bluuebunny/crossref_metadata_2025 huggingface dataset:
Creatine kinase isoform analysis in the detection and assessment of thrombolysis in man.
Authors: Puleo P R , Perryman M B , Bresser M A , Rokey R , Pratt C M , Roberts R
Published: June 2011

Recent demonstrations of the efficacy of intravenous thrombolytic therapy in acute myocardial infarction have emphasized the need for a noninvasive index of successful reperfusion. The tissue form of MM creatine kinase (MM3) is known to undergo posttranslational conversion to modified forms MM2 and MM1 after release into the plasma following acute infarction. Since this conversion is rapid, sustained elevation of plasma MM3 may be a marker of the prolonged creatine kinase release characteristic of nonreperfused infarction. Therefore, we investigated the rate of decline of plasma MM3 in a consecutive series of patients undergoing thrombolytic therapy of acute myocardial infarction, all of whom underwent acute angiography to assess treatment success, as well as in 30 conventionally treated patients. Among 55 patients with angiographically documented successful reperfusion (group IA), the rate of decline of MM3 was 4.18 +/- 1.25%/hr (mean +/- SD); in contrast, the rate of decline was 2.37 +/- 1.11%/hr in 39 patients with angiographically documented unsuccessful reperfusion (group IB) and 1.77 +/- 1.46%/hr among the 30 patients receiving conventional treatment (group II) (p less than .001 for groups IB and II vs group IA). A cutoff value of 3.1%/hr minimized the overlap between the groups; 48/55 (87%) patients with successful reperfusion had a rate of decline of MM3 of 3.1%/hr or more, while 29 of 39 (74%) patients in whom thrombolysis was unsuccessful and 27 of 30 (90%) patients receiving conventional treatment had a rate of decline less than 3.1%/hr (p less than .001 for groups IB and II vs group IA).(ABSTRACT TRUNCATED AT 250 WORDS)
Failure of superoxide dismutase to limit size of myocardial infarction after 40 minutes of ischemia and 4 days of reperfusion in dogs.
Authors: Uraizee A , Reimer K A , Murry C E , Jennings R B
Published: June 2011

Reactive oxygen species such as the superoxide anion (.O2-) have recently been implicated as important agents involved in causing cell death in the setting of myocardial ischemia and reperfusion. When superoxide anion is involved in ischemic injury the administration of superoxide dismutase (SOD) may limit infarct size by reducing the level of superoxide anions in the myocardium. The study described herein was done to determine whether SOD could limit myocardial infarct size when infarcts were produced in dogs by a 40 min occlusion of the circumflex coronary artery followed by 4 days of reperfusion. The animals in the SOD treatment group received a 1 hr intra-atrial infusion of SOD, at a rate of 250 U/kg/min starting 15 min after occlusion and ending 35 min after reperfusion; control dogs received a saline infusion over the same time frame. Infarct size was determined histologically and expressed as a percentage of the anatomic area at risk (AAR). Infarct size was similar in the two groups, averaging 26.2 +/- 2.5% in the control group (n = 10) and 21.1 +/- 4.8% in the SOD group (n = 11) (p = .40). Hemodynamic variables were not statistically different in the two groups during the occlusion. The transmural mean collateral blood flow at 10 min into the 40 min occlusion was 0.13 +/- 0.02 ml/min/g in the controls and 0.17 +/- 0.03 ml/min/g in the SOD group (p = NS); moreover, SOD did not alter collateral blood flow. In control dogs, infarct size was inversely related to collateral blood flow; analysis of covariance showed that SOD did not shift this relationship. Thus, SOD did not limit infarct size in this study. The results of the current study are consistent with our previous study in which allopurinol, a xanthine oxidase inhibitor, did not limit infarct size in this same experimental preparation. The results suggest that superoxide anions that are accessible to the infused SOD are not a major cause of myocyte death caused by 40 min of severe ischemia followed by reperfusion.
Clinical application of atrial natriuretic polypeptide in patients with congestive heart failure: beneficial effects on left ventricular function.
Authors: Saito Y , Nakao K , Nishimura K , Sugawara A , Okumura K , Obata K , Sonoda R , Ban T , Yasue H , Imura H
Published: June 2011

Synthetic alpha-human atrial natriuretic polypeptide was infused in patients with congestive heart failure (CHF) (New York Heart Association class III or IV) and in those without CHF. The infusion of atrial natriuretic polypeptide (ANP) at a rate of 0.1 microgram/kg/min significantly decreased pulmonary capillary wedge pressure and increased stroke volume index in all of the patients with CHF, whereas it decreased pulmonary capillary wedge pressure but caused no significant change in stroke volume index in the patients without CHF. Concomitant significant reductions in total systemic resistance were observed in both groups of patients. The ANP infusion significantly increased the urine volume, the excretion of sodium, and endogenous creatinine clearance in the patients without CHF. In the patients with CHF, it also showed a tendency to increase all these variables, but the urine volume did not correlate with the reduction in pulmonary capillary wedge pressure. The ANP infusion also decreased plasma aldosterone concentrations in these patients, although no significant difference was observed in the decrement of the plasma aldosterone concentration in the patients with and those without CHF. These findings indicate that the ANP infusion improves left ventricular function in patients with CHF, and suggest that this improvement results mainly from the vasodilating activity of ANP.
Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty.
Authors: Barnathan E S , Schwartz J S , Taylor L , Laskey W K , Kleaveland J P , Kussmaul W G , Hirshfeld J W
Published: June 2011

