bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise-induced hypotension in a male population. Criteria, causes, and prognosis.
Authors: Dubach P , Froelicher V F , Klein J , Oakes D , Grover-McKay M , Friis R
Published: June 2011

The objective of this study was to demonstrate the causes, optimal definition, and predictive value of exercise-induced hypotension occurring during treadmill testing. This study included all patients referred for clinical reasons to the Long Beach Veterans Administration Medical Center treadmill laboratory and then followed for a 2-year period for cardiac events. The population consisted of 2,036 patients who underwent testing from April 4, 1984, to May 7, 1987, 131 of whom exhibited exercise-induced hypotension (6.4%). We found that exercise-induced hypotension is usually related to myocardial ischemia or myocardial infarction, is best defined as a drop in systolic blood pressure during exercise below the standing preexercise value, and indicates a significantly increased risk for cardiac events (3.2-fold, p less than 0.005). This increased risk was not found in those having no previous myocardial infarction or no signs or symptoms of ischemia during the exercise test, and the increased risk was also not found in those undergoing a treadmill test within 3 weeks after a myocardial infarction. Exercise-induced hypotension appeared to be reversed by revascularization procedures, but confirmation of a beneficial effect on survival requires a randomized trial. The clinical importance of this study is that we have demonstrated that a drop in systolic blood pressure below standing preexercise values during treadmill testing indicates an increased risk for cardiac events except in certain subsets of patients.
Platelet thrombus formation on collagen type I. A model of deep vessel injury. Influence of blood rheology, von Willebrand factor, and blood coagulation.
Authors: Badimon L , Badimon J J , Turitto V T , Vallabhajosula S , Fuster V
Published: June 2011

Collagen type I is a major component of atherosclerotic vessel wall that is exposed on deep vessel injury, such as in balloon angioplasty or plaque rupture. Collagen type I from pig Achilles tendon was mounted in a tubular perfusion chamber placed within an extracorporeal circuit (carotid artery to jugular vein). The material was exposed to blood from normal pigs (n = 13), severe homozygous von Willebrand factor (vWF)-deficient pigs (vWF less than 3%) (n = 6), and heterozygous vWF-deficient pigs (vWF = 24%) (n = 2). Thrombus formation was measured by autologous 111In-platelet labeling and by ultrastructural morphology. Heparinized and native blood from these pigs was perfused over the substrate for 3 and 5 minutes at local shear rates from 212 to 3,380/sec. On collagen type I exposed to nonanticoagulated blood, for all exposure times studied, thrombus formation in the absence of vWF was significantly reduced at high shear rate typical of stenotic areas but not at low shear rate typical of unobstructed medium-size arteries. A similar inhibition in thrombus formation due to vWF deficiency was observed in both heparinized and native blood; however, thrombus formation was significantly more reduced (p less than 0.05) in the presence of heparin, presumably due to the lack of stability of the accumulated platelets in the absence of fibrin formation. Intermediate levels of vWF, as in heterozygous von Willebrand's disease (vWD), support platelet deposition to extents not significantly different from normal conditions. Therefore, on collagen type I, both the activation of blood coagulation proteins and the presence of vWF contribute significantly to the platelet-platelet interactions necessary for thrombus formation. The effect of vWF occurs primarily at high shear conditions typical intravascularly of flow at the apex of advanced stenotic lesions; thus, these findings may suggest that the absence of vWF may be protective against the development of acute thrombosis in these regions.
High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.
Authors: Gordon D J , Probstfield J L , Garrison R J , Neaton J D , Castelli W P , Knoke J D , Jacobs D R , Bangdiwala S , Tyroler H A
Published: June 2011

The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.
Development of coronary heart disease in familial hypercholesterolemia.
Authors: Mabuchi H , Koizumi J , Shimizu M , Takeda R
Published: June 2011

We studied the development of coronary artery disease in 10 homozygous and 692 heterozygous patients with familial hypercholesterolemia. Seventy-five (22%) male heterozygotes and 35 (10%) female heterozygotes were affected by myocardial infarction, which was first noted in men in the 3rd decade of life and in women in the 4th decade of life. Thirty-eight (70%) out of the deceased 54 heterozygous patients died of coronary heart disease. The mean age at death was significantly less in male heterozygotes (54 years) than in female heterozygotes (69 years). Five homozygous and 105 male and 56 female heterozygous patients received coronary angiographic evaluation. The regression equations between age (X) and coronary stenosis index (Y) obtained by assigning score (0 to 5) to each of 15 coronary artery segments were Y = 1.57X - 20.43 (r = 0.956, p less than 0.05) in the homozygotes, Y = 0.52X - 9.11 (r = 0.438, p less than 0.001) in the male heterozygotes, and Y = 0.47X - 12.54 (r = 0.343, p less than 0.01) in the female heterozygotes. From these data, we can assume that coronary artery stenosis detectable by angiography will occur after 17 and 25 years of age in male and female heterozygotes, respectively, and the treatment of heterozygotes with lipid-lowering drugs can be delayed until late adolescence.
Evidence of endothelial dysfunction in angiographically normal coronary arteries of patients with coronary artery disease.
Authors: Werns S W , Walton J A , Hsia H H , Nabel E G , Sanz M L , Pitt B
Published: June 2011

