Changes In Ventricular Pressure Research Articles

EFFECTS OF LANDIOLOL ON MECHANICAL AND METABOLIC CHANGES IN RAT REPERFUSED ISCHAEMIC HEARTS

1. The aim of the present study was to clarify the effects of landiolol, a short-acting selective beta(1)-adrenoceptor blocking agent, on mechanical and metabolic changes in postischaemic perfused hearts. 2. Rat isolated hearts (n = 30) were randomly separated into non-ischaemic or ischaemic groups. The latter group was further divided into Krebs'-Henseleit solution (KHS)- and landiolol (30, 100 or 300 micromol/L)-treated groups. Ischaemic hearts were subjected to 25 min global ischaemia and 20 min reperfusion under atrial pacing. Time-course changes in left ventricular (LV) end-diastolic pressure (LVEDP), LV developed pressure (LVDP), peak positive velocity of change of LV pressure (LVdP/dt(max)) and coronary flow were observed along with tissue contents of adenosine triphosphate (ATP), creatine phosphate, inorganic phosphate (Pi), malondialdehyde (MDA) and lactate dehydrogenase (LDH) release in coronary effluent. The effects of landiolol on rat isolated aortic preparations under KCl contraction were also investigated. 3. Ischaemia-reperfusion significantly impaired cardiodynamics, such as LVEDP, LVDP and LVdP/dt(max), decreased myocardial ATP content and increased Pi and LDH release. In the 30 micromol/L landiolol-treated group, cardiovascular parameters impaired by ischaemia-reperfusion and increased LDH release were further exacerbated and myocardial MDA content was significantly increased. In the 300 micromol/L landiolol-treated group, cardiac contractile dysfunction was improved and myocardial MDA, ATP and Pi contents were preserved. All measurements in the 100 micromol/L landiolol-treated group were similar to those in the ischaemic KHS group. Furthermore, significant relaxations of isolated aortic preparations were obtained with landiolol 30-1000 micromol/L, suggesting a possible calcium antagonism with landiolol. 4. In conclusion, landiolol, at low concentrations, aggravated myocardial ischaemia-reperfusion injuries, whereas at high concentrations it ameliorated them. The former effect may be mediated by the production of reactive oxygen species, whereas the latter may involve calcium antagonist activity.

Intracoronary Ghrelin Infusion Decreases Coronary Blood Flow in Anesthetized Pigs

The peptide ghrelin has been linked to the atherosclerotic process and coronary artery disease. We planned to study, for the first time, the primary effects of ghrelin on the intact coronary circulation and determine the mechanisms involved. In 24 sodium pentobarbitone-anesthetized pigs, changes in anterior descending coronary blood flow caused by intracoronary infusion of ghrelin at constant heart rate and arterial pressure were assessed using electromagnetic flowmeters. In 20 pigs, intracoronary infusion of ghrelin decreased coronary blood flow without affecting left ventricular maximum rate of change of left ventricular systolic pressure (dP/dt(max)), filling pressures of the heart or plasma levels of GH. In four pigs, this decrease was graded by step increments of infused dose of the hormone. The mechanisms of the above response were studied in the 20 pigs by repeating the experiment after coronary flow had returned to the control values observed before infusion. The ghrelin-induced coronary vasoconstriction was not affected by iv atropine (five pigs) or phentolamine (five pigs). This response was abolished by iv butoxamine (five pigs) and intracoronary N(omega)-nitro-l-arginine methyl ester (five pigs), even after reversing the increase in arterial pressure and coronary vascular resistance caused by the two blocking agents with iv infusion of papaverine. The present study showed that intracoronary infusion of ghrelin primarily caused coronary vasoconstriction. The mechanisms of this response were shown to involve the inhibition of a vasodilatory beta(2)-adrenergic receptor-mediated effect related to the release of nitric oxide.

The assessment of acute load and contractility changes by left ventricular pressure measurements

The aim of this study was to establish whether analysis of the left ventricular pressure waveform provides indicative information about cardiac load and contractility and to develop an algorithm for computer-based assessment of changes in these variables. In eight healthy standard breed anaesthetized open-chest pigs, a high frequency response guide-wire mounted pressure sensor was introduced into the left ventricle. Preload reduction was induced by vena cava occlusion, afterload increase by an i.v. injection of phenylephrine and increased contractility by an i.v. injection of adrenalin. Left ventricular pressure waveform analysis was performed by plotting the slope of the pressure curve during the systolic ejection period versus maximal systolic pressure. The analysis revealed characteristic changes in left ventricular pressure and pressure waveform and identified easily discernible reaction patterns in the slope versus maximal pressure plot, specific for each provocation. Analysis of the left ventricular waveform provides indicative information about loading conditions and contractility. The proposed algorithm can easily be implemented in pressure monitoring systems allowing real-time assessment and discrimination of acute changes in preload, afterload and myocardial performance.

