Elevated Wall Stress Research Articles

Ventricular expression of atrial natriuretic peptide in chronic chagasic cardiomyopathy is not induced by myocarditis

Background: The ventricles of the normal heart are virtually devoid of atrial natriuretic peptide (ANP). Although ANP occurs in ventricles submitted to elevated wall stress, it is not clear whether ANP expression is affected by myocarditis. We investigated the immunohistochemical expression of ANP in chronic chagasic cardiomyopathy, an inflammatory cardiomyopathy caused by infection with the protozoan Trypanosoma cruzi. Methods: Necropsy samples from the left and right ventricles of 16 patients exhibiting chronic chagasic cardiomyopathy were evaluated for myocarditis, fibrosis, T. cruzi parasites and ANP immunoreactivity. The diameters of 50 myocytes per sample were measured. Results: ANP was present in myocytes of the subendocardial region in 13/16 (81.3%) left and 10/16 (62.5%) right ventricular samples ( P=0.25). Myocytes present in the inflammatory foci, near the infiltrating inflammatory cells but distant from the subendocardial region, did not express ANP. Trypanosoma cruzi parasites exhibited intense immunoreactivity for ANP. The mean myocyte diameter and the incidence of myocarditis, fibrosis, and T. cruzi parasites was similar between the left and right ventricular samples. No statistical differences were found between the ANP-positive and ANP-negative cases. Conclusions: In chronic chagasic cardiomyopathy, both ventricles exhibit hypertrophy, fibrosis and ANP in the subendocardial region. The inflammatory infiltrate does not induce ANP expression in the myocytes. Regional stress but not myocarditis itself, is probably responsible for ventricular ANP expression in myocarditis.

Deoxyribonucleic acid damage/repairproteins are elevated in the failing human myocardium due to idiopathic dilated cardiomyopathy

ObjectivesThe study investigated the expression and relationship of deoxyribonucleic acid (DNA) repair enzymes with hemodynamic and nitric oxide (NO)-mediated stress in the failing myocardium. BackgroundThe role of apoptosis in human heart failure is controversial. Experimental studies suggested that NO-mediated stress modulates apoptosis of the cardiac myocytes. Of note, DNA repair enzymes such as redox factor/apurinic/apyridimine endonuclease Ref-1 protein, proliferative cell nuclear antigen (PCNA), the poly (ADP-ribose) polymerase (PARP), and DNA-protein kinase (DNA-PK) determine the cell fate after the DNA damage. MethodsLeft ventricular (LV) endomyocardial biopsies from 23 patients with dilated cardiomyopathy were analyzed by immunohistochemistry. ResultsTerminal deoxynucleotidyltransferase-mediated biotin-dUTP nick-end labeling (TUNEL) or cleaved caspase-3 and cleaved PARP could not be detected. The number of Ref-1-positive myocytes tended to be higher in patients with LV ejection fraction (EF) ≤35% versus LV EF >35% (21.23 ± 4.8% vs. 13.8 ± 5.8%, p = 0.1). The PCNA (7.1 ± 2.8% vs. 0.9 ± 0.6%, p = 0.05) and DNA-PK expressions (39.5 ± 5.4% vs. 8.6 ± 5.5%, p < 0.01) were higher in patients with LVEF ≤35% vs. LVEF >35%. The PCNA, Ref-1, and DNA-PK expression correlated with the LV end-systolic wall stress (r = 0.61, p < 0.01; r = 0.52, p < 0.01; and r = 0.73, p < 0.001, respectively). In addition, the PCNA and DNA-PK expression correlated with inducible NO synthase (r = 0.41, p = 0.05, and r = 0.53, p < 0.01, respectively). ConclusionsIn this study, apoptosis could not be detected in the failing myocardium owing to idiopathic dilated cardiomyopathy. In contrast, failing myocardium was characterized by active DNA repair that was associated with elevated LV wall stress and activation of the inducible NO synthase.

Passive ventricular constraint for the treatment of congestive heart failure

Progressive heart failure is characterized by loss of cardiac function associated with maladaptive changes in myocardial gene expression and neuroendocrine activity, leading to progressive increases in heart size. Elevated ventricular wall stress results from an increase in chamber size, and is thought to play a role in furthering development towards end-stage disease. Reduction of wall stress and stress mediated myocardial stretch may be an important means for mitigating heart failure progression. One possible approach to accomplish this goal is through passive support of the heart with the Cardiac Support Device. Results from preclinical and clinical evaluation give support to this premise.

