Cardiovascular System Kaplan

[Malva Ferster]

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Purpose of review: The mechanisms leading to the development of premature atherosclerosis and vascular injury in systemic lupus erythematosus (SLE) remain to be fully elucidated. This is a comprehensive review of recent research developments related to the understanding of cardiovascular disease (CVD) in lupus.

Recent findings: SLE patients with lupus nephritis display significantly increased risk of myocardial infarction and CVD mortality than SLE patients without lupus nephritis. SLE disease-related parameters could be taken into consideration when calculating CVD risks. The type I interferon pathway is detrimental to the vasculature and may contribute to the development of insulin resistance. The level of low-density granulocytes, a distinct subset of proinflammatory neutrophils present in SLE, was independently associated with coronary plaque burden and endothelial dysfunction. Invariant natural killer T cells may promote an atheroprotective effect in SLE patients with asymptomatic atherosclerotic plaques. Oxidized lupus high-density lipoprotein promotes proinflammatory responses in macrophages.

Summary: Recent discoveries have further strengthened the critical role of SLE-related immune dysregulation and metabolic disturbances in promoting accelerated CVD. Understanding how these pathogenic factors promote vascular injury may provide better molecular candidates for therapeutic targeting, and ultimately to improve CVD outcomes.

Researchers led by a team at NIH have identified a potential treatment to reduce the risk of cardiovascular disease in people with systemic lupus erythematosus (SLE), a chronic autoimmune disease. The researchers examined the effects of tofacitinib, an anti-inflammatory drug, on 30 people diagnosed with SLE, which is often referred to as lupus. The study appeared in the journal Nature Communications.

The findings suggest that short-term use of tofacitinib is not only safe with no serious side effects, but also appears to lower some of the risk factors associated with cardiovascular disease in people with lupus.

Low-density granulocytes have a higher propensity to form structures known as neutrophil extracellular traps, or NETs. The body uses NETs to fight infection, but the structures are also thought to contribute to cardiovascular disease and lupus.

Lupus is also associated with overproduction of cytokines and interferons, molecules that allow communication between immune cells. The signals provided by cytokines and interferons are transmitted within cells by JAKs and STATs. JAK refers to Janus kinase while STAT stands for signal transducer and activator of transcription. Genomewide association studies previously performed by NIH scientists have identified a variation of a gene called STAT4 that is associated with lupus. The JAK/STAT pathway has also been implicated in NET formation.

Tofacitinib is a Janus kinase inhibitor developed in the 1990s by Pfizer in partnership with NIH. Developed for the treatment of rheumatoid arthritis, the drug is now approved for other inflammatory diseases such as psoriatic arthritis, juvenile arthritis and ulcerative colitis.

NIH researchers from NIAMS, the National Heart, Lung, and Blood Institute (NHLBI), NIH Clinical Center, the Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation contributed to this study.

The graph shows two sets of cardiovascular function curves. The solid lines describe the cardiovascular performance of a 60-year-old man, with point "N" indicating normal resting conditions. The two broken lines describe cardiovascular performance in the same man six months after he suffered a myocardial infarction. Auscultation of his chest reveals moderate rales bilaterally.

This patient is in congestive heart failure following his myocardial infarction (MI). MI results in death of myocytes, which reduces overall myocardial contractility. The cardiovascular function curve shifts downward and to the right, reflecting the heart's reduced ability to generate output at any given preload.

In the days and weeks that follow, the renin-angiotensin-aldosterone system (RAAS) promotes salt and water retention, which increases extracellular fluid (ECF) volume (plasma is an ECF component) to increase left ventricular preload and thereby help support CO.

The patient's resting CO is below normal for his age and body size, reflecting the effects of MI on cardiac performance. His MSP is elevated to +11 mm Hg (normal MSP is +7 mm Hg) as a result of salt and water retention. The increased blood volume increases central venous pressure and enhances LV preload.

