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Biomedical subjects

L C Becker

Publications and source records attributed to L C Becker.

At least 55 records · Page 3Linked to original sources
PubMed1996

Ischemic, hemodynamic, and neurohormonal responses to mental and exercise stress. Experience from the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI).

BACKGROUND: The pathophysiology of mental stress-induced myocardial ischemia, which occurs at lower heart rates than during physical stress, is not well understood. METHODS AND RESULTS: The Psychophysiological Investigations of Myocardial Ischemia Study (PIMI) evaluated the physiological and neuroendocrine functioning in unmedicated patients with stable coronary artery disease and exercise-induced ischemia. Hemodynamic and neurohormonal responses to bicycle exercise, public speaking, and the Stroop test were measured by radionuclide ventriculography, ECG, and blood pressure and catecholamine monitoring. With mental stress, there were increases in heart rate, systolic blood pressure, cardiac output, and systemic vascular resistance that were correlated with increases in plasma epinephrine. During exercise, systemic vascular resistance fell, and there was no relationship between the hemodynamic changes and epinephrine levels. The fall in ejection fraction was greater with mental stress than exercise. During mental stress, the changes in ejection fraction were inversely correlated with the changes in systemic vascular resistance. Evidence for myocardial ischemia was present in 92% of patients during bicycle exercise and in 58% of patients during mental stress. Greater increases in plasma epinephrine and norepinephrine occurred with ischemia during exercise, and greater increases in systemic vascular resistance occurred with ischemia during mental stress. CONCLUSIONS: Mental stress-induced myocardial ischemia is associated with a significant increase in systemic vascular resistance and a relatively minor increase in heart rate and rate-pressure product compared with ischemia induced by exercise. These hemodynamic responses to mental stress can be mediated by the adrenal secretion of epinephrine. The pathophysiological mechanism involved are important in the understanding of the etiology of myocardial ischemia and perhaps in the selection of appropriate anti-ischemic therapy.

Adult↗
PubMed1996

Superoxide-mediated actin response in post-hypoxic endothelial cells.

The mechanism leading to changes in the superstructure of endothelial cells exposed to ischemia and reperfusion remains uncharacterized. We show that in post-hypoxic endothelial cells, the simple re-addition of oxygen induces a profound reorganization of the actin cytoskeleton. The total filamentous actin pool increases by 41% and translocation of actin filaments to the submembranous network is observed. Concurrent with the actin polymerization, increased tyrosine phosphorylation of endothelial cell substrates is detected on Western blots. Overexpression of superoxide dismutase using replication incompetent adenovirus inhibits the actin and tyrosine phosphorylation responses to reoxygenation. Inhibition of tyrosine kinases with the isoflavone genistein also suppressed the actin polymerization response to reoxygenation, but unlike superoxide dismutase, genistein also induced the collapse of the superstructure of endothelial cells upon reoxygenation. These experiments support the concept that reoxygenation following a period of hypoxia can induce the remodeling of the actin cytoskeleton in endothelial cells. Such a response requires the intact coupling of superoxide producing pathway(s) with tyrosine kinase pathway(s).

Actins↗
PubMed1996

Dose dependence of chronic positive inotropic effect of vesnarinone in patients with congestive heart failure due to idiopathic or ischemic cardiomyopathy.

Vesnarinone is a novel oral agent that improves survival and symptoms of patients with dilated cardiomyopathy. Although it is thought to have positive inotropic effects, clinical data supporting this mechanism in patients with severe heart failure remain scant. The present study tested whether 3 months of oral vesnarinone therapy increases the inotropic state and whether this response is dose dependent. Twenty-one patients with dilated cardiomyopathy (New York Heart Association class III to IV) were randomized to 30 mg/day (n = 11) or to 60 mg/day (n = 10) of vesnarinone. Cardiac function was assessed before and after therapy by radionuclide ventriculography to measure left ventricular volume and flow and by noninvasive measurement of the central aortic pressure wave. The inotropic effect of vesnarinone was assessed by a recently validated index equal to the ratio of left ventricular maximal ventricular power divided by the square of end-diastolic volume (PWRmax/ EDV2). This ratio is sensitive to inotropic change but is minimally altered by chamber loading. After 3 months of 60 mg/day therapy, PWRmax/EDV2 increased by 28 +/- 32%. Ejection fraction and cardiac output also increased by 21 +/- 14% and 14 +/- 14%, respectively, and arterial load decreased by 10.5 +/- 12.4% (all p < 0.005). End-systolic volume also declined by 7 +/- 10%, suggesting reverse remodeling. These changes were smaller and none achieved statistical significance at the 30 mg/day dose (e.g., 14.2 +/- 35.4% for PWRmax/ EDV2). Heart rate was unchanged with either dose. Thus, chronic vesnarinone treatment dose modestly raises the inotropic state and lowers afterload in patients with dilated cardiomyopathy in a dose-dependent fashion.

