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ABSTRACT: Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation.
The American journal of cardiology 02/2011; 107(9):1255-61. · 3.58 Impact Factor
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ABSTRACT: The benefits of leisure time physical activity (LTPA) in cardiovascular prevention are well established. While cardiac rehabilitation programmes have been demonstrated as improving myocardial infarction (MI) prognosis, the strength of the association between LTPA and post-MI survival has yet to be quantified. We evaluated long-term survival after MI of inactive, irregularly active, and regularly active patients and examined trajectories of LTPA and their relationship to mortality risk. Consecutive patients aged ≤65 years (n = 1,521), discharged from 8 hospitals in central Israel after first MI in 1992-1993, were followed through 2005. Extensive clinical and sociodemographic data, including self-reported LTPA habits, were obtained at baseline and at 4 subsequent interviews. Pre-MI inactive patients (54%) had lower socioeconomic status, higher prevalence of risk factors and comorbidities and more severe MI. The point prevalence rate of regular LTPA at all follow-up interviews was approximately 40% and 18% were regularly active throughout the entire follow-up. Over a median follow-up of 13.2 years, 427 deaths occurred. After multivariable adjustment, no association was observed between pre-MI LTPA and death. However, with LTPA categories modelled as time-dependent variables, providing an estimation of cumulative assessment and accounting for changes in LTPA post-MI, a strong inverse graded association was revealed (multivariable-adjusted hazard ratios, 0.56 [95% CI: 0.42-0.74] for regular and 0.71 [95% CI: 0.54-0.95] for irregular activity vs. none). Similar estimates were obtained among pre-MI sedentary patients. In summary, after MI, regularly active patients had about half the risk of dying compared with inactive patients, irrespective of pre-MI habits.
European Journal of Epidemiology 02/2011; 26(2):109-16. · 4.71 Impact Factor
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ABSTRACT: Previous studies have shown that pre-exposure of the heart to weak magnetic field reduces infarct size shortly after induction of myocardial ischemia. To investigate the role of AC magnetic field with a frequency of 15.95-16 Hz and 80 mT on left ventricular (LV) remodeling following chronic coronary occlusion and a short episode of ischemia followed by reperfusion (I/R). LV dimension and function were measured using echocardiography. Femur bone marrow was isolated and cells were phenotyped for endothelial linage and immuno stained for endothelial cells. The area at risk was measured using triphenyltetrazolium chloride staining. A significant reduction of 27% in shortening fraction (SF) was measured following acute myocardial infarction (AMI) compared with a 7% decrease in animals exposed to magnetic field (p < 0.04). A significantly higher number of colony forming units and endothelial progenitor cells were counted within the treated groups subjected to magnetic field (p < 0.02). Exposing the heart to magnetic field prior to reperfusion did not show any preservation either on SF or on infarct size. Magnetic field was protective in the AMI but not in the I/R model. The mechanisms underlying cardiac protection induced by AC magnetic field following chronic injury deserves further investigation.
Annals of biomedical engineering 07/2009; 37(10):2093-104. · 2.41 Impact Factor
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ABSTRACT: We and others have shown that swimming exercise training performed before irreversible coronary occlusion improves the outcome of the heart injury and alters gene expression at the remodeling phase. The purpose of the current study was to identify temporal changes in the molecular response to myocardial infraction of prior exercise trained rats during the acute, the subacute, and the chronic phases postinfarction.
Rats underwent a 7-wk swimming or sedentary protocol and were subjected to surgical induction of acute myocardial infarction (MI). Hearts were removed before and at 4 h, 2 d, and 4 wk after surgery. RNA extracted from the surviving myocardium of the MI hearts or from corresponding tissues in the non-MI hearts was subjected to multitranscript profiling. Results for representative transcripts were validated by reverse transcription and quantitative polymerase chain reaction amplification.
