Left ventricular rupture threshold during the healing phase after myocardial infarction in the dog

1987 ◽  
Vol 65 (3) ◽  
pp. 307-316 ◽  
Author(s):  
Bodh I. Jugdutt
Keyword(s):  
Left Ventricle ◽  
Dry Weight ◽  
Left Ventricular ◽  
Mechanical Resistance ◽  
Coronary Artery Ligation ◽  
Infarct Zone ◽  
Artery Ligation ◽  
Average Value ◽  
Left Ventricular Stiffness ◽  
Healing Phase

The mechanical resistance of the infarcted left ventricle to rupture, or rupture threshold, was measured by the balloon technique 1–42 days after left anterior descending coronary artery ligation in 70 dogs: 26 without infarction (18 sham, 8 with ligation) and 44 with infarction. Rupture threshold in noninfarcted hearts was higher than in infarcted hearts (1168 ± 165 (SD) vs. 754 ± 223 mmHg (1 mmHg = 133.32 Pa), p < 0.001) and did not change over 6 weeks. In contrast, rupture threshold in infarcted hearts decreased (p < 0.05) after 14 days, the average value for 21–42 days being less than that for 1–14 days: 577 ± 140 vs. 867 ± 191 mmHg, p < 0.001. Passive left ventricular stiffness in infarcted hearts was higher than for noninfarcted hearts throughout the 6 weeks during early filling (11.1 ± 3.9 vs. 7.1 ± 1.4 mmHg/mL, p < 0.001) but decreased (p < 0.05) after 14 days during the prerupture phase (11.3 ± 5.3 vs. 6.2 ± 3.0 mmHg/mL, p < 0.005). Between 7 and 42 days, the infarct zone showed marked increase in hydroxyproline (10.0 ± 2.0 vs. 48.8 ± 19.7 mg/g dry weight, p < 0.001), shrinkage (infarct size, 25 ± 9 vs. 9 ± 5% of the left ventricle, p < 0.005), and thinning (infarct to normal wall thickness ratio, 0.83 ± 0.11 vs. 0.51 ± 0.09, p < 0.001) but little further stretching (expansion index or the ratio of lengths of infarcted and noninfarcted segments, 1.14 ± 0.10 vs. 1.28 ± 0.17, p < 0.2). A mild decrease (p < 0.05) in left atrial pressure and increase (p < 0.05) in diastolic area and fractional change in area (two-dimensional echocardiography) were detected at 6 weeks. The late decrease in rupture threshold and prerupture stiffness of the infarcted left ventricle and thinning of the scar suggest a late decrease in mechanical strength and resistance of the infarcted left ventricle to distension.

Regulation of K+ and Ca2+ channels in experimental cardiac failure

1991 ◽  
Vol 261 (6) ◽  
pp. H1979-H1987 ◽  
Author(s):  
M. Gopalakrishnan ◽  
D. J. Triggle ◽  
A. Rutledge ◽  
Y. W. Kwon ◽  
J. A. Bauer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Right Ventricle ◽  
Cardiac Failure ◽  
Radioligand Binding ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
The Right

To examine the status of ATP-sensitive K+ (K+ATP) channels and 1,4-dihydropyridine-sensitive Ca2+ (Ca2+DHP) channels during experimental cardiac failure, we have measured the radioligand binding properties of [3H]glyburide and [3H]PN 200 110, respectively, in tissue homogenates from the rat cardiac left ventricle, right ventricle, and brain 4 wk after myocardial infarction induced by left coronary artery ligation. The maximal values (Bmax) for [3H]glyburide and [3H]PN 200 110 binding were reduced by 39 and 40%, respectively, in the left ventricle, and these reductions showed a good correlation with the right ventricle-to-body weight ratio in heart-failure rats. The ligand binding affinities were not altered. In the hypertrophied right ventricle, Bmax values for both the ligands were not significantly different when data were normalized to DNA content or right ventricle weights but showed an apparent reduction when normalized to unit protein or tissue weight. Moderate reductions in channel densities were observed also in whole brain homogenates from heart failure rats. Assessment of muscarinic receptors, beta-adrenoceptors and alpha 1-adrenoceptors by [3H]quinuclidinyl benzilate, [3H]dihydroalprenolol, and [3H]prazosin showed reductions in left ventricular muscarinic and beta-adrenoceptor densities but not in alpha 1-adrenoceptor densities, consistent with earlier observations. It is suggested that these changes may in part contribute to the pathology of cardiac failure.

