Haemodynamics in the first seconds after coronary artery occlusion.

The changes in cardiac and in total haemodynamics, occurring during the first seconds of occlusion and the subsequent desocclusion of coronary arteries were studied on 28 dogs. The most intensive changes were observed after the trunk occlusion of the left coronary artery. Simultaneously with decreasing blood inflow into the myocardium its contractility and the systolic pressure in the left ventricle and the outflow from the coronary sinus began to fall rapidly. The systolic pressure in the left ventricle decreased within the first 10 s from 24 to 13-15 kPa (180 to 100-110 mm Hg), which means that the systolic pressure fell about 1 kPa (7-8 mm Hg) per second, or 0.5-0.6 kPa (4-5 mm Hg) per systole. At the same time the end-diastolic pressure in the left ventricle also increased from zero to 3-4 kPa (25-30 mm Hg). After the trunk desocclusion of the left coronary artery the systolic pressure in the left ventricle proceeded to fall by about 2-3 kPa (15-22 mm Hg). Only then, 20-25 s after the desocclusion, blood flow in the left coronary artery began to rise intensively and 4-6 s later the myocardial contractility and the systolic pressure in the left ventricle also increased. After unclamping (50-60 s), there was an overshoot of haemodynamic values above preocclusive values and then followed the compensatory phase. This phase lasted 80-90 s and on its peak the pressure and flow parameters increased by about 50-60% above preocclusive values. During the occlusion of ramus interventricularis anterior or ramus circumflexus for 30-60 s the haemodynamic parameters changed only slightly. The same was observed during trunk occlusion of the right coronary artery (30-60 s), but in that case many extrasystoles occurred.     

Role of the vagus in control of the major conduit coronary artery in the dog.

Using El Badawi and Schenk's modification of Karnovski's method for the demonstration of acetylcholinesterase, the authors found cholinergic fibres both in the perivascular connective tissue and directly in the wall (in the adventitia) of the major coronary arteries; the fibres were distributed regularly around the circumference of the arteries. In the case of the smaller intramyocardial arteries, the cholinergic fibres were concentrated at two poles of the blood vessel; none were present in the wall of the veins. The shape and topography of the coronary cholinergic arterial plexus resemble the shape and topography of the coronary sympathetic adrenergic system. In apparent contradiction of this finding, stimulation of the cervical vagus did not affect the diameter of the large coronary arteries. Since acetylcholine (6--10 micrograms/kg i.v.) produced a mean 7.4% increase in the diameter of the ramus interventricularis ventralis, we concluded that there are no postgangliar cholinergic fibres of vasomotor significance for the large coronary arteries in the cervical vagus. The specific acetylcholinesterase activity found in the wall of these vessels belongs either to cholinergic terminals whose ganglion cells are not located in the vagal ganglion, or to cholinergic axones terminating outside the wall of the large coronary arteries.     

Heart innervation after ligation of the left anterior descending coronary artery (LAD)

Distribution and amount of neuropeptide Y- and synaptophysin-immunoreactive nervous structures within the heart were investigated in dogs 4 days after ligation of the left anterior descending coronary artery (LAD). In the right atrium and posterior left ventricular regions, which were taken as (non-infarcted) control areas, neuropeptide Y-immunoreactive paravascular nerves and a perivascular nerve plexus running within the adventitia of the coronary arteries and their branches down to the arterioles were observed. Morphometric measurements of the area density revealed 0.099 +/- 0.014% for synaptophysin- and 0.037 +/- 0.0072% for neuropeptide Y-immunoreactivity within the posterior wall of the left ventricular myocardium. Four days after ligation of the LAD only single synaptophysin- and neuropeptide Y-immunoreactive nerve fibers were very rarely detected in the infarcted region of the anterior wall of the left ventricle. Above the ligature larger than normal neuropeptide Y-immunoreactive axons within nerves along the LAD indicated a blockage of the axoplasmic transport of this peptide. When investigating this model of experimental myocardial infarction, mechanical traumatization of peri- and paravascular nerves of the LAD by the ligature has to be considered as a major pathogenetic factor, in addition to ischemia leading to denervation of infarcted as well as non-ischemic myocardium.     

