Right Internal Mammary Artery Implantation into Right Ventricular Myocardium for Revascularization of the Entire Heart: Experimental Data and Preliminary Report

The left internal mammary artery implant combined with epicardiectomy and free omental graft provides three extra-coronary sources of blood. This operation tested in dogs with 92% main-stem occlusion of three coronary arteries protected 75% of the animals. Applied clinically in over 100 patients, the operation resulted in 90% improvement. To obtain complete myocardial revascularization, the right internal mammary artery has been used as a fourth source of extra-coronary blood. In 57 animals, the right internal mammary arteries were implanted into the anterior walls of the right ventricle; in 80% this vessel formed anastomoses with the right coronary tree, and in 65% with the right and left coronary arteriolar systems. Six patients are described who underwent right internal mammary artery implantation; five of these in addition had the combined operation of left internal mammary artery implant, epicardiectomy and free omental graft. All patients had completely blocked right coronary arteries; in addition, five had advanced disease of the left coronary arterial tree.     

The Treatment of Multiple Coronary Occlusions by Internal Mammary Artery Implantation and Omental Graft: Report on Two Human Cases

The importance of triple coronary artery disease was evident in 125 patients undergoing internal mammary artery implantation, when some patients died from right coronary artery occlusion. This occurred even when the internal mammary artery was patent and revascularizing the left ventricle.In 1961 the free omental graft operation was developed to revascularize both right and left ventricles. In animals this operation has proved most effective in preventing death after application of Ameroid constrictors to all three coronary arteries. Arteriolar or larger-sized vessels rapidly formed between the aorta and omentum and the pericardium and omentum and the heart and omentum.Two patients with triple coronary artery disease underwent internal mammary artery implantation and free omental graft early in December 1962. Postoperative convalescence was uneventful. They have returned home and appear to be improved. Wrapping the entire heart with the free omental graft has produced little reaction, suggesting that, as in the animal, the grafts are surviving.     

Combined Internal Mammary Artery Implantation and Free Omental Graft Operation: A Highly Effective Revascularization Procedure: (A Study of 17 Cases)

One hundred and forty patients with coronary artery disease treated by internal mammary artery implantation were followed up from six months to 13 years. The mortality rate was 3%; improvement was obtained in 70%. Occlusive disease of all three major coronary arteries, however, requires more blood than can be supplied by the implant procedure, and the free omental graft operation was developed for the management of selected patients with this condition. Normally in animals triple coronary artery ameroid constriction results in 100% mortality. When the free omental graft operation, with or without internal mammary artery implantation, was performed, 80% of such animals survived. The free omental graft forms capillary anastomoses in three days and arteriolar vessels in eight days, which leave the base of the aorta, enter the omentum, thence to the myocardium. A combined internal mammary artery implantation and free omental graft operation was performed in 17 patients with triple coronary artery disease as shown by cine coronary arteriography. There was no operative mortality, and 12 of the patients are free of pain and have returned to work.     

The Continuity of Right and Left Ventricular Myocardial Sinusoidal Spaces and its Relation to Right Ventricular Implants

Evidence is presented which indicates that blood leaving side branches of an internal mammary artery implanted into the anterior wall of the right ventricle flows from the tunnel in which it lies through myocardial sinusoidal spaces of the anterior right ventricular wall across the midline to fill corresponding spaces in the anterior wall of the left ventricle and thence is carried to the left coronary sinus. The myocardial sinusoidal spaces of right and left ventricles have been well outlined, using injections of polyvinyl acetate and the technique of digestion casts. We have been able to show that there is no barrier between the myocardial sinusoids of the right circulation and those related to the anterior descending branch of the left coronary artery. In structure, these myocardial sinusoidal spaces are quite different from the intramyocardial coronary arteriolar zones which, in 93% of human hearts, are separated from one another without collateral communication.The continuity of the right and left ventricular myocardial sinusoids explains why implantation of a right internal mammary artery into the anterior wall of the right ventricle combined with a corresponding left implant, epicardiectomy and free omental graft, has been so effective in our hands in the treatment of far-advanced human coronary artery insufficiency.     

