Differences In Hemodynamic Parameters Research Articles

Resuscitation of severe uncontrolled hemorrhage: 7.5% sodium chloride/6% dextran 70 vs 0.9% sodium chloride.

Resuscitation studies of hypertonic saline using controlled and uncontrolled hemorrhage models yield conflicting results with regard to efficacy. These disparate results reflect the use of models and resuscitation regimens that are not comparable between studies. This study evaluated the effects of comparable and clinically relevant resuscitation regimens of 7.5% sodium chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal uncontrolled hemorrhage model. Thirty-six swine (14.2 to 21.4 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The animals were resuscitated with either NS or HSD administered in volumes that provided equivalent sodium loads at similar rates. Group II (n = 12) was resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12) received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups, crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. One-hour mortality was significantly greater in group I (92%) as compared with group II (33%) and group III (33%) (Fisher's exact test; p = 0.004). Intraperitoneal hemorrhage was significantly greater in group II (34 +/- 20 mL/kg) and group III (31 +/- 13 mL/ kg) as compared with group I (5 +/- 2 mL/kg) (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters between groups II and III. In this model of severe uncontrolled hemorrhage, resuscitation with HSD or NS, administered in volumes that provided equivalent sodium loads at similar rates, had similar effects on mortality, hemodynamic parameters, and hemorrhage from the injury site.

T-0162, A Novel Free Radical Scavenger, Reduces Myocardial Infarct Size In Rabbits

1. We investigated the effects of 1-(3-tert-butyl-2-hydroxy-5-methoxyphenyl)-3-(3-pyridylmethyl)urea hydrochloride (T-0162), a novel low-molecular weight free radical scavenger, on the generation of superoxide anions and hydroxyl radicals in vitro and in vivo and on myocardial infarct (MI) size in an in vivo model of MI in rabbits. 2. It was found that T-0162 scavenged both superoxide anions and hydroxyl radicals in a concentration-dependent manner in vitro. 3. In an in vivo rabbit model with 30 min coronary occlusion and 30min reperfusion, T-0162 scavenged hydroxyl radicals generated in the myocardium during reperfusion. 4. Anaesthetized open-chest Japanese white male rabbits were subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with 10% lecithin solution for 220 min from 10 min before occlusion to 180 min after reperfusion. The pretreatment group (n = 10) was infused with T-0162 dissolved in 10% lecithin solution for 220 min from 10 min before occlusion to 180 min after reperfusion at a rate of 400 microg/kg per min. The post-treatment group (n = 10) was injected with an i.v. bolus of 10 mg/kg T-0162 and was then infused with 400 microg/kg per min T-0162 for 190 min from 10 min before reperfusion to 180 min after reperfusion. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of area at risk (AAR). 5. There was no significant difference in haemodynamic parameters among the three groups throughout the experimental period. The per cent infarct size of the AAR in the T-0162 groups (24.8+/-4.3 and 30.5+/-3.9% for pre- and posttreatment groups, respectively) was significantly reduced compared with control (44.7+/-4.1%; P<0.05). There was no significant difference in the AAR among the three groups. 6. In conclusion, T-0162 reduces MI size through the inhibition of reperfusion injury.

Intravenous AMP 579, a novel adenosine A 1/A 2a receptor agonist, induces a delayed protection against myocardial infarction in minipig

The aim of the study was to probe if acute administration of [1 S-[1 a,2 b,3 b,4 a( S*)]]-4-[7-[[2-(3-chloro-2-thienyl)-1-methylpropyl]amino]-3 H-imidazo[4,5- b] pyridin-3-yl] cyclopentane carboxamide (AMP 579) could provide a delayed protection against myocardial ischemia–reperfusion injury after 24 h. Anesthetized Yucatan minipigs were given an intravenous (i.v.) loading dose (3 μg/kg) of AMP 579 in 2 min followed by a 68-min infusion (0.3 μg/kg/min) and were allowed to recover. After 24 h, the animals were subjected to an open-chest operation and the left anterior descending coronary artery was occluded for 40 min, followed by 3 h of reperfusion. Results indicated that there were no significant differences in hemodynamic parameters between vehicle- and drug-treated groups either during drug infusion or ischemia–reperfusion. Both groups had similar area at risk (24.9% for vehicle and 25.1% for AMP 579-treated). However, the infarct size was 36.5% of area at risk in vehicle group ( n=8) and 12.5% in AMP 579 group ( n=8), representing a 66% reduction of infarct size by AMP 579 ( p=0.011). This is the first report to demonstrate that in a large animal model, a hemodynamically silent, single i.v. dose of an adenosine receptor agonist can result in a delayed protection against myocardial infarction.

