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Biomedical subjects

G A Thomas

Publications and source records attributed to G A Thomas.

At least 19 recordsLinked to original sources
PubMed1997

A glucose-6-phosphate dehydrogenase (G6PD) splice site consensus sequence mutation associated with G6PD enzyme deficiency.

A glucose-6-phosphate dehydrogenase (G6PD) deficient strain of mouse (GPDX) which was developed using the ethylating agent ethylnitrosourea (ENU) has been used to study clonality in epithelial tissues. While the biochemical defect has been quantified, the genetic basis of the deficiency is unknown. The G6PD gene is composed of 13 exons. Exon 1 is not translated, and the ATG start site is near the 5' end of exon 2. Direct sequencing of the exonic regions of the gene from GPDX, C3H, 101, C57BL/6 and BALB/c mice was carried out. The coding region, in which (with a single exception) all mutations found to cause G6PD deficiency in man are situated, showed identical sequences in three of the four strains studied (101 coding region sequence was not examined). However, the G6PD gene in the GPDX mouse showed a single base difference from the other four strains and from the published mouse G6PD sequence (BALB/c) in the 5' splice site consensus sequence at the 3' end of exon 1, part of the untranslated region. The difference was confirmed in four different GPDX mice. This mutation was of the type (A to T transversion) that is known to be induced by ENU; its effect is likely to be exerted through a defect in transcription, splicing or translation, leading to a reduction in protein levels. By Western blot we have found a marked decrease in the G6PD protein levels in the GPDX mouse, with the C3H X GPDX heterozygote showing a lesser decrease. Recently, an increasing number of mutations in the untranslated regions of genes have been found which have effects on protein levels. We believe that the reduced enzyme activity in the GPDX mouse is due to the mutation in the 5' untranslated region (UTR), and that similar mutations may be relevant in other inherited conditions.

Alternative Splicing↗
PubMed1997

Pharmacokinetics of nicotine carbomer enemas: a new treatment modality for ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.

Acrylic Resins↗
PubMed1997

Effect of nicotine on large bowel mucus thickness, eicosanoids and faecal proteinase in ferrets.

BACKGROUND: Following observations on the effect of subcutaneous nicotine on rectal mucosal eicosanoids and mucus in the rabbit we have repeated the work in ferrets which may be a more suitable animal model. AIMS AND METHODS: The effect of nicotine on mucosal eicosanoids, the adherent mucus layer, and faecal proteinases in the large bowel of ferrets was examined in forty animals randomly allocated to five groups, a control and four treatment groups. They were given subcutaneous saline or nicotine via an Alzet pump in doses of 0.3, 0.6, 1.2 and 2.0 mg/kg/day for 10 days and then sacrificed; measurements were made of serum nicotine and cotinine levels, rectal mucosal eicosanoids, adherent rectal and colonic mucus thickness, and faecal proteinases. RESULTS: No significant differences were observed for any measurements, except for serum nicotine and cotinine levels, which were raised consistent with the dose given. CONCLUSION: Nicotine had no effect on measurements, which may possibly be important in the relationship between smoking and ulcerative colitis.

Animals↗
PubMed1996

Heterogeneous mutation of the RET proto-oncogene in subpopulations of medullary thyroid carcinoma.

Mutations in the RET proto-oncogene are associated with the pathogenesis of medullary thyroid carcinoma (MTC). In an attempt to understand this process, we examined microdissected subpopulations from MTC and multiple metastases from these tumors. Approximately 80% of sporadic MTC's had at least one subpopulation with the RET codon 918 mutation, which is a mutation previously detected in sporadic MTC as a somatic mutation and in multiple endocrine neoplasia type 2B as a germline mutation. However, the distribution of this mutation was nonhomogeneous, occurring only in subpopulations in most tumors and among subsets of multiple metastases, thus implying that although the codon 918 mutation could be an early event, it is not necessarily an early or essential event in tumorigenesis. This heterogeneity suggests either that the codon 918 mutation can arise as an event in progression within a metastatic clone or within a single tumor, or that MTC can be of polyclonal origin. Of significance, one of two multiple endocrine neoplasia type 2A MTCs carried a somatic mutation at codon 918, in addition to the RET mutation present in the germline. We found no correlation between the presence of other somatic genetic events, such as loss of heterozygosity on chromosome arms 1p and 22q, and RET mutation status in the various subpopulations of MTC.