Results of 14 Years' Experience in the Surgical Treatment of Human Coronary Artery Insufficiency

Atherosclerosis obstructs the main stems of coronary arteries, restricting the coronary artery inflow tract. Nature develops intramyocardial collaterals but fails to form extracoronary collateral channels. It is only through surgical measures that extracoronary collateral channels may be formed, for example, by internal mammary artery implantation and omental graft without pedicle operations. Preoperative assessment, with particular reference to anginal pain, disease activity, indications for and contra-indications to surgery, is outlined. The importance of cine coronary arteriography is stressed. The results of internal mammary artery implantation with or without omental graft in patients followed up for two to 14 years are presented. Operative mortality in 103 consecutive patients was 2.9%. There was marked improvement in over 70% of 115 patients reviewed. Post-operative examination of 29 implanted internal mammary arteries showed that 76% were open when examined up to 10 years postoperatively; many of these were studied by cineangiography.     

Revascularization of both cardiac ventricles by right ventricular implants

Implantation of the right internal mammary artery into the wall of the right ventricle has been performed in 48 patients whose cases have been followed up for longer than six months. The procedure was done at the same time as a left ventricular implantation or subsequent to this operation because of recurrence or persistence of symptoms. Relief of anginal pain has been achieved in 78% and of chronic left ventricular failure in 75%. Of the 40 patients who had already had one or more myocardial infarctions preoperatively, 36 are still alive, with an average survival of over 5 years.     

Renal norepinephrine content decreases after chronic flow probe implantation.

Electromagnetic flow probes were chronically implanted around the left renal artery in 6 female beagle dogs. 3-10 months after implantation, renal cortex norepinephrine contents of right and left kidneys were compared (liquid chromatography). In 4 out of the 6 dogs investigated 3-6 months after implantation, the norepinephrine content of the left kidney was reduced by 27-72%. In 2 dogs investigated 7 and 10 months after implantation, the difference between left and right kidney was not significant. These findings should be taken into consideration when interpreting results from chronically instrumented kidneys.     

Oxytocic activity of plasma and posterior pituitary lobe after ovariectomy and implantation of stilboestrol or progesterone tablets in female rats

The purpose of this work was to compare the oxytocic activity of plasma and posterior pituitary lobe extract in rats after sham operation, ovariectomy and after subcutaneous implantation of stilboestrol or progesterone tablets in ovariectomized rats. On the 5th day after ovariectomy or implantation of hormones, sample of 2 ml of blood were obtained under urethane anaesthesia from the cephalic end of the right external jugular vein, and the animals were killed by decapitation. The posterior pituitary lobe was removed and homogenized in 0.9% NaCl solution acidified with glacial acetic acid. The oxytocic activity of plasma and extracts of the posterior pituitary lobe was determined by the method of Van Dongen and Hays on fragments of lactating rat mammary tissue. On the 5th day after ovariectomy or implantation of stilboestrol the oxytocic activity was found to be significantly increased in the plasma and posterior pituitary lobe, and after progesterone implantation it was decreased in the posterior pituitary lobe.     

兔颈动、静脉移植桥血管狭窄模型的建立及其电镜观察

目的：建立兔颈动、静脉移植血管桥动物模型,观察移植桥血管内膜增生和狭窄的电镜下表现。方法：通过兔双侧颈动脉进行动脉桥和静脉桥的移植,形成双侧移植血管桥再狭窄动物模型。在第8周施行血管桥移植手术的同时留取右侧颈动静脉标本作为对照血管,再分别于第12周、16周和第20周分别处死模型兔,采集移植桥血管标本,在光镜下测量其内膜厚度、面积、狭窄度,并进行电镜观察。结果：颈动脉和颈静脉桥移植后,随着时间的延长,桥血管的出现平滑肌迁移,脂质沉积,内膜增生,血管狭窄等改变,且以静脉桥血管的病理改变更为明显。结论：在兔形成动脉粥样硬化病变基础上,进行双侧颈动脉血管桥的移植,建立兔双侧颈动脉移植血管桥再狭窄动物模型,有利于设立自身对照,研究术后动静脉桥再狭窄差异机制;建立动、静脉桥后,位于血管中膜的平滑肌细胞出现向血管内膜迁移现象,说明中膜平滑肌细胞迁移进入内膜导致新内膜形成是血管再狭窄的重要环节。     

Coronary stenting using a 6 F. diagnostic catheter: a report of two cases

Standard guiding catheters for coronary interventions may not selectively engage the coronary ostium despite a successful cannulation with a diagnostic catheter of the same curve. This discrepancy is explained by a slight difference in shape between the two catheters (shorter tip of the guiding, absence of tip tapering, etc.). The authors report on the use of 6 F. coronary diagnostic catheters as guiding catheters for coronary angioplasty and stent implantation in two patients with critical stenoses: in the right coronary artery distal to a right internal mammary artery anastomosis in one and in the ostial right coronary artery in the other. In both cases, the use of diagnostic catheters was the key to success despite the vessel orifice being unfavourable for the use of different types of guiding catheters.     

