Epitope mapping of monoclonal antibodies against 4-aminobenzoate hydroxylase from Agaricus bisporus

BACKGROUND: Left ventricular assist devices have been reported previously to reverse ventricular remodeling in patients with dilated cardiomyopathy. In patients with prolonged mechanical support, structural failure of the left ventricular assist device inflow valve can cause regurgitation into the left ventricle, which may affect adversely this process. METHODS: Left ventricular end-diastolic pressure-volume relation of hearts explanted from 8 patients with left ventricular assist device and 8 control subjects with idiopathic cardiomyopathy was determined ex vivo at the time of transplantation. RESULTS: Duration of mechanical support ranged from 210 to 276 days (mean +/- standard deviation = 283 +/- 76 days) in 3 patients with inflow valve regurgitation versus 100 to 155 days (132 +/- 22 days) in 5 patients without (p = 0.005). The end-diastolic pressure-volume relation of all hearts supported mechanically was shifted to the left toward normal controls. This effect was markedly attenuated in patients with inflow valve regurgitation. CONCLUSIONS: Mechanical assistance can cause reverse remodeling in patients with dilated cardiomyopathy as evidenced by the shift in the end-diastolic pressure-volume relation curve to the left. Inflow valve failure, associated with prolonged support, can attenuate changes in left ventricular structure and dimension. Ineffective pressure and volume unloading may explain these observations.     

Left ventricular diastolic stiffness in dogs with congestive cardiomyopathy and volume overload

Mean functional diastolic stiffness, an estimate of the left ventricular resistance to filling during diastole, was measured in 10 normal dogs, 7 dogs with diseases causing volume overload (patent ductus arteriosus and primary mitral valve insufficiency), and 4 dogs with idiopathic congestive cardiomyopathy. It was measured as the increase in pressure during diastole (deltaP), divided by the corresponding increase in volume (deltaV). The pressure was measured at cardiac catheterization, and the volume was derived by a cineangiocardiographic method. There was no increase in diastolic stiffness of the hearts with volume overload compared with the normal hearts, but those with cardiomyopathy had a large increase, although the end-diastolic volumes in cardiomyopathy were generally less than in volume overload.     

An echocardiographic study of the interventricular septum in constrictive pericarditis

Ten patients with constrictive pericarditis were studied echocardiographically with specific reference to inter-ventricular septal dynamics. Abnormal movement of the interventricular septum was present in 8 patients and consisted of flattening in systole and unusual posterior motion in diastole. The aetiology of this type of movement is at present unknown but may be related to restriction of normal cardiac rotational dynamics. The interventricular septum also showed diminished degree of thickening (mean 21-2%). The amplitude of excursion was generally at the upper limit of or greater than normal. Left ventricular posterior wall amplitude of excursion was normal. Flattening of left ventricular posterior wall diastolic movement was seen in 4 patients. Right ventricular end-diastolic dimension was slightly increased (1-2 to 1-7 cm/m2) in 5 of 8 patients with abnormal septal motion, but no haemodynamic evidence of diastolic volume overload was found. Posterior pericardial thickening was noted echocardiographically when posterior calcification was present. We conclude that the most common though non-specific feature of the echocardiogram in patients with constrictive pericarditis is abnormal septal motion. Flattening of left ventricular posterior wall diastolic movement, posterior pericardial thickening, and epicardial-pericardial separation may also occur.     

Comparative efficacy of three indexes of left ventricular performance derived from pressure-volume loops in heart failure induced by tachypacing

