Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MYOCARDIUM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Myocardial gene expression of angiogenic factors in human chronic ischemic myocardium: influence of acute ischemia/cardioplegia and reperfusion.

OBJECTIVE: Angiogenic therapies in animals have demonstrated the development of new blood vessels within ischemic myocardium. However, results from clinical protein and gene angiogenic trials have been less impressive. The present study aimed to investigate the expression of angiogenic genes in human chronic ischemic myocardium and the influence of acute ischemia/cardioplegia and reperfusion on their expression. METHODS: Myocardial biopsies were taken from chronic ischemic and nonischemic myocardium in 15 patients with stable angina pectoris during coronary bypass surgery. Tissue samples were evaluated by oligonucleotide microarray and quantitative real-time PCR for the expression of angiogenic factors. RESULTS: There was identical baseline expression of VEGF-A and VEGF-C mRNA in chronic ischemic myocardium compared with nonischemic myocardium. Reperfusion increased the gene expression of VEGF-A and VEGF-C mRNA both in nonischemic and ischemic myocardium. VEGF-A protein was detected mainly in the extracellular matrix around the cardiomyocytes in ischemic myocardium. CONCLUSION: These data suggest that the nonconclusive VEGF gene therapy trials chronic coronary artery disease was not due to a preexisting upregulation of VEGF in chronic ischemic myocardium. There might be room for further therapeutic angiogenesis in chronic ischemic myocardium.

Aged↗
PubMed1997

Characterization of hibernating and stunned myocardium.

Both the hibernating and the stunned myocardium are characterized by reversible contractile dysfunction. In hibernating myocardium ischaemia is still ongoing, whereas in stunned myocardium blood flow is fully or almost fully restored. Both the hibernating and the stunned myocardium retain an inotropic reserve. In hibernating myocardium the increase in contractile function is at the expense of metabolic recovery whereas in stunned myocardium no metabolic deterioration occurs during inotropic stimulation. Therefore, inotropic stimulation in combination with metabolic imaging may help not only to identify viable, dysfunctional myocardium but also to distinguish between hibernating and stunned myocardium. The therapy of hibernating myocardium is to restore blood flow to the hypoperfused tissue. Myocardial stunning per se requires no therapy at all, since by definition blood flow is normal and contractile function will recover spontaneously. If, however, myocardial stunning is severe, involves large parts of the left ventricle and thus impairs global left ventricular function, it can be reversed with inotropic agents and procedures. In the experimental setting, anti-oxidant agents, calcium antagonists and ACE inhibitors attenuate stunning, most effectively when administered before ischaemia.

Animals↗
PubMed2000

Irreversibly damaged myocardium at MR imaging with a necrotic tissue-specific contrast agent in a cat model.

PURPOSE: To investigate the capability of a necrosis-avid magnetic resonance (MR) contrast agent, bis-gadolinium mesoporphyrins, for assessment of irreversibly damaged myocardium and to evaluate the time course of signal enhancement in the reperfused myocardium. MATERIALS AND METHODS: Nine cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery followed by 90 minutes of reperfusion. Contrast material-enhanced T1-weighted spin-echo images were obtained for 12 hours in five cats and 6 hours in four cats. Pathologic examinations of the resected specimens were performed with 2'3'5-triphenyl tetrazolium chloride (TTC) histochemical staining and electron microscopy. The size of enhanced area on MR images was compared with that of irreversibly damaged myocardium with TTC staining. The time course of signal enhancement was evaluated. RESULTS: The size of enhanced area on MR images was well correlated with that of irreversibly damaged myocardium with TTC staining. Maximum enhancement occurred 1-3 hours after administration of the contrast material, with mean enhancement of 171% that of normal myocardium. Electron microscopic examinations showed severe myocardial damage in the irreversibly damaged myocardium but only mild edematous changes in the reversibly damaged myocardium. CONCLUSION: MR images enhanced with bis-gadolinium mesoporphyrins provide accurate sizing of irreversibly damaged myocardium with a strong and persistent signal enhancement in the reperfused myocardium.

