Depressed Left Ventricular Contractility Research Articles

Reduced left ventricular contractility, increased diastolic operant stiffness and high energetic expenditure in patients with severe aortic regurgitation without indication for surgery.

Recent mortality studies showed worse prognosis in patients (ARNS) with severe aortic regurgitation and preserved ejection fraction (EF) not fulfilling the criteria of current guidelines for surgery. The aim of our study was to analyse left ventricular (LV) systolic and diastolic function and mechanical energetics to find haemodynamic explanations for the reduced prognosis of these patients and to seek a new concept for surgery. Global longitudinal strain (GLS) and echo-based single-beat pressure-volume analyses were performed in patients with ARNS (LV end-diastolic diameter <70 mm, EF >50%, GLS > -19% n = 41), with indication for surgery (ARS; n = 19) and in mild hypertensive controls (C; n = 20). Additionally, end-systolic elastance (LV contractility), stroke work and total energy (pressure-volume area) were calculated. ARNS demonstrated significantly depressed LV contractility versus C: end-systolic elastance (1.58 ± 0.7 vs 2.54 ± 0.8 mmHg/ml; P < 0.001), despite identical EF (EF: 59 ± 6% vs 59 ± 7%). Accordingly, GLS was decreased [-15.7 ± 2.7% (n = 31) vs -21.2 ± 2.4%; P < 0.001], end-diastolic volume (236 ± 90 vs 136 ± 30 ml; P < 0.001) and diastolic operant stiffness were markedly enlarged, as were pressure-volume area and stroke work, indicating waste of energy. The correlation of GLS versus end-systolic elastance was good (r = -0.66; P < 0.001). ARNS and ARS patients demonstrated similar haemodynamic disorders, whereas only GLS was worse in ARS. ARNS patients almost matched the ARS patients in their haemodynamic and energetic deterioration, thereby explaining poor prognosis reported in literature. GLS has been shown to be a reliable surrogate for LV contractility, possibly overestimating contractility due to exhausted preload reserve in aortic regurgitation patients. GLS may outperform conventional echo parameters to predict more precisely the timing of surgery.

Cardiac changes during the peri-menopausal period in a VCD-induced murine model of ovarian failure.

AimCardiovascular disease (CVD) risk is lower in pre‐menopausal females vs age matched males. After menopause risk equals or exceeds that of males. CVD protection of pre‐menopausal females is ascribed to high circulating oestrogen levels. Despite experimental evidence that oestrogen are cardioprotective, oestrogen replacement therapy trials have not shown clear benefits. One hypothesis to explain the discrepancy proposed hearts remodel during peri‐menopause. Peri‐menopasual myocardial changes have never been investigated, nor has the ability of oestrogen to regulate heart function during peri‐menopause.MethodsWe injected female mice with 4‐vinylcyclohexene diepoxide (VCD, 160 mg/kg/d IP) to cause gradual ovarian failure over 120d and act as a peri‐menopausal modelResultsLeft ventricular function assessed by Langendorff perfusion found no changes in VCD‐injected mice at 60 or 120 days compared to intact mice. Cardiac myofilament activity was altered at 60 and 120 days indicating a molecular remodelling in peri‐menopause. Myocardial TGF‐β1 increased at 60 days post‐VCD treatment along with reduced Akt phosphorylation. Acute activation of oestrogen receptor‐α (ERα) or ‐β (ERβ) depressed left ventricular contractility in hearts from intact mice. ER‐regulation of myocardial and myofilament function, and myofilament phosphorylation, were disrupted in the peri‐menopausal model. Disruption occurred without alterations in total ERα or ERβ expression.ConclusionsThis is the first study to demonstrate remodelling of the heart in a model of peri‐menopause, along with a disruption in ER‐dependent regulation of the heart. These data indicate that oestrogen replacement therapy initiated after menopause affects a heart that is profoundly different from that found in reproductively intact animals.

