Ventricular Diastolic Pressure Research Articles

Res-Erection of Viagra as a Heart Drug

In 1998, the world was formally introduced to Viagra (sildenafil), the first oral agent to be approved in the United States for the treatment of erectile dysfunction. Developed by Pfizer chemists, sildenafil inhibited phosphodiesterase type 5 (PDE5), one of the 11-member superfamily of enzymes that hydrolyze cyclic nucleotide monophosphates and among the first discovered that was selective for cGMP. PDE5 had been identified more than 2 decades earlier, first as a protein that bound cGMP and later as one that hydrolyzed it (the binding function turning out to be a mechanism to regulate activity).1 Sildenafil induces vasorelaxation by blocking PDE5-cGMP hydrolysis, raising cGMP levels in smooth muscle to activate protein kinase G (also known as cGK). In platelets, this blunts thrombosis; together, the effects suggested a potential use for coronary vascular disease and hypertension. Pfizer initiated trials targeting coronary ischemia, but, although antianginal effects were disappointing, the study gave a whole new meaning to the term “side effect,” effectively hijacking sildenafil from cardiovascular development to a rather different indication. Article see p 8 There were still some cardiovascular studies performed, but essentially all were limited assessments of volunteer populations, mostly normal and at rest and some with cardiovascular disease; the results were interpreted to support safety for patients taking the drug. In particular, blood pressure changes were slight if present at all, and cardiac function appeared unaltered. Well into the mid 2000s, PDE5 was thought to be expressed in selective vascular beds, lung and corpus cavernosum being dominant, and to have a minor cardiovascular profile elsewhere, with a negligible role in the heart. Sildenafil reemergence as …

Protective effect of erythropoietin on myocardial infarction in rats by inhibition of caspase-12 expression

In the present study, the myocardial protective effects of erythropoietin (EPO) by inhibition of the expression of caspase-12 were investigated in a myocardial infarction rat model. Thirty male SD rats were divided into three groups: sham-operation group, myocardial infarction group and EPO treatment group. The myocardial infarction model was created by ligating the left anterior descending coronary artery. The EPO treatment group was established by injecting rh-EPO (1,000 IU/kg) intraperitoneally every day after the operation, and the other two groups were injected with sodium chloride. Four weeks after induction of myocardial infarction, the left ventricular diastolic pressure (LVDP) was tested by Langendorff apparatus and the pathological changes were analyzed by H&E staining. Caspase-12 expression in the left ventricular myocardium was also measured by immunohistochemistry. Four weeks after induction of myocardial infarction, the improvement in heart function in the EPO treatment group was more distinct compared to that of the myocardial infarction group; LVDP was higher in the EPO treatment group compared to the myocardial infarction group, but lower compared to the control group. H&E staining showed that the myocardial cells in the normal control group were aligned in order with a clear structure and were stained equably, while the myocardial cells in the myocardial infarction model rats lined up in disorder with an augmented cell body appearing to have many granules and interstitial fibrosis. Myocardial fibrosis and disorder were improved in the EPO treatment group. The expression of caspase-12 in the myocardial infarction group was also increased compared to the EPO treatment group rats. The results suggest that EPO improves heart function in myocardial infarction rats by down-regulating the expression of caspase-12, which may protect the myocardium by abrogating endoplasmic reticulum stress-mediated cardiomyocyte apoptosis and improving heart function.

Acute haemodynamic effects of increase in paced heart rate in heart failure patients recorded with an implantable haemodynamic monitor