To test the hypothesis that pretreatment with adequate antiplatelet therapy reduces the likelihood of acute coronary thrombosis during routine percutaneous transluminal coronary angioplasty (PTCA), we reviewed, blinded to treatment group, the films and records of 300 consecutive initially successful PTCAs. Films before PTCA, immediately after, and at least 30 min after the last balloon inflation were assessed for the presence of any thrombus at the PTCA site. We excluded 37 patients who received streptokinase before PTCA or who had 100% occlusion or thrombus on pre-PTCA films. New thrombi were classified as clinically significant (defined as causing 100% occlusion or requiring emergency surgery or streptokinase therapy) or as not significant (not causing an acute problem or requiring intervention). Patients were classified into three groups, based on the type and extent of antiplatelet therapy received. Group 1 (no aspirin, n = 121) consisted of patients who did not receive aspirin either before admission or in hospital before PTCA (with or without dipyridamole). Group 2 (standard treatment, n = 110) received aspirin with or without dipyridamole but did not receive both drugs before admission and in hospital before PTCA. Group 3 (maximal treatment, n = 32) received both aspirin and dipyridamole before admission and in hospital before PTCA. New thrombi were detected at 39 (14.8%) PTCA sites, of which 15 (5.7% of all PTCA sites) were considered clinically significant. Group 1 had the highest incidence of both thrombus (21.5%) and clinically significant thrombus (10.7%). A reduction was seen in group 2 in thrombus (11.8%; p = .07) and in clinically significant thrombus (1.8%; p = .005). Group 3 had no thrombus (p = .001) and no clinically significant thrombus (p = .04). In addition to inadequate pretreatment with antiplatelet therapy, univariate analyses demonstrated several other risk factors for thrombus: higher percent diameter stenosis before PTCA (p less than .008), higher platelet count (p = .013), and current smoking (p = .03). Only higher platelet count (p less than .001) and inadequate pretreatment (p = .001) were associated with clinically significant thrombus. Stepwise logistic regression analysis demonstrated that for thrombus, the lack of effective antiplatelet therapy was the most discriminatory variable, followed by current smoking, higher percent diameter stenosis, and dissection. For clinically significant thrombus, once the lack of pretreatment with effective antiplatelet therapy was considered, no other factors added significant discriminatory information.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of heart rate on ventricular size, stroke volume, and output in the normal human fetus: a prospective Doppler echocardiographic study.
Authors: Kenny J , Plappert T , Doubilet P , Salzman D , Sutton M G
Published: June 2011

The effect of heart rate on cardiac output in the fetal heart is controversial. We used Doppler echocardiography to investigate the effects of increasing heart rate on stroke volume and ventricular output in the normal human fetal heart. Heart rate was increased in 25 human fetuses (mean age 36 weeks) by auditory stimulation with a sound emitter placed on the mother's abdomen. Aortic or pulmonary diameters were measured at valve level from two-dimensional echocardiographic images and cross-sectional areas were calculated. Blood flow velocity spectra from the pulmonary artery or aorta were digitized to obtain flow velocity integrals before and after auditory stimulation. Stroke volume was calculated as the product of the flow velocity integral and the area of the great vessel. Prestimulation mean heart rate was 132 +/- 8 beats/min and increased after auditory stimulation to 158 +/- 9 beats/min (p less than .001). Stroke volume decreased with the increase in heart rate from 3.7 +/- 1.4 ml before stimulation to 3.0 +/- 1.1 ml after stimulation (p less than .001), but ventricular output calculated as the product of stroke volume and heart rate remained unchanged (0.48 +/- 0.18 liter/min before vs 0.48 +/- 0.17 liter/min after stimulation). The decrease in stroke volume was accompanied by a decrease in ventricular end-diastolic area, although there was no change either in end-systolic area or fractional change in area. This study demonstrates that increases in heart rate within the physiologic range in the normal human fetus result in a decrease in ventricular size and stroke volume but no change in ventricular output or ventricular shortening.
Biochemical evidence of a chronic abnormality in platelet and vascular function in healthy individuals who smoke cigarettes.
Authors: Nowak J , Murray J J , Oates J A , FitzGerald G A
Published: June 2011

Cigarette smoking is associated with increased mortality from cardiovascular disease that declines after cessation. This study extends the evidence regarding the effects of chronic smoking on platelets and the vessel wall in vivo. Excretion of a major urinary thromboxane metabolite, 2,3-dinor-thromboxane B2, is significantly (p less than .01) elevated in apparently healthy chronic smokers (20 cigarettes daily) compared with that in nonsmoking control subjects. This difference in excretion of 2,3-dinor-thromboxane B2 was abolished by the administration of 20 mg aspirin twice daily, a dose shown to selectively inhibit platelet cyclooxygenase. After aspirin, the return of the excretion of 2,3-dinor-thromboxane B2 to pretreatment levels paralleled the recovery of platelet cyclooxygenase. These findings indicate that excessive thromboxane A2 generation in chronic smokers predominantly derives from platelets. The urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha also is increased during chronic cigarette smoking, as is the case with other diseases associated with accelerated interaction of platelets with the vessel wall. We have found evidence of platelet and vascular dysfunction in vivo in chronic cigarette smokers before the manifestation of overt cardiovascular disease. The results would also be consistent with the hypothesis that in chronic smokers, the platelet defect is largely reflective of smoking-induced vascular injury.
Postinflammatory mitral and aortic valve prolapse: a clinical and pathological study.
Authors: Tomaru T , Uchida Y , Mohri N , Mori W , Furuse A , Asano K
Published: June 2011