Effect of nitroglycerin and ibuprofen on left ventricular topography and rupture threshold during healing after myocardial infarction in the dog

1988 ◽  
Vol 66 (4) ◽  
pp. 385-395 ◽  
Author(s):  
Bodh I. Jugdutt
Keyword(s):  
Systolic Function ◽  
Left Ventricular ◽  
Mechanical Resistance ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Cross Sectional ◽  
Balloon Technique ◽  
Dimensional Echocardiography ◽  
Improved Function ◽  
And Function

The effect of nitroglycerin and ibuprofen, given between 2 and 7 days after left anterior descending coronary artery ligation, on the mechanical resistance of the infarcted left ventricle to rupture or the rupture threshold (balloon technique), and on topography (computerized planimetry) and function (two-dimensional echocardiography) at 7 days (n = 32) and 42 days (n = 34) postligation was studied in 66 dogs randomly allocated to sham (no infarction, n = 22) and infarction subgroups (15 controls; 15 received nitroglycerin, 30 mg oral isosorbide dinitrate b.i.d; 14 received ibuprofen, 200 mg t.i.d orally). Nitroglycerin decreased mean arterial and left atrial pressures, decreased diastolic cross-sectional area, and improved systolic function, while ibuprofen increased diastolic area. Infarction subgroups showed infarct shrinkage and more infarct hydroxyproline at 6 weeks. Compared with shams, all infarct subgroups showed early expansion and thinning, with further marked late thinning in controls. Nitroglycerin produced less expansion and thinning both at 1 and 6 weeks, while ibuprofen produced marked early thinning. Rupture threshold was less at 6 weeks than 1 week with controls and ibuprofen but remained unchanged with nitroglycerin. Passive prerupture stiffness was less at 6 weeks than at 1 week in controls but remained unchanged with nitroglycerin and ibuprofen. Thus, reduced expansion and thinning with nitroglycerin during the first week after infarction improved function, mechanical strength, and resistance to distension at 6 weeks.

Abstract 402: Vitamin C Deficiency Impairs Cardiac Function and Post-infarction Survival in the Mouse

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Adolfo G Mauro ◽  
Donatas Kraskauskas ◽  
Bassem M Mohammed ◽  
Bernard J Fisher ◽  
Eleonora Mezzaroma ◽  
...  
Keyword(s):  
Vitamin C ◽  
Cardiac Function ◽  
Diastolic Function ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Additional Group ◽  
Gulonolactone Oxidase ◽  
Low Levels ◽  
Systolic And Diastolic Function

Introduction: L-gulonolactone oxidase (Gulo) is the rate limiting enzyme for Vitamin C (VitC) biosynthesis. Humans rely on dietary VitC for collagen synthesis, extracellular matrix formation, and tissue regeneration. VitC deficiency is an unrecognized condition and its role in cardiac homeostasis and post-acute myocardial infarction (AMI) remodeling is unknown. Hypothesis: Low levels of VitC impair cardiac function and tissue repair following AMI. Methods: Adult male Gulo -/- knockout mice (C57BL6 background, N=8) and control C57BL (N=8), which are able to synthesize VitC were used. VitC deficiency was maintained supplying low levels of VitC (30mg/l) to Gulo -/- mice in drinking water. Mice underwent M-mode and Doppler echocardiography to measure left ventricular (LV) diameters and wall thicknesses, fractional shortening (FS), E and A waves, E/A ratio, isovolumetric relaxation time (IRT) and myocardial performance index (MPI). Experimental AMI was induced by coronary artery ligation for 7 days. An additional group of Gulo -/- were mice supplemented with physiological levels of VitC (330 mg/l) and underwent AMI. Results: VitC deficient Gulo -/- mice exhibited significantly reduced LV wall thicknesses, reduced FS, and impaired diastolic function, measured as significantly reduced E/A ratio and longer IRT (Panel A, B & C). Following AMI, 100% (8/8) of deficient Gulo -/- mice died within 5 days. Supplementation with physiological levels of VitC significantly improved survival after AMI (Panel D). Conclusion: VitC deficiency impairs systolic and diastolic function. Moreover, VitC is critical for the post-AMI survival.