Carcinoma, Medullary↗
PubMed1996

Analysis of the RET proto-oncogene in sporadic parathyroid adenomas.

Missense germline mutations of the RET proto-oncogene have recently been identified in the hereditary cancer syndromes MEN2A, MEN2B, and FMTC, all characterized by medullary carcinoma, but also including phaeochromocytoma in MEN2A and MEN2B and parathyroid disease in MEN2A. In addition, somatic RET proto-oncogene mutations have been identified in a subset of sporadic medullary carcinomas and phaeochromocytomas. This study investigated the possibility that RET plays a role in sporadic parathyroid neoplasia. Firstly, normal and neoplastic parathyroid tissues were screened for expression of the RET proto-oncogene, using an RT-PCR approach on autopsy material. Secondly, 20 archival parathyroid adenomas were screened for somatic mutations in the transmembrane region of RET, the region associated with germline mutations in MEN2A and hence parathyroid disease, using a PCR-solid phase direct sequencing approach. RET expression was identified in all the parathyroid tissues analysed. However, no mutations were identified in any of the 20 adenomas, suggesting either that other mechanisms of RET activation occur, such as translocation, or that RET plays a more minor role in the growth control of the parathyroid cells than in C cells or phaeochromocytes.

Adenoma↗
PubMed1996

Skeletal muscle ventricles in circulation: decreased incidence of rupture.

BACKGROUND: Skeletal muscle ventricles (SMVs) are muscular pumping chambers constructed for cardiac assist. Skeletal muscle ventricles can be connected to the circulation in a variety of configurations for both left and right heart assist; when connected to the aorta and stimulated to contract during diastole, they function in a similar fashion as an intraaortic balloon pump. METHODS: Skeletal muscle ventricles were constructed in 18 dogs using the left latissimus dorsi muscle. In 10 of these dogs (group 1), the inner surface of the SMV was lined with autogenous pericardium obtained at the time of construction of the SMV. For the remaining 8, the SMVs were lined by fibrous tissue that forms in reaction to the synthetic mandrel around which the latissimus muscle is wrapped. After the muscles were electrically conditioned to a fatigue-resistant state, the mandrels were removed from the SMVs and the SMVs were connected to the descending thoracic aorta with a specially constructed base cap and two polytetrafluoroethylene conduits. RESULTS: Initial hemodynamic recordings revealed that the mean diastolic blood pressure increased by 24.7% in group 1 and by 29.8% in group 2. Diastolic augmentation was well maintained over time; augmentation in surviving group 1 animals was 30.0% after 18 months of pumping continuously in circulation. Long-term survival was greater in the dogs whose SMVs were constructed using an inner pericardial lining. At 90 days in circulation, 60% of the dogs in group 1 were alive with functioning SMVs, whereas only 13% of the dogs in group 2 were alive. The incidence of SMV rupture in the fibrouslined SMVs was 63%, whereas the incidence in the pericardial-lined SMVs was 0%. No evidence of thromboembolism occurred in either group. CONCLUSIONS: Lining the inner surface of an SMV with pericardium appears to provide structural integrity, which helps to prevent the complication of SMV rupture in this model of cardiac assist.

Animals↗
PubMed1996

Pericardium-lined skeletal muscle ventricles: up to two years' in-circulation experience.