How are cytokines activated in heart failure?

In the dilated and failing heart, elevated LV end-diastolic wall stress causes myocardial expression of cytokines, which directly or indirectly influence LV contractile performance and remodeling [22]. Due to poor diffusion of cytokines into the coronary effluent, the contribution of this myocardial production to the raised plasma levels is probably limited. Raised plasma levels of cytokines in heart failure are therefore more likely the result of extramyocardial production because of altered tissue perfusion and tissue hypoxia possibly modulated by bacterial endotoxin release from the gut.

Ascites in poultry: Recent investigations

In recent years, ascites research has centred on gaining an increased understanding of pulmonary hypertension syndrome together with the potential role of primary cardiac pathologies. The impact at a cellular level of factors which trigger ascites and substances that protect against it has also been documented. Primary pulmonary hypertension has been induced when birds are exposed to hypoxia during incubation. The conditions experienced during this phase of development may impact on the ability of the bird to regulate its basal metabolic rate through endocrine signals controlled by thyroid activity. The extent of ventilation in the lung influences the ability of the bird to oxygenate haemoglobin. Ventilation/ perfusion mismatches may occur prior to or post-hatching. This factor has been studied extensively using the pulmonary artery/bronchus clamp model. At high altitude, a decreased ventilation/perfusion ratio may occur following the effective increase in physiological dead space due to the lowered oxygen tension at the level of the parabronchi. This explains the mechanism by which ascites is triggered by hypoxia in this particular situation. The effects of ascites are ameliorated by the use of beta agonists and dietary arginine, which act by increasing ventilation and blood flow in the lungs and thus correcting a ventilation/perfusion mismatch. Transient bacterial and viral infections may also influence the induction of pulmonary hypertension. The increases in blood viscosity associated with ascites are most probably a consequence of the condition rather than a cause. A bird may alleviate the effects of pulmonary hypertension by decreasing blood viscosity through inhibition of platelet function, increased erythrocyte deformability and the production of coronary relaxants. Evidence is accumulating that primary cardiac pathology may be associated with a number of ascites cases. Broilers that subsequently develop ascites, exhibit lower heart rates than their normal flock mates. Furthermore, during ascites, hypoxic broilers exhibit bradycardia as opposed to the expected tachycardia. In these cases, a tachycardia induced by feed restriction may protect the bird by raising its cardiac output. Right atrio-ventricular regurgitant flow velocities in chickens are relatively slow compared with similar regurgitant flows induced by pulmonary hypertension in other species. The conduction system in the avian heart is specialized and contains a recurrent bundle branch that innervates the right atrio-ventricular valve, thus initiating active valve closure before right ventricular systole. This predisposes the heart to right ventricular volume overload through a valvular incompetance following a failure of valvular innervation. The resultant elevated diastolic wall stress can trigger the production of angiotensin II and its converting enzyme, which mediate ventricular hypertrophy. Subclinical myocardial damage, irrespective of its cause, can be detected by the presence of troponin T in the blood. Reactive oxygen species may damage cell membranes compromising cellular function in a number of body systems. A positive correlation exists between oxidized glutathione concentrations and right ventricular weight ratio. This indicates a failure to cope with oxidative stress at the level of the respiratory membrane. It is not known if it is possible to modulate levels of antioxidants at this location and hence protect the bird. The final description of the ascites aetiology may lie in the concept of a circuit of events between the cardiac, pulmonary and vascular systems that satisfy the metabolic requirements of the bird. A deficit in one of these systems, at a level that prevents adequate compensation from other components, triggers the pathological cascade that results in the end point of clinical ascites.

