Cardiac IGF-I manipulation by growth hormone following myocardial infarction.

Evidence of a role for growth hormone (GH) in cardiac structure and function has been derived from studies of patients suffering either GH excess or deficiency, both of which may lead to reduced life expectancy. The role of GH in the ischaemic heart, however, is less than clear. We therefore investigated the effect of 30 days GH treatment in sheep with myocardial infarction. GH treatment significantly increased circulating IGF-I levels (P<0.01), heart weight (P<0.01), and cardiomyocyte cross-sectional area (P<0.001). IGF-I mRNA in peri-infarct cardiac tissue also increased significantly (P<0.05). We conclude that post-infarct GH treatment increases circulating and cardiac IGF-I levels, resulting in significant cardiomyocyte hypertrophy. This increase in cardiomyocyte size appears to correlate with local IGF-I expression rather than plasma IGF-I levels.

A randomized study of direct coronary stent delivery compared with stenting after predilatation: the NIR future trial. On behalf of the NIR Future Trial Investigators.

This randomized trial compared a strategy of direct stenting without predilatation (n = 39) with conventional stenting with predilatation (n = 42) in patients with suitable lesions in native vessels > or = 2. 5-mm diameter to be covered by either a 9- or 16-mm-length NIR Primo stent. Equipment cost [mean (median) +/- SD] was less in those with direct stenting [$1,199 (979) +/- 526] than in those with predilatation [$1,455 (1,285) +/- 401, P < 0.001]. There was no significant difference in contrast use or fluoroscopy time. Procedural time was shorter in the direct stenting group. The clinical outcome at 1 month was satisfactory in both groups. In selected patients, a strategy of direct stenting is feasible, costs less, and is quicker to perform than the conventional strategy of stenting following predilatation.

Changes in IGFs in cardiac tissue following myocardial infarction.

We have studied changes in the IGF axis in an ovine model of myocardial infarction (MI), in order to determine the relationship between time-based changes in post-infarct myocardium and IGF levels. IGF localization was studied by immunocytochemistry, production by in situ hybridization, and specific binding by radioligand studies. In surviving tissue, IGF-I peptide localized to cardiomyocytes, with strongest immunostaining at 1 and 2 days post-infarct in the immediate border area adjoining the infarct, where IGF-I mRNA also increased, reaching a maximum at 2 days. Binding of radiolabelled IGF-I in surviving tissue was initially lower than that seen in cardiomyocytes in control myocardium, subsequently increasing to become significantly greater by 6 days post-infarct. In necrotic tissue, IGF-I peptide was still detectable in cardiomyocytes at 0.5 days post-infarct, but had cleared from this area by 1 day, becoming detectable again at 6 days post-infarct in macrophages and fibroblasts infiltrating the repair zone. IGF-I mRNA was not detected in necrotic tissue until 6 days, when probe hybridized to macrophages and fibroblasts. Within the necrotic zone, high levels of radiolabelled IGF-I binding to a combination of receptors and binding proteins were observed in cardiomyocytes in islands of viable tissue located close to the border. Weak immunostaining for IGF-II was observed in cardiomyocytes of the surviving tissue. IGF-II mRNA was not detected in either surviving or necrotic areas. Binding of radiolabelled IGF-II was predominantly to macrophages in both surviving and infarct areas, although as with IGF-I, high levels of binding of radiolabelled IGF-II to a combination of receptors and binding proteins were observed in islands of viable tissue close to the border within the necrotic area. We conclude that, following MI, surviving cardiomyocytes at the infarct border show marked changes in IGF-I localization, production, and specific binding, indicating that the IGF axis is directly involved in post-infarct events, possibly in the maintenance of cardiac function by the induction of hypertrophy and in cell survival by decreasing apoptotic cell death, which has been demonstrated in other cell types.

Myostatin, a transforming growth factor-beta superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct.