Welcome to the Cardiology Service at the UC Davis Veterinary Medical Teaching Hospital. Our team in Davis consists of three board-certified faculty veterinarians, five resident veterinarians training to be cardiology specialists, and technical staff dedicated to providing compassionate, state-of-the-art diagnostic and treatment services to animals with cardiovascular disease. We also have two cardiologists at our satellite facility in San Diego.

The majority of our patients are dogs and cats, but we regularly examine horses and exotic pets like birds, reptiles, small mammals and zoo animals. Although many pets are referred to us by primary care veterinarians, anyone may request an appointment for their animal to be examined. Common reasons for cardiac examination in animals include heart murmurs, irregular heartbeats, respiratory complaints, and weakness or fainting. Because heart problems are common in older dogs and cats with other medical problems, we also perform many examinations on animals admitted to other services in the hospital (internal medicine, surgery, etc.), many of which are requested as part of a pre-operative evaluation.

The majority of animals can be completely evaluated using only non-invasive examination methods. We also offer minimally invasive (catheter-based) interventions to repair or improve certain congenital heart defects, and we have extensive experience implanting cardiac pacemakers in dogs with abnormally slow heart beats.

Physical Examination and Consultation

All examinations begin with the owner and animal in an examination room. First, the reason for the animal's visit, the history of the problem, and any previous evaluation or treatment is discussed. This is followed by a cardiac physical examination. The examination may include examination of the animal's mouth or eye membrane color, the large veins in the neck, the palpable heartbeat on the chest, and the arterial pulse, but always includes listening carefully to the heart and lungs. In addition to a resident-in-training and/or faculty doctor, 4th (final) year veterinary students are involved in every examination as part of their two-week clinical training in cardiology. Following the examination, the probable diagnosis or most common possibilities are discussed, as well as the choices of additional recommended diagnostic techniques. Most evaluations can be completed in a few hours, after which a second meeting with the owner is held to discuss the findings and recommendations. Any questions from an owner or agent are discussed, and a written summary of findings and recommendations are provided. If the animal was referred by a primary care veterinarian, they are notified of the visit by telephone as well as a written summary of the examination results and treatment recommendations. One of our goals is to involve the owner in all discussions and decisions and to help educate them and have them understand all available options for treatment.

Blood Pressure Recording

Although arterial hypertension (high blood pressure) is not as common in animals as it is in humans, arterial pressure is measured routinely in many patients, especially those with other medical conditions known to be associated with high blood pressure (kidney disease, thyroid or adrenal gland disease, etc.), and in patients where high blood pressure may be suspected from an echocardiogram. The technique is very similar to that used in humans, involving an inflatable cuff placed around a limb and a monitor to detect flow in the artery within the cuff. Proper technique is critical and the patient must be as relaxed as possible. Dogs and cats with high blood pressure may be prescribed some of the same blood pressure lowering drugs that are used in humans.

In some patients it may be necessary to perform more invasive procedures for diagnosis and treatment of a heart condition. In the cardiac catheterization & intervention lab, catheters are inserted into blood vessels of anesthetized patients and are guided through the heart using fluoroscopic radiography.

Pressure and other data may be recorded in the various heart chambers and adjacent blood vessels, and contrast dye visible to the fluoroscope can be injected to outline the heart chambers and large blood vessels to identify defects. Most animals come to the cath lab, however, for one of three common interventional procedures performed to correct or improve certain specific heart condition

Electrocardiography (resting)

A resting electrocardiogram (ECG or EKG) is performed on many animals with heart disease. The ECG is a graphic recording of electrical potentials that develop on the external surface of the body as a result of the electrical activity of the heart. Every heart beat begins with an electrical signal that is conducted through the heart and stimulated the heart muscle to contract. Because the normal pattern of initiation and conduction through the heart is consistent from beat to beat, the normal pattern on the body surface is also consistent. The ECG is used primarily to evaluate and identify the electrical heart rhythm and to identify abnormal beats (arrhythmias) or abnormally conducted beats (heart block, bundle branch block). It is the only way to rapidly identify such electrical abnormalities, which may cause an abnormally rapid, slow, or irregular heart beat and pulse.

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