Arteriosclerotic Coronary Disease Research Articles

Abnormal mitochondrial function and morphology in heart transplanted patients with cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) remains the Achilles' heel of long-term survival of HTx patients. Mitochondrial dysfunction has been reported in both arteriosclerotic coronary disease and heart failure. However, myocardial mitochondrial function has not been examined in HTx patients with CAV. 43 HTx patients (21 patients with CAV and 22 patients without CAV) ≥12 months after HTx were enrolled. Endomyocardial biopsies were analyzed using high-resolution respirometry for glucose-coupled mitochondrial respiration. Number and area of mitochondria profiles as well as cristae morphology were assessed by transmission electron microscopy. Echocardiography and coronary angiography were used to measure global longitudinal strain (GLS) and grade CAV. Complex I+II-linked respiration was reduced in patients with CAV compared with patients without CAV (82.7 ± 31.9 pmol O2/(s•mg) vs 116 ± 35.9 pmol O2/(s•mg), p=0.003). Mitochondrial respiratory function measured as oxidative phosphorylation coupling efficiency was positively associated with left ventricular GLS (r=0.49, p=0.002) and negatively associated with elevated biomarkers (Troponin T: r=-0.33, p=0.04 and NT-proBNP: r=-0.41, p=0.009). Mitochondrial profile number and area did not differ. However, patients with CAV had a larger proportion of mitochondria with abnormal cristae morphology (p < 0.001). Myocardial mitochondrial respiration is impaired in patients with CAV and is associated with an abnormal cristae morphology. The mitochondrial dysfunction appears to be associated with reduced myocardial contractile function and elevated biomarkers. These results highlight that mitochondrial targeted treatment in patients with CAV should be assessed in future clinical studies.

Atherosclerosis: analysis of the eNOS (T786C) gene polymorphism.

The coronary arteriosclerotic disease is the most common cardiovascular disease. Atherosclerosis affects large- and medium-sized arteries leading to severe thrombosis or artery stenosis that could evolve to myocardial infarction, ischemic stroke, ischemic injury of kidneys and intestines, and several other life-threatening clinical manifestations. Nitric oxide has been shown to be a promising therapeutic agent against cardiovascular diseases. The eNOS gene assumes several important functions, including regulation of vascular tone and regional blood flow, the suppression of vascular smooth muscle cell proliferation, and modulation of leukocyte-endothelium interactions. The T786C polymorphism is an important point mutation, where thymine is changed to cytosine. T786C significantly reduces the activity of the eNOS promoter gene. Two hundred and ninety-seven peripheral blood samples were collected from patients with the previous diagnosis of atherosclerotic disease based on clinical examination and confirmed by imaging methods. Results were compared using the chi-square test and the G-test. In the present study, the TC genotype was more frequent in both case and control groups with no statistically significant difference. Comparing the relation TC/TT and CC genotypes in the case and control groups, there was no statistically significant difference. No significant difference was found when genotypes were analyzed regarding gender and smoking. Our results suggest a strong tendency of the T allele, in single or double dose, to be associated with atherosclerosis that was not confirmed by the scientific data.

A preliminary analysis of the effect of the new rural cooperative medical scheme on inpatient care at a county hospital

BackgroundChina in 2009 committed to reach universal health coverage by promoting three forms of health insurance; NCMS for the rural population, UEBMI for formally employed urban residents and URBMI for other urban residents. NCMS has expanded to near universal coverage in rural China since launching in 2003. The objective of this study aimed to assess the effect of NCMS on inpatient care utilization from 2003 to 2012 at Longyou county hospital, Zhejiang province.MethodsThe research was conducted at Longyou county, Zhejiang province. All registered inpatient admissions from January 1, 2003, to June 30, 2012, were included in the study. The PLSQL Developer software was used to select the interesting variables in the hospital information database and saved in an Excel 2003 file. The interesting variables included the patients’ general information (name, gender, age, payment method), discharge diagnosis, length of hospital stay, and expenditure (total expenditure and out-of-pocket payment). Two common diseases (coronary arteriosclerotic disease and pneumonia) were selected as tracer conditions.Results292,400 rural residents were enrolled in the Longyou county NCMS by 2011, 95.4% of the eligible population. A total of 145,744 inpatient admissions were registered from 1 January 2003 to 30 June 2012. The proportion of inpatients covered by NCMS increased from 30.3% in 2004 to 54.2% in 2012 while the proportion of inpatients covered by UEBMI increased from 7.7% in 2003 to 14.7% in 2012. The average expenditure for UEBMI insured inpatients was higher than the average for NCMS insured inpatients, although the gap was narrowing. The average length of hospital stay increased every year for all inpatients, but was higher for UEBMI inpatients than for NCMS insured inpatients. For both tracer conditions the results were similar to the above findings.ConclusionsNCMS has improved coverage height for its enrollees and resulted in increased cost of care per inpatient admission at the county hospital. However, wide differences persist between the two insurance systems in coverage height. Both systems are associated with increasing lengths of stay and rising cost per inpatient admission. We found that around 30% of inpatients were not covered by any of the two public health insurance systems, which calls for further studies.