OBJECTIVES: The purpose of this study was to serially evaluate the response and variability of the end-systolic pressure-volume relation, the left ventricular end-diastolic volume-peak positive first derivative of left ventricular pressure (dP/dt) relation and the left ventricular end-diastolic volume-stroke work relation in the development of progressive left ventricular dysfunction. BACKGROUND: Evaluation of systolic performance of the failing left ventricle may be enhanced by using relatively load-insensitive measures of left ventricular performance. The end-systolic pressure-volume, left ventricular end-diastolic volume-peak positive dP/dt and left ventricular end-diastolic volume-stroke work relations adequately define left ventricular performance under multiple loading conditions, but efficacy has not been fully assessed in the failing heart, particularly in the intact circulation. METHODS: Fourteen dogs underwent instrumentation and rapid pacing to heart failure. Variably loaded pressure-volume beats were produced by inferior vena cava occlusion. The dogs were evaluated at baseline and at three progressively more severe levels of left ventricular dysfunction. RESULTS: There was a progressive increase in left ventricular volumes at end-diastole ([mean value +/- SE] 60 +/- 28 to 73 +/- 29 ml, p < 0.001) and end-systole (39 +/- 19 to 61 +/- 27 ml, p < 0.001) during the 3 weeks of rapid pacing and a progressive decline in peak positive dP/dt (1,631 +/- 410 to 993 +/- 222 mm Hg/s, p < 0.001) and ejection fraction (37 +/- 8% to 16 +/- 11%, p < 0.001). There was a corresponding decline in the slope of each of the three relations: for end-systolic pressure-volume, 6.3 +/- 2.2 to 2.8 +/- 0.7 (p < 0.05); for left ventricular end-diastolic volume-stroke work, 61.9 +/- 9.1 to 26.5 +/- 2.4 (p < 0.05); and for left ventricular end-diastolic volume-peak positive dP/dt, 47.1 +/- 13.6 to 20.31 +/- 6.8 (p < 0.05). There was also a corresponding increase in position volumes: for end-systolic pressure-volume, 33.6 +/- 3.9 to 61.2 +/- 6.6 ml (p < 0.05); for left ventricular end-diastolic volume-stroke work, 46.2 +/- 3.6 to 89.3 +/- 7.6 ml (p < 0.05); and for left ventricular end-diastolic volume-peak positive dP/dt, 29.1 +/- 19.1 to 68.6 +/- 25.9 ml (p < 0.05). The relative degree of change in each of the three relations was similar as more severe heart failure developed. The coefficients of variation for position were significantly less than the variation for slopes. The response of volume intercepts was heterogeneous. For left ventricular end-diastolic volume-stroke work, the intercept increased as ventricular performance decreased. The intercept of the end-systolic pressure-volume relation was significantly more variable than the left ventricular end-diastolic volume-stroke work relation and did not change with progressive heart failure. The intercept for left ventricular end-diastolic volume-peak positive dP/dt was highly variable and showed no consistent changes as left ventricular function declined. CONCLUSIONS: All three relations consistently describe changes in left ventricular performance brought about by tachypacing. Evolution of left ventricular dysfunction causes a decline in slope and a rightward shift of these relations. The position of the relation is the most sensitive and least variable indicator of left ventricular systolic performance.     

The effect of ventricular volume reduction surgery in the dilated, poorly contractile left ventricle: a simple finite element analysis

OBJECTIVES: Ventricular volume reduction surgery has been proposed by Batista to improve cardiac function in patients with dilated cardiomyopathy. However, limited clinical data exist to determine the efficacy of this operation. A finite element simulation is therefore used to determine the effect of volume reduction surgery on left ventricular end-systolic elastance, diastolic compliance, stroke work/end-diastolic volume (preload recruitable stroke work), and stroke work/end-diastolic pressure (Starling) relationships. METHODS: End-diastole and end-systole were represented by elastic finite element models with different unloaded shapes and nonlinear material properties. End-systolic elastance, diastolic compliance, preload recruitable stroke work, and Starling relationships, as well as energy expenditure per gram of unresected myocardium, were calculated. Two different types of volume reduction surgery (apical and lateral) were simulated at 10% and 20% left ventricular mass reduction. RESULTS: Ventricular volume reduction surgery causes diastolic compliance to shift further to the left on the pressure-volume diagram than end-systolic elastance. Volume reduction surgery increases the slope of the preload recruitable stroke work relationship (dilated cardiomyopathy 0.006 J/mL; 20% lateral volume reduction surgery 0.009 J/mL) but decreases the slope of the Starling relationship (dilated cardiomyopathy 0.028 J/mm Hg; 20% lateral volume reduction 0.023 J/mm Hg). For a given amount of resection, lateral volume reduction has a greater effect than apical volume reduction. Ten-percent and 20% lateral volume reduction reduces energy expenditure by 7% and 17%, respectively. CONCLUSION: Ventricular volume reduction surgery shifts end-systolic elastance and diastolic compliance to the left on the pressure-volume diagram. The net effect on ventricular function is mixed. Volume reduction surgery increases the slope of preload recruitable stroke work, but increased diastolic compliance causes a small decrease in the Starling relationship (3 mm Hg difference between dilated cardiomyopathy and volume reduction surgery at stroke work = 0.5 J).     

