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End-diastolic Pressure (end-diastolic + pressure)
Kinds of End-diastolic Pressure Selected AbstractsThe Effect of Erythropoietin on Exercise Capacity, Left Ventricular Remodeling, Pressure-Volume Relationships, and Quality of Life in Older Patients With Anemia and Heart Failure With Preserved Ejection FractionCONGESTIVE HEART FAILURE, Issue 3 2010Rose S. Cohen MD A prospective, open-label, 3-month study was conducted to evaluate the feasibility and short-term clinical effect of subcutaneous erythropoietin injections in patients with anemia and heart failure with preserved ejection fraction (ejection fraction, 55%±2%). Using a dose-adjusted algorithm to effect a rate of rise in hemoglobin not to exceed 0.4 g/dL,/wk, hemoglobin (10.8±0.3 to 12.2±0.3 g/dL) and red blood cell volume (1187±55 to 1333±38 mL) increased with an average weekly dose of 3926 units. Functional measures increased from baseline (6-minute walk test [289±24 to 331±22 m], exercise time [432±62 to 571±51 s], and peak oxygen consumption [8.2±0.7 to 9.4±0.9 mL/kg/min], all P<.05). End-diastolic volume declined significantly (8% volumetric decrease, 108±3 to 100±3 mL, P =.03), but there were no significant changes in left ventricular mass or estimated left ventricular end-diastolic pressure. Pressure-volume analysis demonstrated a reduction in ventricular capacitance at an end-diastolic pressure of 30 mm Hg without significant changes in contractile state. Congest Heart Fail. 2010;16:96,103. © 2009 Wiley Periodicals, Inc. [source] Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunctionACTA PHYSIOLOGICA, Issue 1 2010H. Post Abstract Aim:, The induction of mild hypothermia (MH; 33 °C) has become the guideline therapy to attenuate hypoxic brain injury after out-of-hospital cardiopulmonary resuscitation. While MH exerts a positive inotropic effect in vitro, MH reduces cardiac output in vivo and is thus discussed critically when severe cardiac dysfunction is present in patients. We thus assessed the effect of MH on the function of the normal heart in an in vivo model closely mimicking the clinical setting. Methods:, Ten anaesthetized, female human-sized pigs were acutely catheterized for measurement of pressure,volume loops (conductance catheter), cardiac output (Swan-Ganz catheter) and for vena cava inferior occlusion. Controlled MH (from 37 to 33 °C) was induced by a vena cava inferior cooling catheter. Results:, With MH, heart rate (HR) and whole body oxygen consumption decreased, while lactate levels remained normal. Cardiac output, left ventricular (LV) volumes, peak systolic and end-diastolic pressure and dP/dtmax did not change significantly. Changes in dP/dtmin and the time constant of isovolumetric relaxation demonstrated impaired active relaxation. In addition, MH prolonged the systolic and shortened the diastolic time interval. Pressure,volume analysis revealed increased end-systolic and end-diastolic stiffness, indicating positive inotropy and reduced end-diastolic distensibility. Positive inotropy was preserved during pacing, while LV end-diastolic pressure increased and diastolic filling was substantially impaired due to delayed LV relaxation. Conclusion:, MH negatively affects diastolic function, which, however, is compensated for by decreased spontaneous HR. Positive inotropy and a decrease in whole body oxygen consumption warrant further studies addressing the potential benefit of MH on the acutely failing heart. [source] Analysis of Left Atrial Volume Change Rate for Evaluation of Left Ventricular Diastolic FunctionECHOCARDIOGRAPHY, Issue 7 2004F.E.S.C., Ming-Jui Hung M.D. An excellent correlation exists between the change in the left atrial (LA) angiographic area and posterior aortic wall motion. The aim of the study was to define the role of posterior aortic wall motion, indicating LA volume change, during the left ventricular (LV) phase for the assessment of LV diastolic function. A total of 155 patients underwent echocardiography after cardiac catheterization. Study patients were classified into four groups according to the ratio of