Early but not delayed continuous arteriovenous hemofiltration improves cardiovascular function in sepsis in dogs.

Continuous arteriovenous hemofiltration (CAVH) has been advocated as treatment to remove inflammatory mediators and thereby to improve hemodynamic parameters in sepsis. However, the results obtained with CAVH have been inconsistent. In a canine model of bacteremic Pseudomonas aeruginosa pneumonia, we tested the hypothesis that the time course of the institution of CAVH may be important in obtaining a beneficial treatment effect. Two protocols were performed in phenobarbital-anesthetized dogs. In the early hemofiltration study (EHS), CAVH for 3 h was initiated 2 h post-pneumonia before mean arterial pressure (MAP) fell. In the late hemofiltration study (LHS), CAVH for 3 h was initiated at 5 h post-pneumonia when a decrease in MAP had already occurred. Hemodynamic measurements included cardiac output (CO), stroke volume (SV), and stroke work (SW). Myocardial depressant activity [filterable cardiodepressant substance (FCS)] found in plasma was assessed by bioassay at each measurement interval. In EHS, after 5 h of sepsis, SW, CO, and SV in the hemofiltered pneumonia group were higher as compared with the nonhemofiltered pneumonia group. In contrast, in LHS, no differences in hemodynamic parameters were found between the two pneumonia groups. In both EHS and LHS, plasma FCS activity was decreased to similar extents by CAVH. These results suggest the time course of institution of CAVH may be important in obtaining a beneficial treatment effect in sepsis.

IL-1ra administration does not improve cardiac function in patients with severe sepsis

Purpose: The purpose of this study was to investigate the effects of interleukin-1 receptor antagonist (IL-1ra) on myocardial function in septic patients. Materials and Methods: A subgroup of patients from a prospective, randomized, double-blind, placebo-controlled, multicenter trial was studied from 63 academic medical centers in the United States, Canada, and Europe. A subgroup of 71 patients with severe sepsis in whom vasoactive support was little altered during the study was included. The patients were randomized to receive either placebo (n = 29) or IL-1ra at a dose of 1 mg/kg/h (n = 20) or 2 mg/kg/h (n = 22). Results: Hemodynamic measurements were taken at baseline, and 1, 2, 3, 4, 8, and 12 hours after placebo or IL-1ra administration. No significant differences in hemodynamic parameters were observed between the groups or over time during the study period. Conclusions: IL-1ra administration has no effect on cardiac function in septic patients.

