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Enalaprilat, a new parenteral angiotensin-converting enzyme inhibitor: rapid changes in systemic and coronary hemodynamics and humoral profile in chronic heart failure.

Systemic and coronary hemodynamic, metabolic and humoral effects of a new intravenous angiotensin-converting enzyme inhibitor, enalaprilat, were evaluated in 14 patients with chronic heart failure. Onset of hemodynamic action occurred within 15 minutes and persisted for 6 hours. At the time of peak effect, there was a significant reduction in mean arterial pressure (-21%) and pulmonary capillary wedge pressure (-33%). Systemic vascular resistance decreased by 32% and stroke volume index increased by 20%. These systemic hemodynamic changes indicate improved left ventricular function. There was a substantial sustained reduction in rate-pressure product initially without a change in coronary sinus blood flow or myocardial oxygen consumption. There was also reduced myocardial oxygen extraction and augmented coronary sinus oxygen saturation at 30 minutes and 1 hour. In three patients, abnormal myocardial lactate extraction, present before enalaprilat, changed to uptake after enalaprilat, indicating amelioration of myocardial ischemia that was not clinically manifest. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma renin activity increased and plasma aldosterone decreased. These findings suggest that enalaprilat produces inhibition of the angiotensin-converting enzyme and consequent beneficial systemic hemodynamic changes in heart failure. In some patients with heart failure, silent myocardial ischemia at rest can occur and can be alleviated with enalaprilat. Decreased myocardial oxygen extraction, increased coronary sinus oxygen saturation and lack of expected decrease in coronary sinus blood flow despite reduced rate-pressure product suggest transient coronary vasodilation by enalaprilat.

Aged↗

Impaired baroreflex sensitivity is correlated with hemodynamic deterioration of sustained ventricular tachycardia.

OBJECTIVES: The goal of this study was to evaluate clinical and autonomic variables (heart rate variability and baroreflex sensitivity) related to hemodynamic tolerability of VT in patients with sustained monomorphic VT and a healed myocardial infarction. BACKGROUND: Sustained ventricular tachycardia (VT) with hemodynamic deterioration is associated with a worse prognosis than that of well tolerated VT. The causes of hemodynamic deterioration of VT are incompletely understood. METHODS: Twenty-four consecutive patients with sustained monomorphic VT and a healed myocardial infarction (mean age +/- SD 66 +/- 8 years, left ventricular [LV] ejection fraction 37 +/- 11%) were assigned to group 1 if the VT was well tolerated (n = 11) or to group 2 if faintness or syncope occurred or if systolic blood pressure was < 90 mm Hg with clinical signs of shock (n = 13). RESULTS: No difference was found between the two groups in age, LV function, rate and duration of the VT or heart rate variability. However, patients in group 2 had a significantly lower baroreflex sensitivity (3.4 +/- 1.1 vs. 7.1 +/- 3.7 ms/mm Hg, p = 0.003). Multiple logistic regression analysis showed that only the value of baroreflex sensitivity (p = 0.0003)-but not age, LV ejection fraction, VT cycle length or SD of the RR interval (all p > 0.25)-correlated with the tolerability of the VT. Finally, LV ejection fraction (p = 0.0001) and baroreflex sensitivity (p = 0.0003)-but not age, cycle length of the tachycardia or SD of the RR interval-predicted cardiac death or unstable VT during follow-up. CONCLUSIONS: These data suggest that an impaired cardiovascular reflex response may play a key role in the hemodynamic deterioration of sustained VT and that the evaluation of baroreflex sensitivity in patients at high risk for sustained VT may become useful both in risk stratification and in the individualization of treatment.

Aged↗

Hemodynamic determinants of Doppler pulmonary venous flow velocity components: new insights from studies in lightly sedated normal dogs.