early-to-late transmitral flow velocity (E/A ratio) and/or LV end-diastolic pressure (EDP): 42 patients with LVEDP < 15 mmHg and E/A ratio >1 (normal filling); 46 patients with E/A < 1 (impaired relaxation); 46 patients with LVEDP , 15 mmHg and E/A > 1 and <2 (pseudonormal filling); 21 patients with E/A > 2, E , 70 cm/s, and E-wave deceleration time ,160 ms (restrictive filling). The slopes of early and late (slopes E and A) diastolic motion of LA wall were derived from M-mode analysis, together with the LV isovolumic time constant Tau from cardiac catheterization. Values of slope E/A decreased in restrictive filling, pseudonormal filling, and impaired relaxation as compared with normal filling (0.41 ± 0.14, 0.69 ± 0.15, and 0.56 ± 0.23 vs 1.25 ± 0.26, P < 0.001, respectively) and correlated inversely with the isovolumic time constant Tau (r = 0.79, P < 0.001). In cases for which a value of slope E/A < 1 was obtained, indicating a relaxation abnormality, the M-mode derived pattern of LA wall motion identified the underlying abnormal LV diastolic function with a sensitivity of 98.3%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 95.2%. Analysis of the slope of LA wall motion, indicating LA volume change rate, during LV diastolic phase is useful in evaluating LV diastolic function. It provides a new noninvasive index that correlates well with invasive index of LV relaxation. [source] Diastolic Blood Pressure-Estimated Left Ventricular dp/dtECHOCARDIOGRAPHY, Issue 2 2002Hüseyin Y, lmaz M.D. Background: Peak dp/dt is one of the best isovolumic phase indexes of the myocardial contractile state requiring invasive procedures or presence of mitral regurgitation severe enough to measure in clinical practice by Doppler echocardiography. In this study, we sought the correlation between two noninvasive methods of measurements for left ventricular dp/dt-diastolic blood pressure- (DBP) estimated and continuous-wave Doppler-derived dp/dt-min electrocardiographic/echocardiographic study to emphasize the clinical feasibility of the DBP-estimated method. Method: Thirty-six randomized patients (27 male, 9 female; 58 ± 8 years) with mild mitral regurgitation were enrolled in this study. DBP-estimated dp/dt was calculated from DBP minus the left ventricular end-diastolic pressure (LVEDP) over the isovolumetric contraction time (IVCT). LVEDP was assumed to be 10 mmHg for all patients. Doppler-determined left ventricular dp/dt was derived from the continuous-wave Doppler spectrum of mitral regurgitation jet by dividing the magnitude of the left ventricular atrial pressure gradient rise between 1 mm/sec,3 mm/sec of mitral regurgitant velocity signal by the time taken for this change. Results: Left ventricular dp/dt by Doppler was 1122 ± 303 mmHg/sec and blood pressure-estimated dp/dt was 1063 ± 294 mmHg/sec. There was a high correlation (r = 0.97, P < 0.001) of dp/dt between the two techniques. Conclusions: DBP and IVCT can generate left ventricular dp/dt without invasive procedures, even in the absence of mitral regurgitation in clinical practice. [source] Calcineurin Inhibition Ameliorates Structural, Contractile, and Electrophysiologic Consequences of Postinfarction RemodelingJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2001LILI DENG M.S. Calcineurin Inhibition and Postinfarction Remodeling.Introduction: After myocardial infarction (MI), the heart undergoes an adaptive remodeling process characterized by hypertrophy of the noninfarcted myocardium. Calcineurin, a Ca2+, calmodulin-regulated phosphatase, has been shown to participate in hypertrophic signal transduction. Methods and Results: We investigated the effects of calcineurin inhibition by cyclosporin A on key structural, contractile, and electrophysiologic alterations of post-MI remodeling. Male Sprague-Dawley rats were divided into four groups: (1) sham-operated; (2) sham + cyclosporin A; (3) post-MI (left anterior descending coronary artery ligation); and (4) MI + cyclosporin A. Cyclosporin A (25 mg/kg/day) was initiated 2 days before surgery and continued for 30 days. Hypertrophy was evaluated by echocardiography and by