In this study we reevaluated whether the sole cause of mitral valve prolapse (MVP) and aortic valve prolapse (AVP) is myxomatous degeneration. Forty-two surgical cases of prolapsed valves with mitral and/or aortic regurgitation were reviewed (AVP in nine, MVP in 27, and combined AVP and MVP [CVP] in six). On microscopic examination, myxomatous degeneration was observed in 20 patients, including six with AVP, 13 with MVP, and one with CVP. In the other 22 patients, including three with AVP, 14 with MVP, and five with CVP, microscopic examination revealed fibrosis with vascularization and scattered infiltration of inflammatory round cells caused by postinflammatory changes with or without chronic inflammation. We coined the term "postinflammatory valve prolapse" (PIVP) to describe these valves. Both postinflammatory and myxomatous degeneration were observed in seven patients with floppy mitral valves attributable to PIVP. Rupture of chordae tendineae was present in six patients with myxomatous mitral valve and three with PIVP. Seven patients with PIVP had a history of rheumatic fever. The results suggest that valvular prolapse is produced not only by myxomatous degeneration but also by postinflammatory changes, including those caused by rheumatic fever.
Black-white differences in cholesterol levels of serum high-density lipoprotein subclasses among children: the Bogalusa Heart Study.
Authors: Srinivasan S R , Freedman D S , Webber L S , Berenson G S
Published: June 2011

Cholesterol levels of serum high-density lipoprotein (HDL) subclasses, HDL2 and HDL3, were examined in a random subsample (n = 561) of children (7 to 17 years of age) from a total biracial community. Overall, black children in younger (7 to 10 years) and older (11 to 17 years) age groups alike had significantly higher HDL2 cholesterol (HDL2-C) and HDL3-C than their white counterparts. In addition, black children had a relatively higher frequency of joint occurrence of high levels of both HDL2-C and HDL3-C. A significant sex-related difference, with girls showing higher values than boys, was noted among younger age groups for HDL2-C. A male-female crossover trend in HDL2-C levels was apparent only among white children, with girls showing higher values after age 11. Both age and sexual maturation were inversely associated with HDL3-C levels in white children, irrespective of sex (p less than .001). Serum triglycerides were inversely related to both HDL2-C and HDL3-C only in white children (p less than .001). A black-white difference in HDL2-C persisted only among boys and girls in the older age group after adjusting for the covariates (sexual maturation, age, adiposity, oral contraceptive use, cigarette smoking, alcohol use, and serum triglycerides). With respect to HDL3-C, the covariate-adjusted difference remained significant only among boys in the older age group. Metabolic variations between the races in response to both physiologic and environmental factors likely account for the divergence in antiatherogenic HDL pattern.
Autologous blood perfusion for myocardial protection during coronary angioplasty: a feasibility study.
Authors: Lehmann K G , Atwood J E , Snyder E L , Ellison R L
Published: June 2011

During coronary angioplasty, inflation of the balloon within the coronary artery produces transient arterial occlusion and frequently results in myocardial ischemia. Delivery of oxygenated autologous blood to the myocardium at risk during inflation may help mitigate this ischemia. Accordingly, we investigated the feasibility and safety of infusing blood through the central lumen of a dilatation catheter around the guidewire using both a model in vitro and clinical trials. In the tests in vitro, fresh blood was infused at flow rates up to 120 ml/min. Hemolysis was minimal at flow rates of 60 ml/min or less (less than or equal to 0.92 +/- 0.18%), but increased exponentially at higher rates (13.64 +/- 2.37% at 120 ml/min, p less than .002). A similar pattern was observed for potassium release. Platelet and leukocyte counts did not vary significantly, and beta-thromboglobulin and muramidase remained at control levels. Although mean erythrocyte volume did not change, erythrocyte histograms and light microscopy demonstrated a subpopulation of red cell fragments averaging 25 to 40 fl in size at higher rates. A randomized, crossover clinical trial was next performed by delivery of blood perfusion at 60 ml/min to 15 patients undergoing coronary angioplasty. Levels of plasma hemoglobin, beta-thromboglobulin, lactate dehydrogenase, and potassium remained constant before and after the perfusion and the control inflations. The maximum pain score was significantly lower with the perfusion inflation (4.1 +/- 0.8 vs 6.0 +/- 0.9, p less than .003). Relative to baseline, the maximum ST segment elevation during the perfusion inflation (0.5 +/- 0.3 mm) was nearly one-fourth that during the control inflation (1.9 +/- 0.6 mm, p less than .02). Thus, myocardial protection with oxygenated autologous blood perfusion at rates of 60 ml/min appears to be a safe and effective technique that may permit increased inflation time and extend the range of coronary angioplasty to include individuals at high risk for the procedure.
Right heart pressure does not equal pericardial pressure in the potassium chloride-arrested canine heart in situ.
Authors: Slinker B K , Ditchey R V , Bell S P , LeWinter M M
Published: June 2011