DETERMINATION OF DOSE RESPONSE FOR INTRATHECAL ROPIVACINE IN LABORING PARTURIENTS

S268 INTRODUCTION: Using the combined spinal epidural (CSE) technique, intrathecal injections of low doses of local anesthetics and/or opioids are being increasingly used for labor analgesia. Ropivacaine, a newly introduced amide local anesthetic, has been shown to be minimally cardiotoxic and results in less motor block than the traditional bupivacaine, [1,2] when used epidurally. Intrathecal ropivacaine has been recently used for general surgery [3] and labor analgesia. [4] The purpose of this study was to determine the ideal intrathecal dose of ropivacaine which would provide adequate labor analgesia with minimal or no motor blockade, and without adversely affecting the mother, fetus, or progress of labor. METHODS: Following institutional approval and written informed consent, twenty healthy, term parturients aged 15-35 years who requested analgesia for labor, participated in the study. All parturients received pulmonary aspiration prophylaxis and 200 cc bolus of lactated Ringer's solution intravenously. The parturients were randomized into five groups in a double blinded manner: Group A - fentanyl 15 mcg (n = 4), Group B - ropivacaine (ropi) 0.5 mg + fentanyl 15 mcg (n = 3), Group C - ropi 1.0 mg + fentanyl 15mcg (n = 6), Group D - ropi 1.5 mg + fentanyl 15mcg (n = 4), Group E - ropi 2.0 mg + fentanyl 15mcg (n = 3). Using the needle through needle technique {Tuohy 17 gauge and Whitacre 27 gauge (11.9cm)}, all parturients received fentanyl 15 mcg intrathecally (with or without ropivacaine), followed by epidural catheter insertion. The epidural block was maintained with ropivacaine 0.1 % and fentanyl 2 mcg/ml infusion after patient's request for further analgesia. Visual analog pain scores (VAS) were assessed before and after the intrathecal dose, and epidural block. Sensory and motor blockade were assessed by pinprick and modified Bromage scale, respectively. Hemodynamic parameters, onset and duration of analgesia, duration of first and second stages of labor, and neonatal Apgar scores were recorded. Parturients were assessed twenty-four hours postpartum for satisfaction with analgesia, and for side effects. RESULTS: There were no demographic differences in the five study groups. All subjects had satisfactory analgesia at 5 minutes after the block. The mean duration of analgesia with intrathecal fentanyl was 80 +/- 10.8 minutes, while in combination with ropivacaine, it was 151.93 +/- 34.45 minutes (p = 0.001), which is statistically significant according to the independent sample T-test. One way ANOVA on the five treatment groups showed significant difference in duration of analgesia across groups (p = 0.001), while multiple comparison analysis determined a significant difference between groups A and C (p = 0.004). The mean duration of the first and second stages of labor were 458.10 +/- 169.77 minutes (p = 0.614) and 35.35 +/- 8.76 minutes (p = 0.328), respectively, with no significant difference across groups. Average time interval between intrathecal injection and delivery was 302.75 +/- 130.61 minutes. Neither the VAS pain scores at 1 and 5 min (p = 0.107, 0.835) nor the changes in VAS pain scores at 1 and 5 min (p = 0.349, 0.883) were significantly different across groups. Fisher's exact test showed no significant difference in motor blockade (detectable weakness of hip flexion) between fentanyl and fentanyl/ropivacaine groups (p = 0.587). Sensory blockade to pin prick was not discernible in 50% of subjects. No significant differences in hemodynamic parameters, umbilical cord gases, or neonatal Apgar scores were noted between the five groups. Two parturients {group C, n=1, group E, n=1} required cesarean section for failure at progression of labor. All patients were satisfied with labor analgesia. None of the parturients experienced postpartum headache, neurological problems, or urinary retention. CONCLUSION: In this ongoing study, our findings suggest that intrathecal ropivacaine (0.5 to 2.0 mg) with fentanyl 15 mcg provides instantaneous analgesia for laboring parturients, without compromising maternal or fetal safety. Our preliminary data, statistically and clinically, suggests that the combination of fentanyl and low dose ropivacaine prolongs the duration of labor analgesia. The addition of ropivacaine does not produce any motor block and may allow ambulation. We recommend the use of low dose ropivacaine and fentanyl 15 mcg intrathecally in the combined spinal epidural technique for labor analgesia.

Hemodynamic heterogeneity of multiorgan donors in Poland

OW L sympathetic activity combined with common hormonal deficiency in the brainstem of dead organ donors frequently lead to marked reduction in systemic vascular resistance. ‘2’ It was confirmed by experimental studies.3 The maintenance of mean arterial pressure above 70 mm Hg might be difficult despite excessive cardiac index sufficient for oxygen transport. Routine acceleration of catecholamines infusion leads to refusal of extrarenal organs acceptance and hastens kidney procurement. In this study, we investigated whether there are any differences in hemodynamic parameters in multiorgan donors referred to the national organization, Poltransplant, from the Cardiac Transplantation Centre, experienced in cardiovascular management, and the centers from the rest of Poland.

Possible contribution of impaired sodium excretion to the development and maintenance of hypertension: a study of the isolated kidneys of the Prague hypertensive rat.