changes in membrane capacitance of isolated myocytes from noninfarcted left ventricle (LV). The effects of cyclosporin A on hemodynamics and cardiac dimensions were investigated, and changes in diastolic function were correlated with changes in protein phosphatase 1 activity and the basal level of phosphorylated phospholamban. The effects of cyclosporin A on Kv4.2/Kv4.3 genes expression and transient outward K + current (Ito) density also were evaluated. One of 12 rats in the post-MI group and 2 of 12 rats in the post-MI + cyclosporin A group died within 48 hours after MI. There were no late deaths in either MI group. There was no evidence of heart failure (lung congestion and/or pleural effusion) in the two groups 4 weeks post-MI. Calcineurin phosphatase activity increased 1.9-fold in post-MI remodeled LV myocardium, and cyclosporin A administration resulted in an 86% decrease in activity. There were statistically significant decreases of LV end-diastolic pressure, LV end-diastolic diameter, and LV relative wall thickness in the post-MI + cyclosporin A group compared with the post-MI group. On the other hand, there was no significant difference in LV end-systolic diameter or peak rate of LV pressure increase between the two post-MI groups. Protein phosphatase 1 activity was elevated by 36% in the post-MI group compared with sham, and this correlated with a 79% decrease in basal level of p16, phospholamban. In the post-MI + cyclosporin A group, the increase in protein phosphatase 1 activity was much less (18% vs 36%; P < 0.05), and the decrease in basal level of p16-phospholamban was markedly ameliorated (20% vs 79%; P < 0.01). The decreases in mRNA levels of Kv4.2 and Kv4.3 and Ito density in the LV of the post-MI + cyclosporin A group were significantly less compared with the post-MI group. Conclusion: Our results show that calcineurin inhibition by cyclosporin A partially ameliorated post-MI remodeled hypertrophy, diastolic dysfunction, decrease in basal level of phosphorylated phospholamban, down-regulation of key K + genes expression, and decrease of K + current, with no adverse effects on systolic function or mortality in the first 4 weeks after MI. [source] Ranolazine Attenuates Palmitoyl- l -carnitine-induced Mechanical and Metabolic Derangement in the Isolated, Perfused Rat HeartJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2000KAZUYASU MARUYAMA The effect of ranolazine, a novel anti-ischaemic drug that stimulates the activity of pyruvate dehydrogenase, on palmitoyl- l -carnitine-induced mechanical dysfunction and metabolic derangement in isolated perfused rat hearts has been studied and compared with the effect of dichloroacetate, an activator of pyruvate dehydrogenase. Rat hearts paced electrically were perfused aerobically at constant flow by the Langendorff technique. Palmitoyl- l -carnitine (4 ,m) increased left ventricular end-diastolic pressure and reduced left ventricular developed pressure (i.e. induced mechanical dysfunction); it also reduced tissue levels of adenosine triphosphate and increased tissue levels of adenosine monophosphate (i.e. induced metabolic derangement). These functional and metabolic alterations induced by palmitoyl- l -carnitine were attenuated by ranolazine (5, 10, and 20 ,m) in a concentration-dependent manner. In contrast, dichloroacetate (1 and 10 mm) did not attenuate palmitoyl- l -carnitine-induced mechanical and metabolic derangement. In the normal (palmitoyl- l -carnitine-untreated) heart, however, ranolazine did not modify mechanical function and energy metabolism. These results suggest that ranolazine attenuates palmitoyl- l -carnitine-induced mechanical and metabolic derangement in the rat heart, and that the beneficial action of ranolazine is not because of the energy-sparing effect or activation of pyruvate dehydrogenase. [source] Estimation of Left Ventricular Filling Pressure by Doppler Echocardiography in Dogs with Pacing-Induced Heart FailureJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2008K.E. Schober Background: Congestive heart failure (CHF) is a common clinical syndrome characterized by elevated