Acetylcholine causes endothelium-dependent dilation of normal arteries in most animal species. The effect of acetylcholine on normal human coronary arteries is controversial. Pathologic studies and epicardial echocardiography have shown that diffuse atherosclerosis is often present despite angiographic evidence of discrete coronary artery disease (CAD). Therefore, we postulated that acetylcholine would cause vasoconstriction of coronary arteries that are angiographically normal in patients with CAD. Coronary artery diameter, measured by automated quantification of digitized cineangiograms, was determined before and after the intracoronary infusion of 0.2 mM acetylcholine at 0.8-1.6 ml/min. The diameter of stenotic or irregular segments of six atherosclerotic coronary arteries decreased from 1.80 +/- 0.42 mm before acetylcholine to 1.26 +/- 0.46 mm after acetylcholine (p = 0.0025). Acetylcholine had a significantly different effect on the diameter of two groups of coronary arteries that are angiographically normal. Acetylcholine caused a 0.16 +/- 0.09-mm increase in the diameter of 14 normal coronary arteries in patients without CAD, whereas it caused a 0.26 +/- 0.12-mm decrease in the diameter of 14 normal coronary arteries in patients with CAD (p less than 0.01). Thus, the normal response to intracoronary acetylcholine is vasodilation, suggesting that endothelium-derived relaxing factor is released from normal human coronary endothelium. The vasoconstrictive effect of acetylcholine in the angiographically normal coronary arteries of patients with CAD suggests the presence of a diffuse abnormality of endothelial function.
Beta-adrenergic stimulation with isoproterenol enhances left ventricular diastolic performance in hypertrophic cardiomyopathy despite potentiation of myocardial ischemia. Comparison to rapid atrial pacing.
Authors: Udelson J E , Cannon R O , Bacharach S L , Rumble T F , Bonow R O
Published: June 2011

Impaired left ventricular relaxation and filling is an important pathophysiologic mechanism in hypertrophic cardiomyopathy. To determine whether isoproterenol, known to improve relaxation in isolated cardiac muscle, could favorably modify this effect, we assessed simultaneous left ventricular volume and regional systolic asynchrony (by radionuclide angiography), left ventricular pressure (by micromanometer catheters), and lactate metabolism in 12 patients with hypertrophic cardiomyopathy. Pressure-volume relations were studied during atrial pacing stress to induce myocardial ischemia and during isoproterenol infusion to similar heart rates. Angina occurred in 10 patients with pacing and in 11 patients during isoproterenol infusion; lactate consumption was reduced in nine patients during isoproterenol compared with pacing, including five patients who produced lactate with isoproterenol. During isoproterenol compared with pacing, peak left ventricular pressure was higher (205 +/- 33 vs. 142 +/- 21 mm Hg, p less than 0.001), ejection fraction was higher (77 +/- 10% vs. 71 +/- 12%, p less than 0.02), and regional systolic nonuniformity was diminished. Despite ischemia, these changes in load and nonuniformity during isoproterenol were associated with enhanced diastolic function compared with pacing tachycardia: isoproterenol reduced T 1/2, the half-time of pressure decline after peak negative dP/dt (from 46 +/- 10 to 33 +/- 6 msec, p less than 0.001), shifted the diastolic pressure-volume curve downward and rightward in 10 of 12 patients, and increased end-diastolic volume (from 77 +/- 18% to 100 +/- 11% of control values, p less than 0.001) with no change in end-diastolic pressure (19 +/- 7 to 19 +/- 5 mm Hg, p = NS). Thus, despite ischemia, isoproterenol improved left ventricular relaxation and filling compared with tachycardia in the absence of beta-adrenergic stimulation. Although isoproterenol is detrimental in hypertrophic cardiomyopathy by provoking ischemia, these data suggest that the adverse effects of ischemia on ventricular relaxation and distensibility may be alleviated by beta-adrenergic stimulation, possibly as a result of enhanced inactivation and restored load sensitivity.
Neutrophil function in ischemic heart disease.
Authors: Mehta J , Dinerman J , Mehta P , Saldeen T G , Lawson D , Donnelly W H , Wallin R
Published: June 2011

Neutrophils contribute to the healing of and scar formation in myocardium after ischemic injury. Many recent studies indicate that neutrophils may be involved in the genesis and propagation of myocardial ischemia. To characterize neutrophil function in ischemic heart disease, neutrophil chemotaxis, leukotriene B4 (LTB4) generation, and elastase release in plasma were measured in 20 patients with stable angina, 17 patients with unstable angina or acute myocardial infarction (AMI), and 20 age-matched control subjects. Neutrophils from patients with stable angina exhibited markedly increased chemotactic activity and LTB4 generation as compared with the age-matched control subjects (p less than 0.01). Neutrophils of nine of 17 patients with unstable angina or AMI clumped spontaneously ex vivo and exhibited marked pseudopod formation and granule extrusion on electron microscopy. Subsequent chemotactic activity and LTB4 generation by neutrophils from these patients was less than in patients with stable angina, suggesting previous in vivo activation. Plasma levels of peptide B beta, a product of fibrin degradation by human neutrophil elastase, were approximately 15-fold higher (p less than 0.001) in patients with unstable angina or AMI (588 +/- 171 pmol/l, mean +/- SEM) compared with those in patients with stable angina (37 +/- 25 pmol/l) or control subjects (40 +/- 22 pmol/l), confirming intense in vivo neutrophil activation. Our study shows enhanced neutrophil function in patients with ischemic heart disease. The increased neutrophil chemotactic activity and LTB4 generation may be markers of stable angina pectoris. Intense neutrophil activation in unstable angina or AMI, as manifested by morphologic changes in neutrophils and elastase release, may relate to ongoing in vivo cellular activation.
Coronary dilation with standard dose dipyridamole and dipyridamole combined with handgrip.
Authors: Rossen J D , Simonetti I , Marcus M L , Winniford M D
Published: June 2011

