cardiovascular-agents and Dilatation--Pathologic

Aortic aneurysm (AA) remains one of the primary causes of death worldwide. Of the major treatments, prophylactic operative repair is used for AA to avoid potential aortic dissection or rupture. To halt the development of AA and alleviate its progression into aortic dissection, pharmacological treatment has been investigated for years. Currently, β-adrenergic blocking agents, losartan, irbesartan, angiotensin-converting-enzyme inhibitors, statins, antiplatelet agents, doxycycline, and metformin have been investigated as potential candidates for preventing AA progression. However, the paradox between preclinical successes and clinical failures still exists, with no medical therapy currently available for ideally negating the disease progression. This review describes the current drugs used for pharmacological management of AA and their individual potential mechanisms. Preclinical models for drug screening and evaluation are also discussed to gain a better understanding of the underlying pathophysiology and ultimately find new therapeutic targets for AA.

Topics: Animals; Aorta; Aortic Aneurysm; Cardiovascular Agents; Dilatation, Pathologic; Disease Models, Animal; Disease Progression; Humans; Signal Transduction; Treatment Outcome; Vascular Remodeling

Abdominal aortic aneurysm (AAA), a progressive segmental abdominal aortic dilation, is associated with high mortality. AAA is characterized by inflammation, smooth muscle cell (SMC) depletion and extracellular matrix (ECM) degradation. Surgical intervention and endovascular therapy are recommended to prevent rupture of large AAAs. Unfortunately, there is no reliable pharmacological agent available to limit AAA expansion. In the past decades, extensive investigations and a body of ongoing clinical trials aimed at defining potent treatments to inhibit and even regress AAA growth.. In this review, we summarized recent progress of potential strategies, particularly macrolides, tetracyclines, statins, angiotensin converting enzyme inhibitors, angiotensin receptor blocker, corticosteroid, anti-platelet drugs and mast cell stabilizers. We also consider recently identified novel molecular targets, which have potential to be translated into clinical practice in the future.

Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Dilatation, Pathologic; Disease Progression; Humans; Risk Factors; Treatment Outcome

Abdominal aortic aneurysm (AAA) is a vascular disease with high mortality. Because of the lack of effective medications to stop or reverse the progression of AAA, surgical operation has become the most predominant recommendation of treatment for patients. There are many potential mechanisms, including inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, oxidative stress, and so on, involving in AAA pathogenesis. According to those mechanisms, some potential therapeutic drugs have been proposed and tested in animal models and even in clinical trials. This review focuses on recent advances in both pathogenic mechanisms and potential pharmacologic therapies of AAA.

Topics: Age Factors; Aged; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Comorbidity; Dilatation, Pathologic; Female; Humans; Male; Middle Aged; Molecular Targeted Therapy; Risk Factors; Sex Factors; Signal Transduction; Smoking

This review describes ongoing efforts to develop a medical therapy to limit abdominal aortic aneurysm (AAA) growth.. Data from animal model studies, human investigations, and clinical trials are described.. Studies in rodent models and human samples have suggested a number of potential targets for slowing or halting AAA growth. A number of clinical trials are now examining the value of medications targeting some of the pathways identified. These trials have a number of challenges, including identifying medications safe to use in older patients with multiple comorbidities, developing accurate outcome assessments, and minimizing the dropout of patients during the trials. Three recent trials have reported no benefit of the antibiotic doxycycline, a mast cell inhibitor, an angiotensin-converting enzyme inhibitor, or a calcium channel blocker in limiting AAA growth. A number of other trials examining angiotensin receptor blockers, cyclosporine, and an antiplatelet agent are currently underway.. Further refinement of drug discovery pathways and testing paradigms are likely needed to develop effective nonsurgical therapies for AAA.

Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Dilatation, Pathologic; Disease Progression; Drug Discovery; Humans

Isolated coronary artery ectasia (CAE) may be associated with stable or unstable coronary events despite the absence of epicardial coronary stenosis. Impaired coronary flow dynamics and myocardial perfusion have been demonstrated in stable patients with ectatic coronary arteries. We aimed to assess whether epicardial flow and tissue-level perfusion would be improved by diltiazem in myocardial regions subtended by the ectatic coronary arteries in patients with isolated CAE. A total of 60 patients with isolated CAE were identified of 9,780 patients who underwent elective coronary angiography. Patients were randomized to 5 mg of intracoronary diltiazem or saline. Coronary blood flow of the microvascular network was assessed using myocardial blush grade (MBG) technique. The thrombolysis in myocardial infarction (TIMI) flow grade and TIMI frame count (TFC) were used to assess epicardial coronary flow. MBG (from 2.4 to 2.6, p = 0.02), TIMI flow grades (from 2.4 to 2.8, p <0.001), and TFC (from 35 to 26, p <0.001) were significantly improved after diltiazem, whereas no significant change was noticed after saline (from 2.4 to 2.4, p = 0.86 for MBG; from 2.3 to 2.3, p = 0.71 for TIMI flow grade; and from 35 to 33, p = 0.43 for TFC). Diltiazem provided amelioration of the altered coronary flow dynamics, which was suggested as the pathophysiological influence of CAE. In conclusion, the favorable effects of the diltiazem on myocardial perfusion were observed at both epicardial and tissue levels.

Topics: Aged; Angina, Stable; Cardiovascular Agents; Coronary Artery Disease; Coronary Circulation; Dilatation, Pathologic; Diltiazem; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Reperfusion; Pericardium; Prospective Studies; Treatment Outcome

We report two cases of early aneurysmal vessel dilatation after a paclitaxel-coated balloon (PCB) was used for angioplasty of the peripheral vessels. The first case refers to a failing vein bypass with a tight proximal anastomotic stenosis, whereas the second refers to a distal tibial artery occlusion. A PCB was used to treat both patients. Aneurysmal dilatation of the previously treated segment was noted in both patients during subsequent follow-up imaging. In the absence of other causal factors, we attribute both cases to PCB application. The aneurysms that formed had no detrimental effect on the patients' health and required no further treatment; however, it is important to bear in mind this potential risk of presumed paclitaxel toxicity.

Topics: Aged, 80 and over; Aneurysm; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Dilatation, Pathologic; Female; Humans; Male; Middle Aged; Paclitaxel; Radiography; Saphenous Vein; Tibial Arteries; Vascular Access Devices

Volume expansion and inotropic stimulation are used clinically to augment cardiac output during acute right ventricular (RV) pressure overload. We previously showed that a brief period of RV pressure overload causes RV free wall dysfunction that persists after normal loading conditions have been restored. However, the impact of volume expansion and inotropic stimulation on the severity of RV dysfunction after acute pressure overload is unknown. We hypothesized that the severity of RV dysfunction after RV pressure overload would be related to the level of RV free wall systolic stress during RV pressure overload, rather than to the specific interventions used to augment RV function. Chloralose-anesthetized, open-chest pigs were subjected to 1 h of RV pressure overload caused by pulmonary artery constriction, followed by 1 h of recovery after release of pulmonary artery constriction. A wide range of RV free wall systolic stress during RV pressure overload was achieved by either closing or opening the pericardium (to simulate volume expansion) and by administering or not administering dobutamine. The severity of RV free wall dysfunction 1 h after RV pressure overload was strongly and directly correlated with the values of two hemodynamic variables during RV pressure overload: RV free wall area at peak RV systolic pressure (determined by sonomicrometry) and peak RV systolic pressure, two of the major determinants of peak RV free wall systolic stress. Opening or closing the pericardium, and using or not using dobutamine during RV pressure overload, had no independent effects on the severity of RV dysfunction. The findings suggest that the goal of therapeutic intervention during RV pressure overload should be to achieve the required augmentation of cardiac output with the smallest possible increase in RV free wall systolic stress.

Topics: Animals; Atropine; Cardiac Catheterization; Cardiotonic Agents; Cardiovascular Agents; Diastole; Dilatation, Pathologic; Disease Models, Animal; Dobutamine; Female; Heart; Hemodynamics; Hexamethonium; Hypertension; Linear Models; Pericardium; Pulmonary Artery; Swine; Systole; Ventricular Dysfunction, Right