The first Gore-Tex femoral-popliteal bypass

In scientific investigation, “Who’s on First” is often an ongoing debate when it comes to medical discoveries and scientific priority. Surgeons embrace the idea of being first to perform an operation, particularly if history later shines upon it a favorable light. Is it important to be first? The Olympic games initiated by ancient Greeks made heroes out of those who came in first in an event. In a presentation to the 25th Anniversary Veith Symposium on “Firsts” in Vascular Surgery: Who Did What “First,” Rich gave the subject an in-depth examination. He found that history is replete with claims of first. Many of these claims were associated with controversy. Firsts in vascular surgery are numerous. It is generally acknowledged that William Harvey was the first to discover circulation. The Chinese, however, claimed they discovered the concept of blood circulation some 2000 years before Harvey. Similarly, coronary arteriosclerosis is often regarded as a Western disease, yet a recent report has found coronary arteriosclerotic disease existed in China >2200 years ago. Besides “first operations,” there are also “famous operations.” Harold Ellis, in his book Famous Operations, divided the “famous operation” into three types: type I is the breakthrough operation. A type II operation may be insignificant itself, but it marks the introduction of some important point in surgical technique. Finally, the type III operation depends entirely on the patient; the operation itself may be routine, but the patient is a famous person, thus an operation, an act between the surgeon and the patient, does carry extra meaning and significance. Among all first operations, none can surpass the “blue baby” operation by Blalock and Taussig, performed at the Johns Hopkins Hospital on November 29, 1944. To qualify as a first operation, DeBakey emphasized that the

Spontaneous Atherosclerosis in Aged Lipoprotein Lipase–Deficient Mice With Severe Hypertriglyceridemia on a Normal Chow Diet

Large-scale epidemiological studies have revealed a strong association between hypertriglyceridemia and coronary arteriosclerotic disease. However, there are conflicting reports whether the severe hypertriglyceridemia caused by lipoprotein lipase (LPL) deficiency is pro- or antiatherogenic. To determine the effect of LPL deficiency on atherosclerosis, we pursued long-term observation of the development of atherosclerotic lesions in an LPL gene deficient mouse model. At 4 months of age, homozygous LPL-deficient mice exhibited severe hypertriglyceridemia but no signs of aortic atherosclerotic lesions. At >15 months of age, these mice developed foam cell-rich atherosclerotic lesions at the aortic root, whereas wild-type and heterozygous mice were lesion-free at the same age. Further investigation revealed that plasma malondialdehyde levels in >15-month-old LPL-deficient mice were significantly higher than those of heterozygous and wild-type mice. Electron spin resonance analysis showed a marked increase in oxidative susceptibility of chylomicrons from the aged LPL-deficient mice. Incubation of chylomicrons from >15-month-old LPL-deficient mice with cultured human umbilical vein endothelial cells showed significantly increased upregulation of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1, markers of enhanced endothelial activation, and enhanced adherence of human THP-1 mononuclear cells. These results clearly demonstrate the occurrence of spontaneous atherosclerosis in aged LPL-deficient mice mediated by the oxidation of chylomicrons and the activation of vascular endothelial cells.

Unstable angina and non-ST-segment elevation myocardial infarction: analysis of consecutive series of patients and later follow-up

According to world statistics, arteriosclerotic coronary disease has been growing worldwide, receiving special attention in ICUs.

