Biomedical subjects

A Giaid

Publications and source records attributed to A Giaid.

At least 19 recordsLinked to original sources

PubMed2001

Successful retrieval and function of lungs from non-heart-beating donors.

BACKGROUND: Lung transplantation has been used effectively as a therapeutic tool in end-stage pulmonary diseases, but organ shortages have restricted its use. There is growing interest in alternative organ sources such as organs from circulation-arrested cadavers, so called non-heart-beating donors. METHODS: We examined the effects of postmortem rapid in situ cadaver lung cooling by bilateral chest cavity flushing (group 2) and by pulmonary artery flush through right heart catheterization followed by pleural cavity flushing (group 3) on pulmonary function and morphology in a rabbit non-heart-beating donor model. The results were compared with those in a control group of heart-beating donors (group 1). RESULTS: At the end of a 2-hour reperfusion period, there were no significant differences in mean pulmonary artery pressure, pulmonary vascular resistance, pulmonary compliance, arteriovenous oxygen, pulmonary wet to dry weight ratio, and lung morphology between the three groups. CONCLUSIONS: Our study demonstrates that using bilateral chest cavity flushing with or without pulmonary flush protects the function and morphology of cadaver lungs and renders them suitable for lung transplantation.

Animals↗

PubMed2001

Nitric oxide system in needle-induced transmyocardial revascularization.

BACKGROUND: Nitric oxide (NO) promotes endothelial proliferation and migration, essential for angiogenesis. The purpose of this study was to determine the cellular expression of inducible and endothelial nitric oxide synthases (iNOS and eNOS) in an ischemic cardiomyopathy animal model of needle-induced transmyocardial revascularization (TMR). METHODS: Myocardial infarction was created in rats by ligating the left coronary artery, and animals were divided into two groups: no-TMR group (served as control) and TMR group (underwent concomitant TMR by the creation of six transmural channels with a 25-gauge needle in the ischemic area). Rats were sacrificed at intervals of 1, 2, 4, and 8 weeks. Immunohistochemistry using specific antisera was performed for iNOS, eNOS, and endothelial cell marker factor VIII. Vascular density and positive staining area with either iNOS or eNOS were assessed in the infarcted myocardium. RESULTS: Vascular density in the infarcted myocardium was significantly increased in the TMR group (p < 0.001). The positive staining area for iNOS and the intensity of iNOS immunoreactivity in cardiomyocytes, vascular endothelium, and macrophages were significantly greater in the TMR group (p < 0.05). However, these differences were seen only in the first 2 weeks after TMR. There was no significant difference in the expression of eNOS between groups. CONCLUSIONS: A mechanical injury using needle puncture in an ischemic myocardium increased vascular density and is associated with increased expression of myocardial iNOS. Increased production of NO derived from iNOS may contribute to the angiogenic response of TMR.

Animals↗

PubMed2001

Effect of endothelin receptor antagonist on lung allograft apoptosis and NOSII expression.

BACKGROUND: It is postulated that apoptosis contributes to ischemia-reperfusion graft dysfunction after lung transplantation. The purpose of this study was to determine whether the improvement in lung function that we previously observed with the use of an endothelin-1 (ET-1) receptor antagonist after ischemia-reperfusion injury is associated with a reduction in inducible nitric oxide synthase (NOSII) expression and programmed cell death. METHODS: Left lung canine allotransplantation was performed. Harvested lung blocks were preserved with modified Eurocollins solution and stored at 4 degrees C for 18 to 20 hours. Lung allografts were tested for the expression of NOSII by immunohistochemistry, and extent of apoptosis by terminal dUTP nick end-labeling (TUNEL). Animals blindly received either an intravenous infusion of saline (control) or the ET-1 receptor antagonist (SB209670) (15 microg/kg/min). Infusion began 30 minutes pretransplantation and continued to 6 hours posttransplantation. RESULTS: Immunohistochemical analysis demonstrated significantly stronger NOSII immunostaining in the allografts of the saline control group (36.5%+/-3.6%) compared with native right lungs (6.9%+/-1.3%, p < 0.001) or the ET-receptor antagonist treatment group (9.6%+/-1.4%, p < 0.001). The TUNEL staining revealed a significantly stronger labeling in the allografts of the saline treatment control group (40.7%+/-6.2%) compared with native right lungs (5.0%+/-0.6%, p < 0.005) or the ET receptor antagonist treatment group (14.1%+/-2.8%, p < 0.01). CONCLUSIONS: We conclude that treatment of lung allografts with the ET-1 receptor antagonist SB209670 reduces the area of NOSII expression and the extent of apoptosis, factors known to contribute to the process of prolonged ischemia-reperfusion injury.

