Coronary arteriosclerosis in salmon: growing old or growing fast?

A review is presented of what we know and what we suspect regarding the formation of coronary arteriosclerotic lesions in salmonids. Coronary lesions are a fact of life for both Atlantic and Pacific species of migrating salmon. Severe forms of lesions, usually restricted to the main coronary artery, are typically found in the majority of a salmon population when they are spawning. Vascular injury to the coronary artery, as a result of the bulbus arteriosus being excessively distended, is proposed as an initiating mechanism for coronary lesion formation, possibly explaining why severe lesions are restricted primarily to the main coronary artery. Evidence is presented that coronary arteriosclerosis in salmonids develops in immature fish, well before maturation, and progresses with age. Growth and growth rate are implicated in lesion progression. A faster growth rate could produce a more stressful life style, which in turn initiates more coronary vascular injury. Dietary factors, especially polyunsaturated fatty acids (and their metabolites), can significantly stimulate vascular smooth muscle proliferation in the salmon coronary artery, but a possible linkage to the progression of coronary lesions has yet to be studied. Whether coronary lesions negatively impact blood flow to the salmon heart has not been properly studied. Nevertheless, the coronary blood supply to the heart has functional importance when salmon exercise and the coronary flow reserve may be reached when fish swim under mild hypoxic conditions. If coronary arterial lesions do adversely affect blood flow to the heart, the selective effects would be most prominent in years when upstream migration conditions are particularly severe.     

Debate: at what level of coronary heart disease risk should a statin be prescribed?

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are effective treatments for the primary and secondary prevention of coronary heart disease, but an outstanding issue is determining who should have such treatment. The benefit from treatment with statins appears to be proportional to the underlying risk of coronary heart disease and independent of the factors increasing risk. Most benefit will therefore be achieved by treating people at increased risk of coronary heart disease. Statins reduce coronary morbidity even when the risk of coronary heart disease is relatively low (6% over 10 years), but reduction in all-cause mortality, the true measure of safety has been shown only when the risk of a major coronary heart disease event is 15% over 10 years or greater. At this level of risk patients appear willing to take treatment to gain the benefit expected from statin treatment, and the cost effectiveness of statin treatment is within the range accepted for other treatments. The major impediments to the systematic introduction of statin treatment at this level of risk are the very high overall cost and the large workload in countries like Britain, where the population risk of coronary heart disease is high. For this reason, recent British guidelines correctly advise statin treatment for secondary prevention and primary prevention when the 10 year coronary heart disease risk is 30% or greater as the first priority, moving to a lower coronary heart disease threshold for primary prevention only when resources permit.     

Cardiac anaphylaxis in isolated guinea pig hearts perfused at constant flow or constant pressure

Acute responses to antigen-antibody interactions (anaphylactic reactions) in isolated guinea pig hearts are reported to include decreases in coronary flow, increases in heart rate, prolongation of impulse propagation, development of arrhythmias, and transient increases followed by substantial decreases in ventricular contractile force. It is not clear from these studies, however, whether all of the changes are direct effects of the mediators released by the antigen-antibody reaction or whether some of them are indirect results of the severe reduction in flow evoked by coronary vasoconstriction. Therefore, the present study was designed to assess cardiac anaphylactic events in isolated hearts of guinea pigs passively sensitized with IgG antibody to ovalbumin under conditions in which coronary perfusion pressure was maintained constant and to compare the responses to those of hearts in which coronary flow was maintained at a constant rate. Our data indicate that when coronary flow decreased during anaphylaxis (constant pressure perfusion), hearts responded to antigen challenge with greater prolongation of the PR interval, duration of arrhythmias, suppression of left ventricular systolic pressure, and release of histamine and adenosine plus inosine into the venous effluent than when coronary flow was maintained during anaphylaxis (constant flow perfusion). The data suggest that maintenance of coronary flow during cardiac anaphylaxis may attenuate the severity of the functional derangement.     

