Significant Increase In Cardiac Index Research Articles

A controlled, randomised study of the effects of 7.5% hypertonic saline / 6% hydroxyethyl starch on haemodynamic, oxygen transport and metabolic parameters in patients undergoing abdominal aortic reconstruction

Objective: To evaluate the effects of 7.5% hypertonic saline / 6% hydroxyethyl starch (HES) against 6% HES as control on haemodynamics, oxygen transport patterns and selected metabolic parameters in patients undergoing abdominal aortic reconstruction. Design: Prospective, randomised controlled study. Setting: Operating theatre and general intensive care unit in a university hospital. Subjects: Fifty patients undergoing abdominal aortic reconstruction were randomised to receive either 7.5% hypertonic saline/6% HES (HTS-HES group, n=25) or 6% HES (HES group, n=25) after aortic clamp release. Measurements and main results: Compared to 6% HES, 7.5% NaCl/6% HES produced a significant increase in cardiac index (3.6±0.9 versus 3.0±0.8 l/min/M2, p<0.05) and a significantly higher mean arterial pressure at the end of surgery (103±14 versus 94±14 mmHg). Oxygen consumption index (VO2I) was significantly higher in the control group of patients given 6% HES after infusion and at the end of surgery (102±23 versus 83...

Hemodynamic benefit of optimizing atrioventricular delay after cardiopulmonary bypass

Background: Shortening of atrioventricular delay (AVD) by sequential cardiac pacing has been proposed to improve hemodynamics in patients with end-stage heart failure. In addition, optimization of prolonged AVD may be associated with a decrease of presystolic mitral insufficiency. The aim of this study was to explore the incidence of prolonged AVD during the early postcardiopulmonary bypass (CPB) period and to evaluate the hemodynamic benefit of its shortening by using sequential cardiac pacing. Methods: Fifty consecutive patients scheduled for coronary artery bypass grafting were prospectively screened. AVD was measured immediately after separation from CPB. Patients presenting with AVD greater than or equal to 200 ms entered the study. Sequential cardiac pacing was introduced with programmed AVD starting at 80 ms and randomly increased by steps of 20 ms until resumption of native anterograde atrioventricular node conduction. Cardiac index (CI) was derived from transesophageal echocardiographic data during each step of this procedure. Results: Nineteen patients were included. Median native AVD was 220 ms. Median optimal AVD was 140 ms. Mean native CI (Cl-nat) was 2.59 ± 0.42 L/min/m 2. Mean optimal Cl (CI-opt) was 3.12 ± 0.45 L/min/m 2. CI-opt/Cl-nat was 1.20 ± 0.07. Cl-opt/CI-nat was significantly inversely correlated with preoperative left ventricular ejection fraction ( r = − 0.83). Conclusions: Prolonged AVD is a common occurrence after CPB. Its artificial shortening by sequential cardiac pacing is always associated with a significant increase of CI. The magnitude of this hemodynamic improvement is inversely correlated with preoperative left ventricular ejection fraction.

A Trial of Antioxidants N-acetylcysteine and Procysteine in ARDS

To determine the levels of glutathione and cysteine in patients with ARDS and examine the effect of treatment with N-acetylcysteine (NAC) and L-2-oxothiazolidine-4-carboxylate (Procysteine; Clintec Technologies Inc; Chicago [OTZ]) on these levels and on common physiologic abnormalities, and organ dysfunction associated with ARDS. Randomized, double-blind, placebo-controlled, prospective clinical trial. ICUs in five clinical centers in the United States and Canada. Patients meeting a predetermined definition of ARDS and requiring mechanical ventilation. Standard care for ARDS and I.V. infusion, every 8 h for 10 days, of one of the following: NAC (70 mg/kg, n=14), OTZ (63 mg/kg, n=17), or placebo (n=15). Both antioxidants effectively repleted RBC glutathione gradually over the 10-day treatment period (47% and 49% increases from baseline values for NAC and OTZ, respectively). There was no difference in mortality among groups (placebo, 40%; NAC, 36%; OTZ, 35%). However, the number of days of acute lung injury was decreased and there was also a significant increase in cardiac index in both treatment groups (NAC/OTZ [+]14%; placebo [-]6%). Our findings suggest that repletion of glutathione may safely be accomplished with NAC or OTZ in patients with acute lung injury/ARDS. Such treatment may shorten the duration of acute lung injury, but larger studies are needed to confirm this.