Administration, Oral↗
PubMed1996

Continuum of cardiovascular performance across a broad range of fitness levels in healthy older men.

BACKGROUND: Although it has become clear that habitual exercise in older individuals can partially offset age-associated cardiovascular declines, it is not known whether the beneficial effects of exercise training in older individuals depend on their prior fitness level. METHODS AND RESULTS: Ten sedentary men (S), age 60.0 +/- 1.6 years (mean +/- SEM), who were carefully screened to exclude cardiac disease underwent exercise training for 24 to 32 weeks, and eight age-matched endurance-trained men (ET) stopped their exercise training for 12 weeks. All underwent treadmill exercise and rest and maximal cycle exercise upright gated blood pool scans at baseline and after the lifestyle intervention. Before the intervention, the treadmill maximum rate of oxygen consumption (Vo2max) was 49.9 +/- 1.9 and 32.1 +/- 1.4 mL.kg-1.min-1 in ET and S, respectively. During upright cycle exercise at exhaustion, although heart rate did not differ between groups, cardiac index, stroke volume index, ejection fraction, and left ventricular contractility index (systolic blood pressure/end-systolic volume index) all were significantly higher, and end-systolic volume index, diastolic blood pressure, and total systemic vascular resistance all were significantly lower in ET versus S. After the partial deconditioning of ET men, Vo2max fell to 42 +/- 2.2 mL.kg-1.min-1, and training of S increased Vo2max to 36.2 +/- 1.6 mL.kg-1.min-1. Training of S had effects on cardiovascular function that were similar in magnitude but directionally opposite those of detraining ET. All initial differences in cardiovascular performance at peak work rate between S and ET were abolished with the intervention. Across the broad range of fitness levels encountered before and after change in training status (Vo2max of 26 to 58 mL.kg-1.min-1), cardiac index, stroke volume index, end-systolic volume index, ejection fraction, and the left ventricular contractility index were all linearly correlated with Vo2max. CONCLUSIONS: Exercise training or detraining of older men results in changes in left ventricular performance that are qualitatively and quantitatively similar, regardless of the initial level of fitness before the intervention.

Aging↗
PubMed1996

A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis.

BACKGROUND: Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and von Willebrand factor, and it has an important role in platelet aggregation. It is known to be involved in the pathogenesis of acute coronary syndromes. Previously, we found a high frequency of a particular polymorphism, PlA2, of the gene encoding glycoprotein IIIa in kindreds with a high prevalence of premature myocardial infarction. METHODS: To investigate the relation between the PlA2 polymorphism and acute coronary syndromes, we conducted a case-control study of 71 case patients with myocardial infarction or unstable angina and 68 inpatient controls without known heart disease. The groups were matched for age, race, and sex. We used two methods to determine the PlA genotype: reverse dot blot hybridization and allele-specific restriction digestion. RESULTS: The prevalence of PlA2 was 2.1 times higher among the case patients than among the controls (39.4 percent vs. 19.1 percent, P=0.01). In a subgroup of patients whose disease began before the age of 60 years, the prevalence of PlA2 was 50 percent, a value that was 3.6 times that among control subjects under 60 years of age (13.9 percent, P=0.002). Among subjects with the PlA2 polymorphism, the odds ratio for having a coronary event was 2.8 (95 percent confidence interval, 1.2 to 6.4). In the patients less than 60 years of age at the onset of disease, the odds ratio was 6.2 (95 percent confidence interval, 1.8 to 22.4). CONCLUSIONS: We observed a strong association between the PlA2 polymorphism of the glycoprotein IIIa gene and acute coronary thrombosis, and this association was strongest in patients who had had coronary events before the age of 60 years.

Acute Disease↗
PubMed1996

Exercise thallium tomography predicts future clinically manifest coronary heart disease in a high-risk asymptomatic population.