OBJECTIVES: We sought to define the hemodynamic determinants of pulmonary venous (PV) flow velocities to assess how these are affected by respiration, heart rate and loading conditions. BACKGROUND: Pulmonary venous flow velocity (PVFV) recorded with pulsed wave Doppler technique is currently used in the noninvasive evaluation of left ventricular (LV) diastolic function and filling pressures. Although previous studies in both animals and humans have shown that PV flow is pulsatile, the hemodynamic determinants of the individual components of this flow remain controversial. Understanding the physiologic mechanisms should help to better define the clinical utility of these Doppler techniques. METHODS: PV flow velocities obtained with transesophageal pulsed wave Doppler imaging were recorded together with PV, left atrial (LA) and LV pressures in 10 sedated, spontaneously breathing normal dogs. PVFV and hemodynamic data were analyzed during apnea, inspiration and expiration, at atrial paced heart rates of 60, 80, 100 and 120 beats/min and mean LA pressures of 6, 12, 18 and 24 mm Hg. RESULTS: The data showed that 1) PV pressure varied depending on recording site, resembling pulmonary artery pressure closer to the pulmonary capillary bed and LA pressure closer to the venoatrial junction; 2) PVFV qualitatively followed changes in the PV-LA pressure gradient; 3) four PVFV components exist under normal conditions-three of which follow phasic changes in LA pressure and one of which (the late systolic component) is more influenced by RV stroke volume and the compliance of the pulmonary veins and left atrium; 4) normal respiration and changes in heart rate significantly alter PVFV variables--in particular, reverse flow velocity at atrial contraction; and 5) increasing LA pressure results in larger PV A wave and PV early systolic flow velocities, as well as an earlier peak in PV late systolic flow velocity and a more prominent velocity minimum before PV diastolic flow. CONCLUSIONS: Using transesophageal pulsed wave Doppler technique, four PVFV components are identifiable and determined by PV-LA hemodynamic pressure gradients. These gradients appear to be influenced by a combination of physiologic events that include RV stroke volume, the compliance of the pulmonary vasculature and left atrium and phasic changes in LA pressure. PV flow velocity components are significantly influenced by heart rate, respiration and LA pressure. These findings have implications for the interpretation of LV diastolic function and filling pressures by current Doppler echocardiographic techniques but require further clinical investigation.

Animals↗

Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure.

OBJECTIVES: The primary purpose of this study was to determine the acute and long-term hemodynamic and clinical effects of irbesartan in patients with heart failure. BACKGROUND: Inhibition of angiotensin II production by angiotensin-converting enzyme (ACE) inhibitors reduces morbidity and mortality in patients with heart failure. Irbesartan is an orally active antagonist of the angiotensin II AT1 receptor subtype with potential efficacy in heart failure. METHODS: Two hundred eighteen patients with symptomatic heart failure (New York Heart Association [NYHA] class II-IV) and left ventricular ejection fraction < or = 40% participated in the study. Serial hemodynamic measurements were made over 24 h following randomization to irbesartan 12.5 mg, 37.5 mg, 75 mg, 150 mg or placebo. After the first dose of study medication, patients receiving placebo were reallocated to one of the four irbesartan doses, treatment was continued for 12 weeks and hemodynamic measurements were repeated. RESULTS: Irbesartan induced significant dose-related decreases in pulmonary capillary wedge pressure (average change -5.9+/-0.9 mm Hg and -5.3+/-0.9 mm Hg for irbesartan 75 mg and 150 mg, respectively) after 12 weeks of therapy without causing reflex tachycardia and without increasing plasma norepinephrine. The neurohormonal effects of irbesartan were highly variable and none of the changes was statistically significant. There was a significant dose-related decrease in the percentage of patients discontinuing study medication because of worsening heart failure. Irbesartan was well tolerated without evidence of dose-related cough or azotemia. CONCLUSIONS: Irbesartan, at once-daily doses of 75 mg and 150 mg, induced sustained hemodynamic improvement and prevented worsening heart failure.

Adolescent↗

Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group.