Recently proposed concepts of pericardial surface pressure, as opposed to liquid pressure, have advanced our understanding of the relationship between pericardial and heart chamber pressures. However, the subsequent suggestion that right heart intracavitary pressure equals, or nearly equals, pericardial surface pressure is not strictly consistent with the physiology of pericardial constraint. If right heart pressure equals pericardial surface pressure, then transmural right heart pressure equals zero. Because of the difficulty in measuring pericardial pressure directly in the beating heart we designed an experiment in the recently arrested canine heart in situ to measure pericardial pressure indirectly and to test the hypothesis that right heart transmural pressure is zero under reasonably physiologic, static equilibrium conditions. According to a static equilibrium analysis of the pressures acting across the walls of the heart, at a given volume the change in right heart pressure caused by removing the pericardium is equal to the pericardial pressure when the pericardium is intact. We found that this drop in pressure caused by pericardiectomy did not equal right heart pressure and therefore that right heart transmural pressure does not equal zero.
Sequence of mitral valve motion and transmitral blood flow during manual cardiopulmonary resuscitation in dogs.
Authors: Feneley M P , Maier G W , Gaynor J W , Gall S A , Kisslo J A , Davis J W , Rankin J S
Published: June 2011

According to the thoracic pump model of cardiopulmonary resuscitation (CPR), the heart serves as a passive conduit for blood flow from the pulmonary to the systemic vasculature, necessitating an open mitral valve and anterograde transmitral blood flow during chest compression. To assess the applicability of this model to manual CPR techniques, two-dimensional echocardiograms were recorded from the right chest wall and/or the esophagus in nine dogs (18 to 26 kg) during manual CPR. The aortic valve opened with chest compression and closed with release, while the pulmonary and tricuspid valve leaflets closed with compression and opened during release. The mitral valve remained open during ventilation alone and during abdominal compressions. With the onset of brief, high-velocity (high-impulse) chest compressions, the mitral valve closed rapidly and the left ventricle was deformed, whether compressions were applied to the sternum or the left mid-chest wall. The mitral valve reopened with release of each compression. Left atrial echocardiographic contrast injections confirmed the absence of anterograde transmitral blood flow during high-impulse compression and its presence during release. Failure of mitral leaflet approximation during chest compression was observed only when a very low-velocity, prolonged (low-impulse) compression technique was used, or when regions that did not directly overlie the heart were compressed. Consistent with these observations, simultaneous recordings of the left ventricular and left atrial pressures during high-impulse sternal compressions in five dogs (19 to 25 kg) demonstrated peak and mean left ventriculoatrial pressure gradients of 38.5 +/- 4.0 and 13.5 +/- 2.9 mm Hg, respectively, and these pressure gradients declined with less impulsive compressions. The observations made during all but low-impulse chest compressions are inconsistent with the thoracic pump model, and support direct cardiac compression as the primary mechanism of forward blood flow with more impulsive manual chest compression techniques.
Preservation of endothelial cell structure and function by intracoronary perfluorochemical in a canine preparation of reperfusion.
Authors: Forman M B , Puett D W , Bingham S E , Virmani R , Tantengco M V , Light R T , Bajaj A , Price R , Friesinger G
Published: June 2011

To determine the effect of intracoronary perfluorochemical on endothelial cell structure and function, 16 dogs were randomized to receive either low-dose (15 ml/kg) intracoronary perfluorochemical (Fluosol-DA) or saline after 90 min of proximal occlusion of the left anterior descending coronary artery (LAD). The animals underwent reperfusion for 60 min with the introduction of perfluorochemical or saline 5 to 10 min after the onset of reperfusion. Endothelium-dependent coronary vasodilatory reserve was determined in vivo both at baseline and 1 hr after reperfusion by infusion of acetylcholine and then serotonin into the distal LAD bed in 12 animals (six in each group). Both agonists significantly increased regional flow measured by 133Xe washout in the two groups before occlusion, but at 1 hr after reperfusion only animals given perfluorochemical demonstrated a significant increase in flow. Vasodilatory reserve was assessed in vitro with cumulative dose-response curves to acetylcholine on LAD rings proximal and distal to the snare in all animals. These studies demonstrated a significant reduction in endothelial cell-mediated relaxation of epicardial arterial segments in the ischemic segment of control but not treated animals. Light microscopy revealed the presence of neutrophils within vessels in the ischemic zones in control animals only. Electron microscopy showed capillary obstruction by endothelial cell protrusions and neutrophil and red cell plugging in control animals in the ischemic region but an intact endothelium and predominantly unobstructed capillaries in treated animals. These findings suggest that the structural and functional endothelial damage after reperfusion may be prevented by the administration of intracoronary perfluorochemical after the onset of reperfusion.
Leukotriene C4- and D4-induced diffuse peripheral constriction of swine coronary artery accompanied by ST elevation on the electrocardiogram: angiographic analysis.
Authors: Tomoike H , Egashira K , Yamada A , Hayashi Y , Nakamura M
Published: June 2011

Effects of leukotriene (LT) C4 and LTD4 on coronary artery spasm in atherosclerotic miniature pigs were examined angiographically. Endothelial balloon denudation of the left circumflex coronary artery was performed in 15 Göttingen miniature pigs; 11 were fed a 2% cholesterol diet and four were fed a regular diet for 3 months. Three months after this denudation, the area of the coronary artery was reduced by 94 +/- 2% and 43 +/- 5% (p less than .01) in the denuded and nondenuded areas by the intracoronary administration of 10 micrograms/kg histamine after pretreatment with 60 mg/kg iv cimetidine. The effects of LTC4 and LTD4 on coronary diameter and the preventive effects of FPL-55712, a LTC4 and LTD4-receptor blocker, or diphenhydramine, a histamine H1-receptor blocker, on histamine-induced coronary spasm were then examined angiographically. Administration of LTC4 or LTD4 in doses of 1 and 10 micrograms into the left coronary artery, or selectively into the left circumflex and left anterior descending coronary arteries in a dose of 5 micrograms, led to the elevations in the ST segment on the electrocardiogram and there was delayed filling of the contrast medium in the peripheral coronary artery. However, these LTs provoked no augmented constrictions at any site on the epicardial coronary arteries (n = 15). Diphenhydramine, 1 mg/kg (n = 6), abolished the histamine-induced coronary spasm FPL-55712, 0.1 mg/kg, with which the LT-induced myocardial ischemia was abolished, did not prevent the histamine-induced coronary artery spasm.(ABSTRACT TRUNCATED AT 250 WORDS)
New developments in lipid-lowering therapy: the role of inhibitors of hydroxymethylglutaryl-coenzyme A reductase.
Authors: Tobert J A
Published: June 2011