ST-segment elevation myocardial infarction: analysis of consecutive series of patients and later follow-up

Arteriosclerotic coronary disease is one of the leading causes of death worldwide. In order to analyze patients admitted with ST-segment elevation myocardial infarction (STEMI) diagnosis, a databank was established to collect information about the clinical condition and late follow-up.

Effect of Medium-Chain Triglycerides on Postprandial Concentrations of Remnant-Like Particles in Healthy Men.

A high concentration of remnant-like particles (RLP) has shown to be an arteriosclerosis risk factor that strongly reflects disorders of chylomicron and VLDL metabolism in patients with hyperlipidemia. The purpose of this study was to determine the serum concentrations of RLP-cholesterol after intake of meals containing medium-chain triglycerides (MCT) or long-chain triglycerides (LCT) in 29 healthy men. Test meals were prepared by a nationally registered dietitian as a pilaf containing 10 g of MCT or LCT and commercial clear soup. Blood samples were collected at 0, 2, 3, 4, 6 and 8 h after intake of the test meals. The concentrations of serum triglyceride, chylomicrons, chylomicron-triglyceride, RLP-cholesterol, VLDL-cholesterol, and VLDL-triglyceride after intake of MCT were lower than those after intake of the same amount of LCT. Moreover, the areas under the time-concentration curves of triglyceride, chylomicrons and RLP-cholesterol after intake of MCT were significantly lower than those after intake of LCT. The increases in concentrations of serum insulin and total ketone bodies after intake of MCT were significantly greater than those after intake of LCT. These results suggest that MCT may reduce the risk of coronary arteriosclerotic disease by attenuating the postprandial increase of RLP that is closely correlated with arteriosclerosis.

Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10-year follow-up study (the CAFES-CAVE study )

Background: Subclinical arteriosclerotic lesions at the carotid and femoral bifurcations may be related to the occurrence of future cardiovascular events and of occult arteriosclerotic coronary disease. B-mode ultrasound of carotid and femoral arteriosclerotic bifurcation lesions may provide a simple screening method to select asymptomatic subjects at risk of future events. Methods and results: 13 221 low-risk, healthy, asymptomatic individuals were included in a 10-year, prospective, follow-up based on carotid and femoral bifurcation morphology defined by B-mode ultrasound. Four classes were considered at inclusion (I: normal wall, II: wall thickening, III: non-stenosing plaques, IV: stenosing plaques). When 10 000 subjects (75.6% of included subjects; 6055 males, 3945 females) completed the 10-year follow-up the study was concluded. At 10 years there were 10 events (out of 7989 subjects) in class I and 81 events in II (930 subjects; incidence=8.6%); 239 events were observed in class III (611 subjects; 39.28%) and 381 events (470 subjects; 81.06%) in IV; 61 deaths occurred in classes III+IV (1081 subjects) producing a death rate within these two classes of 5.5% (51 out of 61=81.5% in class IV). The increased event rates in classes III and IV were significant (log rank; P<0.02) in comparison with I and II. Conclusions: Carotid and femoral morphology identified 2011 subjects (20.1% of the population) in classes II, III, IV including 98.6% of cardiovascular events and deaths in the following 10 years. A higher ( P<0.05) rate of progression in classes III and IV in comparison with I and II was also observed. The ultrasound carotid and femoral classification was useful in selecting subjects at very low risk of cardiovascular events (class I), those at limited risk (class II) and a group at moderate risk (class III). A subpopulation at high risk of cardiovascular events (IV) was identified.