OBJECTIVES: The goal of this study was to further define the role of nesiritide (human b-type natriuretic peptide) in the therapy of decompensated heart failure (HF) by assessing the hemodynamic effects of three doses (0.015, 0.03 and 0.06 microg/kg/min) administered by continuous intravenous (IV) infusion over 24 h as compared with placebo. BACKGROUND: Previous studies have shown beneficial hemodynamic, neurohormonal and renal effects of bolus dose and 6-h infusion administration of nesiritide in HF patients. Longer term safety and efficacy have not been studied. METHODS: This randomized, double-blind, placebo-controlled multicenter trial enrolled subjects with symptomatic HF and systolic dysfunction (left ventricular ejection fraction < or =35%). Central hemodynamics were assessed at baseline, during a 24-h IV infusion and for 4 h postinfusion. RESULTS: One hundred three subjects with New York Heart Association class II (6%), III (61%) or IV (33%) HF were enrolled. Nesiritide produced significant reductions in pulmonary wedge pressure (27% to 39% decrease by 6 h), mean right atrial pressure and systemic vascular resistance, along with significant increases in cardiac index and stroke volume index, with no significant effect on heart rate. Beneficial effects were evident at 1 h and were sustained throughout the 24-h infusion. CONCLUSIONS: The rapid and sustained beneficial hemodynamic effects of nesiritide observed in this study support its use as a first-line IV therapy for patients with symptomatic decompensated HF.

Atrial Natriuretic Factor↗

Non-linear dynamic analysis of hemodynamic parameters in an undulation type artificial heart system.

Undulation pump total artificial heart (UPTAH) is a unique total artificial heart implant (TAH) using an undulation pump that is a continuous blood flow pump. To evaluate the autonomic nerve function mediating the circulation system, we analyzed the hemodynamic parameters during animal experiments with UPTAH using the non-linear mathematical analyzing technique, including chaos and fractal theory. Adult female goats were used for the implantation of UPTAH. The natural heart was replaced with UPTAH under extra-corporal circulation. The conductance- and arterial pressure-based control method (1/R control) was applied on the 5th to 7th post-operative day as the influences of the cardiopulmonary bypass circulation were diagnosed to be terminated. Hemodynamic parameters were recorded on the data recorder, and non-linear mathematical analysis was performed. For the quantitative evaluation of the strange attractor, which was the characteristics of the deterministic chaos, the fractal dimension analysis was carried out. As a result, hemodynamic parameters fluctuated on the time axis and showed fractal characteristics, which were thought to be the characteristics of the deterministic chaos. The reconstructed attractor of the hemodynamics showed various behaviors according to changes in the situation of the goats. These results suggest that non-linear dynamical analysis might be useful in monitoring the circulatory regulatory system in artificial heart circulation.

Animals↗

Myocardial recovery after cardiac surgery: a study of hemodynamic performance and electrophysiology during the first 18 postoperative hours.

Hemodynamic and vectorcardiographic variables were monitored in 23 patients with acquired heart disease, before and during the first 18 postoperative hours of cardiac surgery. The hemodynamic pattern directly after surgery was characterized by left ventricular depression and increased heart rate. Thus, stroke volume index had decreased from the preoperative 29 +/- 1 to 24 +/- 1 mL/beat/m2, and heart rate had increased from 61 +/- 2 to 94 +/- 4 beats/min. During the following hours a gradual normalization of stroke volume occurred, leading to a cardiac index that was adequate after 8 to 10 hours, judging from the mixed venous oxygen saturation (68% +/- 1%). Fourteen patients had an uneventful postoperative course, with no signs of acute myocardial infarction, and did not require inotropic support. These patients had small but consistent vectorcardiographic changes; the QRS vector difference increased moderately, and the ST vector magnitude also increased. No correlation was found between hemodynamic and vectorcardiographic variables, nor between timing of hemodynamic recovery and vectorcardiographic changes. Patients with a perioperative myocardial infarction had a vectorcardiographic pattern that was compatible with acute myocardial infarction. These patients had markedly elevated ST vector magnitude and QRS vector difference values, which were discernible during the first postoperative hours. The present data suggest that the timing of metabolic and electrophysiological recovery of the heart differ, and a computerized vectorcardiographic system may be of value in the early detection of perioperative myocardial infarction.

Adult↗

Hemodynamic improvement and removal of autoantibodies against beta1-adrenergic receptor by immunoadsorption therapy in dilated cardiomyopathy.

