Effects of dibutyryl cyclic AMP on hemodynamics and plasma catecholamine concentrations during ammonium chloride-induced metabolic acidosis in anesthetized dogs

We investigated, using anesthetized dogs, the effect of dibutyryl cyclic AMP (db-cAMP), a derivative of cyclic AMP (cAMP), on cardiovascular variants and plasma catecholamines during metabolic acidosis. These effects were also compared with those of dopamine. The db-cAMP and dopamine were infused at 200 and 20 micrograms/kg.min, respectively. Metabolic acidosis (pH 7.00, PaCO2 40 torr) was induced by the iv infusion of 1-M ammonium chloride solution (NH4Cl). In the normal acid-base state, both db-cAMP and dopamine significantly increased cardiac output and decreased systemic vascular resistance (SVR). During metabolic acidosis, db-cAMP increased cardiac output by 69 +/- 14% and decreased SVR by 36 +/- 2%, while dopamine did not produce changes in cardiac output and increased SVR. Dopamine caused an elevation of epinephrine and norepinephrine in the normal acid-base state, but db-cAMP did not. During metabolic acidosis, dopamine significantly increased the plasma concentration of epinephrine and norepinephrine, while db-cAMP significantly decreased epinephrine concentration. These results suggest that db-cAMP may have a more beneficial effect on hemodynamics compared with dopamine when therapeutic support is needed during circulatory insufficiency with severe metabolic acidosis.     

Impaired effect of dopamine on cardiac output during octopamine infusion

The hemodynamic effects of octopamine (OCT) were studied before and during dopamine (DA) infusion in six normal dogs. Before OCT infusion, DA significantly increased cardiac index (CI) from 3.24 +/- 0.20 to 4.90 +/- 0.30 L/min X m2 and significantly decreased systemic vascular resistance index (SVRI) from 3700.2 +/- 212.5 to 2618.3 +/- 156.6 dyne X sec/cm5 X m2, without changing heart rate. During OCT infusion, DA failed to increase CI or decrease SVRI; however, it significantly increased heart rate from 153.3 +/- 12.9 to 183.0 +/- 17.0 beat/min. This suppression of a DA-related increase in cardiac output may explain why DA is ineffective in those septic patients with elevated plasma OCT levels.     

Effect of reduced glutathione on hemodynamic responses and plasma catecholamine levels during metabolic acidosis

The effects of reduced glutathione (GSH) on plasma catecholamine (CA) levels and hemodynamics were studied in seven severely acidotic dogs, before and after dopamine (DA) infusion. Seven other dogs, also acidotic, received lactated Ringer's solution instead of GSH. Although metabolic acidosis decreased cardiac index (CI) in both groups, the decrease was significantly less in the GSH group. The significantly increased systemic vascular resistance index (SVRI) in the control group was suppressed by GSH infusion, although similarly high plasma CA levels were maintained in both groups. This suggests that GSH has certain vasodilating effects not related to adrenosympathetic activity. CI did not improve and DA infusion significantly increased SVRI in the control group, whereas CI increased with a mild decrease of SVRI in the GSH group. The rise of plasma norepinephrine after DA infusion was low in the GSH group compared to the increase in the control group. This study suggests that during acidosis GSH improves hemodynamics and restores the effects of DA on cardiac output.     

Hydrochloric acid infusion for treatment of metabolic alkalosis associated with respiratory acidosis