Animals↗
PubMed1997

Enhancement of glucose uptake in stunned myocardium: role of glucose transporter.

This study quantifies the myocardial glucose uptake and clarifies the pathway of augmented glucose uptake in myocardium reperfused after a brief period of ischemia (stunned myocardium). The glucose uptake rate was determined from the time course of the sugar phosphate (SP) resonance in rat myocardium (d[SP]/dt) with 31P nuclear magnetic resonance after the substitution of glucose with its analog 2-deoxyglucose. The d[SP]/dt in stunned myocardium [1.03 +/- 0.05 (SE) micromol x g wet wt(-1) x min(-1); n = 8] increased significantly compared with nonischemic control myocardium (0.18 +/- 0.03 micromol x g wet wt(-1) x min(-1); n = 8; P < 0.0001), reaching the maximal stimulatory uptake rate during exposure to insulin (1.05 +/- 0.04 micromol x g wet wt(-1) x min(-1); n = 8). Twenty minutes after reperfusion, the d[SP]/dt was still augmented (0.41 +/- 0.05 micromol x g wet wt(-1) x min(-1); n = 5; P < 0.05 vs. control myocardium). To elucidate further the mechanism of augmented glucose uptake, N6-(L-2-phenylisopropyl)-adenosine (PIA; 100 micromol/l), a potent blocker of the glucose transporter, was administered to stunned hearts and, as a control, to insulin-stimulated hearts. PIA significantly and comparably inhibited the increase in d[SP]/dt in stunned myocardium (0.36 +/- 0.07 micromol x g wet wt(-1) x min(-1); n = 4; P < 0.0001 vs. without PIA) and in insulin-stimulated myocardium (0.38 +/- 0.02 micromol x g wet wt(-1) x min(-1); n = 4; P < 0.0001 vs. without PIA). These results indicate that the augmented glucose uptake in stunned myocardium is maintained by the glucose transporter, the amount of which is almost equal to that which can be maximally recruited by insulin.

Adenosine Triphosphate↗
PubMed1994

Enhancement of regional myocardial efficiency and persistence of perfusion, oxidative, and functional reserve with paired pacing of stunned myocardium.

BACKGROUND: Stunned myocardium reflects postreperfusion dysfunction in myocardium that is destined to ultimately fully recover. Most investigators attribute postreperfusion stunning to a primary defect in excitation-contraction coupling or to an altered sensitivity of the myofilaments to calcium. The aim of the present study was to evaluate the interrelation between myocardial perfusion, oxidative metabolism, and function in an effort to better characterize the phenomenon of myocardial stunning, to define the regional efficiency of stunned myocardium, and to characterize its reserve capacity. METHODS AND RESULTS: Regional myocardial perfusion (measured with radiolabeled microspheres), myocardial oxygen consumption (MVO2) (quantified with positron emission tomography using 1-11C-acetate), and myocardial function (assessed with two-dimensional echocardiography) were evaluated in 12 anesthetized, closed-chest dogs subjected to 15 minutes of left anterior descending coronary artery occlusion followed by reperfusion. To evaluate flow, oxidative, and functional reserve after measurements were obtained 1 hour after reperfusion, dogs were subjected to paired pacing (an inotropic stimulus that does not alter systemic hemodynamics), and measurements were repeated. One hour after reperfusion, stunned myocardium was characterized by near-normal levels of myocardial perfusion (0.57 +/- 0.13 mL/g per minute, 81 +/- 13% of that in remote, normal regions) but severe dyskinesis (echo score, 2.6 +/- 0.7; percent wall thickening, 14 +/- 20%). Despite the low level of contractile function, MVO2 averaged 1.72 +/- 0.7 mumol/g per minute, 71 +/- 27% of that observed in remote myocardium. Regional myocardial efficiency (systolic wall thickening divided by MVO2) was markedly diminished. With paired pacing, myocardial perfusion increased proportional to that in remote myocardium, systolic function improved (echo score, 1.4 +/- 0.7; percent wall thickening, 30 +/- 15%), and regional MVO2 nearly doubled (to 3.41 +/- 1.82 mumol/g per minute, P < .05 for each paired measurement). Importantly, with paired pacing, regional myocardial efficiency nearly normalized in reperfused myocardium. CONCLUSIONS: Stunned myocardium is characterized by near-normal levels of perfusion and oxygen consumption despite marked dyskinesis. Myocardial efficiency is poor. With inotropic stimulation (in the present study, paired pacing), reperfused myocardium demonstrated considerable perfusion, oxidative, and functional reserve and a dramatic improvement in myocardial efficiency. These results may have implications for the treatment of postreperfusion pump failure.

