IMPLANTATION OF AUTOLOGOUS BONE MARROW MONONUCLEAR CELLS INTO ISCHEMIC MYOCARDIUM ENHANCES CORONARY CAPILLARIES AND SYSTOLIC FUNCTION IN MINISWINE

Objective To investigate the therapeutic effectiveness of intracoronary implantation of autologous bone marrow mononuclear cells (BM-MNC) in miniswine model of reperfused myocardial infarction. Methods Sixteen miniswine myocardial ischemic reperfusion injury models made by ligation of the distal one third segment of left anterior descending artery for 90 minutes were randomized into 2 groups. In BM-MNC group (n = 9), (3.54±0.90)×108 BM-MNC were intracoronary injected, and in the control group (n = 7), phosphate buffered saline was injected by the same way. Echocardiographic and hemodynamic results, vessel density, and myocardial infarction size were evaluated and compared before and 4 weeks after cell transplantation. Results In BM-MNC group, there were no differences between before and 4 weeks after transplantation in aspects of left ventricular ejection fraction (LVEF), interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, or +dp/dtmax. In control group, LVEF, interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, and +dp/dtmax decreased significantly 4 weeks after transplantation (P < 0.05). Left ventricular end-diastolic pressure and –dp/dtmax did not change significantly before and after cell transplantation in both groups. Capillary density in BM-MNC group was greater than that in control group [(13.39 ± 6.96)/high power field vs. (3.50 ± 1.90)/high power field, P < 0.05]. Infarction area assessed by tetrazolium red staining and the infarction percentage decreased in BM-MNC group compared with those in control group (P < 0.05). Conclusions Transplantation of BM-MNC into myocardium with ischemic reperfusion injury increases capillary density and decreases infarction area. It has significantly beneficial effect on cardiac systolic function rather than on diastolic function.

Synthesis Hexadecyl 3-{4-[2-Hydroxy-3(isopropylamino)propoxy] phenyl}propionate as Potential Ligand for Liposome Targeting to Ischemic Myocardium

Novel hexadecyl 3-{4-[2-hydroxy-3(isopropylamino)propoxy]phenyl}propionate(HPP)was synthesized and its effect on delivery of liposomes into cultured cardiomyocytes was examined.The structure of HPP was characterized by IH NMR,1R and MS.The amount of cardiomyocytes uptake of HPP-liposome was 3.9-fold higher than plain-liposome,and the increase was 6.2-fold when hypoxia happens.It indicated that HPP was a potential ligand for liposome targeting to ischemic myocardium.

The Effects of Radix Ginseng Rubra on cAMP of Experimental Ischemic Myocardium in Rats

The model of SD rats ligated at the proximate left anterior descend (LAD) of coronary was used. The number and dissociation constant of β receptor were studied by using receptor autoradiography to observe the changes in β receptor and the effects of Radix Ginseng Rubra on cAMP in experimental ischemic myocardium. The result showed that the number of binding site in simple ligation group (B max =0.279) was obviously higher than that in sham operation group (B max =0.093) and the dissociation constant of simple ligation group (Kd=12.431) was higher than that of sham operation group (k d=1.319). There was a significant difference between the two groups ( P <0.05). It proved that the number of β receptor was increased and the activity was elevated in myocardial cell membranes after ligation of LAD. The myocardial cAMP level in simple ligation group (1293.96±519.36)×10 -3 nmol/g was much higher than that in sham operation group (774.44±210.55)×10 -3 nmol/g ; but the level of cAMP in ligation group after receiving Radix Ginseng Rubra treatment (805.02±362.48 pm/g) was obviously lower than that in simple ligation group ( P <0.01), which was close to the result of sham operation. The results indicated that Radix Ginseng Rubra could decrease the cAMP level in ischemic myocardium.

Strain rate imaging in assessing the size of acute ischemic myocardium in dogs

Background Since the size of ischemic myocardium is closely related with both global and regional function of the myocardium, it is of great significance to measure the size of ischemic myocardium with non-invasive methods. Methods Eleven mongrel dogs were subjected to occlusion of the left anterior descending coronary artery for acute ischemia. Strain rate imaging had M-mode of strain-rate （CAMM） curve pointed from the basal segment of the anterior wall to the basal segment of the inferior wall to detect the border of ischemia size. The strain rate （SR） defined the cut-off value of ischemic myocardium in a two-chamber apical view, and marked by the anterior and inferior wall on two-dimensional images respectively. Along the endocardium and epicardium, the ischemic size was curved on two-dimensional images by the trackball method and then compared with the pathologically ischemic size. And then longitudinal strain rates were compared in the cut-off value, adjacent non-ischemic and ischemic segments at which the cut-off point was defined by changing the curve M-mode of strain rate after ischemia. Results Linear correlation existed between pathology and strain rate ischemic size （r=0.884, P 〈0.001）. The SR parameters were lower in ischemia and cut-off point than in non-ischemic segments. The peak SRs of systole （SSR）, early diastole （EsR）, late diastole （ASR）, strain during ejection time （εet）, and the maximum length change during the entire heart cycle （Emax） in ischemic segments lowered （P〈0.05）. Time to onset of regional relaxation （TR） was prolonged （P=0.012）. Conclusion SR imaging can accurately assess the size of ischemic myocardium. Chin Med J 2009; 122（2）： 193-198

