Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0264733 (ventricular dilatation)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of the renin-angiotensin-aldosterone system (RAAS) in left ventricular systolic dysfunction is a critically important determinant in the pathophysiologic processes that lead to progression of heart failure and sudden death. Angiotensin II, acting at the specific angiotensin receptor (AT1-R), activates a series of intracellular signaling sequences which are ultimately expressed within the cardiovascular system as vasoconstriction and associated vascular hypertrophy and remodeling. Angiotensin converting enzyme (ACE) inhibition leads to increases in the vasodilatory peptides bradykinin and substance P and at least an initial reduction in angiotensin II concentrations. AT1-R blocking drugs prevent access of angiotensin II to the AT1-R and thus prevent cellular activation. ACE inhibitors have clearly been demonstrated through a large number of clinical trials to increase survival in congestive heart failure, primarily by reducing the rate of progression of left ventricular dilatation and decompensation. However, this beneficial effect diminishes over time. Preliminary short-term clinical studies evaluating the efficacy of AT1-R blocking drugs in the treatment of heart failure have suggested that they elicit similar hemodynamic and neuroendocrine effects as do the ACE inhibitors. The combination ACE inhibitors and AT1-R blocking drugs offer the theoretical advantage of increasing bradykinin while blocking the actions of angiotensin II, and thus possibly show a synergistic effect. Again, preliminary studies have yielded encouraging results that are difficult to interpret because neither ACE inhibitor nor the AT1-R blocking drug doses were titrated to tolerance. Pharmacological manipulation of the RAAS has led to better understanding of its role in heart failure and improved clinical outcomes.
Prog Cardiovasc Dis
PMID:Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of heart failure caused by left ventricular systolic dysfunction. 1036 49

Oversized dilatation balloons are recommended for relief of valvar pulmonic stenosis in infants and children during cardiac catheterization. Little information exists about the long-term outcome of this practice. Six of 107 consecutive patients undergoing balloon pulmonary valveplasty developed increasing pulmonary valve incompetence during follow-up periods of 0.5-10 years (mean, 7.2 years). Secondary right ventricular dilatation prompted insertion of a bioprosthetic pulmonary valve in one patient 6.8 years after intervention; valve replacement is pending in two additional patients, 4.3 and 10 years after intervention, respectively; and the three remaining subjects are thought likely to require valve replacement during childhood. The six reported subjects differ from the pulmonary valveplasty group as a whole in that they are younger (median age, 3 days vs. 11 months), had a higher degree of obstruction (right/left ventricular systolic pressure ratio prior to valveplasty 1.28 vs. 0.92), and underwent dilatation with relatively oversized balloons (balloon diameter to pulmonary valve annulus ratio 1.44 vs. 1.08). The balloon diameter to valve annulus ratio did not exceed 1.5 in any subject. Caution is advised in the use of oversized dilatation balloons in neonates or young infants with severe or critical pulmonic stenosis. Long-term consequences of substantial pulmonary valve incompetence outweigh, in our opinion, the limited gradient relief achieved with smaller balloons, sometimes requiring a second dilatation of the valve at an older age and larger size. Cathet. Cardiovasc. Intervent. 48:61-65, 1999.
Catheter Cardiovasc Interv 1999 Sep
PMID:Significant pulmonary valve incompetence following oversize balloon pulmonary valveplasty in small infants: A long-term follow-up study. 1062 85

Vasodilator therapy with nitrates has been used for almost a century to bring relief to patients suffering from angina. The acute anti-ischemic effects of nitro-vasodilators for the treatment and prevention of anginal attacks is unquestioned. In addition, nitrates are administered in order to reduce symptomatic and silent ischemic episodes, in patients with proven coronary heart disease who exert ST segment alterations on Holter monitoring. The reduction in total ischemic burden may result in an improved prognosis with regard to infarct prevention and possible prevention of deterioration of left ventricular function due to repetitive episodes of myocardial ischemia. In patients with unstable angina, administration of nitrates significantly diminishes ischemic episodes and reduces the number of clinically symptomatic anginal attacks. The prevention of left ventricular dilatation in patients within the first few days and months following acute myocardial infarction may be due to the reduced preload. In patients with heart failure, preload reduction with nitrates and afterload reduction with hydralazine was tested versus angiotensin converting enzyme (ACE) inhibitors. However, unfortunately, very few data are available concerning the combination therapy of ACE inhibitors and nitrates in heart failure and following acute myocardial infarction. Long-term continuous administration of high doses of nitrates may cause nitrate tolerance, thus reducing the vasodilator potency of these drugs. Since nitrates were introduced into medical therapy many decades before randomized controlled trials were performed, and evidence-based medicine became the basic principal for medical therapy, there are still indications and situations where the full therapeutic potential of nitrates is not being fully appreciated. During recent decades, other anti-ischemic drugs, i.e., beta-receptor agonists and calcium channel blockers, were introduced into the clinical setting and contributed to an optimized therapy for patients with coronary heart disease. Nevertheless, due to their proven and unsurmounted symptomatic efficacy, nitrates will remain one of the cornerstones of acute and long-term therapy of patients with coronary heart disease far beyond the year 2000.
J Cardiovasc Pharmacol 1999 Aug
PMID:Role of nitrates for the therapy of coronary artery disease patients in the years beyond 2000. 1049 56