The aim of this study was to investigate the acute effects of different biventricularly paced heart rates (pHRs) on right ventricular (RV) haemodynamics in heart failure (HF) patients with an implantable haemodynamic monitor (IHM). At rest, seven pHRs, range 60-120 bpm (steps of 10), were randomly programmed and maintained for 60 s in 10 patients (male, 65±12 years, New York Heart Association II-III). Right ventricular systolic (RVSP) and diastolic pressures, estimated pulmonary artery diastolic (ePAD) pressure, and RV+dP/dt were recorded beat-to-beat using the IHM. Cardiac output (CO) was estimated from the RV pressure waveforms and arterial blood pressure was measured (Portapres®). To compare the haemodynamic effects of increased pHR at rest to that of spontaneous, sinus-driven heart rate (HR) increase, patients also performed a symptom-limited bicycle exercise. At rest, RV+dP/dt increased significantly with elevated pHR (P, main effect, <0.001), whereas filling pressures (ePAD and RVSP) decreased significantly in the range 60-100 bpm (P<0.03 and P<0.003, respectively) but tended to increase or level out at pHRs>00 bpm. At a pHR of 100 bpm, ePAD was 1.4 mmHg lower compared with 60 bpm (P<0.01). Cardiac output increased gradually with elevated pHR at rest (P<0.001). Both total peripheral and estimated pulmonary arterial resistance significantly decreased with increased pHR. During exercise-induced maximum HR increase, RV+dP/dt, ePAD, and CO were all significantly higher compared with the corresponding pHR at rest. During cardiac resynchronization therapy in HF patients, the force frequency relationship is present in the RV, as increasing the pHR in the range 60-100 bpm results in decreased filling pressures and increased CO.

Anti-inflammatory effect of hydrogen-rich saline in a rat model of regional myocardial ischemia and reperfusion

To study the possible anti-inflammatory effect of hydrogen-rich saline (H(2) saline) on rat hearts with regional myocardial ischemia and reperfusion (I/R). Sixty-six rats were equally randomized to three groups: sham-operated group, I/R group (control group) and I/R plus H(2) saline treatment group. Myocardial I/R was established by occlusion of the left anterior descending (LAD) coronary artery for 30 min and reperfusion for 24 h. H(2) saline treatment attenuated I/R-induced cardiac cell apoptosis, presenting as significant improvement of heart function parameters 24h after reperfusion, including left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVEDP), +(dP/dt)max and -(dP/dt)max. It also decreased neutrophil infiltration, 3-nitrotyrosine level, expression of intercellular adhesion molecule 1(ICAM-1) and myeloperoxidase (MPO) activity in the area at risk zones (AAR) of rat hearts subjected to regional myocardial I/R, and attenuated the increase of I/R induced proinflammatory cytokine tumor necrosis factor-α (TNF-a) and interleukin-1β (IL-1b) levels in the AAR. H(2) saline has an anti-inflammatory effect on rat hearts with regional myocardial I/R.

Hemodynamic Responses to Continuous versus Pulsatile Mechanical Unloading of the Failing Left Ventricle

Debate exists regarding the merits and limitations of continuous versus pulsatile flow mechanical circulatory support. To characterize the hemodynamic differences between each mode of support, we investigated the acute effects of continuous versus pulsatile unloading of the failing left ventricle in a bovine model. Heart failure was induced in male calves (n = 14). During an acute study, animals were instrumented through thoracotomy for hemodynamic measurement. A continuous flow (n = 8) and/or pulsatile flow (n = 8) left ventricular assist device (LVAD) was implanted and studied during maximum support ( approximately 5 L/min) and moderate support ( approximately 2-3 L/min) modes. Pulse pressure (PP), surplus hemodynamic energy (SHE), and (energy equivalent pressure [EEP]/mean aortic pressure (MAP) - 1) x 100% were derived to characterize hemodynamic energy profiles during the different support modes. Standard hemodynamic parameters of cardiac performance were also derived. Data were analyzed by repeated measures one-way analysis of variance within groups and unpaired Student's t-tests across groups. During maximum and moderate continuous unloading, PP, SHE, and (EEP/MAP - 1) x 100% were significantly decreased compared with baseline and compared with pulsatile unloading. As a result, continuous unloading significantly altered left ventricular peak systolic pressure, aortic systolic and diastolic pressure, +/-dP/dt, and rate x pressure product, whereas pulsatile unloading preserved a normal profile of physiologic values. As continuous unloading increased, the pressure-volume relationship collapsed, and the aortic valve remained closed. In contrast, as pulsatile unloading increased, a comparable decrease in left ventricular volumes was noted. However, a normal range of left ventricular pressures was preserved. Continuous unloading deranged the physiologic profile of myocardial and vascular hemodynamic energy utilization, whereas pulsatile unloading preserved more normal physiologic values. These findings may have important implications for chronic LVAD therapy.