filling pressure. Hypothesis: Doppler echocardiographic (DE) variables of left ventricular (LV) filling can predict a decline of LV end-diastolic pressure (LVEDP) induced by acute preload reduction in dogs with compensated CHF. Animals: Five male hound dogs. Methods: Dogs previously instrumented with a transvenous cardiac pacemaker and a LV pressure gauge were paced at 160,180 bpm to induce mild CHF characterized by LVEDP > 20 mmHg. LVEDP and 9 DE variables of LV filling derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler imaging were measured simultaneously at baseline and 30, 60, 120, and 240 minutes after furosemide (4 mg/kg, IV) or placebo (0.9% saline, IV). Repeated measures analysis of variance and correlation analysis were used to determine the association between the decline of LVEDP after furosemide and DE measures of LV filling pressure (LVFP). Results: Furosemide but not placebo decreased LVEDP (P < .001). The ratio of early transmitral flow velocity to LV isovolumic relaxation time (E : IVRT) predicted LVEDP best (R2= .50; P < .001). Correlations were also found between LVEDP and IVRT, E, ratio between E and late diastolic transmitral flow velocity (E : A), and early diastolic velocity of the mitral annulus (Ea). The ratio of E to Ea (E : Ea) was not useful in the prediction of LVEDP in this model. Conclusion and Clinical Importance: E : IVRT can be used to predict LVFP in dogs with mild left-sided CHF induced by rapid pacing. [source] ,Dynamic' Starling mechanism: effects of ageing and physical fitness on ventricular,arterial couplingTHE JOURNAL OF PHYSIOLOGY, Issue 7 2008Shigeki Shibata Cardiovascular diseases increase with advancing age, associated with left ventricular and arterial stiffening in humans. In contrast, daily exercise training prevents and/or improves both ventricular and arterial stiffening with ageing. We propose a new approach to quantify the dynamics of the Starling mechanism, namely the beat-to-beat modulation of stroke volume (SV) caused by beat-to-beat alterations in left ventricular filling, which we propose reflects the complex interaction between ventricular and arterial stiffness. We hypothesized that the dynamic Starling mechanism would be impaired with ageing, and that this impairment would be prevented and restored by daily exercise training. Two different approaches were employed: (1) a cross-sectional study to assess the effects of ageing and life-long exercise training; and (2) a longitudinal study to assess the effects of one-year endurance training in the elderly. Spectral transfer function gain between beat-to-beat changes in left ventricular end-diastolic pressure and SV was used as an index of the dynamic Starling mechanism. Gain was significantly lower in the sedentary elderly (70 ± 3 years) than in both young individuals (27 ± 6 years) and Masters athletes (68 ± 3 years), and it was significantly lower in Masters athletes than in young controls (elderly: 0.37 ± 0.11; Masters athletes: 0.96 ± 0.55; young: 1.52 ± 0.42 ml m,2 mmHg,1, mean ±s.d.). Gain increased by 65% after one-year exercise training in the elderly, although the response was quite variable (P= 0.108). These findings suggest that the dynamic Starling mechanism is impaired with human ageing possibly due to ventricular,arterial stiffening. Life-long daily exercise training may minimize this impairment, although the effect may be limited particularly when started later in life. [source] Performance of Phonoelectrocardiographic Left Ventricular Systolic Time Intervals and B-Type Natriuretic Peptide Levels in the Diagnosis of Left Ventricular DysfunctionANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2007Brian Moyers M.D. Background: Systolic time intervals measured by echocardiography and carotid artery tracings are validated methods of assessing left ventricular function. However, the clinical utility of phonoelectrocardiographic systolic time intervals for predicting heart failure using newer technology has not been evaluated. Methods: We enrolled 100 adult patients undergoing left heart catheterization. Participants underwent computerized