Significant Decrease In Cardiac Index Research Articles

Haemodynamic effects of an angiotensin-converting enzyme inhibitor and angiotensin receptor antagonist during hypovolaemia in the anaesthetized pig

Renin-angiotensin system antagonists, either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor (AT(1)) antagonists, may interfere with regulation of arterial pressure during anaesthesia. This study aimed to compare the haemodynamic profile of anaesthetized pigs, which were subjected to haemorrhage in the presence of the ACE inhibitor enalaprilat or the AT(1) antagonist valsartan. Thirty-six pigs were assigned randomly to placebo, enalaprilat or valsartan groups. After a 30-min period of stabilization following anaesthesia and injection of the study drug, the animals were bled in two equal steps of 20% of their estimated blood volume (20% BV and 40% BV). After bleeding of 20% BV, the mean arterial pressure (MAP) decreased significantly but similarly in each group (20-25%) but the placebo and the enalaprilat groups had a significant decrease in cardiac index (CI, 22% and 16%, respectively) without significant change in systemic vascular resistance (SVR). Conversely, in the valsartan group, SVR decreased significantly (23%, P<0.02 vs other groups) without significant change in CI (-4%). After bleeding of 40% BV, the CI decreased significantly compared with 20% BV in the three groups (19% in the placebo and enalaprilat groups, 14% in the valsartan group) but the MAP decreased significantly in the enalaprilat group only (23%). The SVR increased significantly in the placebo group (P<0.01 vs each of the other groups), but there were no differences in the change in SVR between the other groups. Blockade of the renin-angiotensin system by either enalaprilat or valsartan leads to a similar decrease in arterial pressure during anaesthesia and haemorrhage but the haemodynamic profiles are quite different.

Hemodynamic effects of chest closure in adult patients undergoing cardiac surgery

Objective: To evaluate hemodynamic effects of sternal retractor removal and sternal closure after cardiopulmonary bypass and to correlate these changes with preoperative and intraoperative variables. Design: Prospective. Setting: University hospital. Participants: Fifty adults undergoing cardiac surgery. Measurements and Main Results: Arterial, pulmonary artery, and transesophageal echocardiography measurements were obtained immediately before and 1 minute after removal of the sternal retractor and immediately before and 1 minute after sternal closure. Retractor removal caused a significant decrease in cardiac index by 5.6% (p < 0.01), stroke volume index by 4.0% (p < 0.05), and mean pulmonary artery pressure by 4.8% (p < 0.001). Sternal closure caused a significant decrease in cardiac index by 7.7%, stroke volume index by 10.2%, and left ventricular end-diastolic area by 9.2% (p < 0.001) There were significant increases in pulmonary capillary wedge pressure and systemic vascular resistance by 9.1% and 10.8% (p < 0.01). There was no significant change in the ejection fraction area. The magnitude of decrease in stroke volume index with sternal closure correlated positively with end-diastolic area immediately before the closure. Conclusion: Chest closure is associated with significant hemodynamic changes and a change in the ventricular transmural pressure-volume relationship. Patients with lower preload immediately before closure are more vulnerable to a decrease in cardiac index. Based on the results of this study, volume appears to be the appropriate preventive and treatment option to limit the impact of chest closure. Copyright © 2001 by W.B. Saunders Company

Hemodynamic effects of terlipressin (a synthetic analog of vasopressin) in healthy and endotoxemic sheep.