BACKGROUND: Exercise testing, even when combined with radionuclide perfusion imaging, does not accurately predict future clinical coronary heart disease (CHD) in low-risk asymptomatic populations. We hypothesized that these tests would perform better in a higher-risk population with a high prevalence of occult CHD. Siblings of persons with premature CHD represent such a group in whom it would be advantageous to identify affected individuals before the occurrence of clinically manifest CHD. METHODS AND RESULTS: Exercise thallium scintigraphy was performed in 264 asymptomatic individuals less than 60 years of age who had a sibling with documented CHD before age 60. Despite an average age of only 46 years at the time of screening, 19 of 264 siblings developed clinical CHD (sudden death in 1, myocardial infarction in 10, coronary revascularization in 8) over a mean of 6.2 years (range, 1 to 9 years) of follow-up. Abnormal thallium scans were observed in 29% of men and 9% of women, while abnormal exercise ECGs occurred in 12% and 5% respectively. Of men >/= 45 years of age, 45% had an abnormal exercise ECG, thallium scan, or both. In contrast, only 3% of women < 45 years of age had an abnormal test result. Although abnormal exercise ECGs and thallium scans were both predictive of future clinical CHD, the thallium scan was associated with a higher relative risk. After adjustment for age, sex, and exercise ECG results, the relative risk of developing clinical CHD was 4.7 for an abnormal scan. Siblings with a concordant abnormal exercise ECG and thallium scan had a relative risk of 14.5. These siblings were all men > 45 years of age at the time of screening and had a strikingly high incidence of CHD (6 of 12, 50%). CONCLUSIONS: Exercise thallium scintigraphy appears to be useful in the risk assessment of asymptomatic siblings of patients with premature CHD, particularly in male siblings who are 45 years of age or older.

Adult↗
PubMed1996

An anti-CD18 antibody limits infarct size and preserves left ventricular function in dogs with ischemia and 48-hour reperfusion.

OBJECTIVES: This study investigated whether an antibody against neutrophil adhesion protein CD18 could limit myocardial infarct size and preserve left ventricular function after prolonged reperfusion in a canine model. BACKGROUND: Myocardial reperfusion injury is mediated in part by accumulation of activated neutrophils. Although antibodies against CD18 have been shown to reduce neutrophil influx and infarct size after ischemia and 3 to 4 h of reperfusion, it is unknown whether protection is sustained beyond this time or whether there is meaningful preservation of ventricular function. METHODS: Dogs undergoing 90-min circumflex coronary artery occlusion and 48-h reperfusion were randomized to receive 1 mg/kg bodyweight of R15.7 (an anti-CD18 antibody, n = 12) or saline (control, n =12) 10 min before reperfusion. Contrast left ventriculography was used to measure left ventricular ejection fraction and regional chord shortening at baseline, during occlusion and at 48 h. Microspheres injected during occlusion were used to measure collateral flow and risk region size. Postmortem infarct size was measured with triphenyltetrazolium chloride. RESULTS: In the dose administered, R15.7 bound to neutrophils in vivo, with >85% saturation of CD18 for >24 h, with sustained antibody excess in the plasma. R15.7 significantly reduced infarct size after adjusting for the effect of collateral flow (p = 0.0002, analysis of covariance). In a subgroup of dogs with collateral flow <30% of nonischemic flow, infarct size was reduced from 34.6 +/- 3.9% (mean +/- SE) of the region at risk in the control group to 19.5 +/- 3.3% in the antibody group (p = 0.008). Ejection fraction and regional chord shortening did not differ between the two groups at baseline or during occlusion, but after 48-h reperfusion, ejection fraction and inferior wall regional cord shortening (representing the infarct zone) were both higher in the R15.7 group than the control group (43.6 +/- 2.9% vs. 28.5 +/- 1.8%, p < 0.01; 2.55 +/- 0.29% vs. 1.06 +/- 0.18%, p < 0.05). CONCLUSIONS: A single injection of an anti-CD18 antibody given before reperfusion can limit myocardial infarct size by nearly 50% and preserve global and regional left ventricular function after 48 h of reperfusion.

Animals↗
PubMed1996

Factors modifying protective effect of anti-CD18 antibodies on myocardial reperfusion injury in dogs.

