Biomedical subjects

G Dellgren

Publications and source records attributed to G Dellgren.

12 recordsLinked to original sources

PubMed2005

Antagonism of the renin-angiotensin system can counteract cardiac angiogenic vascular endothelial growth factor gene therapy and myocardial angiogenesis in the normal heart.

BACKGROUND: The aim of this study was to test the hypothesis that angiotensin converting enzyme inhibition or angiotensin II antagonism can counteract cardiac human vascular endothelial growth factor-A165 (phVEGF-A165) induced angiogenesis. METHODS: Mice were given a single intramyocardial injection of phVEGF-A165. Either enalapril or candesartan was given subcutaneously for 10 consecutive days. Hearts were harvested and capillary count was performed by immunohistochemistry. With similar design, groups of mice were sacrificed after 24 h for the determination of tissue expression of phVEGF-A protein, mRNA expression of mouse VEGF-A, and VEGF receptors 1 and 2, after pEGFP-Luc transfection for luciferase expression. RESULTS: Increased myocardial capillary density (P < .02) induced by phVEGF-A165 was counteracted by both enalapril (P < .07) and candesartan (P < .02) and then did not differ from control values. We found that phVEGF-A165 induced myocardial hVEGF-A expression (110 +/- 15 pg/heart, P < .0001). Both enalapril and candesartan decreased (P < .01) expression of hVEGF-A to a level not different from control values. Although phVEGF-A165 upregulated (P < .0001) mVEGFR-2, addition of candesartan downregulated endogenous mVEGF-A (P < .0001) and mVEGFR-2 (P < .0001) below the level in normal myocardium. Enalapril or candesartan did not effect luciferase expression. CONCLUSIONS: Enalapril and candesartan both specifically inhibit phVEGF-A165 induced myocardial angiogenesis in the normal heart. The mechanism of inhibition is a combination of inhibition of cardiac hVEGF-A expression and of decreased endogenous expression of the mVEGF ligand and receptor system.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2004

Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infarcted rat myocardium.

OBJECTIVE: It is thought that adult human mesenchymal stem cells do not induce immunoreactivity even to xenografts. We wanted to study whether adult human mesenchymal stem cells survive and engraft in experimentally induced ischemic rat myocardium. METHODS: Bone marrow-derived adult human mesenchymal stem cells (2.5 x 10(6)) were injected into the myocardium of 4 Sprague-Dawley rats. One week after injection, peripheral blood rat lymphocytes were added to adult human mesenchymal stem cells in a mixed lymphocyte reaction. Furthermore, an infarction was created by left anterior descending artery ligation of 8 Sprague-Dawley rats, 4 of which were immunosuppressed with tacrolimus (0.1 mg/kg/d) and 4 RNU athymic rats. One week after left anterior descending artery ligation, 2.5 to 3.5 x 10(6) adult human mesenchymal stem cells were injected around the infarcted area. The adult human mesenchymal stem cells were identified with fluorescence in situ hybridization technique and myocardial antigens by immunohistochemistry. The immune response was studied by hematoxylin and eosin staining and by antibodies directed toward macrophages. RESULTS: Significant rat lymphocyte proliferation was observed when adult human mesenchymal stem cells were added to peripheral blood from Sprague-Dawley rats previously exposed to adult human mesenchymal stem cells. No reactivity was seen in lymphocytes from untreated Sprague-Dawley rats and athymic rats. Adult human mesenchymal stem cells could only be identified in the myocardium of athymic rats. Further, in normal Sprague-Dawley rats, there was a significant myocardial infiltration of round cells, mostly macrophages, in the area of injection of adult human mesenchymal stem cells. In RNU rats, this reaction was less intense. CONCLUSION: Adult human mesenchymal stem cells did not induce xenoreactivity in vitro in previously unexposed immunocompetent Sprague-Dawley rats. However, although mesenchymal stem cells are transplantable across allogeneic barriers, transplant rejection can occur in a xenogenic model. When transplanted into an immunoincompetent host, adult human mesenchymal stem cells showed persistent engraftment.

Animals↗

PubMed2004

Simvastatin enhances myocardial angiogenesis induced by vascular endothelial growth factor gene transfer.