A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST)

This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensin-converting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min, resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m 2 ), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death. (Am Heart J 1997;134:44-54)

A Comparison of the Hemodynamic Effects of Amrinone and Sodium Nitroprusside in Infants After Cardiac Surgery

The phosphodiesterase inhibitor amrinone (AMR) increases cardiac output in children after cardiac surgery.In vitro, amrinone has both positive inotropic and vasodilatory effects. However the relative contribution of these effects to the increases in cardiac output observed clinically is unclear, and it has not been demonstrated that amrinone offers a hemodynamic advantage above that of pure vasodilators in infants. We compared the hemodynamic effects of AMR and sodium nitroprusside (SNP) in 10 infants after cardiac surgery. Cardiac index (CI) was measured by thermodilution after SNP administration, titrated to decrease mean blood pressure (MBP) by 20%, and then after a 1.5-mg/kg bolus dose of AMR. Each patient served as his or her own control. Preload, as measured by left atrial pressure and transesophageal echocardiography (in eight patients), was kept constant throughout the protocol. Both SNP and AMR caused significant decreases in MBP and systemic vascular resistance index (SVRI). However, only AMR resulted in a significant increase in CI. The ratio of fractional increase in CI to fractional absolute decrease in MBP was significantly greater for AMR than SNP, indicating greater efficacy for AMR in the treatment of low cardiac output syndrome and suggesting that, in infants after cardiac surgery, AMR has clinically relevant positive inotropic effects. (Anesth Analg 1997;84:294-8)

The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection

Adrenaline is used increasingly in the management of septic shock, but its efficacy and safety are uncertain. In an open, randomised, crossover study we compared the effects of stepped doses of adrenaline 0.1 to 0.5 microgram/kg per min and dopamine 2.5 to 10 micrograms/kg per min on the haemodynamic and acid-base status of 23 patients critically ill with severe sepsis (n = 10) or severe malaria (n = 13). All patients completed the dopamine study whereas in 16 (84%) patients the adrenaline infusion had to be terminated before reaching, or during, the maximum dose because of lactic acidosis (p < 0.0002). Adrenaline was associated with a mean (95% CI) increase in plasma lactate of 3.2 (2.6 to 3.8) mmol/L, and mean falls in arterial pH of 0.052 (0.035-0.068) pH units and base excess of 3.8 (2.8-4.7) mmol/L. The geometric mean (95% CI) lactate increment per unit adrenaline dose was 8.2 (5.8-10.5) mmol/L per microgram/kg per min. In contrast dopamine was associated with a fall in lactate of 1.0 (0.4-1.5) mmol/L, a rise in base excess of 1.4 (0.7 to 2.0) mmol/L (p < 0.0001 in each case), and no effect on arterial pH. Both drugs induced significant increases in cardiac index and oxygen delivery with smaller increases in oxygen consumption and falls in systemic vascular resistance which were similar in severe malaria and severe sepsis (p > 0.1 in each case) [corrected]. Infusion of inotropic doses of adrenaline in severe infections causes lactic acidosis.

Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: Effects on right ventricular function

The short- and mid-term hemodynamic effects of transjugular intrahepatic portosystemic shunt (TIPS) were studied in 16 sedated cirrhotic patients. Indications included relapsing variceal bleeding (n = 10) and refractory ascites (n = 6). The decrease of porto-atrial pressure gradient (from 20.4 +/- 4.2 mm Hg to 10.1 +/- 2.4 mmHg; P < .05) was associated with an increase of mean pulmonary artery pressure (MPAP) (from 12.3 +/- 3.0 mm Hg to 20.3 +/- 5.3 mm Hg; P < .05) and of right atrial pressure (RAP) from 3.4 +/- 2.6 mm Hg to 8.3 +/- 3.7 mm Hg; P < .05), whereas right ventricular end-diastolic volume (RVEDVI) remained unchanged. The significant increase of cardiac index (CI) (from 4.5 +/- 1.2 L/min/m2 to 5.0 +/- 1.1 L/min/m2; P < .05) was essentially attributable to an increase of heart rate (HR) (from 81 +/- 11 to 88 +/- 10 beats/min; P < .05). Systemic vascular resistance (SVR) decreased (from 812 +/- 281 to 666 +/- 191 dynes/sec/cm5; P < .05), whereas pulmonary vascular resistance (PVR) increased (from 60.6 +/- 29.6 to 82.0 +/- 34.6 dynes/sec/cm5; P < .05). After transient shunt occlusion with a balloon catheter, all of the hemodynamic parameters returned to baseline values, except pulmonary artery pressure, which also decreased but remained significantly increased. One month after TIPS, pulmonary pressure remained elevated, and CI further increased. It is concluded that increased PVR is the major hemodynamic alteration occurring after TIPS placement. It correlates with the decrease of porto-atrial gradient and is probably mediated by both mechanical and neurohumoral factors. (Hepatology 1996 May;23(5):982-7)