Dynamic myocardial depression in septic cardiomyopathy

Depression of left ventricular contractility appears in many diseases resulting from various etiology factors. One of the most interesting features of septic cardiomyopathy is the significant dynamic myocardial depression that is commonly observed. In this context, the objective of the present work is to characterize clinically, by laboratory, by echocardiography, and by invasive measures the patients with septic cardiomyopathy.

Physiological Relevance of Quantifying Segmental Contraction Synchrony

Most current indices of synchrony quantify left ventricular (LV) contraction pattern in terms of a single, global (integrated) measure. We report the development and physiological relevance of a novel method to quantify LV segmental contraction synchrony. LV pressure-volume and echocardiographic data were collected in seven anesthetized, opened-chest dogs under several pacing modes: right atrial (RA) (control), right ventricular (RV) (dyssynchrony), and additional LV pacing at either apex (CRTa) or free wall (CRTf). Cross-correlation-based integrated (CCSI(int) ) and segmental (CCSI(seg) ) measures of synchrony were calculated from speckle-tracking derived radial strain, along with a commonly used index (maximum time delay). LV contractility was quantified using either E(es) (ESPVR slope) or ESPVR(area) (defined in the manuscript). RV pacing decreased CCSI(int) at LV base (0.95 ± 0.02 [RA] vs 0.64 ± 0.14 [RV]; P < 0.05) and only CRTa improved it (0.93 ± 0.03; P < 0.05 vs RV). The CCSI(seg) analysis identified anteroseptal and septal segments as being responsible for the low CCSI(int) during RV pacing and inferior segment for poor resynchronization with CRTf. Changes in ESPVR(area) , and not in E(es) , indicated depressed LV contractility with RV pacing, an observation consistent with significantly decreased global LV performance (stroke work [SW]: 252 ± 23 [RA] vs 151 ± 24 [RV] mJ; P < 0.05). Only CRTa improved SW and contractility (SW: 240 ± 19 mJ; ESPVR(area) : 545 ± 175 mmHg•mL; both P < 0.01 vs RV). Only changes in CCSI(seg) and global LV contractility were strongly correlated (R(2) = 0.698, P = 0.005). CCSI(seg) provided insights into the changes in LV integrated contraction pattern and a better link to global LV contractility changes.

Anticoagulation Therapy In Heart Failure Patients With Normal Heart Rhythm: A Review Of The Evidence

Purpose: The purpose of this review is to explore the current clinical trial data to determine if the use of anticoagulants in heart failure patients with systolic dysfunction and without demonstrated rhythm disturbances results in decreased mortality or a reduction in thromboembolic events.Data Sources: A literature search was conducted using Pub Med, CINAHL, and the Cochrane Library databases. The literature review was limited to randomized control trials with primary and secondary end points of all causes of mortality, embolic events (including stroke and myocardial infarction), and frequency of hospitalization that compared oral anticoagulants to control or placebo in patients with left ventricular systolic heart failure.Conclusions: Limited evidence exists to support the use of oral anticoagulation in heart failure patients without the presence of additional risk factors such as atrial fibrillation, severely depressed left ventricular contractility with known history of previous embolic event, or evidence of mural thrombus. Current studies established no significant difference in the primary endpoints for study participants, but demonstrated a trend toward increased risk of bleeding for those patients receiving warfarin therapy.Implications for practice: Health care practitioners should not contribute to the polypharmacy of this vulnerable patient population without clear evidence of benefit. Until more definitive data are available, clinicians should assess the use of oral anticoagulation in heart failure on a case by case basis. The use of oral anticoagulants should be limited to those heart failure patients with additional risk factors.