Proteção da recuperação funcional do miocárdio pelo omeprazol após isquemia-reperfusão em corações isolados de ratos

To evaluate the myocardium contractility alterations of isolated hearts of rats, submitted to ischemia and reperfusion with and without administration of the omeprazole. Twelve Wistar breed rats with 270 g mean body weight was studied. After anesthesia by intraperitoneal injection of ketamine 10mg and xylazine 2mg, their hearts were removed and perfused with Krebs-Henseleit solution (95% of O2 and 5% of CO2, 37 ºC, 110-120 mmHg perfusion pressure, 8 mmHg ventricular diastolic pressure) in the São Francisco de Assis disposable Langendorff system model Comex Ltda, MG. The six hearts of Group I (GI) and of the Group II (GII) were submitted to 20 min ischemia and 30 min reperfusion. In GII hearts, intracoronary injection of omeprazole 200 mcg was done immediately before the ischemia period induction. The following parameters were registered after the stabilization period (t0), and after the reperfusion period (t30): heart rate (HR), coronary flow (CoF), systolic pressure (SP), +dP/dt and -dP/dt. The Kruskal-Wallis test (P<0.05) was applied to statistical analysis. There were no significant differences (P>0.05) between groups among HR and CoF values. Differences (P<0.05) occurred between groups, I e II after the reperfusion period (t30) regarding systolic pressure reduced for 28.0 ± 3.6% in the control group GI and for 79.0 ± 5.9% in GII; The +dP/dtmax declined to be only 31.0 ± 5.6% in GI, preserving 99.4 ± 11.2% values in GII (P<0.05). The t30 -dP/dtmax values were GI 26.0 ± 7.3% and GII 82.0 ± 2.2% (P<0.05). The omeprazole administration before ischemia induction significantly protected the myocardium function recovery.

The Responsibility of Left Atrial Size and Wall Contraction Velocity to Left Atrial Active Emptying in Relation to the Mitral Flow Velocity Pattern

The aim of this study was to investigate the role and limitations of left atrial (LA) preload or contractility as determinants of active LA emptying in patients with heart failure. In 56 healthy individuals (controls) and 30 patients with heart failure, the LA volume before atrial contraction (LAV(pre) I), the LA volume reduction (LASVI) and LA wall contraction velocity (LAWV) during atrial contraction, and the transmitral peak flow velocities during early diastole (E) and atrial contraction (A) were determined using two-dimensional pulsed Doppler or tissue Doppler echocardiography. LAV(pre) I and LASVI were positively correlated in patients whose A/E ratio was ≥1 (r = 0.58) and negatively correlated in those whose A/E ratio was <1 (r =-0.63). LAWV was significantly lower in those with heart failure than in the controls 2.2 (1.2) cm/sec, versus 3.3 (0.8) cm/sec; mean (standard deviation) and negatively correlated with left ventricular end-diastolic pressure (r =-0.37). LAWV and LASVI were significantly correlated (r = 0.71). This correlation was stronger in the patients whose A/E ratio was <1 than in those whose A/E ratio was ≥1. Multivariate regression analysis showed that LAWV was the only factor affecting LASVI. In patients with heart failure and an A/E ratio of <1, the contribution of LA dilatation to active LA emptying may be limited, and LAWV may be the most important determinant of active LA emptying, even if this velocity is decreased because of elevated left ventricular diastolic pressure.

Anti-Apoptotic Effect of Hyperbaric Oxygen Preconditioning on a Rat Model of Myocardial Infarction