Morphological arrangement of the coronary vasculature in a shark (Squalus sucklei) and a teleost (Oncorhynchus mykiss)

The coronary circulation is of great importance in maintaining cardiovascular function and consequently it has been extensively studied in many mammalian species. However, much less attention has been paid to the coronary circulation in other vertebrates. For example, while elasmobranch fishes are of special interest as they are the most ancient lineage of vertebrates to possess a coronary circulation, only qualitative studies exist on their coronary circulation and most concern the architecture of the large arteries. Our study tested the prediction that the coronary circulation of sharks is better developed than previously thought. However, to test this idea, a methodology was needed to quantify vascularity, vessel morphology and oxygen diffusion distances in a heart with predominantly spongy myocardium. Here, we describe this methodology using dogfish and rainbow trout and suggest that the dogfish spongy myocardium appears to rely predominantly on the coronary circulation for its oxygen supply, an arrangement that contrasts with the spongy myocardial tissue of rainbow trout. In support of this suggestion, the density of the microvasculature of the spongy myocardial tissue of dogfish exceeded that of their compact tissue. Although vascularity in the compact myocardium of dogfish was significantly lower than trout, intervascular distances were similar on account of a significantly larger vessel diameter in dogfish, which corresponds to a larger red blood cell size of the dogfish when compared to trout. J. Morphol. 277:896–905, 2016. © 2016 Wiley Periodicals, Inc.     

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.     

Biomechanical signals in the coronary artery triggering the metabolic processes during cardiac overload

Peculiarities in structure and deformability of epicardial conduit coronary arteries are described. The thin wall of animal coronary artery contrasts the human coronary artery in which the remarkable wall thickness is due namely by the intima thickness. Deformation in length and diameter of conduit coronary arteries, due to the left and right ventricle volume increase, has been defined in non-beating canine heart. Ramus interventricularis anterior being firmly tethered to the myocardium undergoes about 3 times larger deformation than ramus circumflexus In anaesthetized dogs a 30% increase in blood pressure, elicited by aortic constriction, induces an increase in diameter of coronary artery, in segment lenght, in blood flow and consequently in shear stress which represents a load for circumferentially running smooth muscle bundles, longitudinally running smooth muscle bundles, as well as for the endothelium. The above load lasting 4 h is already reflected by an increase in total RNA content and [¹⁴C] leucin incorporation in the left ventricle myocardium in the wall of ramus interventricularis anterior, not in ramus circumflexus. The finding fit completely with the different range of deformation of both the above coronary branches and indicates an increase in proteosynthesis not only in myocardium, but in ramus interventricularis anterior as well. An increase in ornithindecarboxylase activity in coronary wall leading to an increase in biogenic polyamines, is present in the case only, when blood pressure increase is induced by infusion of noradrenaline.     

La tomoscintigraphie myocardique

In the last years, cardiac imaging has dramatically developed, with the generalization of ECG-gated myocardial tomoscintigraphy (MTS) for nuclear cardiology, but also with the precise assessments of cardiac function and of infarction sequels, which are now provided by cardiac MRI, and with the development of coronary angiography by multi-slices CT. In this setting, MTS remains, however, the reference imaging technique for assessing myocardial ischemia, especially at exercise, the sole stress method which is physiologic and which results may be extrapolated to daily-life conditions. Because of this specific property, MTS should remain a major investigation for assessing and following patients with chronic coronary artery disease in the future. The assessment of myocardial ischemia at stress remains unanimously recommended before any invasive therapeutic or diagnostic intervention, when patients are not or only poorly symptomatic. However, it is also likely that this technique will markedly change in the future. Considerable efforts are indeed dedicated to research and development for hybrid recording systems, PET tracers and PET cameras, and gamma detectors systems using semi-conductors.     

The coronary bed and its role in the cardiovascular system: a review and an introductory single-branch model

To investigate cardiovascular haemodynamics under normal and pathological conditions, a closed-loop model of the cardiovascular system already presented in the literature¹, has been complemented by a model of the coronary bed. Oxygen available to the myocardium is strictly related to the coronary blood flow; we have developed threshold criteria which correlate cardiac output with the coronary flow. The system utilizes control systems related to the cardiac contractility and frequency, and imitates feedback mechanisms peculiar to the heart. The work exemplifies the autoregulation of events that occur when the equilibrium of the system is disturbed. It is suggested that the heart plays an active role in trying to restore the haemodynamic parameters to their physiological values.     