Animals↗

PubMed2001

Regional distribution of endothelin-1 and endothelin converting enzyme-1 in porcine endotoxemia.

Endothelin-1 (ET-1) levels are markedly increased in sepsis. Since ET-1 is primarily transcriptionally regulated, there should be a corresponding increase in pre-pro-endothelin-1 (ppET-1). Our objective was to determine whether ppET-1 is increased in pigs with a low systemic vascular resistance. We also examined the distribution of ET-1 and the regulation of endothelin-converting enzyme 1 (ECE-1), the rate limiting enzyme in ET-1 production. We anesthetized and ventilated 16 pigs. We measured arterial, pulmonary, and central venous pressures, as well as cardiac output. ET-1 was measured by radioimmunoassay in plasma and in multiple tissues. We infused 20 microg/kg of endotoxin over 2 h and then sacrificed the animals. ppET-1 and ECE-1 mRNA were assessed by Northern analysis. We performed immunohistochemistry for the assessment of tissue ET-1 and ECE-1. The systemic vascular resistance rose at 30 min, but fell by 120 min. Plasma ET-1 more than doubled by 2 h. However, there was no change in the concentration of ET-1 in any tissue except in the pulmonary artery. By immunohistochemistry, there was also no change in ET-1 in aorta, vena cava, heart, lung, liver, and kidney. Distribution of ECE-1 followed that of ET-1 on immunohistochemistry. There was a significant increase in ppET-1 mRNA in liver, kidney papillae, and vena cava, and a tendency for an increase in other tissues. This was paralleled by an increase in ECE-1 mRNA. In conclusion, the amount of ECE-1 mRNA and protein parallel those of ET-1. Endotoxemia is associated with a marked increase in plasma ET-1 and an increase in ppET-1 and ECE-1 mRNA in multiple tissues; however, there was no significant change in tissue ET-1 except in the pulmonary artery. The rise in plasma levels without a change in tissue levels suggests a greater release into the vasculature in sepsis than under normal conditions.

Animals↗

PubMed2000

Inhibition of cyclooxygenase-2 improves cardiac function in myocardial infarction.

Induction of cyclooxygenase-2 (COX-2) in ischemic myocardium is thought to increase the production of proinflammatory prostanoids and contribute significantly to the ischemic inflammation. Left ventricular myocardial infarction (MI) was created by ligating the left coronary artery in Lewis rats. Hemodynamic measurements at 4 weeks showed better cardiac function in the group treated with a selective COX-2 inhibitor (DFU; 5 mg/kg/day) for 2 weeks after induction of MI compared to the vehicle treated group. These results suggest that induction of COX-2 contributes to myocardial dysfunction, and that selective inhibition of COX-2 could constitute an important therapeutic target for the treatment of MI.

Animals↗

PubMed2000

Endothelin and cardiac transplantation.

Endothelins are 21 amino acid peptides that are produced ubiquitously by vascular endothelial cells, smooth muscle cells, and other cells in different organs. Endothelins are secreted as big-endothelins that are converted to active proteins by the endothelin-converting enzyme. These peptides possess many biological activities, such as vasoconstriction and mitogenesis, and are involved in numerous physiological and pathophysiological processes in humans. Elevated plasma levels of endothelin have been associated with heart failure, and increased immunoreactivity for endothelin is observed in transplant coronary artery disease. In this brief review, we will discuss the regulation of endothelin in cardiac transplantation and the pathological role this peptide plays in renal impairment, systemic hypertension, graft rejection and arteriosclerosis after heart transplantation.