HMG-CoA reductase catalyzes the conversion of hydroxymethylglutarate to mevalonate, an important early rate-limiting step in the cholesterol biosynthesis pathway. Since the discovery of compactin, the first HMG-CoA reductase inhibitor, by Endo et al. in 1976, several other inhibitors have been described. Those that have been investigated in the clinic include mevastatin (compactin), lovastatin (mevinolin), simvastatin (synvinolin), eptastatin (CS-514, SQ-31,000), and SRI-62320. These compounds are competitive inhibitors, with Ki values of the hydroxyacid forms of around 10(-9) M. Lovastatin (mevinolin, Mevacor), which is in the late stages of clinical development and has been administered to over 1000 subjects for up to 4 years, is the inhibitor on which the most information is available. It is given in single or divided doses of 20 to 80 mg/day, and is a very effective and usually well-tolerated lipid-lowering agent. At 40 mg bid, lovastatin produces the following approximate mean changes: total plasma cholesterol, -33%; low-density lipoprotein (LDL) cholesterol, -40%; very low-density lipoprotein cholesterol, -35%; plasma triglycerides, -25%; high-density lipoprotein cholesterol, +10%; apolipoprotein B, -20%. The substantial reduction in both LDL cholesterol and apolipoprotein B (the principal protein component of LDL) indicates a reduction in the number of circulating LDL particles. The mechanism probably involves both decreased LDL production and increased LDL clearance.
Determination of stroke volume and cardiac output during exercise: comparison of two-dimensional and Doppler echocardiography, Fick oximetry, and thermodilution.
Authors: Christie J , Sheldahl L M , Tristani F E , Sagar K B , Ptacin M J , Wann S
Published: June 2011

Simultaneous estimates of cardiac output were made during graded upright maximal exercise in 10 male subjects by means of Doppler velocity spectrum of ascending aortic flow, apical two-dimensional echocardiograms, thermodilution, and Fick oximetry. In 15 subjects, aortic annular and root diameters were measured during similar exercise from parasternal two-dimensional echocardiograms. The linear correlation between Doppler, two-dimensional echocardiography, and the invasive estimates ranged from r = .78 to r = .92. Both echocardiographic techniques were able to predict changes in invasive flow estimates with reasonable accuracy. Two-dimensional echocardiographic flow estimates underestimated invasive values by about 60%. The accuracy of Doppler flow estimates varied with the method of estimating aortic cross-sectional area. Greatest accuracy was obtained with areas calculated from diameters measured at the aortic value anulus with the leading edge-to-leading edge method of measurement. Correlation coefficients comparing Doppler and thermodilution flow estimates were generally higher (r = .75 to .96, mean .86) for individuals than for the group, but accuracy of the Doppler estimates in single subjects was quite variable. Aortic diameters did not increase from rest to moderate levels of upright exercise. A 3% to 5% increase in resting aortic diameter was noted in the upright posture as compared with the supine. Doppler flow estimates were obtained in all subjects to maximal exertion but in only a minority of subjects with two-dimensional echocardiography or thermodilution. Thus two-dimensional and Doppler echocardiography offer a noninvasive means of estimating cardiac output during vigorous exercise. The Doppler technique is technically more suitable to the study of exercise than two-dimensional echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)
Nitrate tolerance: the lack of effect of N-acetylcysteine.
Authors: Parker J O , Farrell B , Lahey K A , Rose B F
Published: June 2011

The hemodynamic and antianginal effects of 30 mg of isosorbide dinitrate (ISDN) were assessed in 12 patients with chronic stable angina after initial dosing and after 7 to 10 days of therapy four times daily. During early therapy, ISDN produced significant hemodynamic and antianginal effects that persisted over a 3 hr observation period. During sustained therapy there was attenuation of the hemodynamic effects at rest, and treadmill exercise time to the onset of angina and to the development of moderate angina was increased 1 hr after dosing; no effect was apparent at 3 hr. During this state of nitrate tolerance, patients were treated with an infusion of normal saline or 100 mg/kg N-acetylcysteine and exercise testing was repeated. N-Acetylcysteine did not change the hemodynamic findings at rest or during exercise and there was no improvement in exercise tolerance. It is apparent that the short-term administration of reduced sulfhydryl groups does not reverse tolerance to the hemodynamic and antianginal effects of isosorbide dinitrate in an exercise test model.
Mechanisms of increase in mitral valve area and influence of anatomic features in double-balloon, catheter balloon valvuloplasty in adults with rheumatic mitral stenosis: a Doppler and two-dimensional echocardiographic study.
Authors: Reid C L , McKay C R , Chandraratna P A , Kawanishi D T , Rahimtoola S H
Published: June 2011