Hypotension, vasodilation, and vasoplegia are characteristic signs of septic shock. The vasoconstrictive response to catecholamines typically is reduced. A decreased vasopressive effect of catecholamines can be observed in the late phase of hemorrhagic shock. Interestingly, an unaltered vasopressive response to vasopressin can be demonstrated in hemorrhagic shock. In this study, we investigated the vasoconstrictive response to an agonist of the vasopressin receptor, terlipressin, in healthy sheep as well as in ovine hyperdynamic endotoxemia. Prospective controlled trial. University research laboratory. Six female adult sheep. Healthy sheep, instrumented for chronic study, received terlipressin (15 microg/kg) as a bolus; 30 mins later, norepinephrine was continuously given for 30 mins. Three hours later, a continuous infusion of endotoxin (Salmonella typhosa, 10 ng x kg(-1) x min(-1)) was started in the same sheep and given for the next 23 hrs. After 20 hrs of endotoxemia, terlipressin and norepinephrine were given as described previously. Hemodynamic parameters were measured before and 30 mins after application of terlipressin and after 30 mins of continuous infusion of norepinephrine. Terlipressin significantly increased systemic vascular resistance index in healthy and endotoxemic sheep (p <.05). The increase was higher in endotoxemic compared with healthy animals (p <.05). Only during endotoxemia, terlipressin increased pulmonary vascular resistance index. This was accompanied by a significant decrease in cardiac index, whereas mean pulmonary arterial pressure did not change after application of terlipressin. Additional treatment with norepinephrine did not further increase systemic vascular resistance index or pulmonary vascular resistance index. Terlipressin reversed the hemodynamic changes in ovine endotoxemia. However, its pulmonary vasopressive effect might limit its therapeutic use in septic shock.

Cardiovascular Effects of Sevoflurane, Isoflurane, Halothane, and Fentanyl–Midazolam in Children with Congenital Heart Disease

The cardiovascular effects of halogenated anesthetic agents in children with normal hearts have been studied, but data in children with cardiac disease are limited. This study compared the effects of halothane, isoflurane, sevoflurane, and fentanyl-midazolam on systemic and pulmonary hemodynamics and myocardial contractility in patients with congenital heart disease. Fifty-four patients younger than age 14 scheduled to undergo congenital heart surgery were randomized to receive halothane, sevoflurane, isoflurane, or fentanyl-midazolam. Cardiovascular and echocardiographic data were recorded at baseline and at randomly ordered 1 and 1.5 minimum alveolar concentrations, or predicted equivalent fentanyl-midazolam plasma concentrations. The shortening fraction and ejection fraction (using the modified Simpson rule) were calculated. Cardiac index was assessed by the velocity-time integral method. Halothane caused a significant decrease in mean arterial pressure, ejection fraction, and cardiac index, preserving only heart rate at baseline levels. Fentanyl-midazolam in combination caused a significant decrease in cardiac index secondary to a decrease in heart rate; contractility was maintained. Sevoflurane maintained cardiac index and heart rate and had less profound hypotensive and negative inotropic effects than halothane. Isoflurane preserved both cardiac index and ejection fraction, had less suppression of mean arterial pressure than halothane, and increased heart rate. Isoflurane and sevoflurane preserved cardiac index, and isoflurane and fentanyl-midazolam preserved myocardial contractility at baseline levels in this group of patients with congenital heart disease. Halothane depressed cardiac index and myocardial contractility.

The severity of hyperdynamic circulation may predict the effects of direct hemoperfusion with the adsorbent column using polymyxin B-immobilized fiber in patients with gram-negative septic shock.

It has been reported that direct hemoperfusion with the adsorbent column using polymyxin B-immobilized fiber (DHP with PMX-F column) ameliorates hyperdynamic circulation in septic shock and improves survival rate. However, the clinical characteristics of patients with an improvement of septic shock after DHP with PMX-F column have not been evaluated. To clarify this issue, the clinical profiles of 46 patients who were suggested to have gram-negative septic shock and treated using DHP with PMX-F column were analyzed retrospectively. Of 46 patients, 31 were diagnosed with gram-negative septic shock (G group). Mean arterial pressure (MAP) just before DHP with PMX-F column was not different between the G and the non-G group. As compared with the non-G group, the G group had a higher cardiac index (CI) and a lower systemic vascular resistance (SVR). Significant increases in MAP and SVR with a significant decrease in CI were observed after DHP with PMX-F column in the G group. In the non-G group, MAP was significantly increased after the DHP therapy, but systemic hemodynamics were unchanged. Patients in the G group who fulfilled the following criteria were considered as the effective group: MAP was elevated more than 10 mm Hg or 125% of the basal MAP and/or the dose of vasopressors was reduced after DHP with PMX-F column. Twenty-one patients (67.8%) were in the effective group. In comparison with the effective group, the noneffective group was characterized by a significant increase in CI before DHP with PMX-F column. All patients with a CI less than 6 L/min/m2 were in the effective group. These data suggest that DHP with PMX-F column was useful for patients with gram-negative septic shock who did not have severe hyperdynamic circulation.