Global analysis of the 3686 detected transcripts generated a two-branch dendrogram that distinguished the pre-MI and the 4-h groups from the 2-d and the 4-wk groups and indicated that early after MI, the impact of infarction on the genes expressed overrides the training effect, whereas at 4 wk, the exercised hearts differ markedly from the nonexercised. Clustering the 1500 genes that showed the highest variance over time indicated differential expression of transcription regulators and proapoptotic genes 4 h and 2 d after MI and of stress-related and profibrotic genes 4 wk later in the exercised compared with sedentary hearts.
Swimming exercise training conducted before acute MI reprograms the surviving myocardium for altered molecular response to MI that explains, in part, the protected cardiac phenotype of the exercised animals.
Medicine and science in sports and exercise 05/2009; 41(4):757-65. · 3.71 Impact Factor
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ABSTRACT: To evaluate the feasibility of a new 0.014'' CiTop guidewire to cross total occlusions within normal and diseased blood vessels; proof of concept.
Despite recent advances, chronic arterial occlusions remain the main obstacle of coronary and peripheral interventions.
The OVALUM CiTop 0.014'' guidewire is an over-the-wire catheter designed to penetrate through chronic total occlusions (CTO) and allow for further PCI interventions. The CiTop guidewire was tested in normal peripheral and coronary arteries of swine (n = 7) and in totally occluded arterial lesions within human amputations (n = 10).
The CiTop 0.014'' guidewire was operated successfully in seven peripheral blood vessels and 12 coronary arteries without angiographic or histological evidence of damage to the arterial wall. The CiTop crossed 9 of the 10 occluded segments within the human amputation with no angiographic or histological evidence of arterial damage (90% success rate). Average time to cross the occlusion was 4.6 +/- 5.6 min. In one artery (10%), angiographic evidence of perforation was noted and there was histological evidence for arterial wall damage.
Our data show that the new 0.014'' CiTop guidewire can be well operated within normal peripheral and coronary arteries of swine, and with minimal complications within totally occluded blood vessels from human amputations while effectively penetrating and crossing total arterial occlusions.
Catheterization and Cardiovascular Interventions 02/2009; 74(2):278-85. · 2.29 Impact Factor
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ABSTRACT: Untreated patients with congenital growth hormone deficiency (GHD) and IGF-I deficiency are characterized not only by dwarfism but also by acromicria and organomicria, such as the heart. We assessed cardiac dimensions and function in very young patients with Laron syndrome (LS) undergoing IGF-I replacement therapy.
Two to seven echocardiographic measurements were performed during IGF-I replacement therapy on male (n=4) and female (n=4) LS -patients, mean+/-SD age of 7.1+/-3.6 years (range 1.6-11.6 years), weight 16.1+/-9.7 kg, and height 89.9+/-18.5 cm. As aged- and gender-matched controls served 44 healthy children, age: 8.7+/-5.5 years, weight: 36.1+/-22.4 kg, and height: 129.7+/-33.1cm. Data of LS patients were normalized to body surface area and compared to the control group as well as nomograms of normal echocardiographic parameters for this age group.
Left ventricular diastolic and systolic dimensions (LVDD/ LVSD, mm) and LV mass (gr) were significantly smaller in boys and girls with IGF-I treated LS compared with controls while the shortening fraction (%) and intraventricular septum thickness (mm) were similar. When compared with standard values for this age group, all treated LS patients were within 1 standard deviation of the mean.