Myostatin is a secreted growth and differentiating factor (GDF-8) that belongs to the transforming growth factor-beta (TGF-beta) superfamily. Targeted disruption of the myostatin gene in mice and a mutation in the third exon of the myostatin gene in double-muscled Belgian Blue cattle breed result in skeletal muscle hyperplasia. Hence, myostatin has been shown to be involved in the regulation of skeletal muscle mass in both mice and cattle. Previous published reports utilizing Northern hybridization had shown that myostatin expression was seen exclusively in skeletal muscle. A significantly lower level of myostatin mRNA was also reported in adipose tissue. Using a sensitive reverse transcription-polymerase chain reaction (RT-PCR) technique and Western blotting with anti-myostatin antibodies, we show that myostatin mRNA and protein are not restricted to skeletal muscle. We also show that myostatin expression is detected in the muscle of both fetal and adult hearts. Sequence analysis reveals that the Belgian Blue heart myostatin cDNA sequence contains an 11 nucleotide deletion in the third exon that causes a frameshift that eliminates virtually all of the mature, active region of the protein. Anti-myostatin immunostaining on heart sections also demonstrates that myostatin protein is localized in Purkinje fibers and cardiomyocytes in heart tissue. Furthermore, following myocardial infarction, myostatin expression is upregulated in the cardiomyocytes surrounding the infarct area. Given that myostatin is expressed in fetal and adult hearts and that myostatin expression is upregulated in cardiomyocytes after the infarction, myostatin could play an important role in cardiac development and physiology.

Effect of a single bolus of intracoronary basic fibroblast growth factor on perfusion in an ischemic porcine model.

Basic fibroblast growth factor (bFGF) has been shown to induce angiogenesis in various animal models, but the methods of administration used experimentally are not clinically feasible. The objective of this study was to determine whether a single intracoronary bolus injection of bFGF would improve coronary perfusion in a porcine ischemic model that mimics clinical chronic ischemia. A copper coil studded with gold was delivered into the proximal right coronary artery of juvenile Yorkshire pigs and deployed by interventional techniques. After a four-week interval for stenosis maturation, bFGF (100 micrograms) was administered by bolus injection into the left coronary artery in five animals, and vehicle alone was administered in four animals. Angiogenesis and change in right coronary perfusion area were assessed two weeks later by angiography, myocardial contrast echocardiography and immunohistochemistry. The right coronary perfusion area increased significantly after treatment in all but one of the animals that received bFGF but not in any of the controls. Intimal hyperplasia was not induced by bFGF. Capillary density determined histochemically was not different in the two groups. In conclusion, in a porcine ischemic model, bFGF administered by a single bolus intracoronary injection into the contralateral artery improved antegrade perfusion into the ischemic territory although without histological evidence of angiogenesis. This preliminary work merits further investigation.

Survey of Waikato medical practitioners concerning cardiac pacing.

AIM: To assess the knowledge of Waikato medical practitioners concerning cardiac pacing and its indications. METHOD: Anonymous postal questionnaire. The responses received were compared with those of four New Zealand experts on cardiac pacing. RESULTS: 404 questionnaires were administered of which 204 (50%) were returned, (16.3% physicians, 22.7% JRMO's 61% general practitioners). Virtually all had ready access to diagnostic facilities and were satisfied with the service offered. Physicians were more likely to have referred patients and to have had personal experience with pacing. Practical matters, such as costs and length of the procedure were reasonably well appreciated. The complexity of the procedure, however, was overestimated. Pacemaker function was poorly understood. All practitioner groups were less likely to refer for pacing compared with the experts, but were more likely to refer in the presence of recurrent symptoms, particularly if the patient was elderly. CONCLUSION: A conservative approach to referral for permanent pacing exists in the Waikato region and this is unrelated to access to diagnostic facilities or referral difficulties.

Cauda equina syndrome in ankylosing spondylitis diagnosed by computed tomography.

A patient is described with longstanding ankylosing spondylitis, who develops radicular pain and neurological abnormalities. The diagnosis was cauda equina syndrome. This diagnosis was made on the basis of the clinical findings and the appearance of the computed tomography scan.

Aggressive fibrous histiocytoma of perioral soft tissues: report of case.

A rare case of aggressive fibrous histiocytoma is presented to alert the clinician to the existence of such a lesion and its ability to develop as a perioral soft tissue tumor. The research on these lesions clearly demonstrates the lability of their biologic potential. The clinical characteristics, symptoms, and histiologic makeup are reviewed and further reinforce the conclusion that careful microscopic study and thorough longterm followup to adequate surgical treatment are currently the only effective means in the management of these tumors. Continued reports from clinicians and researchers will perhaps satisfy many questions concerning this curious and potentially destructive and lethal group of lesions.