Coronary heart disease and beta-blocker treatment can increase the use of the Frank-Starling mechanism during exercise. The aim of the study was to assess whether this could be influenced by physical training. Male patients on beta-blocker treatment after myocardial infarction were randomised to four weeks of training (ET, n = 19) or to a control group (Ctr, n = 18). Cardiac output (CO) at rest and at identical submaximal exercise levels in each patient were determined by radionuclide ventriculography at baseline and after the intervention period. CO was calculated as end diastolic volume (EDV) x ejection fraction x heart rate, and deltaCO and deltaEDV as change in parameter from rest to exercise. The mean (SD) deltaCO decreased from 6.5 (2.1) L/min(-1) to 5.1 (2.4) in ET patients and increased from 5.0 (1.7) to 5.8 (2.7) in Ctr, p = 0.004. deltaEDV decreased from 30 (30) mL to 12 (35) in ET and increased from 11 (20) to 36 (33) in Ctr, p = 0.005. When adjusting for baseline dissimilarities between the groups in a multivariate linear regression analysis, these differences were still statistically significant, p = 0.018 and p = 0.044, respectively. Physical training reduces the CO increase needed to perform identical submaximal exercise, and this is accompanied by less left ventricular dilatation, with a potential for reducing exercise-induced ischaemia.
Scand Cardiovasc J 2000 Jun
PMID:Short-term physical training reduces left ventricular dilatation during exercise soon after myocardial infarction. 1093 71

The degree of clinical expression of both obstructive and nonobstructive hypertrophic cardiomyopathy (HCM) is widely variable. Many patients with HCM are asymptomatic or minimally symptomatic. Most patients with mild or moderate HCM respond well to medical therapy, but medical therapy in patients with severe disease is only marginally beneficial. In some instances, medical therapy can even complicate management by producing significant conduction disturbances. Most symptomatic patients with a significant resting outflow tract gradient may respond to atrioventricular sequential electronic pacing. Most of these patients eventually become symptomatic again, however, because of progression of the disease process or other unknown factors. The outcome of myotomy-myectomy depends greatly on the surgeon's experience with this surgical procedure. In patients with very severe hypertrophy or evidence of left ventricular dilatation and systolic dysfunction, cardiac transplantation should be considered earlier than it would be on the basis of symptoms, functional capacity, and other factors.
Curr Treat Options Cardiovasc Med 1999 Oct
PMID:Hypertrophic Cardiomyopathy. 1109 93

The exact mechanism of mechano-electrical feedback and stretch-induced arrhythmias is unknown, but the role of stretch-activated ion channels and specific calcium channels has been proposed. The aim of the present study was to test the hypothesis that stretch-activated ion channels and not calcium channels contribute to stretch-related alterations of repolarization and that these effects can be neutralized by stretch-activated channel block. We studied the interaction of acute ventricular dilatation and the stretch-activated channel blocker streptomycin and the specific calcium channel blocker verapamil in an isolated retrogradely perfused rabbit heart model in which the left ventricular size is modified by abruptly changing the volume of a fluid-filled balloon placed in the left ventricle. Acute ventricular dilatation led to a rate-dependent decrease in repolarization. The mean effective refractory period (ERP) and monophasic action potential duration (MAP90) for cycle lengths between 300 and 1,000 ms decreased from 174.2+/-9 ms and 178.9+/-7 ms to 161.6+/-11 ms and 169.7+/-5 ms, respectively. Streptomycin (80 microM) inhibited this stretch-related shortening of repolarization (ERP: 175.4+/-8 ms; MAP90: 179.7+/-8 ms, p < 0.05) but had almost no effect on already dilated ventricles. Counteraction of the observed electrophysiologic changes could only be achieved by increasing the streptomycin concentration to 200 microM. Streptomycin nearly completely suppressed stretch-related ectopic ventricular complexes. In contrast, verapamil (1 microM) had no effect on stretch-related changes in repolarization and stretch-induced arrhythmias. The present study indirectly implicates stretch-activated ion channels in the genesis of stretch-related changes in repolarization and arrhythmias. The electrophysiologic changes after ventricular dilatation to a degree that increases left ventricular pressure in a clinically relevant range can be influenced by the stretch-activated channel blocker streptomycin but not by specific calcium channel block. This may have clinically important implications for the development of new antiarrhythmic drugs.
J Cardiovasc Pharmacol 2000 Dec
PMID:Modification of stretch-induced shortening of repolarization by streptomycin in the isolated rabbit heart. 1111 70