Abstract P237: Is Ischemia/Reperfusion an Efficient Method for Producing Heart Failure in Rats?

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Ana Carolina M Omoto ◽  
Fábio N Gava ◽  
Mauro de Oliveira ◽  
Carlos A Silva ◽  
Rubens Fazan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Histopathological Examination ◽  
Ischemia Reperfusion ◽  
Mitral Annulus ◽  
Mortality Rates ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation

Myocardium infarction (MI) elicited by coronary artery ligation (CAL) is commonly used to induce chronic heart failure (HF) in rats. However, CAL shows high mortality rates. Given that ischemia-reperfusion (IR) may cause the development of HF, this approach may be useful for obtaining a model of HF with low mortality rates. Therefore, it was compared the model of CAL vs. IR in rats, evaluating the mortality and cardiac morphological and functional aspects. The IR consisted of 30 minutes of cardiac ischemia. Wistar rats were assigned into three groups: CAL: n=18; IR: n=7; SHAM (fictitious IR): n=7. After four weeks of CAL, the subjects were evaluated by echocardiography and ventriculography as well. The statistical analysis consisted of ANOVA combined with Tukey’s posthoc test (p<0.05). There were no deaths in the IR and SHAM groups, whereas in the CAL group the mortality rate was 33.33% (6 out of 18). In the CAL group echocardiography showed increased left ventricular (LV) cavity during systole (8.3 ± 1mm) and diastole (10.5 ± 1mm); decreased LV free wall during systole (1.4 ± 0.5 mm); increased left atrium/aorta (2.3 ± 0.4) ratio. These changes were not significant in IR (4.8 ± 0.5mm, 7.6 ± 0.6mm, 2.6 ± 0.3 mm, 1.6 ± 0.2) and SHAM (4.6 ± 0.6 mm, 7.7 ± 0.8mm, 2.8 ± 0.4mm, 1.5 ± 0.2) groups. There was also the reduction in the ejection fraction in the CAL group (41 ± 12 %) when compared with IR (65 ± 9%) and SHAM (69 ± 7%) groups. The tissue Doppler analysis from the lateral mitral annulus showed reduction in E′ in CAL (-29 ± 8 mm/s) and IR (-31± 9 mm/s) groups when compared with the SHAM (-48 ± 11 mm/s) group. The ventriculography in the CAL group showed smaller maximum dP/dt (6519 ± 1062) and greater end-diastolic pressure (33 ± 8 mmHg) when compared with IR (8716 ± 756 mmHg/s; 9 ± 9 mmHg) and SHAM (7989 ± 1230 mmHg/s; 9 ± 7 mmHg) groups. The CAL group presented transmural infarct size of 40% of the left ventricular wall, measured under histopathological examination. In conclusion, IR for 30 minutes caused only small changes in LV diastolic function, assessed by tissue Doppler; however, the IR was not effective for promoting HF, as observed with CAL. Thus, it is possible that prolonged IR is necessary for promoting significant HF in rats.

Abstract 132: Cardiomyocyte Specific Conditional Overexpression Of Stromal Cell Derived Factor 1 Facilitates Cardiac Regeneration After Permanent Coronary Artery Ligation In Mice.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Detlef Obal ◽  
Kenneth Brittian ◽  
Michael Book ◽  
Aruni Bhatnagar ◽  
Yiru Guo ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Stromal Cell ◽  
Cardiac Regeneration ◽  
Left Ventricular ◽  
Border Zone ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Casein Kinase 1 ◽  
Coronary Ligation ◽  
Stromal Cell Derived Factor