Myocardial function in patients with Shwachman–Diamond syndrome: Aspects to consider before stem cell transplantation

Early studies have suggested increased risk of fatal cardiac complications in infants with Shwachman-Diamond syndrome (SDS), an inherited bone marrow failure syndrome. Patients undergoing stem cell transplantation (STC) have appeared susceptible to organ toxicity, including cardiac involvement. This study assessed anatomical and functional features of the heart in SDS. Eight patients (mean age 24.1 years, range 7-37 years, seven males) with SDS and confirmed SBDS mutations were prospectively assessed for cardiac anatomy, myocardial wall properties, and systolic and diastolic function. The study protocol included conventional echocardiography (n = 8) complemented by exercise Tissue-Doppler echocardiography (n = 7), and by MRI (n = 6). No abnormalities in cardiac anatomy or function were observed in baseline clinical assessment, EKG, or conventional echocardiographic and MRI measurements. Myocardial structure and left ventricular (LV) mass were normal. The maximum isovolumic acceleration (IVA) value during exercise in Tissue-Doppler was significantly lower (P < 0.001), and the right ventricular (RV) ejection fraction (P = 0.02) and peak filling rate (PFR, P = 0.008) at rest in MRI were higher in patients. Children and young adults with SDS and mutations in SBDS had normal cardiac anatomy and myocardial structure. Subtle RV diastolic function alterations at rest and depressed LV contractility during exercise were observed. Further studies are warranted to evaluate the clinical importance of these findings.

Exposure to Anthracyclines During Childhood Causes Cardiac Injury

The use of anthracyclines in the treatment of acute lymphoblastic leukemia is limited by associated cardiotoxic effects, which can result in cardiomyopathy and congestive heart failure, and may be irreversible. Anthracycline-induced cardiotoxicity in long-term survivors of childhood cancer is characterized by reduced left ventricular wall thickness and mass, which is indicative of decreased cardiac muscle and depressed left ventricular contractility which is indicative of unhealthy heart muscle. Risk factors for anthracycline-induced cardiotoxicity include high cumulative anthracycline doses, high anthracycline dose intensity, and radiotherapy. Radiotherapy in patients with cancer treated with anthracyclines can exacerbate anthracycline-induced cardiac tissue damage. Several studies have shown that cardiomyopathy disease progression can be delayed in adults by using angiotensin-converting enzyme inhibitors such as enalapril. Studies in long-term survivors of pediatric cancer showed that enalapril has significant benefits in preventing cardiac functional deterioration on a short-term basis, but this is not sustained. Anthracycline-associated cardiotoxic effects can be combatted by preventing cardiac injury during chemotherapy administration. There is evidence that dexrazoxane significantly reduces the cardiotoxicity associated with anthracyclines such as daunorubicin, doxorubicin, and epirubicin in adult patients with a wide range of tumor types. A study of the efficacy of dexrazoxane in reducing doxorubicin-induced cardiotoxicity in children and adolescents with high-risk acute lymphoblastic leukemia, showed that significantly fewer dexrazoxane-treated patients (21%) had elevated serum cardiac troponin (a biomarker of acute myocardial injury) levels than patients treated with chemotherapy alone (50%; P <.001). Dexrazoxane was also shown to have no effect on the event-free survival rate at 2.5 years, emphasizing that it does not detrimentally affect the efficacy of anthracycline therapy.

Acute pulmonary hypertension causes depression of left ventricular contractility and relaxation

The haemodynamic effects of acute pulmonary hypertension can be largely attributed to ventricular interdependence during diastole. However, there is evidence that the two ventricles also interact during systole. The aim of the present study was to examine the effects of acute pulmonary hypertension on both components of left ventricular systole, i.e. contraction and relaxation, using load-independent indices. Ten pigs were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary pressure catheter. Haemodynamic measurements were performed in baseline conditions and during stable pulmonary vasoconstriction induced by the thromboxane analogue U46619. Contractility was quantified using the end-systolic pressure-volume and preload recruitable stroke work relationships. The tau-end-systolic pressure relationship was used to assess load-dependency of relaxation. Acute pulmonary hypertension caused a decrease in the slope of the left ventricular preload recruitable stroke work relationship (from 6.64 +/- 1.7 to 5.19 +/- 1.9, mean +/- SD; P < 0.05), a rightward shift of the end-systolic pressure-volume relationship (P < 0.05), and an increase in the slope of the tau-end-systolic pressure relationship (from -0.15 +/- 0.5 to 0.35 +/- 0.17; P < 0.05). The diastolic chamber stiffness constant of both ventricles increased during pulmonary hypertension (P < 0.05). In the present model, acute pulmonary hypertension impairs left ventricular contractile function and relaxing properties. The present study provides additional evidence that, besides the well-known diastolic ventricular cross talk, systolic ventricular interaction may play a significant role in the haemodynamic consequences of acute pulmonary hypertension.