Statins have cardioprotective roles. We explored the cardiac angiogenic effects of simvastatin in combination with transient overexpression of vascular endothelial growth factor (VEGF). Compared with normal mice, 1-year-old ApoE(-/-) mice fed on a high-fat diet (HFD) had about 30% less myocardial capillary (P < 0.001) and arteriolar (P < 0.03) densities, associated with decreased VEGF (55%), VEGFR-1 (56%) and VEGFR-2 (78%) mRNA expressions and myocardial endothelial nitric oxide synthase (eNOS) production (58%). By contrast, angiopoietin-1 and angiopoietin-2 mRNA expressions were increased (500% P < 0.02, and 400% P < 0.01, respectively) in the ApoE(-/-) hearts. No change was observed in Tie-2 gene expression. Phosphorylation of antiapoptotic Akt was lower and proapoptotic p38 mitogen-activated protein kinase (MAPK) was higher in the ApoE(-/-) mice compared with controls. Intramyocardial VEGF gene transfer increased capillary and arteriolar densities in the ApoE(-/-) mice, and simvastatin treatment further enhanced capillary density (P < 0.03) to a level similar to that of normal mice. Simvastatin did not change the lipid profile but blocked p38 MAPK phosphorylation in the ApoE(-/-) myocardium. Concurrent with these changes, there were increased levels of expression of mVEGF (P < 0.04) and VEGFR-2 (P < 0.03) mRNAs and increased production of eNOS (P < 0.05) in the ApoE(-/-) mice, while no changes were detected in the angiopoietin system. Thus, increased myocardial angiogenesis in the ApoE(-/-) mice following transient overexpression of VEGF is further increased by additional simvastatin treatment. These effects occurred concurrently with simvastatin-induced stimulation of the VEGF system, increased eNOS production and reduction in p38 MAPK phosphorylation.

Animals↗

PubMed2004

Surgical closure of patent foramen ovale in patients with suspected paradoxical embolism: long-term results.

OBJECTIVE: It is thought that a patent foramen ovale (PFO) is the crucial mechanism in patients with suspected paradoxical embolism and cryptogenic stroke. It has been hypothesized that closure of the PFO would prevent further cerebrovascular incidents. We describe our early and late experience with surgical closure of the PFO in patients with paradoxical embolism. PATIENTS AND METHODS: Between May 1994 and December 2001, 33 patients (26 men, 7 women; mean age, 55.2 +/- 8.7 years; range, 37-74) underwent surgical closure of a PFO at our institution. All patients had preoperatively suffered from a stroke and/or a transient ischemic attack, after which echocardiography showed a PFO. Mean follow-up at 99 +/- 30 months (range, 10-111 months) was 100% complete. RESULTS: All patients survived the operative procedure. Early complications occurred in four patients (12%). Actuarial survival at 1, 5 and 8 years was 97 +/- 3%, 97 +/- 5% and 94 +/- 8%, respectively. At long-term follow-up all but two patients were alive. The deaths of these two patients were related to malignancy and ischemic heart disease, respectively. Two patients (6%) had suffered a residual cerebrovascular event after successful surgery. CONCLUSION: Surgical closure of PFO in patients with paradoxical embolism can safely be performed with a low risk of early mortality. Residual thromboembolic events were rare and in those few it occurred it did so with the interatrial septum being closed, indicating that in those patients the PFO was not the mechanism of the thromboembolic event in the first place.

Adult↗

PubMed2003

Successful off pump coronary artery bypass grafting in a patient with an undiagnosed pheochromocytoma.

We report a successful off pump coronary artery bypass case in a patient with a pre-operatively undiagnosed pheochromocytoma. The patient had no signs of ischemia intra- or post-operatively due to aggressive antihypertensive treatment. We would also like to emphasize the importance of using an adequate stabilizing device in order to safely perform anastomoses in a situation like this.

Adrenal Gland Neoplasms↗

PubMed2001

Redo aortic root replacement: experience with 31 patients.

BACKGROUND: Aortic root re-replacement is being performed with increased frequency. Limited information is available regarding the surgical approaches and clinical outcomes of this reoperation. METHODS: Between May 1980 and May 1999, 31 patients (mean age, 45 +/- 15 years) underwent redo composite replacement of the aortic valve and ascending aorta. Indications for reoperation were prosthetic valve endocarditis in 12 patients (39%), failed biological valve in 17 (55%), and false aneurysm in 2 (6%). At reoperation, mechanical valves were implanted in 24 patients and biologic valves in 7. All patients with endocarditis had annular abscess and required reconstruction of the left ventricular outflow tract before implantation of a new valved conduit. Mechanical valves were used in 24 patients, aortic homograft in 4, and bioprosthetic valves in 3. The coronary button technique was used to reimplant the coronary arteries whenever possible. Extension of one or both coronary arteries with a short segment of saphenous vein or a synthetic graft was used in 16 patients (52%). The aortic arch was replaced in 7 patients (23%). RESULTS: There was one operative death (3%) because of rupture of an abdominal aortic aneurysm. The mean follow-up was 47 +/- 46 months and was 100% complete. There were five late deaths (16%), three of which were cardiac related. The actuarial survival was 71% +/- 12% at 5 years. Three patients experienced recurrent prosthetic valve endocarditis 4 months to 8 years after operation. The 8-year freedom from endocarditis for patients operated on for endocarditis was 82% +/- 11% compared with 100% for those operated on for other reasons (p = 0.1). At the last follow-up, 21 of 25 survivors (84%) were in New York Heart Association functional classes I or II, and 4 were in class III. CONCLUSIONS: Redo aortic root replacement can be performed with good early and late results. Patients operated on for prosthetic root endocarditis may have an increased risk of recurrent late endocarditis.