Losartan reduces cardiac mass and improves coronary flow reserve in the spontaneously hypertensive rat.

To evaluate the effects of losartan administration on cardiovascular mass, systemic and coronary hemodynamics (rest, maximal treadmill exercise, and dipyridamole infusion) and on resting regional hemodynamics in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Although losartan administration (two doses: 10 and 30 mg/kg per day for 3 weeks by gavage) reduced left ventricular mass at the higher dose in WKY rats and with both doses in SHR, only the higher dose reduced arterial pressure in SHR. Losartan administration did not affect cardiac index, myocardial or other organ flows (radiomicrosphere) at rest in both strains. Significant increases in cardiac index and coronary flow and decreases in coronary vascular resistance were observed during exercise in both strains and these responses were not affected by losartan administration. Compared with those in WKY rats, coronary flow and flow reserve (dipyridamole) were decreased and minimal coronary vascular resistance was increased in untreated SHR. Administration of a higher losartan dose increased coronary flow reserve and decreased minimal coronary vascular resistance (measured during dipyridamole infusion) in SHR. These data demonstrated that losartan administration reduced left ventricular mass, a response that did not seem to be solely dependent on afterload. Furthermore, cardiac and stroke indices and coronary flow reserve were not changed in SHR during maximal treadmill exercise after hypertrophy reversal, even with the lower dose of losartan and when the ventricular afterload was similar to that of untreated SHR.

Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: Effects on right ventricular function

The short- and mid-term hemodynamic effects of transjugular intrahepatic portosystemic shunt (TIPS) were studied in 16 sedated cirrhotic patients. Indications included relapsing variceal bleeding (n = 10) and refractory ascites (n = 6). The decrease of porto-atrial pressure gradient (from 20.4 ± 4.2 mm Hg to 10.1 ± 2.4 mmHg; P &lt; .05) was associated with an increase of mean pulmonary artery pressure (MPAP) (from 12.3 ± 3.0 mm Hg to 20.3 ± 5.3 mm Hg; P &lt; .05) and of right atrial pressure (RAP) from 3.4 ± 2.6 mm Hg to 8.3 ± 3.7 mm Hg; P &lt; .05), whereas right ventricular end-diastolic volume (RVEDVI) remained unchanged. The significant increase of cardiac index (CI) (from 4.5 ± 1.2 L/min/m2 to 5.0 ± 1.1 L/min/m2; P &lt; .05) was essentially attributable to an increase of heart rate (HR) (from 81 ± 11 to 88 ± 10 beats/min; P &lt; .05). Systemic vascular resistance (SVR) decreased (from 812 ± 281 to 666 ± 191 dynes/sec/cm5; P &lt; .05), whereas pulmonary vascular resistance (PVR) increased (from 60.6 ± 29.6 to 82.0 ± 34.6 dynes/sec/cm5; P &lt; .05). After transient shunt occlusion with a balloon catheter, all of the hemodynamic parameters returned to baseline values, except pulmonary artery pressure, which also decreased but remained significantly increased. One month after TIPS, pulmonary pressure remained elevated, and CI further increased. It is concluded that increased PVR is the major hemodynamic alteration occurring after TIPS placement. It correlates with the decrease of porto-atrial gradient and is probably mediated by both mechanical and neurohumoral factors.