Acute Disease↗

PubMed2000

An automated interrupted suturing device for coronary artery bypass grafting: automated coronary anastomosis.

BACKGROUND: The purpose of this study was to have a preliminary assessment of the safety and efficacy of an automated vascular suturing device. METHODS: The device (Heartflo, Perclose/Abbott Labs, Redwood City, CA), which delivers 10 interrupted 7-0 polypropylene sutures between side-to-side arteriotomies, was evaluated in animals (8 Yorkshire pigs). RESULTS: Tissue edge capture and quality of anastomosis were highly rated. Time of anastomoses averaged 22 minutes. This time was prolonged primarily due to suture management, tying of interrupted sutures, and learning curve effects. Six of the anastomoses were hemostatic and two required an additional stitch each. Angiography and histology of the anastomosis confirmed patency and quality of the anastomosis. CONCLUSIONS: Our preliminary results indicate that the Heartflo automated anastomotic device is safe and effective. Preclinical and clinical studies to validate its acute and long-term effectiveness will commence shortly.

Anastomosis, Surgical↗

PubMed2000

Chemokine- and cytokine-induced expression of endothelin 1 and endothelin-converting enzyme 1 in endothelial cells.

BACKGROUND: Endothelin 1 (ET-1) is a product of endothelial and many other cell types that possesses a wide range of actions, including vasoconstriction, bronchoconstriction, and mitogenic activity on smooth muscle cells and fibroblasts. ET-1 release and expression is induced in several disease conditions associated with inflammation and cellular injury. OBJECTIVE: The purpose of this study is to determine the effects of alpha-chemokines (IL-8 and melanoma growth-stimulating activator), beta-chemokines (monocyte chemotactic protein 1, macrophage inflammatory protein 1alpha [MIP-1alpha], MIP-1beta, and RANTES), and proinflammatory cytokines (IL-1beta, TNF-alpha, and IFN-gamma) on the expression of both ET-1 and endothelin-converting enzyme 1 (ECE-1) by human umbilical vein endothelial cells. METHODS: Subconfluent monolayers of human umbilical vein endothelial cells were incubated with each chemokine individually for 24 hours or with a mixture (cytomix) of TNF-alpha, IL-1beta, and IFN-gamma for 6 and 24 hours. RESULTS: Incubation with the alpha-chemokines melanoma growth-stimulating activity and IL-8 did not significantly increase ET-1 and ECE-1 messenger (m)RNA expression and had no effect on ET-1 release. Monocyte chemotactic protein 1 exerted the most potent increase in ET-1 and ECE-1 mRNA and ET-1 release among all chemokines studied (P <.05). MIP-1alpha and RANTES exerted a moderate, but significant, increase on the ET system (P <.05). The cytomix resulted in a significant increase in ET-1 and ECE-1 mRNA expression (P <.05). CONCLUSION: These data demonstrate that, like cytokines, chemokines can induce endothelial ET-1 and ECE-1 in vitro and suggest a possible role for these inflammatory mediators in the induction of the ET system in inflammatory and vascular diseases.

Aspartic Acid Endopeptidases↗

PubMed2000

Endothelin receptor antagonist SB209670 decreases lung allograft apoptosis and improves lung graft function after prolonged ischemia.