Heart failure is an increasing problem because of successful therapies in younger age groups and an overall increase in age in the general population. Ischemic cardiomyopathy secondary to myocardial infarction is the most prevalent entity among the several causes for cardiac failure. Among the surgical options for these patients, neither transplantation nor current ventricular assist devices are able to treat a sufficient number of patients. Ventricular restoration, however, may evolve as a surgical option to treat myocardial failure secondary to postinfarction ventricular dilatation. This procedure must be undertaken in high-risk coronary artery bypass graft (CABG) patients in heart failure. We describe the techniques for both the conventional procedure (CABG +/- mitral valve [MV] repair) using cardioplegic methods, and the beating open heart for surgical anterior ventricular restoration (SAVR) for dyskinetic and akinetic areas in ischemic cardiomyopathies. This combined approach allows safe restoration of the ventricular geometry with minimal use of mechanical support (ie, intra-aortic balloon pump [IABP]) in 195 consecutive patients undergoing this procedure by members of an international team called the RESTORE group.
Semin Thorac Cardiovasc Surg 2001 Jan
PMID:The beating open heart for rebuilding ventricular geometry during surgical anterior restoration. 1130 26

Ischemic mitral regurgitation is functional, and caused predominantly by ventricular dilatation, with secondary functional changes related to annular dilatation, tethering of leaflets from distension, and intraventricular widening between papillary muscles, in the absence of chordal rupture. The treatment includes dealing with the mitral-ventricular interaction by combining surgical ventricular restoration and coronary bypass grafts (CABGs) to alter fiber orientation and muscle nourishment, with annuloplasty, decreasing left ventricle (LV) cavitary volume to reduce abnormal lengthening for tethering, and narrowing the distance between papillary muscles to restore a more normal transverse diameter. These interventions are performed during surgical ventricular restoration (SVR), and the annuloplasty is performed within the ventricle. The cavitary size after SVR must not be restrictive, and methods of patch angulation to restore an elliptic chamber, and interventions to avoid too small a LV cavity are discussed as we summarize 10 years of experience with SVR in 924 patients, and analyze interventions for mitral insufficiency in a recent 3-year subset of 363 patients. The integrated response to the vessel, ventricle, and valve are the central themes of management.
Semin Thorac Cardiovasc Surg 2001 Oct
PMID:Surgical ventricular reconstruction and mitral regurgitation: what have we learned from 10 years of experience? 1180 46

The effect of ACE inhibition after myocardial infarction (MI) on MI healing and remodeling in the presence of hypertension is not exactly known. Therefore, the effect of quinapril on scar formation, remodeling and hemodynamics was studied in spontaneously hypertensive rats (SHR). Nine weeks after moderate and large MI, left ventricular end-diastolic pressure (LVEDP) and passive pressure-volume relations were similar in 28-week-old hypertensive and normotensive rats. Chronic therapy with quinapril (6 mg/kg/day, started 30 min post-MI) reduced LVEDP and LV to body weight ratio, yet did not affect pressure-volume relations. Quinapril increased MI size and reduced the content and brightness of collagen fibers in the scar examined by polarized light microscopy. In conclusion, ventricular dilatation after MI was not accelerated in SHR, probably due to LV hypertrophy. Quinapril produced beneficial hemodynamic effects similar to that observed in the normotensive rat model. The significance and timing of ACE inhibitor-induced impairment of scar formation need further evaluation.
Cardiovasc Pathol
PMID:Ventricular remodeling after myocardial infarction and effects of ACE inhibition on hemodynamics and scar formation in SHR. 1193 99

In the heart, collagens are the major extracellular matrix (ECM) protein. The fibrillar collagens of the heart surround and interconnect myocytes and muscle fibers to provide for muscle fiber and myocyte alignment which imparts mechanical support to the myocardium and governs tissue stiffness. Loss of collagen fibrils and struts are said to lead to myocyte slippage, ventricular dilation, and progressive contractile dysfunction. Failed human hearts examined either at autopsy or explantation invariably exhibit alterations of the ECM primarily due to changes in collagen. Modulation of the balance between matrix synthesis and degradation is important in the process of ventricular remodeling and in the pathophysiology of chronic heart failure. Support for the importance of the ECM and activity of matrix metalloproteinases (MMP) in the development of chronic heart failure has been demonstrated both in animal models of heart disease and in humans. A causative role for the ECM in this process was recently revealed in experiments using a transgenic mouse model that expresses the specific collagen-degrading enzyme, MMP-1, in the heart. These studies demonstrated that chronic expression of MMP-1 leads to dynamic changes in the heart and ultimately results in systolic dysfunction. Multiple studies in animal models have also shown that inhibition of MMP activity in animal models of heart failure have attenuated the onset of left ventricular dilatation. Future studies will determine whether inhibition of MMP activity improves morbidity and mortality in patients with heart failure.
Trends Cardiovasc Med 2002 Apr
PMID:Matrix metalloproteinase disruption of the extracellular matrix and cardiac dysfunction. 1200 33


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