phonoelectrocardiographic analysis, left ventricular end-diastolic pressure (LVEDP) measurement, transthoracic echocardiographic measurement of left ventricular ejection fraction (LVEF), and B-type natriuretic peptide (BNP) testing. The heart rate-adjusted systolic time intervals included the time from the Q wave onset to peak S1 (electromechanical activation time, EMAT), Q wave onset to peak S2 (electromechanical systole, Q-S2), and peak S1 to peak S2 (left ventricular systolic time, LVST). Left ventricular dysfunction was defined as the presence of both LVEDP >15 mmHg and LVEF <50%. Results: EMAT (r =,0.51; P < 0.0001), EMAT/LVST (r =,0.41; P = 0.0001), and Q-S2 (r =,0.39; P = 0.0003) correlated with LVEF, but not with LVEDP. An abnormal EMAT ,15 (odds ratio 1.38, P < 0.0001) and EMAT/LVST ,0.40 (OR 1.13, P = 0.002) were associated with left ventricular dysfunction. EMAT ,15 had 44% sensitivity, 94% specificity, and a 7.0 likelihood ratio for left ventricular dysfunction, while EMAT/LVST ,0.40 had 55% sensitivity, 95% specificity, and a 11.7 likelihood ratio. In patients with an intermediate BNP (100,500 pg/mL), the likelihood ratio increased from 1.1 using the BNP result alone to 11.0 when adding a positive EMAT test for predicting left ventricular dysfunction. Conclusions: Phonoelectrocardiographic measures of systolic time intervals are insensitive but highly specific tests for detecting abnormalities in objective markers of left ventricular function. EMAT and EMAT/LVST provide diagnostic information independent of BNP for detecting patients with left ventricular dysfunction. [source] Cardioprotection from ischemia-reperfusion injury due to Ras-GTPase inhibition is attenuated by glibenclamide in the globally ischemic heartCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2007Ibrahim Al-Rashdan Abstract The present study was designed to see if acute local inhibition of Ras-GTPase before or after ischemia (during perfusion) would produce protection against ischemia and reperfusion (I/R)-induced cardiac dysfunction. The effect of glibenclamide, an inhibitor of cardiac mitochondrial ATP-sensitive potassium (mitoKATP) channels, on Ras-GTPase-mediated cardioprotection was also studied. A 40,min episode of global ischemia followed by a 30,min reperfusion in perfused rat hearts produced significantly impaired cardiac function, measured as left ventricular developed pressure (Pmax) and left ventricular end-diastolic pressure (LVEDP). Perfusion with Ras-GTPase inhibitor FPT III before I/R [FPT(pre)], significantly enhanced cardiac recovery in terms of left ventricular contractility. Pmax was significantly higher at the end of 30,min reperfusion in FPT(pre)-treated hearts compared to pre-conditioned hearts. However, the degree of improvement in left ventricular contractility was significantly less when FPT III was given only after ischemia during reperfusion [FPT(post)]. Combination treatment with FPT III and glibenclamide before I/R resulted in significant reduction of FPT III-mediated cardioprotection. These data suggest that activation of Ras-GTPase signaling pathways during ischemia are critical in the development of left ventricular dysfunction and that opening of mitoKATP channels, at least in part, contributes to cardioprotection produced by Ras-GTPase inhibition. Copyright © 2006 John Wiley & Sons, Ltd. [source] Downregulation of survival signalling pathways and increased apoptosis in the transition of pressure overload-induced cardiac hypertrophy to heart failureCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2009Xiao-Mei Li Summary 1.,Transition from compensated left ventricular (LV) hypertrophy to decompensated heart failure was characterized using a pressure-overload induced model to elucidate the temporal relationship between cardiomyocyte apoptosis and survival signalling in this transition. 2.,Mice were subjected to transverse aortic constriction (TAC) or sham operation for 1,16 weeks and were studied by echocardiography, catheterization and histology. Relevant gene expression and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, Akt and glycogen synthase kinase (GSK)-3, were determined. 