Hypercapnia due to respiratory failure can be more severe when accompanied by coexistent metabolic alkalosis. We therefore tested the hypothesis that hydrochloric acid (HCl) infusion could improve PaCO2 in 15 critically ill patients admitted with mixed respiratory acidosis and metabolic alkalosis, and a pH of between 7.35 and 7.45. HCl was infused at a constant rate of 25 mmol/h until the bicarbonate concentration decreased less than 26 mmol/L, or until the pH decreased less than 7.35 (initial pH greater than 7.40) or 7.30 (initial pH less than 7.40). Administration of 170 +/- 53 mmol of HCl decreased the bicarbonate concentration from 34 +/- 3 to 25 +/- 2 mmol/L (p less than .001), the pH from 7.41 +/- 0.03 to 7.33 +/- 0.02 (p less than .001), and the PaCO2 from 54 +/- 8 to 48 +/- 8 torr (p less than .001). Postinfusion PaCO2 could be predicted accurately from the initial status of the patients (r = .95, p less than .001) except in one patient with fixed hypercapnia. PaCO2 increased from 77 +/- 19 to 94 +/- 24 torr (p less than .001) and PaO2/PAO2 increased from 59 +/- 17 to 66 +/- 17% (p less than .001). The effects of HCl were still present 12 h after the end of the infusion. No complications related to the acid infusion were noted. These results indicate that, even in the absence of alkalemia, active correction of metabolic alkalosis by HCl infusion can improve CO2 and oxygen exchange in critically ill patients with mixed respiratory acidosis and metabolic alkalosis.     

Noninvasive measurement of tissue carbon dioxide tension using a fiberoptic conjunctival sensor: effects of respiratory and metabolic alkalosis and acidosis

To evaluate potential clinical applications of a newly developed, noninvasive fiberoptic conjunctival carbon dioxide (PcjCO2) sensor designed to measure continuously tissue PCO2 in a vascular bed supplied by the internal carotid artery, we studied the effects of graded respiratory and metabolic alkalosis and acidosis on PcjCO2 in a hemodynamically stable canine model. Respiratory changes were induced by varying the frequency of ventilation and metabolic changes were induced by incremental infusions of sodium bicarbonate and hydrochloric acid. Continuous measurement of end-tidal carbon dioxide tension (PETCO2) was also performed. During respiratory alkalosis and acidosis, PcjCO2 values correlated well with PaCO2 (r = 0.96, n = 106); linear regression analysis of PcjCO2 vs. PaCO2 produced a slope of 1.01 and a y-intercept of 3.94 over a PaCO2 range of 12 to 76 torr. The mean PcjCO2-PaCO2 gradient was 4 +/- 3 (SD) torr. PETCO2 values also correlated well with PaCO2 (r = 0.91), as well as with PcjCO2 values (r = 0.91). Both PcjCO2 and PETCO2 showed a much weaker correlation with PaCO2 during metabolic alkalosis and acidosis, partly because the variation in PaCO2 was less. Moreover, the PcjCO2-PaCO2 gradient increased during the metabolic portion of the study up to a mean of 10 +/- 8 (SD) torr during metabolic acidosis, implying a build-up and/or lack of washout of CO2 from the conjunctival tissues, despite the normal physiologic range of PaCO2 values. We conclude that in a hemodynamically stable canine model, PcjCO2 and PETCO2 values correlate well with PaCO2 during pure respiratory alkalosis and acidosis; the correlation weakens significantly, however, with metabolic alterations in tissue CO2 levels.     

The dopaminergic regulation of plasma growth hormone secretion in normal subjects

The role of endogenous dopamine (DA) on plasma GH secretion was studied using domperidone (DA receptor blocker which does not cross blood brain barrier) in 16 normal subjects. After a bolus injection of domperidone (10 mg, i.v.), plasma PRL in 11 cases rose quickly and markedly from the basal level of 9.5 +/- 1.2 ng/ml (Mean +/- S.E.) to a maximum of 76.3 +/- 10.6 ng/ml at 30 min. In contrast, plasma GH in these cases showed a delayed and slight increases to domperidone injection where the values at 90 min and 120 min (3.5 +/- 0.8 ng/ml and 3.7 +/- 1.0 ng/ml) were significantly higher than those in control study (1.2 +/- 0.2 ng/ml and 1.0 +/- 0.1 ng/ml; p less than 0.05; n = 8). Domperidone infusion (0.22 mg/min/3 hr) was performed in the remaining 5 subjects. The plasma PRL responses were similar to those in the bolus injection of domperidone. These PRL responses were not modified when L-dopa was administered 30 min after the start of iv infusion of domperidone. Plasma GH showed slight but significant increases 135 min after the infusion compared to control study (4.3 +/- 1.2 ng/ml vs. 1.0 +/- 0.1 ng/ml; p less than 0.05). By the prior infusion of domperidone plasma GH responses to L-dopa was delayed and blunted, i.e., the occurrence of elevation and peak value of GH delayed by 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Venous hypercarbia associated with severe sepsis and systemic hypoperfusion