Hypertrophic remodeling: gender differences in the early response to left ventricular pressure overload

Objectives. To identify gender differences in left ventricular remodeling, hypertrophy, and function in response to pressure overload due to ascending aortic banding in rats.Background. Gender may influence the adaptation to pressure overload, as women with aortic stenosis have greater degrees of left ventricular hypertrophy and better left ventricular function than men.Methods. Fifty-two weanling rats underwent ascending aortic banding (16 males, 18 females), or sham surgery (9 males, 9 females). At 6 and 20 weeks, rats underwent transthoracic echo Doppler studies, and closed-chest left ventricular pressures with direct left ventricular puncture. Perfusion-fixed tissues from eight rats were examined morphometrically for myocyte cross-sectional area and percent collagen volume.Results. At 6 weeks after aortic banding, left ventricular remodeling, extent of hypertrophy, and function appeared similar in male and female rats. At 20 weeks, male but not female rats showed an early transition to heart failure, with onset of cavity dilatation (left ventricular diameter = 155% vs. 121% of same-sex sham), loss of concentric remodeling (relative wall thickness = 102% vs. 139% of sham), elevated wall stress (systolic stress = 266% vs. 154% of sham), and diastolic dysfunction (deceleration of rapid filling = 251% vs. 190% of sham). Left ventricular systolic pressures were higher in female compared with male rats (186 ± 20 vs. 139 ± 13 mm Hg), while diastolic pressures tended to be lower (14 ± 4 vs. 17 ± 4 mm Hg).Conclusions. Gender significantly influences the evolution of the early response to pressure overload, including the transition to heart failure in rats with aortic stenosis.

Regulation of the rat atrial natriuretic peptide gene after acute imposition of left ventricular pressure overload.

The upregulation of left ventricular (LV) atrial natriuretic peptide (ANP) mRNA is a highly conserved marker of cardiac hypertrophy. The aim of this study was to further examine the pathway leading to ANP induction during pressure overload of the heart. Systolic wall stress was imposed acutely on isovolumetrically beating rat hearts in a Langendorff apparatus (sigma-=300 x 10[3] dyne/cm2). Northern and Western blots revealed that elevated wall stress induced LV c-fos and c-jun mRNAs (3.5- and 3-fold, P<.05 after 60 minutes), c-Fos and c-Jun proteins (3.9- and 4.3-fold, P<.05 after 120 minutes), as well as ANP mRNA (2.2-fold, P<.05 after 120 minutes). ANP upregulation was prevented by inhibition of protein synthesis (cycloheximide). Electrophoresis mobility shift assays were performed to link c-Fos and c-Jun (ie, components of the heterodimeric transcription factor AP-1) and ANP induction. A putative AP-1 binding site within the rat ANP promoter (nucleotides -512 to -473) bound specifically to nuclear proteins of wall stress-stimulated hearts. Antibodies directed against c-Fos protein resulted in a shift of this DNA/protein complex, suggesting physical interaction between AP-1 and the ANP promoter. Myocardial transfection of promoter constructs revealed that after acute imposition of wall stress, this AP-1 site enhanced a reporter gene (8- to 10-fold compared with a minimal promoter, P<.05). Interestingly, nuclear extracts of stimulated hearts as well as pure AP-1 protein bound to a putative CRE site (nucleotides -613 to -584) as well. Like the AP-1 site, this cAMP-responsible element (CRE) site was found to enhance the transfected ANP promoter/reporter gene significantly (17.5-fold, P<.05). Mutation of either AP-1 or CRE sites did not decrease reporter gene activity, whereas mutation of both resulted in loss of inducibility. These experiments suggest that LV ANP regulation after acute wall stress includes the activation of AP-1 and/or CRE cis acting elements. However, the transient nature of c-fos and c-jun upregulation also suggests that AP-1 is not the only mediator of ANP induction in LV hypertrophy.

Therapie der dilatativen Kardiomyopathie mit rekombinantem humanem Wachstumshormon (Therapy of dilated cardiomyopathy with human recombinant growth hormone)

Dilated cardiomyopathy is a disease of the myocardium which is characterized by predominant enlargement of the left ventricle, decreased systolic function, and reduced myocardial wall thickness. The reduction in the number and function of myocardial fibers induces hypertrophy and leads to interstitial fibrosis. Ventricular dilatation and reduced wall thickness contributes to a further increase of the already elevated myocardial wall stress and triggers the continuous decrease of myocardial function. The initial myocyte injury by different and mostly unknown causes leads to progressive myocyte damage resulting in a similar uniform clinical picture independent from the initial myocellular derangement. One of the common pathways may be an inadequate response of the heart to human growth hormone (GH). Several studies support this hypothesis: GH deficiency results in a significant reduction of ventricular wall thickness and myocardial function, and GH-substitution is able to normalize the depressed left ventricular function. In addition, Sacca et al. reported in an uncontrolled study that GH-therapy reduced left ventricular wall stress by 40% in 7 patients with dilated cardiomyopathy. There was a parallel increase of the ejection fraction from 34% to 47%. This improvement was accompanied by a decrease of the functional classification of heart failure from NYHA 2.7 to 1.6. This therapeutic approach to alter the myocyte function directly by growth factors may open a new therapeutic concept in dilated cardiomyopathy. If double blind, randomized studies confirm the results of Sacca's study, a new era of therapeutic options may be available for the treatment of dilated cardiomyopathy.