Background: Interruption of cardiac stromal cell derived factor 1 (SDF1)-CXCR4 axis by chronic AMD3100 administration increased myocardial injury after permanent coronary artery ligation demonstrating the important role of this chemokine in cardiac regeneration. Hypothesis: Cardiomyocyte specific conditional overexpression of SDF1 prevents heart failure after permanent coronary ligation and facilitates cardiac regeneration. Methods and Results: Tetracycline-controlled, αMyHC promoter directed overexpression of cardiac SDF1, resulted in a significant increase of SDF1 expression (SDF1: 8.1 ng/mg protein) compared to littermate WT mice (0.02 ng/mg protein) four weeks after doxycycline withdraw. SDF1 overexpression increased AKT and casein kinase 1 levels in the heart. Although there was no difference in cardiac function and scar size 1 week after infarction, SDF1 overexpression improved left ventricular (LV) ejection fraction (SDF1 [n=13]: 47±5% [mean±SEM] vs. WT [n=15]: 29±4%, p<0.05) decreased end-diastolic volume (78±10 vs. 158±30, p<0.05) and reduced infarct size measured by trichrome staining (13±3% vs. 23±3% of LV wall, p<0.05) 4 weeks after permanent ligation. Bromodeoxyuridine (BrdU) staining revealed increased regeneration indicated by a 5-fold increase in BrdU + cardiomyocyte (CM) nuclei in the borderzone of the infarct (22±3% vs. 5±1% CM nuclei, p<0.01). Increased proliferation in SDF1 mice was confirmed by a higher number of KI67 + cells compared to WT mice. Cardiomyocyte cross sectional area in the border zone was significantly reduced in SDF1 mice (365±13 μm 2 vs. 434±10 μm 2 , p<0.001) while capillary density was unchanged (2348±151/ mm 2 vs. 2498±153/ mm 2 ) compared to WT mice. Conclusion: This study demonstrates for the first time that cardiac specific overexpression of SDF1 increases myocardial regeneration and improves LV function 4 weeks after permanent coronary ligation.

Cardiac adaptations to endurance training in rats with a chronic myocardial infarction

1989 ◽  
Vol 66 (2) ◽  
pp. 712-719 ◽  
Author(s):  
T. I. Musch ◽  
R. L. Moore ◽  
P. G. Smaldone ◽  
M. Riedy ◽  
R. Zelis
Keyword(s):  
Myocardial Infarction ◽  
Endurance Training ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Coronary Artery Ligation ◽  
Maximal Heart Rate ◽  
Chronic Myocardial Infarction ◽  
Artery Ligation ◽  
Training Paradigm ◽  
Myosin Isozyme

The hemodynamic response to maximal exercise was determined in sedentary and trained rats with a chronic myocardial infarction (MI) produced by coronary artery ligation and in rats that underwent sham operations (SHAM). Infarct size in the MI groups of rats comprised 28–29% of the total left ventricle and resulted in both metabolic and hemodynamic changes that suggested that these animals had moderate compensated heart failure. The training regimen used in the present study produced significant increases in maximal O2 uptake (VO2max) when expressed in absolute terms (ml/min) or when normalized for body weight (ml.min-1.kg-1) and consisted of treadmill running at work loads that were equivalent to 70–80% of the animal's VO2max for a period of 60 min/day, 5 days/wk over an 8- to 10-wk interval. This training paradigm produced two major cardiocirculatory adaptations in the MI rat that had not been elicited previously when using a training paradigm of a lower intensity. First, the decrement in the maximal heart rate response to exercise (known as “chronotropic incompetence”) found in the sedentary MI rat was completely reversed by endurance training. Second, the downregulation of cardiac myosin isozyme composition from the fast ATPase V1 isoform toward the slower ATPase (V2 and V3) isoforms in the MI rat was partially reversed by endurance training. These cardiac adaptations occurred without a significant increase in left ventricular pump function as an increase in maximal cardiac output (Qmax) and maximal stroke volume (SVmax) did not occur in the trained MI rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of Myocardial Infarction with Sequential Ligation of the Left Anterior Descending Artery and Its Diagonal Branch in Dogs and Sheep

2003 ◽  
Vol 26 (4) ◽  
pp. 351-357 ◽  
Author(s):  
W.G. Kim ◽  
Y.C. Shin ◽  
S.W. Hwang ◽  
C. Lee ◽  
C.Y. Na
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Pulmonary Artery ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Suitable Model ◽  
Artery Ligation ◽  
Diagonal Branch ◽  
Left Anterior Descending Artery ◽  
Arterial Blood