A Clinical Significance of Blood Glucose Control in Coronary Arteriosclerotic Disease with Abnormal Glucose Tolerance

A Clinical Significance of Blood Glucose Control in Coronary Arteriosclerotic Disease with Abnormal Glucose Tolerance

Unusual case of coronary stenosis caused by an external compression

Endocarditis is a pathology with a high rate of a large abscess that extended from the aortic valve complications, some peripheral, such as the embolizaring to the pulmonary artery and the left atrium which tion and the mycotic aneurysms, and others which are obstructed the outflow of the left coronary artery. The directly related, such as abscess, fistulization or patient died shortly after the operation and in the coronary embolization. necropsy no arteriosclerotic coronary disease was We present the case of a 61-year-old man with no detected. cardiovascular risk factors, and with no previous The abscess is a relatively frequent complication of history of cardiac disease who was admitted to the endocarditis that worsens the prognosis and hospital suffering from acute aortic insufficiency requires surgery in most cases. This complication secondary to pneumococcal aortic endocarditis with favours the fistulization between the cardiac champulmonary edema. bers [1], large vessels [2] or both [3]. On the other The patient was urgently operated on, removing a hand, the thoracic pain during an endocarditis is vegetation of 2 cm in diameter which affected the left usually caused by mechanical complications, an coronary cusp and an abscess which effected the embolism or a coronary obstruction, although on aortic ring. A biological prosthesis was implanted some exceptional occasions the pain could be caused with a good follow-up. by other reasons. In this sense, a case of destruction Several episodes of angina started 11 days later, of the arterial wall and two cases of a external and ST-depression in precordial leads V3–V6 was compression have been reported [4,5]. detected with ECG. The patient also developed signs This patient had a good follow-up after the valve and symptoms of pulmonary oedema. An emergency replacement, but suffered a sudden deterioration with angiocardiography was carried out and in the aortogsevere thoracic pain, probably related to an acute ram, a fistulization from the aortic root to an abscess fistulization and an entering of blood in the abscess (Fig. 1A) adjacent to the left coronary artery was which produced an increase in its volume, pressing seen (Fig. 1B). In the angiography a significant the left coronary artery which caused angina, and stenosis of the left main coronary artery and of the showing severe electrocardiographical changes in the proximal circumflex branch without affecting other ECG. vessels was observed (Fig. 2). This case supports the idea that the hemodynamical The patient was urgently re-operated on, removing disestabilization associated with thoracic pain, and especially when showing changes in the ECG in a patient with endocarditis, could be caused by a direct *Corresponding author. Tel.: 134 8 5106100 Ext. 36261; Fax: 134 8 5274688. effect on the coronary arteries. For this reason, a

1053-2 Cath-Lab Assistant: Integrated Image Analysis and Relational Database Program

Cardiac catheterization techniques deal with large amount of image data from which quantitative parameters are extracted. Our program provides relational database organization and management functions for both images and measurement data. In addition, it integrates database with our previously developed image analysis programs for intravascular ultrasound (IVUS) and coronary angiography. The program runs in Microsoft Windows environment and does not require specialized imaging hardware. Program consists of three functional modules: image database system, IVUS contour extraction/analysis module and coronary angiography contour extraction/analysis module, Image database system provides image retrieval, storage and display together with extracted quantitative data. Each database record includes data on patient administration, medical history and noninvasive test results. User is provided with browse and search controls for database navigation, as well as with query by example and lists and reports generation. Analysis programs are incorporated into the database through OLE (Object Linking and Embedding) technique, which enables user to launch appropriate image analysis program simply by clicking the mouse over the chosen image. Extracted analysis data are automatically stored in the appropriate database record. Furthermore, any other image processing/analysis Windows program that supports OLE and can act as OLE server may be linked with the database by simple Clipboard cut and paste operations. All images and data can be exported to other Windows applications (text processors, spreadsheets, statistical and data presentation software). In practical testing the program proved to be user friendly, interactive and flexible. It was particularly useful for integration of both images and quantitative data obtained by coronary angiography and by IVUS, being helpful in the validation of the latter technique, and providing better insight into the extent and severity of coronary arteriosclerotic disease.

SEQUENTIAL ORTHOTOPIC HEART TRANSPLANTATION IN MAN

Between January 1968 and March 1980, 202 hearts had been transplanted into 185 patients at Stanford University Medical Center. Occasionally, patients after transplantation develop myocardial failure which is amenable only to retransplantation. Sixteen patients underwent initial orthotopic allograft using standard techniques. Eight patients developed accelerated arteriosclerotic coronary disease, six had unrelenting rejection, and two had donor heart dysrrhythmia or right ventricular failure requiring retransplantation. One patient required a third transplant because of donor left ventricular ischemia. All sequential transplants were managed similarly to the primary transplant. Of the initial transplant hearts at risk, 60% survived for more than 1 year, and 57% survived for more than 2 years. These results are similar to those of patients not requiring retransplantation. Of the secondary transplant hearts at risk, 31% survived for more than 1 year and 29% survived for more than 2 years. The severity of infection and/or rejection contributed most significantly to secondary heart transplant mortality. Sequential orthotopic cardiac transplantation offers an acceptable alternative to patients with allograft failure. Survival is not as favorable as with initial transplantation because of the prolonged immunosuppression during sequential transplantation.