Exercise testing and training in patients with peripheral vascular disease and lower extremity amputation.

Patients with peripheral vascular disease have a high risk of coronary artery disease. The risk is even greater when the peripheral vascular disease leads to lower extremity amputation. Exercise testing using lower extremity exercise has been the "gold standard" for screening for coronary artery disease, but many patients with peripheral vascular disease and those with amputations have difficulty doing this type of exercise. Arm exercise ergometry has been shown to be a safe and effective alternative for the detection of coronary artery disease in patients who cannot do leg exercise. This test has also been used to determine safe exercise levels and may be able to predict the ultimate level of prosthetic use in amputees. Exercise training with arm ergometry also improves cardiovascular efficiency and upper body strength in poorly conditioned patients. Studies are needed to appreciate fully the role of exercise testing and training in the recovery of these patients after amputation.     

Serum lipoproteins,lipid peroxides and prostacyclin biosynthesis in patients with coronary hear diseases

Serum low-density lipoproteins (LDL)_and high-density lipoproteins (HDL) were prepared by gradient ultracentrifugation and dialysis from 12 healthy subjects and 15 patients with coronary heart disease and hyperlipoproteinemia. In both lipoprotein fractions cholesterol and lipid peroxides were determined. The effect of these lipoproteins on spontaneous prostacyclin biosynthesis in rat aortic slices was studied.Serum lipoproteins were susceptible to peroxidation during the preparation procedure. LDL were more prone to peroxidation than HDL. Little lipid peroxidase were formed in lipoproteins when calcium ions had been removed by EDTA, and when butylated hydroxytoluene (BHT) was present at all stages of their preparation. LDL when prepared without these precautions either from healthy subjects or from patients with coronary heart diseases markedly suppressed prostacyclin generation by rat aortic slices. This inhibition to LDL-lipid peroxides. Peroxide-low LDL prepared from most of the healthy subjects and patients with coronary heart disease and concomitant hyperlipoproteinemia, did not inhibit prostacyclin biosynthesis. However, in one quarter of the patients. LDL was inhibitory. Consequently, in some patients with coronary heart disease, there operate unknown mechanisms which are responsible for the inhbibitory activity of LDL on prosctacylin generation.     

Anticoagulant Therapy in Coronary Artery Disease: A Therapeutic Enigma

The authors'' experience with anticoagulant therapy in both the acute phase and the long-term management of myocardial infarction has proved disappointing. A review of the literature has failed to establish benefit when all patients with coronary artery disease are treated with anticoagulant drugs. A need for well-controlled studies still exists.     

犬冠状动脉狭窄时血浆纤维连接蛋白的消耗

在实验犬上,观察了冠状动脉狭窄对冠状窦静脉血血浆纤维连接蛋白(Fn)含量的变化。结果表明:当冠脉狭窄程度大于75％时,冠状动脉狭窄可引起冠脉急性炎症反应和Fn的减少,此时伴有血小板聚集性和活性的增高。组织病理学检查证实有血管内皮细胞和毛细血管的损伤以及白细胞、血小板的沉积。 这一结果提示冠脉损伤后可引起冠脉循环中防御功能的减弱。     

Current clinical laboratory practice: investigation of plasma lipids--which tests and when?

Clinical interest in the lipoproteins stems mainly from the association between serum cholesterol concentrations and coronary heart disease. Investigations of lipoproteins should be performed in patients with premature coronary heart disease, with a strong family history of coronary heart disease, or with certain cutaneous stigmata of hyperlipoproteinaemia and when fasting serum samples are seen to be lipaemic. Family studies should be performed in appropriate cases to identify relatives at increased risk of developing coronary heart disease. Patients with conditions known to cause secondary hyperlipoproteinaemia should be investigated if they fall into one of these categories but only after treatment of the underlying condition. Non-specialist laboratories should be able to measure total cholesterol and triglyceride concentrations and high density lipoprotein cholesterol concentrations. Lipoprotein electrophoresis has a limited role in such laboratories and is not necessary as a routine procedure. Specialist laboratories should in addition be able to measure individual lipoproteins and identify apolipoprotein E phenotypes.     