Criteria for Internal Mammary Artery Implantation Based on Cine Coronary Arteriography

Preoperative coronary arteriograms were correlated, in a group of 50 patients, with left internal mammary angiograms obtained from 11 to 32 months, with a mean of 17 months, after mammary artery implantation. In all patients in whom the internal mammary artery was patent and considered functional with good angiographic opacification of the anterior descending coronary artery, the preoperative coronary angiogram showed total or subtotal obstruction of the latter vessel, with indirect evidence of decreased flow and pressure distal to the obstruction. This evidence was provided by the presence of a collateral circulation or, in a few cases of subtotal obstruction, delayed opacification of the vessel distal to the obstruction.In patients in whom the internal mammary artery was patent but showed no anastomotic connection with the anterior descending coronary artery or only opacification of small coronary branches, the degree of coronary obstruction was, in most cases, less than 90% of the lumen of the coronary artery in the absence of any collateral circulation or delayed opacification of the vessel distal to the obstruction.Occlusion of the internal mammary artery was seen as often in the presence of total or subtotal obstructions as with lesser degrees of anterior descending coronary artery obstruction, and is believed unrelated to the degree of pre-existing coronary artery disease.Successful internal mammary artery implantation can be related to specific coronary angiographic patterns recognizable before operation; these may serve as reliable criteria for the selection of patients.     

Temporal Profile of Levels of Monoamines and Their Metabolites in Striata of Rats Implanted with Dialysis Tubes

We have measured the levels of monoamines and their metabolites in rat striata implanted with a dialysis tube, in contralateral nonimplanted striata, and in dialysates obtained from the dialysis tube. The perfusion was done with Ringer solution. The animals were perfused either for a continuous period of 7 h at 1 day after implantation or for periods of 2 h on days 1, 4, and 7 after implantation. In animals perfused for 7 h, levels of monoamine metabolites in dialysates remained stable for the first 4 h of perfusion, but a reduction was observed during the last 3 h. In animals perfused for 2 h on days 1, 4, and 7 after implantation, we observed a progressive reduction in levels of metabolites in dialysates with respect to the first day of perfusion. The levels of dopamine and its metabolites in the striata in which a dialysis cannula had been implanted showed a progressive reduction during the period postimplantation comparable to that observed in dialysates. The levels of 3-methoxytyramine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were elevated 24 h after implantation in the implanted striata with respect to the contralateral nonimplanted striata, but 7 days after implantation, the levels of dopamine were decreased in the implanted striata, and the levels of metabolites were unchanged.     

Effects of different schedules of progesterone treatment on mammary tumorigenesis and uterine adenomyosis in SHN virgin mice

As a possible step to estimate the factors controlling the effects of progesterone on mammary tumorigenesis, 3 groups of SHN virgin female mice were treated as follows beginning 2.5–4 months of age: Group A received the subcutaneous implantation of silastic tube containing progesterone (low dose) during the initial 4 months followed by progesterone pellet implantation (high dose) every 2 months. Group B was implanted with progesterone pellet throughout the experiment. Group C was given the vehicle only. Whereas there was little difference among groups in mammary tumorigenesis during the initial 4 months of treatments, tumorigenesis was significantly stimulated in group B thereafter. On the contrary, group A was different little from group C even after progesterone pellet implantation. The results indicate that the effects of progesterone on mammary tumorigenesis are affected by the ‘preceding’ progesterone conditions and that there is a critical period for manifestation of the effects of progesterone on mammary tumorigenesis, which is before 8 months of age at most. While all mice developing mammary tumors developed uterine adenomyosis in each group, the progression was enhanced by both low and high doses of progesterone.     