IGF-I therapy of young patients with Laron syndrome maintain LV dimensions and function within the normal range of aged-matched controls.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 01/2009; 19(3):280-2. · 2.35 Impact Factor
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ABSTRACT: There is accumulating data suggesting that physical activity is associated with reduced total mortality, sudden cardiac death, reduced risk of cardiovascular diseases, colon and breast cancer, osteoporosis, diabetes, hypertension, obesity, cognitive decline, dementia and depression. In addition, physical activity increases work productivity and well-being. Despite these health benefits, only approximately 30% of Israelis engage in regular physical activity. In Israel, the Physical Fitness Law requires a medical clearance prior to participation in physical activity in the gym. However, the medical community does not have written recommendations as to what type of examinations one should undergo. This paper was written following a request by the National Committee for the Prevention and Treatment of Cardiovascular Diseases, Israeli Ministry of Health, joined by the Israeli Heart Society to write new recommendations for the primary health care physician on the medical screening needed prior to the participation in a non-competitive physical activity among healthy Israelis. It includes a self report physical activity readiness questionnaire (PAR-Q), medical examinations, and exercise stress test. Since moderate types of physical activity performed under supervised conditions in a health/fitness facilities are safe, the recommendations for most individuals would be to complete the PAR-Q questionnaire with no further medical examinations. The position of the authors in the current article is similar to that approved by the National Committee for the Prevention and Treatment of Cardiovascular Diseases and the Israeli Heart Society and as was published by the Israel Medical Association.
Harefuah 08/2008; 147(7):611-7, 662, 661.
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ABSTRACT: The reduction in heart rate (HR) during the first minute of recovery immediately after a graded maximal exercise stress test (GXT) has recently been found to be a powerful and independent predictor of cardiovascular and all-cause mortality. Reduced vagal activity has been postulated as the cause, but this has not been proven in a population with slow HR recovery (HRR).
To investigate autonomic contributions to HRR using time-frequency analysis in a group of individuals demonstrating slow HRR.
HRR was defined as the difference in HR between peak exercise and 1 min later; a value < or = 18 bpm was set as threshold and considered abnormal. A modified continuous wavelet transform (CWT) was used to perform time-dependent spectral analysis during the baseline steady state and the following non-steady-state conditions created by GXT. This method provides dynamic measures of low-frequency (LF) and high-frequency (HF) peaks associated with autonomic activity. Individuals (N = 20) with a previous slow HRR underwent a second GXT within 3 months after their initial test. An additional eight subjects whose first GXT disclosed normal HRR were taken as a control group.
Seven of 20 subjects demonstrated slow HRR (14 +/- 5 bpm) on the repeat test, and 13 subjects displayed normal HRR (29 +/- 5 bpm). Subjects with slow HRR in both GXT displayed significantly (P < 0.05) lower HF and LF fluctuations during recovery than those with normal HRR.
Attenuated HRR after GXT, assessed by CWT, is indeed associated with abnormal vagal reactivation and prolonged sympathetic stimulation after termination of maximal exercise.
Medicine & Science in Sports & Exercise 01/2007; 38(12):2095-101. · 4.43 Impact Factor
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ABSTRACT: We investigated the effect of low-intensity ultrasound (US) on tissue blood flow and angiogenesis after limb ischemia in vivo. Rats underwent surgical ligation of the femoral or the iliac arteries. Half the animals were exposed to low-intensity US (0.05 W/cm2) during three consecutive sessions. At 3 weeks postsurgery, limb perfusion was assessed using laser Doppler and angiography. Immunostaining and vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) expression were performed 7 d postsurgery. US irradiation significantly improved limb perfusion in both ischemic models (p = 0.04). Angiography showed increased blood vessels in the moderate ischemia (p = 0.01), but not in the severe ischemia (p = 0.19). Histology demonstrated a significantly higher number of blood vessels and proliferating cells in US-irradiated moderate and severe ischemia (p = 0.002 and p = 0.03, respectively). VEGF mRNA was significantly higher in moderate ischemia (p = 0.02). No differences in apoptotic cell death were evident in the models. Low-intensity US significantly improved tissue blood flow and angiogenesis, irrespective of the extent of the ischemia. (E-mail: ).