We studied 37 patients with severe sepsis and systemic hypoperfusion to assess changes in PvCO2. Before fluid administration, the cardiac index (CI) was 2.64 +/- 0.14 L/min.m2. The PvCO2 was 38 +/- 1 torr and mixed venous pH was 7.32 +/- 0.02. The venous-arterial CO2 tension gradient (P[v-a]CO2) was 6 +/- 1 torr. After fluid administration, the CI increased to 3.45 +/- 0.14 L/min.m2 (p less than .001) and the P(v-a)CO2 decreased to 5 +/- 1 torr. The correlation between the change in CI and the change in P(v-a)CO2 was r = .42, p less than .01. P(v-a)CO2 was elevated in 19 (51%) patients before fluid administration (P[v-a]CO2 greater than 6 torr) (hypercarbic group). The P(v-a)CO2 gradient in this group was 9 +/- 1 compared with 4 +/- 1 torr in 18 patients with a normal P(v-a)CO2 gradient (p less than .001) (normocarbic group). PvCO2 was 41 +/- 2 torr in the hypercarbic group compared with 35 +/- 2 torr in the normocarbic group (p less than .05). No difference was noted in PaCO2. Venous arterial pH and HCO3- gradients were of greater magnitude in the hypercarbic group, -0.05 +/- 0.003 and 2.4 +/- 0.3 mEq/L compared to -0.02 +/- 0.004 (p less than .001) and 1.1 +/- 0.2 mEq/L (p less than .001), respectively. CI in the hypercarbic group was 2.3 +/- 0.2 compared to 3.0 +/- 0.2 L/min.m2 in the normocarbic group (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of epinephrine on intestinal oxygen supply and mucosal tissue oxygen tension in pigs

OBJECTIVE: To study the effects of increasing dosages of epinephrine given intravenously on intestinal oxygen supply and, in particular, mucosal tissue oxygen tension in an autoperfused, innervated jejunal segment. DESIGN: Prospective, randomized experimental study. SETTING: Animal research laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: Sixteen pigs were anesthetized, paralyzed, and normoventilated. A small segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension was measured by using Clark-type surface oxygen electrodes. Microvascular hemoglobin oxygen saturation and microvascular blood flow (perfusion units) were determined by tissue reflectance spectrophotometry and laser-Doppler velocimetry. Systemic hemodynamics, mesenteric-venous acid-base and blood gas variables, and systemic acid-base and blood gas variables were recorded. Measurements were performed after a resting period and at 20-min intervals during infusion of increasing dosages of epinephrine (n = 8; 0.01, 0.05, 0.1, 0.5, 1, and 2 microg x kg(-1) x min(-1)) or without treatment (n = 8). In addition, arterial and mesenteric-venous lactate concentrations were measured at baseline and at 60 and 120 mins. MEASUREMENTS AND MAIN RESULTS: Epinephrine infusion led to significant tachycardia; an increase in cardiac output, systemic oxygen delivery, and oxygen consumption; and development of lactic acidosis. Epinephrine significantly increased jejunal microvascular blood flow (baseline, 267 +/- 39 perfusion units; maximum value, 443 +/- 35 perfusion units) and mucosal oxygen tension (baseline, 36 +/- 2.0 torr [4.79 +/- 0.27 kPa]; maximum value, 48 +/- 2.8 torr [6.39 +/- 0.37 kPa]) and increased hemoglobin oxygen saturation above baseline. Epinephrine increased mesenteric venous lactate concentration (baseline, 2.9 +/- 0.6 mmol x L(-1); maximum value, 5.5 +/- 0.2 mmol x L(-1)) without development of an arterial-mesenteric venous lactate concentration gradient. CONCLUSIONS: Epinephrine increased jejunal microvascular blood flow and mucosal tissue oxygen supply at moderate to high dosages. Lactic acidosis that develops during infusion of increasing dosages of epinephrine is not related to development of gastrointestinal hypoxia.     