Adolescent↗

PubMed2001

Pediatric heart transplantation: improving results in high-risk patients.

OBJECTIVES: Our institutional experience with 73 pediatric patients undergoing cardiac transplantation between January 1, 1990, and December 31, 1999, was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. METHODS AND RESULTS: The introduction of donor blood cardioplegic solution with added insulin was associated with a significant improvement in patient and graft survival (hazard ratio [Cox] = 0.25, P =.08), despite significantly longer ischemic times with this protocol compared with the use of crystalloid-based donor procurement techniques (P <.01). Eleven patients underwent intentional transplantation of ABO-incompatible donor hearts with the aid of a protocol of plasma exchange on bypass. In this subgroup, there were 2 early deaths caused by nonspecific graft failure (n = 1) and respiratory complications with mild vascular rejection (n = 1), and there was 1 late death caused by lymphoma. ABO-incompatible transplantation was not a risk factor for death by multivariate analysis. The postoperative course in these patients suggests minimal reactivity directed against incompatible grafts on the basis of low anti-donor blood group antibody production, in association with a favorable rejection profile. Ten of 13 patients requiring preoperative support with an extracorporeal membrane oxygenator survived transplantation; there were 3 additional late deaths in this subgroup (hazard ratio = 2.88, P =.05). CONCLUSIONS: The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting successful treatment of patients conventionally considered at high risk or unsuitable for transplantation.

ABO Blood-Group System↗

PubMed2001

Pediatric heart transplantation: improving results in high-risk patients.

Our institutional experience with 68 pediatric patients undergoing cardiac transplantation was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. The introduction of donor blood insulin cardioplegia was associated with a significant improvement in patient and graft survival. Among 63 ABO-matched transplant procedures, both the patient and graft loss rate were significantly lower (by multivariable analysis) with the use of the donor blood insulin cardioplegia versus conventional cardioplegia, despite significantly longer ischemic times in the former group. Twenty-three (33.8%) patients were deemed at ultra-high risk: eight of 11 patients with cardiomyopathy transplanted following ECMO support survived without major sequelae; three of four additional patients survived early retransplantation. Ten patients underwent intentional ABO-incompatible transplantation under a protocol of plasma exchange on bypass. There were two early deaths because of nonspecific graft failure and respiratory complications with mild vascular rejection, and one late death because of lymphoma. Among seven surviving ABO-incompatible patients followed up to 31 months, there have been no episodes of humoral rejection despite development of antidonor blood group antibodies in A to O, but not B to O, mismatches. The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting salvage of patients conventionally considered at high risk or nontransplantable.

ABO Blood-Group System↗

PubMed2000

Risk factors for late pulmonary homograft stenosis after the Ross procedure.

BACKGROUND: We reviewed our experience with the Ross procedure to identify the prevalence and predictors of late pulmonary homograft stenosis. METHODS: Between June 1992 and December 1997, 109 consecutive patients (age 34.5 +/- 8.6 years) underwent the Ross procedure, with reconstruction of the right ventricular outflow tract with a cryopreserved pulmonary homograft (22 to 30 mm diameter). There was one early and one late death. Echocardiographic follow-up was available in 105 of 108 patients (97%), with a follow-up of 39 +/- 20 months. Homograft donor and preservation measurements and patient variables were subjected to multivariable analyses to identify independent predictors of late homograft performance. RESULTS: The major physiopathologic finding was homograft stenosis. Peak systolic gradients across the homograft were 20 mm Hg or more in 30 of 105 patients (28.5%) and 40 mm Hg or more in 4 of 105 patients (3.8%). One patient required two re-replacements of her homograft for severe stenosis. Moderate or severe homograft insufficiency was noted in 10 of 105 patients (9.5%). The independent predictors of late pulmonary homograft stenosis were younger donor age (p = 0.03), shorter duration of cryopreservation (p = 0.01), and smaller homograft size (p = 0.06). Beating heart donor status, short homograft ischemic time, and other factors that have been shown to be associated with increased graft viability were associated with graft stenosis but did not reach statistical significance. However, mean gradients across the homograft were significantly related (p = 0.002) to the number of these risk factors in each patient. CONCLUSIONS: Stenosis of the pulmonary homograft can be a significant problem following the Ross procedure, and was predicted by younger donor age and shorter duration of cryopreservation. These factors may be related to increased cellular viability, which might actually predispose to late homograft stenosis in a subgroup of patients.