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone. After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 microm bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4 degrees C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured. All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline. Adding bupivacaine to a depolarizing cardioplegia solution reduces cell damage and improves cardiac function after prolonged storage. Metabolic inhibition may contribute to this phenomenon, which is not entirely explained by sodium channel blockade.

Changes in Plasma N-Terminal proBNP Levels and Ventricular Filling Pressures During Intensive Unloading Therapy in Elderly With Decompensated Congestive Heart Failure and Preserved Left Ventricular Systolic Function

Background Plasma B-type natriuretic peptide (BNP) levels depend on left ventricular (LV) filling pressures and correlate with the state of neurohormonal modulation in patients with congestive heart failure (CHF). In these subjects, therapy of decompensated CHF can determine acute changes in BNP levels. Methods and Results We defined the sequential pattern of N-terminal (T) proBNP in elderly with decompensated CHF and preserved LV systolic function undergoing intensive unloading therapy, assessed the prevalence of patients who significantly reduced NTproBNP at the end of treatment, and verified the relations between changes in NTproBNP and ventricular filling pressures. NTproBNP was measured in 30 patients hospitalized for worsening CHF with LV ejection fraction >50% at admission and after 2 to 4 and 6 to 8 days from the start of treatment. Patients who exhibited a reduction in NTproBNP >35% from baseline to 8-day evaluation were defined as “responders.” Twelve healthy subjects matched for age and sex were used as controls. NTproBNP was significantly higher in CHF patients than controls in all time points, to a greater extent in baseline evaluation (2982 [lower/upper quartile 1273/8146] versus 235 [150/280] pg/mL). A progressive, linear reduction of NTproBNP was detected in CHF patients during unloading. At Day 8, 18 patients (60%) resulted in “responders,” whereas 12 (40%) were “nonresponders.” The former could be predicted through higher pulmonary artery wedge pressure at baseline. Surprisingly, ventricular filling pressures similarly declined in responders and non responders. At Day 8, NTproBNP was yet 7-fold higher in CHF patients than controls. Conclusion Intensive unloading therapy is associated with a significant short-term reduction in NTproBNP in elderly with CHF and preserved LV systolic function. This behavior is progressive and linear during the first week and parallels a reduction in ventricular filling pressures which, however, does not differ between patients who significantly reduce NTproBNP and those who do not. Thus the short-term changes in NTproBNP during intensive unloading therapy in our patients do not depend only on the acute improvement in hemodynamic conditions.

Apex techniques, old and new, hold the key to estimated left ventricular end-diastolic and right ventricular systolic pressure

The clinical syndrome of heart failure is characterised by a raised venous pressure, dilated ventricular cavity, and exercise intolerance. Raised left ventricular (LV) end-diastolic pressure and high left atrial pressure suggest a poor prognosis [1, 2]. Detection of raised filling pressures are important not only in the progression of coronary artery disease and dilated cardiomyopathy, but also because recent evidence suggests that restrictive LV filling may predict non-responders [3] to the increasingly popular intervention of cardiac resynchronisation therapy. Measurements of ventricular long axis function rely on the fact that the cardiac apex is fixed with respect to the chest wall [4]. Atrio-ventricular coupling during systole and diastole is mediated by an anatomically distinct set of sub-endocardial and sub-epicardial fibres organised longitudinally from base to apex [5]. Systolic function is quantified by familiar measurements such as ejection fraction, fractional shortening or peak rate of pressure change (dp/ dt). Wiggers [6] defined diastole as the period in the cardiac cycle from the ‘‘end of aortic ejection until the onset of ventricular tension development’’. Diastole is a complex sequence involving mechanisms of restoring forces and ventricular compliance, changes in atrial and ventricular pressure, transmitral filling, ventricular interaction, and atrial mechanical activity [1]. Consequently, diastolic function has proved more elusive to quantify, accumulating a stable of surrogates indicative of left atrial (LA) pressure, left ventricular end-diastolic pressure (LVEDP), transmitral flow velocities or long axis function. Assessment is further complicated because abnormalities observed in diastole may arise during the isovolumic periods, as well as in systole. Diastolic function is far more age-dependent than systolic function because physiologically normal values in the young may indicate pathologies in the elderly [1]. Isovolumic relaxation time (from A2 [end of ejection] to mitral cusp separation on M-mode) shortens with raised left atrial pressure, but prolongs with age. Normal ranges for isovolumic relaxation time are 60 – 20 ms (M-mode) [1] or 85 – 15 ms (Doppler) [7]; values less than 40 ms indicate raised left atrial pressure, and zero isovolumic relaxation R. Chung AE M. Y. Henein (&) National Heart and Lung Institute, Department of Echocardiography, Royal Brompton Hospital, Sydney Street, SW3 6NP London, UK e-mail: m.henein@rbht.nhs.uk Int J Cardiovasc Imaging (2006) 22: 643–646 DOI 10.1007/s10554-006-9097-4