Apoptosis has been postulated as a contributing factor in ischemia-reperfusion graft dysfunction following lung transplantation. The purpose of this study was to determine whether treatment with an endothelin-A/endothelin-B- (ET(A)/ET(B)) receptor antagonist could reduce the level of apoptosis observed in the lung following ischemia-reperfusion injury. Eleven dogs were subjected to left lung allotransplantation. Heart-lung blocks were harvested from donor dogs and preserved with modified Eurocollins solution and stored at 4 degrees C for 18 to 20 h. We investigated the level of apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), in the lungs of animals receiving an intravenous infusion of saline (control, n = 5) or the ET receptor antagonist SB209670 (n = 6) (15 microg/kg/min). The infusion began 30 min prior to transplantation and continued for up to 6 h thereafter. The TUNEL staining was significantly higher in the airway epithelium and the parenchyma of the saline (control) group (40.67 +/- 6.16), compared with native right lungs (5.00 +/- 0.56) and the treatment group (14.13 +/- 2.84). We conclude that treatment of lung allografts with the mixed ET(A)/ET(B)-receptor antagonist SB209670 can ameliorate lung injury by reducing the level of apoptosis seen in the allograft following ischemia-reperfusion injury.

Animals↗

PubMed2000

Prostaglandin H synthase 2 expression in airway cells from patients with asthma and chronic obstructive pulmonary disease.

Products of the prostaglandin H synthase (PGHS) metabolic pathway are thought to play a role in the pathogenesis of asthma. We determined the level of expression of the constitutive (PGHS-1) and inducible (PGHS-2) isoforms of the enzyme in induced sputum and bronchial biopsies of patients with asthma, patients with chronic obstructive pulmonary disease (COPD), and unaffected control subjects by immunocyto- and immunohistochemistry. Immunoreactivity for PGHS-2 was significantly greater in the induced sputum of patients with asthma and patients with COPD compared with unaffected control subjects. The level of PGHS-2 was greater in asthma than in COPD. Immunoreactivity for PGHS-1 increased in cells in the induced sputum of patients with asthma and patients with COPD compared with that of unaffected control subjects. Immunostained cells included macrophages, eosinophils, and neutrophils. Greater PGHS-2 immunoreactivity was seen in the submucosal inflammatory infiltrate and in the airway epithelium of patients with asthma compared with unaffected control subjects. In summary, we demonstrate an induction of PGHS-2 in asthma, suggesting increased formation of prostanoids, which may contribute to the inflammatory process.

Adult↗

PubMed1999

Immunolocalization of cyclooxygenase-2 in the macula densa of human elderly.

To gain insight into the role of prostanoids in human kidney function, we examined the distribution of cyclooxygenase (COX) 1 and COX-2 by immunofluorescence and immunohistochemistry in human kidneys from adults of various age groups. COX-1 was detected in the collecting ducts, thin loops of Henle and portions of the renal vasculature. COX-2 was detected in the renal vasculature, medullary interstitial cells, and the macula densa. In addition, COX-2 immunoreactivity was noted in afferent arteries and the macula densa of the renal cortex and was more evident in the kidneys of older adults.

Adolescent↗

PubMed1999

Thoracic Surgery Directors Association Award. Angiogenesis in transmyocardial revascularization: comparison of laser versus mechanical punctures.

BACKGROUND: Transmyocardial laser revascularization (TMLR), which has been shown to reduce angina in clinical trials, was originally based on the belief that laser channels are unique and can remain patent. An increasing body of evidence indicates otherwise, and transmyocardial revascularization (TMR) angiogenesis is currently thought to be induced by nonspecific inflammatory response to tissue injuries. We tested the hypothesis that mechanical transmyocardial revascularization (TMMR) may induce angiogenic responses similar to that seen with lasers. METHODS: Ameroid constrictors were implanted around proximal circumflex arteries of porcine hearts. Six weeks later, they were randomly assigned (n = 5 each) to receive 10 transmural channels in the ischemic zone by a carbon dioxide laser (group I) or by a needle (group II). A third group (group III) had 30 needle channels in the same area, while a control group (group IV) received no TMR. The hearts were harvested 1 week later, and, using immunohistochemistry, vascular endothelial growth factor (VEGF) expression was studied and quantified by computerized morphometric analysis. Densities of vascular structures positively stained for VEGF per high-power field (HPF) were also compared. RESULTS: Virtually no TMR channels remained patent histologically. Group III had a significant higher level of total VEGF expression (14.18+/-0.78 mm2) compared with group I (7.07+/-2.06 mm2, p < 0.001) and group II (4.74+/-3.35 mm2, p < 0.001). Vascular density was significantly elevated in all treatment groups compared with the control (group I, 7.7+/-0.8/HPF vs group II, 4.5+/-2.3/HPF vs group III, 8.1+/-0.6/HPF vs group IV, 1.1+/-0.5/HPF). CONCLUSIONS: In view of the significant cost implications, our findings that needle punctures may also induce angiogenic response comparable with that with laser suggest that it is justifiable and desirable to include a TMMR arm for comparison with TMLR in future clinical trials.