Autonomic nerve terminals in relation to contractile and non-contractile structures in the conduit coronary artery of the dog

The ramus interventricularis anterior (RIA), its first- and second-order branch were prepared for EM (perfused with glutaraldehyde under pressure, or simply fixed with KMnO4). No nerve fibres were found in the tunica media of either of the three consecutive segments. In the tunica adventitia axons with varicosities were found at a distance from the tunica media of 0.5-15 microns (about 50% 0.5-4.5 microns) in the RIA, 0.4-12 microns (about 50% 0.5-3.4 microns) in the first-order branch and 0.3-6.0 microns (about 50% 0.3-2.3 microns) in the second-order branch. Varicosities contain small, dense-cored vesicles (35-60 nm) and large, dense-cored vesicles (70-90 nm, exceptionally up to 120 nm); the other type contains small, clear vesicles (35-60 nm) and few large, dense-cored vesicles (70-90 nm). The remarkably large distance between the nerve terminals and smooth muscle cells fits well with the small range of sympathetic control of the conduit coronary artery. Close apposition of nerve terminals to fibroblasts (30-200 nm) was revealed in all three consecutive coronary portions. Moreover, terminal axons often lose the Schwann cell cover on the abluminal site and face the fibroblast.     

Diameter-dependent axial prestretch of porcine coronary arteries and veins

The pressure-diameter relation (PDR) and the wall strain of coronary blood vessels have important implications for coronary blood flow and arthrosclerosis, respectively. Previous studies have shown that these mechanical quantities are significantly affected by the axial stretch of the vessels. The objective of this study was to measure the physiological axial stretch in the coronary vasculature; i.e., from left anterior descending (LAD) artery tree to coronary sinus vein and to determine its effect on the PDR and hence wall stiffness. Silicone elastomer was perfused through the LAD artery and coronary sinus trees to cast the vessels at the physiologic pressure. The results show that the physiological axial stretch exists for orders 4 to 11 (> 24 μm in diameter) arteries and orders -4 to -12 (>38 μm in diameter) veins but vanishes for the smaller vessels. Statistically, the axial stretch is higher for larger vessels and is higher for arteries than veins. The axial stretch λ(z) shows a linear variation with the order number (n) as: λ(z) = 0.062n + 0.75 (R(2) = 0.99) for artery and λ(z) = -0.029n + 0.89 (R(2) = 0.99) for vein. The mechanical analysis shows that the axial stretch significantly affects the PDR of the larger vessels. The circumferential stretch/strain was found to be significantly higher for the epicardial arteries (orders 9-11), which are free of myocardium constraint, than the intramyocardial arteries (orders 4-8). These findings have fundamental implications for coronary blood vessel mechanics.     

金钱豹和猪獾冠状动脉的解剖

为了阐明金钱豹(Panthera pardus)和猪獾(Arctonyx collaris)心冠状动脉的分支分布特征及血供情况,为心脏生物学及动物学研究提供结构基础资料,利用血管铸型和组织透明方法观察研究了金钱豹与猪獾心左、右冠状动脉的分支分布.结果表明,金钱豹和猪獾的心均由左右冠状动脉营养.金钱豹左冠状动脉分为室间隔支、前降支和旋支.前降支又分出左室上支、左室中支和左室下支.右冠状动脉沿途分出右室前支、右室后下支和右室后上支.猪獾左冠状动脉分为前降支和旋支.前降支又分出室间隔支和左室前支,旋支又分出左缘支和左室后支.其右冠状动脉沿途分出右室前支、右缘支和右室后支.金钱豹和猪獾心的室间隔均由发自左冠状动脉的独立的室间隔支营养,二者左右冠状动脉在膈壁的分布属于均衡型.     

Changes of regional myocardial blood flow during and after acute focal experimental ischaemia.

The regional blood flow through the myocardium of the left ventricle was measured in 11 dogs after ligation of the left anterior descending coronary artery, by means of a local injection of 133Xe depot and precordial detection of its washout 2 hours after ligation. Immediately after ligation the blood flow in the ischaemic area declined considerably but at the same time there was a significant increase of blood flow in the non-ischaemic left ventricular myocardium. The regional flow in the ischaemic and non-ischaemic area increased insignificantly for 2 hrs. These changes were not due to alterations in coronary artery pressure, as the mean arterial pressure declined significantly during the first hour. After temporary ischaemia by ligation of the left anterior descending coronary artery for 2--4 minutes, an intensive reactive hyperaemia developed in the ischaemic region (the blood flow reached 221% of control values on the average) which was the more intensive, the greater the drop of blood flow in the ischaemic area after ligation.     