In-Vivo Dynamic Deformation of the Mitral Valve Anterior Leaflet

Surgical techniques have been developed for mitral valve repair for a wide range of pathologies. However, excessive tissue stress and damage have been identified as etiologic factors limiting long-term durability. Before computational models to optimize valve repair can be realistically developed, in-vivo dynamic mitral valve leaflet strain data are required. However, these data do not presently exist. In the present study, a sheep model and sonomicrometry were used to compute the in-surface Eulerian strain tensor of the anterior leaflet over the cardiac cycle at varying afterloads. The anterior leaflet of nine Dorsett sheep (35 kg to 45 kg) was instrumented with nine 1-mm hemispherical piezoelectric transducers in a 15-mm square array. Three-dimensional crystal spatial positions were recorded at 250 Hz over several cardiac cycles, with peak left ventricular pressures varying from 90 mm Hg to 200 mm Hg. The in-surface Eulerian strain tensor was computed from the crystal displacements. The mitral valve anterior leaflet experiences large anisotropic strains and peak strain rates of 400%/s, followed by an absolute cessation of any deformation during systole. Increasing left ventricular pressure also increased the effective leaflet stiffness but not the peak strains. We report the first data on the dynamic in-vivo strain tensor of a functioning mitral valve anterior leaflet, which indicated large anisotropic strains and very high strain rates. Our observations also suggest that changes in left ventricular pressure and annular geometry result in altered effective leaflet stiffness, and may be an important factor in reducing leaflet stress and as such potentially affect mitral valve repair longevity.

Detection of Cardiac Variability in the Isolated Rat Heart

Cardiac variability can be assessed from two perspectives: beat-to-beat performance and continuous performance during the cardiac cycle. Linear analysis techniques assess cardiac variability by measuring the physical attributes of a signal, whereas nonlinear techniques evaluate signal dynamics. This study sought to determine if recurrence quantification analysis (RQA), a nonlinear technique, could detect pharmacologically induced autonomic changes in the continuous left ventricular pressure (LVP) and electrographic (EC) signals from an isolated rat heart-a model that theoretically contains no inherent variability. LVP and EC signal data were acquired simultaneously during Langendorff perfusion of isolated rat hearts before and after the addition of acetylcholine (n = 11), norepinephrine (n = 12), or no drug (n = 12). Two-minute segments of the continuous LVP and EC signal data were analyzed by RQA. Findings showed that%recurrence,%determinism, entropy, maxline, and trend from the continuous LVP signal significantly increased in the presence of both acetylcholine and norepinephrine, although systolic LVP significantly increased only with norepinephrine. In the continuous EC signal, the RQA trend variable significantly increased in the presence of norepinephrine. These results suggest that when either the sympathetic or parasympathetic division of the autonomic nervous system overwhelms the other, the dynamics underlying cardiac variability become stationary. This study also shows that information concerning inherent variability in the isolated rat heart can be gained via RQA of the continuous cardiac signal. Although speculative, RQA may be a tool for detecting alterations in cardiac variability and evaluating signal dynamics as a nonlinear indicator of cardiac pathology.

