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Objectives: Optimal care of potential donors can lead to successful transplantation. Hemodynamic instability is a common complication in deceased potential donors. The most common underlying causes are hormonal and electrolyte disturbances as well as a hyperinflammatory state, which is rooted in activation of the cytokine cascade. In this study, our aim was to evaluate the efficacy of methylprednisolone injection, an agent introduced for inflammation suppression to achieve more stability in cases of hemodynamic disturbances., Materials and Methods: This study covered the period from April 2016 to June 2017 and included 45 randomly selected hemodynamically unstable brain-dead cases (mean arterial pressure < 60 mm Hg). For these cases, primary management included trying to achieve stability; however, after many hours, we experienced hemodynamic instability again. Because of no other correctable methods, we decided to use methylprednisolone injection. The potential deceased donors received a total of 1 g methylprednisolone in two 500-mg divided doses after transfer to the organ procurement unit., Results: Of 45 patients, 26 were male (58%), and the mean age of patients was 33 years. The most common causes of brain death were trauma (33%) and cerebrovascular accident (22%). Systolic and diastolic blood pressures increased significantly after methylprednisolone use. We observed no significant dif ferences in pulse rate. In addition, methylprednisolone could correct pH from 7.33 ± 0.11 to 7.38 ± 0.12 (P = .007)., Conclusions: Use of methylprednisolone in hemodynamically unstable deceased donors could allow better management of these cases. Because there are various factors such as infusion of vasopressor drugs or fluid therapy that could affect the hemodynamic status of these cases, future studies with larger sample sizes are recommended to control these confounding factors.

This study aimed to investigate the effect of air pollution on diurnal variation of performance in anaerobic tests, cardiovascular and hematological parameters, and blood gases on soccer players following the Yo-Yo Intermittent Recovery Test Level-1 (YYIRT1). In a randomized order, 11 healthy soccer players (mean age: 21.8 [range: 20-24] years; height: 178.00 [range: 1.64-1.83] cm; body mass index [BMI]: 23.57 [range: 20.45-28.03] kg.m -2 ) performed a YYIRT1 at two different times of day (TOD) (08:00 h and 18:00 h) in two areas (i.e. polluted (PA) and non-polluted (NPA)) with a recovery period of ≥ 72 h in between, to determine the maximal oxygen uptake (VO2max). In each test session: resting oral temperature is measured, anaerobic performances (pre- and post-YYIRT1) were performed, cardiovascular parameters and blood samples were collected at: rest, 3 min and 60 min after the YYIRT1, to assess blood gases and hematological parameters. Our results showed that, agility performance, VO2max, red blood cells (RBC), hemoglobin (Hb), pH, and bicarbonate levels (HCO3 - ) decrease significantly (p < 0.001) following the YYIRT1 in PA compared to NPA. Likewise, the heart rate (HR), systolic blood pressure (SBP), platelets (PLT), white blood cells (WBC), neutrophiles (NEUT), lymphocytes (LYM), and partial pressure of CO2 levels (P v CO2) were significantly higher (p < 0.001) in PA. This effect was slightly accentuated at 18:00 h for some parameters (i.e. Agility, HCO3 - , HR, P v CO2, RBC, SBP). However, performances of sprint and Sargent jump test (SJT), oral temperature, rate of perceived exertion scales (RPE), partial pressure of O2 (P v O2), diastolic blood pressure (DBP), and monocytes (MON) were not affected by pollution (p > 0.05). In conclusion, pollution seems to be critical for health stability and performance in response to YYIRT1 especially in the evening and the winter season. Therefore, coaches and athletes should draw attention to the potential importance of land use planning in their training sessions and competitions in the morning in polluted area to minimize the risk of pollution exposure.

Purpose: The aim of this study was to characterize the cardiovascular responses to dobutamine and their predictors. Our hypotheses were that dobutamine mainly produces tachycardia and vasodilation and fails to improve the microcirculation of patients with septic shock., Materials and Methods: Systemic hemodynamics and sublingual microcirculation were evaluated with dobutamine (0, 2.5, 5.0, and 10.0 μg kg(-1) min(-1)) in 23 patients with septic shock., Results: Dobutamine increased heart rate, cardiac index, and stroke volume index (SVI). Mean blood pressure was unchanged, and systemic vascular resistance decreased. Individual responses were heterogeneous. Stroke volume index increased in 52% of the patients. These patients showed lower changes in mean blood pressure (3 ± 16 mm Hg vs -10 ± 6 mm Hg, P < .05) and higher increases in cardiac index (1.47 ± 0.93 L m(-1) m(-2) vs 0.20 ± 0.5 L m(-1) m(-2)) than did nonresponders. Changes in SVI significantly correlated with echocardiographic left ventricular ejection fraction (r = 0.55). In the whole group, perfused capillary density remained unchanged (14.0 ± 4.3 mm/mm(2) vs 14.8 ± 3.7 mm/mm(2)), but improved if basal values were 12 mm/mm(2) or less (9.1 ± 4.3 mm/mm(2) vs 12.5 ± 4.8 mm/mm(2))., Conclusions: Dobutamine produced variable hemodynamic effects. Systolic dysfunction was the only variable associated with increases in SVI. Finally, dobutamine only improved sublingual microcirculation when severe alterations were found at baseline., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Administration of the 5-HT(1A) receptor agonist, 8-OH-DPAT, improves cardiovascular hemodynamics and tissue oxygenation in conscious rats subjected to hypovolemic shock. This effect is mediated by sympathetic-dependent increases in venous tone. To determine the role of splanchnic nerves in this response, effects of 8-OH-DPAT (30 nmol/kg iv) were measured following fixed-arterial blood pressure hemorrhagic shock (i.e., maintenance of 50 mmHg arterial pressure for 25 min) in rats subjected to bilateral splanchnic nerve denervation (SD). Splanchnic denervation decreased baseline venous tone as measured by mean circulatory filling pressure (MCFP) and accelerated the onset of hypotension during blood loss. Splanchnic denervation did not affect the immediate pressor effect of 8-OH-DPAT but did reverse the drug's lasting pressor effect, as well as its ability to increase MCFP and improve metabolic acidosis. Like SD, adrenal demedullation (ADMX) lowered baseline MCFP and accelerated the hypotensive response to blood withdrawal but also reduced the volume of blood withdrawal required to maintain arterial blood pressure at 50 mmHg. 8-OH-DPAT raised MCFP early after administration in ADMX rats, but the response did not persist throughout the posthemorrhage period. In a fixed-volume hemorrhage model, 8-OH-DPAT continued to raise blood pressure in ADMX rats. However, it produced only a transient and variable rise in MCFP compared with sham-operated animals. The data indicate that 8-OH-DPAT increases venoconstriction and improves acid-base balance in hypovolemic rats through activation of splanchnic nerves. This effect is due, in part, to activation of the adrenal medulla.

Background: The current pilot study compares the impact of an intravenous infusion of Ringer's lactate to an acetate-based solution with regard to acid-base balance. The study design included the variables of the Stewart approach and focused on the effective strong ion difference. Because adverse hemodynamic effects have been reported when using acetate buffered solutions in hemodialysis, hemodynamics were also evaluated., Methods: Twenty-four women who had undergone abdominal gynecologic surgery and who had received either Ringer's lactate (Strong Ion Difference 28 mmol/L; n = 12) or an acetate-based solution (Strong Ion Difference 36.8 mmol/L; n = 12) according to an established clinical protocol and its precursor were included in the investigation. After induction of general anesthesia, a set of acid-base variables, hemodynamic values and serum electrolytes was measured three times during the next 120 minutes., Results: Patients received a mean dose of 4,054 ± 450 ml of either one or the other of the solutions. In terms of mean arterial blood pressure and norepinephrine requirements there were no differences to observe between the study groups. pH and serum HCO3- concentration decreased slightly but significantly only with Ringer's lactate. In addition, the acetate-based solution kept the plasma effective strong ion difference more stable than Ringer's lactate., Conclusions: Both of the solutions provided hemodynamic stability. Concerning consistency of acid base parameters none of the solutions seemed to be inferior, either. Whether the slight advantages observed for the acetate-buffered solution in terms of stability of pH and plasma HCO3- are clinically relevant, needs to be investigated in a larger randomized controlled trial.