A Radio-telemetric System to Monitor Cardiovascular Function in Rats with Spinal Cord Transection and Embryonic Neural Stem Cell Grafts

High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter connected to a radio transmitter into the femoral artery of rats that underwent a T4 spinal cord transection with or without grafting of embryonic brainstem-derived neural stem cells expressing green fluorescent protein. Compared to other methods such as cannula insertion or tail-cuff, telemetry is advantageous to continuously monitor blood pressure and heart rate in freely moving animals. It is also capable of long term multiple data acquisitions. In spinal cord injured rats, basal cardiovascular data under unrestrained condition and autonomic dysreflexia in response to colorectal distension were successfully recorded. In addition, cardiovascular parameters before and after SCI can be compared in the same rat if a transmitter is implanted before a spinal cord transection. One limitation of the described telemetry procedure is that implantation in the femoral artery may influence the blood supply to the ipsilateral hindlimb.     

Outcomes of Middle Cardiac Vein Arterialization via Internal Mammary/Thoracic Artery Anastomosis

Objective

Cardiac vein arterialization is seldom applied for treating right coronary artery disease. This study aimed to improve outcomes of cardiac vein arterialization in a porcine model using intramammary artery anastomosis.

Methods

A chronic, stenotic coronary artery model was established in 12 of 14 Chinese experimental miniature pigs of either sex, which were randomly divided into equal control (n = 6) and experimental (n = 6) groups. In experimental animals, blood flow was reconstructed in the right coronary artery using intramammary artery. Arterialization involved dissection of right internal mammary artery from bifurcation to apex of thorax followed by end-to-side anastomosis of internal mammary artery and middle cardiac vein plus posterior descending branch of right coronary artery. Intraoperative heart rate was maintained at 110 beats/min. Graft flow assessment and echocardiography were performed when blood pressure and heart rate normalized.

Results

The experimental group had significantly higher mean endocardial and epicardial blood flow postoperatively than control group (mean endocardial blood flow: 0.37 vs. 0.14 ml/(g*min), p<0.001; mean epicardial blood flow: 0.29 vs. 0.22, p = 0.014). Transmural blood flow was also higher in experimental group than in control group (0.33 vs. 0.19, p<0.001); ejection fraction increased from 0.46% at baseline to 0.51% (p = 0.0038) at 6 hours postoperatively, and mean blood flow of internal mammary artery was 44.50, perfusion index 0.73 at postoperative 6 months, 43.33 and 0.80 at 3 months.

Conclusion

Successful cardiac vein arterialization via intramammary artery in a porcine model suggests that this may be a viable method for reconstructing blood flow in chronic, severe coronary artery disease.     

植入血管束的血管化人工神经导管对受损神经功能恢复影响的实验研究

目的:研究植入血管束的血管化人工神经导管修复SD大鼠长段坐骨神经缺损对神经功能恢复的影响。方法:将18只成年雌性SD大鼠制成14mm的大鼠坐骨神经缺损模型后,随机分为3组(每组12条神经),分别采用不同的修复方法。A组:自体神经移植组(自体组);B组:普通PGLA神经导管移植组(导管组);C组:植入自体血管束的普通PGLA神经导管移植组(血管化导管组)。观察术后大鼠后肢皮肤溃疡面积;检测术后6周、12周时步态变化和肌电图。结果:术后各组SD大鼠均出现后肢溃疡,血管化导管组SD大鼠后肢溃疡愈合较导管组早2周。血管化导管组步态检测SFI明显优于导管组,与自体神经移植组无明显差异。肌电图检测表明血管化导管组无论是神经传导速度,还是动作电位振幅均明显大于导管组(P<0.05),与自体神经移植组无明显差异(P>0.05)。结论:植入血管束的血管化人工神经导管能有效地促进受损神经的功能恢复。     

In vitro evaluation of flow divertors in an elastase-induced saccular aneurysm model in rabbit