Anti-CD18 monoclonal antibodies (MAb) have demonstrated variable protection against neutrophil (PMN)-mediated myocardial reperfusion injury. To identify factors contributing to this variability, open-chest dogs underwent coronary artery occlusion for 90 min followed by reperfusion for 3.5 h. Ten minutes before reperfusion the dogs received saline (n = 18) or one of three anti-CD18 MAb: MHM.23, R15.7, or PLM-2 (2, 1, and 1 mg/kg and n = 19, 8, and 4, respectively). Collateral flow was measured with radioactive microspheres, area at risk was assessed with monastral blue dye, and infarct size was measured postmortem by triphenyltetrazolium chloride. In vitro, all three MAb bound to canine PMNs, but only MHM.23 and R15.7 inhibited their adherence to keyhole limpet hemocyanin-coated plastic. In vivo, only MHM.23 and R15.7 significantly reduced infarct size after adjusting for the effect of collateral flow. MHM.23 afforded protection in dogs with moderate ischemia (epicardial collateral flow > 0.1 ml.min-1.g-1, infarct size reduced 46%) but not in dogs with more severe ischemia. Only R15.7 was effective in dogs with severe ischemia. Although MHM.23 and R15.7 produced similar inhibition of tissue PMN accumulation, as reflected by myeloperoxidase activity. R15.7 markedly inhibited H2O2 production by PMNs after exposure to platelet-activating factor, whereas MHM.23 had only a minimal effect. The effectiveness of different anti-CD18 MAb in preventing reperfusion injury appears to be 1) highly dependent on the specific anti-CD18 MAb employed, 2) predicted only partially by in vitro binding to PMNs, static in vitro tests of PMN adherence, or the extent of inhibition of PMN accumulation in vivo, 3) related more to their ability to inhibit oxidant release from activated PMNs, and 4) strongly influenced by the severity of myocardial ischemia before reperfusion.

Animals↗
PubMed1995

Effect of early enalapril therapy on left ventricular function and structure in acute myocardial infarction.

Infarct expansion starts within hours to days after transmural myocardial injury. Previous echocardiographic and left ventriculographic studies demonstrated that angiotensin-converting enzyme (ACE) inhibitor therapy limits left ventricular dilatation, particularly in patients with anterior wall acute myocardial infarction (AMI) or impaired left ventricular function. Forty-three patients with an acute Q-wave AMI were randomized within 24 hours of symptom onset to intravenous enalaprilat (1 mg) or placebo. Patients were then given corresponding oral therapy and followed for 1 month. Predrug and 1-month gated blood pool scans were obtained in 32 patients to evaluate changes in cardiac volumes and ejection fraction. Twenty-three patients underwent magnetic resonance imaging at 1 month to evaluate left ventricular infarct expansion. Blood pressure decreased at 6 hours but returned to baseline in both groups after 1 month of therapy. The change in cardiac volumes from baseline to 1 month differed between the placebo (end-diastolic volume +16 +/- 5 ml, end-systolic volume +8 +/- 6 ml), and enalapril (end-diastolic volume -8 +/- 9 ml and end-systolic volume -14 +/- 7 ml) groups (p < 0.05 vs placebo). Global and infarct zone ejection fractions improved significantly at 1 month in the enalapril group (+6 +/- 3% and 19 +/- 5%, respectively) but did not change over 1 month in the placebo group. Infarct segment length and infarct expansion index by magnetic resonance imaging were significantly less in those treated with enalapril, suggesting less infarct expansion in this group. Thus, early administration of enalaprilat to patients presenting with a first Q-wave AMI prevents cardiac dilatation and infarct expansion.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Physiological basis of myocardial contrast enhancement in fast magnetic resonance images of 2-day-old reperfused canine infarcts.