Myocardial protective effects of nicorandil, an opener of potassium channels on senile rat heart

The purpose of this study was to investigate the cardioprotective effects of nicorandil, an opener of potassium channels, on senile rat hearts from ischemic reperfusion injury. A modified working model of isolated perfused hearts of senile rats was used. After isolation, the hearts underwent 60 min of global hypothermic ischemia treatment, followed by 30 min of reperfusion. These hearts were distributed into three groups, each receiving different cardioplegic solutions: (1) St. Thomas' solution (Group S), (2) 100 micromol/L nicorandil (Group N), (3) St. Thomas' solution combined with 100 micromol/L nicorandil (Group S+N). The pre- and post-ischemic myocardial function were assessed by the percentage recovery of the heart rate (HR), +/- dp/dt(max) (maximal rate of change of left ventricular pressure) and cardiac output (CO). Upon reperfusion, the cardioplegic solution was collected from the coronary sinus and tested for lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity. During 30 min of reperfusion, the percentage recovery of HR, +dp/dt and left ventricular stroke work (LVSW) were significantly higher in Group S+N than in Group S and Group N (p < 0.05). The percentage of recovery in CO was higher in Group N and Group S+N than in Group S. The electrical activities arresting time (EAT) and mechanical activities arresting time (MAT) were longer in Group N than in Group S and Group N+S (p < 0.01). There were no statistical significance between Group S and Group N+S (p > 0.05). There were no significant differences in the levels of LDH and CK-MB. Electron microscopic examination revealed better preservation of the ultrastructures of the myocardial tissue in Group N+S than the other two groups. These results indicate that nicorandil combined with St. Thomas' solution can improve the left ventricular function of the post-ischemic senile rat and offer a better myocardial protective effect on the ischemic senile myocardium.

Changes in end-to-end interactions of tropomyosin affect mouse cardiac muscle dynamics

The ends of striated muscle tropomyosin (TM) are integral for thin filament cooperativity, determining the cooperative unit size and regulating the affinity of TM for actin. We hypothesized that altering the alpha-TM carboxy terminal overlap end to the beta-TM counterpart would affect the amino-terminal association, which would alter the end-to-end interactions of TM molecules in the thin filament regulatory strand and affect the mechanisms of cardiac muscle contraction. To test this hypothesis, we generated transgenic (TG) mouse lines that express a mutant form of alpha-TM in which the first 275 residues are from alpha-TM and the last nine amino acids are from beta-TM (alpha-TM9aaDeltabeta). Molecular analyses show that endogenous alpha-TM mRNA and protein are nearly completely replaced with alpha-TM9aaDeltabeta. Working heart preparations data show that the rates of contraction and relaxation are reduced in alpha-TM9aaDeltabeta hearts. Left ventricular pressure and time to peak pressure are also reduced (-12% and -13%, respectively). The ratio of maximum to minimum first derivatives of change in left ventricular systolic pressure with respect to time (ratio of +dP/dt to -dP/dt, respectively) is increased, but tau is not changed significantly. Force-intracellular calcium concentration ([Ca2+]i) measurements from intact papillary fibers demonstrate that alpha-TM9aaDeltabeta TG fibers produce less force per given [Ca2+]i compared with nontransgenic fibers. Taken together, the data demonstrate that the rate of contraction is primarily affected in TM TG hearts. Protein docking studies show that in the mutant molecule, the overall carbon backbone is perturbed about 1.5 A, indicating that end-to-end interactions are altered. These results demonstrate that the localized flexibility present in the coiled-coil structures of TM isoforms is different, and that plays an important role in interacting with neighboring thin filament regulatory proteins and with differentially modulating the myofilament activation processes.

Norepinephrine-induced diastolic dysfunction with aortic valve opening under calcium-loading in rats

Heart failure associated with a high plasma level of norepinephrine (NE) has an extremely poor prognosis with NE being the most powerful predictor of all-cause mortality. An increase in the diastolic intracellular calcium level (Ca2+) occurs in left ventricular dysfunction; however, the cause-and-effect relationships among Ca2+loading, high plasma NE, and an increase in diastolic ventricular pressure is unclear. Here, we examined the relationship between diastolic dysfunction and NE with and without Ca2+loading in rats. Animals were studied in four groups: Ca2+loading for 45 min (Ca2+group), NE alone for 25 min (30 µg/kg/min NE for 25 min; NE group), Ca2+loading and NE for 25 min after Ca2+loading (Ca2+-NE group), and a vehicle group. Hemodynamics were examined using a micromanometer-tipped pressure catheter, and diastolic function was studied using Doppler echocardiography. Significantly increased left ventricular end-diastolic pressure (LVEDP) and decreased E and Ea waves and deceleration time (DCT) were found in the Ca2+-NE group, compared with the Ca2+and NE groups. There were no changes in left ventricular pressure (LVP) and LV ejection fraction (EF) among the four groups. NE-induced diastolic contracture (NEIDC) with aortic valve opening occurred in the diastole when LVP overshot the aortic pressure after co-administration of NE and Ca2+after Ca2+loading, and pulmonary hemorrhage was observed in all animals of the Ca2+-NE group. The results support the suggestion that NE may be an important factor in the development of diastolic dysfunction in ischemic heart disease. Drug Dev. Res. 67:511–518, 2006. © 2006 Wiley-Liss, Inc.