Animals↗
PubMed1996

Only hibernating myocardium invariably shows early recovery after coronary revascularization.

BACKGROUND: The aims of this study were to identify hibernating myocardium (hypocontractile, hypoperfused viable myocardium that regains contractility after revascularization) in the clinical setting and to predict functional outcome in patients with coronary artery disease after coronary revascularization. METHODS AND RESULTS: Preoperative data related to the anterior free wall of the left ventricle were collected in 50 coronary bypass surgery candidates (positron emission tomography [PET], [13N]NH3 for flow, and [18F]FDG for metabolism [MET]; equilibrium-gated nuclear angiography [EGNA] for regional ejection fraction [REF]; and histological data from myocardial biopsies for percentage fibrosis and viable myocytes). Three months after surgery, the patients had follow-up PET and EGNA investigations. A principal-components analysis identified four patient clusters. Cluster 1 (n = 9) had normal viable myocardium. Cluster 2 (n = 18) had viable hypocontractile myocardium (REF, 39 +/- 12%) showing a PET mismatch pattern. Cluster 3 (n = 16) had viable hypocontractile myocardium associated with morphological myocyte injury showing a matched moderate decrease in flow (66 +/- 11%) and MET (70 +/- 11%). Cluster 4 (n = 7) had hypocontractile myocardium with mainly scar tissue (fibrosis, 74 +/- 12%). After surgery, only cluster 2, with hibernating myocardium, showed significant improvement in REF (from 39 +/- 12% to 50 +/- 13%, P < .05). Cluster 3, with sites of morphological myocyte injury, showed no recovery. The stepwise logistic regression showed a combination of low preoperative REF and high MET to be the best predictor of functional recovery (P < .008). CONCLUSIONS: Multivariate analysis identifies hibernating myocardium showing early postrevascularization recovery, as opposed to viable but myolytic myocardium with no early recovery. Postrevascularization recovery can be predicted (combination of low REF and high MET) by noninvasive techniques.

Adult↗
PubMed1999

Tissue characterization of myocardial cells by use of high-frequency acoustic microscopy: differential myocyte sound speed and its transmural variation in normal, pressure-overload hypertrophic, and amyloid myocardium.

The purpose of the present study was to evaluate the acoustic properties of myocytes in normal, pressure-overload hypertrophic, and amyloid myocardium. Myocardial tissue specimens at autopsy were obtained from 10 subjects without cardiovascular disease, six patients with left ventricular (LV) hypertrophy, and six patients with cardiac amyloidosis. Sound speed of myocytes was measured at subendocardial and subepicardial regions in myocardium by use of a high-frequency (450 MHz) acoustic microscope. In normal myocardium, the sound speed of myocytes was significantly higher in subendocardial region (1,728+/-19 m/sec) than in subepicardial region (1,645+/-22 m/sec) (p<0.0001). A significantly higher sound speed of myocytes was observed in the subendocardial region in LV hypertrophic myocardium (1,779+/-19 m/sec) than that in normal myocardium (p<0.001). In amyloid myocardium, a significantly lower sound speed of myocytes was observed in subendocardial (1,560+/-8 m/sec) and subepicardial (1,594+/-48 m/sec) regions than that in respective regions of the normal myocardium (p<0.0001 and p<0.05, respectively). Transmural variation in sound speed of myocytes measured by high-frequency acoustic microscopy existed in normal left ventricle. The differential myocyte sound speed and its transmural variation was observed in LV hypertrophic and amyloid myocardium as compared with normal myocardium. High-frequency acoustic microscopy can be a promising technique for myocardial tissue characterization at the myocyte level.