Phenylephrine is effective for the management of spinal anesthesia-induced hypotension in parturients undergoing cesarean delivery under spinal anesthesia. While ephedrine was previously considered the vasopressor of choice in obstetric patients, phenylephrine is increasingly being used. This is largely due to studies suggesting improved fetal acid-base status with the use of phenylephrine as well as the low incidence of hypotension and its related side effects with prophylactic phenylephrine regimens. This review highlights the effects of phenylephrine compared with ephedrine on maternal hemodynamics (arterial blood pressure, heart rate, and cardiac output), and occurrence of intraoperative nausea and vomiting. The impact of the administration of phenylephrine as a bolus for the treatment of established hypotension compared with its administration as a prophylactic infusion is discussed. This article also reviews the impact of phenylephrine compared with ephedrine on uteroplacental perfusion, and fetal outcomes such as neonatal acid-base status and Apgar scores. The optimum dosing regimen for phenylephrine administration is also discussed.

Background: Hemodynamic and global oxygen transport variables have failed to reflect splanchnic hypoperfusion, resulting in a failure to recognize inadequately treated hemorrhagic shock. Volemic expansion after fluid resuscitation is essential to improve global and regional oxygen in hemorrhagic shock. We hypothesized that, in contrast to conventional plasma expanders, the smaller volemic expansion from 7.5 NaCl/6% hydroxyethyl starch (HHES) solution administration in hemorrhagic shock may provide lesser systemic oxygen delivery and gastric perfusion. We used hemorrhaged dogs to compare intravascular volume expansion and the early systemic oxygenation and gastric perfusion effects of fixed fluid bolus administration, which are usually used in clinical situations with severe hemorrhage, of HHES, lactated Ringer (LR), and 6% hydroxyethyl starch (HES) solutions., Methods: Thirty dogs were bled (30 mL · kg(-1)) to hold mean arterial blood pressure at 40 to 50 mm Hg over 45 minutes and were resuscitated in 3 groups: LR (n = 10) at 3:1 ratio to shed blood; HES (mean molecular weight 130 kDa, degree of substitution 0.4) (n = 10) at 1:1 to shed blood; and HHES (n = 10), 4 mL · kg(-1). Intravascular volume expansion (Evans blue and hemoglobin dilution), hemodynamic, systemic oxygenation, venous-to-arterial CO(2) gradient (Pv-aCO(2)), and gastric intramucosal-arterial PCO(2) gradient (PCO(2) gap) variables were measured at baseline, after 45 minutes of hemorrhage, and 5, 45, and 90 minutes after fluid resuscitation., Results: HHES increased blood volume because of the high volume expansion efficiency, but intravascular volume expansion with this solution was the smallest of the solutions (P < 0.05). All 3 solutions induced a similar hemodynamic performance but HHES showed lower mixed venous PO(2) and higher systemic oxygenation extraction, Pv-aCO(2), and PCO(2) gap than LR and HES (P < 0.05)., Conclusions: In dogs submitted to pressure-guided hemorrhagic shock and fixed-volume resuscitation, the smaller intravascular volume expansion from HHES solutions provides worse recovery of systemic oxygenation and gastric perfusion compared with LR and HES solutions despite its high volume expansion efficiency, which was limited by low infused volume.

Objective: Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume-driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance., Methods: Controlled hemorrhagic shock (40% of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9% NaCl), Lactated Ringer's Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed., Results: The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringer's Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions., Conclusion: Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.

Background: Optimising the fluid resuscitation of patients with severe malaria is a simple and potentially cost-effective intervention. Current WHO guidelines recommend central venous pressure (CVP) guided, crystalloid based, resuscitation in adults., Methods: Prospectively collected haemodynamic data from intervention trials in Vietnamese adults with severe malaria were analysed retrospectively to assess the responses to fluid resuscitation., Results: 43 patients were studied of whom 24 received a fluid load. The fluid load resulted in an increase in cardiac index (mean increase: 0.75 L/min/m(2) (95% Confidence interval (CI): 0.41 to 1.1)), but no significant change in acid-base status post resuscitation (mean increase base deficit 0.6 mmol/L (95% CI: -0.1 to 1.3). The CVP and PAoP (pulmonary artery occlusion pressure) were highly inter-correlated (r(s) = 0.7, p<0.0001), but neither were correlated with acid-base status (arterial pH, serum bicarbonate, base deficit) or respiratory status (PaO(2)/FiO(2) ratio). There was no correlation between the oxygen delivery (DO(2)) and base deficit at the 63 time-points where they were assessed simultaneously (r(s) = -0.09, p = 0.46)., Conclusions: In adults with severe falciparum malaria there was no observed improvement in patient outcomes or acid-base status with fluid loading. Neither CVP nor PAoP correlated with markers of end-organ perfusion or respiratory status, suggesting these measures are poor predictors of their fluid resuscitation needs.

Background: A concentrate for bicarbonate haemodialysis acidified with citrate instead of acetate has been marketed in recent years. The small amount of citrate used (one-fifth of the concentration adopted in regional anticoagulation) protects against intradialyser clotting while minimally affecting the calcium concentration. The aim of this study was to compare the impact of citrate- and acetate-based dialysates on systemic haemodynamics, coagulation, acid-base status, calcium balance and dialysis efficiency., Methods: In 25 patients who underwent a total of 375 dialysis sessions, an acetate dialysate (A) was compared with a citrate dialysate with (C+) or without (C) calcium supplementation (0.25 mmol/L) in a randomised single-blind cross-over study. Systemic haemodynamics were evaluated using pulse-wave analysis. Coagulation, acid-base status, calcium balance and dialysis efficiency were assessed using standard biochemical markers., Results: Patients receiving the citrate dialysate had significantly lower systolic blood pressure (BP) (-4.3 mmHg, p < 0.01) and peripheral resistances (PR) (-51 dyne.sec.cm-5, p < 0.001) while stroke volume was not increased. In hypertensive patients there was a substantial reduction in BP (-7.8 mmHg, p < 0.01). With the C+ dialysate the BP gap was less pronounced but the reduction in PR was even greater (-226 dyne.sec.cm-5, p < 0.001). Analyses of the fluctuations in PR and of subjective tolerance suggested improved haemodynamic stability with the citrate dialysate. Furthermore, an increase in pre-dialysis bicarbonate and a decrease in pre-dialysis BUN, post-dialysis phosphate and ionised calcium were noted. Systemic coagulation activation was not influenced by citrate., Conclusion: The positive impact on dialysis efficiency, acid-base status and haemodynamics, as well as the subjective tolerance, together indicate that citrate dialysate can significantly contribute to improving haemodialysis in selected patients.

Systemic and microvascular hemodynamic responses to hemorrhagic shock volume resuscitation with hypertonic saline followed by infusion of polymerized bovine hemoglobin (PBH) at different concentrations were studied in the hamster window chamber model to determine the role of plasma oxygen-carrying capacity and vasoactivity during resuscitation. Moderate hemorrhagic shock was induced by arterial controlled bleeding of 50% of blood volume (BV), and a hypovolemic state was maintained for 1 h. Volume was restituted by infusion of hypertonic saline (7.5% NaCl), 3.5% of BV, followed by 10% of BV of PBH at 2 different concentrations. Resuscitation was followed for 90 min and was carried out using 13 gPBH/dL (PBH13), PBH diluted to 4 gPBH/dL in albumin solution at matching colloidal osmotic pressure (PBH4), and an albumin-only solution at matching colloidal osmotic pressure (PBH0). Systemic parameters, microvascular hemodynamics, and functional capillary density were determined during hemorrhage, hypovolemic shock, and resuscitation. The PBH13 caused higher arterial pressure without reverting vasoconstriction and hypoperfusion. The PBH4 and PBH0 had lower MAP and partially reverted vasoconstriction. Only treatment with PBH4 restored perfusion and functional capillary density when compared with PBH13 and PBH0. Blood gas parameters and acid-base balance recovered proportionally to microvascular perfusion. Tissue PO2 was significantly improved in the PBH4 group, showing that limited restoration of oxygen-carrying capacity is beneficial and compensates for the effects of vasoactivity, a characteristic of molecular hemoglobin solutions proposed as blood substitutes.