The removal of beta(1)-adrenergic receptor (beta(1)AR) autoantibodies by immunoadsorption (IA) has been proposed as a potential mechanism for the improvement of the left ventricular function in dilated cardiomyopathy (DCM). In the present study, the possible association between removal of the autoantibodies against the human beta(1)AR with the hemodynamic improvement induced by IA was investigated.IA was performed in 22 DCM patients (n=22; NYHA III-IV, EF<30%, stable medication). The beta(1)AR autoantibodies from column eluents (CE) were detected by enzyme-linked immunosorbent assay (ELISA) and BIAcore methods. CE of 32% (7/22) of the patients was found to be antibody-positive with ELISA or BIAcore. In addition, a bioassay system was also used for the detection of this autoantibody. Seventy-three percent (16/22) of the patients were found to be antibody-positive by this method. However, independent of the beta(1)AR antibody detection method, both antibody-positive and antibody-negative groups showed similar acute and prolonged hemodynamic improvements during IA therapy. Furthermore, antibody-positive and -negative groups received a comparable improvement of left ventricular ejection fraction. These results suggest that different mechanisms are involved in the hemodynamic improvement induced by IA. The beneficial hemodynamic effects induced by IA are not directly associated with the removal of beta(1)AR autoantibodies.

Autoantibodies↗

Hemodynamic changes during laparoscopic cholecystectomy in patients with severe cardiac disease.

STUDY OBJECTIVE: To evaluate the hemodynamic changes and need for pharmacologic interventions during laparoscopic cholecystectomy in patients with severe cardiac dysfunction. DESIGN: Prospective open study. SETTING: University hospital. PATIENTS: 17 ASA physical status III and IV patients with severe cardiac dysfunction undergoing elective laparoscopic cholecystectomy. INTERVENTIONS: A standardized general anesthetic and surgical technique was used for all patients. In addition to routine monitoring, invasive hemodynamic monitoring included radial and pulmonary artery (PA) cannulation. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were recorded prior to induction of anesthesia, 5 minutes after induction of anesthesia but prior to incision, 5 minutes after carbon dioxide (CO2) insufflation and head-up tilt, every 10 minutes after change of position, after deflation of the abdomen and return to supine position, and 10 minutes after attaining supine position. Need for any pharmacologic interventions [to maintain mean arterial pressure (MAP) < 100 mmHg and/or systemic vascular resistance (SVR) < 2,000 dynes sec/cm-5, and/or cardiac index (CI) > 1.5 L/min/m2] and the incidence of any myocardial morbidity and mortality was noted. CI decreased significantly (p < 0.05) following insufflation and remained low until exsufflation. MAP, SVR, and PA occlusion pressure increased significantly (p < 0.05) after CO2 insufflation. Three of the 17 patients required administration of nitroglycerin to maintain the MAP and SVR within the accepted limits, one of whom also required administration of dobutamine to maintain CI. There was no myocardial morbidity or mortality in the perioperative period. CONCLUSION: Laparoscopic cholecystectomy in patients with severe cardiac dysfunction results in significant hemodynamic changes.

Adult↗

Effects of tramadol and meperidine on respiration, plasma catecholamine concentrations, and hemodynamics.

STUDY OBJECTIVE: To evaluate the effects of high analgesic doses of tramadol and meperidine on respiration, plasma catecholamine concentrations, and hemodynamic parameters. STUDY DESIGN: Randomized, double-blind, cross-over, controlled volunteer study. SETTING: Laboratory at a university hospital. SUBJECTS: 8 healthy male volunteers. INTERVENTIONS: Tramadol was given as a 150 mg bolus plus a succeeding 3-hour steady infusion of 250 mg (83.3 mg/hr). Meperidine was given in a similar manner as a bolus dose of 112.5 mg plus 187.5 mg in a 3-hour steady infusion (62.5 mg/hr). Experimental pain was induced using a tourniquet. MEASUREMENTS AND MAIN RESULTS: Respiration was studied noninvasively with respiratory inductive plethysmography and pulse oximetry. Arterial line was used for measurement of hemodynamics and blood sampling. Tramadol did not have any clinically significant effects on respiration, breathing pattern, or hemodynamics, but an increase in plasma epinephrine levels was noted. Meperidine bolus decreased tidal volume (p < 0.05, difference from baseline) and pulse oxygen saturation (from 97% to 94%, p < 0.05), but during the succeeding infusion, the respiratory drive, measured as mean inspiratory flow, was enhanced (p < 0.05 difference from baseline), and the respiratory parameters returned to baseline level. No change in hemodynamics was noted, but a significant increase in plasma norepinephrine and epinephrine levels (from 0.9 to 1.6 nmol/L and from 0.3 to 0.8 nmol/L, respectively; p < 0.05) was observed after meperidine administration. Tramadol caused nausea more often than meperidine (p < 0.05, between treatments). CONCLUSIONS: Tramadol exhibited a minimal effect on respiration and breathing pattern in healthy volunteers. The respiratory effects of meperidine bolus were predictable with decreasing tidal volume and pulse oxygen saturation. In contrast, during meperidine infusion, adequate respiration was preserved despite the large amount of meperidine infused.