Dobutamine stress echocardiography in the evaluation of late anthracycline cardiotoxicity in childhood cancer survivors.

Late anthracycline cardiotoxicity has been of increasing concern to pediatric oncologists. An increasing number of patients with cardiac dysfunction has been reported without a good correlation between cardiac function or symptoms and routine echocardiographic follow-up. We studied dobutamine stress echocardiography in patients who had received moderate doses of anthracyclines years before. Twenty-three patients (14 male, 9 female; 7-25 y) who completed chemotherapy with moderate doses of anthracyclines (180-380 mg/m2) more than 2 y previously underwent dobutamine stress echocardiography and were compared with a control group of 26 healthy young people (15 male, 11 female; 6-26 y) matched for age and weight. Dobutamine was administered in three periods up to a rate of 5 micro g/kg/min. Eighty-five percent of the patients showed an abnormal response to dobutamine. Both systolic and diastolic functions were affected. The systolic dysfunction was not related to diminished contractility but to an elevated systolic wall stress due to inadequate cardiac muscle thickening. The diminished wall thickening was related to the length of follow-up. Dobutamine proved to be a very sensitive method to detect clinical and subclinical cardiac dysfunction in patients post anthracycline chemotherapy and questions the concept of a safe dose.

Alteration of growth responses in established cardiac pressure overload hypertrophy in rats with aortic banding.

We examined the acute effects of elevated wall stress, norepinephrine, and angiotensin II on cardiac protein synthesis as well as protooncogene expression in hearts with established pressure overload left ventricular hypertrophy. Isolated rat hearts with chronic hypertrophy (LVH) were studied 12 wk after ascending aortic banding when systolic function was fully maintained. New protein synthesis (incorporation of [3H]phenylalanine [Phe]) was analyzed in isolated perfused rat hearts after a 3-h protocol; c-fos, c-jun, c-myc, and early growth response gene-1 (EGR-1) mRNA levels (Northern blot) were studied over a time course from 15 to 240 min of perfusion. Under baseline conditions (i.e., before mechanical or neurohormonal stimulation), [3H]-Phe-incorporation (280 nmoles/gram protein/h) and protooncogene mRNA levels were similar in age-matched control and LVH hearts. However, hearts with chronic LVH were characterized by a markedly blunted or absent [3H]-Phe-incorporation after acute imposition of isovolumic systolic load (90 mmHg/gram left ventricle), as well as norepinephrine (10(-6)M), or angiotensin II infusion (10(-8)M plus prazosin 10(-7)M) compared with nonhypertrophied control hearts. Similarly, stimulation of LVH hearts with acute systolic load or norepinephrine was associated with a significantly blunted increase of protooncogene mRNA levels relative to control hearts. The blunted induction of c-fos mRNA in LVH hearts was not due to feedback inhibition, since cycloheximide perfusion of hearts exposed to elevated wall stress further increased the differences between age-matched control and LVH hearts. The data suggest that acute molecular growth responses to mechanical or neurohormonal stimulation are altered in rat hearts with established LVH relative to nonhypertrophied control hearts. This alteration of molecular adaptations in hearts with compensatory hypertrophy may prevent inappropriate excess cardiac growth in response to mechanical and neurohormonal stimuli.

Critical review of heart failure: the role of left ventricular remodeling in the therapeutic response.