Acoustics↗
PubMed2002

[Changes in adrenomedullin and receptor activity-modifying protein 2 mRNA in myocardium and vessels during L-NNA-induced hypertension in rats].

To explore the changes in adrenomedullin (ADM) and receptor activity-modifying protein 2 (RAMP2) mRNA in myocardium and vessels in hypertension, a hypertensive rat model was prepared by administering L-NNA. Contents of ADM in plasma, myocardium and vessels were measured by radioimmunoassay (RIA). The levels of pro-ADM mRNA of myocardium and vessels were determined by competitive quantitative RT-PCR. The results showed that L-NNA induced hypertension and cardiomegaly. The ratio of heart to body weight increased by 35.5% (P<0.01). In hypertensive rats the ir-ADM in plasma, myocardium and vessels was increased by 80%, 72% and 57% (P<0.01), respectively compared with the control. The amounts of ADM mRNA in myocardium and vessels were increased by 50% and 109.2% (P<0.05), respectively, and the amounts of RAMP2 mRNA was increased by 132% and 87% (P<0.01), respectively, compared with control. The levels of ADM in myocardium and vessels were positively correlated with RAMP2 mRNA, the correlation coefficients were 0.741 and 0.885 (P<0.01), respectively. The results obtained indicate that in hypertensive rats, ADM is elevated in plasma, myocardium and ves-myocardium and vessel, and ADM and RAMP2 mRNA are up-regulated in myocardium and vessel. The ADM/RAMP2 system may play an important role in the pathogenesis of hypertension.

Adrenomedullin↗
PubMed1992

Direct measurement of oxygen free radicals following cardiac failure of ischemic dog myocardium with the electron spin resonance technique.

OBJECTIVE: To determine whether the involvement of oxygen-derived free radicals in the pathogenesis of ischemic cardiac failure in dogs. DESIGN: Free radicals were measured in normal and ischemic myocardium from dogs with cardiac failure induced by acute coronary occlusion. The changes in free radical production in ischemic myocardium (compared with normal myocardium with or without polymorphonuclear leukocytes) were studies, with plasma superoxide dismutase and malondialdehyde analyzed concurrently. MAIN RESULTS: The results showed that the oxygen free radicals in the ischemic myocardium were about 42.5% higher than those in the normal myocardium, about 67.8% higher than those in the normal myocardium washed with normal saline and about 60.5% higher than those in the ischemic myocardium washed with normal saline (P < 0.05). Compared with controls, the concentration of malondialdehyde in ischemic dog myocardium was increased markedly. The activity of plasma superoxide dismutase was not significantly different between control dogs and dogs with ischemic cardiac failure. CONCLUSIONS: The current results indicate that there was increased production of free radicals and peroxidative damage in ischemic myocardium of dogs with cardiac failure. Polymorphonuclear leukocytes appear to be a main source of free radicals in dog with ischemic cardiac failure.

Animals↗
PubMed1995

[Ultrasonic tissue characterization of diseased myocardium by scanning acoustic microscopy].

Ultrasonic tissue characterization of the myocardium has become very important because the requirement for evaluating local cardiac function has increased. In the present study, the acoustic properties of the tissue elements in myocardial infarction were measured by a specially developed scanning acoustic microscope (SAM) system, and the echo intensity of the infarcted myocardium was assessed. Ten samples of infarcted myocardium obtained at autopsy were formalin-fixed, paraffin-embedded and cut into 10 microns thick slices. The SAM system was operated in the frequency range of 100 to 200 MHz. The values of the attenuation constant and sound speed were measured in five tissue elements, normal myocardium, degenerated myocardium, fibrosis, granulation, and hemorrhage by comparing the optical microscopic image and acoustic images. The density of each tissue element was measured by the CuSO4 method, and the specific acoustic impedance was calculated by multiplying the sound speed and the density of each tissue element. The specific acoustic impedance was 1.75 x 10(6) Ns/m3 in normal myocardium, 1.69 x 10(6) Ns/m3 in degenerated myocardium, and 1.85 x 10(6) Ns/m3 in fibrosis. The intensity of the reflected ultrasound at the interface between two different tissue elements was calculated by the difference of specific acoustic impedance. Using the sensitivity changing method in clinical echocardiography, the intensity of myocardial scar was -15 dB compared to the pericardial echo. The corrected ideal ultrasonic reflection between degenerated myocardium and fibrosis was calculated as -15.4 dB. The results suggest that measurement of acoustic properties is very important to provide basic data for ultrasonic characterization of myocardium tissue.