To study the mechanism of increase in the mitral valve area (MVA) and the anatomic features of the mitral valve that may affect the results of catheter double-balloon valvuloplasty (CBV) in adult patients with mitral stenosis, Doppler and two-dimensional echocardiography was performed in 12 patients before and immediately after CBV. Immediately after CBV, there was an increase in the transverse diameter of the mitral valve orifice from 18 +/- 1.6 to 25 +/- 2.8 mm (mean +/- SD, p less than .001). The anterior angles at the commissure increased from 33 +/- 6 to 57 +/- 20 degrees (p less than .05) and the posterior angles from 36 +/- 9 to 54 +/- 14 degrees (p less than .05). The MVA was greater after CBV in patients with pliable mitral valves (2.6 +/- 0.7 cm2) compared with those with rigid mitral valves (1.9 +/- 0.8 cm2; p = .08). After CBV, MVA was smaller in patients with calcification (2.1 +/- 0.2 cm2) compared with those without (2.7 +/- 0.5 cm2; p = .10) and in those with subvalvular disease (2.0 +/- 0.6 cm2) compared with those without (2.9 +/- 0.9 cm2;p = .03). The MVA by Doppler ultrasound before CBV (1.0 +/- 0.2 cm2) correlated well with MVA by cardiac catheterization (1.0 +/- 0.3 cm2; r = .8, SEE = 0.2 cm2). After CBV, the correlation of MVA by Doppler ultrasound (2.0 +/- 0.5 cm2) with MVA by cardiac catheterization (2.4 +/- 0.8 cm2) was poor (r = .3, SEE = 0.44 cm2).(ABSTRACT TRUNCATED AT 250 WORDS)
Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion.
Authors: Puett D W , Forman M B , Cates C U , Wilson B H , Hande K R , Friesinger G C , Virmani R
Published: June 2011

To explore the role of oxygen free radicals produced by the xanthine oxidase pathway on infarct size and left ventricular function, the effect of oxypurinol, an active metabolite of allopurinol and a potent noncompetitive inhibitor of xanthine oxidase, was assessed in a 90 min, closed-chest, canine preparation of occlusion-reperfusion. Animals were randomized to receive 25 mg/kg iv oxypurinol (n = 13) or saline (n = 13) 60 min after occlusion. Regional myocardial blood flow was measured with radioactive microspheres and regional ventricular function with contrast ventriculography. Hemodynamic variables, regional myocardial blood flow, and size of the occluded bed were similar in the two groups. Oxypurinol failed to reduce infarct size 24 hr after reperfusion when expressed as a percentage of the area at risk (36.3 +/- 4.9% vs 36.0 +/- 5.6%; p = NS). Both groups exhibited comparative radial shortening at baseline and similar degrees of dyskinesia 1 hr into occlusion (-6.6 +/- 1.2% vs -4.9 +/- 1.0%). However, oxypurinol-treated animals demonstrated an improved regional ventricular function at 3 hr after reperfusion (0.7 +/- 2.6% vs -2.8 +/- 2.0%) and a significant improvement at 24 hr (5.4 +/- 2.5% vs -3.2 +/- 1.7%; p less than .05). A reduced neutrophil infiltrate was observed in the border zone in treated animals. These findings suggest that oxygen free radicals derived from the xanthine oxidase pathway contribute to stunning of reversibly damaged myocardium but do not determine the final extent of myocardial necrosis in a canine preparation of reperfusion.
Quantification of the contractile response to injury: assessment of the work-length relationship in the intact heart.
Authors: Morris J J , Pellom G L , Murphy C E , Salter D R , Goldstein J P , Wechsler A S
Published: June 2011

We used a sonomicrometric determination of ventricular dimension to examine the effect of ischemia and reperfusion on the work-length relationship in the intact heart to develop a useful and precise variable of ventricular contractile response to injury. Twenty anesthetized dogs were instrumented with epicardial ultrasonic dimension transducers to record right ventricular free wall chord length and left ventricular minor-axis length, micromanometers to record ventricular pressures, and an electromagnetic probe to record pulmonary arterial (n = 8) or aortic (n = 7) flow. Dogs were subjected to either 20 min (n = 7) or 30 min (n = 13) of global cardiac ischemia supported by cardiopulmonary bypass. Data were acquired over a range of end-diastolic volumes produced by transient (5 to 10 sec) vena caval occlusion before and after ischemia. In both ventricles, systolic epicardial dimensional shortening correlated with flow probe-measured stroke volume (mean r = .969) and regional stroke work calculated as the integral of instantaneous ventricular pressure and epicardial dimension correlated with measured global stroke work (mean r = .960), confirming the validity of dimensional measurements. Regression analysis demonstrated a highly linear relationship between calculated regional stroke work and end-diastolic length in the right ventricle (mean r = .973) and left ventricle (mean r = .967), quantifiable by a slope (Mw) and x intercept (Lw). Change in afterload produced by pulmonary arterial or aortic constriction resulted in no significant changes in Mw or Lw in either ventricle. Ischemia and reperfusion decreased Mw and shifted Lw to the right in both ventricles. The decrease in Mw with 30 min ischemia exceeded the decrease with 20 min ischemia by 29% in the right ventricle and by 32% in the left (p less than .04) with up to 1 hr of reperfusion. Changes in Lw were not related to severity of injury. After ischemia, infusion of calcium increased Mw by 177% in the right ventricle and by 67% in the left (p less than .03) without significant changes in Lw. Independent of load conditions, the slope Mw, of the linear stroke work vs end-diastolic length relationship is a valid and precise index of right and left ventricular contractile response to global ischemia in the intact circulation. This variable may be useful in evaluating therapies designed to limit myocardial injury and enhance ventricular functional performance.
Hierarchy of levels of ischemia-induced impairment in regional left ventricular systolic function in man.
Authors: Zeiher A M , Wollschlaeger H , Bonzel T , Kasper W , Just H
Published: June 2011