We have shown previously that in the Prague Hypertensive Rat (PHR) "hypertension travels with the kidney" and that the kidney appears to produce an as yet unknown "hypertensogenic" substance. Since enhanced sodium retention could also contribute to this type of hypertension, this possibility was tested in isolated perfused kidneys from PHR and from its normotensive substrain, PNR, bred from the same parent pair as PHR, at two levels of perfusion pressure (PP), i.e 110 and 150 mmHg (where 1 mmHg = 133.3 Pa). Young (6-week-old) and adult (12-week-old) animals of both substrains were used. In young PHR and PNR, there was no significant difference in haemodynamic parameters when the kidneys were perfused at either low or high PP. Surprisingly, water and sodium excretion rates were also the same at both PP values in both substrains, which thus--at this age--do not exhibit the well known "pressure diuresis and natriuresis". In adult PNR, perfusate flow and glomerular filtration rates (GFR) were independent of the level of PP (autoregulation) whereas water and sodium excretion rates were significantly higher at 150 than at 110 mmHg, a finding similar to those found in vivo studies (pressure diuresis and natriuresis). In adult PHR, however, both perfusate flow rate and GFR were pressure dependent: only at the high PP were values of both GFR and perfusate flow obtained which were similar to those in the PNR at low pressure. Sodium excretion was lower, and its tubular reabsorption higher, in PHR than in PNR at both levels of perfusion. Again, in PHR, the higher PP was needed to achieve the same rate of sodium excretion as in PNR at the lower pressure. Thus, the kidneys of PHR retain sodium at a given PP compared with the kidneys from PNR. This may contribute to the development and/or maintenance of hypertension in the PHR.

A prospective, randomized trial limiting perioperative red blood cell transfusions in vascular patients

Patients undergoing major arterial reconstruction have traditionally been transfused with red blood cells to keep hemoglobin concentrations above 10 g/dL in order to prevent anemia-induced myocardial ischemia. There are no data to support this practice. The hypothesis that vascular patients will tolerate a hemoglobin concentration of 9 g/dL was examined. Ninety-nine patients undergoing elective aortic and infrainguinal arterial reconstructions were prospectively randomized preoperatively to receive transfusions to maintain a hemoglobin level of either 10 g/dL or 9 g/dL. Despite significantly different postoperative hemoglobin levels of 11.0 +/- 1.2 versus 9.8 +/- 1.3 g/dL (P <0.0001), there were no differences in mortality or cardiac morbidity rates or length of hospital stay. There were no differences in hemodynamic parameters. Oxygen delivery was lower in the group with lower hemoglobin levels, but there was no difference in O2 consumption between the groups. A lower hemoglobin concentration was tolerated without adverse clinical outcome. Patients did not compensate for anemia by increased myocardial work, but by increasing O2 extraction in the peripheral tissues.

Genistein, a tyrosine kinase inhibitor, blocks the "second window of protection" 48 h after ischemic preconditioning in the rabbit.

We have previously reported a delayed or "second window of protection" against infarction 24-72 h after ischemic preconditioning in the rabbit. This phenomenon has also been associated with the protein kinase C signalling pathway. In the present study, we expanded our investigation to ascertain whether protein tyrosine kinase was in any way associated with this phenomenon in the rabbit heart. We found that 48 h after ischemic preconditioning with 4x5 min coronary occlusions the percentage of myocardium infarcting within the risk zone following a 30-min coronary occlusion and 120-min reperfusion (I/R) was reduced from 39. 6+/-3.3% to 18.0+/-3.7% (P<0.01). However, an i.v. bolus administration of genistein (5 mg/kg), a tyrosine kinase inhibitor, 5 min before ischemic preconditioning stimulus, abolished this protection (I/R=39.0+/-3.4%). Genistein per se had no significant effect on infarction 48 h later. Risk zone volume after coronary ligation was not significantly different between intervention groups. There were no differences in hemodynamic parameters between groups throughout the experimental period. We conclude that the second window of protection, 48 h after preconditioning, is mediated by tyrosine kinase activation in the rabbit heart.

Vascular reactivity during combined ultrafiltration-hemodialysis: influence of dialysate-derived contaminants.