Noninvasive visualisation of coronary atherosclerosis with multislice computed tomography

Computed Tomography (Electron Beam Tomography: EBCT and multislice computed tomography: MSCT) have recently emerged as non-invasive diagnostic modalities that can quantify coronary calcium which is not only as indicator of coronary risk, but also permits assessment of the coronary lumen. The 16-slice MS-CT, the most recent CT-scanner has a very high resolution, which allows non-invasive assessment of coronary plaques. This has led to a stimulus for further research to assess the role of MSCT coronary plaque imaging in the identification of high-risk coronary plaques.     

Soluble thrombomodulin and coronary heart disease

PURPOSE OF REVIEW: Endothelial thrombomodulin is a major vasoprotective molecule. The membrane thrombomodulin is digested by proteases and the degradation products are detectable in circulating blood. The purpose of this review is to provide recent information regarding the relationship of soluble thrombomodulin with coronary heart disease. RECENT FINDINGS: Results from a population-based, prospective, coronary heart disease, case-cohort study reveal an inverse relationship between plasma soluble thrombomodulin and the relative risk of coronary heart disease. Participants in this study were healthy subjects without acute thrombotic events. They were followed, and coronary heart disease events were ascertained. Individuals with a high level of soluble thrombomodulin are associated with a significant reduction in the relative risk of coronary heart disease events. There is a significant interaction between soluble thrombomodulin and soluble intercellular adhesion molecule-1 in predicting the risk of coronary heart disease events. Individuals with a high soluble thrombomodulin level do not have an increased risk of coronary heart disease, even when soluble intercellular adhesion molecule-1 is at the highest levels. In contrast, at low soluble thrombomodulin levels, soluble intercellular adhesion molecule-1 has a 'dose-dependent' association with coronary heart disease risk. These results suggest an interplay between vasoprotective and pro-inflammatory endothelial molecules. Soluble thrombomodulin and its parent molecule appear to play a predominant role in determinations of the risk of coronary heart disease events. SUMMARY: The soluble thrombomodulin level in plasma is an independent risk factor for coronary heart disease. It is inversely associated with coronary heart disease risk. Combinatorial analysis of soluble thrombomodulin and soluble intercellular adhesion molecule-1 provides a more specific assessment of coronary heart disease risk in middle-aged subjects.     

Qualitative and quantitative description of myocardial ischemia by means of magnetocardiography.

In the framework of this study quantitative parameters are presented which, derived from magnetocardiographic maps, aid in making a conclusion about ischemia in the myocardium. The analysis is based on the examination of 86 patients with unstable angina, of which 53 exhibited myocardial ischemia with high probability (Group I: angiographically proven stenosis of at least 50% in a coronary artery of first or second order and positive troponin), while in the 33 other patients myocardial ischemia could be ruled out with high probability (Group II: angiographically clean coronary bed and normal troponin values). The negative predictive value (the probability that there is no myocardial ischemia when the magnetocardiogram (MCG) is negative) is 96.2%; the positive predictive value (the probability that there is actually coronary heart disease when the magnetocardiogram is positive) is 91.2%. A 12-lead ECG taken at the same time as the MCG achieved a positive predictive value of 92.8%, but a negative predictive value of 53.4%. Consequently, the boundary values of the parameters selected lead to a markedly distinct separation between patients with myocardial ischemia from those without. For ruling out coronary heart disease in patients with unstable angina the MCG is superior to 12-lead ECG.     

Nutritional properties of trans fatty acids

The role of trans fatty acids (TFA) present in partially hydrogenated fats widely consumed in food and their link with coronary heart disease has been examined in this review. Most of the studies carried out have been on the effects of TFA on blood-lipid profile. The perceived effects of TFA intake depend on the fat or oil with which they are compared and appears to be in between that of dietary saturated fats and monounsaturated fatty acids. When compared to saturated fat, TFA intake shows lower levels of total and LDL-cholesterol in blood. But when both TFA and saturated fatty acids are compared with cis fatty acids or native unhydrogenated oil, increase in total and LDL-cholesterol are noted. The effects of TFA on HDL-cholesterol and Lp(a) are not clearly established. The undesirable effects of TFA can be overcome by inclusion of essential fatty acids at a minimum of 2 energy per cent level in the diet. The link between trans fatty acid intake and coronary heart disease (CHD) are not unequivocally established.     