Purpose: Intravenous infusion of lidocaine attenuates the stress response to surgery. We aimed to evaluate the effects of perioperative lidocaine on the hemodynamic and hormonal responses for cesarean delivery., Methods: After the gaining of ethical approval, 90 patients scheduled for elective cesarean delivery were randomly allocated to receive either lidocaine 1.5 mg x kg(-1) i.v. bolus 30 min before induction, followed by an infusion of 1.5 mg x kg(-1) x h(-1) until 1 h after surgery (n = 45), or saline placebo (n = 45). Anesthesia was maintained with 50% nitrous oxide in oxygen with 0.7% isoflurane. Hemodynamic variables, plasma cortisol, maternal and neonatal lidocaine concentrations, Apgar scores at 1 and 5 min, neonatal acid-base status, and the neurologic and adaptive capacity score (NACS) were recorded., Results: After induction, patients receiving lidocaine had a smaller increase in heart rate and mean arterial blood pressure (P < 0.02) and lower plasma cortisol concentrations (31.1 +/- 9.91 vs 45.6 +/- 8.43 microg x dL(-1); P < 0.001). There were no differences between the two groups in Apgar scores, NACS, or neonatal acid-base status. After delivery, maternal and umbilical venous concentrations and umbilical vein-to-maternal vein ratios of lidocaine were 2.05 +/- 0.42 microg x mL(-) and 1.06 +/- 0.31 microg x mL(-1), and 0.52 +/- 0.07, respectively., Conclusion: Perioperative lidocaine is safe and effective in attenuating the maternal stress response to surgery for cesarean delivery.

Objective: University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the 2 most commonly used liver preservation solutions. The aim of this study was to compare cardiovascular stability, acid-base status, and potassium concentrations between patients who received grafts preserved in either UW or HTK solution in orthotopic liver transplantation (OLT)., Patients and Methods: In this retrospective study, 87 patients who underwent living donor OLT were divided into 2 groups: UW (n = 28) and HTK (n = 59). Group HTK was subdivided into group NF-HTK (n = 31; nonflushed before reperfusion) and group F-HTK (n = 28; flushed before reperfusion). We determined mean arterial pressure (MAP) and heart rate every minute for 5 minutes after reperfusion and the maximum change in these values and incidence of postreperfusion syndrome (PRS). Body temperature, cardiovascular and acid-base parameters, as well as potassium concentrations were compared at 5 minutes before and 5 and 30 minutes after reperfusion., Results: The maximum decreases in MAP within 5 minutes after reperfusion were significantly greater in both the NF-HTK and the F-HTK groups. The rate of PRS was significantly greater in the NF-HTK compared with the UW group. Flushing with HTK solution decreased the rate of PRS; there was no significant difference between the F-HTK and UW groups. All serial changes in body temperature, cardiovascular and acid-base parameters, as well as potassium concentrations were similar among the 3 groups., Conclusions: The incidence of PRS was greater using HTK compared with UW solution during the reperfusion period. Therefore, careful hemodynamic management is advised when using HTK solution.

Activation of the poly(ADP-ribose)polymerase (PARP), a highly energy-consuming DNA-repairing enzyme, plays a crucial role in the pathogenesis of multiorgan failure. Most results, however, were derived from experiments with hypodynamic shock states characterized by a markedly decreased cardiac output (CO) and/or using a pretreatment approach. Therefore, we investigated the effects of the novel potent and selective PARP-1 inhibitor PJ34 in a posttreatment model of long-term, volume-resuscitated porcine endotoxemia. Anesthetized, mechanically ventilated and instrumented pigs received continuous intravenous (i.v.) lipopolysaccharide (LPS) over 24 h. Hydroxyethyl starch was administered to maintain a mean arterial pressure > 65 mmHg. After 12 h of LPS infusion, the animals were randomized to receive either vehicle (Control, n = 9) or i.v. PJ34 (n = 6; 10 mg/kg over 1 h followed by 2 mg/kg/h until the end of the experiment). Measurements were performed before as well as at 12, 18, and 24 h of LPS infusion. In all animals CO increased because of reduced systemic vascular resistance (SVR) and fluid resuscitation. PJ34 further raised CO (P < 0.05 vs. control group) as the result of a higher stroke volume indicating its positive inotropic effect. In addition, it diminished the rise in the ileal mucosal-arterial PCO2 gap, which returned to baseline levels at 24 h of LPS, and improved the gut lactate balance (P = 0.093 PJ34 vs. control) together with significantly lower portal venous lactate/pyruvate ratios. By contrast, it failed to influence the LPS-induced derangements of liver metabolism. Incomplete PARP inhibition because of dilutional effects and/or an only partial efficacy when used in post-treatment approaches may account for this finding.

Although hypertonic saline has been proposed as an intravenous resuscitation fluid, the beneficial effects of the sodium load are associated with potentially deleterious effects of chloride. Since the physiological lactate anion is well metabolized, hypertonic lactate solution could represent an interesting alternative. The aim of this study was to compare metabolic and hemodynamic effects of hypertonic infusion of sodium lactate versus sodium chloride in three groups of surgical patients who underwent elective coronary artery bypass grafting (CABG). Hypertonic lactate solution was infused to patients 14 to 16 h after surgery either involving a cardiopulmonary bypass (CPB-Lac, n = 20) or on-off pump (OPCAB-Lac, n = 20), whereas the third group consisted of patients undergoing cardiopulmonary bypass but receiving hypertonic saline solution (CPB-NaCl, n = 20). An equal fluid and sodium load (2.5 mL/2.5 mmol x kg(-1)) was infused in all patients over 15 min. Plasma glucose and sodium increased after infusion in the three groups, but the changes, although significant, were small. As expected, lactate rose only in CPB-Lac and OPCAB-Lac groups, the changes being more marked in CPB-Lac, indicating a slower lactate metabolism in this group compared with OPCAB-Lac. Although both solutions produced significant increases in cardiac index and oxygen delivery, there was a significant decrease in oxygen extraction only in groups receiving sodium lactate (CPB-Lac and OPCAB-Lac) and not in CPB-NaCl. Finally, hypertonic NaCl infusion induced a modest, although significant, decrease in arterial pH and bicarbonate, whereas hypertonic lactate infusion increased these two parameters in both CPB-Lac and OPCAB-Lac. This study demonstrates that hypertonic lactate infusion is safe and well tolerated in patients undergoing elective cardiac surgery.

Study Objectives: To investigate the changes in hemodynamic profile during cardiopulmonary bypass, and determine the effect of intravenous (IV) heparin on serum chemistry and acid-base status., Design: Prospective study., Setting: Three Canadian hospitals., Patients: 43 consecutive patients undergoing elective aortocoronary bypass., Interventions: Anesthetic technique was standarized. Hemodynamic profile, blood gases, and serum electrolytes were measured immediately before IV heparin for cardiopulmonary bypass, and 5 minutes after., Results: Mean arterial pressure (MAP) decreased by a mean of 11.2 mmHg (12.5%, p = 0.0001) in all patients, of whom 28% were treated with vasoactive drugs to restore MAP. Mean systemic vascular resistance decreased by 418 dyne sec/cm(5) (25%, p = 0.0001), and mean serum potassium increased by 0.14 meq/L (p = 0.0002). The reduction in MAP correlated strongly with the reduction in SVR (p = 0.004), but not with changes in potassium or other variables., Implications: Mean arterial pressure is significantly affected by IV heparin for cardiopulmonary bypass. The hemodynamic mechanism is systemic vasodilation, implying that treatment with a short-acting vasoconstrictor is appropriate, if necessary. Unlike earlier studies, the increase in serum potassium observed, although reproducible, was trivial.