Adult↗

Hemodynamic changes during off-pump CABG surgery.

OBJECTIVES: The purpose of this study was to assess the patients' hemodynamics during off-pump coronary artery bypass graft (OPCABG) surgery. METHODS: Continuous monitoring of the mean systemic arterial pressure (SAP), mean pulmonary arterial pressure (PAP), mixed venous oxygen saturation (SvO(2)) and cardiac output index (COI) was done on 55 patients undergoing complete OPCAB revascularization. Hemodynamic changes were recorded at the completion of the anastomosis before releasing coronary snaring and stabilization and compared to baseline. RESULTS: The mean age of the patients was 66.4+/-9.2 years, and on average 3.3+/-0.8 grafts per patient were performed. The average SAP drop after manipulations was -8.3+/-16.9 mmHg for the left anterior descending artery (LAD), -13.5+/-19.6 mmHg for the diagonal artery (DG), -14.6+/-13 mmHg for the optuse marginal artery (OM), and -14.2+/-13.5 mmHg for the right coronary artery. This was significant for all territories (P<0.01). The PAP significantly increased in all territories except OM (LAD: 3.7+/-6.3 mmHg, DG: 4.3+/-8.6 mmHg, OM: 1.1+/-7.2 mmHg, posterior descending artery: 2.7+/-5.6 mmHg; P<0.05). Variations in COI were significant in all territories (P<0.01) but more significantly in LAD and DG territories (-15+/-3% and -13+/-9%, respectively). The SvO(2) variations were <10% for all territories and reached only borderline significance (P=0.05) in all territories except OM. All these hemodynamic changes were well tolerated by all patients. CONCLUSIONS: Manipulation of the beating heart during OPCABG surgery brings significant fluctuations in the patients' hemodynamics. Mean PAP increase and COI drop were more significant during manipulation of the anterior territories suggesting a more severe diastolic restrictive disease during anterior wall manipulation.

Aged↗

Hemodynamics optimization during off-pump coronary artery bypass: the 'no compression' technique.

OBJECTIVE: Heart manipulation during OPCAB may cause hemodynamical instability in particular for access to the posterior and lateral walls. The 'no compression' technique involves enucleation of the heart without any compression on the cavities, and stabilization of the target area with a suction device. The impact of this technique on hemodynamics is assessed. METHODS: In order to analyze a homogeneous group, 26 consecutive patients with triple grafts, one to each side of the heart in the same sequential order (posterior, lateral and anterior wall successively) were selected. Heart rate (HR), mean pulmonary arterial pressure (PAP, mmHg), pulmonary capillary wedge pressure (PCWP, mmHg), mean arterial pressure (MAP, mmHg), cardiac output index (COI, l/min per m(2)), and central venous saturation (SvO(2),%) were monitored. A coronary shunt was used for all the anastomoses. RESULTS: HR was stable with baseline value of 60+/-10 and the highest value for the anterior wall, 63.6+/-8 (P=0.23). PAP and PCWP exhibited their highest increase, when compared with baseline, for the lateral wall, 23.9+/-4.7 vs. 20.7+/-6.2 (P=0.06), and 17.2+/-4.7 vs. 14.9+/-5.6 (P=0.16), respectively. MAP, COI and SvO(2), exhibited their largest drop, when compared with baseline, for the lateral wall too, 73.1+/-9.1 vs. 77.1+/-7.5 (P=0.12), 1.99+/-0.47 vs. 2.26+/-0.55 (P=0.09), and 70.5+/-8.4 vs. 74.8+/-9.3 (P=0.12), respectively. CONCLUSIONS: None of the hemodynamical parameter differed significantly from baseline value for all three territories. While hemodynamics was perfectly maintained during the posterior and anterior walls revascularization, exposure of the lateral wall led to marginal changes only.