522 Assessment of tricuspid annular motion using tissue Doppler imaging before and after mitral valvuloplasty, correlation with changes in the right ventricular systolic pressure and mitral valve area

522 Assessment of tricuspid annular motion using tissue Doppler imaging before and after mitral valvuloplasty, correlation with changes in the right ventricular systolic pressure and mitral valve area

935 Left ventricular remodeling and blood pressure changes after arteriovenous fistula closure in renal transplant recipients

935 Left ventricular remodeling and blood pressure changes after arteriovenous fistula closure in renal transplant recipients

In Vivo Cardiac Electrophysiologic Effects of a Novel Diphenylphosphine Oxide IKur Blocker, (2-Isopropyl-5-methylcyclohexyl) Diphenylphosphine Oxide, in Rat and Nonhuman Primate

The voltage-gated potassium channel, Kv1.5, which underlies the ultrarapid delayed rectifier current, I(Kur), is reported to be enriched in human atrium versus ventricle, and has been proposed as a target for novel atrial antiarrhythmic therapy. The administration of the novel I(Kur) blocker (2-isopropyl-5-methyl-cyclohexyl) diphenylphosphine oxide (DPO-1) (0.06, 0.2, and 0.6 mg/kg/min i.v. x 20 min; total doses 1.2, 4.0, and 12.0 mg/kg, respectively) to rat, which exhibits I(Kur) in both atria and ventricle, elicited significant, dose-dependent increases in atrial and ventricular refractory period (9-42%) at all doses tested, with no changes in cardiac rate or indices of cardiac conduction. Plasma levels achieved in rat at the end of the three infusions were 1.1, 4.1, and 7.7 microM. Reverse transcription-polymerase chain reaction analysis of African green monkey atria and ventricle demonstrated an atrial preferential distribution of Kv1.5 transcript. The administration of DPO-1 (1.0, 3.0, and 10.0 mg/kg i.v.; 5-min infusions) to African green monkey elicited significant increases in atrial refractoriness (approximately 15% increase at the 10.0 mg/kg dose), with no change in ventricular refractory period, ECG intervals, heart rate, or blood pressure. Plasma levels of DPO-1 achieved in African green monkey were 0.58, 1.12, and 5.43 microM. The concordance of effect of DPO-1 on myocardial refractoriness with distribution of Kv1.5 in these two species is consistent with the I(Kur) selectivity of DPO-1 in vivo. Moreover, the selective increase in atrial refractoriness in primate supports the concept of I(Kur) blockade as an approach for the development of atrial-specific antiarrhythmic agents.

Left ventricular volume and function after endoventricular patch plasty for dyskinetic anteroapical left ventricular aneurysm in sheep

Endoventricular patch plasty (the Dor procedure) has gained favor as a surgical treatment for heart failure associated with large anteroapical myocardial infarction. We tested the hypothesis that the Dor procedure reduces left ventricular volume, increases end-systolic elastance, decreases diastolic compliance, and maintains left ventricular function. In 6 male Dorsett sheep, the left anterior descending coronary artery and its second diagonal branch were ligated 40% of the distance from apex to base. Sixteen weeks after myocardial infarction, a Dor procedure was performed with a Dacron patch that was 50% of the infarct neck dimension. Absolute left ventricular volume was measured with magnetic resonance imaging, and left ventricular pressure and relative left ventricular volume changes during pharmacologic preload reduction were measured with a volume conductance catheter 2 weeks before and 2 and 6 weeks after the Dor procedure. End-systolic elastance, diastolic compliance, and Starling relationships were calculated from the resultant left ventricular pressure/volume loops. Two weeks after the Dor procedure, the left ventricular volume at end systole and end diastole was significantly reduced, and there was no redilation at 6 weeks. Six weeks after the Dor procedure, the ejection fraction was significantly increased. Although stroke volume increased slightly at 6 weeks, the change was not significant. The slopes of end-systolic elastance, diastolic compliance, and Starling relationships were unchanged at 2 and 6 weeks. The Dor procedure significantly reduces left ventricular volume. Unlike linear repair, left ventricular volume changes seem stable. The ejection fraction is improved, and left ventricular function (stroke volume and the Starling relationship) is maintained.

