The positive inotropic effect of phosphodiesterase type 8 inhibitor of PF-04957325 in rats and its underlying mechanism / 中国药理学通报

Aim To investigate the inotropic effect of PF-04957325, a phosphodiesterase type 8 inhibitor, in normal rats and its underlying molecular mechanism. Methods The techniques of in vivo rat left ventricular pressure-volume loop (P-V loop) and isolated perfusion rat heart were used to analyze the hemodynamics and positive inotropic effect of rat hearts. The Ca transient induced by field stimulation was used to analyze the hemodynamics of sarcoplasmic reticulum (SR) Ca + uptaking. Western blot was used to analyze the phosphorylation levels of SR phospolamban (PLB) and ryanodine receptor type 2 (RyR2). Results The P-V loop experiment indicated that PF-04957325 (0.5 mg · kg

Comparison of three different techniques of endotracheal tube cuff inflation: just seal, stethoscope guided and pressure volume loop: a prospective randomized study

Background: Cuffed endotracheal tubes not only ensure a proper seal during positive pressure ventilation, but at the same time also prevent aspiration of gastric secretions. The aim of this prospective, randomized study was to compare three methods of ETT cuff inflation-- palpation of the leak in suprasternal notch (Just seal), a stethoscope guided method of tracheal tube cuff inflation and PVL guided cuff inflation.Methods: After approval by institutional ethical committee, 192 patients of either sex in age group of 18-50 years belonging to ASA physical status I or II were enrolled. Each patient was randomly allocated into one of three groups: one group received standard 'just seal' method of tracheal cuff inflation (JS), the second group, the stethoscope-guided method (SG) and in third group cuff was inflated using Pressure Volume Loop (PVL). Volume of air introduced into the cuff and pressure within the cuff was recorded.Results: A total of 192 patients were recruited to the study. The median (IQR [range]) tracheal cuff pressure was 12 (10-22 [6-28]) cm H2O, 16 (12-24[6-38]) and 14 (10-22[8-32]) cmH2O in JS, SG and PVL group respectively. Cuff pressures within the recommended range of 20-30 cm H2O fell in 25% of the patients in both JS and SG group and 31% patients in PVL group. The mean volumes of air introduced in the cuff and the resultant mean cuff pressure in all groups was found to be statistically insignificant (p= 0.4, 0.18 respectively). Tidal volume discrepancy was more and 75% of cuff pressures were less than the recommended range in JS than the other two groups.Conclusions: Real time PVL displayed on most modern anaesthesia machine is a good alternative to check for proper ETT cuff inflation, avoid high cuff pressure and monitor air leak.

Effect of gemigliptin on cardiac ischemia/reperfusion and spontaneous hypertensive rat models

Diabetes is associated with an increased risk of cardiovascular complications. Dipeptidyl peptidase-4 (DPP-IV) inhibitors are used clinically to reduce high blood glucose levels as an antidiabetic agent. However, the effect of the DPP-IV inhibitor gemigliptin on ischemia/reperfusion (I/R)-induced myocardial injury and hypertension is unknown. In this study, we assessed the effects and mechanisms of gemigliptin in rat models of myocardial I/R injury and spontaneous hypertension. Gemigliptin (20 and 100 mg/kg/d) or vehicle was administered intragastrically to Sprague-Dawley rats for 4 weeks before induction of I/R injury. Gemigliptin exerted a preventive effect on I/R injury by improving hemodynamic function and reducing infarct size compared to the vehicle control group. Moreover, administration of gemigliptin (0.03% and 0.15%) powder in food for 4 weeks reversed hypertrophy and improved diastolic function in spontaneously hypertensive rats. We report here a novel effect of the gemigliptin on I/R injury and hypertension.