Halothane anesthesia suppresses reflex tachycardia caused by calcitonin gene-related peptide in dogs

Calcitonin gene-related peptide (CGRP) is known to produce vasodilation, hypotension, and tachycardia. To investigate the interaction between CGRP and anesthetics, the hemodynamic response to infusions of CGRP was studied in dogs anesthetized with halothane or pentobarbital. In halothane-anesthetized dogs given 0.4 μg·kg(-1) of CGRP, mean arterial pressure (MAP) did not change significantly. However, there was a significant reduction in systemic vascular resistance (SVR) associated with significant increases in cardiac index (CI) and stroke volume index (SVI). Higher doses (4 and 40 μg·kg(-1)) of CGRP produced dose-dependent decreases in MAP accompanied by a reduction in SVR. Further, both CI and SVI significantly increased at 4 μg·kg(-1) CGRP but remained unchanged at the 40 μg·kg(-1) infusion rate. Heart rate (HR) was not increased at all doses but was decreased at 40 μg·kg(-1). In pentobarbital-anesthetized dogs, CGRP at doses of 4 μg·kg(-1) produced a qualitatively similar cardiovascular responses as that observed in halothane-anesthetized dogs, but with one exception: HR was significantly increased. The results show that the hemodynamic profiles induced by CGRP during halothane or pentobarbital anesthesia are a decrease in MAP accompanied by a reduction in SVR and no consistent alterations in CI. However, CGRP effects on HR showed in a different way. The results also show that HR response differs depending on the anesthetics used: HR increases during pentobarbital anesthesia, while it does not increase during halothane anesthesia.

Dopexamine Hydrochloride in Septic Shock

To test whether dopexamine hydrochloride, by its beta 2-adrenoreceptor and dopaminergic 1 (DA1) and dopaminergic 2 (DA2) agonistic properties, can improve oxygen consumption (VO2) in hyperdynamic patients with septic shock. Prospective, single-cohort study. ICU, university hospital. Twenty-nine postoperative, hemodynamically stabilized, hyperdynamic patients with septic shock. Short-term application (30 min) of dopexamine hydrochloride at a dose of 2 microgram/kg/min. Complete hemodynamic profile with O2 transport-related variables at baseline, 30 min after starting the dopexamine infusion, and 30 min after stopping the infusion. The dopexamine infusion resulted in significant increases in cardiac index (17%) (p<0.001) and O2 delivery (DO2) (16%) (p<0.001). VO2 increased slightly but significantly about 4% (p<0.001) by respiratory gas exchange measurements and 9% (p<0.001) by cardiovascular Fick calculations. The O2 extraction ratio decreased about 8% (0.001). The addition of dopexamine hydrochloride at a dose of 2 microgram/kg/min resulted in significant increases of DO2 and to a lesser extent VO2. Much of the global DO2 increase was not utilized, because O2 extraction ratio decreased. Direct calorigenic effects of dopexamine and an increase in myocardial VO2 likely account for a large portion of the increase in global VO2. Whether any of the VO2 increase reflects improvement in regions of jeopardized tissue oxygenation remains to be clarified before the definite value of this drug in septic shock can be established.

Combined alpha-beta blockade ( doxazosin plus metoprolol) compared with beta blockade alone in chronic congestive heart failure

There has been growing evidence for the benefits of β blockers, but α blockers have not shown sustained benefits in chronic congestive heart failure (CHF). Thirty patients with moderate to severe CHF (New York Heart Association class II to IV) were sequentially assigned to receive metoprolol 6.25 mg with the α-1 antagonist doxazosin 4 mg/day or metoprolol alone. The dose of metoprolol was gradually increased to a target dose of 50 mg orally twice daily. Hemodynamic measurements were obtained before drug therapy, 2 hours after the first dose of combined α-β therapy or metoprolol alone, and after 3 months of continuous treatment. Nucleur ejection fraction, plasma norepinephrine, and submaximal and maximal exercise capacity were also measured before and after chronic therapy. With initial combined drug administration, mean arterial pressure, left ventricular filling pressure, and systemic vascular resistance decreased significantly compared with results after metoprolol alone. However, after 3 months of continuous therapy, both treatment groups showed similar and significant reductions in systemic vascular resistance and heart rate, with significant increases in cardiac index, stroke volume index, stroke work index, ejection fraction, and exercise capacity. Furthermore, the next dose of chronic combined medication no longer showed vasodilating effects. Chronic therapy with fixed-dose doxazosin and increasing doses or metoprolol produced identical effects as those seen in patients receiving metoprolol alone.