Studies on the relationship between plasma free fatty acids and growth hormone secretion in man

The influence of plasma free fatty acid (FFA) concentration on the secretion of human growth hormone (HGH) was investigated. (a) FFA depression was produced by means of a nicotinic acid (NA) infusion for either 1 or 5 hr in the presence of glucose-induced hyperglycemia. Controls received only saline. (b) FFA depression was also produced by a 90 min NA infusion and then rapid FFA elevation by a lipid-plus-heparin (lipid) infusion. This procedure was compared with a similar NA infusion not followed by lipid. (c) FFA elevation was produced either by a lipid or by a norepinephrine (NE) infusion and then HGH secretion was stimulated by insulin-induced hypoglycemia. Each subject in this group received both the lipid and the NE infusion on seperate days as well as two control tests (insulin alone and NE alone).Depression of FFA resulted in an increase of HGH with a lag period of approximately 2 hr. Maximal HGH rise after 1 hr NA infusion was 7.7+/-1.9 ng/ml and with 5 hr NA infusion 14.3+/-3.6 ng/ml (both significantly higher than during saline infusion, P < 0.025 and < 0.005 respectively) and occurred despite continuous hyperglycemia. Lipid infusion just before the expected HGH increase prevented the HGH response to FFA depression. HGH rise during insulin hypoglycemia (32.2+/-6.5 ng/ml) was significantly inhibited by prior FFA elevation whether achieved by lipid infusion (maximum HGH rise 11.4+/-1.6 ng/ml) or by NE infusion (maximum HGH rise 19.0+/-6.2 ng/ml).The results are suggestive of a negative feedback loop between plasma FFA and HGH secretion, of importance for subacute rather than acute changes in the plasma FFA concentration. FFA lack itself seems to be the signal for HGH release despite the lag period between FFA decrease and HGH increase. Glucose and FFA can at least not fully replace each other in their respective influence on HGH release.     

Renal effects of norepinephrine used to treat septic shock patients

Twenty-four patients with septic shock (cardiac index [CI] greater than or equal to 4 L.min-1.m-2, systemic vascular resistance index [SVRI] less than or equal to 350 dyne.sec.cm-5.m-2, systolic BP less than or equal to 90 mm Hg, oliguria less than 30 ml/h) were treated with norepinephrine (NE) infused either alone or in combination with dopamine and/or dobutamine. In all patients, NE resulted in either an increase in BP, no change, or an increase in CI and restored SVRI to the normal range. In 20 patients, normalization of systemic hemodynamics was followed by re-establishment of urine flow, decrease in serum creatinine, and increase in creatinine clearance. None of these 20 patients received low dose dopamine or furosemide. Four patients remained oliguric. Two of these four patients died and two developed acute renal failure. These findings suggest that NE infusion does not worsen renal ischemia related to hemodynamic disturbances in septic shock patients, and may have beneficial effects on renal function.     

Effects of norepinephrine on renal function in septic patients with normal and elevated serum lactate levels

Effects of iv norepinephrine (NE) on renal function were investigated retrospectively in 15 patients with hyperdynamic septic shock. All patients had either a low systolic BP less than 80 mm Hg, and/or oliguria less than 0.5 ml/kg-h. We examined their serum creatinine level (SCr), daily urine flow (UF), 24-h creatinine clearance (Ccr), and hemodynamic indices before and during NE infusion. Before NE administration, the patients were divided into those with with a serum lactate level (Lac) less than 20 mg/dl (group A, n = 9) and greater than 20 mg/dl (group B, n = 6). NE was infused continuously at rates between 0.05 and 0.24 microgram/kg.min which increased systolic BP by greater than or equal to 20 mm Hg. Cardiac index was not significantly changed in either group. In group A, NE increased both UF (p less than .05), and systemic vascular resistance index (SVRI) (p less than .01), but did not affect Ccr. In group B, NE did not increase UF nor SVRI, and decreased Ccr significantly (p less than .05). It is concluded that NE increased UF and SVRI only when Lac was in normal range; otherwise, NE reduced renal function. Thus, when administering NE to increase UF, both Lac and renal function should be monitored carefully.     