Construction of right ventricular pulmonary artery coupling model in patients with pulmonary hypertension / 中国介入心脏病学杂志

Objective To study the mechanism of right ventricular pulmonary artery coupling by fitting the pressure volume loop of pulmonary arterial hypertension patients and calculating the related parameters.Methods During January of 2015 to December of 2015,34 patients with pulmonary hypertension and 5 patients with patent oval foramen(PFO)were admitted in Wuhan Asian Heart Hospital,. Inclusion criteria for the pulmonary hypertension group were in accordance with the newest European guidelines for pulmonary hypertension . All of the patients were conducted invasive pressure catheter intervention and MRI. All the pressure data were digitized by GetData software and the CMR tools3D was used to derive right ventricular volume data, fitting the pressure volume loop and calculate the Pmax, Ees, Ea and other related parameters. 5 patients with PFO and 34 patients with pulmonary hypertension were divided into three groupswhich included:the control group (i.e. the patients with PFO), patients with pulmonary artery mean pressure less than 50 mmHg as group A and pulmonary artery mean pressure greater than or equal to 50 mmHg as group B. The pressure volume loop of the three groups were compared and the related parameters were calculated.Results The right ventricular Pmax were(53.05±12.87) mmHg, (134.73±26.38) mmHg, (207.88±65.67) mmHg, in the control group, group A and B respectively. There were significant differences when compared among the 3 groups. There was no statistical difference in Ees between the control group and group A(P>0.05). The Ees of group B was significantly higher than the control group[(1.53±0.97)vs.(0.60±0.28),P<0.05]. The Ea of group B was higher than the control[(1.34±0.74) vs.(0.39±0.15),P<0.05]. The overall ratio of Ees/Ea was lower in group B as compared to the control group [(1.12±0.47)vs.(1.62±0.51),P<0.05].Conclusions In the early stage of pulmonary hypertension, right ventricular contractility preserves and can overcome the slightly elevated afterload .The right ventricle and pulmonary artery coupled with good work. With the increasing mean pulmonary artery,the afterload of right ventricular increases and right ventricular contractility needs further increase to fight against the elevated afterload. The elevation of contractility cannot overcome the change of afterload, resulting in the off paired of mechanical efflciency, causing the right ventricle- pulmonary artery coupling decreases.

Assessment of right ventricular function in mice with pulmonary hypertensive by pressure-volume loops / 中国介入心脏病学杂志

Objective To study on the evaluation of haemodynamics in the normal and pulmonary hypertensive mouse hearts using pressure volume loops measured by electric catheter.Methods Compared the difference in haemodynamics between mice exposed to chronic hypoxia for 10 days,which causes hypoxia-induced pulmonary hypertension (experimental group,n =8),and mice raised under normal atmospheric pressure (control group,n =8).The right carotid artery was cannulated with a 1.2 F catheter and advanced into the ascending aorta,then punctured towards the right ventricular apex.A 1.2 F admittance pressure-volume catheter was introduced using a 20-gauge needle to obtain the pressure-volume measurements and calculate hemodynamic parameters.Results There were no significant differences in average by weight,ratio of right atrial weight to body weight,left atrial weight/body weight,left ventricular free wall and septum weight/body weight between the 2 groups(all P ＞ 0.05).The ratio of right rentricle/left rentricle and septum weight as well as right rentricular weight/body weight was increased in the experimental group and of significant difference when compared to the control.The mice in in the experimental group had a 61％ mean decrease in cardiac output,a 55％ decrease in ejection fraction,and a 63％ decrease in ventricular compliance(P ＜0.05).The increase in dP/dtmax-EDVand PRSWfound in the experimental group reflected significant increase in myocardial contractility.Increase in Ees was observed but without significant difference as compared to the control.Ea significantly increased in the experimental group resulting in significant decrease in Ees/Ea from (0.71 ±0.27) to (0.35 ±0.17) (P＜ 0.005).Conclusion This study demonstrates the feasibility of obtaining RV pressure-volume measurements in mice using electric catheter.These measurements provide insight into right ventricular-pulmonary artery interactions in healthy and diseased conditions.

Feasibility of simultaneous cardiac catheterization and 2D echocardiogram in the measurement of right rentricular pressure-volume loops / 中国介入心脏病学杂志

Objective To investigate the feasibility of the simultaneous measurement of right ventricular pressure-volume loops by cardiac catheterization and 2D electrocardiogram. Methods Patients referred for pulmonary hypertension underwent right heart catheterization in our hospital between June 1st, 2015 and June 1st, 2017 are to be enrolled in this study. The right ventricular volume was measured simultaneously by catheter and electrocardiogram. The pressure-volume loops were constructed by the parameters of the pressure and volume in the same cardiac cycle. Results The study completed in four cases and their pressure-volume loops were drawn. The obtained images were irregular and there was no relationship among them. As a result, the construction was a failure. Conclusions The construction of the right ventricular pressure-volume loops of pulmonary hypertension patients by simultaneous catheterization and 2D electrocardiogram is difficult to overcome the technology defects.