In our previous study, it was indicated that hyperbaric oxygen preconditioning (HOP) could induce a preconditioning against myocardial infarction and promote neovascularization. In this study, attempts were made to investigate whether a modified short-term pre-exposure protocol could also induce cardioprotection, and its potential mechanisms. Adult male Sprague Dawley rats were divided into seven groups; group 1 was sham surgery (SHAM) and group 2 was pre-exposed to normal air (CTL), and the other groups to HOP 1, 6, 24, 48, and 72 h (H1, H6, H24, H48, H72 groups) before permanent ischemia. The infarct size was measured by triphenyltetrazolium chloride staining, and left ventricular function parameters were recorded. The extent of apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive staining. Caspase-3 activity, Bcl-2, and Bax expression were also measured. Compared with CTL group, myocardial infarct size was significantly decreased as well as cardiac cell apoptosis in area at risk zones (AAR) in H48 group. Meanwhile, the activity of caspase 3 was reduced, the ratio of Bcl-2/Bax expression was up-regulated, and the heart function parameters, including left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVEDP), +(dP/dt)(max), and -(dP/dt)(max) were also significantly improved after preconditioning in H48 group. The results indicate that short-term HOP could induce cardioprotection and may not last for more than 24 h. HOP prevents myocardium from permanent ischemia injury by suppression of apoptotic pathways.

Prognostic Value of Tissue Doppler‐Derived E/e′ on Early Morbid Events after Cardiac Surgery

The tissue Doppler-derived surrogate for left ventricular diastolic pressure, E/e', has been used to prognosticate outcome in a variety of cardiovascular conditions. In this study, we determined the relationship of intraoperative E/e' to the use of inotropic support, duration of mechanical ventilation (MV), length of intensive care unit stay (ICU-LOS), and total hospital stay (H-LOS) in patients requiring cardiac surgery. The records of 245 consecutive patients were retrospectively reviewed to obtain 205 patients who had intraoperative transesophageal echocardiography examinations prior to coronary artery bypass grafting and/or valvular surgery. Cox proportional hazards and logistic regression models were used to analyze the relation between intraoperative E/e' or LVEF and early postoperative morbidity (H-LOS, ICU-LOS, and MV) and the probability that a patient would require inotropic support. With adjustments for other predictors (female gender, hypertension, diabetes, history of myocardial infarction, emergency surgery, renal failure, procedure type, and length of aortic cross-clamp time), an elevated E/e' ratio (>or=8) was significantly associated with an increased ICU-LOS (49 versus 41 median h, P = 0.037) and need for inotropic support (P = 0.002) while baseline LVEF was associated with inotropic support alone (P < 0.0001). These data suggest that the tissue Doppler-derived index of left ventricular diastolic filling pressure may be a useful indicator for predicting early morbid events after cardiac surgery, and may even provide additional information from that of baseline LVEF. Further, patients with elevated preoperative E/e' may need more careful peri- and postoperative management than those patients with E/e' <8.

Estimation of Left Ventricular End Diastolic Pressure by Tissue Doppler Imaging in Patients with Acute Myocardial Infarction

Objective: To evaluate sensitivity and specificity of E / Ea > 10 for prediction of LVEDP > 15 mmHg in patients with coronary artery disease undergoing left heart catheterization. Materials and Methods: Sixty patients of acute transmural myocardial infarction at Jinnah Hospital Lahore were enrolled in study from December 2008 to December 2009. Patients with sinus rhythm were included in the study. Patients with val-vular heart disease, complete right/left bundle branch block, Pacemaker dependence, Atrial fibrillation and Post mitral valve replacement were excluded. All patients were examined by performing transthoracic Doppler echocardiography. The trans-mitral LV filling signal was traced manually and the following variables were obtained: peak early (E) and late (A) trans-mitral velocities, and E/A ratio. Tissue – Doppler derived indices were recorded at the lateral mitral annulus. These indices included systolic velocities (S'), early diastolic (Ea) velocities and late diastolic (Aa) velocities. Finally, the dimensionless index of E/Ea was calculated. All were averaged from at least three beats. Cardiac cathetrization was performed via trans-femoral / trasradial route using six French (6F) sheaths. Left ventricular diastolic pressure was directly measured by fluid filled pigtail catheter attached to a pressure transducer. Results: Mean age of the study population was 56.8 ± 12.7 years. There were 47 (78.3%) males and 13 (21.7%) females. Diabetes mellitus was present in 12(20%), hypertension in 32 (53.3%), smoking in 35 (58.3%), dyslipidemia in 24 (40%). Anterior wall myocardial infarction occurred in 44 (73.3%) and inferior wall MI in 16 (26.7%). Grade I diastolic dysfunction was present in 22 (36.7%), Grade II in 31 (51.7%) and Grade III in 7 (11.7%) patients. E/E 15 in 9 (15%). Overall 21 patients were true positive, 6 were false positive, 25 were true nega-tive and 8 were false negative. By applying 2 × 2 table sensitivity was 77.7%, specificity was 80.6%, positive predictive value was 77.7% and negative predictive value was 75.7%. Conclusion: Doppler echocardiography provided major insights into the pathophysiology of diastolic LV dysfunction. E/Ea ratio is a reasonably good index for predicting elevated left ventricular filling pressure. E/Ea significantly correlated with LVEDP in the population with high prevalence of coronary artery disease. This method is the standard in measuring pres-sures in most clinical settings. Key Words: Acute myocardial infarction; Coronary artery disease; Doppler echocardiography; Tissue Doppler imaging; Diastolic dysfunction.

