Anthropomorphic cardiac phantom for dynamic SPECT.

BACKGROUND: As myocardial blood flow measurement (MBF) in SPECT systems became recently available, significant effort has been devoted to its validation. For that purpose, we have developed a cardiac phantom that is able to mimic physiological radiotracer variation in the left ventricle cavity and in the myocardium, while performing beating-like motion. The new phantom is integrated inside a standard anthropomorphic torso allowing a realistic tissue attenuation and gamma-ray scattering METHODS AND RESULTS: A mechanical cardiac phantom was integrated in a commercially available anthropomorphic torso. Using a GE Discovery 530c SPECT, measurements were performed. It was found that gamma-ray attenuation effects are significant and limit the MBF measurements to global/three-vessel resolution. Dynamic SPECT experiments were performed to validate MBF accuracy and showed mean relative error of 14%. Finally, the effect of varying radiotracer dose on the accuracy of dynamic SPECT was studied CONCLUSIONS: A dynamic cardiac phantom has been developed and successfully integrated in a standard SPECT torso. A good agreement was found between SPECT-reported MBF values and the expected results. Despite increased noise-to-signal ratio when radiotracer doses were reduced, MBF uncertainty did not increase significantly down to very low doses, thanks to the temporal integration of the activity during the measurement.

Dose-consistent dynamic SPECT.

BACKGROUND: Coronary flow reserve (CFR) values measured by dynamic SPECT systems are typically consistent with other modalities (e.g., PET). However, large discrepancies are often observed for individual patients. Positioning of the region-of-interest (ROI), representing the arterial input function (AIF) could explain some of these discrepancies. We explored the possibility of positioning the ROI in a manner that evaluates its consistency with patient-based injected radiotracer doses. METHODS: Dose-consistent dynamic SPECT methodology was introduced, and its application was demonstrated in a twenty-patient clinical study. The effect of various ROI positions was investigated and comparison to myocardial perfusion imaging was performed. RESULTS: Mean AIF ratios were consistent with the injected dose ratios for all examined ROI positions. Good agreement (> 80%) between total perfusion deficit and CFR was found in the detection of obstructive CAD patients for all ROIs considered. However, for individual patients, significant dependence on ROI position was observed (altering CFR by typically 30%). The proposed methodology's uncertainty was evaluated (~ 7%) and found to be smaller than the variability due to choice of ROI position. CONCLUSION: Dose-consistent dynamic SPECT may contribute to evaluating uncertainty of CFR measurements and may potentially decrease uncertainty by allowing improved ROI positioning for individual patients.

Preliminary study of thermal density distribution and entropy analysis during cycling exercise stress test using infrared thermography.

Considerable differences related to the results of temperature changes acquired during exercise exist, and in many cases, these lead to poor correlation with physiological variables. In this preliminary study we investigated the temperature changes and the temperature distribution (entropy) of the torso during a graded cycling exercise stress test using thermal imaging and studied the correlation between the increase in pulmonary ventilation (VE) and the changes in the surface temperature of the anterior torso during exercise. Thermal images of the anterior torso were captured every 30 s during the exercise, while the resistance was gradually increased every minute until exhaustion. The thermal images were processed to obtain a mean temperature in the regions of interest (ROI) (chest, forehead, and abdomen). We also developed an algorithm to calculate the distribution of temperature and texture (entropy) within each ROI. No changes were found in absolute temperatures. However, the entropy of the chest surface area increased significantly throughout the exercise test, compared with baseline temperature at rest. This increase in entropy was significantly correlated with exercise duration and intensity (p < 0.001). Furthermore, a high correlation between the increase in VE and chest entropy during exercise was detected (r = 0.9515). No correlations were found between the increase in entropy and the abdomen or the forehead compared with the VE. The non-invasive IR thermal imaging during graded exercise, combined with advanced image processing, successfully correlates surface thermography with exercise duration and pulmonary ventilation.

A new cardiac phantom for dynamic SPECT.