It has been suggested that hemodynamic instability and impaired vascular reactivity during combined ultrafiltration-hemodialysis are related to bioincompatibility factors such as dialysate-derived contaminants or the dialyzer. The study presented here investigated whether vascular reactivity could be improved by the use of sterile dialysate. Forearm vascular resistance and venous tone (measured by strain-gauge plethysmography) as well as arterial blood pressure (by Dinamap) and heart rate (by electrocardiogram) were measured in ten stable dialysis patients (age range, 28 to 71 yr) during 2 h of combined ultrafiltration-hemodialysis (bicarbonate; ultrafiltration rate 1.0 L/h). In addition, a dialysate sample was obtained for culture and limulus amebocyte lysate testing while blood was withdrawn for the estimation of plasma bactericidal/permeability increasing factor (measured by ELISA) and the soluble tumor necrosis factor receptor p75 (measured by ELISA). Patients served as their own control, comparing dialysis with nonsterile and sterile dialysate. No bacterial growth was observed in sterile dialysate, whereas all samples were positive for Pseudomonas in culture in nonsterile dialysis. All limulus amebocyte lysate tests were negative. Bactericidal/permeability increasing factor tended to increase during nonsterile dialysis (P = 0.063) and remained unchanged during sterile dialysis. In both treatments, tumor necrosis factor receptor p75 increased significantly (P < 0.01). There were no significant differences in hemodynamic parameters between the treatment modalities. Despite use of sterile dialysate, forearm vascular resistance remained unchanged whereas venous tone decreased significantly. These results indicate that vascular reactivity during combined ultrafiltration-hemodialysis is not improved by the use of sterile dialysate.

Influence of intrinsic limb vasodilator capacity on exercise tolerance in patients with recent myocardial infarction

To investigate the influence of intrinsic limb vasodilator capacity on exercise performance, limb reactive hyperemic flows and their relations to exercise capacity during upright bicycle exercise were examined in 52 patients with recent myocardial infarction. Reactive hyperemic flow was measured in the forearm and the calf by venous occlusive plethysmography after 5 min of arterial occlusion. Calf reactive hyperemic flow correlated significantly with cardiac output, systemic vascular resistance, and oxygen consumption at peak exercise, whereas flow in the forearm did not. In patients with preserved exercise capacity (group 1, n = 20) compared with those with exercise impairment (group 2, n = 32), calf reactive hyperemic flow was significantly augmented, but forearm flow was similar in the two groups. There were no significant differences in hemodynamic parameters at rest between the two groups. At peak exercise, however, cardiac output was lower and systemic vascular resistance was higher in group 2 than in group 1, whereas arterial blood pressure was maintained identically in the two groups. Thus, intrinsic calf but not forearm vasodilator capacity was linked to exercise hemodynamic responses and exercise capacity in patients with recent myocardial infarction. In addition, reduced calf vasodilation and concomitant enhanced vascular tone seemed to be useful for preserving arterial blood pressure in the setting of decreased cardiac output response to exercise in patients with exercise impairment.

The beneficial effects of atrial natriuretic peptide on arrhythmias and myocardial high-energy phosphates after reperfusion.

The aim of this investigation was to test whether the administration of atrial natriuretic peptide (ANP) has cardioprotective effects against ischaemic and reperfusion injury. Thoracotomized dogs underwent a 30 min left circumflex coronary artery occlusion and 60 min of reperfusion (control group; n = 16). The ANP group (n = 9) received a 20 micrograms bolus injection of synthetic alpha human ANP (SUN 4936) followed by infusion at a dose of 0.1 microgram/kg/min from the beginning of coronary occlusion to the end of the procedure. Administration of exogenous ANP increased plasma ANP immediately and maintained levels at 3000 pg/ml, resulting in an 8-fold increase in plasma cyclic guanosine monophosphate (cGMP) levels. Plasma ANP and plasma cGMP levels did not change at all in controls. There were no significant differences in haemodynamic parameters during ischaemia and reperfusion between the groups. In the ANP group, the prevalence and frequency of ventricular extrasystoles within 10 min after reperfusion decreased markedly [ANP 22% vs. control 100%, P < 0.01, and ANP 1 (1) vs. control 92 (50), P < 0.05, respectively]. No dog in the ANP group had ventricular fibrillation (VF), but the incidence of VF was not statistically significant between the groups [ANP 0% vs. control 25%]. ATP content in the inner layers of the ischaemic myocardium in the ANP group was higher than in controls (P < 0.05) [1.92 (0.28) vs. 1.18 (0.13) mumol/g wet weight]. There was no significant difference in the content of myocardial tissue angiotensin II between the groups. These data show that the infusion of ANP has cardioprotective effects on myocardial ischaemia and reperfusion in this model. These beneficial effects are probably due to direct effects through cGMP rather than haemodynamic changes.