BACKGROUND: Contrast-enhanced fast magnetic resonance (MR) images of acute, reperfused human infarcts demonstrate regions of hypoenhancement and hyperenhancement. The relations between the spatial extent and time course of these enhancement patterns to myocardial risk, infarct, and no-reflow regions have not been well characterized. METHODS AND RESULTS: The proximal left anterior descending coronary artery was occluded in 11 closed-chest dogs for 90 minutes followed by 2 days of reperfusion. Regional blood flow was determined by use of radioactive microspheres. The animals were studied at the 2-day time point with contrast-enhanced fast MRI (Signa 1.5 T, General Electric). Thioflavin-S was administered to demarcate no-reflow regions. The hearts were then excised, sectioned into five base-to-apex slices, stained with 2,3,5-triphenyltetrazolium chloride (TTC), and photographed under room light (for TTC) and ultraviolet light (for thioflavin). The spatial extents of thioflavin-negative, TTC-negative, and risk regions were compared planimetrically with MRI hypoenhanced and hyperenhanced regions. The spatial locations of subendocardial hypoenhancement in MR images correlated closely with those of thioflavin-negative regions. Microsphere blood flow in these regions was significantly reduced compared with remote regions (0.37 +/- 0.09 versus 0.88 +/- 0.10 mL/min per gram, respectively, P < .001) and with baseline (0.37 +/- 0.09 versus 0.87 +/- 0.15 mL/min per gram, P < .01). The spatial extent of hyperenhancement was smaller than the risk region (r = .64, slope = 0.48, P < .001) but highly correlated with TTC-negative regions and were, on average, 12% larger (r = .93, slope = 1.12, P = .035). CONCLUSIONS: In contrast-enhanced MR images of 2-day-old reperfused canine infarcts, myocardial regions of hypoenhancement are related to the no-reflow phenomenon. Approximately 90% of the myocardium within hyperenhanced regions is nonviable.

Animals↗
PubMed1995

Cardiac single-photon emission tomography with a 90 degrees dual-head system.

Dual-head single-photon emission tomography (SPET) systems which permit a 90 degrees orientation of the heads provide a twofold increase in sensitivity for 180 degrees SPET compared with single-head systems. Since such systems have additional mechanical and electrical alignment and stability requirements, clinical equivalency for myocardial perfusion SPET must be demonstrated. Accordingly, we studied 26 subjects who underwent exercise thallium scintigraphy consecutively with both single-head and dual-head systems. Image acquisition was similar, except that the dual-head study took one-half the time. Image reconstruction was identical. Images were interpreted in a blinded fashion, and rated for technical quality. All 26 studies were equivalently interpreted for the presence or absence of perfusion defects. Fourteen of the studies were judged to be technically equivalent; seven were judged to be slightly better with the single-head system; three were judged to be slightly better with the dual-head system; and two were judged to be definitely better with the dual-head system. We conclude that dual-head 90 degrees systems provide equivalent clinical performance in half the acquisition time.

Aging↗
PubMed1995

Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women.

To examine whether age differentially modifies the physiological response to exercise in men and women, we performed gated radionuclide ventriculography with measurement of left ventricular volumes at rest and during peak upright cycle exercise in 200 rigorously screened healthy sedentary volunteers (121 men and 79 women) aged 22-86 yr from the Baltimore Longitudinal Study of Aging. At rest in the sitting position, age-associated declines in heart rate (HR) and increases in systolic blood pressure occurred in both sexes. Whereas resting cardiac index (CI) and total systemic vascular resistance (TSVR) in men did not vary with age, in women resting CI decreased 16% and TSVR increased 46% over the six-decade age span. Men, but not women, demonstrated an age-associated increase of approximately 20% in sitting end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and stroke volume index over this age span. Peak cycle work rate declined with age approximately 40% in both sexes, but at any age it was greater in men than in women even after normalization for body weight. At peak effort, ejection fraction (EF), HR, and CI were reduced similarly with age while ESVI and TSVR were increased in both sexes; EDVI increased 35% with age and stroke work index (SWI) rose 19% in men, but neither was related to age in women; and stroke volume index did not vary with age in either sex. When hemodynamics were expressed as the change from rest to peak effort as an index of cardiovascular reserve function, both sexes demonstrated age-associated increases in EDVI and ESVI and reductions in EF, HR, and CI. However, the exercise-induced reduction in ESVI and the increases in EF, CI, and SWI from rest were greater in men than in women. Thus, age and gender each have a significant impact on the cardiac response to exhaustive upright cycle exercise.

Adult↗
PubMed1995

Functional coupling between glycolysis and sarcoplasmic reticulum Ca2+ transport.