Hemodynamics after orthotopic liver transplantation: study of associated factors and long-term effects

Among 68 liver transplant recipients, 190 hemodynamic studies were performed to evaluate the role of sepsis, anemia, acute graft rejection, and persistent portosystemic shunts. The hemodynamic outcome after orthotopic liver transplantation (OLT) in stable patients was also determined. Patients with sepsis showed a significant increase in cardiac index (5.1 ± 0.9 vs. 3.4 ± 0.7 L/min m 2) and hepatic venous pressure gradient (6.3 ± 2.9 vs. 3.3 ± 2.1 mm Hg), compared with patients without sepsis. Cardiac index was higher in patients with, than in patients without, anemia (4.1 ± 0.6 vs. 3.0 ± 0.6 L/min m 2). The hepatic venous pressure gradient was higher in patients with than in patients without acute graft rejection (5.1 ± 2.9 vs. 2.6 ± 1.2 mm Hg). Among patients with acute rejection, the hepatic venous pressure gradient was higher in patients with severe rejection than in those with moderate or mild rejection (7.2 ± 3.3 vs. 4.6 ± 2.4 and 2.8 ± 0.9 mm Hg). In the postoperative period, in patients undergoing transplantation for acute liver failure, the hepatic blood flow was normal and significantly lower than in patients receiving transplant for cirrhosis (1.15 ± 0.37 vs. 1.96 ± 0.71 L/min). In patients undergoing transplantation for cirrhosis, cardiac index, azygos, and hepatic blood flows significantly decreased after 1 year compared with the first 6 postoperative months. Multivariate analysis showed that sepsis, anemia, and time after OLT were independent variables influencing cardiac index. Sepsis, time after OLT, and the existence of portosystemic shunts were independent variables influencing hepatic blood flow. These results show that sepsis, anemia, acute graft rejection, and persistent portosystemic shunts induce modifications in hemodynamics in liver transplant recipients. Furthermore, in patients who undergo OLT for cirrhosis, the posttransplantation hyperdynamic syndrome tends to normalize with time.

Hemodynamics after orthotopic liver transplantation: Study of associated factors and long-term effects

Among 68 liver transplant recipients, 190 hemodynamic studies were performed to evaluate the role of sepsis, anemia, acute graft rejection, and persistent portosystemic shunts. The hemodynamic outcome after orthotopic liver transplantation (OLT) in stable patients was also determined. Patients with sepsis showed a significant increase in cardiac index (5.1 +/- 0.9 vs. 3.4 +/- 0.7 L/min m2) and hepatic venous pressure gradient (6.3 +/- 2.9 vs. 3.3 +/- 2.1 mm Hg), compared with patients without sepsis. Cardiac index was higher in patients with, than in patients without, anemia (4.1 +/- 0.6 vs. 3.0 +/- 0.6 L/min m2). The hepatic venous pressure gradient was higher in patients with than in patients without acute graft rejection (5.1 +/- 2.9 vs. 2.6 +/- 1.2 mm Hg). Among patients with acute rejection, the hepatic venous pressure gradient was higher in patients with severe rejection than in those with moderate or mild rejection (7.2 +/- 3.3 vs. 4.6 +/- 2.4 and 2.8 +/- 0.9 mm Hg). In the postoperative period, in patients undergoing transplantation for acute liver failure, the hepatic blood flow was normal and significantly lower than in patients receiving transplant for cirrhosis (1.15 +/- 0.37 vs. 1.96 +/- 0.71 L/min). In patients undergoing transplantation for cirrhosis, cardiac index, azygos, and hepatic blood flows significantly decreased after 1 year compared with the first 6 postoperative months. Multivariate analysis showed that sepsis, anemia, and time after OLT were independent variables influencing cardiac index. Sepsis, time after OLT, and the existence of portosystemic shunts were independent variables influencing hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

The Efficacy of Amrinone or Adrenaline on Low Cardiac Output Following Cardiopulmonary Bypass in Patients with Coronary Artery Disease Undergoing Preoperative ß-Blockade