Unlabelled: We retrospectively investigated the effects of continuous arginine vasopressin (AVP) infusion on systemic hemodynamics, acid/base status, and laboratory variables in patients (mean age [mean +/- SD]= 66.3 +/- 10.1 yr) with catecholamine-resistant septic (n = 35) or postcardiotomy shock (n = 25). Hemodynamic and acid/base data were obtained before; 30 min after; and 1, 4, 12, 24, 48, and 72 h after the start of AVP infusion. Laboratory examinations were recorded before and 24, 48, and 72 h after the start of AVP infusion. For statistical analysis, a mixed-effects model was used. The overall intensive care unit mortality was 66.7%. AVP administration caused a significant increase in mean arterial pressure (+29%) and systemic vascular resistance (+56%), accompanied by a significant decrease in heart rate (-24%) and mean pulmonary arterial pressure (-11%) without any change in stroke volume index. Norepinephrine requirements could be reduced by 72% within 72 h. During AVP infusion, a significant increase in liver enzymes and total bilirubin concentration and a significant decrease in platelet count occurred. Arginine vasopressin was effective in reversing systemic hypotension. However, adverse effects on gastrointestinal perfusion and coagulation cannot be excluded., Implications: In this retrospective analysis, the influence of a continuous infusion of an endogenous hormone (arginine vasopressin) on systemic hemodynamics and laboratory variables was assessed in patients with vasodilatory shock unresponsive to conventional therapy. Arginine vasopressin was effective in reversing systemic hypotension. However, adverse effects on gastrointestinal perfusion and coagulation cannot be excluded.

Background: Hypertonic sodium acetate-dextran solution (HAD) causes vasodilatation and buffers metabolic acidosis. In controlled hemorrhage models, HAD in small volumes increases cardiac output without increasing blood pressure, thus creating a "high flow-low pressure" state. The objective of this study was to determine whether limited resuscitation of uncontrolled hemorrhage with HAD solution improves gut perfusion as measured by intestinal mucosal tonometry., Methods: Three groups of 10 swine were bled 25 mL/kg by means of a femoral artery catheter to produce a mean blood pressure of 30 mm Hg. A 4-mm abdominal aortic laceration was then produced by pulling out a preimplanted wire loop. Groups were then randomly assigned to be resuscitated with either lactated Ringer's solution, a hypertonic saline-dextran solution or HAD solution sufficient to maintain a mean blood pressure of 45 mm Hg for 5 hours or until death. Outcomes were measured by survival, intraperitoneal blood loss, hemodynamic monitoring, and ileal mucosal tonometry., Results: HAD infusions caused transient worsening of hypotension and were associated with increased mortality (p = 0.038). Blood loss and volumes required for resuscitation were significantly increased in the lactated Ringer's solution group. HAD showed significant buffering effect against metabolic acidosis in arterial blood only, but intestinal ileal mucosal tonometry was not different among the groups., Conclusion: HAD did not improve gut perfusion despite buffering the systemic acidosis of shock and caused increased mortality. Limited resuscitation with any of these solutions is associated with significant mucosal acidosis.

It is commonly believed that during hyperbaric oxygen (HBO) treatment, in spite of the vasoconstriction induced by the increased O2 content in the breathing gas, the elevated carrying capacity of O2 in the arterial blood results in augmented O2 delivery to tissues. The experiments described here tested the hypothesis that HBO treatment would be more efficient in delivering O2 to poorly perfused tissues if the vasoconstriction induced by elevated O2 could be abolished or attenuated by adding CO2 to the breathing gas. Organ blood flow (QOBF), systemic hemodynamics, and arterial blood gases were measured before, during and after exposure to either 300 kPa O2 (group 1) or 300 kPa O2 with 2 kPa CO2 (group 2), in awake, instrumented rats. During the HBO exposure the respiratory frequency (fb) fell (4 breaths x min(-1) x 100 kPa O2(-1)), with no changes in arterial CO2 tension (PaCO2), but when CO2 was added, fb and PaCO2 increased. The left ventricular pressure (LVP) and the systolic arterial pressure (SBP) increased. The maximum velocity of LVP (+dP/dt) rose linearly with LVP whether CO2 was added or not (r2 = 0.72 and 0.75 respectively). Similarly, the cardiac output (Qc) and heart rate (fc) fell, while the stroke volume (SV) was unaltered, independent of PaCO2. There was a general vasoconstriction in most organs in both groups, with the exception of the central nervous system (CNS), eyes, and respiratory muscles. HBO reduced the blood flow to the CNS by 30%, but this vasoconstriction was diminished or eliminated when CO2 was added. In group 2, the blood flow to the CNS rose linearly with increased PaCO2 and decreased pH. After decompression fc and SBP stayed high, while Qc returned to control values by reducing the SV; CNS blood flow remained markedly elevated in group 2, while in group 1, it returned to control levels. We conclude that the changes in fc, Qc, LVP, dP/dt, SBP and most QOBF values induced by HBO were not changed by hypercapnia. Blood flow to the CNS decreased during HBO treatment at a constant PaCO2. Hypercapnia prevented this decline. Elevated PaCO2 augmented O2 delivery to the CNS and eyes, but increased the susceptibility to O2 poisoning. A prolonged suppression of O2 supply to the CNS occurred during the HBO exposure and in air following the decompression in the absence of CO2. This suppression was offset by the addition of CO2 to the breathing gas.

The aim of the present study was to test the hypothesis that nebulization of the nitric oxide donor sodium nitroprusside may selectively reduce pulmonary vascular resistance and improve oxygenation in lung-lavaged newborn piglets. Thirteen anesthetized piglets (1-3 d old) were subjected to repeated lung lavages and then randomly assigned to one of the following two groups: 1) an SNP group, which received SNP nebulization, and 2) a saline group, which received saline nebulization. Pulmonary arterial pressure and pulmonary vascular resistance increased significantly after lung lavage, whereas cardiac output decreased significantly in both groups. After SNP nebulization, pulmonary arterial pressure decreased from 32+/-1 to 17+/-1 mm Hg (p < 0.01) and PVR decreased from 255+/-20 to 172+/-15 mm Hg L(-1) min(-1) kg(-1) (p < 0.01). The arterial tension of oxygen concomitantly increased from 9.4+/-4.0 to 17.0+/-3.0 kPa (p < 0.01), and the arterial/alveolar ratio of oxygen tension increased from 0.11+/-0.01 to 0.22+/-0.03 (p < 0.01). Systemic hemodynamics were not modified significantly during nebulization of SNP. On the other hand, all variables were stable during nebulization of saline. These data suggest that SNP nebulization produces a selective pulmonary vasodilatation and improves oxygenation in lung-lavaged newborn piglets.

We tested the hypothesis that angiotensin II (ANG II) contributes to ventilatory and acid-base adaptations during 3-4 h of hypoxia (partial pressure of O2 in arterial blood approximately 43 Torr) in the conscious dog. Three protocols were carried out over 3-4 h in five dogs: 1) air control, 2) 12% O2 breathing, and 3) 12% O2 breathing with ANG II receptors blocked by infusion of saralasin (0. 5 microg . kg-1 . min-1). After 2 h of hypoxia, expired ventilation and alveolar ventilation progressively increased, and the partial pressure of CO2 in arterial blood and the difference between the arterial concentrations of strong cations and strong anions ([SID]) decreased. When the hypoxic chemoreceptor drive to breathe was abolished transiently for 30 s with 100% O2, the resultant central apneic time decreased between 0.5 and 2.5 h of hypoxia. All these adaptive responses to hypoxia were abolished by ANG II receptor block. Because plasma ANG II levels were lower during hypoxia and hypoxic release of arginine vasopressin from the pituitary into the plasma was prevented by ANG II receptor block, the brain renin-angiotensin system was likely involved. It is possible that ANG II mediates ventilatory and acid-base adaptive responses to prolonged hypoxia via alterations in ion transport to decrease [SID] in brain extracellular fluid rather than acting by a direct neural mechanism.