Usefulness of Mitral Annulus Velocity for the Early Detection of Left Ventricular Dysfunction in a Rat Model of Diabetic Cardiomyopathy

BACKGROUND: Diabetic cardiomyopathy (DMCMP) is characterized by myocardial dysfunction regardless of coronary artery disease in diabetic patients. The features of LV dysfunction in rat model of type 1 DM induced by streptozocin, are variable and controversial. Thus, we tested the usefulness of tissue Doppler imaging in the early detection of ventricular dysfunction in a rat model of DMCMP. METHODS: Diabetes was induced by intra-peritoneal injection of streptozocin (70 mg/kg) in 8 weeks of Sprague-Dawley rat. Diagnosis of diabetes was defined as venous glucose level over 350 mg/dL 48 hrs after streptozocin injection. Echocardiography was done at baseline and 10 weeks after diabetes induction both in diabetes group (n=15) and normal control (n=10). After echocardiography at 10 weeks, invasive hemodynamic measurement using miniaturized conductance catheter was done in both groups. RESULTS: Ten weeks after diabetes induction, heart and lung mass indexes of diabetes were larger than those of normal control (3.2+/-0.3 vs. 2.4+/-0.2 mg/g, p<0.001, 5.5+/-1.1 vs. 3.6+/-0.6 mg/g, p<0.001, respectively). In echocardiographic data, s' (2.4+/-0.4 vs. 3.1+/-0.5 cm/s, p<0.001), e' velocity of mitral annulus (2.9+/-0.6 vs. 3.8+/-1.1 cm/s, p<0.001), and E/e' ratio (27.1+/-5.6 vs. 19.7+/-2.6, p<0.001) were impaired in diabetes group. In hemodynamic measurement, there were no differences in ejection fraction, peak dP/dt between the diabetic group and normal control. However, load independent indexes of contractility, the slope of the end-systolic pressure volume relation (0.18+/-0.07 vs. 0.62+/-0.18 mmHg/microL, p<0.001) and preload recruitable stroke work (51.8+/-22.0 vs. 90.9+/-22.5 mmHg, p<0.001) were impaired in diabetic group compared to normal control. CONCLUSION: In a rat model of diabetic cardiomyopathy, tissue Doppler imaging of mitral annulus can be a good modality for early detection of myocardial dysfunction.

Análisis matemático de la curva presión-volumen del ventrículo izquierdo / Análisis matemático de la curva presión-volumen del ventrículo izquierdo

Objetivo. Presentar una aproximación práctica a los factores determinantes de la función cardiaca, basada en los conceptos físicos y matemáticos que subyacen a la curva presión-volumen del ventrículo izquierdo. métodos. Análisis teórico de la curva presión-volumen del ventrículo izquierdo. Conclusiones. La reanimación de los pacientes críticamente enfermos se basa en la obtención de información indirecta de los factores determinantes de la función ventricular, obtenida muy frecuentemente a partir de métodos invasivos. Son evidentes la limitación teórica de la información calculada mediante el catéter en la arteria pulmonar y la necesidad de desarrollar nuevas metodologías que permitan reproducir la curva presión-volumen del ventrículo izquierdo.

Objective: To present a practical approach to cardiac performance factors based upon physical and mathematical foundations that lie under the left ventricular pressure volume loop. methods: Theoretical analysis of the left ventricular pressure volume loop. Conclusions: The process of reanimation in the critically-ill population depends on indirect measurements of left ventricular performance factors, often derived from invasive maneuvers. Theoretical limitations from pulmonary artery catheter-derived calculations become obvious, and warrant the development of new methods that allow displaying left ventricular pressure-volume loop at the bedside.