Intravenous dipyridamole is widely used to produce coronary vasodilation during cardiac imaging procedures. However, the routinely used dose of dipyridamole (0.56 mg/kg IV over 4 min) does not always result in maximal coronary dilation. The addition of isometric handgrip during dipyridamole coronary dilation has been reported to substantially increase coronary blood flow over dipyridamole alone. We compared the coronary vasodilation resulting from infusion of the standard dose of dipyridamole with that resulting from a maximally dilating dose of intracoronary papaverine in 12 patients with angiographically normal coronary arteries. We also assessed the effect on coronary blood flow velocity of the addition of isometric handgrip during dipyridamole coronary dilation. Changes in coronary blood flow velocity were measured with a 3F coronary Doppler catheter. The coronary flow reserve (peak/resting coronary flow velocity ratio) after dipyridamole (3.7 +/- 1.2 [mean +/- SD] was less than that seen after papaverine (4.4 +/- 0.5, p less than 0.05), and the coronary vascular resistance index during dipyridamole coronary vasodilation (0.28 +/- 0.09) was greater than during papaverine (0.22 +/- 0.03, p less than 0.05). The dipyridamole coronary flow reserve was less than 3.0 in four subjects and was 2.0 or less in two subjects. The addition of isometric handgrip to dipyridamole coronary vasodilation produced an 8% increase in mean heart rate and a 17% increase in mean arterial pressure, but coronary flow reserve was unchanged (3.8 +/- 1.1 before handgrip vs. 4.0 +/- 1.1 with handgrip). Quantitative angiography in six patients revealed no change in coronary caliber with the addition of handgrip.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of magnesium on anginal attack induced by hyperventilation in patients with variant angina.
Authors: Miyagi H , Yasue H , Okumura K , Ogawa H , Goto K , Oshima S
Published: June 2011

To examine whether or not magnesium suppresses coronary spasm, the effect of magnesium infusion on anginal attacks induced by hyperventilation was studied in 20 patients with variant angina. In all patients, anginal attacks associated with ischemic ST segment changes on the electrocardiogram were repeatedly induced by hyperventilation. The study was performed in the early morning successively for 3 days. On days 1 and 3 (control studies), 50 minutes before the hyperventilation test, a 5% glucose solution was infused as a placebo. On day 2 (magnesium study), 50 minutes before the hyperventilation test, magnesium sulfate (0.27 mM/kg body wt) was infused during a 20-minute period. During the control studies, anginal attack was induced by hyperventilation in all 20 patients, whereas during the magnesium study, anginal attack was induced by hyperventilation in only six (30%) of the 20 patients (p less than 0.001 vs. control studies). The changes in arterial blood pH and PCO2 caused by hyperventilation were not significant between the control study and the magnesium study. Mean serum magnesium concentration increased from 2.2 +/- 0.2 to 6.0 +/- 0.5 mg/dl immediately after infusing magnesium and was 4.5 +/- 0.6 mg/dl before the hyperventilation test during the magnesium study. We conclude that magnesium suppresses anginal attacks induced by hyperventilation in patients with variant angina.
Limitation of myocardial reperfusion injury by intravenous perfluorochemicals. Role of neutrophil activation.
Authors: Bajaj A K , Cobb M A , Virmani R , Gay J C , Light R T , Forman M B
Published: June 2011

Neutrophil activation and infiltration into the ischemic myocardium after reperfusion may limit the amount of salvageable myocardium (reperfusion injury). The effects of intravenous perfluorochemicals (Fluosol-DA) on infarct size, ventricular contractility, and neutrophil function were assessed in an occlusion-reperfusion canine model. Closed-chest dogs were subjected to 90 minutes of left anterior descending artery occlusion followed by 24 hours of reperfusion. Animals were randomized to receive either Fluosol-DA (FDA, n = 8) or Ringer's lactate (CONT, n = 10) intravenously over 30 minutes just before left anterior descending artery reperfusion. Neutrophil demargination and infiltration into the myocardium were assessed in vivo with In111. Neutrophil chemotaxis, superoxide radical production, and lysozyme degranulation were evaluated ex vivo at baseline, 1 hour after occlusion, and 1 hour after reperfusion. Perfluorochemicals significantly reduced infarct size expressed as percent of area at risk (FDA, 7 +/- 4%; CONT, 24 +/- 6%; p less than 0.01). This was associated with positive wall motion in the jeopardized zone of Fluosol-DA animals compared with dyskinesis in control animals (FDA, +4.4 +/- 2.1%; CONT, -1.1 +/- 1.5%; p less than 0.05). Electron microscopy showed reduced neutrophil and erythrocyte plugging of capillaries with relative preservation of endothelial cells in the Fluosol-DA animals. Myocardial blood flow was greater in the ischemic endocardium of Fluosol-DA animals 1 hour after reperfusion (FDA, 1.23 +/- 0.21; CONT, 0.62 +/- 0.08 ml/g/min; p less than 0.01). Neutrophil demargination and infiltration into the ischemic myocardium was reduced in the animals treated with Fluosol-DA. (FDA, 2.5 +/- 0.7 x 10(3); CONT, 14.1 +/- 2.7 x 10(3) neutrophils/g; p less than 0.01). Neutrophil chemotaxis and lysozyme release were also markedly suppressed in the Fluosol-DA groups ex vivo. These results show that intravenous Fluosol-DA significantly reduces reperfusion injury with greater salvage of myocardium and improved left ventricular function. The chief mechanism of action of Fluosol-DA appears to be the suppression of neutrophil function.
Determination of left ventricular mass by magnetic resonance imaging in hearts deformed by acute infarction.
Authors: Shapiro E P , Rogers W J , Beyar R , Soulen R L , Zerhouni E A , Lima J A , Weiss J L
Published: June 2011