A randomized crossover study was designed using the chronically instrumented pregnant sheep preparation to study the possible effects of epidural injection of adrenaline as a single compound on the circulation of mother and fetus. Three consecutive identical doses of adrenaline were administered epidurally with a 30 min interval between treatments. In a randomized crossover fashion two dosages (10 and 15 micrograms) were tested on different days. The day after the last epidural experiment the same doses of adrenaline were given intravenously (i.v.). Between the two i.v. doses a 30 min interval was allowed for values to return to baseline. Twenty-seven experiments were performed in eight ewes. Epidural administration of adrenaline did not affect maternal mean arterial pressure, maternal heart rate, uterine blood flow, fetal mean arterial pressure, fetal heat rate, or maternal and fetal blood gases and acid-base status. After i.v. administration of adrenaline the uterine blood flow decreased in a dose-dependent fashion, but the other haemodynamic variables were not affected. In conclusion, this study indicates that consecutive epidural injections of adrenaline have no significant effect on maternal and fetal haemodynamic responses, uterine blood flow, blood gases and acid-base status in the gravid ewe. However, an i.v. injection of 10 or 15 micrograms adrenaline decreases the uterine blood flow and could compromise the fetus.

Objective: To evaluate buffering capacity and side effects of equivalent doses of tromethamine (THAM) and sodium bicarbonate (BIC)., Animals: 18 purebred dogs., Procedure: Acidosis was induced by having dogs breathe a hypoxic gas mixture (FIO2 = 0.10) until arterial base balance < or = -7.5 mEq/L was reached. Dogs then received a 30-minute infusion of 5% BIC (n = 6) or 0.3M THAM (n = 8), and FIO2 increased to 0.30. Drug doses were calculated to correct base balance to zero., Results: During hypoxia, for BIC- and THAM-treated groups, median (interquartile range [Q1, Q3]) pHa and arterial base balance decreased to 7.16 (7.07, 7.38) and 7.19 (7.11, 7.31), -14 (-16, 9) and -12 (-16, -11) mEq/L, respectively, and mixed venous lactate concentration increased to 7 (2, 15) and 6 (3, 13) mmol/L, respectively. Immediately after each infusion, acid-base and cardiopulmonary variables returned toward baseline. For respective BIC- and THAM-treated groups, pHa increased to 7.37 (7.26, 7.44) and 7.40 (7.33, 7.49) and base balance increased to 0 (-4, 7) and 0 (-4, 2) mEq/L. Lactate concentration decreased only slightly to 5 (2, 6) and 5 (2, 9) mmol/L, but continued to decrease throughout the study. The only significant (P < or = 0.05) difference between groups was hypernatremia after BIC administration that persisted for 60 minutes. The PaCO2 in BIC-treated dogs increased immediately after infusion, compared with values during hypoxia. Standardized ionized calcium values initially decreased in both groups, but returned to baseline by 60 minutes., Conclusion: The buffering capacity of THAM is equal to that of BIC, although THAM does not cause the transient hypernatremia or hypercapnia observed after BIC administration. Hypocalcemia may be transient after administration of either solution. Thus, THAM is an acceptable alternative to BIC for treatment of metabolic acidosis in selected anesthetized dogs.

Objective: To assess the usefulness of glycopyrrolate (GLY) in preventing the decrease in cardiac index (CI) usually caused by xylazine (XYL)/ketamine (KET)-induced anesthesia in horses., Animals: 6 healthy horses., Procedure: Horses were treated with saline solution or 2.5 micrograms of GLY/kg of body weight, administered i.v. 15 minutes later, XYL (1 mg/kg) was administered i.v., followed 5 minutes later by KET (2 mg/kg) administration. The horses were positioned in left lateral recumbency, insufflated with 15 L of oxygen/min, and maintained for 30 minutes on the infusion of 0.05 mg of XYL and 0.1 mg of KET/kg/min. Mean, systolic, and diastolic arterial blood pressures, mean pulmonary arterial and central venous pressures, heart rate, CI, and arterial and mixed venous blood gas tensions were recorded up to 40 minutes after anesthesia induction. Intestinal motility was assessed by auscultation of 4 abdominal quadrants for 24 hours after induction. Data were analyzed by Wilcoxon's rank-sum test for nonparametric observations, and by ANOVA for repeated measures and Scheffé's test for continuous parametric variables., Results: Horses given GLY had significantly higher heart rate; mean, systolic, and diastolic arterial blood pressures; CI; oxygen delivery; and mixed venous oxygen tensions, with significantly less tissue oxygen extraction, compared with saline-treated horses. Both groups had complete loss of intestinal motility associated with general anesthesia., Conclusions: GLY significantly reduced the cardiovascular dysfunction attributable to general anesthesia with XYL and KET. The return of intestinal motility was delayed by 3 to 6 hours without causing any serious side effects.

Background: Adrenaline is used increasingly in the management of septic shock, but its efficacy and safety are uncertain., Methods: 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)., Findings: 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]., Interpretation: Infusion of inotropic doses of adrenaline in severe infections causes lactic acidosis.

Abdominal CO2 insufflation has been shown to cause hypercarbia, acidemia, and decreased oxygenation in a pediatric animal model. Such metabolic derangements have prompted a search for alternative insufflation gases. This study compares the hemodynamic and ventilatory changes that occur during pneumoperitoneum with CO2 and helium. Four juvenile swine were intubated and given general anesthesia. Minute ventilation was adjusted to obtain a baseline Pco2 of between 32 and 36 mm Hg, and was kept constant for the duration of the experiment. The subjects initially were insufflated with CO2 or helium at a pressure of 10 mm Hg. Peak ventilatory pressure, end-tidal CO2 (ETCO2) arterial pH, Pco2, Po2, and right atrial and inferior vena caval pressures were measured before and during a 1-hour insufflation period. After desufflation, Pco2 and pH were restabilized. The same parameters were then measured during reinsufflation with the alternate gas. CO2 insufflation caused significant decreases in pH, from 7.51 +/- 0.03 to 7.32 +/- 0.06, and Po2 increased from 261 +/- 49 to 189 +/- 33 mm Hg. Pco2 increased from 35.0 +/- 1.4 to 57.9 +/- 6.3 mm Hg. ETCO2 also increased, from 29.0 +/- 2.2 to 47.2 +/- 5.0 mm Hg. Helium insufflation caused pH to decrease from 7.51 +/- 0.01 to 7.42 +/- 0.04. Pco2 increased from 32.8 +/- 0.8 to 43.5 +/- 3.9 mm Hg, and ETCO2 increased from 27.8 +/- 0.5 to 36.8 +/- 3.1 mm Hg. These alterations were significantly less than those with CO2 pneumoperitoneum. Po2 decreased as well-from 266 +/- 30 to 212 +/- 21 mm Hg. During insufflation with both gases, peak ventilatory pressure and right atrial pressure increased significantly. Abdominal insufflation with CO2 or helium causes hypercarbia, acidemia, and increased ETCO2 in this juvenile animal model. These derangements are significantly less with helium. This gas may prove to be the more suitable insufflation agent for pediatric patients.