Animals↗

PubMed1999

Angiogenic response induced by mechanical transmyocardial revascularization.

BACKGROUND: Angiogenesis is the proposed mechanism of transmyocardial revascularization. We evaluated mechanical transmyocardial revascularization in a chronically ischemic porcine model by measuring myocardial angiogenic response. METHODS: Ameroid constrictors were implanted 6 weeks before mechanical transmyocardial revascularization. Group I (n = 5) and group II (n = 3) animals received 30 punctures with an 18-gauge needle and samples were harvested at 1 and 4 weeks, respectively, after the operation. Group III (n = 5) had sternotomy only and served as the control group. Myocardial samples were immunohistochemically stained for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor beta (TGF-beta) using specific antibodies. Growth factor expression was quantified by means of computer-assisted morphometry. Vascular density was assessed by immunohistochemical stain for VEGF and factor VIII. RESULTS: Compared with group III, increased angiogenic factor levels were found in group I (VEGF 0.47 +/- 0.03 mm(2) vs 0.05 +/- 0.05 mm(2), P =.000; bFGF 0.67 +/- 0.14 mm(2) vs 0.03 +/- 0.03 mm(2), P =. 000; TGF-beta 1.40 +/- 0.18 mm(2) vs 0.09 +/- 0.06 mm(2), P = 0.000), and in group II (VEGF 0.34 +/- 0.06 mm(2) vs 0.05 +/- 0.05 mm(2), P =.003; bFGF 0.06 +/- 0.02 mm(2) vs 0.03 +/- 0.03 mm(2), P =.135; TGF-beta 0.28 +/- 0.09 mm(2) vs 0.09 +/- 0.06 mm(2), P =.042). Vascular densities after mechanical transmyocardial revascularization were also increased (group I, VEGF stain 8.1 +/- 0. 6 vs 1.1 +/- 0.5, P =.000; factor VIII stain 5.1 +/- 2.7 vs 0.4 +/- 0.3, P =.018; group II, VEGF stain 1.9 +/- 0.5 vs 1.1 +/- 0.5, P = 0. 107; factor VIII stain 2.3 +/- 0.4 vs 0.4 +/- 0.3, P =.004). CONCLUSIONS: Mechanical transmyocardial revascularization is associated with increased angiogenic factor expression and concomitant neovascularization at up to 4 weeks. These changes are indistinguishable from those of laser transmyocardial revascularization. Myocardial perfusion studies are needed to establish the functional significance of these angiogenic changes.

Animals↗

PubMed1999

Endothelial expression of endothelial nitric oxide synthase and endothelin-1 in human coronary artery disease. Specific reference to underlying lesion.