BACKGROUND: In recent years, with the advance of myocardial blood flow (MBF) measurement capability in dynamic single photon emission computerized tomography (SPECT) systems, significant effort has been devoted to validation of the new capability. Unfortunately, the mechanical phantoms available for the validation process lack essential features-they either have a constant radiotracer concentration or they have rigid (static) walls unable to simulate cardiac beating. METHODS AND RESULTS: We have developed a mechanical cardiac phantom that is able to mimic physiological radiotracer variation in the left ventricle (LV) cavity and in the myocardium (M), while performing beating-like motion. We have also developed a mathematical model of the phantom, allowing a description of the radiotracer concentrations in both regions (LV, M) as a function of time, which served as a tool for experiment planning and to accurately mimic physiological-like time-activity curves (TACs). A net retention model for the phantom was also developed, which served to compute the theoretical (i.e., expected) MBF of the phantom from measured quantities only, and thus validate the MBF reported by the SPECT system. In this paper, phantom experiments were performed on a GE Discovery NM 530c SPECT system. CONCLUSIONS: A novel dynamic cardiac phantom for emission tomography has been developed. The new phantom is capable of producing a wide range of TACs that can mimic physiological (and potentially in the future, pathological) curves, similar to those observed in dynamic SPECT systems. SPECT-reported MBF values were validated against known (measured) activity of the injected radiotracer from phantom experiments, which allowed to determine the accuracy of the GE Discovery 530c SPECT system.

Emergence of the concept of platelet reactivity monitoring of response to thienopyridines.

Clinical trials have demonstrated the beneficial impact of clopidogrel in preventing major adverse cardiovascular events (MACE), particularly in patients undergoing percutaneous coronary intervention (PCI). The concept of biological clopidogrel resistance emerged with the finding of persistent platelet activation despite clopidogrel therapy in some patients. Further, a link between biological clopidogrel resistance and thrombotic recurrence after PCI was observed and a threshold of platelet reactivity (PR) for thrombotic events was suggested. Consistently, in recent trials, enhanced PR inhibition translated into a reduction in the rate of MACE after PCI. This review aims to present the emergence of the concept of PR monitoring in patients undergoing PCI following recent advances in this field.

How do normals move during prolonged wheelchair-sitting?

The clinical practice for minimizing the risk of pressure sores (PS) is to relief pressures under bony prominences of immobilized patients by changing their postures frequently. The US Department of Health advises to relief sitting pressures at least every 1 hour, and every 15 minutes for individuals who are body-abled. Surprisingly, there is paucity of information in the literature concerning motion of healthy subjects during prolonged sitting, which can be compared with these recommendations. Considering that healthy individuals are able to sit for hours without suffering injuries, such information seems particularly important. Accordingly, our objective was to measure frequency of postural changes and extent of motion during postural changes among healthy subjects who sit in a wheelchair (N=10), in order to provide information that is missing in the literature of PS biomechanics. Subjects were asked to sit comfortably for 90 minutes, during which their trunk's frontal and sagittal motions and sitting pressures were measured. We found that normals change their posture every 9 +/- 6 minutes in the sagittal plane, and independently, every 6 +/- 2 minutes in the frontal plane. Shoulders, thoracic-spine and lumbar-spine frontal plane motions were 8 +/- 4 degrees , 14 +/- 7 degrees and 15 +/- 7 degrees , respectively, and sagittal trunk-thigh movement was 10.3 +/- 7 degrees . The frequency of postural changes in normals, measured herein, was higher than frequencies reported in the literature for patients who suffered PS. This small study population therefore supports the hypothesis that prolonged immobilization contributes to PS onset.

Obese adults with primary growth hormone resistance (Laron Syndrome) have normal endothelial function.

