Clinical and experimental evidences on the prothrombotic properties of neutrophils

Epidemiologic studies have shown that the neutrophil count correlates with the risk of myocardial infarction and stroke and identify patients more susceptible to reinfarction and in-hospital death. In particular, neutrophils action was initially associated to blood rheological changes, or to the effect of neutrophil-derived eicosanoids or proteases. Animal models indicate that platelet-leukocyte P-selectin dependent cross-talk contributes to fibrin deposition during in vivo thrombus formation. In fact, platelet P-selectin, through its leukocyte counter-receptor PSGL-1, determines the activation of leukocyte ?2 integrins, the binding of fibrinogen and the expression of tissue factor on leukocyte surface. Monocytes stimulated in vitro with LPS, PMA and P-selectin synthesize and express tissue factor. fMLP, P-selectin, TNFalpha and C5a are effective stimuli that trigger the synthesis and expression of biologically active tissue factor in neutrophils. The experimental evidence well agrees with clinical observations: patients with acute coronary syndromes, acute respiratory distress syndrome, antiphospholipid syndromes, giant cell arteritis and myeloproliferative syndromes have increased the expression of tissue factor on leukocyte surface. Moreover circulating neutrophils express mRNA codifying for fulllength and/or alternatively spliced tissue factor, suggesting a new important link between thrombosis and inflammation. All together, clinical and experimental evidence suggest that the leukocyte thrombogenic profile is a relevant player in patients with a high risk of thromboembolic events and possibly represents a suitable target for molecular intervention

Cardiac syndrome X: Clinical characteristics and left ventricular function Long-term follow-up study

Objectives.Our aim was to study the clinical characteristics and evolution of symptoms and left ventricular function in a clinically homogeneous group of patients with syndrome X (angina pectoris, positive exercise test results and normal coronary arteriograms).Background.The syndrome of angina with normal coronary arteriograms is heterogeneous and encompasses different pathogenetic entities. These characteristics may contribute to the existing controversy concerning the cause of syndrome X.Methods.We studied 99 patients with syndrome X (78 women, 21 men; mean age ± SD 48.5 ± 8 years). All underwent clinical characterization, ambulatory electrocardiographic (ECG) monitoring and echocardiographic assessment of left ventricular function during a follow-up period of 7 ± 4 years.Results.The syndrome was more common in women than in men. Of the women, 61.5% were postmenopausal before the onset of chest pain. All 99 patients had exertional angina, and 41 also had rest angina. The average duration of episodes of chest pain was > 10 min in 53% of patients. Sublingual nitrate was effective for relief of pain in 42% of patients. Transient ST segment depression was observed during ambulatory ECG monitoring in 64 patients and myocardial perfusion abnormalities in 22. During the first stage of the exercise test, 32 patients had an increase > 20 mm Hg in systolic blood pressure and showed an earlier onset of ST depression and shorter exercise time than did patients whose blood pressure increased ≤20%. During follow-up, no deaths or myocardial infarctions occurred, ventricular function was unchanged (shortening fraction 35.4 ± 4% vs. 35.6 ± 3%; heart failure developed in only one patient), systemic hypertension occurred in eight patients and conduction disturbances in four. Symptoms lessened in 11 patients, were variable or unchanged in 64 and worsened in 24.Conclusions.Syndrome X, as defined in this study, occurs predominantly in postmenopausal women. Patients usually have chest pain typical for angina, but conventional antianginal treatment is not often successful. Myocardial perfusion abnormalities occur in a small proportion of patients. Long-term survival is not adversely affected, and deterioration of cardiac function rarely occurs

Large, sustained cardiac lipid peroxidation and reduced antioxidant capacity in the coronary circulation after brief episodes of myocardial ischemia