Acoustics↗
PubMed1994

Angiotensin II receptor subtypes in bovine and human ventricular myocardium.

Angiotensin II (AII) binding sites in bovine and human ventricular myocardium were characterized by a radioreceptor assay. The specific binding of [125I]AII to myocardial membranes appeared to be saturable, and it was of high affinity with apparent dissociation constants of 1.60 nM (bovine) and 1.09 nM (human). The Bmax values were 39.7 fmol/mg protein (bovine) and 6.07 fmol/mg protein (human). Both losartan (angiotensin type 1 receptor subtype selective antagonist) and PD123177 (the angiotensin type 2 receptor subtype selective antagonist) inhibited specific [125I]AII binding to bovine myocardium, and their Hill coefficients were less than unity. Nonlinear least-squares regression analysis has suggested the existence of two populations of [125I]AII binding sites that have high and low affinity for losartan or PD123177. The relative proportions of high- and low-affinity sites for losartan in bovine myocardium were 68% and 32%, and those for PD123177 were 33% and 67%, respectively. On the other hand, specific [125I]AII binding in human myocardium was inhibited by losartan with much lower affinity and also by PD123177 with higher affinity, compared with bovine myocardium. The Hill coefficients for both drugs were close to one. Dithiothreitol enhanced specific [125I]AII binding to bovine myocardium in the presence of losartan, but it reduced [125I]AII binding in the presence of PD123177. This agent markedly enhanced specific [125I]AII binding to human myocardium. Thus, it is possible that bovine myocardium has both angiotensin type 1 receptor and the angiotensin type 2 receptor subtypes of AII receptors whereas human myocardium has predominantly the angiotensin type 2 receptor subtype.

Aged↗
PubMed1998

Influence of forskolin on the force-frequency behavior in nonfailing and end-stage failing human myocardium.

UNLABELLED: End-stage failing human myocardium is characterized by a negative force-frequency relationship (FFR), possibly as a result of reduced SR Ca2+ uptake capacity. We investigated the effects of the direct adenylate cyclase stimulator, forskolin, on force of contraction and FFR in isolated human myocardium from 7 nonfailing hearts (NF) and end-stage failing hearts (NYHA IV) due to either ischemic (ICM; n = 13) or dilated cardiomyopathy (DCM; n = 16). METHODS: Isolated left ventricular muscle strips, isometric contraction, electrical stimulation at a basal stimulation rate of 1 Hz (37 degrees C). Inotropic responses: Cumulative concentration-response curves for forskolin (0.01-10 microM) and for Ca2+ (2.5-15 mM). Force-frequency experiments: stepwise increase in stimulation rate from 0.5 to 3.0 Hz without and in the presence of 0.3, 1.0 or 3.0 microM forskolin. RESULTS: Forskolin concentration-dependently increased force of contraction to 386 +/- 28% (n = 5) in NF, to 256 +/- 48% (n = 7) in ICM, and to 212 +/- 13% (n = 14) in DCM. The effectiveness of forskolin was significantly reduced in failing myocardium. Ca2+ increased force of contraction to maximally 438 +/- 108% in NF, to 267 +/- 15% in ICM, and to 292 +/- 20% in DCM. Again, the effectiveness of Ca2+ was significantly reduced in failing myocardium. Forskolin activated contractile reserve to similar extents in all types of myocardium (90%, 95%, and 82%, respectively). Force of contraction continuously increased with increasing stimulation rates in nonfailing myocardium (positive FFR), but was blunted or inversed in ICM and DCM. Prestimulation with forskolin (0.3 microM) further enhanced frequency-potentiation in nonfailing, and normalized the slope and optimum stimulation frequency in ICM and DCM. However, at higher concentrations of forskolin, FFR was blunted or inversed in non-failing myocardium, and further impaired in failing myocardium. CONCLUSION: Low concentrations of forskolin with only marginal inotropic effects may partially normalize the inverse force-frequency relation in end-stage failing human myocardium. Reduced cAMP levels in conjunction with reduced expression of SR Ca2+ ATPase may be the underlying cause for altered excitation-contraction coupling in diseased human hearts.