Heart innervation after ligation of the left anterior descending coronary artery (LAD)

Summary Distribution and amount of neuropeptide Y- and synaptophysin-immunoreactive nervous structures within the heart were investigated in dogs 4 days after ligation of the left anterior descending coronary artery (LAD). In the right atrium and posterior left ventricular regions, which were taken as (non-infarcted) control areas, neuropeptide Y-immunoreactive paravascular nerves and a perivascular nerve plexus running within the adventitia of the coronary arteries and their branches down to the arterioles were observed. Morphometric measurements of the area density revealed 0.099±0.014% for synaptophysin- and 0.037±0.0072% for neuropeptide Y-immunoreactivity within the posterior wall of the left ventricular myocardium. Four days after ligation of the LAD only single synaptophysin-and neuropeptide Y-immunoreactive nerve fibers were very rarely detected in the infarcted region of the anterior wall of the left ventricle. Above the ligature larger than normal neuropeptide Y-immunoreactive axons within nerves along the LAD indicated a blockage of the axoplasmic transport of this peptide.When investigating this model of experimental myocardial infarction, mechanical traumatization of peri- and paravascular nerves of the LAD by the ligature has to be considered as a major pathogenetic factor, in addition to ischemia leading to denervation of infarcted as well as nonischemic myocardium.This study was supported by the SFB 320 within the Deutsche Forschungsgemeinschaft (DFG)Parts of the results were presented at the 59. Scientific Session of the American Heart Association (1986) and at the Congress of the Deutsche Gesellschaft für Herz- und Kreislaufforschung 1987.     

Sandostatin inhibits development of medial proliferation of pulmonary arteries in a rat model of pulmonary hypertension

We investigated the effects of subcutaneous administration of 50 and 100 μg/kg/day of sandostatin on monocrotaline-induced medial proliferation of pulmonary arteries and right ventricular overload in rats. In a dosage of 100 μg/kg/day, sandostatin significantly reduced right ventricular systolic pressure, the mass ratio of the right ventricular free wall to the left ventricle, the right ventricular wall thickness, the right ventricular myofiber diameter, the percent medial pulmonary artery thickness, the percent area of smooth muscle cell, and proliferating cell nuclear antigen activity. Our results suggest that sandostatin inhibits development of medial proliferation of pulmonary arteries and right ventricular overload in a dosage of 100 μg/kg/day.     

Influence of coronary artery diameter on eNOS protein content

The purpose of this study was to test the hypothesis that the content of endothelial nitric oxide synthase (eNOS) protein (eNOS protein/g total artery protein) increases with decreasing artery diameter in the coronary arterial tree. Content of eNOS protein was determined in porcine coronary arteries with immunoblot analysis. Arteries were isolated in six size categories from each heart: large arteries [301- to 2,500-microm internal diameter (ID)], small arteries (201- to 300-microm ID), resistance arteries (151- to 200-microm ID), large arterioles (101- to 150-microm ID), intermediate arterioles (51- to 100-microm ID), and small arterioles(<50-microm ID). To obtain sufficient protein for analysis from small- and intermediate-sized arterioles, five to seven arterioles 1-2 mm in length were pooled into one sample for each animal. Results establish that the number of smooth muscle cells per endothelial cell decreases from a number of 10 to 15 in large coronary arteries to 1 in the smallest arterioles. Immunohistochemistry revealed that eNOS is located only in endothelial cells in all sizes of coronary artery and in coronary capillaries. Contrary to our hypothesis, eNOS protein content did not increase with decreasing size of coronary artery. Indeed, the smallest coronary arterioles had less eNOS protein per gram of total protein than the large coronary arteries. These results indicate that eNOS protein content is greater in the endothelial cells of conduit arteries, resistance arteries, and large arterioles than in small coronary arterioles.     

Early changes of protein synthesis in myocardium and coronary arteries induced by NO synthase inhibition.