Measurement of left ventricular (LV) mass by magnetic resonance imaging (MRI) is accurate in normal hearts. Because determination of mass by MRI does not require assumptions about ventricular shape, this method may be well suited for evaluating hearts distorted by infarction. To test this hypothesis, gated MRI was performed in 15 dogs before and after acute myocardial infarction. The LV mass of each dog was calculated from five short-axis images acquired at end systole, when shape distortion is greatest, at end diastole, and also from slices at varying phases of the cycle with a multiphase mode that required only one acquisition. Correlation was excellent between actual mass and end-systolic mass before infarction (p less than 0.001, r = 0.98, and SEE = 5.1 g) and after infarction (p less than 0.001, r = 0.97, and SEE = 6.6 g). Likewise, values correlated closely at end diastole before (p less than 0.001, r = 0.96, and SEE = 6.7 g) and after infarction (p less than 0.001, r = 0.94, and SEE = 8.7 g). Surprisingly, measurements of mass by a multiphase mode were also very accurate before (p less than 0.001, r = 0.98, and SEE = 5.1 g) and after (p less than 0.001, r = 0.95, and SEE = 6.49 g) infarction. Therefore, at the same phase and at multiphases of the cardiac cycle, MRI permits accurate determination of LV mass in distorted hearts.
Effects of regional alpha- and beta-blockade on resting and hyperemic coronary blood flow in conscious, unstressed humans.
Authors: Hodgson J M , Cohen M D , Szentpetery S , Thames M D
Published: June 2011

Our purpose was to determine if there are basal adrenergic influences on the coronary circulation in humans. We studied 56 patients with denervated hearts after cardiac transplantation and 19 normally innervated patients with angiographically normal coronary arteries. Coronary blood flow velocity was measured during cardiac catheterization with a subselective 3F intracoronary Doppler catheter. Heart rate was controlled by atrial pacing. Epicardial coronary artery diameter was measured by automated analysis of digital coronary angiograms. Coronary flow reserve was assessed by intracoronary papaverine hydrochloride (12 mg) injections. Regional sympathetic blockade was produced by intracoronary injections of phentolamine (3 mg, alpha) and propranolol (2 mg, beta) or metoprolol (3 mg, beta 1). After alpha-blockade, mean arterial pressure fell significantly (p less than 0.05) in both the denervated transplant (-5.8 +/- 1.5%) (mean +/- SEM) and normally innervated patients (-12.6 +/- 3.2%). Reductions in coronary flow velocity also were observed in these groups (-8.2 +/- 2.3% and -9.2 +/- 5.8%, respectively). Calculated coronary vascular resistance was unchanged. Similar changes were seen when patients were pretreated with beta-blockade before alpha-blockade. Nonspecific beta-blockade did not affect mean arterial pressure but decreased coronary velocity (innervated, -11.6 +/- 3.9%; denervated, -9.3 +/- 2.4%) and increased coronary vascular resistance (innervated, 15.4 +/- 6.7%; denervated, 10.2 +/- 3.7%). Coronary vascular resistance did not rise in either group after selective beta 1-blockade with metoprolol. Coronary flow reserve did not change in either patient group after either alpha- or beta-blockade. Changes in epicardial coronary artery diameter were small and generally not significant. These data suggest that alpha-receptor-mediated vascular tone is negligible in both denervated transplant patients and normally innervated patients. Additionally, the increase in vascular resistance after nonselective beta-blockade is the result of direct beta 2 vascular effects. Our data further suggest that there is little adrenergically mediated epicardial artery tone (either humoral or neural) at rest and that maximal vasodilator responses are not limited by adrenergically mediated vasomotor tone.
Endothelium-dependent arterial vasoconstriction after balloon angioplasty.
Authors: Fischell T A , Nellessen U , Johnson D E , Ginsburg R
Published: June 2011