Effects of the Sitting Position on the Distribution of Blood Volume in Patients Undergoing Neurosurgical Procedures

The use of the sitting position in neurosurgery is often associated with decreased arterial pressure (MAP) and stroke volume index (SVI). A shift in blood from the intra- to the extrathoracic compartment may be responsible for this cardiovascular response. However, little is known of the amount of shift in blood volume after transfer from the supine to the sitting position. Therefore, we measured simultaneously changes in intrathoracic blood volume (ITBV) caused by a change in body position in anaesthetized patients. Measurements of cardiac index (CI), ITBV, pulmonary (PBV) and total circulating (TBVcirc) blood volumes were performed in the supine and sitting position. CI, ITBV, PBV and TBVcirc were measured using a thermodye dilution technique. Fluid input was restricted to 14 ml kg-1 before induction of anaesthesia. Change in body position caused a significant decrease in ITBV and was accompanied by a significant decrease in CI, SVI and MAP. Changes in ITBV correlated (r = 0.78) with changes in SVI. Thus a change in blood volume distribution between the intra- and extrathoracic compartment occurred after a change from the supine to the sitting position. Indicator dilution enables quantification of this shift and may be helpful in guiding fluid therapy in selected patients.

Comparison of Various Hemoglobin Polyoxyethylene Conjugate Solutions as Resuscitative Fluids after Hemorrhagic Shock

Previous research suggested that splanchnic hypoperfusion occurs after resuscitation with certain acellular hemoglobin solutions. We examined the influence of maltose content and oxygen affinity on resuscitation with various hemoglobin polyoxyethylene conjugate solutions after hemorrhage. Fifteen swine underwent hemorrhage and equal volume resuscitation with pyridoxalated hemoglobin polyoxyethylene conjugate containing 0% or 8% maltose, or low P50 conjugate, which also contained 8% maltose. Five control animals were monitored but not bled. Regional blood flow was determined by using radioactive microspheres, gastric mucosal perfusion was estimated with tonometry, and gut histopathology was evaluated. All hemoglobin solutions produced vasoconstriction, manifested by elevated mean systemic and pulmonary artery pressures without a significant decrease in cardiac index compared with the sham group. Resuscitation with maltose-containing solutions elevated arterial and regional PCO2 and depressed arterial pH and gastric pHi (p < 0.05 for all). Splanchnic and renal blood flows were reduced in the low P50 + 8% maltose group (p < 0.05 vs. sham and baseline for renal blood flow), possibly indicating greater regional vasoconstriction in this group. Ileal mucosal damage was more severe in the maltose-containing groups and correlated with decreased pHi. Vasoconstriction occurred in all groups but was more severe in the low P50 + 8% maltose group. Maltose-containing solutions caused respiratory acidosis, decreased pHi, and histologic evidence of mucosal injury. Pyridoxalated hemoglobin polyoxyethylene conjugate without maltose was a superior resuscitation solution in this swine model.

Effects of the sitting position on the distribution of blood volume in patients undergoing neurosurgical procedures

The use of the sitting position in neurosurgery is often associated with decreased arterial pressure (MAP) and stroke volume index (SVI). A shift in blood from the intra- to the extrathoracic compartment may be responsible for this cardiovascular response. However, little is known of the amount of shift in blood volume after transfer from the supine to the sitting position. Therefore, we measured simultaneously changes in intrathoracic blood volume (ITBV) caused by a change in body position in anaesthetized patients. Measurements of cardiac index (CI), ITBV, pulmonary (PBV) and total circulating (TBVcirc) blood volumes were performed in the supine and sitting position. CI, ITBV, PBV and TBVcirc were measured using a thermodye dilution technique. Fluid input was restricted to 14 ml kg-1 before induction of anaesthesia. Change in body position caused a significant decrease in ITBV and was accompanied by a significant decrease in CI, SVI and MAP. Changes in ITBV correlated (r = 0.78) with changes in SVI. Thus a change in blood volume distribution between the intra- and extrathoracic compartment occurred after a change from the supine to the sitting position. Indicator dilution enables quantification of this shift and may be helpful in guiding fluid therapy in selected patients.