AbstractOBJECTIVESWe sought to investigate whether a brief episode of myocardial ischemia produces a detectable cardiac oxidative stress in patients undergoing elective coronary angioplasty (PTCA).BACKGROUNDAlthough cardiac oxidative stress has been clearly demonstrated in experimental models of ischemia-reperfusion, its presence in patients after transient myocardial ischemia is still unclear.METHODSIn order to evaluate oxidative stress in ischemic cardiac regions, plasma conjugated dienes (CD), lipid hydroperoxides (ROOHs) and total antioxidant capacity (TRAP), independent indexes of oxidative stress, were measured in the aorta and great cardiac vein (GCV) before (t0), 1, (t1), 5 (t5) and 15 min (t15) after first balloon inflation in 15 patients undergoing PTCA on left anterior descending coronary artery (Group 1); six patients with right coronary artery stenosis (Group 2), which is not drained by the GCV, were studied as controls.RESULTSIn Group 1 at baseline, CD and ROOHs levels were higher in GCV than in aorta (p < 0.01 for both), and TRAP levels were lower (p < 0.01). Aortic levels of CD, ROOHs and TRAP did not change at any time after t0; venous levels of CD and ROOHs levels markedly increased at t1, at t5and remained elevated at t15(p < 0.01 for all comparisons vs. t0); venous levels of TRAP decreased at t1and t5(p < 0.01 vs. t0) and returned to normal at t15. In Group 2, CD, ROOHs and TRAP levels were similar in the aorta and GCV and did not change throughout the study.CONCLUSIONSShort episodes of myocardial ischemia during PTCA induce a sustained oxidative stress, which is detectable in the venous effluent of reperfused myocardium

Transcript of The Dory Derby Accident

This story is an excerpt from a longer interview that was collected as part of the Launching through the Surf: The Dory Fleet of Pacific City project. In this story, Don Grotjohn recounts an accident that occurred during a Dory Derby competition

Frequency and severity of myocardial perfusion abnormalities using Tc-99m MIBI SPECT in cardiac syndrome X

BACKGROUND: Cardiac syndrome X is defined by a typical angina pectoris with normal or near normal (stenosis <40%) coronary angiogram with or without electrocardiogram (ECG) change or atypical angina pectoris with normal or near normal coronary angiogram plus a positive none-invasive test (exercise tolerance test or myocardial perfusion scan) with or without ECG change. Studies with myocardial perfusion imaging on this syndrome have indicated some abnormal perfusion scan. We evaluated the role of myocardial perfusion imaging (MPI) and also the severity and extent of perfusion abnormality using Tc-99m MIBI Single Photon Emission Computed Tomography (SPECT) in these patients. METHODS: The study group consisted of 36 patients with cardiac syndrome X. The semiquantitative perfusion analysis was performed using exercise Tc-99m MIBI SPECT. The MPI results were analyzed by the number, location and severity of perfusion defects. RESULTS: Abnormal perfusion defects were detected in 13 (36.10%) cases, while the remaining 23 (63.90%) had normal cardiac imaging. Five of 13 (38.4%) abnormal studies showed multiple perfusion defects. The defects were localized in the apex in 3, apical segments in 4, midventricular segments in 12 and basal segments in 6 cases. Fourteen (56%) of all abnormal segments revealed mild, 7(28%) moderate and 4 (16%) severe reduction of tracer uptake. No fixed defects were identified. The vessel territories were approximately the same in all subjects. The Exercise treadmill test (ETT) was positive in 25(69%) and negative in 11(30%) patients. There was no consistent pattern as related to the extent of MPI defects or exercise test results. CONCLUSION: Our study suggests that multiple perfusion abnormalities with different levels of severity are common in cardiac syndrome X, with more than 30 % of these patients having at least one abnormal perfusion segment. Our findings suggest that in these patients microvascular angina is probably more common than is generally believed