Modulation of Monocrotaline-Induced Cor Pulmonale by Grape Juice

The study was designed to test whether the ingestion grape juice (GJ) could modulate monocrotaline (MCT)-induced Cor pulmonale resulting from antioxidant properties. Three-week-old male Wistar rats received GJ (10 mL/kg/day) by gavage for 6 weeks. A single injection of MCT (60 mg/kg body weight intraperitoneally) was administered at the end of the third week. Animals were divided in four groups: control, MCT, GJ, and GJ + MCT. MCT promoted a significant increase in right ventricle (36%) and lung (70%) weight to body weight ratio. There was an increase in the right systolic (38%) as well as in the end diastolic (70%) ventricular pressures. MCT caused a significant decrease in lung endothelial nitric oxide synthase (20%) but increase in lipid peroxidation (13%) and catalase (43%). MCT-induced decrease in the endothelial nitric oxide synthase and increase in the right ventricular end diastolic pressure were prevented by GJ, whereas right systolic ventricular pressure and lung weight to body weight ratio were corrected only partially. MCT-induced increase in heart and right ventricle to body weight ratios was not changed by GJ. GJ blunted MCT-induced increase in lipid peroxidation but had no effect on the changes in catalase and superoxide dismutase activities. GJ appears to offer some protection against MCT-induced Cor pulmonale and right ventricle function changes.

Influence of the estrous cycle on hypoxic failure in the female rat heart

Clinical studies have shown that fluctuation in the plasma concentrations of estrogen during the menstrual cycle has an effect on myocardial health in premenopausal women. When estrogen levels are low, the number of ischemic events experienced is increased. To determine whether the increased ischemic events reported with low plasma estrogen concentrations in women could be reproduced in an animal model, cardiac function was measured during hypoxia in the female rat at different time points of the estrous cycle. Hearts from female Sprague-Dawley rats were perfused in the working mode at the diestrous (low estrogen; n = 7) and proestrous (high estrogen; n = 6) phases of the estrous cycle, confirmed by plasma estradiol concentrations. Hearts were perfused under aerobic conditions with 5.5 mM glucose, 100 muU/mL insulin, and 1.2 mM palmitate, followed by a 30-minute period of hypoxia with 95% N(2)-5% CO(2) gassing. There were no significant differences in heart function between diestrous and proestrous groups prior to hypoxia. However, hypoxia induced perturbations in function that were dependent on the estrous cycle. Reductions in left ventricular systolic and diastolic pressure occurred with hypoxia, but no significant differences in these pressures were observed between groups. Left ventricular pulse pressure and coronary flow also decreased significantly during hypoxia (both, P < 0.05), but hearts from the proestrous group maintained a significantly higher pulse pressure (P < 0.05). Hearts from the proestrous group also maintained significantly higher rates of coronary flow during hypoxia (P < 0.05), compared with hearts from the diestrous group. However, despite the effect of proestrus, correlation coefficients between plasma estradiol concentrations and indices of cardiac function were not significant. Our findings indicate that the estrous cycle of the female rat affects cardiac function during hypoxia. This model may be useful to study the impact of the estrous cycle on metabolic and cardiovascular function.