The mechanism of beta-adrenergic receptor blockade-induced elevation of arterial blood pressure in rats

Beta-adrenergic blockade increases peripheral vascular resistances acutely and paradoxically lowers arterial blood pressure in most species but not in the rat. In this study the hypothesis has been tested of a significant participation of unopposed alpha-adrenergic mediated vasoconstriction following beta-adrenergic blockade in blood pressure regulation of conscious rats. Alpha-adrenergic blockade in propranolol-pretreated rats significantly decreased mean arterial blood pressure by 22%, heart rate by 20%, and total peripheral resistance by 14% when compared to rats treated only with propranolol, whereas cardiac output was similar in the two groups. A significant 28% reduction of coronary blood flow in rats treated with alpha- and beta-adrenergic blockers, when compared to rats treated only with propranolol, is most likely related to phentolamine's indirect effects on the coronary vasculature. Cerebrovascular and renovascular resistances were similar in these groups. All changes reported were significant at the 95% confidence level. It is concluded that the mechanism of increased blood pressure following beta-adrenergic blockade in rats is related at least in part to unmasking of unopposed alpha-receptor tone, which, however, is minimal in the coronary, cerebral and renal circulations.     

Matching coronary blood flow to myocardial oxygen consumption.

At rest the myocardium extracts approximately 75% of the oxygen delivered by coronary blood flow. Thus there is little extraction reserve when myocardial oxygen consumption is augmented severalfold during exercise. There are local metabolic feedback and sympathetic feedforward control mechanisms that match coronary blood flow to myocardial oxygen consumption. Despite intensive research the local feedback control mechanism remains unknown. Physiological local metabolic control is not due to adenosine, ATP-dependent K(+) channels, nitric oxide, prostaglandins, or inhibition of endothelin. Adenosine and ATP-dependent K(+) channels are involved in pathophysiological ischemic or hypoxic coronary dilation and myocardial protection during ischemia. Sympathetic beta-adrenoceptor-mediated feedforward arteriolar vasodilation contributes approximately 25% of the increase in coronary blood flow during exercise. Sympathetic alpha-adrenoceptor-mediated vasoconstriction in medium and large coronary arteries during exercise helps maintain blood flow to the vulnerable subendocardium when cardiac contractility, heart rate, and myocardial oxygen consumption are high. In conclusion, several potential mediators of local metabolic control of the coronary circulation have been evaluated without success. More research is needed.     

A Device for Performing Automated Balloon Catheter Inflation Ischemia Studies

Coronary collateral growth (arteriogenesis) is a physiological adaptive response to transient and repetitive occlusion of major coronary arteries in which small arterioles (native collaterals) with minimal to no blood flow remodel into larger conduit arteries capable of supplying adequate perfusion to tissue distal to the site of occlusion. The ability to reliably and reproducibly mimic transient, repetitive coronary artery occlusion (ischemia) in animal models is critical to the development of therapies to restore coronary collateral development in type II diabetes and the metabolic syndrome. Current animal models for repetitive coronary artery occlusion implement a pneumatic occluder (balloon) that is secured onto the surface of the heart with the suture, which is inflated manually, via a catheter connected to syringe, to effect occlusion of the left anterior descending coronary artery (LAD). This method, although effective, presents complications in terms of reproducibility and practicality. To address these limitations, we have designed a device for automated, transient inflation of balloon catheters in coronary artery occlusion models. This device allows repeated, consistent inflation (to either specified pressure or volume) and the capability for implementing very complex, month-long protocols. This system has significantly increased the reproducibility of coronary collateral growth studies in our laboratory, resulting in a significant decrease in the numbers of animals needed to complete each study while relieving laboratory personnel from the burden of extra working hours and enabling us to continue studies over periods when we previously could not. In this paper, we present all details necessary for construction and operation of the inflator. In addition, all of the components for this device are commercially available and economical (Table S1). It is our hope that the adoption of automated balloon catheter inflation protocols will improve the experimental reliability of transient ischemia studies at many research institutions.