The efficacy of nicorandil, calcium chloride and nitroglycerin in treatment of ropivacaine-induced cardiotoxicity

Background and objective: The amide-linked local anaesthetics, bupivacaine and ropivacaine, can cause depression of cardiac contractility and dysrhythmias. In a previous study, we observed decreased contractility and ST segment depression following ropivacaine administration in anaesthetized dogs. The efficacy of intravenous (i.v.) and intracoronary nicorandil (30 and 100 μg kg−1), i.v. nitroglycerin (glyceryl trinitrate) (5 μg kg−1) and calcium chloride (1, 2 and 4 mmol) in reversing the cardiotoxic effects of intracoronary ropivacaine were studied following the administration of intracoronary ropivacaine. Methods: Six dogs were studied. The dogs were anaesthetized with i.v. pentobarbital (30 mg kg−1). A left-sided thoracotomy was performed and the left circumflex coronary was cannulated. For each dog, the dose of ropivacaine was identified, which produced measurable cardiotoxicity. In each case, ropivacaine was followed by one of the three resuscitation drugs. The effects of each resuscitation drug on ST segments and left ventricular contractility (dP/dt) produced by ropivacaine alone were compared with those produced by ropivacaine followed by each of the three resuscitation drugs using Fisher's exact test. Results: The doses of ropivacaine required to produce depression of left ventricular dP/dt and ST segments ranged from 1 to 8 mg. Ropivacaine-induced depression of left ventricular contractility (dP/dt) was more rapidly and completely reversed by calcium chloride than by either nitroglycerin or nicorandil (P = 0.008). Conclusions: Calcium chloride may be effective in the treatment of inadvertent intravascular administration of amide local anaesthetic agents.

Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy.

Left ventricular noncompaction (LVNC) is a reportedly uncommon genetic disorder of endocardial morphogenesis with a reportedly high mortality rate. The purpose of this study was to identify the clinical characteristics of children with LVNC. We retrospectively reviewed 36 children with LVNC evaluated at Texas Children's Hospital (TCH) from January 1997 to December 2002. Five children had associated cardiac lesions. There were 16 girls and 20 boys. The median age at presentation was 90 days (range, 1 day to 17 years). The median duration of follow-up was 3.2 years (range, 0.5 to 12 years). Twenty-seven patients (75%) had ECG abnormalities, most commonly biventricular hypertrophy (10 patients, 28%). Both ventricles were involved in 8 patients (22%) and only the left ventricle in 28 patients (78%). Left ventricular systolic function was depressed in 30 patients (83%), with a median ejection fraction of 30% (range, 15% to 66%) at diagnosis. Nine patients presenting in the first year of life with depressed left ventricular contractility had a transient recovery of function; however, ejection fraction deteriorated later in life, at a median interval of 6.3years (range, 3 to 12 years). Two patients had an "undulating" phenotype from dilated to hypertrophic cardiomyopathy. Two patients (6%) were identified with an underlying G4.5 gene mutation. Five patients (14%) died during the study. LVNC does not have an invariably fatal course when diagnosed in the neonatal period. A significant number of patients have transient recovery of function followed by later deterioration, which may account for many patients presenting as adults, some manifesting an "undulating" phenotype.