Norepinephrine and vital organ blood flow

OBJECTIVE: To test whether norepinephrine (NE) infusion at 0.4 microg kg(-1) min(-1) adversely affects regional blood flow in the normal mammalian circulation. DESIGN AND SETTING: Randomized cross-over experimental animal study in a university-affiliated physiology institute. SUBJECTS: Six merino ewes. INTERVENTIONS: Staged insertion of transit-time flow probes around the ascending aorta and circumflex coronary, superior mesenteric and left renal arteries. In conscious animals with chronically embedded flow probes randomization to either 6 h of placebo (saline) or drug (NE at 0.4 microg kg(-1) min(-1)). MEASUREMENTS AND RESULTS: Compared to placebo, NE significantly increased mean arterial pressure (84.4 vs. 103.8 mmHg), heart rate (61.0 vs. 74.6 bpm) and cardiac output (3.76 vs. 4.78 l/min). These changes were associated with an increase in coronary blood flow (24.2 vs. 37.4 ml/min) and renal blood flow (215.2 vs. 282.0 ml/min) but no change in mesenteric blood flow. The increase in renal and coronary blood flow was associated with an increase in regional conductance (regional vasodilatation), while mesenteric conductance fell (mesenteric vasoconstriction). Urine output (91+/-17 vs. 491+/-360 ml/h) and creatinine clearance (61+/-18 vs. 89+/-12 ml/min) increased during NE infusion. CONCLUSIONS: NE infusion does not induce vital organ ischaemia in the normal mammalian circulation. Furthermore, it results in a significant increase in coronary and renal blood flow with a concomitant improvement in urine output and creatinine clearance.     

CO2 reactivity and brain oxygen pressure monitoring in severe head injury

OBJECTIVE: To investigate the effect of hyperventilation on cerebral oxygenation after severe head injury. DESIGN: A prospective, observational study. SETTING: Neurointensive care unit at a university hospital. PATIENTS: A total of 90 patients with severe head injury (Glasgow Coma Scale score < or =8), in whom continuous monitoring of brain tissue oxygen pressure (PbrO2) was performed as a measure of cerebral oxygenation. INTERVENTIONS: Arterial PCO2 was decreased each day over a 5-day period for 15 mins by increasing minute volume on the ventilator setting to 20% above baseline. Arterial blood gas analysis was performed before and after changing ventilator settings. Multimodality monitoring, including PbrO2, was performed in all patients. Absolute and relative PbrO2/PaCO2 reactivity was calculated. Outcome at 6 months was evaluated according to the Glasgow Outcome Scale. MEASUREMENTS AND MAIN RESULTS: Effective hyperventilation, defined by a decrease of PaCO2 > or =2 torr (0.27 kPa), was obtained in 218 (84%) of 272 tests performed. Baseline PaCO2 averaged 32.3 +/- 4.5 torr (4.31 +/- 0.60 kPa). Average reduction in PaCO2 was 3.8 +/- 1.7 torr (0.51 +/- 0.23 kPa). PbrO2 decreased by 2.8 +/- 3.7 torr (0.37 +/- 0.49 kPa; p < .001) from a baseline value of 26.5 +/- 11.6 torr (3.53 +/- 1.55 kPa). PbrO2/PaCO2 reactivity was low on day 1 (0.8 +/- 2.3 torr [0.11 +/- 0.31 kPa]), increasing on subsequent days to 6.1 +/- 4.4 torr (0.81 +/- 0.59 kPa) on day 5. PbrO2/PaCO2 reactivity on days 1 and 2 was not related to outcome. In later phases in patients with unfavorable outcome, relative reactivity was increased more markedly, reaching statistical significance on day 5. CONCLUSIONS: Increased hyperventilation causes a significant reduction in PbrO2, providing further evidence for possible increased risk of secondary ischemic damage during hyperventilation. The low PbrO2/PaCO2 reactivity on day 1 indicates the decreased responsiveness of cerebral microvascular vessels to PaCO2 changes, caused by generalized vascular narrowing. The increasing PbrO2/PaCO2 reactivity from days 2 to 5 suggests that the risk of compromising cerebral oxygenation by hyperventilation may increase over time.     