We examined 20 patients undergoing coronary bypass grafting for coronary artery disease with NYHA classifications of II and III who had been treated with beta-blocking agents. Patients were randomised for administration of either adrenaline (0.1 microgram/kg/min) or amrinone (bolus 1 mg/kg, continuous infusion of 5-10 micrograms/kg/min), if following cardiopulmonary bypass their cardiac index was < 2.4 L/min/m2 with normal peripheral resistance and normal or increased right- or left-ventricular filling pressures. Over a period of 1 hour, the hemodynamic parameters mean arterial pressure (MAP), cardiac index (CI), heart rate (HR), coronary perfusion pressure (CPP), total peripheral resistance (TPR), as well as the pressure-work index (PWI) were registered or calculated. By means of a coronary sinus catheter myocardial arterio-venous oxygen content difference (AVDO2cor), myocardial blood flow (MBF), using the thermodilution method, and myocardial oxygen consumption (MVO2) could be measured or calculated. Simultaneously, arterial and myocardial lactate concentrations and, using the arterio-venous lactate ratio, myocardial lactate extraction or production were quantified. Using a transseptal approach, the left-ventricular pressure curve was measured and used to differentiate for myocardial contractility (dp/dtmax). Following induction of anesthesia and after cardiopulmonary bypass, plasma levels of the used beta-blocking agent were determined. Both substances caused a significant increase in myocardial contractility, with adrenaline showing a more potent effect than amrinone. Both substances caused a significant increase in CI with a mild increase in HR. Amrinone caused a significant drop in TPR, while MAP remained practically constant.(ABSTRACT TRUNCATED AT 250 WORDS)

実験的僧帽弁閉鎖不全犬におけるニトログリセリン軟膏の口腔粘膜塗布効果

The hemodynamic effect of nitroglycerin ointment (NGO) administered on oral mucosa was investigated at 30 min intervals in five normal and five experimental mitral regurgitation (MR) dogs. After administration of 15 or 100 mg, the mean arterial pressure (MAP) decreased in all cases. MAP were observed attaining the lowest at 90 and 30 min in the normal and MR groups respectively and subsequently returning to the level before administration except for the MR-15 mg cases. Showing a significant increase even after 150 min. The mean pulmonary arterial pressure (MPAP) decreased and subsequently returned to the level before administration except for the MR-15 mg cases. Showing significant increase after 300 min. In the normal-15 mg cases, there were significant increase in cardiac index at 270 min and in heart rate at 30 min but not in other cases. The double product (systolic arterial pressure × heart rate) decreased in all cases, later significantly increased at 240 min in the MR-15 cases.

Effect of Nω-nitro- l-arginine methyl ester on cardiac haemodynamic responses to adenosine infusion in conscious rats

1. 1. The aim of the present study was to evaluate the role of NO in the cardiovascular effects of adenosine in conscious rats. 2. 2. Cardiac index was determinated by thermodilution. In a group of rats, three doses of adenosine were infused (i.v.) at a rate of 150, 300 and 450 μg/kg/min in the absence and in the presence of l-NAME (10 mg/kg). In a second group of rats, the experimental protocol was the same as that of the first group, except an infusion of methoxamine (50 μg/kg/min) was given during the second adenosine administration, instead of L-NAME. 3. 3. In the absence of l-NAME or methoxamine, adenosine induced a dose-dependent decrease in mean arterial pressure and an increase in vascular conductance although adenosine did not affect cardiac index. 4. 4. l-NAME administration attenuated the decreasing effect on the mean arterial pressure in response to the two lower doses of adenosine. In the presence of L-NAME, adenosine induced a significant increase in cardiac index from 18.7 ± 1.5 to 29.1 ± 1.9 and 26.2 ± 1.4 ml/min/100 g. Administration of l-NAME significantly attenuated the adenosine-induced increase in vascular conductance. 5. 5. Methoxamine infusion induced an enhanced response to adenosine infusion. In the presence of methoxamine, adenosine induced a significant greater decrease in mean arterial pressure, and increase in cardiac index and vascular conductance. 6. 6. These results indicate that part of the cardiovascular effects of adenosine can be mediated by NO, since L-NAME administration partially blocked the adenosine-induced vasodilatation.

Acute hemodynamic effects of the prostacyclin analog 15AU81 in severe congestive heart failure