Prognostic significance of the left ventricular contractility index in patients with essential hypertension

The aim of the study was to assess the relationship between the left ventricular (LV) contractility index, cardiac function and extracardiac organ damage in essential hypertension (EH). We have studied 142 patients (pts) with EH, age 43–52 years, free of signs of heart failure, normal values of the LV ejection fraction and fractional shortening. From M-mode Echo midwall fractional shortening (mFS)(de Simone method), end-systolic stress ESS (Reichek method) were calculated. LV contractility index was assessed as mFS in relation to ESS(mFS/ESS). Early filling velocity (E), late filling velocity (A), E/A ratio, isovolumic relaxation time (IVRT) and deceleration time (DT) were determined by Doppler-Echo. Albuminuria was measured as albumin to creatinine ratio (ACR). Retinal vascular changes were evaluated by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of LV hypertrophy and depressed LV contractility were 68.0 and 43.0%, respectively. The pts with depressed LV contractility index showed high prevalence of LV hypertrophy (86.7% vs 32.3%, p<0.001), especially eccentric hypertrophy (58.0% vs 14.2%, p<0.001). Pts with depressed mFS/ESS had longer IVRT and DT with significant difference in peak E-, A-wave and E/A ratio (IVRT-157.5±9.40 vs 120.0±10.0 ms; 292.5 ±23.4 vs 214.0±6.1 ms; E-60.5±2.43 vs 70.2±1.28 cm/s; A-71.2±2.70 vs 52.0±1.64 cm/s; E/A-0.96 ±0.04 vs 1.20 ±0.08, p<0.01 for all). IVRT and DT showed a strong relation to mFS/ESS (r=−0.67 and r=−0.69, respectively, p<0.01 for both). Moreover hypertensives with depressed mFS/ESS showed early signs of extracardiac damage namely increased ACR (3.2±0.6 vs 1.2 ±0.08, p<0.01) and serum creatinine (3.6±1.2 vs 1.0±0.06 mg%, p<0.05), a higher prevalence of retinopathy (fundoscopy grade II or beyond) compared with subjects with preserved contractility (89.0% vs 40.0%, p<0.001). Furthermore, mFS/ESS was strongly associated with ACR and serum creatinine level in an univariate analysis (r=−0.59 and r=−0.62, respectively, p<0.01 for both) and these associations were still present after stepwise multivariate analysis. Pts with depressed contractility show a higher prevalence of LV hypertrophy, diastolic dysfunction and early signs of extracardiac vascular damage. The evaluation of LV contractility index might improve the prognostic stratification of hypertensive pts and it might be suitable to recognize subset of pts at higher risk.

Protective effect of 3-deazaadenosine in a rat model of lipopolysaccharide-induced myocardial dysfunction.

Severe sepsis is accompanied by a profound depression of myocardial contractility. Leukocyte adhesion with subsequent local excess nitric oxide and reactive oxygen species production play major roles for this deleterious effect. We hypothesized that 3-deazaadenosine (c3Ado), an adenosine analogue with anti-inflammatory properties, prevents endotoxin-induced myocardial dysfunction. Wistar rats (8 per group) were treated with Escherichia coli lipopoly-saccharide (LPS, 1 mg/kg, i.p., strain 0111:B4) +/- c3Ado (10 mg/kg, i.p.) 8 h before their hearts were harvested for isolated perfusion, histochemical analysis, or electrophoretic mobility shift assay. LPS induced a marked depression of left ventricular contractility. Immunohistochemistry revealed an upregulation of the adhesion molecules VCAM-1, ICAM-1, and P-selectin within the postcapillary venules. c3Ado inhibited VCAM-1 and ICAM-1 upregulation, but not P-selectin, and prevented cardiodepression. Electrophoretic mobility shift assay revealed inactivation of the transcription factor nuclear factor-kappaB and immunohistochemical staining for gp91phox, ED1, and CD11b demonstrated that c3Ado prevented local recruitment of monocytes and polymorph nuclear neutrophils to the myocardium. Accordingly, significantly fewer leukocytes producing nitric oxide or reactive oxygen species accumulated within the myocardium. Intravital microscopy of intestinal venules confirmed that LPS-induced adhesion of leukocytes was prevented by c3Ado. Additionally, c3Ado prevented LPS-induced elevation of serum tumor necrosis factor-alpha levels. Our results imply that c3Ado may prove to have clinical relevance for inflammatory disease processes.