To investigate whether the energy derived from glycolysis is functionally coupled to Ca2+ active transport in sarcoplasmic reticulum (SR), we determined whether glycolytic enzymes were associated with SR membranes and whether metabolism through these enzymes was capable of supporting 45Ca transport. Sealed right-side-out SR vesicles were isolated by step sucrose gradient from rabbit skeletal and cardiac muscle. Intravesicular 45Ca transport was measured after the addition of glycolytic substrates and cofactors specific for each of the glycolytic reactions being studied or after the addition of exogenous ATP and was expressed as transport sensitive to the specific Ca(2+)-ATPase inhibitor thapsigargin. We found that the entire chain of glycolytic enzymes from aldolase onward, including aldolase, GAPDH, phosphoglycerate kinase (PGK), phosphoglyceromutase, enolase, and pyruvate kinase (PK), was associated with SR vesicles from both cardiac and skeletal muscle. Iodoacetic acid, an inhibitor of GAPDH, eliminated 45Ca transport supported by fructose-1,6-diphosphate, the substrate for aldolase, but transport was completely restored by phosphoenolpyruvate (the substrate for PK), indicating that both of the ATP-producing glycolytic enzymes, GAPDH/PGK and PK, were associated with the SR and functionally capable of providing ATP for the Ca2+ pump. Addition of a soluble hexokinase ATP trap eliminated 45Ca transport fueled by exogenous ATP but had markedly less effect on 45Ca transport supported by endogenously produced ATP (via glycolysis). Similarly, at very low concentrations of ATP and ADP (10 to 50 nmol/L), ATP that was produced endogenously from ADP and phosphoenolpyruvate supported 15-fold more 45Ca transport than ATP that was supplied exogenously at the same concentration. These results are consistent with functional coupling of glycolytic ATP to Ca2+ transport and support the hypothesis that ATP generated by SR-associated glycolytic enzymes may play an important role in cellular Ca2+ homeostasis by driving the SR Ca2+ pump.

Adenosine Triphosphate↗
PubMed1994

Risk factors for exercise-induced silent myocardial ischemia in healthy volunteers.

This study determined the risk factors for exercise-induced silent ischemia (SI) in 281 apparently healthy volunteers aged 40 to 87 years and compared their risk factor profiles with those of 132 patients with overt coronary artery disease (CAD). SI (concordant exercise-induced asymptomatic ST-segment depression on electrocardiography and perfusion defects on tomographic thallium-201 scintigraphy) was detected in 37 of 225 men (16%), versus 2 of 56 women (4%, p < 0.05). The prevalence of SI increased with age from 6% in men aged < 55 years to 18% in men aged 55 to 70 years, and to 25% in men aged > 70 years (p < 0.001). Compared with the 118 men with concordant normal exercise electrocardiogram and thallium scan (normals), men with SI were older (p < 0.001), and had a higher waist-to-hip ratio (p < 0.005), higher plasma triglyceride levels (p < 0.001), and lower high-density lipoprotein (HDL) cholesterol levels (p < 0.001). In stepwise logistic regression analysis, age, waist-to-hip ratio, and HDL levels were independent predictors of SI in men. Compared with 108 men with overt CAD, men with SI were younger (67 +/- 2 vs 73 +/- 1 years, p < 0.001) but had similar plasma lipids and waist-to-hip ratio. Thus, older age, male gender, abdominal obesity, and reduced HDL levels--all well-established risk factors for overt CAD--were risk factors for exercise-induced SI in these asymptomatic volunteers.

Age Factors↗
PubMed1994

Quantification of neutrophil migration following myocardial ischemia and reperfusion in cats and dogs.

Endothelial cell dysfunction and cardiac myocyte injury resulting from ischemia and reperfusion have been associated with accumulation of neutrophils in the myocardium. To determine whether the accumulation is related primarily to intravascular sequestration or extravascular infiltration of neutrophils during the early period of reperfusion, we morphometrically quantified the tissue distribution of neutrophils in cats and dogs. At the end of the reperfusion period, the base of the heart was cross-clamped to preserve neutrophil location at the moment of death. Point-counting methods were used to determine the distribution of neutrophils inside and outside coronary arterioles and venules (< or = 100 microns in diameter) as well as coronary capillaries 5-10 microns in diameter in 0.5-microns-thick, plastic-embedded sections. Ischemia-reperfusion resulted in a threefold increase in neutrophil number in the lumen of arterioles and venules at 60 min of reperfusion and up to a sevenfold increase at 270 min of reperfusion (P < .05) compared to time-matched control nonischemic hearts. The ratio of intravascular neutrophils in venules to arterioles was 2:1. Intracapillary neutrophils increased, but not significantly, at 60 min of reperfusion. At 270 min of reperfusion, intracapillary neutrophils increased 11-fold (P < .05). The percentage of total neutrophils that accumulated outside arterioles and venules in cat hearts was 8% at 60 min of reperfusion (not significant, NS) and 28% at 270 min of reperfusion (P < .05). In dog hearts, the percentages were 26% (NS) and 44% (P < .05), respectively. The percentage of total neutrophils that accumulated outside capillaries was < 6% in both cat and dog hearts (NS). The combination of rapid intravascular sequestration, delayed extravascular infiltration, and low incidence of neutrophil-cardiac myocyte contact in situ in these two species suggests that neutrophil-mediated cardiac myocyte injury during early reperfusion may initially depend on diffusion of inflammatory mediators and subsequently require direct contact between neutrophils and cardiac myocytes.