We tested the hypothesis that different subsets of ischemia-induced wall motion disorders are characterized by specific patterns of abnormal regional left ventricular systolic function. Regional contraction was quantitatively assessed from two-dimensional echocardiograms by an automated integrative analysis considering the time course of wall motion during the entire contraction sequence in 20 patients with chronic myocardial infarction, in 13 patients with impending myocardial infarction (less than 2 hr after the onset of symptoms), and in nine patients during transient myocardial ischemia. Wall motion abnormalities were detected in all patients by the integrative analysis. In contrast, the sensitivity for detecting wall motion abnormalities was 80% during chronic infarction, 77% during impending infarction, and 56% during transient ischemia if only end-diastolic and end-systolic frames were compared for assessment of overall regional systolic function. There were distinct differences in the time course of abnormal wall excursion between the three groups. Chronic infarction was characterized by a monophasic contraction pattern, with abnormal synergy in regional contractile events occurring predominantly during early systole. In contrast, transient ischemia caused predominantly mid-to-late systolic abnormal synergy followed by late systolic shortening corresponding to a polyphasic contraction pattern. During impending infarction, an intermediate temporal contraction pattern was present with both early and mesosystolic abnormal synergy.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial blood flow during exercise in dogs with left ventricular hypertrophy produced by aortic banding and perinephritic hypertension.
Authors: Bache R J , Dai X Z , Alyono D , Vrobel T R , Homans D C
Published: June 2011

This study tested the hypothesis that for similar degrees of left ventricular hypertrophy, subendocardial blood flow would be facilitated by the increased diastolic coronary perfusion pressure associated with arterial hypertension, as compared with hypertrophy produced by banding the ascending aorta. Left ventricular hypertrophy was produced with perinephritic hypertension in seven adult dogs and by banding the ascending aorta in nine adult dogs. Left ventricular/body weight ratios were 6.15 +/- 0.59 g/kg in the hypertensive animals and 6.87 +/- 0.47 g/kg in dogs with aortic banding, as compared with 4.23 +/- 0.23 g/kg in seven normal dogs (p less than .01). Studies were performed at rest and during two stages of treadmill exercise to achieve heart rates of 195 and 260 beats/min. Diastolic aortic pressure was increased in animals with hypertension but not in dogs with aortic banding. Systolic ejection period was prolonged in dogs with aortic banding but not in hypertensive dogs. Mean blood flow per gram of myocardium measured with microspheres was similar at rest and during light exercise in all three groups of animals, whereas during heavy exercise blood flow was significantly greater than normal in both groups with hypertrophy. In normal dogs subendocardial/subepicardial (endo/epi) flow ratios did not change significantly during exercise. In both groups with hypertrophy, endo/epi ratios were normal at rest but decreased significantly during exercise. During heavy exercise the endo/epi ratio decreased to 0.73 +/- 0.08 in dogs with aortic banding as compared with 1.07 +/- 0.12 in hypertensive dogs (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of dietary supplementation with cod-liver oil on endothelium-dependent responses in porcine coronary arteries.
Authors: Shimokawa H , Lam J Y , Chesebro J H , Bowie E J , Vanhoutte P M
Published: June 2011

To study the effect of dietary supplementation with fish oil on endothelium-dependent responses, Yorkshire pigs were maintained on a normal diet or on a low (0.6 ml/kg/day) or a high (1.0 ml/kg/day) dose of cod-liver oil for 4 weeks. Endothelium-dependent responses were examined in vitro in rings of proximal left anterior descending coronary arteries taken from control and treated animals studied in parallel. Endothelium-dependent relaxations in response to bradykinin, serotonin, adenosine diphosphate, and thrombin were facilitated in arteries from treated but not in those from control animals, whereas the relaxations in response to A23187 were unaltered. The facilitated relaxations were not altered by indomethacin but significantly inhibited by methylene blue. Aggregating platelets from control and treated pigs induced comparable, facilitated endothelium-dependent relaxations in rings taken from treated pigs. The platelet-induced contractions were significantly reduced in rings with endothelium taken from treated pigs, and they were comparable in rings without endothelium in both groups. Aggregating platelets from control and treated pigs released comparable amounts of serotonin and thromboxane A2. Endothelium-dependent relaxations induced by arachidonic acid and eicosapentaenoic acid were unaltered, whereas transient endothelium-dependent contractions induced by arachidonic acid were significantly reduced by the treatment with cod-liver oil. Relaxations to sodium nitroprusside or isoproterenol,and contractions to potassium chloride or serotonin were not different in rings without endothelium from control or treated pigs. These results indicate that dietary supplementation with cod-liver oil facilitates endothelium-dependent relaxations and inhibits endothelium-dependent contractions in porcine coronary arteries.
Improvement of postischemic myocardial function and metabolism induced by administration of deferoxamine at the time of reflow: the role of iron in the pathogenesis of reperfusion injury.
Authors: Ambrosio G , Zweier J L , Jacobus W E , Weisfeldt M L , Flaherty J T
Published: June 2011