Non-invasive assessment of rejection in pediatric transplant patients: serologic and echocardiographic prediction of biopsy-proven myocardial rejection

Background: Cardiac allograft rejection is a multifocal immune process that is currently assessed using biopsy-guided histologic classification systems (International Society for Heart and Lung Transplantation). Cardiac troponin T and I are established serologic markers of global myocyte damage. The use of load-independent measures of contractility have also been shown to accurately assess the presence of ventricular dysfunction. Little is known about their utility in accurately predicting rejection in the pediatric age group. We undertook the present study to compare rejection grade with echocardiographic and serologic estimates of transplant rejection–related myocardial damage. Methods We compared histologic rejection grades (0 to 4) with patient characteristics, echocardiographic measurements, catheterization measurements, and biochemical markers for 86 evaluations in 37 transplant recipients at Children’s Hospital. Results In univariate analyses, biopsy scores correlated ( p < 0.05) inversely with left ventricular systolic function (shortening fraction) and contractility (stress velocity index, SVI), and directly with mitral E-wave amplitude. In multivariate analyses, lower contractility and higher mitral E-wave amplitude remained significantly ( p ≤ 0.01) associated with rejection (SVI, p = 0.002, odds ratio = 0.393; E wave, p = 0.0002, odds ratio = 228). Most rejection episodes were associated with elevation of biochemical markers of myocardial injury. Although troponin I was weakly associated with differences between rejection grades ( p = 0.034), troponin T, creatine kinase–MB fraction, and C-reactive protein did not differ with biopsy-rejection scores. Serum markers had a poor predictive capacity for biopsy-detected rejection. Troponin T and I did correlate with increased left ventricular wall thickness and mass. Conclusion Progressively depressed left ventricular contractility and diastolic function are found with worsening pediatric heart transplant rejection–biopsy score; however, sensitive and specific serum markers do not correspond to the degree of active myocardial injury. The use of echocardiographic measures of contractility is associated with a specificity of 91.8% but low sensitivity of 66.7%. Overall we found poor concordance between serum markers and grade of rejection. It is unclear whether myocardial injury as assessed by serum markers, echocardiography, or histologic scoring is more important for assessment of acute rejection or long-term outcome, but it does not appear that serum and tissue markers of rejection can be used interchangeably.

Hemofiltrate from patients with severe sepsis and depressed left ventricular contractility contains cardiotoxic compounds.

Myocardial dysfunction due to sepsis is common in patients with multiple organ dysfunction syndrome and is believed to be produced by inflammatory mediators. Some of these mediators may be eliminated by continuous hemofiltration, which is a standard procedure in an ICU for renal replacement therapy. This study was designed to directly compare the effects of ultrafiltrates from patients with sepsis (UFs) with ultrafiltrates from healthy volunteers (UFh) in well-characterized cardiomyocyte culture systems. Isovolemic hemofiltration (filtration rate: 2 L/h, polyamide membrane) was performed during 12 hours in 5 patients with severe sepsis (Elebute Score >20) and simultaneously reduced left ventricular contractility (left ventricular stroke work index [LVSWI] <30 g m/m2) and in 5 healthy volunteers. Inflammatory mediator concentrations (interleukin [IL]-1beta, IL-6, IL-8, tumor necrosis factor [TNF] alpha, C3a, and C5a) were measured in plasma and ultrafiltrate samples taken shortly after the beginning of the hemofiltration procedure. Cell culture experiments were done comparing UFs with UFh by using spontaneously beating or electrically driven neonatal rat cardiomyocyte cultures. UFs contained significantly higher amounts of IL-1, IL-8, and C3a when compared to UFh. Simultaneously, UFs induced a decrease in the contraction frequency of electrically-stimulated cardiomyocytes, whereas UFh had no effect. The cardiotoxic effect could be reversed by the addition of a high concentration (2.4 mM) of Ca++. Hemofiltration did not alter parameters of cardiac performance during 12 hours in patients with sepsis. UFs induced significant cardiotoxic effects in rat cardiomyocytes, whereas UFh showed no cardiotoxicity. Contact of blood with the hemofiltration membrane did not induce activation of cardiotoxic mediators. Significantly higher filtration rates may be required to improve left ventricular contractility in patients with sepsis by hemofiltration.