Ultrasound in Medicine & Biology 02/2006; 32(1):139-45. · 2.29 Impact Factor
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ABSTRACT: Deep pressure sores (DPS) are associated with inadequate soft tissue perfusion and excessive tissue deformation over critical time durations, as well as with ischemia-reperfusion cycles and deficiency of the lymphatic system. Muscle tissue shows the lowest tolerance to pressure injuries, compared with more superficial tissues. In this communication, we present new histopathology data for muscle tissue of albino (Sprague-Dawley) rats exposed to pressures for 15 or 30 min. These data are superimposed with an extensive literature review of all previous histopathology reported for albino rat skeletal muscles subjected to pressure. The pooled data enabled a new mathematical characterization of the pressure-time threshold for cell death in striated muscle of rats, in the form of a sigmoid pressure-time relation, which extends the previous pressure-time relation to the shorter exposure periods. We found that for pressure exposures shorter than 1 h, the magnitude of pressure is the important factor for causing cell death and the exposure time has little or no effect: even relatively short exposures (15 min - 1 h) to pressures greater than 32 kPa (240 mmHg) cause cell death in rat muscle tissue. For exposures of 2 h or over, again the magnitude of pressure is the important factor for causing cell death: pressures greater than 9 kPa (67 mmHg) applied for over 2 h consistently cause muscle cell death. For the intermediate exposures (between 1 and 2 h), the magnitude of cell-death-causing pressure strongly depends on the time of exposure, i.e., critical pressure levels drop from 32 to 9 kPa. The present sigmoidal pressure-time cell death threshold is useful for design of studies in albino rat models of DPS, and may also be helpful in numerical simulations of DPS development, where there is often a need to extrapolate from tissue pressures to biological damage.
Journal of Biomechanics 02/2006; 39(14):2725-32. · 2.43 Impact Factor
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ABSTRACT: Currently, Doppler echocardiography analysis is performed manually. An automated method that analyzes the Doppler signal can potentially improve accuracy and result in a powerful tool for noninvasive evaluation of cardiac hemodynamics, especially for patients with atrial fibrillation, where multiple samples are needed to obtain an accurate averaged measurement. The aim of this study was to develop an automated method for Doppler analysis based on image processing and computer vision algorithms. Images were obtained from the mitral valve and the tricuspid valve Doppler tracings from 45 patients, 20 with normal sinus rhythm and 25 with atrial fibrillation. The proposed algorithm automatically detects the maximal velocity envelope of the spectral Doppler ultrasound tracings. Averaged values for the time velocity integral, peak mitral inflow velocity and peak tricuspid regurgitation velocity were calculated for multiple beats available in a single screen frame. Measurements extracted automatically from the maximal velocity envelope were compared to measurements obtained manually by two expert technicians. High linear correlation (r) was found between the automatically- and the manually-extracted parameters (0.95 < r < 0.99). A smaller variation was found in most cases between the manually-calculated average beat and the automated average beat (bias value between 3.8% and 5.2%) than between the manually-calculated average beat and the selection of a representative beat (bias value between 6.2% and -2.6%). The newly-developed automated method offers a new, accurate and reliable clinical tool, particularly for the assessment of patients with irregular heart rate.
Ultrasound in Medicine & Biology 08/2005; 31(8):1031-40. · 2.29 Impact Factor
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ABSTRACT: The aim of this research was to investigate the structural, functional, and molecular features of the remodeling heart in prior swim-trained infarcted rats.
Physical exercise training is a known protective factor against cardiovascular morbidity and mortality. The structural and molecular aspects underlying this protection in the remodeling heart have not been investigated.
After seven weeks of swimming exercise training, rats underwent surgical ligation of the left coronary artery followed by a four-week sedentary period. Untrained control rats underwent the same surgical protocol. Left ventricular function was assessed by echocardiography four weeks after infarction, and hearts were sampled for histological and molecular analysis. Ribonucleic acid from the surviving left ventricle was analyzed by complementary deoxyribonucleic acid arrays followed by Northern blotting or quantitative reverse transcription polymerase chain reaction of selected messenger ribonucleic acids (mRNAs).