Acute hemodynamic interventions shift the diastolic pressure-volume curve in man

Frame-by-frame analysis of angiograms in 16 patients revealed that hemodynamic interventions are capable of producing substantial shifts in the diastolic pressure-volume curve. Angiotensin raises blood pressure and shifts the entire pressure-volume curve up, and nitroprusside lowers blood pressure and shifts the curve down. Indirect measurements of pleural pressure in seven patients (via esophageal pressure) showed that pleural pressure changes were too small to account for these shifts. Analyzing our results in terms of a theoretical pressure-volume equation previously validated in dog studies did not show the observed shifts to be the product of acute changes in the elasticity of the myocardium itself. This same analysis suggested that indirect changes in the external mechanical constraints acting on the left ventricle such as the right ventricular pressure, the pericardium, and perhaps viscoelastic effects related to changes in filling rate account for the pressure-volume curve shifts with intervention. The fact that one cannot in general relate a specific volume to a given pressure in the face of hemodynamic interventions calls into question the use of end-diastolic pressure interchangeably with end-diastolic fiber length when interpreting systolic events in terms of the Frank-Starling mechanism.     

Cardiac amyloidosis, contrictive pericarditis and restrictive cardiomyopathy

Cardiac amyloidosis is not characterized by a single hemodynamic pattern. Some of the cases present the clinical findings of restrictive cardiomyopathy and in these differentiation from constrictive pericarditis remains difficult in spite of the introduction of techniques designed to assess myocardial contractility and ventricular diastolic compliance. The clinical features and the demonstration of left ventricular diastolic pressure greater than right remain the most useful means of distinguishing restrictive cardiomyopathy from constrictive pericarditis. In other cases of cardiac amyloidosis the diastolic pressure is elevated throughout diastole and ventricular ejectile ability is lost. These cases do not simulate constrictive pericarditis and should not be classified as restrictive cardiomyopathy.     

Congestive heart failure in patients with valvular aortic stenosis. A clinical and echocardiographic Doppler study

The aim of this study was to evaluate echographically anatomic and functional features of the left ventricle in adult patients with valvular aortic stenosis according to the presence or absence of congestive heart failure and the level of ventricular performance. Fifty-six adult patients with moderate-to-severe aortic stenosis underwent echocardiographic Doppler examination in order to evaluate left ventricular mass and dimensions, systolic function and filling dynamics. Twenty-seven patients had no heart failure and were symptomatic for angina (5), syncope (4) or were symptom-free (group I); the other 29 had heart failure (group II): 16 with normal left ventricular systolic performance (fractional shortening > 25%, group IIa) and 13 with systolic dysfunction (fractional shortening < or = 25%, group IIb). Despite a similar left ventricular mass, compared to group IIa, group IIb showed a significant left ventricular dilatation (end-diastolic diameter: 61 +/- 6.5 vs. 45.5 +/- 6.1 mm, p < 0.001) and mild or no increase in wall thickness (11.5 +/- 1.6 vs. 14.9 +/- 2 mm, p < 0.001). Indices of left ventricular filling on Doppler transmitral flow were also significantly different between the two groups, with a higher early-to-late filling ratio and a shorter deceleration time of early filling in group IIb (2.8 +/- 1.9 vs. 1.2 +/- 0.85, p < 0.01, and 122 +/- 66 vs. 190 +/- 87 ms, p < 0.05, respectively), both indirectly indicating higher left atrial pressure. Finally, heart failure was generally more severe in group IIb patients. In some patients with aortic stenosis, symptoms of heart failure may be present despite a normal left ventricular systolic function and seem to depend on abnormalities of diastolic function. The presence of systolic or isolated diastolic dysfunction appears to be related to a different geometric adaptation of the left ventricle to chronic pressure overload.     