Muscle metaboreflex control of ventricular contractility during dynamic exercise

When oxygen delivery to active skeletal muscle is insufficient for the metabolic demands, afferent nerves within muscles are activated, which elicit reflex increases in heart rate (HR), cardiac output (CO), and arterial pressure (AP), termed the muscle metaboreflex (MMR). To what extent the increases in CO are the result of increased ventricular contractility is unclear. A widely accepted index of contractility is maximal left ventricular elastance (Emax), the slope of the end-systolic pressure-volume relationship, such as during rapidly imposed reductions in preload. The objective of the present study was to determine whether MMR activation elicits increases in Emax. Experiments were performed using conscious dogs chronically instrumented to measure left ventricular pressure and volume at rest and during mild or moderate treadmill exercise with and without partial hindlimb ischemia to elicit MMR responses. At both workloads, MMR activation significantly increased CO, HR, AP, and maximum rate of change of left ventricular pressure. During both mild and moderate exercise, MMR activation increased Emax to 159.6 +/- 8.83 and 155.8 +/- 6.32% of the exercise value under free-flow conditions, respectively. We conclude that the increase of ventricular elastance associated with MMR activation indicates that a substantial increase in ventricular contractility contributes to the rise in CO during dynamic exercise.

Dynamic changes in right ventricular pressures during haemodialysis recorded with an implantable haemodynamic monitor

Intermittent and chronic volume overload contributes to the development of cardiovascular disease in patients on maintenance haemodialysis (HD). Continuous monitoring of central haemodynamic parameters may provide valuable information to improve volume control, particularly in patients with left ventricular dysfunction. Five patients on HD, age 53-76 years, with systolic and/or diastolic dysfunction (EF 20-50%) received an implantable haemodynamic monitor (IHM) (Chronicle model 9520, Medtronic). The IHM consists of a memory device implanted subcutaneously and a transveneous right ventricular (RV) lead carrying a pressure sensor. It continuously records heart rate, RV systolic (RVSP) and diastolic pressures (RVDP), RV dP/dt and an estimate of pulmonary artery diastolic pressure (ePAD). Continuous haemodynamic profiles were recorded in all patients. During dialysis RVSP and ePAD dropped by a mean of 39 and 50%, respectively. RVDP decreased by 6.6 mmHg. The lowest pressures occurred during the first 90 min of dialysis and were partly restored at the end of the procedure. Long-term haemodynamic monitoring unmasked severe volume overload in one patient, when dry weight was kept stable despite a decrease in lean body mass. In another patient with recurrent dyspnea after dialysis, paroxysmal atrial fibrillation, regularly occurring during dialysis, was identified as the cause of symptoms. The implanted haemodynamic monitor was a sensitive indicator for changes in volume load. Continuous haemodynamic monitoring may offer a valuable tool to improve volume management in dialysis patients with left ventricular dysfunction.

Coronary Vasodilator Effects of Endogenous Cannabinoids in Vasopressin-Preconstricted Unpaced Rat Isolated Hearts