Recent clinical investigations have provided new insights into physiologic alterations taking place as heart failure progresses. As a result, new end points may be more relevant to monitor in patients, rather than the classical assessment of severity based on subjective evaluation of functional capacity. Structural changes of the myocardium, referred to as remodeling, have profound effects on the performance of the left ventricle and on long-term prognosis. Left ventricular ejection fraction may serve as a clinical marker for remodeling changes. Remodeling changes involve hypertrophy of the muscle mass, dilation of the left ventricle, and a change in the shape of the ventricle. Histologically, these changes are produced by myocyte lengthening, interstitial growth, and myocyte slippage. The consequences of remodeling include an abnormal bio-energetic state because of the augmented wall stress and accentuated myocardial oxygen consumption. The elevated wall stress promotes further hypertrophy. Superimposed on the remodeling changes is neurohormonal activation. Both remodeling and neurohormonal activation are directly related to mortality. An experimental canine model has been used successfully to investigate the potential impact of pharmacologic intervention on remodeling. Angiotensin-converting enzyme inhibitors and the combination of hydralazine and isosorbide dinitrate have been shown in clinical trials to reduce long-term mortality and increase ejection fraction. The effects of these drugs appear to be mediated in part by alterations in remodeling and neurohormonal activation. Thus, left ventricular ejection fraction can be used as a clinical marker for remodeling processes, and plasma norepinephrine levels can be used as a marker for neurohormonal activation.

Different left ventricular remodelling and function in two models of pressure overload as assessed in vivo by magnetic resonance imaging.

To follow the development of left ventricular structure and function in vivo in two different models of pressure-overload hypertrophy. From age 6 weeks, left ventricular structure and function changes in spontaneously hypertensive (SHR) and renal hypertensive (RHR) rats were followed in vivo by magnetic resonance imaging over 7 months. Wistar-Kyoto rats served as controls. Systolic blood pressure (SBP) was measured once a week by the tail-cuff method. Transverse left ventricular sections were obtained at end-diastole and end-systole by electrocardiogram-gated magnetic resonance imaging, allowing the determination of left ventricular mass, wall thickness and volume. Angiotensin II (Ang II) plasma levels were determined at 2 and 4 weeks into the study. At the end of the study functional parameters were obtained by left ventricular catheterization. After 4 weeks both SHR and RHR showed a similar degree of hypertension. At 4 weeks Ang II levels were significantly elevated in RHR and suppressed in SHR relative to controls. The extent of left ventricular hypertrophy was essentially the same in SHR and RHR, but the diastolic left ventricular wall thickness: volume ratio was substantially increased in RHR only. During the first 11 weeks of the study, a small end-systolic volume and an increased end-systolic wall thickness allowed the systolic wall stress in RHR to be maintained near control values. Thereafter a discrete deterioration of left ventricular function was observed, as demonstrated by the steady increase in end-systolic volume. In contrast, SHR did not show an increase in end-systolic wall thickness at any time, resulting in an elevated systolic wall stress. However, left ventricular function was stable during the observed period. Despite similar SBP and left ventricular mass, left ventricular remodelling and function were different in RHR and SHR. SHR appeared to be stable during the 30-week observation period, whereas RHR exhibited a progressive functional impairment after week 11. The distinct involvement of the renin-angiotensin system in the pathogenesis of hypertension in these models may account for these differences.

Angiotensin II–Induced Growth Responses in Isolated Adult Rat Hearts

Cardiac myocyte hypertrophy often occurs in response to both hemodynamic and neurohumoral factors. To study whether activation of the renin-angiotensin system by itself may induce a cardiac growth response, the acute effects of angiotensin II on cardiac protein synthesis were studied in isolated rat hearts. New protein synthesis in isolated buffer-perfused adult rat hearts was measured by incorporation of [3H]phenylalanine into cardiac proteins during a 3-hour perfusion protocol. Angiotensin II (1 x 10(-8) mol/L), administered alone or in combination with the alpha 1-blocker prazosin (1 x 10(-7) mol/L), stimulated protein synthesis in both ventricles. The rate of [3H]phenylalanine incorporation into cardiac proteins was 3.9-fold (P < .005) and 2.6-fold (P < .01) higher in angiotensin II-perfused (n = 6) than in vehicle-perfused (n = 6) left and right ventricles, respectively. The induction of new protein synthesis by angiotensin II was blocked by the angiotensin II type 1 (AT1) receptor antagonist losartan (1 x 10(-7) mol/L, n = 5). To study the pathways of angiotensin signal transduction, protein kinase C (PKC)-epsilon as well as cardiac c-fos and c-jun mRNA levels were analyzed. Angiotensin II (1 x 10(-8) mol/L, n = 20) resulted in a transient translocation of PKC-epsilon from the cytosol to the cellular membrane. However, compared with phorbol ester stimulation (phorbol 12-myristate 13-acetate [PMA], 1 x 10(-7) mol/L; n = 20), angiotensin II effects on PKC translocation were significantly less pronounced and required a more prolonged stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of left ventricular hypertrophy, afterload, and contractility to left ventricular performance in Goldblatt hypertension.