Nitric oxide and endothelin-1 (ET-1) are two major endothelium-derived factors with opposing effects on the function and structure of the vessel wall. We investigated the endothelial expression of endothelial nitric oxide synthase (eNOS) and ET-1 in coronary artery disease (CAD) with special reference to the types of underlying lesions. Immunohistochemistry and in situ hybridization were performed in coronary arteries of heart transplant recipients with (n = 16) and without (n = 11) CAD. All coronary arteries from patients with CAD (n = 23) had concentric fibrous or advanced lesions, whereas most of the arteries (25 of 31) from patients with non-CAD showed normal appearance (myointimal thickening only) or eccentric lesions alone. Normal coronary segments consistently showed apparent endothelial immunoreactivity and mRNA signals for both eNOS and ET-1. In atherosclerotic coronary segments, endothelial expression of eNOS and ET-1 was reduced in most lesion sites, particularly in severe subendothelial lesions with dense fibrosis or macrophage accumulation, but not with smooth muscle cells only. Conversely apparent ET-1, compared with weak or focal eNOS signals, were more frequently seen in coronary segments with concentric severe lesions from CAD but not non-CAD patients. Immunoreactivity and mRNA signals for ET-1 were co-localized with those for ET converting enzyme-1 in the endothelium, as well as in the underlying macrophages and smooth muscle cells. These results indicate the presence of differential endothelial expression of eNOS and ET-1 in diseased human coronary arteries with severe concentric atherosclerotic lesions, a finding that was rare in atherosclerotic lesions of coronary arteries of non-CAD patients. Altered expression of endothelium-derived factors may contribute to abnormality of coronary vasomotor tone and the formation of subendothelial lesions in CAD.

Aspartic Acid Endopeptidases↗

PubMed1998

Endothelin receptor antagonist improves pulmonary hemodynamics during lung ischemia/reperfusion injury.

BACKGROUND: We have previously shown that elevated release of endothelin-1 is associated with increased pulmonary vascular resistance (PVR) immediately after reperfusion of the transplanted lung. In the present study, we investigated the effect of ET receptor blockage on pulmonary hemodynamics and function in an ex vivo lung reperfusion model after 6 hr of cold ischemia. METHODS: Eighteen rabbits were divided into three groups: no ischemia followed by 3 hr of reperfusion (group I) and 6 hr of cold ischemia followed by 3 hr of reperfusion with either blood (group II) or blood + SB209670 (mixed ETA/ETB receptor antagonist) (group III). RESULTS: Shortly after reperfusion, mean pulmonary artery pressure, PVR, and pulmonary edema were increased, and pulmonary compliance and PO2 were decreased in group II compared with group I. Treatment with SB209670 resulted in a significant decrease in mean pulmonary artery pressure, PVR, and pulmonary edema, and improvement in pulmonary compliance and PO2. CONCLUSION: The data suggest an important role for ET-1 in lung ischemia/reperfusion injury and that the use of ET receptor antagonist immediately after transplantation may provide a new therapeutic tool in the management of early graft dysfunction.

Animals↗

PubMed1998

Induction of cyclooxygenase-2 and activation of nuclear factor-kappaB in myocardium of patients with congestive heart failure.

BACKGROUND: Chronic heart failure is associated with induction of secondary inflammatory mediators, including prostanoids. The latter exert diverse functional and morphological effects on cardiac myocytes. Induction of cyclooxygenase (COX), the enzyme responsible for generating prostanoids, requires activation of nuclear factor-kappaB (NF-kappaB). The aim of the present study was to determine the expression of COX-2 and activation of NF-kappaB in the failing human heart. METHODS AND RESULTS: Myocardial tissue from 27 patients with end-stage heart failure (various etiologies: ischemic heart disease, n=16; idiopathic dilated cardiomyopathy, n=10; and valvular heart disease, n=1), 2 septic patients, and 8 normal control subjects was immunostained with antisera to COX-2 and NF-kappaB. Western blotting was performed and showed high anti-COX-2 antibody specificity and the presence of COX-2 protein in the sample tissues. In situ hybridization and immunohistochemistry showed little or no expression of COX-2 and NF-kappaB in the control hearts. In contrast, there was abundant expression of COX-2 mRNA and protein in myocytes and inflammatory cells in areas of fibrotic scar compared with regions of normal morphology in all cases of heart failure, except the cases with sepsis, which showed an abundance of COX-2 throughout the myocardium. Sites of NF-kappaB activation were associated with those of COX-2 expression. CONCLUSIONS: We demonstrate induction of COX-2 and activation of NF-kappaB in the myocardium of failing human hearts. Induction of both molecules appears to be associated with the presence of inflammation and scar formation.

