Indices Of Pump Function Research Articles

Hemodynamic and transcriptomic studies suggest early left ventricular dysfunction in a preclinical model of severe mitral regurgitation

ObjectivePrimary mitral regurgitation is a valvular lesion in which the left ventricular ejection fraction remains preserved for long periods, delaying a clinical trigger for mitral valve intervention. In this study, we sought to investigate whether adverse left ventricular remodeling occurs before a significant fall in ejection fraction and characterize these changes. MethodsSixty-five rats were induced with severe mitral regurgitation by puncturing the mitral valve leaflet with a 23-G needle using ultrasound guidance. Rats underwent longitudinal cardiac echocardiography at biweekly intervals and hearts explanted at 2 weeks (n = 15), 10 weeks (n = 15), 20 weeks (n = 15), and 40 weeks (n = 15). Sixty age- and weight-matched healthy rats were used as controls. Unbiased RNA-sequencing was performed at each terminal point. ResultsRegurgitant fraction was 40.99 ± 9.40%, with pulmonary flow reversal in the experimental group, and none in the control group. Significant fall in ejection fraction occurred at 14 weeks after mitral regurgitation induction. However, before 14 weeks, end-diastolic volume increased by 93.69 ± 52.38% (P < .0001 compared with baseline), end-systolic volume increased by 118.33 ± 47.54% (P < .0001 compared with baseline), and several load-independent pump function indices were reduced. Transcriptomic data at 2 and 10 weeks before fall in ejection fraction indicated up-regulation of myocyte remodeling and oxidative stress pathways, whereas those at 20 and 40 weeks indicated extracellular matrix remodeling. ConclusionsIn this rodent model of mitral regurgitation, left ventricular ejection fraction was preserved for a long duration, yet rapid and severe left ventricular dilatation, and biological remodeling occurred before a clinically significant fall in ejection fraction.

The effect of repolarization duration on the indices of the pump function of the heart ventricles in animals with different types of activation of the myocardium under ectopic excitation of ventricles

Background — The aim of the work was to study the influence of myocardial repolarization on the indices of the pump function in animals with different types of the myocardial activation (dog, amphibians) under ectopic excitation of the ventricles. Material and Methods — Intraventricular blood pressure in animals was measured using a hemodynamic Prucka MacLab 2000 system under basal and apical locations of the stimulating electrode on the ventricles of the heart. The activation-recovery intervals (ARIs) were determined from unipolar myocardial electrograms recorded in the intramural layers of apical and basal parts of the ventricles in dog (n=16) and amphibians (toads Bufo bufo, n=11; frogs Rana temporaria, n=23). Data are presented as median with lower and upper quartiles. Results — The pacing of the left ventricle apical area in dogs with more prolonged ARIs, as compared with the base, does not change the isovolumic indices of the left ventricle pump function. However, ARIs were longer at the ventricular base – 248 (206, 260) ms for dog’s right ventricle and 742 (680, 929) ms for froggy ventricle, as compared with the apex in the canine right ventricle – 238 (219, 249) ms, and the ventricle in the amphibians – 692 (637, 860) ms. Therefore, pacing of the right ventricle in the apical area in dog and ventricular apex in amphibians leads to a significant decrease of their pump function. Conclusion — In the animals with successive (amphibians) and flash-successive (dog) types of activation of the myocardium, parameters of the pump function of ventricles were better at pacing of the area with the longest repolarization at the baseline and worse at pacing of the shortest repolarization area.

Protective effects of a modified apelin-12 and dinitrosyl iron complexes in experimental cardioplegic ischemia and reperfusion

The maintenance of nitric oxide (NO) bioavailability has been recognized as an important component of myocardial protection during cardiac surgery. This study was designed to evaluate the efficacy of using two NO-donating compounds in cardioplegia and reperfusion: (i) a modified peptide apelin-12 (MA12) that activates endothelial NO synthase (eNOS) and (ii) dinitrosyl iron complexes with reduced glutathione (DNIC-GS), a natural NO vehicle. Isolated perfused working rat hearts were subjected to normothermic global ischemia and reperfusion. St. Thomas' Hospital cardioplegic solution (STH) containing 140μM MA12 or 100μM DNIC-GS was used. In separate series, 140μM MA12 or 100μM DNIC-GS was administered at early reperfusion. Metabolic state of the hearts was evaluated by myocardial content of high-energy phosphates and lactate. Lactate dehydrogenase (LDH) activity in myocardial effluent was used as an index of cell membrane damage. Cardioplegia with MA12 or DNIC-GS improved recovery of coronary flow and cardiac function, and reduced LDH leakage in perfusate compared with STH without additives. Cardioplegic arrest with MA12 significantly enhanced preservation of high-energy phosphates and decreased accumulation of lactate in reperfused hearts. The overall protective effect of cardioplegia with MA12 was significantly greater than with DNIC-GS. The administration of MA12 or DNIC-GS at early reperfusion also increased metabolic and functional recovery of reperfused hearts. In this case, recovery of cardiac contractile and pump function indices was significantly higher if reperfusion was performed with DNIC-GS. The results show that MA12 and DNIC-GS are promising adjunct agents for protection of the heart during cardioplegic arrest and reperfusion.