We report a comparison of the effects of myocardial infarction in dogs and sheep using sequential ligation of the left anterior descending artery (LAD) and its diagonal branch (DA), with hemodynamic, ultrasonographic and pathological evaluations. Five animals were used in each group. After surgical preparation, the LAD was ligated at a point approximately 40% of the distance from the apex to the base of the heart, and after one hour, the DA was ligated at the same level. Hemodynamic and ultrasonographic measurements were performed preligation, 30 minutes after LAD ligation, and 1 hour after DA ligation. As a control, two animals in each group were used for the simultaneous ligation of the LAD and the DA. Two months after the coronary ligation, the animals were evaluated as previously, and killed for postmortem examination of their hearts. All seven animals in the dog group survived the experimental procedures, while in the sheep group only animals with sequential ligation of the LAD and DA survived. Statistically significant decreases in systemic arterial blood pressure and cardiac output, and an increase in the pulmonary artery capillary wedge pressure (PACWP) were observed one hour after sequential ligation of the LAD and its DA in the sheep, while only systemic arterial pressures decreased in the dog. Ultrasonographic analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all sheep, but in no dogs. Data two months after coronary artery ligation showed significant increases in central venous pressure, pulmonary artery pressure, and PACWP in the sheep, but not in the dog. Left ventricular end-diastolic dimension and left ventricular end-systolic dimension in ultrasonographic studies were also increased only in the sheep. Pathologically, the well-demarcated thin-walled transmural anteroseptal infarcts with chamber enlargement were clearly seen in all specimens of sheep, and only-mild-to-moderate chamber enlargements with endocardial fibrosis were observed in the dog hearts. In conclusion, this study confirms that the dog is not a suitable model for myocardial infarction with failure by coronary artery ligation despite negligent operative mortality, when compared directly with an ovine model.

Infarct size is increased in female post-MI rats treated with rapamycin

2009 ◽  
Vol 87 (6) ◽  
pp. 460-470 ◽  
Author(s):  
Claude Lajoie ◽  
Viviane El-Helou ◽  
Cindy Proulx ◽  
Robert Clément ◽  
Hugues Gosselin ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Female Rats ◽  
Coronary Artery Ligation ◽  
Female Rat ◽  
Sprague Dawley ◽  
Ischemic Insult ◽  
Fibrotic Response ◽  
Artery Ligation ◽  
Sprague Dawley Rats ◽  
Scar Healing

Rapamycin represents a recognized drug-based therapeutic approach to treat cardiovascular disease. However, at least in the female heart, rapamycin may suppress the recruitment of putative signalling events conferring cardioprotection. The present study tested the hypothesis that rapamycin-sensitive signalling events contributed to the cardioprotective phenotype of the female rat heart after an ischemic insult. Rapamycin (1.5 mg/kg) was administered to adult female Sprague–Dawley rats 24 h after complete coronary artery ligation and continued for 6 days. Rapamycin abrogated p70S6K phosphorylation in the left ventricle of sham rats and the noninfarcted left ventricle (NILV) of 1-week postmyocardial-infarcted (MI) rats. Scar weight (MI 0.028 ± 0.006, MI+rapamycin 0.064 ± 0.004 g) and surface area (MI 0.37 ± 0.08, MI+rapamycin 0.74 ± 0.03 cm2) were significantly larger in rapamycin-treated post-MI rats. In the NILV of post-MI female rats, rapamycin inhibited the upregulation of eNOS. Furthermore, the increased expression of collagen and TGF-β3 mRNAs in the NILV were attenuated in rapamycin-treated post-MI rats, whereas scar healing was unaffected. The present study has demonstrated that rapamycin-sensitive signalling events were implicated in scar formation and reactive fibrosis. Rapamycin-mediated suppression of eNOS and TGF-β3 mRNA in post-MI female rats may have directly contributed to the larger infarct and attenuation of the reactive fibrotic response, respectively.