3.,Transverse aortic constriction resulted in myocyte hypertrophy and fibrosis from Week 4 and a progressive increase in left ventricular (LV) dimensions and wall thicknesses with maintained contractile function by Week 12. However, a sharp decline in contractile function and elevated LV end-diastolic pressure from 12 to 16 weeks were observed after TAC, indicating functional decompensation. 4.,Following TAC, mRNA levels of atrial natriuretic peptide, B-type natriuretic peptide, ,-myosin heavy chain (MHC) and transforming growth factor-,1 were increased time dependently, whereas mRNA expression of ,-MHC, sarcoplasmic/endoplasmic reticulum calcium ATPase 2a and Bcl-2 were decreased. The ratio of Bcl-2/Bax was decreased and this was consistent with progressively increased myocyte apoptosis demonstrated by terminal deoxyribonucleotidyl transferase-mediated dUTP,digoxigenin nick end-labelling staining. Phosphorylation of ERK1/2 was increased by Week 4, but decreased thereafter. Levels of phosphorylated Akt declined from Week 8, whereas GSK3, phosphorylation increased from 1 to 8 weeks, then decreased from Week 12 after TAC. 5.,In conclusion, TAC resulted in early concentric and late eccentric hypertrophy with eventual development of LV dysfunction. This transition was temporally associated with a progressive increase in cell size, fibrosis and myocyte apoptosis. Downregulation of ERK1/2, Akt and GSK3, and enhanced cardiomyocyte apoptosis are implicated as important mechanisms in the transition from compensated hypertrophy to heart failure. [source] An antidiabetic thiazolidinedione induces eccentric cardiac hypertrophy by cardiac volume overload in ratsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2004Kenji Arakawa Summary 1.,To assess the involvement of volume overload in the development of cardiac hypertrophy during treatment with an antidiabetic thiazolidinedione, changes in cardiac anatomy and parameters of cardiac volume overload were evaluated in female Sprague-Dawley rats treated with the thiazolidinedione derivative T-174. 2.,Two week administration of T-174 (13 and 114 mg/kg per day) increased absolute and relative heart weights by 11,24%, demonstrating the development of cardiac hypertrophy. There was no evidence of oedema in hearts from treated rats. 3.,Both plasma and blood volumes were increased in T-174-treated rats without any changes in systolic blood pressure and heart rate, whereas haematocrit was decreased. In accordance with the existence of volume overload, both left ventricular end-diastolic pressure and right atrial pressure were increased. Morphometric analysis of hearts revealed that T-174 induced eccentric heart hypertrophy, as characterized by a small increase in wall thickness and a large increase in the chamber volume, which is characteristic of volume overload. Volume overload is suggested as the possible trigger mechanism because blood volume expansion preceded cardiac hypertrophy and there was a high correlation between heart weight and blood volume. 4.,T-174-treated streptozotocin-induced diabetic rats also exhibited blood volume expansion and cardiac hypertrophy. 5.,These findings suggest that cardiac volume overload is induced by plasma volume expansion and contributes to the development of eccentric cardiac hypertrophy during treatment with antidiabetic thiazolidinediones. Although thiazolidinediones are insulin-sensitizing agents, these cardiac effects are likely to be mediated independently of insulin. [source] Impaired Heart Function And Noradrenaline Release After Ischaemia In Stroke-Prone Spontaneously Hypertensive RatsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2000Hong Chen SUMMARY 1. Stroke-prone spontaneously hypertensive rats (SHRSP) are a strain of rat that exhibit severely high blood pressure and stroke attacks at an early age, but their heart function in vitro has seldom been studied in detail. Although the activity of the sympathetic nervous system is known to increase after myocardial ischaemia, there is little information about the cardiac release of noradrenaline (NA) associated with heart function after ischaemia in SHRSP. The aim of the present study was to examine heart function and cardiac NA release after ischaemia in SHRSP. 