The mechanisms by which cannabinoids alter coronary vascular tone and cardiac performance are controversial. We investigated the effects of various cannabinoids in spontaneously beating Langendorff-perfused rat hearts. Bolus injections of anandamide (0.1-1 micromol) caused no change in coronary flow (CF) or left ventricular systolic pressure (LVSP). In hearts preperfused with vasopressin to induce vasoconstrictor tone, anandamide or the selective CB1 receptor agonist ACEA (1-100 nmol) dose-dependently increased CF by up to 267% and LVSP by 20 mm Hg. The metabolically stable endocannabinoid derivatives, R-methanandamide and noladin ether, displayed similar effects. In contrast, Delta-THC (10-100 nmol), the major psychoactive ingredient of cannabis, strongly decreased CF and LVSP. The CB2 receptor agonist JWH-133 (10-100 nmol) elicited vasodilator and positive inotropic effects only at higher doses. The CB1 antagonists SR141716A and AM-251 as well as the potassium channel inhibitors tetraethylammonium and iberiotoxin blocked the anandamide-induced increases in CF and LVSP, whereas the CB2 antagonist SR144528 and the putative "CB3 antagonist" O-1918 did not have an inhibitory effect. Immunohistochemistry revealed the presence of cardiac CB1 but no CB2 receptors. Anandamide and 2-arachidonoylglycerol were detected in heart tissue. However, combined application of fatty acid amidohydrolase inhibitors and the transport inhibitor AM-404 to augment tissue levels of endocannabinoids was without effect on CF or LVSP. We conclude that in the rat isolated heart with reestablished vasoconstrictor tone, cannabinoids including anandamide elicit coronary vasodilation and a secondary increase in contractility via CB1 receptors and potassium channels.

Effects of bupivacaine used with sevoflurane on the rhythm and contractility in the isolated rat heart.

The effects of sevoflurane on bupivacaine cardiotoxicity are mainly attributed to systemic effects. The purpose of this study was to investigate the direct myocardial effects of sevoflurane on bupivacaine toxicity. Hearts of 30 Wistar albino rats were isolated and mounted on a Langendorff apparatus perfused by modified Tyrode solution. Experimental groups were: a sevoflurane group (Group S, n = 10)--following baseline and 20 min (Stage 1) recordings, sevoflurane was added in doses of 1.4% (1 MAC) and 2.8% (2 MAC). In the two bupivacaine groups, bupivacaine 5 micromol (Group B5, n = 10) and bupivacaine 10 micromol (Group B10, n = 10) was added to the solution at Stage 1, and sevoflurane was added to the system as in Group S. Haemodynamic variables, i.e. heart rate, PR interval, QRS duration, left ventricular systolic pressure, contractility (+dp/dtmax), relaxation, time to reach peak systolic pressure, change in left ventricular diastolic pressure from baseline, and rate-pressure product were recorded. In Group S, there was no change in cardiac rhythm. In bupivacaine groups, severe rhythm disturbances occurred and both the PR intervals and QRS complexes were prolonged significantly. All contractility variables deteriorated and the rate-pressure product decreased by 67-90% with the addition of bupivacaine. In all groups, 2 MAC sevoflurane lowered +dp/dtmax further. Sevoflurane does not have any untoward effect on bupivacaine-induced cardiotoxicity in clinically relevant doses in the isolated rat heart.

On the relationship between encapsulated ultrasound contrast agent and pressure

Noninvasive measurement of pressure within the heart cavities and other internal organs ( e.g., kidney, liver) has significant clinical value, but currently is not feasible. Noninvasive pressure estimation using encapsulated ultrasound (US) contrast agents (UCA) as sensors is a challenge because they supposedly respond to their ambient pressure, but they are more rigid and less sensitive to pressure than gas microbubbles. Here, Optison® sensitivity was studied (f resonance = ≈ 2 MHz) to varying pressures, when excited at 2 times and also at 0.5 times f resonance. Cyclic momentary increases in ambient pressure of 0 to 5, 0 to 10, 0 to 15 or 0 to 20 kPa at 1.0 Hz, mimicking left ventricular (LV) pressure changes, caused amplitude decrease of echoes at 0.5, 1 and 2 times the transmitted frequency and decrease of attenuation. Changes at 0.5 times the transmitted frequency correlated best, but only after 70 to 150 s. The correlations (mean ± SD) during 150 to 300 s were 0.706 ± 0.072 for 0 to 10 kPa, 0.844 ± 0.042 for 0 to 15 kPa and 0.859 ± 0.031 for 0 to 20 kPa. Attenuation presented less correlation. For 1.0 Hz, 10 to 15 kPa or 15 to 20 kPa pressures, mimicking systemic pressures, the attenuation decayed fast and even faster for slow (0.05 Hz) cyclic varying pressures, or elevated steady-state pressures (of 10 kPa and 20 kPa). Thus, cyclic pressure effects on UCA are demonstrated to be reversible, but elevated static pressures cause UCA destruction. This allows cyclic pressure variations to be detected, using the subharmonics of the transmitted frequency, down to 10 kPa. (E-mail: dan@bm.technion.ac.il)