The role of heart rate in the modulation of the decreased cardiac output induced by acute nitric oxide synthesis inhibition in anaesthetized dogs.

1. The role of the heart rate modulating the decrease in cardiac output induced by the nitric oxide synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) was investigated in anaesthetized dogs. This was achieved in dogs in which a positive pacemaker (PM) cable was located at the right ventricle. 2. The haemodynamic events were evaluated: mean arterial blood pressure (MABP), systemic vascular resistance index (SVRI), stroke volume index (SVI), heart rate (HR) and cardiac index (CI). 3. The infusion of L-NAME (0.01-10 mg kg(-1)) in the animals with the PM off caused a dose-dependent rise in MABP and SVRI, accompanied by significant decreases of HR and SVI. A resulting decrease in CI was observed at all doses of L-NAME used. 4. In the animals with the PM on, HR was maintained stable. Under this condition, the increase in MABP and SVRI as well as the decrease in SVI induced by the L-NAME infusion did not significantly differ from the PM-off animals. However, the resulting decreased CI was markedly attenuated compared to PM-off animals but significant decreases in CI were still observed at higher doses of L-NAME. 5. The results suggest that HR plays an important role in the L-NAME-mediated decreased cardiac output but other factors might also be involved.

MYOCARDIAL PROTECTION BY ISCHEMIC PRECONDITIONING AND ENFLURANE ANESTHESIA DURING CORONARY SURGERY WITHOUT CARDIOPULMONARY BYPASS

Introduction. Coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) is gaining popularity as an alternative technique of myocardial revascularization of one or two vascular grafts. Technical and anesthetic techniques were proposed to support the surgical team during the procedure, but specific methods for protection of the myocardium are also mandated. We examined how methods such as myocardial ischemic preconditioning (IP) or administration of enflurane anesthesia may protect the heart from the injurious effect of ischemia and subsequent reperfusion. Methods. With IRB approval and patient informed consent, a prospective randomized study was conducted on 24 patients undergoing single - graft CABG via mid - sternotomy. All patients were managed in similar fashion in regard to anesthesia and fluid management. Three groups of patients: control, enflurane anesthesia, and IP (5 min ischemic interval) were evaluated for hemodynamic data by arterial and pulmonary artery catheters, and by biochemical analysis of arterial and coronary sinus venous blood. Enflurane, 1.7% or 0.8% if blood pressure dropped, was given 15 min prior-, to 10 min after ischemia. The study also examined production of hydroxyl ([center dot]OH) free radicals from the ischemic myocardium using the method of [center dot]OH radicals - mediated conversion of salicylate to its 2,3- and 2,5-dihydroxybenzoate (DHBA) derivatives. For this purpose the patient received 1gr aspirin P.O. with premedication. The DHBAs were analyzed by HPLC with electrochemical detection. Data analysis (mean +/- SEM) was performed by ANOVA; p value < 0.05 was considered statistically significant. Results. With no significant change in blood pressure and in the filling pressures between groups, a significant decrease in cardiac index (CI) was observed only in control group. Oxygen content values in coronary sinus blood (cO2 cs) indicate that O2 utilization by the myocardium was preserved in the presence of IP and enflurane anesthesia. The acute increase in CPK, myoglobin, 2,3- and 2,5- DHBAs production was also attenuated in both study groups. Table 1Table 1Discussion. The present study confirms that both interventions, IP and enflurane anesthesia have been effective in attenuating the deleterious effects of ischemia and reperfusion on cardiac performance, metabolic status and free radical production. It supports the approach of including physiologic and pharmacological interventions against cardiac depression during off-bypass coronary revascularization. Supported by grants from the Hebrew University and Hadassah and the Administrator General office.