Aged↗

Eleven years' experience with the Biocor stentless aortic bioprosthesis: clinical and hemodynamic follow-up with long-term relative survival rate.

OBJECTIVE: The long-term durability and hemodynamics of stentless valves are largely unknown. Our aim was to prospectively investigate long-term hemodynamic function and clinical outcome after aortic valve replacement with the Biocor stentless aortic bioprosthesis. PATIENTS AND METHODS: Between October 1990 and November 2000 we inserted the Biocor stentless aortic valve in 112 patients (male/female: 38:74) with a mean age of 78.5 years (median 79.3, range 60-88). The predominant diagnosis was aortic stenosis in 86% of the patients. Concomitant coronary artery bypass surgery was performed in 31% of the patients. Average prosthetic valve size was 23.3+/-1.6 mm. All patients were followed in a prospective study with a mean follow-up of 66+/-33 months. The follow-up was 100% complete with a closing interval from October 1 to December 31, 2001. The observed actuarial survival of patients was compared to expected survival for an age- and gender-matched comparison population as calculated from Swedish life tables by Statistics Sweden. Relative survival rates were calculated annually for the patient population. RESULTS: Early mortality was 7% (8/112). Late mortality was 38% (43/112). Actuarial survival at 5 and 9 years was 74+/-5% and 38+/-7%, respectively. Observed survival among patients was not different from the expected survival for the comparison population and calculation of relative survival rates indicates a 'normalized' survival pattern for the patient population. At 5 and 9 years the actuarial freedom from valve-related death was 94+/-3% and 86+/-6%; from cardiac death, 82+/-4% and 57+/-8%; from valve reoperation, 96+/-2% and 87+/-6%; from structural valve degeneration, 96+/-2% and 87+/-6%; from thromboembolism, 89+/-4% and 71+/-9%; and from endocarditis, 96+/-2% and 90+/-5%. At 9 years the transvalvular mean pressure difference for all valves was 7.3+/-1.3 mmHg (range 6-10 mmHg) measured with Doppler echocardiography. Aortic regurgitation progressed slowly over time in a few patients and necessitated reoperation in two patients. CONCLUSION: The Biocor stentless bioprosthesis has an excellent hemodynamic function and confers a good long-term outcome. This patient population could be regarded as 'cured' from valve disease since the observed survival did not differ from the expected survival for an age- and gender-matched Swedish comparison population, a conclusion that is also supported by a constant relative survival after the first postoperative year. However, despite excellent long-term hemodynamics, patients with stentless bioprostheses need to be evaluated with echocardiography at regular intervals to discover the rare cases of progressive aortic regurgitation.

Aged↗

Hemodynamics and wall mechanics of a compliance matching stent: in vitro and in vivo analysis.

PURPOSE: Evidence is emerging that the abrupt compliance mismatch that exists at the junction between the stent ends and the host arterial wall disturbs both the vascular hemodynamics and the natural wall stress distribution. These stent-induced alterations are greatly reduced by smoothing the compliance mismatch between the stent and host vessel. A stent that provides this smooth transition in compliance, the compliance matching stent (CMS), has been developed. This study attempts to evaluate the hemodynamics and wall mechanical consequences of the CMS both in vitro and in vivo. MATERIALS AND METHODS: Finite element analysis was used to assess the solid mechanical behavior (compliance and stress) of the CMS in a stent/artery hybrid structure. A similar analysis was performed with a Palmaz stent. In vivo hemodynamics and wall mechanical changes induced by the CMS were investigated in a swine model from direct measurements of flow, pressure, diameter, and histology in the stented segment of superficial femoral arteries after 7 days. RESULTS: Finite element analysis showed that the abrupt compliance mismatch was substantially smoothed between the vessel portions with and without the stent with CMS segments. Circumferential stress was also markedly reduced with the CMS compared to other stent. The in vivo results showed that the CMS was efficient in compliance matching and did not dampen flow or pressure waves downstream the stent. Concurrent histology showed limited thrombus and inflammatory cell accumulation around the stent struts. CONCLUSION: These results indicate that the stent/artery hybrid structure can be compliance matched with proper stent design and that this structure limits solid mechanical stress and hemodynamic disturbances. It remains to be seen whether compliance-matched vascular stents reduce in-stent restenosis.