A case of post-radiation constrictive pericarditis developing 12 years after radiation therapy

A 70-year-old woman underwent radical mastectomy for carcinoma of the left breast in 1982. Postoperative radiation therapy was given in a total dose of 50 Gy for parasternal and left subclavian nodes. Symptoms of heart failure such as exertional dyspnea, facial edema, and hepatomegaly manifested in 1992. Cardiac catheterization revealed marked elevation of mean right atrial pressure and right ventricular end-diastolic pressure. The pressure wave form of the right ventricle showed the so called "dip and plateau" feature. Pericardiectomy without using extracorporeal circulation was performed in 1994. Operative findings and pathological study results were compatible with radiation-induced constrictive pericarditis. She rapidly recovered from heart failure after this operation, and has done very well to date.     

Effects of exercise on plasma level of brain natriuretic peptide in congestive heart failure with and without left ventricular dysfunction

This study was designed to determine whether plasma brain natriuretic peptide (BNP) increases in response to exercise in patients with congestive heart failure and to show what kind of hemodynamic abnormalities induce increased secretion of BNP during exercise. Plasma levels of atrial natriuretic peptide (ANP) and BNP and hemodynamic parameters were measured during upright bicycle exercise tests in seven patients with dilated cardiomyopathy and nine with mitral stenosis. At rest, there were no intergroup differences in cardiac output or pulmonary capillary wedge pressure; however, the group with dilated cardiomyopathy had higher left ventricular end-diastolic pressures and lower left ventricular ejection fractions than did the group with mitral stenosis. Plasma ANP levels were comparable between the dilated cardiomyopathy group (170 +/- 77 [SE] pg/ml) and the mitral stenosis group (106 +/- 33 pg/ml) (p, not significant), whereas BNP was significantly higher in the dilated cardiomyopathy group (221 +/- 80 pg/ml) than in the other group (37 +/- 10 pg/ml) (p < 0.05). The plasma concentration of BNP but not of ANP significantly correlated with left ventricular end-diastolic pressure and volume. Exercise increased plasma ANP and BNP in the two groups. The dilated cardiomyopathy group had a larger increment in BNP (+157 +/- 79 pg/ml) than did the mitral stenosis group (+17 +/- 5 pg/ml) (p < 0.05), although the increase in pulmonary capillary wedge pressure was greater in the mitral stenosis group. Thus exercise increases plasma levels of BNP, and impaired left ventricular function may be a main factor in the greater increment in BNP during exercise in patients with congestive heart failure.     

Pericardiectomy for pericardial constriction

Constrictive pericarditis is a pathologic condition that may lead to significant morbidity. Definitive management of constrictive pericarditis requires pericardiectomy. A retrospective review of pericardiectomy for constrictive pericarditis at the Ochsner Clinic was undertaken. Twenty-one patients (17 male, four female) underwent pericardiectomy for constrictive pericarditis between January 1969 and June 1994. Ages ranged from 15 to 66 years (mean 41.5 years). Pedal edema, dyspnea, fatigue, and chest pain were the most common symptoms. Fifteen patients had important comorbidities. Preoperative New York Heart Association (NYHA) class was I (2), II (8), III (6), IV (5). Mean preoperative catheterization data, available in 17 patients (81%), demonstrated elevated intracardiac pressures (right atrial 17.4 mm Hg, right ventricular end-diastolic 22.4 mm Hg, pulmonary artery 26.2 mm Hg, pulmonary capillary wedge 20.2 mm Hg, left ventricular end-diastolic 20.1 mm Hg). A total pericardiectomy was performed in nine patients (sternotomy 8, thoracotomy 1). Pericardiectomy limited anteriorly to the phrenic nerves was performed in 11 patients (sternotomy 9, thoracotomy 2). One partial pericardiectomy was performed through a sternotomy. Cardiopulmonary bypass was used in six patients (29%). Mean hospital stay was 12 days (preoperative 4.2, postoperative 7.67). All patients achieved NYHA Class I postoperatively. Sixteen patients were discharged in sinus rhythm. No early mortality (<30 days), or major postoperative complications were observed. Pericardiectomy for pericardial constriction can be performed safely low morbidity and mortality and can favorably impact the natural history of this debilitating condition.     