Reperfusion of ischemic myocardium has been postulated to result in a specific oxygen radical-mediated component of tissue injury. In a previous study we demonstrated improved recovery of ventricular function and metabolism when the superoxide radical scavenger superoxide dismutase was administered at the time of postischemic reflow. Studies in vitro, have suggested that superoxide toxicity might be mediated via the generation of more reactive hydroxyl radicals in an iron-catalyzed reaction. The present study was designed to test the hypothesis that myocardial reperfusion injury might be reduced by administration of the iron chelator deferoxamine at the time of reflow, most likely by preventing hydroxyl radical formation. Sixteen isolated Langendorff rabbit hearts, perfused within the bore of a superconducting magnet, were subjected to 30 min of normothermic (37 degrees C) total global ischemia followed by 45 min of reperfusion. At reflow eight treated hearts received a 10 ml bolus containing 50 mumol of deferoxamine followed by an infusion of 11 mumol/min for the first 15 min of reflow. The hearts were then perfused with standard perfusate for an additional 30 min. Eight untreated control hearts received a similar bolus of perfusate followed by 45 min of standard reperfusion. Serial 5 min 31P nuclear magnetic resonance spectra were recorded. Myocardial phosphocreatine (PCr) content fell to 5% to 7% of control during ischemia in both groups of hearts. Deferoxamine-treated hearts recovered 99 +/- 10% of control PCr content, while untreated hearts recovered 60 +/- 16% (p less than .05). Intracellular pH fell to 5.9 during ischemia in both groups, before showing more rapid and complete recovery in treated hearts (p less than .01). Recovery of developed pressure reached 70 +/- 6% of control in treated hearts compared with 35 +/- 10% in untreated hearts (p less than .05). Iron content of the perfusate was 7 microM, and by electron paramagnetic resonance spectroscopy was in the form of Fe3+-EDTA complexes. In the effluent of treated hearts iron was in the form of Fe3+-deferoxamine chelates. In summary, administration of the iron chelator deferoxamine at the time of postischemic reflow results in greater recovery of myocardial function and energy metabolism, which supports the hypothesis that iron plays an important role in the pathogenesis of reperfusion injury.
The functional border zone in conscious dogs.
Authors: Gallagher K P , Gerren R A , Ning X H , McManimon S P , Stirling M C , Shlafer M , Buda A J
Published: June 2011

Studies focusing on the functional border zone have been performed largely with anesthetized, open-chest preparations. Therefore, we instrumented 14 dogs at sterile surgery with sonomicrometers arrayed to measure systolic wall thickening across the perfusion boundary produced by circumflex coronary occlusion. We fitted sigmoid curves to the data to model the distribution of wall thickening impairment as a function of distance from the perfusion boundary, which was delineated with myocardial blood flow (15 micron diameter microspheres) maps. Using this approach, we defined the functional border zone as the distance from the perfusion boundary to 97.5% of the sigmoid curve's nonischemic asymptote. The lateral extent of the functional border zone, measured 10 min and 3 hr after occlusion, was 32 and 28 degrees of circumference, respectively. To evaluate the severity of nonischemic dysfunction, we measured average systolic wall thickening within the functional border zone. It was reduced from 3.69 +/- 1.10 (mean +/- SD) mm to 2.98 +/- 1.07 mm (p less than .01) and 2.74 +/- 1.12 mm (p less than .01) early and late after coronary occlusion. Thus, a narrow functional border zone was evident during circumflex coronary occlusion in conscious dogs. Its lateral extent was limited to approximately 30 degrees (similar to findings in open-chest, anesthetized dogs), severe dysfunction was restricted to the immediate vicinity of the perfusion boundary, and the average severity of nonischemic dysfunction within the functional border zone was mild.
Isolated atrial septal defect with pulmonary vascular obstructive disease--long-term follow-up and prediction of outcome after surgical correction.
Authors: Steele P M , Fuster V , Cohen M , Ritter D G , McGoon D C
Published: June 2011

We examined the cases of 702 patients found to have isolated atrial septal defect of the secundum or sinus venosus type at catheterization from 1953 to 1978. Forty patients (6%), 34 women and six men, had pulmonary vascular obstructive disease, with a total pulmonary resistance greater than 7 U/m2; of these patients 26 (mean age 47 years) underwent surgical closure and 14 (mean age 44 years) received medical treatment. All patients were followed for at least 4 years, with a median follow-up of 12 years. At the most recent follow-up, 17 of the 40 patients were dead. Of the 22 surgically treated patients with total pulmonary resistance less than 15 U/m2, 19 were alive with significant regression of symptoms. All four surgically treated patients with total pulmonary resistance greater than or equal to 15 U/m2 were dead. Of the five medically treated patients with total pulmonary resistance less than 15 U/m2, four had died, and one was alive with significant progression of symptoms. Of the nine medically treated patients with total pulmonary resistance greater than or equal to 15 U/m2, six had died and the three survivors had progression of symptoms. In the surgically treated group, the following variables correlated with survival: total pulmonary resistance (p less than .00001), pulmonary arteriolar resistance (p less than .00001), pulmonary-to-systemic resistance ratio (p = .004), systemic arterial oxygen saturation (p = .005), and pulmonary arterial oxygen saturation (p = .007). In conclusion: (1) Atrial septal defect with high total pulmonary resistance is uncommon and predominates in adult female patients.(ABSTRACT TRUNCATED AT 250 WORDS)