The question was addressed whether short-term (4 hour) NO deficiency, inducing an increase in blood pressure in anaesthetized dogs, does influence proteosynthesis in the myocardium and coronary arteries. A potentially positive answer was to be followed by the study of the supporting role of ornithine decarboxylase for the polyamines pathway. N(G)-nitro-L-arginine-methyl ester (L-NAME) (50 mg/kg per hour) was administered i.v. to inhibit NO synthase. After the first L-NAME dose diastolic blood pressure increased from 131.8+/-2.0 to 149.4+/-3.9 mm Hg (p<0.001) and was maintained at about this level till the end of the experiment. Systolic blood pressure only increased after the first dose (from 150.8+/-1.1 to 175.0+/-5.8 mm Hg, p<0.01), returning thereafter to the control level. Similarly, the heart rate declined only after the first dose (from 190.4+/-5.3 to 147.6+/-4.5 beats/min, p<0.01). Total RNA concentrations increased in the left cardiac ventricle (LV), the left anterior descending coronary artery (LADCA) and left circumflex coronary artery (LCCA) by 15.9+/-0.7, 29.7+/-1.3 and 17.6+/-1.0%, p<0.05, respectively. The same applied to [14C]leucine incorporation (by 86.5+/-5.0, 33.5+/-2.6, 29.3+/-4.1%, p<0.05, respectively). The above parameters indicated an increase of proteosynthesis in the LV myocardium and both coronary arteries LADCA and LCCA after short-term NO deficiency. Surprisingly, the ornithine decarboxylase activity in the LV myocardium decreased significantly by 40.2+/-1.6% (p<0.01) but the changes were not significant in the coronary arteries. This unexpected finding makes the role of polyamines in increasing proteosynthesis during a pressure overload due to NO deficiency questionable.     

Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries

Coronary arteries bring blood flow to the heart muscle. Understanding the developmental program of the coronary arteries provides insights into the treatment of coronary artery diseases. Multiple sources have been described as contributing to coronary arteries including the proepicardium, sinus venosus (SV), and endocardium. However, the developmental origins of coronary vessels are still under intense study. We have produced a new genetic tool for studying coronary development, an AplnCreER mouse line, which expresses an inducible Cre recombinase specifically in developing coronary vessels. Quantitative analysis of coronary development and timed induction of AplnCreER fate tracing showed that the progenies of subepicardial endothelial cells (ECs) both invade the compact myocardium to form coronary arteries and remain on the surface to produce veins. We found that these subepicardial ECs are the major sources of intramyocardial coronary vessels in the developing heart. In vitro explant assays indicate that the majority of these subepicardial ECs arise from endocardium of the SV and atrium, but not from ventricular endocardium. Clonal analysis of Apln-positive cells indicates that a single subepicardial EC contributes equally to both coronary arteries and veins. Collectively, these data suggested that subepicardial ECs are the major source of intramyocardial coronary arteries in the ventricle wall, and that coronary arteries and veins have a common origin in the developing heart.     

Determination of layer-specific mechanical properties of human coronary arteries with nonatherosclerotic intimal thickening and related constitutive modeling

At autopsy, 13 nonstenotic human left anterior descending coronary arteries [71.5 +/- 7.3 (mean +/- SD) yr old] were harvested, and related anamnesis was documented. Preconditioned prepared strips (n = 78) of segments from the midregion of the left anterior descending coronary artery from the individual layers in axial and circumferential directions were subjected to cyclic quasi-static uniaxial tension tests, and ultimate tensile stresses and stretches were documented. The ratio of outer diameter to total wall thickness was 0.189 +/- 0.014; ratios of adventitia, media, and intima thickness to total wall thickness were 0.4 +/- 0.03, 0.36 +/- 0.03, and 0.27 +/- 0.02, respectively; axial in situ stretch of 1.044 +/- 0.06 decreased with age. Stress-stretch responses for the individual tissues showed pronounced mechanical heterogeneity. The intima is the stiffest layer over the whole deformation domain, whereas the media in the longitudinal direction is the softest. All specimens exhibited small hysteresis and anisotropic and strong nonlinear behavior in both loading directions. The media and intima showed similar ultimate tensile stresses, which are on average three times smaller than ultimate tensile stresses in the adventitia (1,430 +/- 604 kPa circumferential and 1,300 +/- 692 kPa longitudinal). The ultimate tensile stretches are similar for all tissue layers. A recently proposed constitutive model was extended and used to represent the deformation behavior for each tissue type over the entire loading range. The study showed the need to model nonstenotic human coronary arteries with nonatherosclerotic intimal thickening as a composite structure composed of three solid mechanically relevant layers with different mechanical properties. The intima showed significant thickness, load-bearing capacity, and mechanical strength compared with the media and adventitia.     

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.     