Effects of amrinone on left ventricular function following open heart surgery--analysis with left ventricular pressure volume loops

The effects of Amrinone on cardiac function soon after extracorporeal circulation (ECC) were studied in 5 patients including mitral valvuloplasty, VSD closure, Fontan operation and coronary AV fistel closure. In all patients, left ventricular volume load decreased postoperatively. To evaluate the efficacy, we obtained left ventricular pressure-volume loops (P-V loop) before and after ECC and after intravenous administration of Amrinone (1 mg/kg) following ECC. P-V loops were produced by measuring left ventricular pressure using a Miller catheter which was retrogradely advanced from the ascending aorta into the left ventricle and by measuring left ventricular diameter to calculate left ventricular volume with Teichholtz' formula. Although no apparent difference of Emax was recognized before and after ECC, Emax increased from 3.2 +/- 2.5 mmHg/cm3 to 5.9 +/- 4.7 mmHg/cm3 after the administration of Amrinone. The left ventricular "systolic" pressure-volume area (PVA) which is the sum of stroke work (SW) and elastic potential energy decreased from 34.4 +/- 16.4 gm to 30.9 +/- 17.8 gm after Amrinone. No difference was also recognized in left ventricular end-diastolic pressure. Ejection fraction increased from 50 +/- 17.5% to 56.1 +/- 17.3%. These results suggested that Amrinone could improve the left ventricular function without prominent change in myocardial oxygen consumption immediately after open heart surgery.     

Mitochondrial dysfunction in neurodegenerative disorders

Left ventricular hypertrophy with adequate wall thickness, preserved adult phenotype and extracellular matrix may be useful in the prevention of heart failure. Because activation of subtype 1 of angiotensin II (AT1) receptors is thought to be involved in the hypertrophic response of cardiomyocytes, we tested the potential of systemic AT1 blockade to modify the development of left ventricular hypertrophy due to pressure overload. Sham-operated rats and rats with ascending aorta constriction were treated with losartan (30 mg/kg/day) for 8 weeks. Left ventricular geometry, dynamics of isovolumic contractions, hydroxyproline concentration as well as myosin isozymes (marker of fetal phenotype) were assessed. Rats with aortic constriction exhibited a marked increase in left ventricular weight and the diastolic pressure-volume relationship was shifted to smaller volumes. An enlarged ventricular pressure-volume area and increased (p < 0.05) peak values of +dP/dtmax and- dP/dtmax demonstrated an enhanced overall ventricular performance. Signs of congestive heart failure were not apparent. In contrast, parameters of myocardial function (normalized length-stress area, +d delta /dtmax and -d delta /dtmax) were depressed (p < 0.05), indicating an impaired myocardial contractility. The hydroxyproline concentration remained unaltered. However, the proportion of beta-myosin heavy chains (MHC) was increased (p < 0.05). Administration of losartan decreased (p < 0.05) blood pressure and body weight in sham operated and pressure overloaded rats. By contrast, neither the concentric left ventricular hypertrophy or depressed myocardial function nor the increased beta-MHC expression were significantly altered. Thus, activation of AT1 receptors appears not to be involved in the initial expression of the fetal phenotype of pressure overloaded heart which may be responsible for the progressive functional deterioration of the hypertrophied ventricle.     

