Sudden death and exercise.
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Death, Sudden↗
Biomedical subjects
R Virmani
Publications and source records attributed to R Virmani.
Glutathione redox pathway and reperfusion injury. Effect of N-acetylcysteine on infarct size and ventricular function.
Glutathione peroxidase is an important enzyme in the degradative cascade of reactive oxygen free radicals. N-Acetylcysteine (NAC) is a low molecular weight compound that has been used clinically to replenish glutathione. To assess the role of the glutathione redox pathway on reperfusion injury, 23 animals underwent 90 minutes of proximal left anterior descending coronary artery occlusion followed by 24 hours of reperfusion with the administration of NAC (n = 11) or saline (n = 12) beginning 30 minutes into occlusion and continuing for 3 hours after reperfusion. Regional ventricular function was measured with contrast ventriculography, and regional myocardial blood flow was determined with microspheres. At 24 hours, the area at risk was defined in vivo with Monastral Blue, and the area of necrosis was defined by incubation in triphenyltetrazolium. Biopsies were taken from the ischemic and nonischemic zones to determine levels of total glutathione, superoxide dismutase and glutathione peroxidase activity, and reactivity to thiobarbituric acid, an index of lipid peroxidation. The rate-pressure product and myocardial blood flow were similar in the two groups throughout the study. No significant differences were noted in infarct size expressed as a percentage of the area at risk (28.6 +/- 5.3% vs. 36.6 +/- 6.0%) and of the total left ventricle (14.4 +/- 3.2% vs. 16.5 +/- 3.1%), and no differences were noted between the two groups on examination of the ischemic subendocardium by light and electron microscopy. Both groups exhibited similar degrees of dyskinesis during occlusion; however, treated animals showed significant improvement in regional radial shortening at 3 hours (3.4 +/- 2.4% vs. -2.4 +/- 2.1%, p less than 0.02) and 24 hours (9.2 +/- 2.2% vs. -2.5 +/- 6.3%, p less than 0.001) after reperfusion. No differences were present in total glutathione, thiobarbituric acid reactivity, or superoxide dismutase and glutathione peroxidase activity in the ischemic zones of the two groups. This study suggests that N-acetylcysteine treatment before reperfusion may reduce myocardial stunning but does not limit myocyte death after reperfusion.
Acetylcysteine↗
Ventricular/vascular coupling and regional arterial dynamics in the chronically hypertensive baboon: correlation with cardiovascular structural adaptation.
Ventricular/vascular coupling dynamics and regional hemodynamics of five hypertensive baboons with concentric left ventricular (LV) hypertrophy (mean arterial pressure +/- SD, 148 +/- 16 mm Hg; LV mass/body weight ratio 3.42 +/- 0.8) were compared with five normotensive controls (mean arterial pressure 89 +/- 3 mm Hg; LV mass/body wt ratio 2.73 +/- 0.5) at different mean arterial pressures. Ventricular/vascular dynamics were assessed by aortic input impedance, pulsatile/total power ratio, effective arterial elastance and compliance from a three-element Windkessel "lumped" model of the circulation. Regional arterial dynamics were assessed by pulse-wave velocities and local reflection coefficients. Systemic arterial compliance was similarly decreased with elevated pressure in both groups but was significantly more reduced for the hypertensive group compared with control animals at control (0.49 +/- 0.16 vs. 0.96 +/- 0.09 ml/mm Hg; p less than 0.05) and acutely lowered arterial pressure (0.62 +/- 0.26 vs. 1.41 +/- 0.24 ml/mm Hg, respectively). Changes in compliance were paralleled by differences in effective arterial elastance derived from cineventriculographic pressure-volume ratios. Regional foot-foot and apparent phase pulse-wave velocities were significantly increased for distal aortic segments of the hypertensive animals during elevated pressures compared with controls (cff, 17.5 +/- 7.5 vs. 8.7 +/- 3.0 m/sec; p less than 0.05). Histology of the aorta revealed significant increases in collagen content (microgram/mg dry wt) from proximal to distal aortic segments (27 +/- 2 vs. 38 +/- 6; p less than 0.005) in hypertensive animals but not in controls (27 +/- 2 vs. 32 +/- 6; NS). With pharmacological normalization of systemic arterial pressures, hypertensive baboons developed aortic wave speeds similar to controls but manifested significantly reduced compliance compared with controls. In contrast, with acute elevations of pressure, systemic arterial aortic compliances were similar for both groups, but distal pulse-wave velocities were significantly increased for hypertensive animals compared with controls. We conclude that measures of ventricular/vascular coupling and arterial dynamics are determined by both the level of arterial pressure and the physical characteristics of the cardiovascular system in chronic systemic hypertension and pressure overload ventricular hypertrophy.