Metabolic and functional effects of carbachol and ischaemic preconditioning in rat isolated heart.

1. Metabolic and functional effects of ischaemic preconditioning (IP), pretreatment with carbachol (Ch) and combined interventions were studied in rat isolated working hearts subjected to 20 min global ischaemia (37 degrees C) and 40 min reperfusion. Prior to the ischaemic period, hearts were either perfused according to Langendorff (control group), ischaemically preconditioned by 5 min global ischaemia and 5 min reperfusion (IP group), perfused with 0.1 mumol/L Ch for 5 min and then with Ch-free Krebs'-Henseleit buffer for 5 min (Ch group) or perfused with 0.1 mumol/L Ch for 5 min and then subjected to IP (Ch + IP group). 2. Although Ch exerted slight negative chronotropic and inotropic effects during pre-ischaemic Langendorff perfusion, it did not affect myocardial contents of ATP and phosphocreatine (PCr) prior to sustained ischaemia. At the end of final reperfusion, the IP and Ch groups showed similar recovery of aortic output (67.5 +/- 5.0 and 56.8 +/- 5.4%, respectively), cardiac output (65.4 +/- 5.4 and 63.5 +/- 5.7%, respectively) and stroke volume (73.4 +/- 7.5 and 67.0 +/- 6.7%, respectively) expressed as a percentage of steady state values. These indices were higher than those in the control group (42.8 +/- 4.7, 53.8 +/- 4.3 and 56.1 +/- 5.6%, respectively; P < 0.05). The Ch + IP group exhibited complete recovery of all indices of pump function, including cardiac work, expressed as the cardiac output-mean aortic pressure (CO-MAP) product. 3. There were no differences in ATP recovery between the groups after reperfusion: the ATP content was, on average, 73.1 +/- 3.5% of the initial ATP content. However, all treated groups had enhanced PCr recovery and better preservation of total creatine (sigma Cr = PCr + Cr), an index of cell membrane integrity, than control. Metabolic efficacy of the pre-ischaemic interventions can be ranked as follows: IP < or = Ch < Ch + IP. In all groups, myocardial content of sigma Cr was positively correlated with percentage recovery of the CO-MAP product at the end of reperfusion (r = 0.79, P < 0.05). 4. The results demonstrate that Ch treatment combined with IP provides significantly greater postischaemic myocardial salvage. The similarity of the metabolic and functional effects of Ch treatment and IP strongly suggests muscarinic M2 acetylcholine receptor involvement in acute adaptation of rat heart to ischaemia/reperfusion stress.

Effects of unloading and positive inotropic interventions on left ventricular function in asymptomatic patients with chronic severe aortic insufficiency.

The effect of an unloading (nifedipine, 20 mg sublingually) and of a combined unloading and positive inotropic intervention (nifedipine plus digoxin, 0.5 mg intravenously) on left ventricular performance was assessed in 48 patients with chronic severe aortic insufficiency. The left ventricular pump function-myocardial contractility relation (ejection fraction, EF vs. peak arterial pressure to end-systolic volume ratio, PAP/ESV), and the pump function-afterload relation (EF vs. mean systolic wall stress, MWS) were constructed by means of quantitative M-mode and two-dimensional echocardiography. In patients with normal control pump function (n = 14), nifedipine markedly decreased MWS, moving the patients to a new, more advantageous EF-MWS relation. In the 34 patients with abnormal pump function, the myocardial contractility level was the mean factor conditioning the response to pharmacological intervention. Patients with a value of PAP/ESV greater than 2.5 (n = 22) had normalization of EF after nifedipine and were upgraded to a more advantageous outlook for left ventricular mechanics EF-MWS and EF-PAP/ESV relations. Of the 12 patients without normalization of EF after nifedipine, only the 4 patients with PAP/ESV greater than 2 had normalization of pump function indices after combined administration of nifedipine and digoxin.

The role of diastolic abnormalities in the mechanisms of early stages of heart failure

Widely spread methods of diagnostics of early, including latent, heart failure are based mainly on systolic, pump function indices. Limited spread of diastolic myocardial function studies is probably due to the absence of clear criteria for evaluation of existing diastolic process parameters and their comparison with the generally accepted division of heart failure into stages.