Biomechanical Phenomena↗
PubMed1991

Differentiation of reperfused-viable (stunned) from reperfused-infarcted myocardium at 1 to 3 days postreperfusion by in vivo phosphorus-31 nuclear magnetic resonance spectroscopy.

Thrombolytic therapy has increased the need for a technique to assess the viability of recently reperfused myocardium. This study examined the ability of in vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy to distinguish reperfused-viable (stunned) from reperfused-infarcted myocardium at 6, 30, and 54 hours following coronary artery occlusion in a canine model. A 15-minute occlusion produced reperfused-viable myocardium in five animals and a 360-minute occlusion produced reperfused-infarcted myocardium in six animals. Postreperfusion risk zone myocardial phosphocreatine (PCr) concentration measured by P-31 NMR spectroscopy was significantly depressed throughout the 3-day study period in infarcted but not in viable myocardium (p less than 0.01 between groups, all time points). The postreperfusion ratio of inorganic phosphate (Pi) to PCr concentration, as determined by NMR spectroscopy, was elevated throughout the study period in infarcted but not in viable reperfused myocardium (p less than 0.01 between groups, all time points). Postreperfusion Pi concentration was elevated at 6 hours but not subsequently in reperfused-infarcted myocardium, and was not elevated in reperfused-viable myocardium. Logistic regression models selected PCr concentration and the Pi/PCr ratio as providing the best discrimination between reperfused-viable and reperfused-infarcted myocardium. The accuracy of P-31 NMR variables selected by logistic regression analysis for determining myocardial viability ranged from 97% to 100%.

Animals↗
PubMed1992

Measurement of myocardium at risk by technetium-99m sestamibi: correlation with coronary angiography.

Previous studies have shown that tomographic perfusion imaging with technetium-99m sestamibi (RP-30A) can accurately measure the myocardium at risk during acute myocardial infarction. The ability of coronary angiography to predict the wide variability in myocardium at risk was studied in 21 patients with their first acute myocardial infarction. In blinded fashion, two experienced angiographers provided an overall "best estimate" of the percent of left ventricular myocardium at risk considering multiple angiographic variables--infarct-related artery, location of stenosis (proximal or nonproximal), vessel diameter, length, territory and the number and size of proximal branches and collateral vessels. Many of these individual variables showed a significant association with myocardium at risk. The most important angiographic variable was the mean best estimate of the two angiographers (r = 0.89, p less than 0.0001). However, the SEE was large (8.6% of the left ventricle) and angiography significantly (p less than 0.002) overestimated myocardium at risk. When patients with an anterior or an inferior infarct were considered separately, the angiographic best estimate had a weaker correlation with myocardium at risk measured by technetium-99m sestamibi in patients in both groups (anterior infarction r = 0.65, p = 0.04; inferior infarction r = 0.65, p = 0.04. Seven patients with an inferior infarct and myocardium at risk ranging from 7% to 32% of the left ventricle had identical angiographic best estimates. Although angiographic estimates correlate closely with measurements of myocardium at risk in groups of patients, their ability to predict the myocardium at risk in individual patients is limited.

Adult↗
PubMed2005

Implantation of bone marrow mononuclear cells using injectable fibrin matrix enhances neovascularization in infarcted myocardium.