To analyze the determinants of left ventricular (LV) performance (myocardial afterload, chamber size, mass, and contractility) in Goldblatt hypertension, 19 anesthetized one-kidney, one-clip (1K1C) and 28 two-kidney, one-clip (2K1C) male Wistar rats were studied 58 to 62 days after clipping, together with 19 sham-operated and 13 normal rats (controls), by M-mode echocardiography using necropsy-validated methods of measurement. The LV fractional shortening was inversely related to end-systolic stress in all groups (r = -0.89 to -0.95, all P less than .00001): 7 2K1C (25%) and 9 1K1C (47%) had fractional shortening above the upper confidence limit in control animals. Both 1K1C and 2K1C with high LV performance had severe hypertension, inadequate LV hypertrophy, with resultant high wall stress (both P less than .005), increased LV chamber dimension (P less than .005 and P less than .05, respectively) and high afterload-corrected fractional shortening (both P less than .001); 2K1C also had high plasma renin activity and atrial natriuretic factor levels (both P less than .01). Rats with normal LV performance exhibited mild hypertension, adequate LV hypertrophy (normalizing wall stress), and normal LV chamber size and afterload-corrected fractional shortening. Thus, 8 1/2 weeks after clipping, adequate LV hypertrophy allows maintenance of normal LV function by normalizing myocardial afterload in a majority of rats with Goldblatt hypertension, whereas increased LV contractility (and possibly use of preload reserve in 1K1C) maintains normal LV function in the presence of inadequate LV hypertrophy and elevated wall stress, in a substantial minority of rats that developed more severe Goldblatt hypertension.

The effect of ACE inhibition on myocardial energy metabolism

There are several indications that the oxygen supply to the myocardium is inadequate in chronic heart failure. This is due to an increased intramyocardial vascular resistance, elevated filling pressures, and a shortened diastolic perfusion time. In parallel, the myocardial oxygen demand is heightened due to elevated wall stress, heart rate and contractility. This imbalance between myocardial oxygen supply and demand might be the cause of the adaptive metabolic changes seen in severe chronic heart failure. We showed increased LDH 5, decreased LDH 1 and increased ADP/ATP-carrier concentration in the myocardium from patients with chronic heart failure. After ACE-inhibitor treatment in 33 patients with chronic heart failure, LDH 1 increased from 38.7 +/- 6.7% to 42.3 +/- 5.5% (P less than 0.005) paralleled by a decrease in LDH 5 from 20.8 +/- 7.0% to 15.8 +/- 4.7% (P less than 0.001). The ADP/ATP-carrier concentration also decreased significantly within the normal range. This shift in the LDH isoenzyme pattern and decrease in the ADP/ATP-concentration can be interpreted as an indication for an improvement of myocardial energy balance in chronic heart failure under ACE-inhibitor therapy. This might help interrupt the self-perpetuation of chronic heart failure which is partially caused by a progressive subendocardial perfusion deficit.

Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy

Because idiopathic dilated cardiomyopathy is characterized by elevated wall stress and a more spherical left ventricle, the relations among shape, afterload and survival were examined. Thirty-six patients with cardiomyopathy were prospectively studied by two-dimensional echocardiography. Data included echocardiographic short- and long-axis cavity dimensions, their ratio and, with cuff systolic blood pressure, meridional and circumferential end-systolic stresses and their ratios. Survivors (n = 16) were followed up for 52 months (range 40 to 76); nonsurvivors (n = 20) died an average of 11 months after study.Survivors had a smaller left ventricular end-diastolic short-axis dimension (6.4 versus 7.1 cm, p < 0.03) but a similar long-axis length (8.6 versus 8.3 cm). However, overall cavity shape or the ratio of short- to long-axis end-diastolic dimensions was more spherical in those with poorer survival (ratio 0.76 versus 0.68, p 0.02). Meridional and circumferential end-systolic stresses were similar in the two groups, but stress was more evenly distributed in the long- and short-axis planes in nonsurvivors (meridional/circumferential stress ratio 0.57 versus 0.52 in survivors, p < 0.05). Improved survival was associated with an end-diastolic short-axis dimension <7.6 cm, a short- to long-axis ratio <0.76 and a meridional to circumferential stress ratio <0.54. Life table analysis revealed a 28% mortality rate in patients with all three of these characteristics compared with 100% in patients with none. Survivors and nonsurvivors did not differ in systolic cavity dimension, wall thickness, relative wall thickness, cavity volume, percent posterior wall thickening or fractional shortening.In conclusion, a poorer survival was associated with a more spherical ventricle and a more uniform distribution of afterload. In contrast, there was no association between survival and wall thickness, systolic function and endsystolic stress. Two-dimensional echocardiographic determinations of cavity dimension, shape and load distribution may provide useful prognostic information in dilated cardiomyopathy.