Abstract 12648: Deletion of 12/15 Lipoxygenase Improves Left Ventricle Function and Survival by Resolving Inflammation Post Myocardial Infarction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Vasundhara Kain ◽  
Kevin A Ingle ◽  
Janusz Kabarowski ◽  
Sumanth D Prabhu ◽  
Ganesh V Halade
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricle ◽  
Survival Rates ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Lv Remodeling ◽  
Early Expression ◽  
Cox 2

12/15 lipoxygenase (LOX) is crucial in the inflammatory process leading to diabetes and atherosclerosis. However, the role of 12/15 LOX in myocardial infarction (MI) and left ventricle (LV) remodeling is unclear. We assessed the role of 12/15 LOX in resolving inflammation in post-MI LV remodeling. 8-12 weeks old C57BL/6J wild-type (WT; n=67) and 12/15 LOX (LOX –/– ; n=78) male mice were subjected to permanent coronary artery ligation surgery and monitored through day (d)1 and d5. No MI surgery mice were maintained as d0 naïve controls. LOX -/- mice showed higher survival rate, improved fractional shortening with reduced remodeling and edema index than WT at d1 and d5 post-MI (all p<0.05). LOX -/- mice showed increased Cxcl5 expression at d1 post-MI, consistent with stimulated neutrophil recruitment in the infarct region that was decreased at d5 compared to WT. LOX -/- mice infarct had increased expression of Ccl2 and Cxcl1, that stimulated an earlier recruitment of monocytes with increased macrophages population at d5 (all p<0.05) compared to WT. The altered kinetics of immune cells post-MI indicates a rapid resolving phase, through increase in alternative macrophage phenotypes with reduced collagen density in LOX -/- mice compared to WT mice at d5 post-MI. LOX -/- mice showed a coordinated COX-1 and COX-2 response at d1 post MI, leading to an evident increase in 5-LOX and hemoxygenase-1 (HO-1) at d5 post-MI. 12/15 LOX deletion enhanced the recruitment of alternative macrophages with secretion of HO-1 to resolve inflammation. In-vitro addition of LOX metabolite 12 hydroxyeicosatetraenoic acid to LOX -/- fibroblast induced early expression of COX-2 and 5-LOX compared to WT, indicating 5LOX role in resolution of inflammation. Post-MI increased expression of TIMP-1 and decrease in MMP-9 at d1 and α-SMA at d5 in LOX -/- mice suggested controlled differentiation of fibroblast-to-myofibroblast which is key event during ventricular tissue repair and resolving phase. This change is supported by increased expression of tgf-βi, ctgf and admats-2 (all P<0.05) at d5 post MI. In conclusion, absence of 12/15 LOX improves post-MI survival rates and attenuates LV dysfunction by resolving inflammation through coordination of 5-LOX and HO-1 as key inflammation resolving enzymes.

Intramyocardial Transplantation of Autologous Myoblasts

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Bruno Pouzet ◽  
Jean-Thomas Vilquin ◽  
Albert A. Hagège ◽  
Marcio Scorsin ◽  
Emmanuel Messas ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Coronary Artery Ligation ◽  
Skeletal Myoblast ◽  
Artery Ligation ◽  
Ventricular Ejection Fraction ◽  
Muscle Conditioning ◽  
2D Echocardiography ◽  
Complex Process ◽  
Autologous Myoblasts

Background —Autologous skeletal myoblast (SM) transplantation improves function of infarcted myocardium, but pretransplantation cultures remain a complex process. This study assessed whether it could be optimized by muscle preconditioning with the local anesthetic bupivacaine or even bypassed with the use of the so-called mince technique. Methods and Results —Muscle preconditioning consisted of intramuscular injections of the tibialis anterior of rats, 2 days before harvest. After 7 days of culture, the number of available myoblasts was significantly increased compared with nonconditioned controls (1 683 147 versus 85 300, P =0.0013). The mince technique was then assessed. A myocardial infarction was created in 66 rats by coronary artery ligation. One week later, rats were reoperated on and intramyocardially injected with culture medium alone (controls, n=23), autologous cultured SM (3.5×10 6 , n=21), or autologous muscle minced into a fine slurry, which was immediately transplanted (n=22). All muscles had been preconditioned. Left ventricular function was assessed by 2D echocardiography. Whereas end-diastolic volumes expanded over time in all groups, left ventricular ejection fraction (%, mean±SEM) was increased only in the cultured SM–transplanted group at 1 ( P =0.0006) and 2 months ( P =0.0008) versus baseline (37.52±1.92 and 40.92±2.17 versus 30.34±1.74), with a significant additional benefit between 1 and 2 months ( P =0.0069). Conclusions —Cell culture remains mandatory for SM transplantation to be successful but, in a clinical perspective, this process can be made more expeditious by preharvest muscle conditioning with bupivacaine, which greatly enhances the baseline cell yield.

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