Scar area was 1.6-fold smaller (p = 0.0002), arteriolar density was 1.7-fold higher (p = 0.0002), and left ventricular shortening fraction was 1.9-fold higher (p = 0.003) in the exercise-trained compared with sedentary hearts. Eleven genes whose expression level varied by at least +/-1.5-fold distinguished the prior exercised rats from their sedentary counterparts. Compared with sedentary, the exercised hearts displayed 9- and 2.4-times lower levels of atrial natriuretic peptide and aldolase mRNA (p = 0.03 and 0.04, respectively), and a 2.7- and 1.9-fold higher abundance of cytochrome c-oxidase and fatty acid binding protein, respectively (p < 0.03, each).
Swimming exercise training before acute myocardial infarction reduces scar size, increases arteriole density, and manifests adaptation of stress- and energy-metabolism-related genes that may contribute to the improved heart function observed during remodeling.
Journal of the American College of Cardiology 04/2005; 45(6):931-8. · 14.16 Impact Factor
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ABSTRACT: The effect of exercise training prior to acute myocardial infarction (AMI) on left ventricular (LV) remodeling is poorly understood. This study investigated the protective effect of 3 weeks of swimming exercise training prior to AMI on cardiac morphology and function. Male Sprague-Dawley rats (n = 35) were randomly assigned to 3 groups: swimming training (n = 14, 90 min, 5 days/wk, 3 wk), sedentary (n =14), and controls (n = 7, no exercise, no MI). At the end of the training/sedentary period, rats were subjected to AMI (ExMI and SedMI) induced by surgical ligation of the left coronary artery. Thereafter, the rats remained sedentary for a 4-wk recovery period. Trans-thoracic echocardiography was performed in each group at the end of the exercise/sedentary period (pre-AMI), 24 hr after AMI, and following recovery (4 wk after AMI). No differences were observed in LV dimensions and function pre-AMI among the 3 groups; however, LV-end systolic diameter (LVESD) and LV-end systolic area (LVES-area) were significantly lower in the prior trained rats, 24 hr post-AMI with no additional change 4 wk post-AMI, during remodeling. Both LV-shortening fraction (SF%) and fractional area change (FAC%) were higher in the trained animals 4 wk post-AMI (39+/-12% vs 23+/-8%; p 0.002, and 48+/-14% vs. 38+/-9%; p 0.07, respectively). In conclusion, 3 wk of swimming exercise training prior to AMI significantly attenuated LV remodeling and improved LV function, despite no changes in LV dimensions or systolic function at the end of the exercise session. The data suggest that even a short-term training period is sufficient to induce cardiac protection.
Annals of clinical and laboratory science 02/2005; 35(1):73-8. · 0.96 Impact Factor
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ABSTRACT: The time to occurrence of cardiovascular complications after the beginning of an exercise rehabilitation program is variable. It is not clear whether such complications are related to the duration in the program. The aim of the present study was to assess the timing of cardiovascular events occurring during the activity and the long-term safety of a medically supervised cardiac rehabilitation program performed in the community, in a large cohort. We retrospectively evaluated 3,511 patients with a history of myocardial infarction, coronary artery bypass grafting and risk factors for coronary artery disease, participating in exercise training, for 69 months. The total number of patient-hours was 338,688 with an event rate of 1/58,902 patient-hours/year (0.02%). Non-fatal events occurred in 11 patients and fatal cardiovascular events in 2 patients; 1 was successfully resuscitated. Most of the non-fatal events (62%) occurred during the first 4 weeks from the beginning of the exercise program. One third of the patients who experienced cardiovascular events, resumed the exercise program with no further complications. Medically supervised cardiac rehabilitation program is accompanied by a very low incidence of cardiovascular events. Nevertheless, special caution should be undertaken during the first sessions of the program.