OBJECTIVE: Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity. The aim of the current study was to investigate the impact of long-term IGF-I deficiency on flow-mediated dilation (FMD) in 11 non-IGF-I-treated LS adults with long-term IGF-I deficiency who on stress echocardiography were found to have reduced cardiac dimensions and output, but normal left ventricular (LV) ejection fraction at rest and LV contractile reserve following stress. DESIGN: Following an overnight fast we assessed percent improvement in endothelium-dependent FMD (%FMD) and endothelium-independent nitroglycerin (%NTG)-mediated vasodilation non-invasively in the brachial artery, using high resolution ultrasound in 11 non-treated adult patients with LS without known coronary artery disease, and compared them to 11 age- and sex-matched healthy controls. All subjects underwent symptom-limited exercise testing (Bruce protocol). RESULTS: LS patients had a significantly higher body mass index (29+/-6 vs. 25+/-2 kg/m(2), p=0.04), lower low-density lipoprotein cholesterol (142+/-28 vs. 176+/-12 mg/dl, p=0.03) and a smaller mean brachial artery diameter (4.63+/-0.72 vs. 5.70+/-1.06 mm, p=0.01) compared to controls. However, brachial artery %FMD and %NTG were not significantly different between the LS patients and controls (13.1+/-6.2% vs. 15.4+/-5.2%, p=0.28 and 22.3+/-6.0% vs. 18.9+/-6.2%, p=0.30; respectively). Cardiac performance, assessed by exercise duration time and metabolic equivalents (METs), was significantly greater in control subjects than in LS patients (10.3+/-2.0 vs. 6.0+/-1.4 min, p<0.01 and 10.2+/-2.0 vs. 7.2+/-1.4 METs, p<0.01; respectively). CONCLUSIONS: FMD was found to be within normal limits in non-IGF-I-treated adult patients with LS, despite congenital absence of IGF-I and obesity.

Short- and long-term swimming exercise training increases myocardial insulin-like growth factor-I gene expression.

UNLABELLED: OBJECTIVES. We investigated the effect of short- and long-term swimming exercise, with or without insulin-like growth factor (IGF)-I administration, on the expression of myocardial IGFs and contractile proteins. METHODS: Sprague-Dawley male rats (n=36) were subjected to swimming exercise for 2 or 6 weeks. IGF-I (0.5mg/rat) was administered continuously for 1 week, using alzet osmotic pumps. Control groups remained sedentary. IGF-I, IGF-I receptor (IGF-IR), IGF-II, skeletal alpha-actin (sk-actin), and beta myosin heavy chain (beta MHC) mRNAs were measured using Northern blot analysis and RT-PCR. RESULTS: A significant 2-fold increase in myocardial IGF-I mRNA was found after 2 and 6 weeks of swimming in both IGF-I treated and untreated rats (p<0.001). IGF-IR mRNA was significantly (p<0.05) increased after 6 weeks of training only in the IGF-I treated animals. IGF-II mRNA remained unchanged at all time points. While beta MHC mRNA was significantly decreased (p=0.003) at 2 and 6 weeks, sk-actin mRNA remained unchanged. CONCLUSIONS: Short- and long-term swimming exercise training increase myocardial expression of IGF-I mRNA. Exogenous administration of IGF-I, during the first week of the exercise session, did not produce any effect on myocardial IGF-I but was associated with increased IGF-IR signal after the long-term exercise training. These data suggest a relationship between IGF-I expression and cardiac adaptation to exercise training.

Insulin-like growth factor I and II preserve myocardial structure in postinfarct swine.