BACKGROUND: Skeletal muscle ventricles (SMVs) are autologous pumping chambers constructed from skeletal muscle. Skeletal muscle ventricular rupture and thromboembolism have complicated chronic models of this method of skeletal muscle cardiac assist. METHODS: The SMVs were constructed from the latissimus dorsi muscle in 10 dogs. The inner surface of each SMV was lined with autologous pericardium harvested at the time of SMV construction. After a 3-week period of vascular delay and 6 weeks of electrical conditioning to convert the muscle to a fatigue-resistant state, SMVs were connected to the descending thoracic aorta and stimulated to contract during cardiac diastole. RESULTS: Initial hemodynamics revealed that SMV contraction at 33 Hz increased diastolic pressure 24.7% (60.8 +/- 7.3 mm Hg versus 80.3 +/- 8.8 mm Hg). Skeletal muscle ventricle relaxation decreased presystolic pressure 14.4% (59.9 +/- 7.7 mm Hg versus 51.3 +/- 7.5 mm Hg) and decreased peak systolic pressure 4.1% (90.2 +/- 7.3 mm Hg versus 86.5 +/- 5.8 mm Hg). Hemodynamics were assessed at 1 to 2 weeks, then at 1, 2, 3, and 6 months, and at 6-month intervals thereafter. Hemodynamic performance remained stable for the duration of this study. After 2 years of pumping continuously in circulation, SMV contraction resulted in a 34.8% augmentation of diastolic pressure (63.6 +/- 6.6 mm Hg versus 85.3 +/- 6.4 mm Hg), a 17.2% decrease in presystolic pressure (54.7 +/- 3.73 mm Hg versus 45.3 +/- 4.1 mm Hg), and a 4.2% decrease in peak systolic pressure (95.3 +/- 10.4 mm Hg versus 91.3 +/- 12.3 mm Hg). Three dogs survived to 2 years with the SMVs in circulation. No animal showed evidence of thromboembolism during serial echocardiography or at autopsy and no SMVs ruptured. CONCLUSIONS: These data demonstrate that SMVs can provide effective hemodynamic assist over an extended period without specific complications related to the SMVs.

Animals↗
PubMed1996

RET activation in adult and childhood papillary thyroid carcinoma using a reverse transcriptase-n-polymerase chain reaction approach on archival-nested material.

Activation of the RET tyrosine kinase domain occurs in a proportion of thyroid papillary carcinomas. Three chromosomal rearrangements have been described, of which PTC1 is the commonest. Wide differences (2.5-25%) in frequency of PTC1 in different populations have been reported; it is not clear whether these are due to environmental factors, racial differences or technical reasons. We have developed a simple and rapid reverse transcriptase nested polymerase chain reaction (RT-nPCR) method enabling the detection of gene expression from single 5 microns sections of formalin-fixed paraffin wax-embedded archival material. We have applied this approach to detect expression of the RET tyrosine kinase domain, allowing identification of RET activation resulting from any rearrangement, whether characterised or not, or from overexpression. A retrospective study was performed on 22 adult and 21 childhood papillary carcinomas. Thirteen of 22 (59%) adult and 10 of 21 (48%) childhood carcinomas showed evidence of RET activation, demonstrating a major role for the RET oncogene in UK thyroid papillary carcinogenesis. This study also shows a similar frequency of RET activation in both children and adults. The use of a technique that allows reliable amplification of RNA from archival material, using primers chosen in different exons so that amplified products are readily distinguished from genomic DNA, will allow correlation of translocations and chromosomal rearrangements with a variety of specific tumour types.

Actins↗
PubMed1996

Skeletal muscle ventricles: frontiers in 1995.

Skeletal muscle ventricles (SMVs) constructed from electrically conditioned latissimus dorsi muscle (LDM) may become an alternative for assisting the failing heart. Left and right heart circulatory assist using SMVs has been performed successfully in both acute and chronic animal models. The configurations used to connect SMVs to the circulation have included a left atrium to aorta bypass, a left ventricle apex to aorta bypass, aortic counterpulsators, a cavopulmonary bypass, and a right ventricle to pulmonary artery bypass. One SMV used as an aortic counterpulsator functioned effectively in the circulation for more than 27 months. Recent application of the pericardium to the SMV as an inner layer and design changes in the connection of the SMV to the circulation have reduced the risk of thrombus formation and SMV rupture. Although several problems have yet to be solved, the goal of the SMV as a permanent circulatory assist device without the limitation of an external power source seems within reach.