Profound circulatory shock following heroin overdose

A 17-year-old previously healthy girl with profound circulatory shock following a heroin overdose is reported. Except for opiates no other substances and specifically no cocaine were found in the blood and urine samples. Even though the mechanism of shock is not completely understood, severe depression of left ventricular contractility seems to be the predominant reason. Acute right heart failure with decreased pulmonary capillary wedge pressure and arterial vasodilatation resulting in maldistribution of cardiac output cannot be ruled out as possible contributing factors. The shock was successfully reversed with volume loading and a high dose of dobutamine. The recovery was uneventful and the patient was discharged with normal cardiac function.

Comparison of cardiovascular changes after administration of gadodiamide injection and gadopentetate dimeglumine in dogs

The authors compared the cardiovascular effects of gadodiamide injection and gadopentetate dimeglumine. Gadodiamide injection or gadopentetate dimeglumine, each at doses of 0.3 or 1.5 mmol per kilogram of body weight, or saline volume control was administered intravenously in the cephalic vein of anesthetized dogs. Hemodynamic parameters, electrocardiographic parameters, and peripheral flow were measured. Neither the low or high dose of gadodiamide injection caused statistically significant (P < .05) changes in any of the measured cardiovascular parameters. High doses of gadopentetate dimeglumine, however, significantly decreased left ventricular and systemic blood pressure and significantly depressed left ventricular contractility (P < .05). Gadodiamide injection caused no observable cardiovascular effects, whereas high doses of gadopentetate dimeglumine caused cardio-depressive and hypotensive effects.

Transcatheter ablation of ectopic atrial tachycardia in young patients using radiofrequency current.

Ectopic atrial tachycardia (EAT) is a reversible cause of cardiomyopathy but may be quite difficult to control with conventional therapy. Transcatheter ablation with radiofrequency current was tested as an alternative to medical or surgical treatment of this condition. Twelve young patients (aged 10 months to 19 years) with drug-resistant EAT were treated with direct transcatheter ablation of the ectopic focus using radiofrequency (RF) energy. All had depressed left ventricular contractility by echocardiographic criteria, involving shortening fractions of 10-26% (median, 20%; normal, 28-35%). The EAT was mapped to the left atrium in seven cases and to the right atrium in five. Local atrial activation at the ectopic site preceded the onset of the surface P wave by 20-60 msec (median, 42 msec). Tachycardia terminated 0.5-13.0 seconds (median, 2.0 seconds) into a successful RF application. The ablation effectively eliminated EAT in 11 of 12 patients (92%), all of whom were discharged in sinus rhythm without medications after a median hospital stay of 48 hours. Ablation was unsuccessful in one patient with diffuse dysplasia of the anterior right atrium, who eventually did well after surgical resection of abnormal atrial tissue. Transient depression of sinus node function was noted in one patient who had successful ablation of an EAT focus in close proximity to the sinus node, although normal sinus node function returned within 72 hours. No other complications were encountered. During follow-up (3-21 months; median, 13 months), one patient had recurrence of a slower and less-sustained EAT that was successfully eliminated at a second ablation session. All others remained in sinus rhythm, and all 12 subjects recovered normal ventricular function. RF ablation appears to be a safe and effective therapeutic option for drug-resistant ectopic atrial tachycardia and may be the preferred first-line therapy for those patients with depressed ventricular function.