Change in Cardiovascular Indices with Position and Isometric Exercise Throughout Pregnancy: Assessment by Impedance Cardiography and Oscillometric Sphygmomanometry

Background The poor predictive values of the supine pressor and isometric handgrip exercise tests for pregnancy-induced hypertension may relate to interobserver errors asSociated with mercury column sphygmomanometry or to the timing of blood pressure measurements relative to position change or isometric exercise.Objective: To evaluate the Bomed NCCOM-3, in combination with oscillometric measurement of mean arterial pressure (MAP), as a means of assessing beat-to-beat changes in hemodynamic indices at various stages of pregnancy.Setting: The Prince of Wales Hospital, teaching hospital to the Chinese University of Hong Kong.Methods: A longitudinal study of 20 normotensive Chinese women to assess the normal hernodynamic responses to changes in posture and isometric handgrip exercise; cardiac index (CI) obtained from a Bomed NCCOM-3 impedance cardiograph, and MAP from a Finapres digital blood pressure monitor.Results: Position change did not significantly alter CI. Significant changes in MAP and, hence, total peripheral resistance index (TPRI) following position change were observed at all gestational ages and in the puerperium. Regression analysis shows that the major contributing factor to changes in TPRI was change in CI with a variable effect of change in MAP. Isometric handgrip exercise caused significant decreases in CI in the second and third trimesters and also in the puerperium, but not in early pregnancy. Increases in TPRI following isometric exercise were significant at all gestations tested and in the postnatal period. Regression analysis shows that the changes are equally effected by the increase in MAP and the decreases in CI.Conclusions: The combination of impedance cardiography and oscillo-metric sphygmomanometry provides excellent recordings of beat-to-beat changes in hemodynamic indices during physiological testing. The changes observed throughout normal pregnancy were similar to those reported using Doppler ultrasound with echocardiography, remaining consistent after 20–24 weeks' gestation, with the exception of a significant rise in TPRI between the second and third trimesters.

Aminoguanidine corrects hyperdynamic circulation without ameliorating portal hypertension and portal hypertensive gastropathy in anesthetized portal hypertensive rats

Background/Aims: Portal hypertension and hyperdynamic circulation (i.e. generalized vasolidation and increased cardiac output and regional organ blood flows) may play an important role in the development of portal hypertensive gastropathy. This study investigated the effect of chronic administration of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to portal hypertensive rats on hemodynamics and the development of portal hypertensive gastropathy. Methods: Partial portal vein-ligated or sham-operated rats were randomly assigned to receive either placebo (distilled water) or aminoguanidine (∼100 mg/kg per day subcutaneously) for 2 days prior to and 14 days. Hemodynamic studies with a thermodilution technique and gastric morphometric analysis were performed at 14 days after the operation. Results: In rats given placebo, portal vein-ligated rats had a significantly lower mean arterial pressure and systemic vascular resistance associated with a significantly higher cardiac index and portal pressure than sham-operated rats ( p<0.05). In portal vein-ligated rats aminoguanidine induced a significant increase in mean arterial pressure and systemic vascular resistance accompanied by a significant decrease in cardiac index ( p<0.05) without changes in portal pressure ( p<0.05). Despite persistence of portal hypertension, the aminoguanidine-treated portal vein-ligated rats had similar mean arterial pressure, cardiac index, and systemic vascular resistance as seen in placebo-treated sham-operated rats. The mean cross-sectional area of gastric mucosal vessels was significantly higher in placebo-treated portal vein-ligated than in placebo-treated sham-operated rats ( p<0.05). Treatment with aminoguadinidine did not induce changes in the mean cross-sectional area of gastric mucosal vessels in either portal vein-ligated or sham-operated rats ( p<0.05). Conclusion: The results show that in portal hypertensive rats long-term aminoguanidine therapy corrects the hyperdynamic circulation without inducing changes in portal pressure and ameliorating the development of portal hypertensive gastropathy. This study suggests that, instead of correcting hyperdynamic circulation, treatment of portal hypertensive gastropathy should be aimed at reducing portal pressure.