Animals↗
PubMed1996

Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of non-smokers. Previous controlled trials have shown benefit with transdermal nicotine when given with 5-aminosalicylic acid in active disease but not when given alone as maintenance therapy. OBJECTIVE: To examine nicotine alone compared with prednisolone in active disease. PATIENTS AND METHODS: Sixty-one patients with active ulcerative colitis were treated with either transdermal nicotine patches or 15 mg prednisolone for 6 weeks in a randomized, double-blind study. Incremental doses of nicotine were given for the first 9 days; patients tolerated between 15 and 25 mg daily. Most patients were taking mesalazine at entry which was discontinued at day 10; a few were taking topical steroids which were discontinued at the onset. Clinical, sigmoidoscopic and histological assessments were made at baseline and 6 weeks, or at premature withdrawal. Symptoms were recorded on a diary card, and the clinician made a global clinical assessment. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. RESULTS: Forty-three patients completed the 6-week trial; of these, 6 of 19 in the nicotine group achieved full sigmoidoscopic remission compared with 14 of 24 with prednisolone (P = 0.08). In those who completed the 6-week study, there was significant improvement within both the nicotine and prednisolone group for the St Mark's score (P < 0.05 and P < 0.01, respectively), Global Clinical Grade (P < 0.01 for both), blood in the stool (P < 0.05 and P < 0.01), abdominal pain (P < 0.05 and P < 0.01) and sigmoidoscopic score (P < 0.01 and P < 0.001); differences between groups tend to favour prednisolone, but none reach statistical significance. However, on intention-to-treat analyses there is little clear evidence of improvement in either group apart from sigmoidoscopic score in which prednisolone was associated with a significantly greater improvement than nicotine (P < or = 0.05). The nicotine group had more withdrawals than the prednisolone group, 11 versus 7, respectively (P = 0.23), both for deterioration (6 vs. 5) and side effects (5 vs. 2, P = 0.15). Side effects were more frequently reported in the nicotine group (average 1.47 episodes per person) than the prednisolone group (average 0.61; P = 0.03), the most common of which were nausea, light-headedness and tremor. CONCLUSION: In those who managed to complete the 6-week study, nicotine alone appeared to be of only very modest benefit in acute colitis and was not as effective as 15 mg of prednisolone daily.

Administration, Cutaneous↗
PubMed1995

Transdermal nicotine as maintenance therapy for ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Having found previously that treatment with transdermal nicotine patches and mesalamine (5-aminosalicylic acid) has a beneficial effect on active colitis, we examined the value of transdermal nicotine for the maintenance of remission. METHODS: We treated 80 patients with ulcerative colitis in remission with either transdermal nicotine or placebo patches for six months in a randomized, double-blind study. Incremental doses of nicotine were given for the first three weeks to achieve a maintenance dose; most patients tolerated 15 mg for 16 hours daily. All patients were taking mesalamine preparations as maintenance treatment at entry into the study; this treatment was stopped once the maintenance dose of nicotine was achieved. Clinical, sigmoidoscopic, and histologic assessments were made at the beginning and the end of the study, or at relapse. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. RESULTS: There was no significant difference in the number of relapses between the groups. Twenty-two patients in the nicotine group were prematurely withdrawn from the study, 14 because of relapse and 8 for other reasons, including side effects and protocol violations. In the placebo group, 20 patients were withdrawn prematurely, 17 because of relapse and 3 for other reasons. Among patients using 15-mg nicotine patches, serum nicotine and cotinine concentrations were lower than expected and may reflect poor compliance. Side effects were reported by 35 patients--21 in the nicotine group and 14 in the placebo group--the most common of which were nausea, lightheadedness, and itching. CONCLUSIONS: Transdermal nicotine alone was no better than placebo in the maintenance of remission of ulcerative colitis, and premature withdrawal due to side effects was more common in the nicotine group.

Administration, Cutaneous↗
PubMed1995

Skeletal muscle ventricles: improved left ventricular performance associated with a prolongation of ventricular relaxation.