Effects of recombinant adeno-associated virus-mediated heme oxygenase-1 gene transfection on inflammatory cytokine in isolated rat hearts with myocardial ischemia-reperfusion injury

Objective To investigate the effects of recombinant adeno-associated virus (rAAV)-mediated heme oxygenase-1 (HO-1) gene transfer on inflammatory cytokine in isolated rat hearts with myocardial ischemia-reperfusion (I/R) injury. Methods Thirty male SD rats weighing 220-280 kg were randomly divided into 3 groups: group Ⅰ normal control (n=6); group Ⅱ normal saline + I/R (n=12) and group Ⅲ rAAV-HO-I +I/R (n=12). In group Ⅲ rAAV-mediated HO-1 was injected intramuscularly at 4 points on the anterior and posterior wall of left ventricle along the left anterior descending branch of coronary artery. In group Ⅱ normal saline was injected instead of rAAV- HO-1 gene. Six animals in each group were sacrificed 3 months after the gene delivery in group Ⅱ and Ⅲ The expression of HO-1 in the injected myocardium was determined by immuno-histnchemical technique. The isolated rat hearts were perfased with an oxygenated (95% O_2-5% CO_2) K-H solution at 37℃ in a Langendorff apparatus and subjected to 40 min of global ischemia followed by 45 min of reperfusion in group Ⅱ and Ⅲ. The left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) anti ±dp/dt_(max) were measured recorded at 15 min of post-preparation equilibration and at 15, 30 and 45 min of repcrfusion. TNF-α and IL-6 contents in myocardium were measured Results The HO-1 expression was significantly higher in group Ⅲ than in group Ⅱ (P < 0.05 or 0.01). The left ventricular function was significantly better and TNF-α and IL-6 contents in myocardium were significantly lower in group Ⅲ than in group Ⅱ (P <0.05 or 0.01). Conclusion rAAV-mediatcd HO-1 gene transfer can protect myocardium against I/R injury in isolated rat hearts through inhibition of inflammatory cytokine production. Key words: Heme oxygenase (decyclizing); Myocardial reperfusion injury; Transfection; Adenoviridae

Hydrogen-Rich Saline Protects Myocardium Against Ischemia/Reperfusion Injury in Rats

Protective effect of hydrogen (H(2)) gas on cardiac ischemia-reperfusion (I/R) injury has been demonstrated previously. This study was designed to test the hypothesis that hydrogen-rich saline (saline saturated with molecular hydrogen), which is easy to use, induces cardioprotection against ischemia (30 min) and reperfusion (24 h) injury in rats. Adult male Sprague-Dawley rats underwent 30-min occlusion of the left anterior descending (LAD) coronary artery and 24-h reperfusion. Intraperitoneal injection of hydrogen-rich saline before reperfusion significantly decreased plasma and myocardium malondialdehyde (MDA) concentration, decreased cardiac cell apoptosis, and myocardial 8-hydroxydeoxyguanosine (8-OHdG) in area at risk zones (AAR), suppressed the activity of caspase-3, and reduced infarct size. The heart function parameters including left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), +(dP/dt)(max) and -(dP/dt)(max) were also significantly improved 24 h after reperfusion. It is concluded that hydrogen-rich saline is a novel, simple, safe, and effective method to attenuate myocardial I/R injury.

Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

Myocardial infarction leads to compensatory ventricular remodeling. Disturbances in myocardial contractility depend on the active transport of Ca2+ and Na+, which are regulated by Na+-K+ ATPase. Inappropriate regulation of Na+-K+ ATPase activity leads to excessive loss of K+ and gain of Na+ by the cell. We determined the participation of Na+-K+ ATPase in ventricular performance early and late after myocardial infarction. Wistar rats (8-10 per group) underwent left coronary artery ligation (infarcted, Inf) or sham-operation (Sham). Ventricular performance was measured at 3 and 30 days after surgery using the Langendorff technique. Left ventricular systolic pressure was obtained under different ventricular diastolic pressures and increased extracellular Ca2+ concentrations (Ca2+e) and after low and high ouabain concentrations. The baseline coronary perfusion pressure increased 3 days after myocardial infarction and normalized by 30 days (Sham 3 = 88 +/- 6; Inf 3 = 130 +/- 9; Inf 30 = 92 +/- 7 mmHg; P < 0.05). The inotropic response to Ca2+e and ouabain was reduced at 3 and 30 days after myocardial infarction (Ca2+ = 1.25 mM; Sham 3 = 70 +/- 3; Inf 3 = 45 +/- 2; Inf 30 = 29 +/- 3 mmHg; P < 0.05), while the Frank-Starling mechanism was preserved. At 3 and 30 days after myocardial infarction, ventricular Na+-K+ ATPase activity and contractility were reduced. This Na+-K+ ATPase hypoactivity may modify the Na+, K+ and Ca2+ transport across the sarcolemma resulting in ventricular dysfunction.