BACKGROUND: Insulin-like growth factors (IGF) I and II improve myocardial function after coronary occlusion in different animal models. OBJECTIVES: To investigate the mechanism of improved myocardial function after administration of IGF-I or IGF-II in acute myocardial infarction. METHODS: Female pigs (mean (SD) weight 25 (5) kg) were subjected to acute myocardial infarction by microembolisation with 75-150 micrometer affigel blue beads. The beads contained and slowly released 150 microgram/pig of IGF-I (n = 6), IGF-II (n = 6), or pig albumin (n = 6). Echocardiography, perfusion imaging, and haemodynamic measurements were performed before infarction and during four weeks after infarction. Regional wall motion of different left ventricular segments was scored semiquantitatively on the basis of a three point scoring system, from normal = 0 to dyskinesia = 3. Serum cardiac troponin I concentration was measured before, immediately after, and three hours after the infarct. Excised hearts were analysed for actin, desmin, blood vessel density, and DNA laddering within the infarct, border, and normal myocardial areas. RESULTS: Myocardial function of the infarct related area improved significantly during the four weeks of follow up in both the IGF groups (p = 0.01). Myocardial perfusion, heart rate, and blood pressure were similar in all the animals during the study. Treated animals had lower serum cardiac troponin I concentration (p = 0.001), more actin in the border area (p = 0.01) and infarct area (p = 0.0001), and reduced DNA laddering in the infarct area compared with the controls (p < 0.05). IGF groups had more blood vessels in the border area (p = 0.04) and the infarct area (p = 0.003). CONCLUSIONS: Both types of IGF improved myocardial function and the improvement was associated with preservation of myocardial structure. IGF-I was more effective than IGF-II.

Echocardiographic dimensions and function in adults with primary growth hormone resistance (Laron syndrome).

Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p<0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p<0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress.

Basic fibroblast growth factor induces myocardial hypertrophy following acute infarction in rats.

Basic fibroblast growth factor (bFGF) is a potent mitogen which induces growth of collateral vessels in ischaemic and infarcted myocardium. The effect of systemically administered bFGF on left ventricular (LV) function, myocardial hypertrophy and LV remodelling following acute myocardial infarction (MI) have not yet been fully investigated. Thirty Sprague-Dawley male rats were randomized to receive bFGF (0.5 mg) or rat albumin intraperitoneally for 1 week, beginning immediately after the induction of MI. Five animals served as controls and did not undergo any operation. Animals were killed 6 weeks after surgery and the hearts were perfused and fixed at physiological pressure. Transverse cross-sections from infarcted areas were stained with antibodies against proliferating cell nuclear antigen (PCNA) and Masson-trichrome and analysed with a coloured-image analyser for LV area (mm2), LV cavity diameter (mm), infarcted area (%), and wall thickness (mm) in infarcted and non-infarcted regions. LV area was similar in MI rats and in controls (41.7 +/- 6.9 and 43.0 +/- 1.5 mm2, respectively) and was significantly larger in MI bFGF-treated (MI/bFGF) animals (47.6 +/- 7.1 mm2) (P = 0.023). LV cavity diameter was significantly larger in the MI group than in MI/bFGF and control animals (6.0 +/- 0.8, 4.9 +/- 1.4, and 4.4 +/- 0.8 mm, respectively, P = 0.018). Wall thickness in the non-infarcted region was significantly smaller in MI animals (1.4 +/- 0.3 mm) than in MI/bFGF animals (1.6 +/- 0.4 mm) and the control group (1.6 +/- 0.1 mm) (P = 0.015). The ratio between LV cavity diameter/non-MI wall thickness was higher in MI than in control and MI/bFGF groups (4.8 +/- 1.6, 2.7 +/- 0.6 and 3.3 +/- 1.8, respectively, P = 0.03). Proliferating endothelial cells were significantly more abundant in infarcted than in normal areas in both MI and MI/bFGF groups, but with no significant differences between the groups. Intraperitoneal administration of bFGF did not cause any untoward extracardiac effects. Thus, systemic bFGF administration following acute MI in rats prevents dilatation of the LV, induces hypertrophy of the non-infarcted myocardium and exerts no untoward effects on extracardiac organs.

Continuous administration of insulin-like growth factor-I and basic fibroblast growth factor does not affect left ventricular geometry after acute myocardial infarction in rats.

We examined the long-term effect of exogenous administration of bFGF and IGF-I on myocardial geometry in 72 Sprague-Dawley male rats subjected to AMI. A preloaded miniature osmotic pump subsequently implanted in the peritoneum for continuous infusion (1 week) of IGF-I, bFGF, IGF-I+bFGF or rat albumin. Six weeks following AMI the rats were killed and cross-section slices were analyzed for left ventricular geometry. No differences were observed between IGF-I-treated, bFGF-treated, IGF-I+bFGF-treated and control groups in all parameters of the left ventricle.