To determine whether balloon angioplasty can provoke arterial vasoconstriction independent of platelet aggregation and neurogenic input, we studied the spontaneous vasomotor effects of balloon dilatation in isolated, perfused whole-vessel segments of rabbit aorta and pig carotid artery. Freshly dissected rabbit thoracic aortas were mounted in a muscle bath-perfusion chamber, perfused with physiologic saline solution at 70 mm Hg, and allowed to equilibrate. The proximal or distal half of the aortas were dilated with either a "large" (5 mm, 31-51% stretch beyond relaxed diameter) or a "small" (4 mm, 5-16% stretch) balloon angioplasty catheter with the other half of the vessel serving as the control. A similar series of experiments were performed in pig carotid arteries using "large" (6 or 8 mm, 48-90% stretch) balloon catheters. The spontaneous vasomotor effects of balloon angioplasty were examined with long-axis, high-frequency ultrasonic imaging combined with computerized edge detection image processing to measure changes in segmental internal vessel diameters. Additional experiments were carried out in rabbit aortas to determine the roles of the endothelium, extracellular calcium, indomethacin, ibuprofen, and calcium-channel blockade in modulating angioplasty-induced vasoconstriction. Significant arterial vasoconstriction was observed in the balloon angioplasty segments after dilatation with 5-mm balloons but not with 4-mm balloons. After dilatation with 5-mm balloons, the angioplasty segments' cross-sectional areas decreased by an average of 31% versus 4% for the nondilated (control) segments (p less than 0.0001). Similar postangioplasty vasoconstriction was observed in the pig carotid arteries (decrease in minimal vessel cross-sectional area of 41% [angioplasty segment] versus 2% [control segment]) (p less than 0.005). This angioplasty-induced vasoconstriction was prevented by endothelial denudation before angioplasty, removal of extracellular calcium, and pretreatment with indomethacin or ibuprofen. The vasoconstriction was only partially inhibited by calcium channel blockade with verapamil. These findings demonstrate that stretch-pressure-induced arterial vasoconstriction may occur after balloon angioplasty, independent of platelet aggregation and neurogenic input. This angioplasty-induced vasoconstriction appears to be mediated by an endothelially derived cyclooxygenase product(s).
Monitoring of fibrin generation during thrombolytic therapy of acute myocardial infarction with recombinant tissue-type plasminogen activator.
Authors: Rapold H J , Kuemmerli H , Weiss M , Baur H , Haeberli A
Published: June 2011

Fibrinopeptide A (FPA) is a very sensitive marker of fibrin generation in vivo. Because an imbalance between thrombogenic and thrombolytic forces may be responsible for the failure to recanalize and for reocclusion of coronary arteries, such a marker could be of eminent value during thrombolytic treatment of acute myocardial infarction. Thirty-four consecutive patients with acute myocardial infarction (peak creatine kinase level, 1,869 +/- 1,543 IU/l) were treated with 100 mg recombinant tissue-type plasminogen activator (rt-PA) 3.1 +/- 1.1 hours after onset of chest pain. Angiography 12.5 +/- 6.1 days later revealed an 81% patency rate of the infarct-related vessel. FPA plasma levels (normal, 1.9 +/- 0.5 ng/ml) were 34 +/- 46 ng/ml on admission and 93 +/- 86 ng/ml (538 +/- 674% with respect to each patient's admission level) after 90 minutes of rt-PA infusion (p less than 0.01). In patients without evidence of reocclusion (including three primary failures), FPA levels fell under continuous heparin infusion to 6.7 +/- 9.7 ng/ml (24 +/- 33%, p less than 0.01) within 30 minutes and were 3.1 +/- 2.2 ng/ml (15 +/- 15%, p less than 0.01), 1.6 +/- 1.1 ng/ml (8 +/- 10%, p less than 0.01), and 2.5 +/- 3.0 ng/ml (12 +/- 16%, p less than 0.01) 30 minutes, 9 hours, and 21 hours, respectively, after completion of rt-PA therapy. Five patients sustained intermittent or permanent coronary reocclusion after primary thrombolytic success. Their early postlytic FPA levels (13-51 ng/ml) remained high or increased again despite adequate anticoagulation. FPA allows the monitoring of fibrin generation during acute myocardial infarction and thrombolytic therapy. Despite successful recanalization, fibrin generation is increased under rt-PA administration before anticoagulation. Patients under anticoagulation with postlytic FPA levels less than 5 ng/ml or below their admission value seem to be at low risk of reocclusion for several days. FPA levels that are persistently high or that increase again despite adequate anticoagulation indicate ongoing fibrin generation. However, whether FPA can indeed be considered a useful marker of reocclusion remains to be confirmed in a larger population of patients with acute myocardial infarction.
Long-term results of catheter ablation of a posteroseptal accessory atrioventricular connection in 48 patients.
Authors: Morady F , Scheinman M M , Kou W H , Griffin J C , Dick M , Herre J , Kadish A H , Langberg J
Published: June 2011

Forty-eight patients with a posteroseptal accessory atrioventricular (AV) connection underwent catheter ablation of the accessory AV connection with 200-400 J shocks delivered by a standard defibrillator. Cathodal shocks were delivered through the proximal pair of electrodes of a 6F quadripolar electrode catheter positioned in the coronary sinus such that the proximal electrodes straddled the ostium (12 patients) or the third electrode from the tip was at the ostium (36 patients). A 16-cm patch electrode positioned on the back or anterior chest served as the anode. Two to 4 shocks were delivered (total, 635 +/- 198 J, mean +/- SD). The cathether ablation procedure was clinically successful in eliminating symptomatic tachycardias in in 32 of 48 patients (67%) during a mean follow-up of 26 +/- 19 months. A long-term follow-up electrophysiology study was performed in 27 of the 32 patients who had a successful clinical outcome, and this showed that conduction through the accessory AV connection was completely absent in 25 patients and present but impaired in two patients. The success rate was significantly higher in patients with a concealed accessory AV connection (13 of 13, 100%) than in patients with manifest preexcitation (19 of 35, 54%; p less than 0.001). Among the 12 patients in whom the proximal electrodes of the ablation catheter straddled the ostium of the coronary sinus, one patient developed cardiac tamponade requiring needle pericardiocentesis; there were no instances of cardiac tamponade among the 36 patients in whom the third electrode from the tip was at the ostium of the coronary sinus. Other complications were AV block requiring a permanent pacemaker and transient atrial tachycardia in one patient each and an asymptomatic pericardial effusion in three patients. In conclusion, with the catheter ablation technique described in this study, a successful clinical outcome may be achieved in approximately two thirds of patients who have a posteroseptal accessory AV connection, and the risk of serious complications is low. This technique is particularly well suited to patients with a concealed posteroseptal accessory AV connection, in whom the success rate is higher than in patients with manifest preexcitation.
Assessment of ventricular contractile state and function in patients with univentricular heart.
Authors: Sano T , Ogawa M , Taniguchi K , Matsuda H , Nakajima T , Arisawa J , Shimazaki Y , Nakano S , Kawashima Y
Published: June 2011