Animals↗

Sevoflurane versus isoflurane in patients undergoing coronary artery bypass grafting: a hemodynamic and recovery study.

OBJECTIVE: To determine if sevoflurane provides comparable hemodynamics and recovery characteristics to isoflurane in cardiac anesthesia. DESIGN: A prospective, crossover, dose-response study using sevoflurane and isoflurane before the start of surgery, followed by randomization to sevoflurane or isoflurane for surgery with blinded assessment for recovery. SETTING: Tertiary referral cardiac clinic and intensive care. PARTICIPANTS: Sixteen elective patients scheduled for coronary artery bypass grafting. INTERVENTIONS: A pulmonary artery catheter was used to obtain a complete hemodynamic profile during the dose response study before surgery. Transesophageal echocardiography (TEE) and an electrocardiogram (ECG) were used to assess myocardial ischemia. MEASUREMENTS AND MAIN RESULTS: Both agents showed similar hemodynamic effects at 0.5 and 1.0 minimum alveolar concentration (MAC). There was a tendency toward decreases in heart rate, blood pressure, vascular resistance, and cardiac output with a rise in central pressures. Ischemic changes were not detected by TEE or ECG. Times to eye opening and extubation were similar for both agents. CONCLUSION: At MAC equivalent doses, sevoflurane showed comparable hemodynamics to isoflurane. Both agents when used as the primary anesthetic showed similar recovery characteristics, with no statistical difference between them at any stage of the study.

Aged↗

Endovascular aortic repair is associated with greater hemodynamic stability compared with open aortic reconstruction.

OBJECTIVE: Examination of overall hemodynamic stability in patients undergoing endovascular aortic repair (EAR) compared with open aortic repair (OAR). DESIGN: Retrospective study. SETTING: University hospital setting. PARTICIPANTS: Seventy-two patients undergoing OAR and 17 patients undergoing EAR were studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physiologic parameters were extracted every 15 seconds from computerized anesthesia records. Median values were calculated for every 2-minute epoch, and the absolute value of the fractional change in median (|FCM|) from epoch to epoch was calculated for a maximum of 5 hours during the intraoperative period. The incidence of extremes in hemodynamic parameters was compared. Data are presented as median and interquartile ranges. The frequency of |FCM| greater than 0.06 for mean arterial pressure (MAP) was significantly greater in the OAR compared with the EAR group (0.37 [0.30, 0.46] vs 0.14 [0.11, 0.21], p < 0.0001), implying greater stability in MAP during EAR. Similarly, the mean pulmonary artery pressures (MPAPs) were significantly more stable during EAR compared with OAR (frequency of |FCM| > 0.07: EAR, 0.20 [0.16, 0.27] vs OAR, 0.32 [0.26, 0.391; p < 0.01). No intergroup differences were detected in heart rate (HR), systolic (SPAP) or diastolic pulmonary artery pressures (DPAP), or central venous pressures (CVPs). With the exception of a greater incidence of low CVP during EAR, there were no significant differences in the frequency of extremes of hemodynamic values between groups. CONCLUSION: These results show improved hemodynamic stability during EAR compared with OAR.

Aged↗

Dobutamine stress echocardiography predicts myocardial improvement in patients supported by left ventricular assist devices (LVADs): hemodynamic and histologic evidence of improvement before LVAD explantation.