Doppler Echocardiography Yields Dubious Estimates of Left Ventricular Diastolic Pressures

Quantification of left ventricular (LV) diastolic function is necessary to diagnose heart failure (HF) when LV systolic function is normal.1–4 Furthermore, repetitive assessment of LV filling pressures is an important guide for titration of diuretic treatment and can predict survival of HF patients.5 Because of patient discomfort and the risks involved in invasive procedures, a noninvasive estimate of diastolic LV function and pressures is highly desirable. In current cardiological practice, noninvasive evaluation of diastolic LV function is based on Doppler echocardiographic visualization of LV inflow and/or LV tissue reextension. LV inflow and LV tissue reextension, however, are only indirectly related to LV filling pressures through laws of physics such as the Bernoulli principle and Laplace law. Noninvasive estimates of LV filling pressures can therefore be offset not only by limitations of the imaging technique but also by shortcomings inherent to derivation of pressures from inflow or reextension signals. As a result of these problems with noninvasive estimates of LV diastolic function and pressures, the cardiological community has witnessed over the past 20 years repetitive cycles in which a Doppler echocardiographic index was first proposed as robust and shortly thereafter discredited by contradictory evidence. The latest of such cycles involved the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/E′). The value of the E/E′ ratio as a reliable estimate of LV filling pressures was demonstrated in a variety of cardiac diseases6–10 and endorsed by European and American consensus statements on diastolic HF4 and diastolic LV dysfunction11 before being seriously questioned both in hypertrophic12 and dilated cardiomyopathy.13 This continuing uncertainty14 surrounding the value of noninvasive estimates of LV filling pressures and diastolic LV dysfunction asks for a reappraisal of physiological assumptions linking LV filling pressures to myocardial reextension …

Letter by Lancaster et al Regarding Article, “Tissue Doppler Imaging in the Estimation of Intracardiac Filling Pressure in Decompensated Patients With Advanced Systolic Heart Failure”

To the Editor: The echo Doppler–derived ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/Ea) has recently become an accepted noninvasive method to estimate left ventricular (LV) diastolic pressures for a variety of clinical conditions.1 However, the reliability of this measurement in patients with decompensated heart failure has been questioned in the article by Mullens et al.2 Their study compared pulmonary capillary wedge pressure (PCWP) to E/Ea in consecutive patients with symptomatic heart failure in intensive care and found a poor …

Acute Valvular Regurgitation

Acute severe valvular regurgitation is a surgical emergency, but accurate and timely diagnosis can be difficult. Although cardiovascular collapse is a common presentation, examination findings to suggest acute regurgitation may be subtle, and the clinical presentation may be nonspecific. Consequently, the presentation of acute valvular regurgitation may be mistaken for other acute conditions, such as sepsis, pneumonia, or nonvalvular heart failure. Although acute regurgitation may affect any valve, acute regurgitation of the left-sided valves is more common and has greater clinical impact than acute regurgitation of right-sided valves. Data to guide appropriate management of patients with acute regurgitation are sparse; there are no randomized trials, and much of the literature describes either small series or the experiences of specific centers. Despite these limitations, the available data are sufficient to allow identification of general principles as well as development of applicable guidelines from both the American College of Cardiology/American Heart Association and European Society of Cardiology. The guidelines recommend valve surgery for symptomatic patients with aortic or mitral regurgitation, including those with acute regurgitation.1–3 The data and guidelines emphasize overarching clinical principles, including the need for a high clinical suspicion of acute regurgitation, timely use of echocardiography, and, in the majority of patients, rapid progression to surgery. Causes of acute regurgitation overlap with causes of chronic regurgitation and vary depending on the valve affected (Table 1). Endocarditis may affect either the aortic or mitral valve, whereas other causes are unique to the specific valve involved. The majority of causes of acute regurgitation present as an acute or subacute event. However, acute regurgitation can occur in patients with chronic regurgitation, when regurgitant severity is exacerbated by factors such as coronary ischemia, chordal rupture, or leaflet perforation from endocarditis. Acute regurgitation of either the aortic or mitral valve may result from procedural …