To elucidate the ventricular contractile state and function in patients with univentricular heart, the ventricular volume, mass, ejection phase index, and wall stress were evaluated with biplane ventriculography and pressure measurement in 41 patients: 18 with left ventricular (LV) type (age, 6.4 +/- 6.1 years) and 23 with right ventricular (RV) type (age, 5.7 +/- 4.1 years), and data from patients with univentricular heart were compared with data from 19 normal control subjects (age, 7.2 +/- 4.3 years). Although the end-diastolic and end-systolic volumes were significantly greater in both types of univentricular heart than in the normal control group, the volumes for the LV and RV type patients did not differ from each other. The ejection fraction (EF) was depressed in both patient types of univentricular heart and was significantly (p less than 0.005) lower in the RV type than in the LV type patients (0.56 +/- 0.05 for LV type, 0.50 +/- 0.07 for RV type, and 0.64 +/- 0.03 for the control group). The ventricular mass was larger in both patient types of univentricular heart than in that of the control group, whereas the ratio of ventricular mass to end-diastolic volume was significantly (p less than 0.001) lower in the RV type patients than in the LV type patients and the control group (0.79 +/- 0.18 g/ml for LV type, 0.51 +/- 0.10 for RV type, and 0.82 +/- 0.13 for control group). End-systolic stress was significantly elevated in both types of univentricular heart (241 +/- 45 for LV type, 328 +/- 52 for RV type, and 205 +/- 26 kdynes/cm2 for the control group) and significantly (p less than 0.001) greater in the RV type than in the LV type patients. There was a significant inverse correlation (p less than 0.001) between end-systolic stress and the ratio of mass to end-diastolic volume in all the patients. In 27 patients (12 patients for LV type, 15 for RV type) the mean normalized systolic ejection rate corrected for heart rate (MNSERc) clearly fell below the 95% confidence limit of the normal end-systolic stress-MNSERc relation. The end-systolic stress:end-systolic volume ratio was also significantly depressed in both patient types of univentricular heart (3.49 +/- 1.77 for LV type, 4.07 +/- 2.13 for RV type, and 7.20 +/- 1.32 for the control group). In these variables, however, there were no significant differences between LV and RV type patients of univentricular heart.(ABSTRACT TRUNCATED AT 400 WORDS)
Restenosis after coronary angioplasty. Potential biologic determinants and role of intimal hyperplasia.
Authors: Liu M W , Roubin G S , King S B
Published: June 2011

Restenosis after successful PTCA remains a major problem limiting the efficacy of the procedure. The pathophysiologic mechanism of restenosis has been enigmatic so far, but accumulated evidence strongly suggests that intimal hyperplasia is the major mechanism. Based on current understanding of the process of intimal hyperplasia, one unifying concept may be that there are at least two major local biologic determinants influencing this process, lesion characteristics and regional flow dynamics. Lesion characteristics include the plaque structure and the quantity of smooth muscle. These may provide the anatomic substrate that determines the extent of injury and the degree of smooth muscle cell proliferation. The amount of smooth muscle cells in the stenotic lesion activated by injury to undergo proliferation may determine the eventual bulk of the restenotic lesion. In addition, low wall shear stress could promote intimal hyperplasia and cause structural change of vessels to decrease the lumen, whereas high wall shear stress exerts the opposite effects. Intimal hyperplasia after balloon injury is a complex process involving platelets, growth factors, endothelial cells, smooth muscle cells, mechanical injury, wall shear stress, and probably other unknown factors. Platelets not only contribute growth factors such as PDGF but also cause organized thrombus. Different growth factors may be involved in initiating smooth muscle cell proliferation and may come from many different sources, including smooth muscle cells, endothelial cells, and macrophages. Intact confluent endothelial cells may produce heparin sulfates and inhibit intimal proliferation; however, regenerating endothelial cells may have the opposite effect. Thus, the proliferative potential of smooth muscle cells, endothelial recovery, extent of injury, wall shear stress, and other unknown factors may all influence this process. Based on these concepts concerning the biology of restenosis, some research directions concerning potential forms of therapy are proposed.
Distribution of extracellular potassium and electrophysiologic changes during two-stage coronary ligation in the isolated, perfused canine heart.
Authors: Coronel R , Fiolet J W , Wilms-Schopman J G , Opthof T , Schaapherder A F , Janse M J
Published: June 2011