Adaptation, Physiological↗
Heterogeneity of pathologic lesions in familial primary pulmonary hypertension.
We analyzed lung specimens from 23 affected members of 13 families with known familial primary pulmonary hypertension. In this heritable disease, the pathogenetic basis of disease should be distinct within families, and the pathologic lesions should reflect the underlying biologic mechanisms. Two pathologic types of primary pulmonary hypertension have been proposed to exist, "plexogenic" and "thromboembolic." The purpose of this study was to determine the nature and variety of pathologic lesions in families with familial primary pulmonary hypertension and to discover whether the pattern of pathologic lesions found supported the existence of two types of disease. We found marked heterogeneity of pathologic lesions within and among families, including frequent coexistence of thrombotic and plexiform lesions. We conclude that the lesions found in primary pulmonary hypertension are not specific but represent different manifestations of the same pathologic process. Thus, plexiform and thrombotic lesions of the pulmonary arterioles may not arise from distinctly different biologic processes but may simply be different manifestations of the same process. Further insights in primary pulmonary hypertension must come from study of the biologic aspects of the intimal lesion.
Fibrosis↗
The pathology of mitral valve prolapse.
The gross criteria for diagnosing prolapsing mitral valve are: 1. interchordal hooding of the involved leaflets, 2. hooding or doming of leaflets towards the left atrium, 3. elongation of the involved leaflets resulting in an increase in valve area, 4. dilatation of the valve annulus in patients with severe mitral regurgitation. The posterior leaflet is most frequently affected. The involved leaflets, in general, are thickened, soft, greyish white and have a smooth atrial surface. Chordae tendineae are described as elongated, tortuous and attenuated or thinned. Deviations from normal chordal insertion have recently been observed which possibly appear to represent the underlying abnormality. Microscopic findings include significant thickening of the spongiosa and the fibrosa, changes in dense collagen fibers in the atrialis layer, occasionally, with fibrin platelet deposits. Histochemical characterization of changes in the spongiosa may also be helpful in the diagnosis. Ultrastructurally, there may be changes in collagen and elastic fibers as well as myxoid areas. On comparison of findings in surgically-removed mitral valves with those of control specimens from autopsy patients with no cardiac abnormalities, the length of the anterior and posterior leaflet as well as the annular ring diameter was larger in the valves with prolapse. Two-dimensional echocardiography accurately assessed leaflet length when compared to morphologic measurements, however, the annular diameter during systole or diastole was smaller. In patients with mitral regurgitation requiring surgery, mitral valve prolapse is the most common cause. Annular ring dilatation and chordae tendineae rupture appear to contribute substantially to incurrence of the mitral regurgitation. The heart weight is increased in the majority of patients with symptomatic mitral valve prolapse but normal, however, in those without symptoms. The most frequent complication of mitral valve prolapse is mitral regurgitation with or without congestive heart failure. Patients with redundant leaflets may be at high risk of sudden death. Young women with abnormal resting ECG, prolonged Q-T interval, family history of sudden death or complex ventricular arrhythmias may also be at a greater risk of sudden death. The incidence of infective endocarditis appears higher in those with redundant than in those with nonredundant valves. The incidence of cerebral ischemic events is low.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
The effect of verapamil cardioplegia on myocardial ultrastructure.
The calcium channel blocker, verapamil, was evaluated as an adjunct to cold cardioplegia in 16 randomized patients with unstable angina pectoris who received saphenous vein bypass grafts. Myocardial biopsies taken before cardioplegia showed various degrees of ischemic change as assessed by ultrastructural parameters (mitochondrial swelling, matrix clearance, and sarcotubular dilatation). After reperfusion, the majority of the patients had progressive changes of ischemia, with marked mitochondrial and sarcotubular swelling, depletion of glycogen, chromatin clumping, and myofibrillar disruption; amorphous mitochondrial densities were occasionally seen. The ultrastructural changes after cardioplegia were dependent primarily on the extent of preexisting ischemic damage and did not correlate with the use of verapamil. Verapamil did not protect the ischemic myocardium during cold cardioplegia as assessed ultrastructurally.
Biopsy↗
Aortocoronary saphenous vein bypass grafts.