Cerebrovascular mental stress reactivity is impaired in hypertension

<p>Abstract</p> <p>Background</p> <p>Brachial artery reactivity in response to shear stress is altered in subjects with hypertension. Since endothelial dysfunction is generalized, we hypothesized that carotid artery (CA) reactivity would also be altered in hypertension.</p> <p>Purpose</p> <p>To compare (CA endothelium-dependent vasodilation in response to mental stress in normal and hypertensive subjects.</p> <p>Methods</p> <p>We evaluated CA reactivity to mental stress in 10 young healthy human volunteers (aged 23 ± 4 years), 20 older healthy volunteers (aged 49 ± 11 years) and in 28 patients with essential hypertension (aged 51 ± 13 years). In 10 healthy volunteers and 12 hypertensive subjects, middle cerebral artery (MCA) PW transcranial Doppler was performed before and 3 minutes after mental stress.</p> <p>Results</p> <p>Mental stress by Stroop color word conflict, math or anger recall tests caused CA vasodilation in young healthy subjects (0.61 ± 0.06 to 0.65 ± 0.07 cm, p < 0.05) and in older healthy subjects (0.63 ± 0.06 to 0.66 ± 0.07 cm, p < 0.05), whereas no CA vasodilation occurred in hypertensive subjects (0.69 ± 0.06 to 0.68 ± 0.07 cm; p, NS). CA blood flow in response to mental stress increased in young healthy subjects (419 ± 134 to 541 ± 209 ml, p < 0.01 vs. baseline) and in older healthy subjects (351 ± 114 to 454 ± 136 ml, p < 0.01 vs. baseline) whereas no change in blood flow (444 ± 143 vs. 458 ± 195 ml; p, 0.59) occurred in hypertensive subjects. There was no difference in the CA response to nitroglycerin in healthy and hypertensive subjects. Mental stress caused a significant increase in baseline to peak MCA systolic (84 ± 22 to 95 ± 22 cm/s, p < 0.05), diastolic (42 ± 12 to 49 ± 14 cm/s, p < 0.05) as well as mean (30 ± 13 to 39 ± 13 cm/s, p < 0.05) PW Doppler velocities in normal subjects, whereas no change in systolic (70 ± 18 to 73 ± 22 cm/s, p < 0.05), diastolic (34 ± 14 to 37 ± 14 cm/s, p = ns) or mean velocities (25 ± 9 to 26 ± 9 cm/s, p = ns) occurred in hypertensive subjects, despite a similar increase in heart rate and blood pressure in response to mental stress in both groups.</p> <p>Conclusion</p> <p>Mental stress produces CA vasodilation and is accompanied by an increase in CA and MCA blood flow in healthy subjects. This mental stress induced CA vasodilation and flow reserve is attenuated in subjects with hypertension and may reflect cerebral vascular endothelial dysfunction. Assessment of mental stress induced CA reactivity by ultrasound is a novel method for assessing the impact of hypertension on cerebrovascular endothelial function and blood flow reserve.</p

Cyclical coronary flow reductions in conscious dogs equipped with ameroid constrictors to produce severe coronary narrowing

In conscious dogs equipped with ameroid constrictors to produce gradual coronary occlusion, coronary flow velocity was monitored prior to complete occlusion when coronary constriction was severe (resting flow velocity reduced by 10–50% from control recordings made 7–10 days after ameroid implantation). In six of the ten dogs, we observed spontaneous cyclical variations in coronary flow velocity, characterized by gradual reduction in flow followed by very abrupt restoration of flow. The cyclic coronary flow reductions were observed between 20 and 31 days after ameroid implantation. These changes in flow bear striking similarity to those observed by previous investigators using anesthetized, open-chest canine preparations, in which the role of platelets was clearly demonstrated. Consequently, we hypothesize that spontaneous platelet aggregation and de-aggregation within the severely narrowed coronary lumen (enclosed by the ameroid constrictors) could account for our observations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41746/1/395_2005_Article_BF01906748.pd

Acute ischemic heart disease and interventional cardiology: a time for pause

BACKGROUND: A major change has occurred in the last few years in the therapeutic approach to patients presenting with all forms of acute coronary syndromes. Whether or not these patients present initially to tertiary cardiac care centers, they are now routinely referred for early coronary angiography and increasingly undergo percutaneous revascularization. This practice is driven primarily by the angiographic image and technical feasibility. Concomitantly, there has been a decline in expectant or ischemia-guided medical management based on specific clinical presentation, response to initial treatment, and results of noninvasive stratification. This 'tertiarization' of acute coronary care has been fuelled by the increasing sophistication of the cardiac armamentarium, the peer-reviewed publication of clinical studies purporting to show the superiority of invasive cardiac interventions, and predominantly supporting (non-peer-reviewed) editorials, newsletters, and opinion pieces. DISCUSSION: This review presents another perspective, based on a critical reexamination of the evidence. The topics addressed are: reperfusion treatment of ST-elevation myocardial infarction; the indications for invasive intervention following thrombolysis; the role of invasive management in non-ST-elevation myocardial infarction and unstable angina; and cost-effectiveness and real world considerations. A few cases encountered in recent practice in community and tertiary hospitals are presented for illustrative purposes The numerous and far-reaching scientific, economic, and philosophical implications that are a consequence of this marked change in clinical practice as well as healthcare, decisional and conflict of interest issues are explored. SUMMARY: The weight of evidence does not support the contemporary unfocused broad use of invasive interventional procedures across the spectrum of acute coronary clinical presentations. Excessive and unselective recourse to these procedures has deleterious implications for the organization of cardiac health care and undesirable economic, scientific and intellectual consequences. It is suggested that there is need for a new equilibrium based on more refined clinical risk stratification in the treatment of patients who present with acute coronary syndromes