Neovascularization may improve cardiac function and prevent further scar tissue formation in infarcted myocardium. A number of studies have demonstrated that bone marrow-derived cells have the potential to induce neovascularization in ischemic tissues. In this study, we hypothesized that implantation of bone marrow mononuclear cells (BMMNCs) using injectable fibrin matrix further enhances neovascularization in infarcted myocardium compared to BMMNC implantation without matrix. To test this hypothesis, infarction was induced in rat myocardium by cryoinjury. Three weeks later, rat BMMNCs were mixed with fibrin matrix and injected into the infarcted myocardium. Injection of either BMMNCs or medium alone into infarcted myocardium served as controls. Eight weeks after the treatments, histological analyses indicated that implantation of BMMNCs using fibrin matrix resulted in more extensive tissue regeneration in the infarcted myocardium compared to BMMNC implantation without matrix. Examination with fluorescence microscopy revealed that cells labeled with a fluorescent dye prior to implantation survived in the infarcted myocardium at 8 weeks of implantation. Importantly, implantation of BMMNCs using fibrin matrix resulted in much more extensive neovascularization in infarcted myocardium than BMMNC implantation without matrix. The microvessel density in infarcted myocardium was significantly higher (p < 0.05) when BMMNCs were implanted using fibrin matrix (350 +/- 22 microvessels/mm2) compared to BMMNC implantation without matrix (262 +/- 13 microvessels/mm2) and medium injection (76 +/- 9 microvessels/mm2). In addition, average internal diameter of microvessels was significantly larger (p < 0.05) in BMMNC implantation with fibrin matrix group (14.6 +/- 1.2 microm) than BMMNC implantation without matrix group (10.2 +/- 0.7 microm) and medium injection group (7.3 +/- 0.5 microm). These results suggest that fibrin matrix could serve as a cell implantation matrix that enhances neovascularization efficacy for myocardial infarction treatment.

Animals↗
PubMedDate not supplied

The effect of percutaneous transmyocardial laser revascularization on left ventricular function in a porcine model of hibernating myocardium: a pilot study.

BACKGROUND: Hibernating myocardium is defined as a state of persistently impaired myocardial function at rest due to reduced coronary blood flow that can partially or completely be restored to normal if the myocardial oxygen supply/demand relationship is favorably altered. Percutaneous laser revascularization (PMR) is an emerging catheter-based technique that involves creating channels in the myocardium, directly through a percutaneous approach with a laser delivery system, and has been shown to reduce symptoms in patients with severe refractory angina; however, its effect on improving regional wall motion abnormalities in hibernating myocardium has not been clearly established. We sought to determine the effect of PMR using the Eclipse System (Cardiogenesis) on left ventricular function in a porcine model of hibernating myocardium. METHODS: A model of hibernating myocardium was created by placement of an ameroid constrictor in the proximal left anterior descending artery of a 35 kg male Yorkshire pig. The presence of hibernating myocardium was confirmed with dobutamine stress echocardiography (DSE) and defined as severe hypocontractility at rest, with an improvement in systolic wall thickening with low-dose dobutamine in myocardial regions with a subsequent deterioration in function at peak stress (biphasic response). After the demonstration of hibernating myocardium, PMR was performed in the area of hypocontractile function, and the serial echocardiography was performed. The echocardiograms were reviewed by an experienced echocardiologist blinded to the results, and regional wall motion was assessed using the American Society of Echocardiography Wall Motion Score. Six weeks after PMR, the animal was sacrificed and the heart sent for histopathologic studies. RESULTS: A comparison of the regional wall motion function of the area distal to the ameroid constrictor and in the contralateral wall at baseline, post-ameroid placement, and post-PMR was performed. Hibernating myocardium was demonstrated 4 weeks after ameroid placement by DSE. Coronary angiography demonstrated a discrete 90%stenosis in the proximal LAD at the site of ameroid constrictor placement without evidence of collaterals. Using PMR, 17 bursts were successfully delivered to the anterior wall distal to the ameroid constrictor. Four weeks after PMR, there was improvement in wall motion function in the region distal to the ameroid placement by echocardiography. Histopathologic analysis demonstrated the absence of myocardial infarction in the anterior wall distal to the ameroid constrictor. CONCLUSIONS: The performance of PMR in a porcine model of hibernating myocardium is feasible and is associated with an improvement regional wall motion function after 4 weeks.