Endovascular coiling is an acceptable treatment of intracranial aneurysms, yet long term follow-ups suggest that endovascular coiling fails to achieve complete aneurysm occlusions particularly in wide-neck and giant aneurysms. Placing of a stentlike device across the aneurysm neck may be sufficient to occlude the aneurysm by promoting intra-aneurysmal thrombosis; however, conclusive evidence of its efficacy is still lacking. In this study, we investigate in vitro the efficacy of custom designed flow divertors that will be subsequently implanted in a large cohort of animals. The aim of this study is to provide a detailed database against which in vivo results can be analyzed. Six custom designed flow divertors were fabricated and tested in vitro. The design matrix included three different porosities (75%, 70%, and 65%). For each porosity, there were two divertors with one having a nominal pore density double than that of the other. To quantify efficacy, the divertors were implanted in a compliant elastomeric model of an elastase-induced aneurysm model in rabbit and intra-aneurysmal flow changes were evaluated by particle image velocimetry (PIV). PIV results indicate a marked reduction in intra-aneurysmal flow activity after divertor implantation in the innominate artery across the aneurysm neck. The mean hydrodynamic circulation after divertor implantation was reduced to 14% or less of the mean circulation in the control and the mean intra-aneurysmal kinetic energy was reduced to 29% or less of its value in the control. The intra-aneurysmal wall shear rate in this model is low and implantation of the flow divertor did not change the wall shear rate magnitude appreciably. This in vitro experiment evaluates the characteristics of local flow phenomena such as hydrodynamic circulation, kinetic energy, wall shear rate, perforator flow, and changes of these parameters as a result of implantation of stentlike flow divertors in an elastomeric replica of elastase-induced saccular aneurysm model in rabbit. These initial findings offer a database for evaluation of in vivo implantations of such devices in the animal model and help in further development of cerebral aneurysm bypass devices.     

Morphogenesis of Mouse Mammary Epithelium In Vivo in Response to Biomatrix Prepared from a Stimulatory Fetal Mesenchyme

Insoluble "biomatrix" of mesenchyme is a stimulator of mammary cell differentiation in vitro , but its effect in the morphogenesis is unknown. Fetal salivary mesenchyme induces intense local duct formation when implanted into adult mammary gland. We have therefore tested whether biomatrix prepared from fetal salivary mesenchyme retains this abillity to stimulate duct formation in vivo . Salivary mesenchyme isolated from mouse fetuses at 13.5–14.0 days of gestation, extracted sequentially with water and with 1 M NaCl, then digested with DNAse and RNAse was implanted into mammary glands of female mice and left for periods of 1–35 days. In approximately 40% of recipients, the local epithelium either formed cyst like structures, or else "spikes" of mammary epithelium penetrated the matrix forming a simplified ductwork inside it. Similar responses were elicited by salivary mesenchyme killed by freezing and also by biomatrix prepared from fetal mammary fat pad precursor tissue, mesenchyme of fetal lung, and fetal heart, liver, and brain. However when mesenchyme was either fixed with glutaraldehyde or sonicated and embedded in polymer blocks before implantation, no epithelial response was noted. These observations suggest that the biomatrix provides a passive scaffolding that contributes to morphogenesis of mammary ducts, is insufficient to support normal morphogenesis.     

选择性冠状静脉动脉化搭桥术中不同移植物的应用疗效比较

目的:对比选择性冠状静脉动脉化(SCVBG)搭桥治疗弥漫性右冠状动脉狭窄病变中选择乳内动脉和大隐静脉作为桥血管的治疗效果。方法:选择2008年10月到2014年10月在我院行SCVBG搭桥的84例患者资料,其中选择大隐静脉作为桥血管进行冠状静脉动脉化搭桥患者46例(大隐静脉桥组),选择乳内动脉作为桥血管进行冠状静脉动脉化搭桥患者38例(乳内动脉桥组)。随访记录两组患者的生存情况、近期复查超声心动图、冠状动脉CTA及心绞痛复发率。结果:乳内动脉桥组患者总生存率(100%)明显高于大隐静脉桥组(82.6%)(P0.05)。乳内动脉桥组患者桥血管和心中静脉通畅率(100%)明显大于大隐静脉桥组(54.35%)(P0.05)。两组患者左心室射血分数(LVEF)较治疗前明显增加,左心室舒张期末内径(LVEDD)较治疗前明显减小(P0.05)。治疗后,乳内动脉桥组患者心绞痛复发率明显小于大隐静脉桥组(P0.05)。结论:SCVBG搭桥治疗弥漫性右冠状动脉狭窄病变中,选择乳内动脉桥效果优于大隐静脉桥,能明显提高桥血管和心中静脉通畅率,降低心绞痛复发率。