Hemodynamic Profile of Neuropeptide Y in Dogs: Effect of Ganglionic Blockade

Hashim, M. A., W. W. Harrington, A. J. Daniels and A. S. Tadepalli. Hemodynamic profile of neuropeptide Y in dogs: Effect of ganglionic blockade. Peptides 18(2) 235–239, 1997.—The hemodynamic effects of neuropeptide Y (NPY) were examined over a dose range of 0.03–30 nmol/kg, IV, in anesthetized, open-chest, ventilated dogs with and without ganglionic blockade. In normal (non-ganglion-blocked) animals, NPY produced significant, dose-dependent, and sustained (lasting 15–45 min) increases in mean arterial blood pressure and systemic vascular resistance (SVR) with a threshold dose of 0.3 nmol/kg and a maximum effective dose of 10 nmol/kg. Cardiac index (CI) decreased at doses > 1 nmol/kg, but stroke volume was not altered; heart rate (HR) decreased significantly at and above the 3 nmol/kg dose. No significant changes were observed in the left ventricular dP/dt (LVdP/dt) or the contractility index (LVdP/dt ÷ systolic pressure). In ganglion-blocked animals, pressor and SVR responses to NPY were similar to those seen in normal animals but HR was not affected and a small but significant decrease in CI was seen only at the 30 nmol/kg. Furthermore, whereas LVdP/dt of ganglion-blocked dogs increased significantly at and above the 1 nmol/kg dose, the contractility index increased slightly only with the 10 and 30 nmol/kg doses. These data indicate that NPY produces sustained hypertension in dogs secondary to peripheral vasoconstriction, has a weak, direct positive inotropic action on the heart, and lacks chronotropic effects.

Propofol-alfentanil versus fentanyl-midazolam in coronary artery surgery

To compare intraoperative hemodynamics profiles and recovery characteristics of propofol-alfentanil with fentanyl-midazolam anesthesia in elective coronary artery surgery. Prospective, randomized study. University hospital. Fifty patients with impaired or good left ventricular function. In group 1, (n = 25) anesthesia was induced with an infusion of propofol, 3 to 4 mg/kg/h, alfentanil, 500 micrograms, and pancuronium 0.1 mg/kg, and maintained with propofol, 3 to 6 mg/kg/h (variable rate), and alfentanil infusions, 30 micrograms/kg/h (fixed rate). Additional boluses of alfentanil, 1 mg, were administered before noxious stimuli; group 2 (n = 25) received a loading dose of fentanyl, 25 micrograms/kg, midazolam, 1.5 to 3 mg, and pancuronium, 0.1 mg/kg for induction, followed by an infusion of fentanyl, 7 micrograms/kg/h, for maintenance. Additional boluses of midazolam (1.5 to 3 mg) and fentanyl (250 micrograms) were administered before noxious stimuli. MEASUREMENTS AND MAIN RESULTS. Cardiovascular parameters at eight intraoperative time points as well as time to extubation, morphine consumption, and pain scores were recorded. Induction of anesthesia was associated in both groups with a small but significant decrease in mean arterial pressure (1: 15 mmHg (15%); 2: 8 mmHg (8%) with significant decreases in cardiac index (1: 8%; 2: 8%) and left ventricular stroke work index (1: 24%; 2: 21%). Throughout surgery, hemodynamic profiles were comparable between groups except after intubation when the MAP was significantly lower in group 1 (75 +/- 12 mmHg) than in group 2 (89 +/- 17 mmHg). Group 1 required less inotropic support. Extubation was performed faster in group 1 (7.6 h) than in group 2 (18.0 h). Morphine requirements and pain scores were comparable between groups. Propofol-alfentanil anesthesia provides good intraoperative hemodynamics and allows early extubation after coronary artery surgery.

Alterations of cardiovascular performance during laparoscopic colectomy: a combined hemodynamic and echocardiographic analysis.