BACKGROUND: Cardiac function may improve in patients with end-stage heart failure who receive long-term support (>30 days) with left ventricular assist devices (LVADs). Dobutamine stress echocardiography (DSE) has been used to quantitate myocardial recovery in patients with heart failure supported with LVADs. By recording the hemodynamic response with the use of DSE, we evaluated and applied the resulting data to patients receiving LVAD support. METHODS AND RESULTS: The study population included 16 patients who underwent LVAD implantation, regained functional capacity on full LVAD support, and tolerated decreased mechanical support with no worsening of dyspnea or fatigue. All 16 patients underwent dobutamine stress with increasing doses of dobutamine (from 5 to 40 mcg/kg/min). Hemodynamics and 2-dimensional (2-D) echocardiography was performed at each dose level. In addition, paired myocardial samples were obtained and analyzed histologically to determine myocyte size and collagen content. Dobutamine stress separated the study population into 2 groups: those who had favorable responses to dobutamine (9/16) and those who had unfavorable responses (i.e., experienced hemodynamic deterioration; 7/16). Favorable dobutamine responses were characterized by improved cardiac index, improved force-frequency relationship in the left ventricle (dP/dt), improved left ventricular ejection fraction, and decreased left ventricular end-diastolic dimension. All 9 favorable responders underwent LVAD explantation, and 6 survived for more than 12 months. In all patients studied, LVAD support resulted in decreased myocyte size (n = 14, 33.9 +/- 0.9 microm before vs 16.6 +/- 0.8 microm after support, p = 0.0001; normal, 5-15 microm) but resulted in no consistent changes in collagen content. CONCLUSIONS: Dobutamine stress echocardiography with hemodynamic assessment may be a useful tool in assessing physiologic improvement in myocardial function of patients with end-stage heart failure who receive LVAD support. It may help predict which patients can tolerate LVAD removal. Prospective analysis of cardiac function is now warranted to better define myocardial recovery in patients supported with LVADs.

Adult↗

Neurohumoral and hemodynamic effects of the selective endothelin antagonist darusentan in advanced chronic heart failure.

BACKGROUND: Endothelin antagonists represent a new approach to neurohumoral treatment in patients with chronic heart failure. In this study, the new selective endothelin-A receptor antagonist, darusentan, was compared with placebo for 3 weeks in patients with severe heart failure on top of standard treatment that included angiotensin-converting enzyme (ACE) inhibitors and beta-blockers. Effects on neurohormones and hemodynamics were evaluated. METHODS: Consecutive patients with severe heart failure (New York Heart Association [NYHA] Grade III) were included in this neurohumoral sub-study of an international, multi-center, double-blind, placebo-controlled study of darusentan, and randomized to darusentan (n = 23) or placebo (n = 8). The mean left ventricular ejection fraction was 19 +/- 6% at the beginning of the study. Patients were randomized to different dosage levels of darusentan (30, 100, or 300 mg) for 3 weeks. Hemodynamics were obtained by right heart Swan-Ganz catheterization at entry and end of study. Serial assessment of plasma brain natriuretic peptide (BNP), big-endothelin, and pro-atrial natriuretic peptide (pro-ANP) was performed. In the active treatment group, 1 patient died due to worsening heart failure, 1 patient received elective heart transplantation, and 2 patients stopped taking the medication due to vertigo. In the placebo group, 1 patient was excluded due to non-compliance. RESULTS: Overall, the mean dose of darusentan was 144 +/- 125 mg/day (30 mg: n = 8; 100 mg: n = 4; 300 mg: n = 7). Significant benefits in hemodynamic variables were found after 3 weeks only in patients receiving darusentan (baseline vs end of study: cardiac index: 2.0 +/- 0.3 vs 2.6 +/- 0.5 liters/min m(2), p < 0.0001; mean pulmonary artery pressure: 35 +/- 9 vs 33 +/- 8 mm Hg, p < 0.05; heart rate: 79 +/- 16 vs 71 +/- 10 beats/min, p < 0.01). A significant reduction in mean arterial blood pressure was observed with the endothelin antagonist (baseline 80 +/- 8 vs end 73 +/- 8 mm Hg, p < 0.01). BNP decreased significantly in patients with darusentan (90 +/- 87 at entry vs 63 +/- 67 fmol/ml after 3 weeks, p < 0.01), whereas big-endothelin remained unchanged. Pro-ANP tended to decrease in the active treatment group, but did not reach statistical significance. CONCLUSION: Significant hemodynamic and neurohumoral benefits were observed in patients with severe heart failure receiving the selective endothelin antagonist darusentan.

Atrial Natriuretic Factor↗