Cardiology 02/2005; 103(3):113-7. · 1.71 Impact Factor
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Mickey Scheinowitz
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ABSTRACT: One of the main goals in the treatment of myocardial ischemia is the development of effective therapy for angiogenesis and neovascularization. The first evidence demonstrating alleviation of myocardial ischemia and increased number of collateral blood vessels was reported in the early 90s following intra-coronary administration of basic fibroblast growth factor protein in canine. This study established the ground for extensive investigations to demonstrate the use of other angiogenic growth factor proteins, genes administered directly or incorporated in viruses, and more recently, endothelial progenitor stem cells (embryonic and adults). The positive results observed in animals failed, in most cases, to repeat themselves in clinical-trials in human patients. Therefore, additional experiments are warranted to allow full understanding of the mechanism underlying new blood vessel formation before further clinical studies are undertaken. This review will explore the milestones of angiogenic investigations and their clinical application.
Molecular and Cellular Biochemistry 10/2004; 264(1-2):75-83. · 2.06 Impact Factor
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ABSTRACT: Primary IGF-I deficiency (Laron syndrome, LS) may decrease exercise capacity as a result of a lack of an IGF-I effect on heart, peripheral muscle or lung structure and/or function.
Eight patients (six females) who had never received treatment with IGF-I, with mean age of 36 +/- 10 (SD) years (range 21-48), weight 47 +/- 9 kg (31-61), height 126 +/- 12 cm (112-140) and body mass index of 29 +/- 4 kg/m2 (24-34), and 12 age-matched controls, underwent lung function tests and incremental cycling to the limit of tolerance (CPX, MedGraphics). Predicted values for the patients were derived from adult equations based on height.
In LS patients, lung function was near normal; vital capacity was 84 +/- 11% of expected (66-103). Peak exercise O2-uptake and the anaerobic threshold were reduced, 57 +/- 20% of predicted and 33 +/- 9% of predicted peak (P = 0.005 vs. controls), despite normal mean exercise breathing reserve. All parameters were normal in the controls.
Exercise capacity in untreated adults with LS is significantly reduced. The limitation for most patients was not ventilatory but resulted either from low cardiac output and/or from dysfunction of the peripheral muscles. However, the relative contribution of each of these elements and/or the role of poor fitness needs further study.
Clinical Endocrinology 01/2004; 59(6):763-7. · 3.17 Impact Factor
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ABSTRACT: Growth hormone (GH) replacement during childhood has been shown to increase stature; however, there is little information on its long-term effect on the heart is not yet clear. The aim of this study was to assess cardiac size and function in patients with childhood-onset GH deficiency in whom GH treatment had been stopped at the achievement of final height and the effect of a second course of GH replacement in adult age.
Cardiac dimensions and function, obtained with echocardiography, of 21 patients (5 women and 16 men, mean age 28 +/- 8 years), all of whom were treated during childhood, were compared with 21 age- and sex-matched healthy control subjects. Eight of these patients (2 women and 6 men, mean age 28 +/- 8 years) were given a second course of GH replacement therapy for 15 +/- 3 months.
The stature and all cardiac dimensions of patients with GH deficiency who were treated during childhood were significantly smaller than those of the control subjects. After the second course of GH in adulthood, the only significant change observed was an increase in left ventricular (LV) mass (93 +/- 21 vs 106 +/- 24 g, P =.007) and LV mass index (59 +/- 12 vs 66 +/- 13 g/body surface area, P =.005).
The stature and cardiac dimensions of patients with childhood-onset GH deficiency measured in adult age were smaller than those of control subjects, despite long-term GH replacement therapy during childhood. A second course of GH treatment during adulthood caused a significant increase in the estimated LV mass index in patients with both isolated and multiple pituitary hormone deficiency.