THE EFFECT OF ACUTE MYOCARDIUM ISCHEMIC ON HEART FUNCTION OF PREGNANCY RAT

Objective To investigate the effect of acute myocardium ischemic on heart function of pregnancy rat. Methods 13 female SD rats and 6 early pregnancy rats were divided into normal group, unpregnant group with acute myocardial infarction and early pregnant group with acute myocardial infarction. The anterior branch of the left coronary artery was ligated. 3 weeks later, Image 1.31 software was used to measure areas of myocardial infarction, and to evaluate hemodynamics of heart with powerLAB4.12, and cardiac tissues were stained with Massion. Results Compared with unpregnant group with acute myocardial infarction , the early pregnant group with acute myocardial infarction had less myocardial infarction area (28.86% vs. 36.8%),and had a higher left ventricle end systolic pressure, ±dp/dt _ max , and lower left ventricle end diastolic pressure. Massion stain showed the amount of collagen of the lesion was less in the early pregnant group with acute myocardial infarction than that in unpregnant group. Conclusion The early pregnant group with acute myocardial infarction had better heart contractive and diastolic function .

Pig model of chronic myocardial ischemia and its investigation by ultrasonic integrated backscatter and Doppler tissue imaging

Objective: To construct an animal model of chronic ischemic myocardium, and evaluate it by ultrasonic integrated backscatter (IBS) and Doppler tissue imaging (DTI). Methods: An Ameroid constrictor was placed around the porcine left circumflex coronary artery (LCX). The calibrated average image intensity (%AII), cyclic variation of IBS (CVIB), transmural gradient index (TGI) of CVIB in lateral-posterior wall (LPW), and DTI spectrum of LPW in left ventricular papillary muscle level short axis view (LVPM-SAM) and apical four chamber view (AP-4CV) at normal state, 2, 4, 6 and 8 weeks postoperatively were measured. Results: Normal %AII, CVIB and TGI were 2.29±0.32, 9.69±2.22dB and 0.22±0.08, respectively. The %AII increased gradually postoperatively. The CVIB decreased also gradually, and the decrease was higher in subepicardium than in subendocardium. Most of TGI decrease occurred from 2 to 4 weeks postoperatively and became zero at 8 weeks (P<0.01); Normal V S (peak systolic velocity) of AP-4CV was higher than that of LVPM-SAM (P<0.01). V E (peak early diastolic velocity) of AP-4CV was lower than that of LVPM-SAM (P<0.05). V S and V E were all decreased after operation (P<0.01). The decrease of V S in AP-4CV was greater than that in LVPM-SAM. Conclusion: The pathological changes of the myocardium in human ischemic heart disease (IHD) are similar to that of Ameriod model. IBS and DTI can detect echo changes and ventricular wall motion in chronic ischemic myocardium, and provide more information for clinical investigation and treatment of IHD.

Treatment of chronical myocardial ischemia by adenovirus-mediated hepatocyte growth factor gene transfer in minipigs

Growth factor gene transfer-induced therapeutic angiogenesis has become a novel approach for the treatment of myocardial ischemia. In order to provide a basis for the clinical application of an adeno- virus with hepatocyte growth factor gene (Ad-HGF) in the treatment of myocardial ischemia, we estab- lished a minipig model of chronically ischemic myocardium in which an Ameroid constrictor was placed around the left circumflex branch of the coronary artery (LCX). A total of 18 minipigs were ran- domly divided into 3 groups: a surgery control group, a model group and an Ad-HGF treatment group implanted with Ameroid constrictor. Ad-HGF or the control agent was injected directly into the ischemic myocardium, and an improvement in heart function and blood supply were evaluated. The results showed that myocardial perfusion remarkably improved in the Ad-HGF group compared with that in both the control and model groups. Four weeks after the treatment, the density of newly formed blood vessels was higher and the number of collateral blood vessels was greater in the Ad-HGF group than in the model group. The area of myocardial ischemia reduced evidently and the left ventricular ejection fraction improved significantly in the Ad-HGF group. These results suggest that HGF gene therapy may become a novel approach in the treatment of chronically ischemic myocardium.