A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders

To evaluate the difference in left ventricular function during exercise after successful aortic valve replacement, left ventricular function was investigated using radionuclide angiography in 12 patients with normal resting left ventricular systolic function. Patients were divided into two groups: Group 1 was comprised of 5 patients after aortic valve replacement for aortic stenosis and group 2 was comprised of 7 patients for aortic insufficiency. Left ventricular ejection fraction increased significantly during exercise in both groups. The increase in systolic arterial pressure to left ventricular end-systolic volume was significantly larger in group 1 than group 2, whereas the increase in left ventricular end-diastolic volume was significantly larger in group 2 than group 1. Thus, increase in left ventricular contractility played an important role in regulating increased left ventricular ejection fraction during exercise in patients with aortic prostheses for aortic stenosis, whereas increase in left ventricular end-diastolic volume played an important role in patients with aortic prostheses for aortic insufficiency.     

Indirect measurement of end-diastolic pressure-volume relation in the in situ canine heart

We developed a new method to estimate the end-diastolic pressure-volume relation (EDPVR) of the ejecting ventricle without directly measuring the ventricular volume. The following equation is derived from the ventricular elastance concept; Pes = Ees (Ved-Vo-Vj), where Pes is end-systolic pressure; Ees, end-systolic elastance; Ved, end-diastolic volume; Vo, an empirical constant; and Vj, ejected volume at end-systole. Therefore, under a constant preload and contractility; two sets of Pes and Vj, i.e, (Pes 1, Vj 1) and (Pes 2, Vj 2), yield an equation of Ve = (Pes 1 Vj 2-Pes 2 Vj 1)/(Pes 1-Pes 2), where Ve is effective end-diastolic volume, Ved-Vo. Repeated measurements of Ve under various levels of end-diastolic pressure (Ped) allow us to determine the EDPVR. In 8 anesthetized dogs with the chest open, we obtained two sets of Pes and Vj under a given Ped as mentioned above, one in a normally ejecting condition and the other in a clamping condition of the descending aorta to increase afterload of the left ventricle. We then calculated the Ve from the equation mentioned above. We repeatedly determined the Ve varying preload levels to obtain the EDPVR. We compared the EDPVR estimated by the present method with that directly measured by the balloon method in the arrested ventricle. These two EDPVRs were correlated very well. To compare more quantitatively, the chamber stiffness constant was obtained. The chamber stiffness constant derived from the estimated EDPVR was linearily related to that derived from the directly measured EDPVR (y = 1.043x + 0.003, r = 0.987). Furthermore, in order to test whether the EDPVR derived from our present method can detect changes in left ventricular compliance in the in situ ventricle, we obtained the EDPVRs under the three different (intact, opened, and closed) conditions of the pericardium in six dogs. The EDPVR was shifted upward in the closed condition compared with that in the intact condition, while it was shifted downward in the opened condition. Thus, the changes of the left ventricular diastolic compliance were correctly evaluated by the developed method. Therefore, we conclude that the EDPVR obtained using our indirect method is reliable to estimate the ventricular diastolic properties of the in situ heart.     

Flow in pulmonary veins

Pulmonary venous flow can be evaluated by means of pulsed Doppler echocardiography during a transthoracic or transesophageal echocardiography examination. In most cases a three-peak spectral curve with highest positive wave during ventricular systole, a lower positive wave during ventricular diastole and a small negative wave during the left atrial contraction are recorded. Multiple factors affect the systolic and diastolic components of pulmonary venous flow. Pulmonary venous flow measurement may prove to be an important tool in routine judgment of diastolic left ventricular and atrial function. With regard to clinical importance, the pulmonary venous flow is a useful parameter for left atrial pressure quantification and for differential diagnosis of restrictive cardiomyopathy and constrictive pericarditis.     