We investigated cardiovascular performance in 12 patients (mean age 66 +/- 12 yr) with significant coexisting cardiopulmonary disease (hypertension, coronary artery disease, chronic obstructive pulmonary disease) during laparoscopic colectomy under general anesthesia. Hemodynamic monitors included arterial and pulmonary artery catheters in combination with transesophageal echocardiography. Hemodynamic and echocardiographic data were obtained at five epochs: baseline (after induction of anesthesia), insufflation (after pneumoperitoneum, supine position), Trendelenburg 5 (5 min after placement into Trendelenburg's position), Trendelenburg 20 (at 20 min in Trendelenburg's position), and end (after release of the pneumoperitoneum, supine position). Hemodynamic responses to peritoneal insufflation resulted in significant increases in systemic vascular resistance (SVR) as well as endsystolic area (ESA) and significant decreases in cardiac index (CI) and ejection fraction area (EFa) compared with baseline. Trendelenburg's positioning augmented ventricular preload and performance, resulting in significant increases in pulmonary capillary wedge pressure, CI, end-diastolic area, and EFa compared with insufflation. At the final epoch, end, a hyperdynamic state occurred as evidenced by a significantly decreased ESA and SVR while heart rate, CI, and EFa increased significantly compared to baseline and insufflation. In an elderly population with significant coexisting cardiopulmonary disease, intraoperative maneuvers required for laparoscopic colectomy resulted in previously undescribed alterations of cardiovascular performance, which persisted after release of the pneumoperitoneum.

Effects of a sinus node inhibitor on the normal and failing rabbit heart.

The effects on cardiac function of slowed frequency produced by a sinus node inhibitor (zatebradine, or UL-FS 49) were studied in the conscious rabbit under control conditions (n = 16) and after heart failure was produced by rapid atrial pacing for an average of 18.5 days (n = 8). Echocardiography was used to verify severe left ventricular (LV) dysfunction, and high-fidelity micromanometry and cardiac output measurements (Doppler echo) were performed. Echocardiographic fractional shortening was 40.3 +/- 4.1 % (SD) in controls; in heart failure it was 18.0 +/- 1.6 %, and the LV was enlarged. In controls, as heart rate (HR) was decreased from 279 beats per minute (bpm) by incremental doses of zatebradine (up to 0.75 mg/kg), maximal changes occurred when the heart reached 218 bpm with a maximum decrease of the first derivative of LV pressure (LV dP/dtmax) of 15.9 %; LV enddiastolic pressure (EDP) increased from 4.3 to 8.4 mmHg along with a significant decrease in cardiac index (CI) of 15.2 %, while LV systolic pressure (SP) was stable. In heart failure, LV dP/dtmax and CI were markedly reduced compared to controls and with reduction of HR from 257 to 221 bpm LV dP/dtmax was unchanged, LVEDP increased slightly (NS), LVSP was unchanged and CI fell by 13.5 % at the highest dose. In subgroups (control n = 9, failure n = 6), in order to eliminate the hemodynamic effects of cardiac slowing by zatebradine the sinus rate present before zatebradine was matched by atrial pacing; this procedure eliminated all hemodynamic abnormalities accompanying cardiac slowing in both groups. In conclusion, slowed HR due to a sinus node inhibitor was well tolerated in severe heart failure, and all negative hemodynamic responses in both controls and in heart failure were due entirely to a negative forcefrequency effect, without a direct depressant action of zatebradine on the myocardium.

Growth Hormone Improves Cardiac Performance in Experimental Heart Failure

Growth hormone has been shown to increase maximum isometric active force of the left ventricular papillary muscle of rats in vitro. Administration of growth hormone causes an increase in myocardial contractility in normal humans. Our preliminary study suggests that treatment with growth hormone results in increased ventricular contractility in rats with left ventricular dysfunction. In the present study, the effects of growth hormone on cardiac function, including cardiac output, stroke volume, and peripheral vascular resistance, were determined in a rat model of heart failure. Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, recombinant human growth hormone (2 mg/kg per day SC) or vehicle then was administered for 15 days. The animals were catheterized after 13 days of the treatment. Cardiac output, measured by a thermodilution method, and other hemodynamic parameters were measured in the conscious animals 2 days after catheterization. The infarct sizes induced by left coronary ligation were comparable between growth hormone-treated and vehicle-treated rats. Six weeks after ligation, rats treated with vehicle exhibited significant decreases in cardiac index, stroke volume index, and left ventricular maximum dP/dt and increases in left ventricular end-diastolic pressure compared with sham rats. In the ligated rats, treatment with growth hormone increased cardiac index, stroke volume index, and left ventricular maximum dP/dt (P < .05) and reduced left ventricular end-diastolic pressure and systemic vascular resistance (P < .05). In sham rats, growth hormone slightly reduced arterial pressure but did not significantly alter cardiac performance. There was no significant difference in heart rate between the experimental groups. These results suggest that growth hormone treatment may improve cardiac function by both increased myocardial contractility and decreased peripheral vascular resistance in heart failure.