Hemodynamic Evaluation and Exercise Tolerance Comparison before and after Operation in Closed versus Open Mitral Valvotomy in Pure Mitral Stenosis

The relative merits and efficacy of open versus closed mitral valvotomy remains controversial. The purpose of this study was to compare improvement of the hemodynamic parameters and exercise tolerance capacity of the 2 operations in 59 patients with pure mitral stenosis in sinus rhythm. Patients were randomly assigned to 1 of 2 groups: 29 patients in group 1 were operated on with the closed technique and 30 patients in group 2 were operated by the open technique. Preoperatively, the hemodynamic parameters and exercise capacity were similar in the two groups. Cardiac catheterization and exercise treadmill test were performed on all patients before and 3 months after each operation. Hemodynamic parameters as well as exercise tolerance capacity were significantly improved by both open and closed valvotomy ( p &lt; 0.0001). However, postoperatively the improvement in exercise capacity was similar in both groups ( p = NS) and there was no significant difference in hemodynamic parameters in both groups, except for reduction in pulmonary artery pressure and increment in cardiac output. Complication rates were similar in both groups, except for atrial arrhythmias, which were more common in group 2. This study suggested that the closed technique, when performed by experienced surgeons, achieved similar hemodynamic and functional results as the open method. It also has the potential advantage of cost savings in addition to avoiding the complications of cardiopulmonary bypass. It clearly has a place in properly selected patients with mitral stenosis.

Influence of IL-1 receptor blockade on the human response to endotoxemia.

Although the experimental administration of IL-1 induces several aspects of the inflammatory response, such as fever, tachycardia, and acute phase proteinemia, the contribution of IL-1 to the human responses to injury or infection remains unclear. A specific IL-1R antagonist (IL-1ra), which effectively blocks the actions of IL-1, was utilized to evaluate the influence of endogenous IL-1 during experimental human endotoxemia. Eighteen healthy volunteers each underwent one control study day, followed 3 days later by one of three randomly chosen treatments: a 6-h infusion of IL-1ra alone (133 mg/h), 20 U/kg national reference endotoxin alone, or both endotoxin and IL-1ra infusion. IL-1ra administration alone was not associated with any observable response. Despite achieving high circulating levels of IL-1ra (34 +/- 3 micrograms/ml), there were no significant differences in hemodynamic parameters, core temperature, or resting energy expenditure in those endotoxemic volunteers receiving IL-1ra when compared with those who did not. Furthermore, leukocyte kinetic and circulating cytokine, acute phase protein, and endocrine responses were similar in both endotoxemic groups. However, IL-1 blockade did significantly reduce the subjective severity of symptoms experienced by the endotoxemic volunteers (p < 0.05). This study demonstrates that an endogenous IL-1 response does not play a significant role in the hemodynamic, immunologic, and metabolic responses to mild endotoxemia in humans.