The effect of left ventricular pressure or volume overload on ventricular dimension in children. Left ventricular volume determination from one or two ventricular dimensions

The effect of pressure or volume overload on the geometry of the left ventricle (LV) was determined in order to examine the feasibility and accuracy of LV volume determinations from one minor axis or two dimensions (one minor axis and the longest length). The longest length (LL) and minor axis (MA) in both the anteroposterior (AP) view and lateral (LAT) view were determined from the LV cine silhouette in patients with normal LV volume and pressure (group 1), LV pressure (LVP) overload group (LVP greater than 140 mm Hg, group 2), and LV volume overload group (LV end-diastolic volume greater than 124% of normal, group 3). The ratio of the MA to the LL, which represents the spherical configuration of the LV, was less than "normal" in group 2, and higher than "normal" in group 3. In all groups the LV was less spherical at end-systole than at end-diastole. Additionally, the (MA)3 had a different relationship to true LV volume (biplane LV volume) in the three groups and from diastole to systole in each group. Left ventricular volume calculation from one minor axis was associated with a large error. In contrast, left ventricular volume can be accurately determined from two ventricular dimensions using either the anteroposterior or lateral ventricular image (r larger than or equal to 0.97).     

Desflurane, sevoflurane, and isoflurane impair canine left ventricular-arterial coupling and mechanical efficiency

BACKGROUND: The effects of desflurane, sevoflurane, and isoflurane on left ventricular-arterial coupling and mechanical efficiency were examined and compared in acutely instrumented dogs. METHODS: Twenty-four open-chest, barbiturate-anesthetized dogs were instrumented for measurement of aortic and left ventricular (LV) pressure (micromanometer-tipped catheter), dP/dtmax, and LV volume (conductance catheter). Myocardial contractility was assessed with the end-systolic pressure-volume relation (Ees) and preload recruitable stroke work (Msw) generated from a series of LV pressure-volume diagrams. Left ventricular-arterial coupling and mechanical efficiency were determined by the ratio of Ees to effective arterial elastance (Ea; the ratio of end-systolic arterial pressure to stroke volume) and the ratio of stroke work (SW) to pressure-volume area (PVA), respectively. RESULTS: Desflurane, sevoflurane, and isoflurane reduced heart rate, mean arterial pressure, and left ventricular systolic pressure. All three anesthetics caused similar decreases in myocardial contractility and left ventricular afterload, as indicated by reductions in Ees, Msw, and dP/dtmax and Ea, respectively. Despite causing simultaneous declines in Ees and Ea, desflurane decreased Ees/Ea (1.02 +/- 0.16 during control to 0.62 +/- 0.14 at 1.2 minimum alveolar concentration) and SW/PVA (0.51 +/- 0.04 during control to 0.43 +/- 0.05 at 1.2 minimum alveolar concentration). Similar results were observed with sevoflurane and isoflurane. CONCLUSIONS: The present findings indicate that volatile anesthetics preserve optimum left ventricular-arterial coupling and efficiency at low anesthetic concentrations (< 0.9 minimum alveolar concentration); however, mechanical matching of energy transfer from the left ventricle to the arterial circulation degenerates at higher end-tidal concentrations. These detrimental alterations in left ventricular-arterial coupling produced by desflurane, sevoflurane, and isoflurane contribute to reductions in overall cardiac performance observed with these agents in vivo.     