Skeletal muscle ventricles (SMV) have been shown to pump blood effectively in both acute and chronic models. In this study SMVs were placed in circulation in series with the descending thoracic aorta to function as diastolic counterpulsators. The SMVs were stimulated to contract at a 1:2 ratio with the heart. The R-wave delay and the burst duration were varied, both as a percentage of the total R-R' interval to determine the effect of the SMV on left ventricular (LV) relaxation in relation to other parameters of LV function. Optimal hemodynamic benefit was obtained using a 40% R-wave delay and a 30% burst duration. At these settings, the time constant of LV relaxation (tau) increased from a control value of 29.1 +/- 1.6 to 39.8 +/- 2.1 msec (P < 0.001). The tension time index decreased from a control value of 15.24 +/- .31 to 13.88 +/- .7 mm Hg-sec-1 (P < 0.001). The endocardial viability ratio, an indicator of myocardial blood flow, improved from 1.12 +/- .11 to 1.55 +/- .16 (P < 0.001) and LV dP/dt increased from 1555 +/- 180 to 2320 +/- 210 mm Hg-sec-1 (P < 0.05). In conclusion, this study demonstrates SMV diastolic counterpulsation results in improved LV performance which is associated with a prolongation of LV relaxation. A 40% R-wave delay interval and a 30% burst duration were the stimulation parameters which benefitted myocardial function optimally in this study.

Animals↗
PubMed1995

Endothelial cell-lined skeletal muscle ventricles in circulation.

Skeletal muscle ventricles were constructed from the latissimus dorsi in six dogs by wrapping the muscle around a polypropylene mandrel. Jugular vein endothelial cells were harvested enzymatically and grown in tissue culture. After 3 weeks of vascular delay and 4 weeks of electrical conditioning, five skeletal muscle ventricles were seeded with 5 to 8 x 10(6) autologous endothelial cells by percutaneous injection of a cellular suspension into the lumen of the skeletal muscle ventricle; one skeletal muscle ventricle was injected with culture medium alone as an unseeded control. The autologous endothelial cells were all prelabeled with a lipid-bound cellular marker, PKH-26. After an additional 4 weeks of electrical conditioning, the mandrels were removed and the skeletal muscle ventricles were connected to the descending thoracic aorta and activated to contract during cardiac diastole at a 1:2 ratio with the heart. After 3 hours of continuous pumping, mean diastolic pressure was increased by 35% (58 +/- 7 versus 78 +/- 6 mm Hg, p < 0.05). At this time, the skeletal muscle ventricles were excised for histologic examination. Sections stained with hematoxylin and eosin revealed a continuous cellular layer lining the skeletal muscle ventricle; no cells were present on the lumen of the control skeletal muscle ventricle. All seeded skeletal muscle ventricles exhibited fluorescence as a result of the PKH-26 cellular marker. Immunofluorescent staining with antibodies to von Willebrand factor and ultrastructural analysis with an electron microscope confirmed the endothelial character of these cells lining the lumen of the skeletal muscle ventricles. The ability to create endothelial cell-lined muscular pumping chambers holds important implications for the resolution of thrombotic events in cardiac assist devices as well as toward the clinical application of skeletal muscle ventricles.

Animals↗
PubMed1995

Evidence for mutual interdependence of epithelium and stromal lymphoid cells in a subset of papillary carcinomas.

We have correlated the morphological features of 30 human thyroid carcinomas with the cellular localisation of insulin-like growth factor 1 (IGF-1) mRNA and IGF-1 receptor peptide using in situ hybridisation with digoxigenin-labelled oligoprobes and immunohistochemistry. Four of the five follicular carcinomas studied showed a consistent, uniform, strong positivity for IGF-1 mRNA in tumour cells compared with weakly positive surrounding normal follicular tissue and negative stroma. The majority of papillary carcinomas showed weak to moderate epithelial positivity for IGF-1 mRNA and negative stroma. Immunohistochemistry for IGF-1 receptor showed moderate positivity confined to the tumour epithelial cells in both follicular and the majority of papillary carcinomas. However, in a subgroup of papillary carcinomas characterised by a diffuse stromal lymphoid infiltration (n = 5), the stromal cells showed a much stronger reactivity for IGF-1 mRNA than the tumour or background thyroid, and the tumour cells showed a uniformly high level of immunoreactivity for IGF-1 receptor. These results are compatible with the growth of the papillary carcinoma in these cases being the result of a symbiotic relationship between the stromal lymphoid cells and the tumour epithelium with the lymphoid cells responding to an antigen produced by the tumour cells and the tumour cells responding to a growth factor produced by the lymphoid infiltrate. We suggest that this mechanism may be important in other tumours regularly associated with a widespread lymphoid infiltrate.