Animals↗
PubMed1994

Effect of body fat on exercise hemodynamics in sedentary older men.

Morbid obesity is often associated with cardiac dilatation and left ventricular dysfunction. The present study investigated whether a similar relationship exists between mild and moderate obesity and left ventricular reserve function in 28 middle aged and older men (58.6 +/- 6.1 years, mean +/- SD). Subjects had a body mass index of 26.4 +/- 2.9 kg/m2, a percent body fat determined by hydrodensitometry ranging from 9.5% to 33.8%, and were carefully screened to exclude cardiovascular disease. Left ventricular function was assessed by gated blood pool scans at rest and during exhaustive upright cycle exercise. There were no significant relationships between resting or exercise cardiac volumes or ejection fraction with percent body fat; however, peak work rate/kg correlated inversely with percent body fat (r = -0.68, p < 0.0001). Heart rate reserve, defined as heart rate at peak work rate minus resting heart rate, declined significantly with increasing percent body fat (r = -0.47, p = 0.01). End diastolic volume index reserve also tended to decline with increasing percent body fat, but stroke volume index and cardiac index reserve were maintained because the decrease in end systolic volume index from rest to maximal exercise was greatest in those subjects with highest percent body fat (r = -0.41, p = 0.03). Therefore, rest and exercise left ventricular function are not related to percent body fat in healthy older men. However, older more obese men have a smaller increase in heart rate and end diastolic volume and a greater decrease in end systolic volume from rest to peak effort as a mechanism to augment exercise cardiac output.

Body Mass Index↗
PubMed1994

Hemodynamic vascular forces contribute to impaired endothelium-dependent vasodilation in reperfused canine epicardial coronary arteries.

OBJECTIVES: We studied canine coronary arterial vasoreactivity after occlusion and reperfusion to examine whether reduced flow or pressure contributed to the abnormalities observed. BACKGROUND: Ischemia and reperfusion alter endothelial and myocardial function. Causative factors may include altered flow, complement activation or free radical production by endothelial or white blood cells after reoxygenation and neutrophil activation. METHODS: The coronary arteries of anesthetized, open chest dogs were subjected to 90-min occlusion +/- 2 h of reperfusion. The effect of reperfusion on arterial responses to intracoronary acetylcholine, nitroprusside and phenylephrine was studied using in vivo ultrasound. Arterial segments were also harvested, perfused ex vivo with cell-free buffer and exposed to potassium chloride, nitroprusside, acetylcholine and bradykinin. The effect of ex vivo flow cessation with or without maintained intralumen pressure was also studied. RESULTS: Results are expressed as mean value +/- SEM. In vivo arterial cross-sectional area increased during infusion with acetylcholine (10(-5) mol/liter [18.5 +/- 9%]) and nitroprusside (10(-5) mol/liter [22.5 +/- 10%]) and decreased with phenylephrine (10(-5) mol/liter [7.6 +/- 7%]). After reperfusion, acetylcholine caused 13.5 +/- 9% vasoconstriction. Nitroprusside and phenylephrine responses were unchanged. Reperfused arterial segments also showed impaired vasodilation in response to 10(-6) mol/liter of acetylcholine (10.6 +/- 5.1% vs. 47.1 +/- 4.9% in control vessels) and 10(-8) mol/liter of bradykinin (4.4 +/- 6.7% vs. 27.9 +/- 8% in control vessels). Ex vivo flow cessation impaired acetylcholine-mediated vasodilation, but this abnormality was prevented when high intralumen pressure was maintained during the no-flow period. CONCLUSIONS: Reduction in flow and intralumen pressure contribute to the impaired acetylcholine-mediated vasodilation seen after coronary occlusion. This is prevented by maintaining high intralumen pressure during the no-flow period, suggesting that hemodynamic forces may change endothelial function independent of circulating complement or blood cell elements.

Acetylcholine↗