Microcystin-LR, a cyclic peptide from the cyanobacterium Microcystis aeruginosa, given at acutely toxic doses causes severe hepatic interstitial hemorrhage. Hemodynamic, calorimetric and acid-base balance changes after i.v. microcystin were measured. The effect of isoproterenol, dopamine, methylprednisolone and whole-blood volume expansion on the immediate hemodynamic effects after toxin administration were also evaluated. A dose of 100 micrograms kg-1 was invariably lethal for rats in all studies. Pathophysiological changes included: a sustained, rapid decline in cardiac output and stroke volume; an acute hypotension responsive to volume expansion with whole blood; a decreased heart rate, responsive to both isoproterenol and dopamine; an early decline in oxygen consumption, carbon dioxide production and metabolic rate accompanied by progressive hypothermia; and acid-base balance changes indicating partially compensated metabolic acidosis. The lethal effects of microcystin-LR were previously attributed to hypovolemic shock as a result of hepatic interstitial hemorrhage. These results indicate that, in addition, there may be a cardiogenic component that limits the physiological cardiac reserve, compromising a normal response to circulatory inadequacy.

The systemic haemodynamic and acid-base effects of the administration of phenylbutazone (4.4 mg kg-1 intravenously) to standing and running horses were investigated. Phenylbutazone, or a placebo, was administered to each of six mares either 15 minutes before, or after 30 minutes of a 60-minute submaximal exercise test which elicited heart rates approximately 55 per cent of maximal, and to the same horses at rest. The variables examined included the cardiac output, heart rate, systemic and pulmonary arterial pressures, right atrial and right ventricular pressures, and arterial and mixed venous blood gases and pH. Serum sodium, potassium and chloride concentrations, and plasma thromboxane B2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and prostaglandin E2 (PGE2) concentrations were measured in separate studies using similar protocols in the same horses. Running produced increases in heart rate, cardiac output, mean arterial and right ventricular pressure, and decreases in total peripheral resistance. The acid:base responses to exertion were characterised by respiratory alkalosis. Exertion did not significantly influence plasma 6-keto-PGF1 alpha or PGE2 concentrations but plasma thromboxane B2 concentrations were increased significantly by 60 minutes of exertion in the untreated horses. This exercise-induced increase in plasma thromboxane B2 concentration was inhibited by the previous administration of phenylbutazone, but phenylbutazone did not produce detectable changes in systemic haemodynamic or acid-base variables in either standing or running horses.

Background: Historically, ephedrine has been the vasopressor of choice for treatment of most cases of hypotension in obstetric patients. However, the choice of vasopressor in the parturient receiving a beta-adrenergic agent for tocolysis has not been evaluated extensively. The current study evaluated whether ephedrine or phenylephrine better restores uterine blood flow and fetal oxygenation during ritodrine infusion and epidural anesthesia-induced hypotension in gravid ewes., Methods: Fourteen chronically instrumented gravid ewes between 0.8 and 0.9 timed gestational age were used. On separate days, each animal underwent the experimental protocol with one of three agents: ephedrine, phenylephrine, and normal saline-control. The experimental protocol was as follows: (1) at time zero, intravenous infusion of ritodrine was begun; (2) at 120 min, 2% lidocaine was given epidurally to achieve a sensory level of at least T6; and (3) at 135 min, an intravenous bolus of either ephedrine, phenylephrine, or normal saline-control was given, followed by a continuous intravenous infusion of the same agent for 30 min. In the ephedrine and phenylephrine experiments, the rate of infusion was adjusted to maintain maternal mean arterial pressure close to baseline., Results: Ritodrine infusion alone significantly increased maternal heart rate and cardiac output in all three groups. Epidural anesthesia during ritodrine infusion significantly decreased maternal mean arterial pressure, heart rate, cardiac output, uterine blood flow, and fetal arterial oxygen tension for each of the three groups. Both ephedrine and phenylephrine restored maternal mean arterial pressure to baseline, as designed. Ephedrine significantly increased uterine blood flow and fetal arterial oxygen tension when compared with normal saline--control, but phenylephrine did not. Phenylephrine significantly increased uterine vascular resistance when compared with normal saline--control, but ephedrine did not., Conclusions: Although ephedrine and phenylephrine provided similar restoration of maternal mean arterial pressure, ephedrine was superior to phenylephrine in restoring uterine blood flow during ritodrine infusion and epidural anesthesia-induced hypotension in gravid ewes. Also, ephedrine, but not phenylephrine, significantly improved fetal oxygenation, when compared to normal saline--control.

The use of bicarbonate buffer in dialysis is more physiological than acetate. The aim of this prospective study was to compare the hemodynamic stability, acid-base and electrolyte balance changes in a group of 5 hospital hemodialysis (HD) patients, with 3 different dialysis fluids: one with 30 mEq/l of bicarbonate (B30), another with 34 mEq/l of bicarbonate (B34) and the last with acetate (ACE). All the patients had more than 12 months in HD. Each patient had HD treatment with one of the 3 different dialysis fluids: ACE, B30, B34. Each HD had a duration of 4 hours, with less than 5% dry weight ultrafiltration (UF) and continuous cardiac monitoring. The following clinical and laboratory data were evaluated: arterial blood pressure (BP), cardiac rate (CR), respiratory rate (RR), cardiac arrhythmias, blood urea, creatinine, sodium, potassium, magnesium, total calcium (Ca), ionised calcium (Ca++), pH, bicarbonate (HCO3-) and pCO2. Statistic analysis was performed using Student's paired t test and ANOVA with Bonferroni correction. Clinical evaluation showed a CR increase only in the ACE group (pre X = 78.4 to 4 degrees h X = 102.6 p < 0.001). Analytical results demonstrated, at the 1st h, Ca++ stability in the B30 group; in the first 30' the pH decreased in the ACE group (pre X = 7.35 to 30' X = 7.34); during HD, HCO3- was not corrected in the ACE group (pre X = 19.4 to 4th h X = 20.0); at 4th, pCO2 also decreased in this group (pre X = 34.5 to 4th h X = 28.4 p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Sixty ASA Grade II-III patients, without clinical symptoms of ventricular dysfunction and scheduled for elective bifemoral grafting for abdominal aneurysms, were allocated randomly to three equal groups to receive 150 micrograms sufentanil intravenously, epidurally or intrathecally. All patients received midazolam, vecuronium and nitrous oxide. Except for right ventricular stroke work index and pulmonary vascular resistance, all haemodynamic measurements decreased after sufentanil injection, but to the greatest extent after intravenous injection. Response to abdominal incision reversed the haemodynamic changes, although this was not accompanied by an increase in heart rate and coronary perfusion pressure after intrathecal injection. Four patients given intravenous, and four patients given epidural sufentanil required additional sufentanil after abdominal incision. Despite the changes in systemic vascular resistance and the concordant alterations in cardiac index after aortic cross-clamping and revascularization, intrathecal sufentanil provided more stability in heart rate than intravenous or epidural sufentanil. In conclusion, intrathecal sufentanil produced the most stable heart rate. Two patients in the intrathecal group developed spinal headaches post-operatively.

Based upon the hypothesis that vasopressin (antidiuretic hormone) may increase vascular resistance during ventricular fibrillation, the effects of this potent vasoconstrictor were studied in a porcine model of ventricular fibrillation. Vasopressin therapy was compared to epinephrine by randomly allocating 14 pigs to receive either 0.045 mg/kg of epinephrine (n = 7) or 0.8 U/kg of vasopressin (n = 7) after 4 min of ventricular fibrillation and 3 min of open-chest cardiopulmonary resuscitation. During cardiopulmonary resuscitation, myocardial blood flow before and 90 s and 5 min after drug administration was 57 +/- 11, 84 +/- 11, and 59 +/- 9 mL.min-1 x 100 g-1 (mean +/- SEM) in the epinephrine group, and 61 +/- 5, 148 +/- 26, and 122 +/- 22 mL.min-1 x 100 g-1 in the vasopressin group (P < 0.05 at 90 s and 5 min). At the same times, mean cardiac index was not significantly different between the groups. After drug administration, coronary venous PCO2 was significantly higher and coronary venous pH was significantly lower in the epinephrine as compared to the vasopressin group. All pigs in both groups were resuscitated and survived the 2-h observation period. We conclude that vasopressin improves vital organ perfusion during ventricular fibrillation and cardiopulmonary resuscitation. Vasopressin seems to be at least as effective as epinephrine in this pig model of ventricular fibrillation.

