Biomedical subjects

M T Speakman

Publications and source records attributed to M T Speakman.

3 recordsLinked to original sources

PubMed2000

Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat--angiogenesis and angioma formation.

OBJECTIVES: The effects of direct intramyocardial injection of the plasmid encoding vascular endothelial growth factor (phVEGF165) in the border zone of myocardial infarct tissue in rat hearts were investigated. BACKGROUND: Controversy exists concerning the ability of VEGF to induce angiogenesis and enhance coronary flow in the myocardium. METHODS: Sprague-Dawley rats received a ligation of the left coronary artery to induce myocardial infarction (MI). At 33.1 +/- 6.5 days, the rats were injected with phVEGF165 at one location and control plasmid at a second location (500 microg DNA, n = 24) or saline (n = 16). After 33.1 +/- 5.7 days, the hearts were excised for macroscopic and histologic analysis. Regional blood flow ratios were measured in 18 rats by radioactive microspheres. RESULTS: phVEGF165-treated sites showed macroscopic angioma-like structures at the injection site while control DNA and saline injection sites did not. By histology, 21/24 phVEGF165-treated hearts showed increased focal epicardial blood vessel density and angioma-like formation. Quantitative morphometric evaluation in 20 phVEGF165-treated hearts revealed 44.4 +/- 10.5 vascular structures per field in phVEGF165-treated hearts versus 21.4 +/- 4.7 in control DNA injection sites (p < 0.05). Regional myocardial blood flow ratios between the injection site and noninfarcted area did not demonstrate any difference between phVEGF,165-treated hearts (0.9 +/- 0.2) and saline-treated hearts (0.7 +/- 0.1). CONCLUSIONS: Injection of DNA for VEGF in the border zone of MI in rat hearts induced angiogenesis. Angioma formation at the injection sites did not appear to contribute to regional myocardial blood flow, which may be a limitation of gene therapy for this application.

Animals↗

PubMed2000

A new model of ventricular plication: a suturing technique to decrease left ventricular dimensions, improve contractility, and attenuate ventricular remodeling after myocardial infarction in the rat heart.

BACKGROUND: The Batista procedure (cardio-reduction) is a surgical technique in patients with dilated cardiomyopathy that results in improvement of ventricular function. The purpose of this study was to test a new suturing technique without resection for cardio-reduction of myocardial infarct scars in rats. METHODS AND RESULTS: Myocardial infarction (MI) was induced by occluding the left coronary artery 4 weeks before enrollment. Animals then were randomized to a control (n = 11) or treatment group (n = 11). A pursestring suture was placed within the border zones of the infarcted area and was either tightened (treated) or not (controls). Echocardiography was used to measure left ventricular diameters before, 1 hour, and 6 to 7 weeks after plication. Acutely after plication, end-diastolic length (EDL) decreased from 0.70 +/- 0.03 cm to 0.53 +/- 0.02 cm, P < .001; end-systolic length (ESL) decreased from 0.51 +/- 0.03 cm to 0.23 +/- 0.02 cm, P < .001; and fractional shortening (FS) increased from 27.6 +/- 1.5% to 57.6 +/- 2.3%, P < .001, whereas controls were unchanged. In control rats EDL increased from baseline at 0.73 +/- 0.02 cm to 0.82 +/- 0.04 cm at 6 weeks postsurgery, P < .05; ESL increased from 0.54 +/- 0.02 cm to 0.66 +/- 0.04 cm, P < .005; and FS decreased from 26.9 +/- 1.1% to 19.2 +/- 1.2% at 6 weeks, P < .05. In contrast, at 6 weeks in plicated animals, EDL was significantly less than controls at 0.64 +/- 0.02 cm, P < .005; ESL was significantly less than controls at 0.39 +/- 0.03 cm, P < .005, and FS was significantly better than controls at 40.5 +/- 2.2%, P < .005. CONCLUSION: The progressive LV enlargement between 4 and 10 weeks after MI reflects late ventricular remodeling. Plication by suturing infarcted tissue acutely decreases diameters and improves function. At 6 weeks, function remains improved over untreated animals.

Animals↗

PubMedDate not supplied

Hibernating myocardium: is there evidence for chronic flow reduction?

Myocardial hibernation is defined as a state of chronically reduced contractility in response to a reduction in blood supply and the ability to recover function after revascularization. There is controversy about the chronicity of a reduction in myocardial perfusion for induction of the adaptive mechanisms of hibernation. A search was conducted of the clinical literature for evidence showing that myocardial perfusion is chronically reduced in hibernating myocardium. Ninety-three clinical studies in patients with dysfunctional but viable myocardium (hibernating myocardium) and revascularization were reviewed. Contractile function, as assessed by ventriculography, radionuclide ventriculography, or echocardiography, was measured before revascularization in 91 studies (97.8%). Viability was assessed before revascularization using nuclear imaging--particularly 18-fluorodeoxyglucose positron emission tomography (PET) or (201)thallium-201 single-photon emission tomography (SPECT)--or pharmacologic stress echocardiography in 66 studies (71%). Myocardial perfusion measurements using (99m)Tc sestamibi SPECT, (13)N-ammonia, or (15-)O-water in PET, were obtained before revascularization in 68 studies (73.1%). There were no studies that measured myocardial perfusion more than once before revascularization. After revascularization, contractile function was assessed in 85 studies (91.4%), viability in 19 studies (20.4%), and myocardial perfusion in 28 studies (30.1%). Multiple measurements of perfusion, viability, and contractile function were performed after revascularization in two (2.2%), two (2.2 %), and ten (10.8%) studies, respectively. There was a lack of evidence in the clinical literature for chronic reduction in myocardial perfusion in patients with hibernating myocardium, because multiple measurements of perfusion have not been systematically performed at different time points with respect to revascularization.

Coronary Circulation↗