Serum basic fibroblast growth factor levels in patients with ischemic heart disease.

BACKGROUND: Being a potent promoter of endothelial and smooth muscle cell proliferation, basic fibroblast growth factor (bFGF) is presumed to play a key role in coronary collateral development and atherogenesis. PURPOSE: To characterize serum bFGF levels in patients with ischemic heart disease. METHODS: The study population consisted of patients with angina (n=33) and after uncomplicated myocardial infarction (n=12). The number of significantly stenosed (> or = 50%) vessels and angiographic coronary collateral score were noted. Blood was drawn immediately prior to elective coronary angiography in study patients for bFGF levels. Twenty healthy, age-matched subjects served as control for serum bFGF. RESULTS: Serum bFGF levels were undetectable in all 20 control subjects, but were detectable in 15/33 (45%) patients with angina and 3/12 (25%) post-infarction patients, respectively (P=0.002). Serum bFGF levels were detectable in 13/23 (57%) patients with 0- or 1-vessel disease, as compared with 5/22 (23%) patients with 2- or 3-vessel disease (P<0.05). Detectable serum bFGF levels were not in correlation with coronary collateral score (P=1). CONCLUSIONS: Serum levels of bFGF are elevated in patients with ischemic heart disease, particularly in those with minimal coronary artery disease. We postulate that detectable serum bFGF levels reflect active atherogenesis rather than myocardial collateral development.

The role of insulin-like and basic fibroblast growth factors on ischemic and infarcted myocardium: a mini review.

Current therapeutic techniques in acute myocardial infarction (AMI) are inadequate since restoration of blood flow through the obstructed coronary artery does not always preserve the ischemic myocardium. Therefore, deterioration of cardiac function and detrimental left ventricular remodeling may follow. Alternative therapeutic modalities are now being actively sought. Insulin-like growth factor (IGF) and fibroblast growth factor (FGF) are two polypeptides found in wide distribution and high concentrations in the normal myocardium. They play a key role in vascular growth (FGF) and affect the differentiation of cardiac myocytes (IGF). IGF has been found to promote physiological forms of cardiac hypertrophy, and FGF induces neovascularization. During myocardial ischemia and infarction there is a marked elevation in the concentration of these growth promoting factors in the myocardium concomitant with increased coronary collateral blood flow, neovascularization and peri-infarct hypertrophy. In animal models of myocardial infarction, exogenous administration of FGF and IGF induced neovascularization and cardiac hypertrophy thus, preserving cardiac function. We assume that these growth factors may become an additional tool in the future treatment of patients with AMI.

Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury.

BACKGROUND: We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for > or = 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell-specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo. METHODS AND RESULTS: Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n = 9), VEGF 0.72 mg (n = 9), or saline (n = 10) as a daily left atrial bolus (days 10 to 16). Additional dogs were randomized to VEGF 0.72 mg (n = 6) or saline (n = 5); however, treatment was delayed by 1 week. Coincident with the institution of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased maximal collateral flow but did not exacerbate neointimal accumulation. VEGF had no discernible effect on maximal collateral flow, but it exacerbated neointimal thickening after vascular injury. CONCLUSIONS: Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation at sites of vascular injury. Although VEGF did not increase collateral development as administered in this study, it significantly exacerbated neointimal accumulation. These data provide support for the clinical investigation of bFGF in selected patients with ischemic heart disease.

Increased serum concentrations of interleukin-1 beta in patients with coronary artery disease.