We reported that a second rat atrial peptide, iso-atrial natriuretic peptide (iso-rANP(1-45)) and a potential putative homologue, iso-rANP(17-45) (identical with rat brain natriuretic peptide except for one amino acid) elicited circulatory and renal responses in anesthetized rats. In the present studies, low-dose intravenous infusions of iso-rANP(1-45) (6.3-25 pmol kg-1 min-1) and iso-rANP(17-45) (12.5-50 pmol kg-1 min-1) into conscious dogs produced subtle circulatory effects compared to control studies. Relative to oxygen consumption, cardiac output was lower and total peripheral resistance higher with both iso-rANP(1-45) and iso-rANP(17-45). Heart rate tended to be slightly lower relative to control studies during peptide infusions, and the highest infusion doses caused a decrease in mean arterial pressure. Plasma protein increased and plasma osmolality decreased with iso-rANP(1-45); infusion of iso-rANP(17-45) caused a decrease in the respiratory exchange ratio. The mechanism of action of iso-rANP may have been direct, via an active receptor. However, we previously reported for these same experiments that infusion of iso-rANP(1-45) and iso-rANP(17-45) increased plasma ANP and decreased plasma renin activity. Thus, circulatory changes during infusion of iso-rANP were consistent with an indirect mechanism related to increased endogenous ANP.

This study has examined the acute haemodynamic effects of 7% sodium bicarbonate solution 1 mmol kg-1 (1.2 ml kg-1) administered into the right atrium over 5 s in 25 anaesthetized dogs allocated randomly to respiratory (arterial pH (pHa) 7.18, PaCO2 10.1 kPa (n = 8)) or metabolic acidosis (pHa 7.27, base deficit -9.0 mmol litre-1 (n = 7)) or metabolic neutrality (pHa 7.39 (n = 10)). The pHa and PaCO2 in the respiratory acidosis group differed from those in the two other groups (P < 0.01). One dog with respiratory acidosis developed progressive circulatory depression and cardiac arrest 6 min after injection of sodium bicarbonate. In the remaining seven dogs with respiratory acidosis, administration of sodium bicarbonate 1 mmol kg-1 produced transient decreases in mean arterial pressure, right ventricular dP/dt, and pulmonary blood flow, with increased right atrial pressure, followed by a gradual return of these variables to the baseline. The magnitude of reduction in pulmonary blood flow after sodium bicarbonate was greater in dogs with respiratory acidosis (P < 0.05) compared with the changes in the two other groups. The haemodynamic depression after bicarbonate was pronounced during respiratory acidosis and this may be attributed to a smaller pHa in the respiratory acidosis group, further reduction of intracellular pH, or both. It is suggested that when metabolic acidosis is corrected, bicarbonate should be administered with caution in the presence of respiratory acidosis.

Horses with colic may be endotoxaemic and subsequently develop hypotension during anaesthesia for surgical operation. The aim of this study was to evaluate the efficacy of dopamine as a means to improve cardiovascular function in anaesthetised endotoxaemic horses. Nine horses (five in group 1 and four in group 2) were anaesthetised with thiopentone and guaifenesin and anaesthesia was maintained with halothane. After approximately one hour, facial artery pressure, heart rate, pulmonary artery pressure, cardiac output, temperature, pHa, PaCO2, PaO2, base excess, packed cell volume, plasma protein concentration and white cell count were measured (time 0). Escherichia coli endotoxin was infused intravenously over 15 minutes in both groups. Group 2 horses were given an intravenous infusion of dopamine (5 micrograms kg-1 min-1) starting five minutes after the start of the endotoxin infusion and continuing for 60 minutes. Measurements were made at 15 minute intervals for 120 minutes. In group 1, one horse died during the endotoxin infusion and in two other horses mean facial artery pressures decreased to 50 mm Hg. Total pulmonary vascular resistance and packed cell volume were significantly increased. Cardiac output, cardiac index and change in mean arterial pressure were significantly greater in group 2 horses than in group 1 horses. Conversely, diastolic pulmonary artery pressure, total vascular resistance and total pulmonary resistance were significantly less in group 2 than in group 1. PaO2, base excess and white blood cell count were significantly decreased in both groups. It was concluded that dopamine improved cardiovascular function in the presence of endotoxaemia and attenuated the rate of haemoconcentration, but had no effect on the development of decreased PaO2 or metabolic acidosis.

The purpose of this study was to determine whether indomethacin alters the maternal and fetal hemodynamic response to magnesium sulfate (MgSO4) infusion and hemorrhage in gravid ewes. We studied seven chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included: 1) at time 0, indomethacin, 2 mg/kg, or vehicle only intravenously (IV) over 5 minutes; 2) at 60 minutes, MgSO4 4 g IV over 5 minutes; 3) at 65 minutes, MgSO4 infusion at 4 g/hour; 4) at 150 minutes, maternal hemorrhage, 20 mL/kg, over 60 minutes; and 5) at 215 minutes, reinfusion of maternal blood over 60 minutes. Each animal was studied with and without indomethacin. Indomethacin, but not vehicle only, transiently increased maternal and fetal mean arterial pressure (MAP), decreased maternal and fetal heart rate, and decreased maternal cardiac output. Magnesium sulfate significantly decreased uterine vascular resistance and increased uterine blood flow both with and without indomethacin. Hemorrhage significantly decreased maternal MAP, heart rate, cardiac output, and uterine blood flow in both groups. The magnitude of each change was similar between the groups. For example, at the end of hemorrhage, maternal MAP was 36 +/- 7% below baseline (P = .0001) with indomethacin and 41 +/- 2% below baseline (P = .0001) in the vehicle-only group (P = not significant between groups). Hemorrhage significantly decreased fetal heart rate, pH, and PO2, and increased fetal MAP and PCO2 in both groups. We conclude that indomethacin did not alter the maternal or fetal hemodynamic response to MgSO4 infusion and hemorrhage in gravid ewes.

Circulatory and respiratory effects of five h of constant 1.06 per cent alveolar halothane in oxygen were identified in eight healthy horses, which breathed spontaneously, were otherwise unmedicated and positioned in sternal recumbency. Only a few important significant (P less than 0.05) changes occurred with time. Total peripheral resistance was about 15 per cent lower after two hours of constant dose halothane than after 30 mins of constant dose (P less than 0.05) and accounted for the significant 10 per cent reduction in mean carotid arterial blood pressure. By 5 h, the reduction in resistance and arterial blood pressure was 20 and 25 per cent respectively. Heart rate increased progressively with time and the increase became significant at 5 h (15 per cent increase). However, the heart rate change was not large enough to alter cardiac output. There were no major time-related changes in PaO2 or PaCO2. Three of four horses recovered from anaesthesia had markedly elevated serum creatine kinase levels and clinical signs of severe post anaesthetic myopathy.

Opinions differ on the use of isotonic sodium chloride and Ringer lactate solution for extracellular volume depletion. We have compared changes in serum electrolyte concentrations and acid-base and haemodynamic status after rapid infusion of 2 litre of either isotonic sodium chloride or Ringer lactate solution in healthy volunteers. Changes within groups were small and statistically insignificant. Central venous pressure changes were associated with secretion of atrial natriuretic peptide, but this response was delayed.

