0.037). There was a 7% prolongation of the CITF from 347+/-10 to 371+/-17 (SE) s (P=0.245). This study suggests that the Xylum Clot Signature Analyzer can measure changes in platelet function in response to a modest platelet inhibitor, and may be a useful clinical tool for the monitoring of antiplatelet therapies in patients.

Adult↗

PubMed2002

Coronary collateralization: determinants of adequate distal vessel filling after arterial occlusion.

BACKGROUND: The protective effect of collateral vessels in coronary artery disease (CAD) is well established. Little is known, however, about factors that influence collateral formation. METHODS: We studied the coronary angiograms of 200 consecutive patients with single-vessel coronary artery occlusion. Patients were excluded if obstructive stenoses were present in other vessels or if prior revascularization had been undertaken. Collateral circulation to the occluded artery was graded as 'poor' (no or incomplete filling) or 'rich' (complete filling). Patient characteristics, including mode of presentation, medications and CAD risk factors, were assessed. RESULTS: Positive univariate correlates of rich collaterals included increasing age [odds ratio (OR) 1.03, P = 0.016], 'statin' use (OR 2.50, P = 0.005), nitrate use (OR 1.96, P = 0.034), calcium-channel blocker (CCB) use (OR 4.07, P < 0.001), presentation with stable angina (OR 2.34, P = 0.006), longer time since diagnosis of CAD (OR 1.12, P = 0.002) and history of hyperlipidemia (OR 3.55, P < 0.001). Significantly poorer collateralization was observed in the setting of acute myocardial infarction (MI) (OR 0.23, P < 0.001), diabetes mellitus (OR 0.33, P = 0.003), impaired left ventricular function (OR 0.64, P = 0.015) and occlusion of the left anterior descending coronary artery (LAD) (OR 0.28, P < 0.001). On multivariate analysis, rich collateralization was associated with hyperlipidemia (P = 0.003) and CCB use (P = 0.028). Independent predictors of poor collaterals were presence of diabetes (P < 0.001), LAD occlusion (P = 0.001) and presentation with acute MI (P = 0.017). CONCLUSION: Diabetes mellitus, occlusion of the LAD and presentation with acute MI are independently associated with poor distal vessel collateralization, whereas hyperlipidemia and use of CCBs are associated with rich collateralization. Factors determining coronary collateral formation may in turn influence outcomes after coronary artery occlusion.

Australia↗

PubMedDate not supplied

Clinical assessment of endothelial function.

The endothelium is crucial in the maintenance of normal vascular function and disturbance of this balance is a key early event in the development of vascular disease. A wide range of techniques currently exists for assessment of endothelial function in both the coronary and the peripheral vasculature. Many of these in vivo tests have concentrated on measuring nitric oxide bioavailability, however more recently methods for measuring other vascular parameters, such as tissue-plasminogen activator release, have been used. Furthermore indirect systemic measurements of endothelial function and endothelial progenitor cells have been investigated. These methods have given great insights into the pathophysiology of atherosclerosis and have aided in the development of a number of antiatherosclerotic therapies. Importantly the methods used to date for assessing endothelial function in vivo are accurate, reproducible and correlate with the future risk of cardiovascular events. The development of new techniques and the constant refinement of established techniques suggest that many more insights are to be gained from clinical assessment of endothelial function.

Brachial Artery↗