We studied the relation between [K+]o and the electrophysiologic changes during a "Harris two-stage ligation," which is an occlusion of a coronary artery, preceded by a 30-minute period of 50% reduction of flow through the artery. This two-stage ligation has been reported to be antiarrhythmic. Local direct current electrograms and [K+]o signals from up to 48 intramural sites were simultaneously recorded in isolated, perfused dog hearts. A second period of one-stage ligation was compared with a consecutive two-stage ligation because reproducibility in [K+]o and electrophysiologic changes are established only after the first period of ischemia. In control experiments, no difference was found between the second and third period of one-stage ligation in the electrophysiologic changes and in increases in [K+]o. After complete occlusion during two-stage ligation, activation block in the ischemic tissue occurred about 6 minutes earlier than during one-stage ligation, but the average potassium concentration at which block occurred was identical. This [K+]o during total ischemia was achieved earlier during two-stage ligation than during one-stage ligation. No indication was found for a large decrease of intracellular potassium content during the period of low flow perfusion. Early activation block may explain the previously reported reduced incidence of ventricular fibrillation during two-stage ligation.
Electrophysiologic spectrum of concealed intranodal conduction during atrial rate acceleration in a model of 2:1 atrioventricular block.
Authors: McKinnie J , Avitall B , Caceres J , Jazayeri M , Tchou P , Akhtar M
Published: June 2011

Concealed anterograde penetration of the atrioventricular (AV) node has been used to explain a wide variety of electrocardiographic findings. The effects of atrial rate acceleration on this phenomenon remain undefined. To examine the dynamic interrelations between conducted and nonconducted beats at different atrial rates, a unique atrial pacing protocol of functional 2:1 AV block was used in 10 patients. The pacing protocol involved abrupt transitions from 2:1 to 1:1 AV conduction and enabled quantification of conduction delay produced by nonpropagated impulses over extremes of atrial rate. Stable 2:1 AV conduction was maintained over a mean range of atrial paced cycle lengths of 289 +/- 29.6 to 223 +/- 33.0 msec, respectively. The mean AV conduction time during 2:1 and corresponding 1:1 drives at the longest atrial paced rates were 169 +/- 33.5 and 136.5 +/- 26.9 msec, respectively--revealing a significant effect of nonpropagated impulses on subsequent conduction. Surprisingly, at the shortest atrial paced rates, the mean AV conduction times were 191.5 +/- 31.8 and 161.0 +/- 23.3 msec, respectively. The lack of significant changes in conduction time between 2:1 and 1:1 drives at the extremes of atrial rate (32.5 vs. 30 msec, p = NS) suggests that the effect of concealed conduction is "fixed" and independent of rate. Clinical implications and postulated electrophysiologic mechanisms are discussed.
Stiffness of systemic arteries in patients with myocardial infarction. A noninvasive method to predict severity of coronary atherosclerosis.
Authors: Hirai T , Sasayama S , Kawasaki T , Yagi S
Published: June 2011

The static elastic properties of arterial tree (abdominal aorta and common carotid artery) were studied in 19 normal subjects and in 49 patients with myocardial infarction with an ultrasonic phase-locked echo-tracking system that allows continuous transcutaneous measurement of the arterial diameter. The stiffness index beta, which represented the mechanical properties in the arterial wall, was calculated from the relation between systemic blood pressure and the diameter of the artery. Patients with myocardial infarction underwent coronary angiography in their convalescent period to determine involved vessels. In 11 patients, coronary artery was patent; 15 patients had one-vessel disease, 12 had two-vessel disease, and the remaining 11 patients had three-vessel disease. In normal subjects, increasing age was associated with an increase in arterial stiffness. An average value of the stiffness index of the abdominal aorta was 8.58 +/- 3.02 (mean +/- SD) and that of common carotid artery was 9.17 +/- 2.22. In patients with three-vessel disease, these values were significantly higher (22.37 +/- 4.29 in abdominal aorta and 13.17 +/- 4.56 in common carotid artery) than those in normal subjects. Stiffness index of patients with two- or one-vessel disease was also increased but lower than those in patients with three-vessel disease (p less than 0.05). Forty-four of 49 patients with infarction had an arterial stiffness index of abdominal aorta higher than the 95% confidence limits of the normal data (p less than 0.05). Twenty-eight patients were outside the nomogram of common carotid artery (p less than 0.05). The mechanical properties of these elastic arteries provided sufficiently reliable information on changes caused by atherosclerosis.
Two-dimensional and Doppler-echocardiographic and cardiac catheterization correlates of survival in primary pulmonary hypertension.
Authors: Eysmann S B , Palevsky H I , Reichek N , Hackney K , Douglas P S
Published: June 2011

To determine correlates of survival in primary pulmonary hypertension, we compared 41 echocardiography-Doppler and nine catheterization parameters with outcome in 26 patients. Mean follow-up was 19.7 months in survivors; mean survival was 4.8 months in 16 nonsurvivors. Cox life-table univariate analysis correlated two echocardiographic, three Doppler, and three catheterization variables with poor survival (p less than or equal to 0.05), and chi 2 analysis ensured the best critical values: severity of pericardial effusion, heart rate of more than 87 beats/min, pulmonic flow acceleration time of less than 62 msec, tricuspid early flow deceleration (T-DEC) equal to or less than -300 cm2/sec, mitral early flow-to-atrial flow velocity ratio (M-E/A) equal to or less than 1.0, catheterization cardiac index (CI) equal to or less than 2.3 l/min/m2, mean pulmonary artery pressure of more than 61 mm Hg, and diastolic pulmonary artery pressure of more than 43 mm Hg. Multivariate life-table analysis of noninvasive variables revealed the severity of pericardial effusion to be independently significant (p = 0.006), whereas analysis of catheterization variables revealed cardiac index to be independently significant (p = 0.014). Combined multivariate analysis did not differ from the noninvasive results alone. Categorical modeling of the eight significant variables split at their critical values (present or absent) revealed M-E/A, T-DEC, and CI to be independently significant by multivariate analysis (p = 0.0014). Analysis of the five echocardiography-Doppler variables alone revealed M-E/A, T-DEC, and heart rate to be independently significant (p = 0.0016). In both cases, mortality increased with the number of critical values reached.(ABSTRACT TRUNCATED AT 250 WORDS)
Isoproterenol-induced alterations in myocardial blood flow, systolic and diastolic function in conscious dogs with heart failure.
Authors: Hittinger L , Shannon R P , Kohin S , Lader A S , Manders W T , Patrick T A , Kelly P , Vatner S F
Published: June 2011