OBJECTIVE: To assess serum interleukin-1 beta (IL-1 beta) concentrations in patients with ischaemic heart disease, to characterise subgroups of patients with raised IL-1 beta concentrations, and to examine whether serum IL-1 beta concentrations correlate with non-specific indices of inflammation. DESIGN: Survey study of patients with ischaemic heart disease. SETTING: Cardiac catheterisation laboratory of a tertiary medical centre. PATIENTS: Consecutive patients with angina pectoris and patients recovering from uncomplicated acute myocardial infarction and undergoing elective coronary angiography. RESULTS: Mean(SD) serum IL-1 beta concentrations were higher (P < 0.001) in patients with angina and < 50% coronary artery stenosis (n = 11; 18.8(19.9) pg/ml), patients with angina > or = 50% stenosis (n = 23; 10.2(11.4) pg/ml), and patients 8(0.8) days post-infarction (n = 13; 4.4(5.8) pg/ml) than in 15 healthy, age-matched controls (0.3(0.5) pg/ml). Serum IL-1 beta concentrations did not correlate with total blood leucocyte counts (r = -0.07, P = NS), blood lymphocyte counts (r = -0.24, P = NS), and blood monocyte counts (r = -0.29, P = NS), or with fibrinogen (r = -0.16, P = NS) and C-reactive protein concentrations (9(10.5) mg/dl v 14.1(19) mg/dl for patients with undetectable and detectable concentrations, respectively, P = NS). CONCLUSION: Serum IL-1 beta concentrations are raised in patients with ischaemic heart disease, in particular in those with minimal coronary artery disease and angina. The precise role of IL-1 beta in coronary artery disease remains to be determined.

Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart.

BACKGROUND: Recently we reported that intracoronary administration of basic fibroblast growth factor (bFGF), a potent angiogenic peptide, increases collateral blood flow in dogs subjected to progressive left circumflex coronary artery (LCx) occlusion. The aim of the present study was to examine the effect of systemically administered bFGF on collateral blood flow and to assess its pharmacokinetics and potential side effects. METHODS AND RESULTS: Forty-seven dogs were subjected to progressive ameroid-induced occlusion of the LCx, an intervention known to induce the development of collateral vessels. In phase I of the investigation, dogs were randomized to receive bFGF 1.74 mg/d (n = 10) or saline (n = 9) as a left atrial injection for 4 weeks. Relative collateral blood flow was assessed serially with radiolabeled microspheres in the conscious state during maximal coronary vasodilatation. Initiation of bFGF treatment was temporally associated with a marked acceleration of collateral development; however, collateral flow in control dogs improved toward the end of the study, approaching that of bFGF-treated dogs at the 38-day end point. Phase II of the investigation was a three-armed study of extended duration to determine whether bFGF caused a sustained increase in collateral function. Dogs were randomized to receive bFGF 1.74 mg/d for 9 weeks (n = 7), bFGF 1.74 mg/d for 5 weeks followed by placebo for 4 weeks (n = 11), or placebo for 9 weeks (n = 10). Relative and absolute collateral blood flow were assessed serially with microspheres during maximal coronary vasodilatation. Between the 10th and 17th days after ameroid placement, bFGF-treated dogs exhibited marked improvement in collateral flow such that maximal collateral conductance exceeded that of controls by 24% at the 5-week crossover point. Final collateral conductance was similar in dogs receiving bFGF for 5 and 9 weeks despite withdrawal of treatment in the former group. bFGF administration was associated with a 21% increase in final collateral conductance as well as a 49% increase in collateral zone vascular density. Prolonged bFGF administration was also associated with a decrease in arterial pressure, moderate thrombocytopenia, and moderate, reversible anemia. CONCLUSIONS: Systemic administration of bFGF enhanced collateral conductance in dogs with progressive single-vessel coronary occlusion. The beneficial effect of bFGF occurred primarily between the 7th and 14th days of therapy, and regression of collateral development was not noted after withdrawal of treatment. The present investigation provides impetus to the concept that collateral development can be enhanced pharmacologically-specifically by bFGF-raising the possibility that such an intervention might eventually be applied clinically.

The effects of short-term exercise on the cognitive orientation for health and adjustment in myocardial infarction patients.