Adult↗

PubMed1998

Heterogeneous expression and activity of endothelial and inducible nitric oxide synthases in end-stage human heart failure: their relation to lesion site and beta-adrenergic receptor therapy.

BACKGROUND: Recent reports have suggested that excessive amounts of endogenous NO may contribute to the myocardial dysfunction and injury in heart failure. In the present report, we investigate the cellular expression and activity of endothelial (eNOS) and inducible (iNOS) NO synthase in failing human hearts with special reference to the underlying lesion and drug therapy. METHODS AND RESULTS: Myocardial tissues were obtained from 28 failing human hearts with various pathogeneses and 4 nonfailing hearts as controls. Only weak or focal expression of both eNOS and iNOS was seen in ventricles of nonfailing hearts. In failing hearts, immunoreactivity and hybridization signals for eNOS were increased only in cardiac myocytes of subendocardial areas. Signals for iNOS in cardiac myocytes were consistently seen in heart failure of various pathogeneses and were apparent in both infarcted and noninfarcted regions of ischemic cardiomyopathy. Apparent signals for iNOS were also seen in infiltrating macrophages in infarcted regions of ischemic cardiomyopathy, myocarditis, and septic hearts. The expression of eNOS but not iNOS in the myocytes was intimately associated with beta-adrenergic therapy before the operation, being more abundant in patients on beta-blockers compared with diminished presence in patients on beta-agonists. In contrast to immunohistochemical data, iNOS activity was more variable than constitutive NOS activity and correlated significantly with the density of infiltrating macrophages. CONCLUSIONS: These results suggest that whereas increased eNOS and/or iNOS expression in failing cardiac myocytes may in general contribute to myocardial dysfunction, myocyte injury or death associated with inflammatory lesions may be caused in part by abundant iNOS expression within infiltrating macrophages rather than cardiac myocytes.

Adrenergic beta-Antagonists↗

PubMed1998

Angiogenesis and growth factor expression in a model of transmyocardial revascularization.

BACKGROUND: The mechanism by which transmyocardial revascularization (TMR) exerts a beneficial effect remains unknown. We hypothesize that the myocardial punctures of TMR cause a myocardial injury, leading to an angiogenic response mediated by a number of growth factors. METHODS: Fifty-three rats underwent ligation of the left coronary artery. Group I (n = 25) served as controls, whereas group II (n = 28) underwent concomitant TMR by the creation of six transmural channels with a 25-gauge needle in the ischemic zone. Surviving animals in both groups were sacrificed at intervals of 1, 2, 4, and 8 weeks (n = 5 in each subgroup). Immunohistochemistry in the infarct areas was performed for factor VIII to assess vascular density. Immunohistochemistry using specific antibodies was also performed for transforming growth factor-beta, basic-fibroblast growth factor, and vasoendothelial growth factor. Growth factor expression was quantitated by comparing areas of staining (in mm2) with computerized morphometric analysis. RESULTS: Mortality was similar in both groups (5/25 versus 8/28; not significant). Group II had significantly greater vascular density than group I (5.65 versus 4.06 vessels/high-power field; p < 0.001), with a peak at 1 week postoperatively (9.12 versus 5.56 vessels/high-power field; p < 0.0001) in both groups. Overall, levels of both transforming growth factor-beta and basic-fibroblast growth factor were significantly higher in the TMR group compared with the control group (0.207 versus 0.141 mm2/mm2, p < 0.05; and 0.125 versus 0.099 mm2/ mm2, p < 0.05). CONCLUSIONS: This model of TMR is associated with a significant angiogenic response, which appears to be mediated by the release of certain angiogenic growth factors such as transforming growth factor-beta and basic-fibroblast growth factor. With the long-term patency of laser-created myocardial channels in clinical TMR increasingly in doubt, its mechanism of myocardial revascularization may be similar to that observed in our model.

Animals↗