Effects of myocardial constraint on the passive mechanical behaviors of the coronary vessel wall

The large epicardial coronary arteries and veins span the surface of the heart and gradually penetrate into the myocardium. It has recently been shown that remodeling of the epicardial veins in response to pressure overload strongly depends on the degree of myocardial support. The nontethered regions of the vessel wall show significant intimal hyperplasia compared with the tethered regions. Our hypothesis is that such circumferentially nonuniform structural adaptation in the vessel wall is due to nonuniform wall stress and strain. Transmural stress and strain are significantly influenced by the support of the surrounding myocardial tissue, which significantly limits distension of the vessel. In this finite-element study, we modeled the nonuniform support by embedding the left anterior descending artery into the myocardium to different depths and analyzed deformation and strain in the vessel wall. Circumferential wall strain was much higher in the untethered than tethered region at physiological pressure. On the basis of the hypothesis that elevated wall strain is the stimulus for remodeling, the simulation results suggest that large epicardial coronary vessels have a greater tendency to become thicker in the absence of myocardial constraint. This study provides a mechanical basis for understanding the local growth and remodeling of vessels subjected to various degrees of surrounding tissue.     

Myocardial blood flow regulation relative to left ventricle pressure and volume in anesthetized dogs

The influence of left ventricle pressure and volume changes on coronary blood flow was investigated in eight anesthetized dogs. Coronary artery pressure-flow relationships were determined at two levels of left ventricular pressure and volume. The distribution of blood flow within the myocardium was also determined when these relationships varied. Reducing left ventricle pressures and volumes increased heart rate. Rate-pressure product, diastolic coronary pressure, myocardial O2 consumption, total, subendocardial and subepicardial flow decreased. Hematocrit and blood gas data were unchanged. The pressure-flow relationships were shifted leftward (p = 0.001) but the range of autoregulation was not altered. At low left ventricle pressures and volumes, the lower coronary artery pressure limit was shifted leftward (from 75 to 45 mm Hg (1 mm Hg = 133.3 Pa)), while total, subendocardial, and subepicardial blood flow did not change compared with the control. Below the lower coronary artery pressure limit, subendocardial but not subepicardial flow decreased, resulting in maldistribution of flow across the left ventricular wall. When coronary pressure was reset between control and the lower coronary artery pressure limit, subendocardial flow was restored. These results show that the lower coronary artery pressure limit can be shifted leftward while the distribution of blood flow across the left ventricular wall is preserved.     

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.     

Study of the evolution of the shear stress on the restenosis after coronary angioplasty

In this article, we analyze the influence of fluid dynamics variables on the development of obstructive coronary artery disease in the medium term after percutaneous coronary intervention with stent implantation. We have analyzed a group of seven patients and the study is focused on the mid-right coronary artery. In these patients we have studied the relationship between wall shear stress and arterial wall thickness both immediately after stent implantation and six months later. The realistic three-dimensional (3D) reconstruction of the arteries is performed with the data obtained with intravascular ultrasound (IVUS) and angiography. The commercial code Fluent is used to solve the Navier-Stokes equations. Special attention is paid to the shear stress on the wall arteries and the corresponding thickness. The results show that there is a negative correlation for most of the cases between the wall shear stress and increase in wall thickness. A model is proposed to study the instability at the wall, and qualitative agreement is found.     

The Anatomy of the Circulatory System in the Arminid Nudibranch Armina maculata Rafinesque, 1814 (Gastropoda: Opisthobranchia)

In Armina maculata the heart lies anteriorly and has a large muscular ventricle and a delicate auricle running obliquely to the antero-posterior axis. The auriculoventricular valve and the aortic valve are disposed at the anterior end of the auricle and ventricle respectively. The aortic trunk is located just anterior to the ventricle and gives off several arteries, which extend through the whole body. The main arteries are: the cephalic artery (to the buccal apparatus); the posterior artery (to the notum, digestive glands, ovotestis and renal chamber); the pedal artery (to the foot); and the genital arteries (supplying the different organs of the reproductive system). These data are compared with those of other arminacean species.     

Arterial supply of the atrio-ventricular bundle and its right branch by the first diagonal artery: a dual vascularization

A case is described in which a septal artery originating from the first artery contributed to the vascular supply of the atrio-ventricular bundle, its right branch, the moderator band and the anterior papillary muscle of the right ventricle. Postmortem coronary angiograms and microdissection were use to determine the course of the arteries. The different patterns of origin of the anterior septal arteries were reviewed, and the role of these arteries as an anastomotic route in situations of proximal stenosis of the anterior interventricular artery is discussed.