The effects of isoproterenol were examined in 10 conscious, chronically instrumented adult dogs with left ventricular (LV) failure after pressure overload hypertrophy induced by aortic banding at 8-10 weeks of age (LV free wall plus septum-to-body weight ratio, 8.6 +/- 0.5 g/kg) and also in eight control dogs (LV free wall plus septum-to-body weight ratio, 5.1 +/- 0.3 g/kg). Baseline values of heart rate, LV end-diastolic pressure, LV end-diastolic stress, and LV systolic wall stress were greater in the LV failure dogs (p less than 0.01), whereas the ejection phase index, rate of change of LV short-axis diameter, LV dD/dt, was depressed compared with control animals. In the control animals, isoproterenol infusion increased Vcf and LV dD/dt significantly (p less than 0.05), whereas LV systolic wall stress did not change. In the LV failure dogs, the increases in Vcf and LV dD/dt were less (p less than 0.01), and LV systolic wall stress increased (p less than 0.01). In the control animals, LV end-diastolic pressure, LV end-diastolic stress, LV end-diastolic stress-dimension ratio, diastolic radial myocardial stiffness, and the time constant of isovolumic relaxation decreased (p less than 0.05), whereas in the LV failure dogs, LV end-diastolic pressure, LV end-diastolic stress, diastolic radial myocardial stiffness, and the LV end-diastolic stress-dimension ratio increased. In the LV failure group, the endocardial to epicardial blood flow ratio fell to 0.59 +/- 0.06 during isoproterenol infusion, that is, significantly lower than in control dogs (0.93 +/- 0.06). These data support the concept that potent sympathomimetic amines exert deleterious effects on systolic and diastolic function in the failing heart, potentially related to subendocardial hypoperfusion.
Influence of inflation pressure and balloon size on the development of intimal hyperplasia after balloon angioplasty. A study in the atherosclerotic rabbit.
Authors: Sarembock I J , LaVeau P J , Sigal S L , Timms I , Sussman J , Haudenschild C , Ezekowitz M D
Published: June 2011

To evaluate the effect of balloon size and inflation pressure on acute and subsequent outcome following balloon angioplasty (BA), 70 New Zealand White rabbits with bilateral femoral atherosclerosis were assigned to four groups: group 1, oversized balloon, low inflation pressure (n = 35 vessels; balloon size, 3.0 mm/inflation pressure, 5 atm); group 2, oversized balloon, high inflation pressure (n = 36; 3.0 mm/10 atm); group 3, appropriate size, low inflation pressure (n = 17; 2.5 mm/5 atm); and group 4, appropriate size balloon, high inflation pressure (n = 19; 2.5 mm/10 atm). Angiograms were obtained before, 10 minutes after, and 28 days after BA and read by two blinded observers using electronic calipers. The in vivo balloon-to-vessel ratio was measured for each group. There were eight non-BA controls. Rabbits were sacrificed either immediately (n = 34) or at 28 days after BA (n = 36), with the femoral vessels pressure perfused for histologic and morphometric analysis. The latter was performed at 28 days only. Absolute angiographic diameters increased in all groups immediately after BA (p less than 0.01). Acute angiographic success, defined as greater than 20% increase in luminal diameter, was higher using high inflation pressure (group 2, 32/36 [89%] and group 4, 16/19 [84%] vs. group 1, 23/35 [66%] and group 3, 9/17 [53%]; p less than 0.05). A 3.0-mm balloon resulted in significant oversizing irrespective of inflation pressure (balloon-to-vessel ratio, 1.5 +/- 0.1 vs. 1.1 +/- 0.1 to 1, for the 2.5-mm balloon). Vessels exposed to high inflation pressure had a significantly higher incidence of mural thrombus, dissection (p less than 0.01), and medial necrosis versus low pressure (p less than 0.05). At 28 days, the rates of restenosis (defined as greater than 50% loss of initial gain) were 14/20 (70%), 11/16 (69%), 5/10 (50%), and 5/10 (50%) for groups 1 through 4 (p = NS; a trend in favor of the groups using an oversized balloon). There was an increase in the degree of intimal hyperplasia by morphometric analysis in all groups, being most marked in group 2 (oversized balloon and high inflation pressure, 1.7 +/- 0.9 vs. 0.5 +/- 0.2 mm for controls, p less than 0.001). We reached two conclusions. First, all protocols resulted in a significant increase in luminal diameter immediately after angioplasty with the highest success rate in vessels subjected to high pressure dilatation.(ABSTRACT TRUNCATED AT 400 WORDS)