American heart journal 04/2003; 145(3):549-53. · 4.65 Impact Factor
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Mickey Scheinowitz,
Yuval Heled,
Pierre Chouraqui,
Zvi Vered,
Yfat Hayardeni,
Arkady Kotlyar,
David Castel,
Shy Livschitz,
Vivian Barak,
Naphtali Savion,
Michael Eldar
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ABSTRACT: BACKGROUND: Heparin and low molecular weight heparin (LMWH) derivatives are considered angiogenic factors in ischemic and infarcted myocardium. However, the effect of dalteparin sodium (fragmin, a LMWH derivative) on angiogenesis post infarction has not yet been investigated.Purpose. To assess the effect of systemically-administered dalteparin sodium on left ventricular perfusion and function during remodeling in swine subjected to acute microembolization infarction (MI).Methods. MI was induced in 12 anesthetized female pigs which randomly received dalteparin sodium (12,500U) or placebo through intra-peritoneal osmotic pump, for one week, beginning immediately after the MI. Myocardial perfusion and function were measured using radionuclear scan and echocardiography, respectively, at baseline, immediately post MI, and at 2 and 4 weeks post MI. Dobutamine stress echocardiography was performed 4 weeks post MI. Serum level of basic fibroblast growth factor (bFGF) was analyzed using a commercially available ELISA kit.Results. No differences were observed in myocardial perfusion at all time points following MI. No significant changes were observed in myocardial function and wall motion during the 4 weeks follow-up period, or after dobutamine administration. Serum bFGF did not change throughout the study period.Conclusion. Under the setting of the current experiment, one week of dalteparin sodium administration does not affect myocardial perfusion and function following acute infarction in swine, either at rest or following pharmacological stress.
Cardiovascular Drugs and Therapy 08/2002; 16(4):303-9. · 3.13 Impact Factor
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ABSTRACT: Previous studies have demonstrated myocardial salvage by basic fibroblast growth factor administration following chronic myocardial ischemia or acute myocardial infarction.
To study the effect of bFGF on left ventricular morphometry following coronary occlusion and reperfusion episode in rats.
bFGF (0.5 mg) or placebo was continuously administered for a period of one week using an implanted osmotic pump. Animals were sacrificed 6 weeks after surgery and myocardial cross-sections were stained with Massontrichrome and with anti-proliferating cell nuclear antigen antibody.
LV area, LV cavity diameter, LV cavity/wall thickness ratio, and injury size were unchanged compared with control animals. Proliferating endothelial cells were significantly more abundant in injured compared with normal myocardium, but with no differences between animals treated or not treated with bFGF.
One week of systemic bFGF administration following coronary occlusion and reperfusion had no additional effect on LV geometry or cellular proliferation in rats.
The Israel Medical Association journal: IMAJ 03/2002; 4(2):109-13. · 1.02 Impact Factor
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Alexander Battler, Mickey Scheinowitz,
Amir Bor,
David Hasdai,
Zvi Vered,
Elio Di Segni,
Nira Varda-Bloom,
Devorah Nass,
Santiago Engelberg,
Michael Eldar,
Michael Belkin,
Naphtali Savion
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ABSTRACT: Objectives. This study was performed to examine the effect of intracoronary exogenous basic fibroblast growth factor (bFGF) on angiogenesis in infarcted myocardial regions.Background. Exogenous bFGF is a potent promoter of angiogenesis. Little information is available on its effect on myocardial angiogenesis.Methods. Myocardial infarction was induced in 10 pigs by intracoronary injection of microscopic beads. Four pigs served as a control group; in six pigs slow-release bFGF was delivered by the beads. Cardiac performance was evaluated by repeated echocardiographic measurement and angiogenesis was evaluated by immunohistochemical studies 14 days later.Results. As compared with control pigs, pigs treated with bFGF had higher microvessel counts (mean ± SEM) in both viable tissue (141 ± 27 per field vs. 39 ± 4, p = 0.01) and nonviable tissue (329 ± 26 per field vs. 95 ± 7, p < 0.001) within the infarct area. No significant differences in total regional left ventricular wall motion were noted between the two groups throughout the 14-day study period.Conclusions. In the swine, direct intracoronary application of bFGF to infarcted myocardium enhances myocardial neovascularization within 2 weeks.
Journal of the American College of Cardiology 12/1993; · 14.16 Impact Factor