Previous studies have shown that cardiovascular patients benefit from exercise. The explanations are partly physical and partly psychological, yet evidence for the latter is contradictory, possibly because only selected samples start and maintain prolonged exercising. The authors examined psychological effects of short-term exercise started as soon as possible after myocardial infarction, focusing on the motivation for health of 62 male and female patients who had had a myocardial infarction 7 to 10 days earlier. Patients were divided into those who exercised for a week in a recovery camp, those who merely stayed for a week in the camp, and those who did not stay in the camp. Results of before and after tests indicated that two scores of the motivation for health (goals and norms) of patients in the exercise group increased, even when complications, former exercising, and infarct location were considered. A month later, 53 of the patients completed a cardiological adjustment questionnaire. The exercise group scored higher than the others on 8 of 9 domains, including subjective health state, sexuality, and work. Even short-term supervised exercise, if done immediately after infarction, has a great potential for beneficial psychological effects, the authors concluded.

Neointimal proliferation in canine coronary arteries. A model of restenosis permitting local and continuous drug delivery.

BACKGROUND: A number of experimental preparations have been used to elucidate the pathophysiology of restenosis after percutaneous transluminal coronary angioplasty; however, few models have been advanced that address restenosis in coronary arteries, and none provides an effective means of continuous local drug delivery. In this report, we describe a model of restenosis in coronary arteries with the provision for local, continuous delivery of cytotoxic and/or anti-proliferative agents. EXPERIMENTAL DESIGN: An ameroid constrictor was placed on the left circumflex coronary artery of 17 normocholesterolemic dogs. One month later, after substantial collateral development had ensued, a segment of the left circumflex coronary artery distal to the ameroid was mechanically compressed using surgical forceps for 10 (N = 4), 15 (N = 4), 20 (N = 2), or 30 minutes (N = 5). In two dogs, an indwelling left circumflex catheter and implanted pump maintained a continuous infusion of saline at the injury site. In addition, the pump side port provided transcutaneous access for serial, selective coronary arteriography. The animals were maintained on a normal diet, without cholesterol or fat supplementation. RESULTS: Three weeks after vascular injury, significant neointimal proliferation was observed in all dogs that was morphologically similar to the proliferation seen after percutaneous transluminal coronary angioplasty in human coronary arteries. The extent of neointimal formation was linearly related to the duration of injury: neointimal/medial area ratios were 0.35 +/- 0.10, 0.46 +/- 0.10, 0.58 +/- 0.03, and 1.16 +/- 0.26 (mean +/- SE) after 10, 15, 20, and 30 minutes of mechanical compression injury, respectively. CONCLUSIONS: This model produces striking neointimal proliferation in the coronary arteries of normocholesterolemic dogs, morphologically similar to that seen in human coronary restenosis specimens. The model appears suitable to test the efficacy of agents with the potential to inhibit neointimal formation, providing continuous intracoronary drug delivery, as well as transcutaneous access for serial, selective arteriography.

Normal cardiopulmonary responses during incremental exercise in 20- to 70-yr-old men.

Healthy men (N = 1424, age 20-70 yr) underwent a progressive incremental treadmill exercise test to volitional maximum. Cardiopulmonary variables were measured breath-by-breath. The aerobic power (VO2max) declined at an average yearly rate of 0.33 ml.kg.-1min-1, HRmax declined 0.685 beats.min-1.yr-1, and max O2 pulse declined at an annual rate of 0.115 ml.beat-1.kg-1*100. Gas exchange threshold (GET) expressed as percentage of VO2max was 58% and 69% in the youngest (20-30 yr) and oldest (61-70 yr) decades, respectively. The average decline in VE, Vt, f, and PETCO2 over the entire age range was 29%, 10%, 21%, and 7%, respectively. There were increases in VE/VO2, and VE/VECO2, from age 20-70 yr of 13% and 14%, respectively, but no changes across 5 decades in PETO2. Physical (height and weight) as well as life-style characteristics (leisure time activity, place of residency, smoking), were found to be potent predictors in most of the cardiopulmonary values at maximal exercise and therefore should be incorporated in the predictive equations for such variables. Normal response patterns of most cardiopulmonary variables throughout the range of exercise intensities were shown to be age-affected and thus should be standardized for age decades.