Left Ventricular Diastolic Filling Pressures During Dobutamine Stress Echocardiography: Relationship to Symptoms and Ischemia

Limited information exists regarding the relationship of left ventricular diastolic filling parameters measured by Doppler echocardiography during dobutamine stress echocardiography (DSE) and stress-induced symptoms or myocardial ischemia. To determine if there is an association between Doppler parameters of left ventricular filling and symptoms and ischemic wall motion abnormalities during DSE, the authors prospectively studied 219 patients (mean age, 66+/-11 years; 55% men) referred for clinically indicated DSE. Pulsed-wave Doppler measurements of mitral inflow and medial annular tissue velocities at baseline, 20 microg/kg/min, peak stress, and recovery were made. Patients were classified as having stress-induced ischemia (n=70) or no ischemia (n=149) on the basis of the development of new or worsening wall motion abnormalities. Patients who developed ischemia had lower baseline and peak stress diastolic annular tissue velocities (e') (5.7+/-1.9 vs 6.4+/-1.9 cm/s at baseline, P=0.02; 5.2+/-1.6 vs 7.4+/-2.4 cm/s at peak stress, P<.0001). At peak stress, the E/e' ratio was higher (13.1+/-6.3 vs 10.2+/-4.2, P=.003); these differences persisted into recovery. The increase in E/e' from 20 microg/kg/min to peak stress was greater (0.9+/ 2.1 vs -0.8+/-3.1, P=.0009) in patients who developed symptoms during DSE and in patients who presented with dyspnea (0.3+/-2.6 vs -1.0+/-3.2, P=.02). The change in e' velocity from baseline to peak stress, the change in E/e' from baseline to recovery, known coronary artery disease, and the development of symptoms during DSE were independently associated with ischemia. The development of symptoms and myocardial ischemia during DSE are both associated with an increase in E/e'. The prognostic implications of elevated E/e' during DSE have yet to be elucidated.

Transapical off-pump removal of the native aortic valve: A proof-of-concept animal study

This study evaluates the feasibility of off-pump native aortic valve removal in preparation for transapical aortic valve replacement. Off-pump aortic valve replacement is performed by balloon predilatation of the native valve followed by insertion of a stented prosthesis. In patients with calcified annuli and cusps, particulate embolization, suboptimal prosthesis sizing, and perivalvular leaks may occur. Therefore, native valve removal may improve outcomes after transapical aortic valve replacement. The aortic cusps were sequentially removed from 10 pigs in an off-pump procedure. A temporary valve was inserted percutaneously into the ascending aorta to prevent aortic regurgitation. The electrocardiogram, coronary blood flow, and arterial, left atrial, and ventricular pressures were continuously monitored. Removal of the aortic cusps caused a drop in diastolic arterial pressure and its equalization with left ventricular diastolic pressure. Systolic pressure decreased by 13.5%. Left atrial pressure increased by 86.0%. Coronary blood flow decreased by 39.9% and its pattern changed from mostly diastolic to mostly systolic. Electrocardiographic signs of ischemia appeared almost immediately. Percutaneous insertion of a temporary valve in the ascending aorta increased diastolic pressure and caused a tendency toward echocardiographic normalization. Aortic valve removal in a healthy beating heart causes acute massive aortic regurgitation, hemodynamic instability, and the rapid onset of myocardial ischemia. Reduction of left ventricular volume overload, by placement of a temporary valve in the ascending aorta, mitigates myocardial distress, helps stabilize hemodynamic parameters, and may be a useful tool to allow surgical manipulations of the aortic valve and annulus during transapical aortic valve replacement procedures.