Myocardial dysfunction after successful resuscitation from cardiac arrest

OBJECTIVE: To investigate the functional and metabolic changes in the myocardium after successful resuscitation from cardiac arrest. DESIGN: Prospective, randomized, sham-controlled study. SETTING: Animal laboratory at a university center. SUBJECTS: Domestic pigs. INTERVENTIONS: Electric induction of ventricular fibrillation by alternating current delivered to the right ventricular endocardium through a pacing electrode. Electric defibrillation was attempted after an interval of 12 mins of ventricular fibrillation, which included 4 mins of untreated ventricular fibrillation and 8 mins of precordial compression in 13 animals, seven of which were successfully resuscitated. Seven additional animals were randomized to serve as "sham" controls, in which cardiac arrest was not induced. MEASUREMENTS AND MAIN RESULTS: Left ventricular pressure-volume relationships utilizing the conductance method were obtained in conjunction with conventional hemodynamic and metabolic measurements at baseline and during a 6-hr interval after successful cardiac resuscitation. Progressive and striking increases in left ventricular volumes were observed after successful cardiac resuscitation. The end-diastolic volume increased from a prearrest level of 89 +/- 21 mL to a maximum of 154 +/- 53 mL (p<.05) at 360 mins after successful resuscitation. The time-coincident end-systolic volume increased from 54 +/- 21 to 126 +/- 54 mL (p<.05), such that the ejection fraction was reduced from 0.41 +/- 0.10 to 0.20 +/- 0.07 ( p<.05). Ventricular dilation was associated with marked reductions in stroke volume and ventricular work. However, compensatory increases in heart rate maintained cardiac output at levels that sustained adequate systemic oxygen delivery. The slope of the end-systolic pressure-volume relationships progressively decreased from 5.04 +/- 1.88 to 2.00 +/- 0.57 mm Hg/mL (p<.05) at 360 mins after successful resuscitation. The volume intercept at left ventricular pressure of 100 mm Hg increased from 43 +/- 19 to 94 +/- 51 mL (p=.03). Both the decrease in the slope and the increase in the volume intercept were characteristic of progressive impairment in contractile function. The rate of left ventricular pressure decrease was unchanged. Accordingly, no substantial changes in lusitropic properties were identified. Despite large increases in end-diastolic volume, the end-diastolic pressure remained unchanged. CONCLUSION: Postresuscitation myocardial dysfunction in this animal model was characterized by impaired contractile function, decreased work capability, and ventricular dilation.     

Mechanism of adenosine-induced elevation of pulmonary capillary wedge pressure in humans

BACKGROUND: Continuous intravenous administration of adenosine to humans often results in a paradoxical rise in pulmonary capillary wedge pressure (PCWP), whereas arterial resistance is lowered and cardiac output and heart rate increase. This is believed to be due to diastolic stiffening of the ventricle or to a negative inotropic effect. In the present study, we tested these and other mechanisms by using pressure-volume (PV) analysis and echocardiography. METHODS AND RESULTS: Fifteen patients with normal rest left ventricular function underwent cardiac catheterization and received adenosine at a rate of 140 micrograms/kg per minute IV for 6 to 10 minutes. PV relations were measured in 9 patients (without coronary artery disease) using the conductance catheter method. In 6 additional patients with coronary artery disease, echocardiograms were used to assess wall thickness and function, and aortic and coronary sinus blood, lactate, oxygen, and adenosine levels were measured. Adenosine increased PCWP by 19% (+2.6 mm Hg) in both patient groups while lowering arterial load by 30% and increasing cardiac output by 45% (all P < .001). There was no significant effect of adenosine on mean linear chamber compliance or monoexponential elastic stiffness, as the diastolic PV relation was unchanged in most patients. Diastolic wall thickness also was unaltered. Thus, the PCWP rise did not appear to be due to diastolic stiffening. Adenosine induced a rightward shift of the end-systolic PV relation (ESPVR) (+12.7 +/- 3.7 mL) without a slope change. This shift likely reflected effects of afterload reduction, as other indexes (stroke work-end-diastolic volume relation and dP/dtmax at matched preload) were either unchanged or increased. Furthermore, this modest shift in ESPVR was more than compensated for by vasodilation and tachycardia, so reduced systolic function could not explain the increase in PCWP. There also was no net lactate production to suggest ischemia. Rather than arising from direct myocardial effects, PCWP elevation was most easily explained by a change in vascular loading, as both left ventricular end-diastolic volume and right atrial pressure increased (P < .05). This suggests that adenosine induced a redistribution of blood volume toward the central thorax. CONCLUSIONS: PCWP elevation in response to adenosine primarily results from changes in vascular loading rather than from direct effects on cardiac diastolic or systolic function.