Adolescent↗

PubMed1999

Angiotensin-converting enzyme gene polymorphism influences degree of left ventricular hypertrophy and its regression in patients undergoing operation for aortic stenosis.

Insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with increased left ventricular hypertrophy (LVH) in patients with cardiomyopathy and congestive heart failure. Patients with aortic stenosis (AS) have varying degrees of LVH at a given valve area. The aim of this study was to examine the relation between ACE gene polymorphism and the degree of LVH in patients undergoing operation for AS. Eighty-two patients who underwent operation for AS with a stentless valve were followed prospectively with echocardiographic assessments of left ventricular mass index (LVMI). ACE gene polymorphism was determined by polymerase chain reaction. The genotype (DD, ID, and II) frequency was the same as in healthy controls. The pressure difference across the aortic valve did not differ between genotypes. Patients with the DD genotype of the ACE gene had a higher LVMI (197 +/- 47 g/m2) preoperatively than those with ID (175 +/- 41 g/m2) or II (155 +/- 43 g/m2) genotypes (p = 0.01). LVMI decreased significantly in DD (p <0.001) and ID (p <0.001) genotypes but not in the II genotype during follow-up (mean 15 months). There was a significant difference in regression of LVMI over time between genotypes (p = 0.0056), with no significant difference between genotypes at follow-up. The DD genotype of the ACE gene is associated with increased preoperative LVH in patients treated surgically for AS. The DD genotype appears to be an important factor which increases hypertrophic myocardial reactivity to pressure overload.

Aged↗

PubMed1999

The extended Biocor stentless aortic bioprosthesis. Early clinical experience.

In the "Extended" Biocor stentless aortic bioprosthesis, supra- and subvalvular extensions to a bovine pericardium ring carry three porcine leaflets. The extensions cover the "non-coronary" sinus of the prosthesis and allow optional enlargement of the aortic root down towards the mitral valve as well as upwards into the aortotomy. Seventy-one patients with this stentless valve (62 with predominantly aortic stenosis, 28 with concomitant CABG) are being prospectively studied. This paper reports follow-up one year after insertion. The upper and lower pericardial extensions were used in 61 and 11 patients, respectively. The average prosthetic valve size was 23.2 +/- 1.6 mm. Early mortality was 7% (5/71); late mortality (4/66, 5%/patient year) was not valve-related. Symptoms of thromboembolism (new neurological defects) occurred in four patients. There was no valve failure or late endocarditis. One year postoperatively the transvalvular mean pressure difference for all valves was 7.9 (3.1-18.4) mmHg. None of the patients had haemodynamically significant aortic regurgitation at follow-up; nine had trivial regurgitation. The "Extended" Biocor stentless bioprosthesis thus has a favourable haemodynamic profile and can be advantageous in elderly patients with narrow aortic roots, and often with thin and/or calcified aortic walls.

Aged↗

PubMed1999

The Toronto SPV: hemodynamic data at 1 and 5 years' postimplantation.

The Toronto-SPV (T-SPV) bioprosthesis has been used for aortic valve replacement (AVR) since July 1991. There is no published data on its mid-term hemodynamic performance. This study compares the hemodynamic data of a consecutive series of patients at 1 and 5 years after AVR. The first 109 consecutive patients who had AVR with a T-SPV have been monitored for a minimum of 5 years and have had annual Doppler echocardiographic studies. There were 80 men and 29 women in the study; mean age was 62 years (range 34 to 80 years). Concomitant coronary artery bypass surgery was done in 35 patients. One operative and nine late deaths occurred. The mean systolic gradient across the T-SPV in all patients was 3.9+/-2.4 mm Hg at 1 year and 4.1+/-3.3 mm Hg at 5 years (P = .27). The mean aortic valve area was 2.2+/-0.6 cm2 at 1 year and 2.3+/-0.7 cm2 at 5 years (P = .43). The mean left ventricular mass index (LVMI) was 104+/-31 g/m2 at 1 year and 97+/-24 g/m2 at 5 years (P = .08). Multivariate linear regression analysis showed that preoperative coronary artery disease (P<.0001) and hypertension (P<.01) were independent predictors of higher LVMI over time. Aortic insufficiency was none/trivial in 94% of patients and mild in 6% at 1 year. At 5 years, aortic insufficiency was none/trivial in 88% of patients, mild in 10%, and moderate in 2%. The aortic leaflets remained thin and pliable in all patients as assessed by echocardiography. Most patients (85%) were in New York Heart Association functional class I. The hemodynamic performance of the T-SPV remained unchanged during the first 5 years after implantation. The LVMI continued to decrease after the first year and tended to normalize in most patients. The aortic valve remained competent, and the leaflets did not change their thickness or show evidence of calcification.

Adult↗