Effect of carbocromen induced coronary vasodilatation on myocardial metabolism in coronary artery disease.

Myocardial metabolism was studied during coronary vasodilatation by carbocromen during atrial pacing in patients with coronary arteriosclerotic disease. Coronary sinus flow was measured by the continuous infusion thermodilution technique. Carbocromen increased myocardial flow by the same amount at rest and during pacing-induced tachycardia. The administration of carbocromen did not interfere with myocardial oxygen consumption, free fatty acid (FFA) uptake, pulmonary or systemic hemodynamics. Atrial pacing above the anginal threshold increased lactate and hypoxanthine excretion to the coronary sinus, but to a greater extent during carbocromen treatment. Thus, carbocromen is a specific coronary vasodilator acting independently of pacing induced vasodilatation. Metabolic data indicate a small but unfavourable effect on ischemic metabolism which might be due to a "coronary steal".

Effect of nifedipine (Adalat) on coronary haemodynamics in patients with coronary arteriosclerotic disease.

Effects of the new Ca++ antagonist nifedipine (Adalat) on coronary haemodynamics were studied in 8 patients with documented ischaemic heart disease. The continuous infusion thermodilution technique was used to measure cardiac venous blood flow. Sublingual application of 10 mg nifedipine caused a significant increase (16%) in myocardial blood flow and a decrease (18%) in coronary arteriolar resistance at rest, but not during a submaximal atrial pacing test. There was no change in coronary arteriovenous oxygen difference, myocardial oxygen consumption, oxygen consumption per unit of heart rate blood pressure index or left ventricular efficiency index. The effects on the coronary haemodynamics are discussed in relation to the simultaneous changes in general haemodynamics. Systolic aortic pressure was slightly reduced, significantly only at rest, while peripheral vascular resistance decreased and cardiac output increased also during atrial pacing. No change in free fatty acid metabolism was observed. It is concluded that nifedipine is a mild coronary vasodilator. No effect was observed on myocardial oxygen demand. The oxygen cost of left ventricular work was unchanged by the drug both at rest and during the submaximal stress test.

The treatment of coronary artery disease with disodium EDTA: A reappraisal

At the end of four years of treatment in 10 patients and after one and a half to three years in 28 others, a re-appraisal of the effect of EDTA therapy on arteriosclerotic coronary disease is reported. Whereas after three months of treatment 66 per cent of these 38 patients exhibited improved anginal patterns (their own impressions and measured exercise tolerance) and 40 per cent showed improved electrocardiographic patterns, none of these effects was lasting. At the time of this report 12 of the 38 were dead of their original disease (32%) and only 40 per cent remained clinically improved. At present we believe that chelation as used in this study did not benefit patients more than other commonly used therapeutic methods. It is not a useful clinical tool in the treatment of coronary disease at the present time.

Race and the incidence of acute myocardial infarction; incidence of acute myocardial infarction among autopsies of 9064 white and 8003 Negro patients, with special reference to age, sex, and diabetes mellitus.

In a recent study1-2of the incidence of acute myocardial infarction in white patients among the cases which came to autopsy at Washington University for the period 1910-1954, several striking facts were apparent. The incidence of acute myocardial infarction had increased markedly over the years, especially among elderly women. The relative incidence had changed from two males to one female in the period 1910-1939 to one to one in the period 1940-1954. Because of these findings, we believe a review of many of the established concepts regarding the incidence of the disease entity is indicated. One feature that requires further investigation is the incidence among Negroes. Previous reports3-8from the United States (including a study by one of us)8and Africa9-10documented a much lower occurrence of coronary arteriosclerotic disease and its complications among Negroes. However, some recent reports11-12have suggested a marked increase of