Left ventricular contractility is depressed in IgE-mediated anaphylactic shock in dogs

To determine whether myocardial dysfunction contributes to vascular collapse in anaphylactic shock, we examined left ventricular (LV) contractility, coronary blood flow, and myocardial lactate metabolism during antigen challenge in eight dogs that were sensitized to ragweed pollen extract (anaphylaxis group). Findings in the anaphylaxis group were contrasted to those in another group of dogs in which mean blood pressure was decreased to the same extent by arteriolar vasodilation with nitroprusside. The animals were examined under nonhypoxic conditions while anesthetized and ventilated. LV mechanics were examined with subendocardial crystals placed primarily along the anterior-posterior minor axis of the LV. During antigen challenge, a depression in LV contractility was observed in the anaphylaxis group as assessed by fractional dimensional shortening, stroke volume, and the slope of the end-systolic pressure-dimension relationship. During anaphylaxis, moreover, coronary vasodilation rather than coronary vasoconstriction was observed, and evidence of myocardial ischemia as assessed by altered myocardial lactate metabolism was not found. Our results indicate that depressed LV contractility occurs in anaphylactic shock. The results further suggest that the mechanism may be due to a direct effect of mediators of anaphylaxis on the myocardium to produce systolic dysfunction.

Effect of lactic acidosis on canine hemodynamics and left ventricular function

Hypoperfusion states cause lactic acidosis, and the acidemia further reduces the inadequate cardiac output. Conceivably, the adverse effect of lactic acidemia on cardiac output is due to depressed contractility demonstrated in isolated myocardium. Alternatively, factors governing venous return cause a relative hypovolemic state and/or acidemic pulmonary vasoconstriction-induced right ventricular dysfunction. We reasoned that examination of left ventricular pressure-volume relationships at end systole and end diastole would determine which of these potential mechanisms accounted for reduced cardiac output during progressive lactic acidosis in anesthetized, mechanically ventilated dogs. Left ventricular (LV) volume was estimated from two pairs of epicardial ultrasonic crystals placed in the anterior-posterior and longitudinal planes, and LV pressure was obtained rom a catheter-tipped transducer. During progressive acidemia induced by a continuous intravenous infusion of 0.5 N lactic acid, cardiac output, stroke volume, and mean systemic arterial pressure fell significantly while mean pulmonary artery pressure and right atrial pressure increased significantly. These variables did not change with time in control (no-acid infusion) dogs. Lactic acidemia caused a 40% reduction in stroke volume, which could be attributed to depressed LV contractility, characterized by a decrease in maximum dP/dt as well as a fall in slope (Emax) with no change in volume intercept (Vo) of the left ventricular pressure-volume relationship at end systole. Neither the measured left ventricular end-diastolic pressure nor the estimated left ventricular end-diastolic volume (LVEDV) decreased with acidemia, suggesting that the reduced venous return did not result from relative hypovolemia. However, acidemic pulmonary hypertension may have interfered with the expected response to myocardial depression, which is an increase in LVEDV.

Optimal matching between canine left ventricle and afterload.

A parabolic relationship exists between ventricular external work and arterial load at given preload and contractility. Previous data indicate that the working point falls close to the parabola optimum. By combining the left ventricular (LV) end-systolic pressure-volume relationship (ESPVR) and an equation describing external stroke work, optimum values of stroke volume (SV), the slope (Emax) of the ESPVR, and arterial resistance (Rp) corresponding with the optimum (i.e., mSV, mEmax, mRp) were obtained. Experiments in anesthetized dogs were performed to test whether mSV, mEmax, and mRp also correspond to observed SV, Emax, and Rp at three different levels of volume load (right atrial pressure, RAP) before and after acute depression of LV contractility. Comparisons of observed and optimal values of SV, Emax, and Rp were made before and after LV depression. Before embolization, the ratios were SV/mSV 1.10-1.20 (RAP 5-15 mmHg); Emax/mEmax 1.21-1.41; and Rp/mRp 0.84-0.69. After LV depression, SV/mSV was 0.80-0.83, Emax/mEmax was 0.78-0.71, and Rp/mRp was 1.56-1.46. The ratios were all significantly changed (P less than 0.01) by the induced LV depression. The present analysis may offer a new tool to detect nonoptimal relations between cardiac and arterial functions.