Animals↗
PubMed1995

Endothelial lined skeletal muscle ventricles: open and percutaneous seeding techniques.

Twelve bilateral skeletal muscle ventricles (SMVs) were constructed in six dogs by wrapping each latissimus dorsi muscle around a cylindrical, plastic mandrel (volume 30 cc). After 6 to 10 weeks, five dogs had one of their SMVs seeded with allogeneic cultured canine endothelial cells (8 x 10(6) cells/pouch) via an open technique, whil the contralateral SMV was seeded by percutaneous injection of cells into the space around the mandrel. After 1 week, the SMVs were excised. Viable, adherent endothelial cells were present in all seeded pouches; this was confirmed via fluorescent microscopy with several endothelial cell markers; KLH-2, dilacetylated low-density lipoprotein and antibodies to von Willebrand factor. The inner lining of the SMVs were also examined with scanning and transmission electron microscopy; the highest concentration of cells were seen at the apex where a continuous endothelial monolayer was observed. No significant difference in the distribution or the morphology of the endothelial lining was noted between the open and percutaneous seeding techniques. These data show that SMVs can be seeded with an endothelial monolayer using both open and percutaneous techniques.

Animals↗
PubMed1995

Chronic changes of end-systolic pressure-volume relationship after regional myocardial infarction.

The chronic changes of the end-systolic pressure-volume relationship (ESPVR) after regional myocardial infarction were evaluated in a sheep model. Pressure-volume area (PVA) obtained from the pressure-volume diagram and left ventricular oxygen consumption (LVO2) were studied. The regional myocardial infarction was created by ligating distal branches of the left coronary artery. ESPVR was obtained using a conductance catheter during transient inferior vena cava occlusion. Measurements were performed at baseline (n = 13), 1 hour (n = 8), 3 months (n = 9), and 6 months (n = 4) after infarction. Ees, the slope of the ESPVR did not change at 1 hour after infarction and remained the same at 3-month and 6-month measurements (baseline 2.26 +/- 1.24 mmHg/mL, 1 hour 2.71 +/- 1.06, 3 months 3.46 +/- 1.51, 6 months 2.45 +/- 0.64, NS). Because of the ventricular dilatation, which was demonstrated as an increase in changes of end-systolic volume (Ves) correlating with the time course after infarction (y = -3.21 + 0.12x, r = 0.454, p < 0.05), V0, the volume intercept of the ESPVR increased at 1 hour after the infarction, and showed a tendency to increase at 3 months and 6 months after the infarction (baseline -18.0 +/- 22.5 mL; 1 hour -0.9 +/- 11.6; 3 months 5.4 +/- 10.9, 6 months 9.2 +/- 23.1, baseline vs 3 months p < 0.05, baseline vs 6 months p < 0.05). PVA and LVO2 were unchanged over time after infarction (PVA: baseline 2097 +/- 1526 mmHg/mL per 100 g-1; 1 hour 1771 +/- 699; 3 months 2483 +/- 1086; 6 months 1,608 +/- 1,010, NS), (LVO2: baseline 40.6 +/- 13.1 x 10(-3) mL/100 g-1 per beat-1; 1 hour 42.9 +/- 9.7; 3 months 35.0 +/- 8.6; 6 months 31.2 +/- 18.1, NS). Chronic regional infarction in the sheep model did not affect Ees over 6 months, but significantly increased V0 after the increase in the acute phase. PVA and LVO2 were not affected by this regional infarction either acutely or over 6 months.

Animals↗