Animals↗
PubMed1998

Effect of dopamine and atrial pacing on stunned myocardium.

OBJECTIVE: Post-ischaemic stunned myocardium shows an impaired function at restored coronary blood flow, but performance can be normalized by positive inotropic stimulation. The power of stunned myocardium, however, is not augmented with increasing heart rate by atrial pacing, which is in contrast to intact areas. This pathological response is mitigated by inhibiting the degradation of cyclic AMP. The present experiments studied the effect of stimulating cyclic AMP formation by dopamine on the response of stunned myocardium to atrial pacing. METHODS: In anaesthetized (piritramide) open chest pigs, heart rate, left ventricular and aortic pressure, left descending (LAD) and circumflex (LCX) coronary artery and aortic blood flow, myocardial systolic shortening in the LAD and LCX area were monitored, and myocardial power was calculated. The LAD region was subjected to ischaemia and reperfused for 2 h. Subsequently, heart rate was raised by right atrial pacing before and during intravenous infusion of dopamine (10 microg/kg per min). The ischaemic/reperfused area was sliced post mortem and stained by triphenyl tetrazolium chloride to exclude myocardial infarction. Data from 11 experiments are presented. RESULTS: After 2 h LAD reperfusion, LAD blood flow and power were 100% and 36% of pre-ischaemic control, respectively, indicating myocardial stunning. The power of the intact area was not changed significantly (111% of control). Increasing heart rate by +36 and +70 from 94 beats/min increased the power of the intact area to 161% and 183% of control; the power of the stunned myocardium decreased to 34% and 19% of pre-stunning control. Dopamine increased the power of the stunned region to 143% of the pre-stunning level and the power of the intact area to 206% of control. Increasing heart rate by +34 and +70 from 113 beats/min during dopamine, increased the power of the intact myocardium to 288% and 344% of control and the power of the stunned region to 177% and 174% of the pre-stunning level. CONCLUSIONS: The data confirm the pathological response of stunned myocardium to atrial pacing and the recruitment of a functional reserve by catecholamines. The adverse effect of pacing on the function of stunned myocardium is abolished by positive inotropic stimulation. Possibly, the cyclic AMP system is involved in the normal response to pacing and this pathway is disturbed in stunned myocardium; other defects are not excluded or supported, however. Physiologically increased heart rate by an increased activity of the sympathetic nervous system, is probably not accompanied by a reduced power of stunned myocardium, due to the associated positive inotropic stimulation.

Animals↗
PubMed1995

Characterization of hibernating and stunned myocardium.

Both the hibernating and the stunned myocardium are characterized by reversible contractile dysfunction. In hibernating myocardium, perfusion is still reduced, whereas in stunned myocardium blood flow is fully or almost fully restored. Both the hibernating and the stunned myocardium retain an inotropic reserve. In hibernating myocardium the increase in contractile function is at the expense of metabolic recovery, whereas in the stunned myocardium no metabolic deterioration occurs during inotropic stimulation. Therefore, inotropic stimulation in combination with metabolic imaging may help not only to identify viable, dysfunctional myocardium but also to distinguish hibernating and stunned myocardium. The therapy of hibernating myocardium is to restore blood flow to the hypoperfused tissue. Myocardial stunning per se requires no therapy at all, since, by definition, blood flow is normal and contractile function will recover spontaneously. If, however, myocardial stunning is severe, and it involves large parts of the LV and thus impairs global LV function, it can be reversed with inotropic agents and procedures. In the experimental setting, anti-oxidant agents, calcium antagonists and ACE inhibitors attenuate stunning, but most effectively when administered before ischaemia.

Animals↗