Clinic study to evaluate left ventricular chamber stiffness by catherization and simultaneous echocardiography / 中华超声影像学杂志

Objective To establish the method of depict ing the left ventricular (LV) pressure-volume loop automatically by computer which incorporates LV catherization simultaneous with LV acoustic quantification echocardiography and to assess echocardiography non-invasive evaluation LV chamber stiffness. Methods Thirteen patients with hypertrophic cardiomyopathy (HCM) underwent LV catherization simultaneously with echocardiography. LV pressure and volume curves were sent to computer, and LV pressure-volume loop was depicted automatically and modulus of LV chamber stiffness (Kc) was obtained. Pulsed Doppler echocardiography of mitral intraventricular flows was obtained in patients with HCM. Results Patients with HCM had significantly higher Kc obtained from LV pressure-volume loop ( 0.43 ? 0.11 vs 0.27 ). R-E 3/R-E 0, (R-E 2)-(R-E 1), (R-A 3)-(R-A 2) were correlated to Kc(r= 0.61 , 0.57 , 0.58 ,respectively). Conclusions This method provides a simple and reliable technique for automatically tracing pressure-volume loop and should facilitate further investigation of the left ventricular diastolic function in clinical practice. R-E 3/ R-E 0, (R-E 2)-(R-E 1), (R-A 3)-(R-A 2) offer new non-invasive indices in evaluating LV chamber stiffness.

The evaluation of left ventricular function by pressure-volume loop in patients with different extents of coronary stenosis / 中国介入心脏病学杂志

Objective To evaluate the left ventricular function in patients with different extents of coronary stenosis by the left ventricular pressure volume loop Methods In 65 patients who were undergoing coronary angiography and left ventriculography examinations, materials of clinical and cardiac catheter examinations were collected In right anterior oblique 30 degrees the left ventriculography was progressed The pressure curves of the left ventricle and the aorta were recorded continuously and volumes of the left ventricles were measured with the dot tracing method Pressure volume loop was set up and ventricular energy indexes embodied by the pressure volume loop were measured and calculated Results In normal group, pressure volume loop was located in the left and lower portion of the coordinate system Along with the levels of the coronary stenosis becoming more severe, pressure volume loops moved to the right and upper portion of the coordinate system Little changes occurred in ejection fraction except that there was a decreasing in patients with lesions of three branches; Stroke work showed no obvious changes; Filling energy became larger; Total energy increased obviously in both groups with lesions of double branches and three branches; End systolic energy increased gradually while energy efficiency decreased gradually Conclusion The ventricular pressure volume loop can be obtained in routine ventriculography which can reflect many indexes of ventricular function quantitatively The ventricular energy indexes change correspondingly with coronary artery lesions and may be useful to assess ventricular function in patients with different levels of coronary stenosis

Analysis of the Left Ventricular Contractile Reserve Using End-systolic Pressure-Volume Relation (ESPVR) in Idiopathic Dilated Cardiomyopathy: Its Correlation with Pathologic Findings

BACKGROUND: Left ventricular (LV) end-systolic pressure volume relation (ESPVR) is considered as a load independent contractile index. However, its application in human beings has been limited by the difficulty in the accurate real time measurement of the LV volume changes. With introduction of the echocardiographic automatated edge detection method, on-line generation of multiple LV pressure volume-loops has become possible to assess ESPVR. This study was performed to investigate the correlation of the degree of myocardial damages with myocardial contractility and contractile reserve assessed by ESPVR as a surrogate of contractility index. METHODS: Studies were attempted in ten patients with idiopathic dilated cardiomyopathy. Baseline two-dimensional and Doppler echocardiography, cardiac catheterization for hemodynamic assessment and endomyocardial biopsy were performed. Generation of multiple LV pressure-volume loops during occlusion and release of the inferior vena cava by a balloon catheter was performed using the volume signals from the echocardiographic automatated edge detection method and the pressure signals from a 5F fluid-filled lumen catheter. ESPVR was measured at the baseline and after 3 minutes of dobutamin infusion (10 microgram/Kg/min). RESULTS: No correlation was observed between the degree of myocyte hypertrophy change or interstitial fibrosis and the two-dimensional echocardiographic or hemodynamic data. However, restrictive LV filling pattern was more common in the patients with severe degree of myocyte hypertrophy change. Myocardial contractility and contractile reserve were also significantly reduced in this patient group. The degree of interstitial fibrosis did not affect myocardial contractility or contractile reserve in this particular patient group. CONCLUSION: Assessment of ESPVR using the echocardiographic automatated edge detection method was feasible in the patients with idiopathic dilated cardiomyopathy. The degree of myocardial hypertrophy change was prominent in the patients with reduced contractility and contractile reserve.