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Coronary Artery Bypass↗
Early and late healing responses of normal canine artery to excimer laser irradiation.
Acute in vitro histologic studies have shown that the pulsed xenon chloride excimer laser causes precise microablation without the surrounding thermal tissue injury associated with frequently used continuous-wave lasers such as the argon, carbon dioxide, and neodymium:yttrium aluminum garnet lasers. However, the in vivo healing response of artery wall to excimer laser injury is not known. Accordingly, a xenon chloride excimer laser (308 nm, 40 nsec pulse width, 39 mJ/mm2/pulse) was transmitted via a 600 micron fused silica fiber to create 420 craters of varying depths (30 to 270 micron) in 21 normal canine femoral and carotid arteries. At 2 hours, 2 days, 10 days, and 42 days after excimer laser ablation, the artery segments were perfusion fixed in situ and analyzed by light, scanning, and transmission electron microscopy. At 2 hours, craters were covered by a carpet of platelets and entrapped red blood cells. Fibrin and exposed collagen fibers were seen at the crater base. There was a sharp demarcation of the crater-artery wall interface without lateral laser tissue injury. At 2 days, adherent platelets persisted with thrombus covering the base of the craters. Early healing responses were present, consisting of polymorphonucleated leukocytes and new endothelial cells, which extended over the crater rims. At 10 days, no thrombi were seen, and healing continued with almost complete reendothelialization. Macrophages, fibroblasts, fibrin, and entrapped red blood cells were present below the reendothelialized surface. At 42 days, healing was complete with obliteration of the craters by fibrointimal ingrowth. The surface was completely covered by a smooth monolayer of axially aligned endothelial cells. There were no aneurysms or surface hyperplastic responses. These favorable healing responses in normal canine arteries suggest that pulsed lasers with high tissue absorption coefficients, such as the xenon chloride excimer laser, may be suitable energy sources for clinical laser angioplasty procedures. However, further studies in atherosclerotic animals are required before human clinical responses can be accurately predicted.
Animals↗
Abnormal chordal insertion: a cause of mitral valve prolapse.
Although the morphology of mitral valve prolapse (MVP) has been described, abnormalities of chordal arrangement and insertion have not been emphasized. We retrospectively reviewed 23 surgically-excised MVP and 10 control mitral valves removed at necropsy. Two-dimensional echocardiograms (2DE) were available in 10 MVP and in six additional controls. 2DE accurately assessed the length of anterior leaflet (AL) and posterior leaflet (PL) of the mitral valve (3.2 +/- 0.7 cm and 2.2 +/- 0.6 cm, respectively) as compared to morphologic measurements (3.0 +/- 0.4 cm and 2.1 +/- 0.4 cm, respectively). However, annular diameter as assessed by echocardiography was significantly less (4.6 +/- 0.7 cm) than that derived by morphologic measurements of annular circumference (AC) (5.3 +/- 0.7 cm). The AL and PL lengths and the mitral anuli were significantly larger in patients with MVP as compared to controls (p less than 0.01) when assessed both by 2DE and by morphology. The ratio of the maximum distance of chordal separation/AC was 0.11 +/- 0.04 in MVP and 0.13 +/- 0.02 in controls (p less than 0.05). Chordal divisions were increased in MVP (4.2) compared to controls (3.1, p less than 0.01). The most striking morphologic feature of MVP was abnormal chordal insertion and a random, unpredictable pattern of chordal distribution. We postulate that abnormal chordal architecture may be responsible for unequal stress on the valve leaflets and may thus lead to MVP.
Adult↗
Cardiac pathology and sports medicine.
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Adolescent↗
Mitral valve prolapse.
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Chordae Tendineae↗
Infective endocarditis: changing trends and general approach for examination.
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Adult↗
Right ventricular hypertrophy is an important determinant of right ventricular infarction complicating acute inferior left ventricular infarction.