This multicenter, open-label study provides the first assessment of the safety and acute hemodynamic effects of a short-term infusion of 15AU81, a chemically stable analog of prostacyclin, in patients with New York Heart Association class III or IV heart failure. Twelve patients underwent sequential dose escalation by increasing the rate of the infusion at 15-minute intervals until the drug was no longer tolerated. Patients then received a 90-minute infusion at their maximum tolerated dose. The infusion was then discontinued and the subjects were observed during a 90-minute washout segment. Serial hemodynamic measurements were made throughout the dose-ranging, maintenance, and washout segments. A significant decrease in systemic vascular resistance (1,935 +/- 774 vs 1,243 +/- 351 dynes.s.cm-5; p < 0.001) and pulmonary vascular resistance (395 +/- 335 vs 223 +/- 198 dynes.s.cm-5; p = 0.008) occurred from the infusion of vehicle to the maximum tolerated dose. During dose titration, there was a a significant increase in cardiac index (1.9 +/- 0.7 vs 2.6 +/- 0.6 liters/min/m2; p < 0.001) and a tendency for a mild reduction in pulmonary artery wedge pressure (18 +/- 7 vs 17 +/- 6; p = 0.055) for the 8 patients with values on vehicle and maximum tolerated dose. These hemodynamic changes persisted during the maintenance infusion and disappeared rapidly during the washout segment. The most common adverse event to limit dose-ranging was headache, which occurred at a mean maximum tolerated dose of 36 +/- 15 ng/kg/min. Administration of 15AU81 was associated with significant acute hemodynamic improvement in patients with severe heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Pentoxifylline improves the tissue oxygen extraction capabilities during endotoxic shock.

Pentoxifylline (PTX), a xanthine derivative used in the treatment of circulatory insufficiency, has been found to have protective effects in different models of sepsis. We hypothesized that this drug might improve the cellular oxygen availability following endotoxin challenge by increasing oxygen delivery (DO2) and/or tissue oxygen extraction. The oxygen extraction capabilities were studied during a reduction in blood flow induced by cardiac tamponade. Fourteen anesthetized, ventilated, and paralyzed dogs, received intravenous 2 mg/kg of Escherichia coli endotoxin followed by a continuous infusion of 20 ml/kg.h of saline. 30 min later tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Seven dogs were pretreated with PTX as an intravenous bolus of 20 mg/kg, followed by a continuous infusion at 20 mg/kg.h, and the other seven dogs served as a control group. PTX largely attenuated the systemic and pulmonary vasoconstriction observed in the control group and resulted in significant increases in cardiac index, DO2 and oxygen consumption (VO2). PTX also improved ventilation/perfusion matching in the lungs as indicated by a higher PaO2 and PvO2 and a lower venous admixture than in the untreated group during cardiac tamponade (both p < .05). In addition, the critical DO2 (DO2 crit) was lower and the critical oxygen extraction ratio was higher in the PTX treated than in the control group (9.1 +/- 1.8 vs. 11.6 +/- 2.4 ml/kg.min, and 70.6 +/- 14.0 vs. 49.3 +/- 14.6%, both p < .05). The VO2/DO2 dependency slope was also steeper in the PTX-treated than in the control group (.80 +/- .28 vs. .43 +/- .19, p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Heart Failure Therapy with Cilazapril

The efficacy and safety of cilazapril in chronic heart failure have been extensively investigated in an international clinical program in patients with underlying chronic heart failure with ischemic heart disease or dilated cardiomyopathy. Cilazapril in single doses of 1.25-5 mg produced a significant dose-dependent reduction in pulmonary capillary wedge pressure and systemic vascular resistance and a significant increase in cardiac index. In placebo-controlled studies, 1-5 mg of cilazapril once daily for 12 weeks prolonged predose exercise test duration and improved New York Heart Association classification status and signs and symptoms of chronic heart failure, including paroxysmal nocturnal dyspnea. Up to 86% of patients receiving these dosages had improvement, with only 12% of patients requiring the higher dose, 5 mg. These data indicate that cilazapril is effective when administered once daily to patients with chronic heart failure receiving concomitant therapy with digitalis and/or a diuretic. The safety of cilazapril in patients with chronic heart failure has been evaluated in 1,163 patients administered from 0.5 to 15 mg once daily for treatment periods ranging from 1 day to 57 months. Cilazapril was administered to 500 patients for at least 6 months, 264 patients for at least 1 year, and 101 patients for at least 2 years. The most frequently occurring adverse events were dizziness, coughing, dyspnea, fatigue, angina pectoris, and headache. Cilazapril was equally well tolerated by young and elderly patients. Treatment was discontinued due to adverse events in 12.9% of patients, mainly as a result of coughing (1.7%) and dizziness (1%). Forty-four patients (3.8%) died during cilazapril therapy or during a period without treatment. Of these deaths, 93% were due to cardiac causes, especially rhythm disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)