2. Isolated hearts of 4- and 8-month-old SHRSP and age-matched Wistar-Kyoto (WKY) rats were perfused in a working heart preparation and were subjected to 30 min ischaemia followed by 30 min reperfusion. Heart function and coronary flow were monitored throughout the experiment. Coronary effluent was collected for determination of NA using high- performance liquid chromatography coupled with electrochemical detection. 3. Under baseline conditions, cardiac output of 4-month-old SHRSP was slightly but significantly decreased compared with that of WKY rats (P < 0.05), although coronary flow was maintained normally at this age. Eight-month-old SHRSP showed a further impairment of systolic heart function, with lower coronary flow and higher coronary vascular resistance under baseline conditions. Elevated left ventricular end-diastolic pressure was evident in SHRSP at both ages before ischaemia. Heart function was severely damaged after 30 min global ischaemia in SHRSP from both age groups. Stroke-prone spontaneously hypertensive rats also showed lower coronary flow and higher coronary vascular resistance during reperfusion. 4. Coronary NA was not detectable in WKY rats or SHRSP at 4 months of age under baseline conditions. In 8-month-old SHRSP, pre-ischaemic NA release was significantly higher than that in age-matched WKY rat controls. The concentration of NA in the coronary effluent of SHRSP during reperfusion was also significantly higher than that of WKY rats at both ages. 5. These data demonstrate that SHRSP have early impairment of both systolic and diastolic heart function compared with WKY rats. Severe damage of heart function and coronary flow after ischaemia in SHRSP was accompanied with an increased release of NA, which may play a harmful role in heart function impairment in SHRSP after ischaemia. [source] Effects Of The Na+/H+ Exchange Inhibitor Cariporide (HOE 642) On Cardiac Function And Cardiomyocyte Cell Death In Rat Ischaemic,Reperfused HeartCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2000Hajime Otani SUMMARY 1. Na+/H+ exchange has been implicated in the mechanism of reperfusion injury. We examined the effects of the cardiac-specific Na+/H+ exchange inhibitor cariporide (HOE 642) on postischaemic recovery of cardiac function and cardiomyocyte cell death (i.e. necrosis and apoptosis). 2. Rat isolated and buffer-perfused hearts were subjected to 25 min normothermic global ischaemia followed by 120 min reperfusion. Cariporide (10 ,mol/L) or its vehicle (0.01% dimethylsulphoxide) was administered for 15 min before ischaemia and for the first 30 min after reperfusion. 3. Cariporide significantly improved the recovery of isovolumic left ventricular function (heart rate, left ventricular developed pressure and left ventricular end-diastolic pressure) and coronary flow throughout reperfusion. Creatine kinase release during reperfusion was significantly less in the cariporide-treated heart. In situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL)- positive cardiomyocytes were also significantly less in the cariporide-treated heart after 120 min reperfusion. Electron microscopy showed necrotic changes without typical apoptotic features in cardiomyocytes after reperfusion. Such necrotic changes were mitigated by cariporide. Simultaneous detection of necrotic and apoptotic cardiomyocytes using propidium iodide (PI) and Annexin V revealed that cardiomyocytes in the infarct area were stained with only PI or both PI and Annexin V. Cariporide did not alter the pattern of cardiomyocyte staining with PI and Annexin V, although the number of cardiomyocytes stained with PI or PI plus Annexin V was less than that in vehicle-treated hearts. 4. These results suggest that apoptosis is not a major manifestation of cardiomyocyte cell death in the ischaemic, reperfused myocardium and a cariporide-sensitive mechanism of reperfusion injury promotes both necrotic and apoptotic processes of cell death. [source] | |||||||||||||