Temperature-dependency of nifedipine as a protective agent during cardioplegia in the rat.

An isolated working rat heart preparation was used to characterise the temperature-dependency of the anti-ischaemic properties of nifedipine. In this study hearts were subjected to pre-ischaemic infusion with the St Thomas' cardioplegic solution with or without added nifedipine (0.075 mumol X litre-1). Hearts were then rendered globally ischaemic for various periods, (35, 42, 48, 56, 55, 65, 80, 105 or 130 min) at various temperatures (37.0, 35.5, 34.0, 32.5, 31.0, 29.0, 27.0, 24.0 or 20.0 degrees C, respectively). The duration of ischaemia at each temperature was selected to produce a post-ischaemic (37 degrees C) recovery of aortic flow that was approximately 50% of its pre-ischaemic (37 degrees C) control. In addition to functional indices (aortic flow, cardiac output, coronary flow, aortic pressure and heart rate) creatine kinase leakage during reperfusion was measured. At all temperatures at or above 31 degrees C the addition of nifedipine enhanced significantly (maximal value = 43%) the post-ischaemic recovery of aortic flow and other indices of pump function, while at the same time reducing significantly (by up to 56%) enzyme leakage. At ischaemic temperatures below 31 degrees C nifedipine failed to afford any significant additional protection when assessed functionally or enzymatically. It would therefore appear that hypothermia either blocks the action of nifedipine or, by acting on some common mechanism, renders the actions of the drug redundant.

Mitral E point septal separation: A reliable index of left ventricular performance in coronary artery disease

The diagnostic value of E point septal separation (EPSS) was assessed in 108 patients with coronary artery disease who underwent coronary angiography and M-mode echocardiography within a 2-year period at LAC/USC Medical Center. In patients with anterior myocardial infarction, EPSS correlated well with angiographic ejection fraction, with a specificity of 85% and sensitivity of 82%. In inferior myocardial infarction, a 21% frequency of falsely elevated EPSS values was encountered; the sensitivity for detecting reduced ejection fraction was 100% and the specificity was 67%. In combined anterior and inferlor myocardial infarction, EPSS accurately estimated abnormal ejection fractions with a sensitivity and specificity of 100%. An abnormal EPSS (more than 7 mm) was found to be more sensitive (87%) and specific (75%) in detecting individuals with angiographically reduced ejection fraction (less than 50%) compared to other echocardiographic indices of pump function. Importantly, EPSS was effective in estimating left ventricular function in the presence of left bundle branch block, paradoxical septal motion, and angiographic septal, posterior, and anterior wall motion abnormalities.

Dissociation between Indices of Pump Performance and Contractility in Patients with Coronary Artery Disease and Acute Myocardial Infarction

An analysis of ventricular performance comparing pump function and muscle function indices was performed in 13 patients with acute myocardial infarction, ten patients with normal coronary arteries, and 15 patients with coronary artery disease. Pump function was described by plotting left ventricular stroke work index as a function of left ventricular end diastolic pressure. This description provided a clear separation between normal patients, and surviving and nonsurviving patients with acute myocardial infarction. Values of contractile element velocity (VCE5 as an estimate of Vmax) did not separate between normals and surviving or nonsurviving patients with acute myocardial infarction. In 15 patients with acute coronary artery disease there was no correlation between values of VCE5 and the ventricular function curve. Changes in performance following the stress of ventriculography, angiotensin infusion, or isometric hand grip exercise also did not show any correlation between pump function and muscle function indices. It is concluded that pump function indices are a better indicator of ventricular performance in patients with acute myocardial infarction and coronary artery disease.

Comparison of indices of muscle and pump performance in patients with coronary artery disease.

During diagnostic cardiac catheterization of 20 patients, 19 of whom had coronary artery disease (CAD), left ventricular (LV) performance was assessed by both muscle function indices and pump function indices. Muscle function indices included max dP/dt, Vpm, Vce5, and Vmax, the latter derived from both total pressure (TP) and developed pressure (DP) using catheter-tip manometry. Pump function indices included LV ejection fraction (EF) and percent abnormally contracting segment (ACS), determined from biplane LV angiography. Muscle and pump function indices were also compared to the presence of the S3 (ventricular diastolic) gallop. Correlations existed between EF and Vmax (TP), EF and Vpm, percent-ACS and Vmax(TP), and percent-ACS and Vpm, with r values of 0.760, 0.777, -0.884, and -0.841, respectively. Vmax(TP) and Vpm also correlated quantitatively with the presence of the S3 gallop (p less than 0.0005). Total pressure-derived muscle function indices appear to adquately describe mean LV performance in patients with CAD and ACS, but these muscle function indices are probably highly dependent upon the size of the myocardial scar.