Effects of hydralazine on pressure-volume and stress-volume relations in congestive heart failure secondary to idiopathic dilated cardiomyopathy

The mechanism by which hydralazine improves cardiac function in patients with heart failure is not well characterized. Hydralazine may improve left ventricular (LV) function by decreasing afterloading wall stress or by increasing myocardial contractility. The effect of intravenous hydralazine was assessed in 8 patients with severe idiopathic dilated cardiomyopathy. Hydralazine increased stroke volume index (from 24 ± 8 to 40 ± 9 ml/m 2, p < 0.01) and decreased systemic vascular resistance (from 1,603 ± 619 to 810 ± 317 dynes s cm −5, p < 0.01) and peak LV wall stress (from 476 ± 118 to 410 ± 68 kdynes/cm 2, p = 0.02). Two groups were defined by normal or high LV wall stress. Patients with high LV stress had higher LV end-diastolic pressure (38 ± 12 vs 17 ± 8 mm Hg, p < 0.01), LV end-diastolic volume index (184 ± 24 vs 149 ± 7 ml/m 2, p < 0.01) and systemic vascular resistance (1,423 ± 686 vs 846 ± 293 dynes s cm −5, p = 0.01). Hydralazine decreased stress more in these patients (−101 ± 57 vs −6 ± 9 kdynes/cm 2, p = 0.02), LV end-diastolic pressure (−12 ± 7 vs 2 ± 2 mm Hg, p = 0.02), systolic pressure (−15 ± 13 vs 3 ± 4 mm Hg, p = 0.03) and systemic vascular resistance (−1,053 ± 247 vs −363 ± 83 dynes s cm −5, p < 0.01) than in patients with normal LV stress. Decreased LV stress was caused by decreased systolic and diastolic pressures and/or volumes. Late systolic pressure-volume relations in patients with normal LV stress suggested increased myocardial contractility, but this was not confirmed by LV dP/dt. Hydralazine improves LV function in patients with dilated cardiomyopathy by reducing elevated LV wall stress, with little inotropic effect.

Relation between exercise-induced changes in ejection fraction and systolic loading conditions at rest in aortic regurgitation

To examine the role of systolic wall stress at rest in determining left ventricular performance during exercise in aortic regurgitation (AR), systolic wall stress (measured by M-mode echocardiography) was related to changes in left ventricular function during maximal exercise (evaluated by radionuclide ventriculography) in 30 patients with chronic aortic regurgitation. Of these 30 patients, 7 had a normal exercise response, defined as an absolute increase in ejection fraction of 5% or greater (Group I) and 23 had abnormal exercise response, defined as no change (less than 5% change) or a decline (less than or equal to 5%) in ejection fraction (Group II). Patients in Group I had a significantly lower radius/wall thickness ratio (2.5 +/- 0.2 versus 3.1 +/- 0.1, p less than 0.01) and lower peak systolic wall stress (123 +/- 11 versus 211 +/- 12 X 10(3) dynes/cm2, p less than 0.01) than patients in Group II. An increase in ejection fraction during exercise was seen in 6 of the 9 patients with normal systolic wall stress at rest (less than 150 X 10(3) dynes/cm2), but in only 1 of 21 patients with elevated systolic wall stress (p less than 0.001). Peak systolic wall stress at rest varied linearly, and inversely with changes in left ventricular ejection fraction during exercise (r = 0.60, p less than 0.001). Groups I and II did not differ in ejection fraction at rest, clinical symptoms or maximal work load achieved.(ABSTRACT TRUNCATED AT 250 WORDS)