932-90 Transient Adenosine Infusion and Washout Before Ischemia Protects the Heart Against Metabolic Damage During Ischemia and Reperfusion, but Does not Attenuate Stunning in Pigs – Comparison with Ischemic Preconditioning

Recent studies indicate that ischemic preconditioning (IP) may be mediated by adenosine (ADO) receptor stimulation. This study compared the effects of adenosine pretreatment on myocardial metabolism and function with those of IP. Control hearts (C) underwent 15 min LAD occlusion (occl) followed by 120 min reperfusion (R). ADO (200/μg/kg/min) was infused into left atrium for 15 min starting at 20 min before LAD occl. IP was elicited by two cycles of 5 min occl & 5 min R. Tissue levels of ATP. creatine phosphate (CP) and pH in the area at risk were measured by 31 P-MRS, and %segment shortening (%SS) by sonomicrometry ADO infusion decreased blood pressure (–26%) and heart rate (–13%), and increased three times regional myocardial blood flow (RMBF). However, within 5 min after stopping ADO infusion, hemodynamic parameters returned to baseline. During sustained ischemia and reperfusion, there were no differences in hemodynamic parameters or RMBF among three groups. 15 min occl 120 min R 120 min R Groups ATP CP pH ATP CP %SS C(n = 10) 64 ± 7% 7 ± 6% 6.3 ± 0.2 71 ± 7% 105 ± 12% 39 ± 16% ADO (n = 10) 76 ± 6% * 9 ± 6% # 6.5 ± 0.1 * 90 ± 8% * 101 ± 6% # 29 ± 6% IP(n = 10) 74 ± 9% * 18 ± 6% * 6.6 ± 0.1 * 91 ± 90% 126 ± 7% 32 ± 16% ATP, CP and %SS values; % of baseline * p &lt; 0.05 vs C # p &lt; 0.05 vs IP ADO pretreatment and IP had similar effects on ATP and pH, but not on CP. In spite of the protective effects on myocardial metabolism during ischemia and reperfusion, neither of the interventions improved %SS after ischemia.

Hemodynamic responses of horses to anesthesia and surgery, before and after administration of a low dose of endotoxin.

Seven horses, which were part of an investigation of the effect of endotoxin administration on vascular reactivity, were anesthetized on two separate occasions for surgical excision of 4-cm sections of palmar digital artery and vein. On the first occasion, the horses were given an infusion of 1 L 0.9% NaCl solution intravenously (i.v.) just before induction of anesthesia (control); on the second occasion, the horses received an infusion of 1 L 0.9% NaCl containing Escherichia coli endotoxin, 0.1 microgram/kg (endotoxin). On both occasions, anesthesia was induced with xylazine, guaifenesin, and ketamine, and maintained with halothane in oxygen. Hemodynamic measurements were made with the horses under anesthesia immediately before beginning surgery (period 1), during skin incision (period 2), during dissection and excision of the vessels (period 3), during skin suturing (period 4), and after completion of surgery during bandaging (period 5). Hemoglobin concentration and mixed venous oxygen content were greater at all periods in horses that received endotoxin. Otherwise, there were no significant differences in hemodynamic parameters between control horses and horses administered endotoxin before beginning surgery (period 1). During surgery and bandaging, horses administered endotoxin had significantly higher heart rate (periods 3, 4, and 5), cardiac index (periods 3, 4, and 5), and oxygen delivery (periods 2, 3, 4, and 5) than did control horses, and mean arterial blood pressure (period 2) and systemic vascular resistance (periods 2, 3, 4, and 5) were less than in control horses. Compared with period 1, surgical stimulation in control horses was associated with increased mean arterial blood pressure and systemic vascular resistance (periods 2, 3, 4, and 5), but cardiac index and oxygen delivery were decreased (periods 3, 4, and 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II effects in a swine model of cardiac arrest

To evaluate the effect of different doses of the vasopressor angiotensin II on aortic diastolic and coronary perfusion pressures in a swine model of cardiac arrest. Immature swine were anesthetized and hemodynamically monitored. Ventricular fibrillation was induced; CPR was begun after ten minutes of ventricular fibrillation. Aortic and right atrial pressures were recorded continuously throughout the experiment. Animal research laboratory. Immature swine weighing 21 to 32 kg. Angiotensin II was administered in doses of 25, 50, 75, and 100 micrograms/kg at 13 minutes of ventricular fibrillation. Each dose was tested in four swine. Except for animals receiving 25 micrograms/kg, aortic diastolic pressure increased significantly in all groups after administration of angiotensin II compared with groups receiving CPR alone. Coronary perfusion pressure increased significantly only with 50- and 75-micrograms/kg doses. There were no significant differences in hemodynamic parameters among the different dose groups. Angiotensin II in doses of 50, 75, and 100 micrograms/kg significantly increased aortic diastolic pressure, and doses of 50 and 75 micrograms/kg significantly increased coronary perfusion pressure in this model of cardiac arrest.