To explore the role of right ventricular hypertrophy and chronic obstructive pulmonary disease in the pathogenesis of right ventricular infarction, 27 consecutive patients with a first inferior left ventricular infarction were prospectively studied. Right ventricular infarction was diagnosed using established hemodynamic criteria. Right ventricular hypertrophy was defined as right ventricular free wall thickness greater than or equal to 5 mm. Patients were classified into two groups: Group I patients with right ventricular infarction (n = 15), and Group II patients without right ventricular infarction (n = 12). The ratio of forced expiratory volume over forced vital capacity (FEV1/FVC) and forced expiratory flow between 25 and 75% expired volume (FEF) as a percent of predicted values were significantly reduced in Group I versus Group II (90 +/- 5 versus 105 +/- 6% and 63 +/- 13 versus 103 +/- 15%, respectively; p less than 0.05). This was associated with increased right ventricular wall thickness (Group I 5.5 +/- 0.3 mm versus Group II 3.9 +/- 0.2 mm, p less than 0.001). Multiple logistic regression analysis demonstrated that right ventricular wall thickness was the strongest predictor of right ventricular infarction (p less than 0.0005). No significant difference was found in the site of right coronary occlusion, collateral blood supply or extent of coronary artery disease between the two groups. These findings suggest that right ventricular hypertrophy predisposes patients with acute inferior myocardial infarction to right ventricular infarction independent of the site or extent of coronary artery disease.
Adult↗
Beneficial long-term effect of intracoronary perfluorochemical on infarct size and ventricular function in a canine reperfusion model.
The administration of a drug soon after reperfusion that could enhance myocardial salvage would have important clinical application. The aim of this study was to assess the long-term effect of the perfluorochemical, Fluosol DA 20%, on infarct size, infarct morphology, ventricular ectopic activity and serial regional ventricular function in a 2 week closed chest canine model. After 90 minutes of proximal left anterior descending artery occlusion, animals randomly received either oxygenated Fluosol DA (n = 9) or saline solution (n = 9) intracoronary at 15 ml/kg body weight over 20 to 30 minutes. Hemodynamic variables were similar in the two groups except for transient elevation of left ventricular filling pressure immediately after infusion in the treated group. Infarct size was markedly reduced in the perfluorochemical-treated animals when expressed as a percent of the risk region (10.8 +/- 1.8% versus 28.9 +/- 5.5%, p less than 0.02) or as a percent of the total left ventricle (3.7 +/- 1% versus 10.8 +/- 8%, p less than 0.006). This was associated with greater improvement in radial shortening in the jeopardized zone at 2 weeks after reperfusion (15.3 +/- 2.8% versus 5.2 +/- 2.1%, p less than 0.01). Histologic examination revealed adequate healing in the treated animals with an increased number of swollen mononuclear cells in the border zones. Holter electrocardiographic recordings demonstrated a low frequency of ventricular ectopic beats in both groups. This study suggests that the perfluorochemical, Fluosol DA, may be a potentially useful agent in enhancing myocardial salvage after successful reperfusion.
Animals↗
Pathologic features of sudden cardiac death: an overview.
Sudden cardiac death is a frequent initial manifestation of underlying heart disease. We review the most frequent pathologic cardiovascular findings in victims of sudden cardiac death. We also discuss the role of exercise as a precipitant of sudden cardiac death.
Cardiomyopathies↗
Preservation of endothelial cell structure and function by intracoronary perfluorochemical in a canine preparation of reperfusion.
To determine the effect of intracoronary perfluorochemical on endothelial cell structure and function, 16 dogs were randomized to receive either low-dose (15 ml/kg) intracoronary perfluorochemical (Fluosol-DA) or saline after 90 min of proximal occlusion of the left anterior descending coronary artery (LAD). The animals underwent reperfusion for 60 min with the introduction of perfluorochemical or saline 5 to 10 min after the onset of reperfusion. Endothelium-dependent coronary vasodilatory reserve was determined in vivo both at baseline and 1 hr after reperfusion by infusion of acetylcholine and then serotonin into the distal LAD bed in 12 animals (six in each group). Both agonists significantly increased regional flow measured by 133Xe washout in the two groups before occlusion, but at 1 hr after reperfusion only animals given perfluorochemical demonstrated a significant increase in flow. Vasodilatory reserve was assessed in vitro with cumulative dose-response curves to acetylcholine on LAD rings proximal and distal to the snare in all animals. These studies demonstrated a significant reduction in endothelial cell-mediated relaxation of epicardial arterial segments in the ischemic segment of control but not treated animals. Light microscopy revealed the presence of neutrophils within vessels in the ischemic zones in control animals only. Electron microscopy showed capillary obstruction by endothelial cell protrusions and neutrophil and red cell plugging in control animals in the ischemic region but an intact endothelium and predominantly unobstructed capillaries in treated animals. These findings suggest that the structural and functional endothelial damage after reperfusion may be prevented by the administration of intracoronary perfluorochemical after the onset of reperfusion.
Animals↗