Tumor necrosis factor α: A major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats

Background/Aims : Portal hypertension is often accompanied by a hyperdynamic circulatory syndrome. Tumor necrosis factor (TNF) α causes vasodilatation and a hyperdynamic state in mammals by activating nitric oxide synthesis. The aim of this study was to investigate whether TNF-α plays a role in developing the hyperdynamic syndrome in portal hypertension. Methods : Portal-hypertensive rats, induced by partial ligation of the portal vein (PVL), were used. In experiment 1, rats that underwent PVL were treated with polyclonal anti-mouse TNF-α or placebo intravenously the same day of the PVL operation and 24 hours before hemodynamic studies. Hemodynamic studies were performed 5 days after PVL. In experiment 2, rats that underwent PVL received anti-TNF-α or placebo intravenously 3 days and 24 hours before hemodynamics as in experiment 1. Hemodynamics were performed 14 days after the PVL operation. TNF-α blood levels were measured using a bioassay. Results : Anti-TNF-α treatment induced a significant increase in mean arterial pressure, heart rate, and systemic vascular resistance and a significant decrease in cardiac index, portal pressure, and TNF-α levels in comparison with placebo animals. No significant effects were observed in sham rats. Conclusions : Anti-TNF-α treatment in rats that underwent PVL significantly blunts the development of the hyperdynamic circulation and reduces portal pressure. TNF-α may play a role in the hemodynamic abnormalities of portal hypertension.

The effects of chronic endoscopic variceal sclerotherapy on systemic and splanchnic hemodynamics in patients with cirrhosis.

The aim of this study was to determine whether endoscopic variceal sclerotherapy affects systemic or splanchnic hemodynamics. We measured hemodynamic parameters before and after the first course of sclerotherapy in 35 patients with cirrhosis. Following sclerotherapy, there was a significant decrease in cardiac index and a significant increase in systemic vascular resistance. Changes in hepatic venous pressure gradient varied from patient to patient with no statistically significant change in the group overall. However, all 20 patients with a decline in the hepatic venous pressure gradient had a concomitant decrease in cardiac index and/or a large extravariceal shunt. The multivariate analysis disclosed that the decrease in cardiac index was a statistically significant contributor for the decline in hepatic venous pressure gradient. We conclude that the obliteration of esophageal varices by sclerotherapy significantly reverses the hyperdynamic circulatory state in patients with cirrhosis. Spontaneous changes in systemic hemodynamics and the interaction with hepatic hemodynamics must be taken into account when evaluating hepatic hemodynamics in patients undergoing variceal sclerotherapy.

Effects of insufflation on hemodynamics during thoracoscopy

Thoracic procedures once requiring open thoracotomy are now being performed with video-assisted thoracoscopy. To visualize adequately the intrathoracic structures, creation of an artificial pneumothorax by carbon dioxide insufflation under positive pressures has been advocated. We hypothesized that positive-pressure insufflation during thoracoscopy would cause significant hemodynamic compromise. Eight healthy female pigs underwent general endotracheal anesthesia and placement of monitoring lines. After placement of a thoracoscope, baseline hemodynamic measurements were obtained at 0 mm Hg (atmospheric pressure). Measurements were taken randomly at 5, 10, and 15 mm Hg using carbon dioxide insufflation after stabilization at each pressure. Data were analyzed using Page's test for nonparametric variables. Insufflation pressures of 5 mm Hg or greater resulted in significant decreases in cardiac index, mean arterial pressure, stroke volume, and left ventricular stroke work index, whereas central venous pressure increased (p < 0.001). Changes in heart rate were not significant. We do not recommend routine positivepressure insufflation during thoracoscopy because of the significant hemodynamic compromise in our experimental model.