Live E. coli were infused i.v. in cats to induce gastrointestinal mucosal injury and the gastric mucosa was exposed to bile and a luminal pH of 1. A gastric lesion index was calculated and intestinal injury was graded. The effects of i.v. methylprednisolone before and after induction of bacteremia were compared with those of intragastric misoprostol combined with i.v. superoxide dismutase (SOD) and catalase and with a control group. Methylprednisolone, but not misoprostol/SOD/catalase, significantly reduced the gastric lesion index (p less than 0.05). The duodenum/small intestine was significantly injured in 4/6, 2/6 and 4/6 cats in the misoprostol/SOD/catalase, methylprednisolone and control groups, respectively (NS). End gastric luminal pH was 3.9, 2.7 and 4.5 in the respective groups (p less than 0.05), with systemic arterial pH 7.15, 7.15 and 7.32 (NS). Mean arterial pressure and cardiac output were improved with methylprednisolone. Misoprostol/SOD/catalase reduced late hypotension. Pulmonary arterial pressure rose to c. 200% of basal in all groups. Methylprednisolone, but not misoprostol/SOD/catalase, thus protected the gastric mucosa from sepsis-induced gastric injury concomitant with reduced disappearance of protons from the gastric lumen, but did not significantly affect small-bowel damage. Hemodynamic responses were significantly improved in methylprednisolone-pretreated cats.

The acute hemodynamic effects of 50 mg. of the alpha- and beta-receptor blocking agent AH 5158, administered intravenously, on the systemic and pulmonary circulation were studied in 13 hypertensive patients at rest in the supine and erect positions, and during exercise, with right heart and brachial artery catheterization. AH 5158 induced a significant fall of systemic blooc pressures under all conditions, whereas the pulmonary systolic and mean pressures were lower at rest and unaltered during exercise. The left ventricular filling pressure largely remained unchanged. Blood pressure was lowered predominantly by a reduction in systemic vascular resistance together with a reduction in cardiac output. These effects were particularly pronounced in the erect position and during exercise. Cardiac output was lowered solely by the reduction of heart rate; stroke volume was unchanged or even increased. The arterial-mixed venous oxygen difference increased in the erect position and during exercise. The pattern of AH 5158-induced hemodynamic adaptation comprising a reduction of both vascular resistance and cardiac output, without evidence of significant negative inotropic action, offers a novel basis for treating hypertension with a single drug. Its pharmacological and hemodynamic profile suggests considerable potential in the treatment of hypertensive patients.

Caffeine citrate in doses of 6.96 mg/kg (equivalent to 3.50 mg/kg of caffeine) of combined maternal and fetal weight and 69.6 mg/kg (35.0 mg/kg of caffeine) was administered in 1-dl solutions intravenously over ten minutes to chronically prepared pregnant sheep. The ewes and their fetuses were monitored for cardiovascular and acid-base status. The mean maternal and fetal caffeine concentrations were simultaneously evaluated with a two-compartment pharmacokinetic model. Fetal concentrations in excess of 80% of maternal concentrations were rapidly achieved and maintained. Caffeine was undetectable in all the maternal and fetal samples obtained 48 hours after the infusion. Both doses caused similar but slight reductions in uterine blood flow without adversely affecting fetal and maternal acid-base status. Only the higher concentration of the drug produced a significant maternal and fetal tachycardia. The high fetal concentrations of caffeine were believed to be responsible for the persistent fetal tachycardia.

The maternal and fetal effects of nicotine sulfate (15 mg/10 min) upon the hemodynamics and acid-base balance were evaluated in 9 intravenous infusions to 5 chronically instrumented pregnant sheep preparations of 97-117 days of gestation. Experiments were performed from 2 to 11 days postoperatively. Maternal (n = 9) and fetal (n = 8) arterial blood samples were simultaneously drawn at 0, 10, 30 and 60 min from the start of infusion. Maternal arterial pH transiently increased from 7.47 +/- 0.01 to 7.51 +/- 0.01 units (p less than 0.01) at 10 min. Maternal arterial base deficit simultaneously fell from -2.41 +/- 1.3 to -0.3 +/- 1.1 mEq/l (p less than 0.01). Maternal blood pressure increased during the infusion from 90.8 +/- 3.8 to 118.7 +/- 5.6 mm Hg (p less than 0.005) at 10 min, remaining elevated at 30 min. Maternal heart rate transiently rose from 97 +/- 6 to 107 +/- 6 beats/min (p less than 0.01) at 1 min, returning to control levels by 10 min. 10 min into infusions a decrease in uterine blood flow was recorded as 28.7 +/- 9.0% (p less than 0.02) below preinfusion values. A gradual recovery to -8.5 +/- 2.9% ws observed (p less than 0.025) at 60 min. Fetal blood pressure also decreased transiently from 52.6 +/- 2.3 to 50.2 +/- 2.0 mm Hg (p less than 0.05) during the infusion. Fetal arterial PCO2 fell from 41.1 +/- 3.1 to 37.2 +/- 2.5 mm Hg (p less than 0.05) at 10 min. A transient increase was seen in fetal heart rate from 197 +/- 12 to 215 +/- 15 beats/min (p less than 0.05) at 30 min. No significant changes were seen in fetal arterial PO2 and O2% saturation of hemoglobin. All maternal and fetal values except uterine blood flow returned to preinfusion levels by 60 min.

The aim of this work was to study the cardiovascular effects, the acid-base balance in serum electrolytes and chlorides in 50 patients during diagnostic laparoscopy, comparing the use of CO2 and N2O for pneumoperitoneum. The CO2 group showed a significant decrease in pH, a significant increase in pCO2 and a significant decrease in pO2, while the changes in HCO3 and base change were insignificant. In the N2O group, the changes in pH, pCO2, pO2, HCO 3 and base excess were statistically insignificant. The heart rate during CO2 and N2O pneumoperitoneum revealed that both groups showed a significant increase, but in the recovery stage there was a significant increase in the CO2 group (p less than 0.025) and insignificant increase in the N2O group (p greater than 0.05). The other circulatory and electrocardiographic changes are described. CO2 pneumoperitoneum induced a significant decrease in serum chlorides but an insignificant increase in Na and an insignificant decrease in potassium, while the N2O pneumoperitoneum group did not show any significant change in serum electrolytes.

10 adult, female Göttingen minipigs were anaesthetized with isoflurane under controlled ventilation. A mixture of O2: N2O = 1:3 was used to vaporize isoflurane in an inspiratory concentration of 1.75-2.0 Vol%. Electrocardiogram, blood pressure, cardiac output and central venous pressure were continuously monitored. To determine the maximum rate of rise of intraventricular pressure (dp/dt max) as an indirect measure of myocardial contractility we placed a micro-tip manometer in the left ventricle before and during (30 min value) the experiment. Acid-base balance was controlled by collecting arterial blood samples anaerobically. We found a negative chronotropic and marked inotropic effect of isoflurane on the heart-muscle. This probably is the main cause for the depression of arterial pressure, though peripheral vasodilatation has some effect. All cardiovascular changes were fully reversible within a few minutes of completing anaesthesia. After only 15 min all animals were fully conscious and data values had returned to control levels. Because of its deficient metabolism and toxicity isoflurane seems to be well qualified for use in experimental medicine in minipigs, especially when the animals require long or multiple exposure. But we recommend the use of isoflurane in combination with a basic anaesthesia, for example NLA or Ketamine to reduce cardiovascular depression.

The effects of intravenously injected 4-dimethylaminophenol and Co2EDTA on peripheral circulation, respiration, acid-base balance, and several other physiological and biochemical parameters were studied on dogs. DMAP increased the respiratory minute volume and mean arterial pressure, diminished the lactate-to-pyruvate ratio, and induced an increase in arterial oxygen pressure caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin. A study in vitro of the fate of the oxygen during the reaction between DMAP and oxyhemoglobin showed that only 30--40% of the oxygen released by the formation of ferrihemoglobin appeared in the gas phase. Co2EDTA caused circulatory depression, hyperventilation, and metabolic acidosis resulting in a decrease in base-excess and pH. The concentrations of lactate, pyruvate, potassium, and urea nitrogen and the hemoglobin content were increased by Co2EDTA. The side effects of Co2EDTA in therapeutic doses were more serious than those of DMAP. Thus the latter is superior in the therapy of cyanide poisoning, all the more since it detoxifies more cyanide.