Fluid Resuscitation Improves Survival of Endotoxemic or Septicemic Rats: Possible Contribution of Tumor Necrosis Factor

The present study was designed to investigate the effects of fluid administration on survival in endotoxemic or septicemic male Sprague-Dawley rats. Endotoxemia was induced by intravenous injection of Escherichia coli lipopolysaccharide (LPS), and septicemia produced by cecal ligation and puncture (CLP). In endotoxemic animals deprived of fluid resuscitation, 7-day survival following injection of LPS at doses of 1, 3, or 10 mg/kg LPS were 70% (n = 10), 30% (n = 10), and 0% (n = 10), respectively. In rats resuscitated with 3.3 ml/kg/h of 0.9% NaCl, the dose-response curve for survival was shifted 5-fold rightward in a parallel manner (p < 0.001, between the fluid-resuscitated and nonfluid resuscitated LPS groups), indicating a reduced sensitivity to the effects of LPS following fluid resuscitation. LPS increased serum tumor necrosis factor (TNF alpha) concentrations in fluid-resuscitated endotoxemic animals from a baseline value of 20 U/ml to 2,350 U/ml at 1 h, which returned to 200 U/ml at 2 h. In endotoxemic animals not receiving fluid resuscitation, serum TNF alpha levels at 1 and 2 h were 5-fold and 27-fold higher, respectively, than in fluid-resuscitated animals. There were no differences in arterial blood pressure or heart rate between the two groups of endotoxemic animals; total peripheral resistance was significantly lower at 1 h, and cardiac index was significantly greater at 3 h in the fluid-resuscitated LPS group; otherwise there were no further differences in hemodynamic parameters between the two groups. The survival rate at 4 days following CLP without fluid resuscitation was 14%, whereas CLP with fluid resuscitation improved survival to 74% (p < 0.01). TNF alpha was undetectable (i.e., < 20 U/ml) in the serum of animals subjected to CLP. The improvement in survival with fluid infusion in the LPS and CLP models cannot be attributed to catheter implantation, or to improved hemodynamic parameters in the LPS model. The improvement in survival in the LPS model with fluid infusion was associated with attenuated increases in TNF alpha levels. Furthermore, these studies illustrate that fluid-resuscitated and nonfluid-resuscitated experimental animal models should not be considered equivalent.

Adrenergic modulation of potassium metabolism in uremia

The effect of chronic beta adrenergic blockade on potassium homeostasis during moderate intensity exercise (40% of VO2 max) was examined in seven end-stage renal patients who were being maintained on chronic dialysis treatment. Subjects participated in three study protocols: 1) exercise alone, 2) exercise plus propranolol (a nonselective beta-1, beta-2 antagonist), and 3) exercise plus metoprolol (a specific beta-1 antagonist). The basal potassium concentration was similar in all three studies and averaged 4.95 +/- 0.12 mEq/liter. During Study 1 (exercise alone), plasma potassium rose by 0.26 +/- 0.09 mEq/liter. During exercise with propranolol, plasma K concentration rose significantly higher (delta plasma K = 0.44 +/- 0.26 mEq/liter; P less than 0.05 vs. exercise alone). In contrast, the rise in plasma K during exercise with metoprolol (delta plasma K = 0.20 +/- 0.08 mEq/liter) was similar to that observed with exercise alone. Differences in potassium homeostasis between metoprolol and propranolol could not be explained by differences in hemodynamic parameters, levels of potassium regulatory hormones, or acid base status. Thus, the higher rise in potassium concentration during exercise with propranolol could only be explained by adrenergic blockade at the beta-2 receptor site. These results support the concept that adrenergic control of extrarenal potassium homeostasis in dialysis patients is mediated at the beta-2 receptor. Since a deterioration in potassium homeostasis during exercise is observed with beta-2, but not beta-1 blockade, selective beta-1 adrenergic blocking agents may be safer in dialysis patients.