Haemodynamic response to acute hypovolaemia, rapid blood volume expansion and adrenaline administration in an infant animal model

We performed a prospective experimental animal study in seven sedated and mechanically ventilated piglets weighing 9+/-0.8 kg, to assess the haemodynamic response to acute hypovolaemia, rapid blood volume expansion and adrenaline (epinephrine) administration in an infant animal model. Withdrawal of 20 mL/kg of blood (hypovolaemia), rapid infusion of 20 mL/kg of blood (expansion) and the administration of 0.01 mg/kg of adrenaline were made in each animal. Heart rate, mean blood pressure (MBP), central venous pressure (CVP), pulmonary capillary pressure (PCP), cardiac index (CI), systemic vascular resistance index (SVRI), left ventricular contractility (Dp/dtmax), blood volume variables, including intrathoracic blood volume index (ITBI), global end-diastolic volume (GEDVI) and extravascular lung water index (ELWI). Hypovolaemia produced a significant decrease in the pressure, volume and CI variables, with an increase in SVRI and a decrease in Dp/dtmax. After expansion, all variables returned towards normal, with persistence of the SVRI increase and Dp/dtmax decrease. Changes in the blood volume variables (ITBI and GEDVI) were larger than in the pressure variables (CVP, PCP) in the case of both hypovolaemia and expansion. Adrenaline caused a slight increase in heart rate, MBP, CVP, PCP and Dp/dtmax with a greater increase in SVRI. None of the interventions led to changes in ELWI. We conclude that acute hypovolaemia produces an increase in SVRI and a decrease in Dp/dtmax that does not return fully to normal with restoration of blood volume. ITBI and GEDVI are more sensitive to changes in blood volume than CVP and PCP. Rapid blood volume expansion and adrenaline administration do not affect extravascular lung water.     

L-arginine and endothelin receptor antagonist bosentan counteract hemodynamic effects of modified hemoglobin

Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), a nitric oxide scavenger, causes systemic and pulmonary vasoconstriction in normal and septic sheep. We studied the effect of L-arginine and the endothelin-1 (ET-1) antagonist bosentan on the PHP response to determine whether the PHP-induced vasoconstriction resulted predominantly from the action of ET-1 or solely from removal of NO. After 24 h of carrier solution (nonseptic sheep), sheep received PHP (20 mg/kg/h; n = 5), PHP plus L-arginine (at 28 h, 100 mg/kg bolus and 500 mg/kg for 1 h) plus bosentan (at 32 h, 10 mg/kg; n = 6), and only L-arginine and bosentan (n = 5). These protocols were repeated after 24 h of Pseudomonas aeruginosa (S, 6x10(6) colony-forming units/kg/h). PHP induced vasoconstriction in septic and nonseptic sheep for the duration of its infusion. In nonseptic sheep, neither L-arginine nor bosentan significantly lowered systemic (SVRI) and pulmonary (PVRI) vascular resistance and did not antagonize the PHP-induced vasoconstriction. During sepsis, SVRI fell and cardiac index (CI) rose. L-arginine and bosentan further decreased SVRI (L-arginine: 34+/-2%*, p<.05; bosentan: 35+/-5%*, p<.05) and PVRI (L-arginine: 28+/-2%*, p<.05; bosentan: 33+/-7%*, p<.05) and increased CI (L-arginine: 29+/-4%*, p<.05; bosentan: 11+/-5%, NS). Both agents antagonized the PHP-induced vasoconstriction lowering SVRI (L-arginine: 29+/-3%*, p<.05; bosentan: 26+/-5%*, p<.05) and PVRI (L-arginine: 27+/-4%*, p<.05; bosentan: 32+/-4%*, p<.05) to levels before PHP administration. Plasma ET-1 levels increased during sepsis (from 9.8+/-.2 to 15.6+/-.7* pg/mL, p<.05) and fell during PHP infusion (to 9.7+/-1.6* pg/mL, p<.05). In nonseptic sheep, ET-1 levels decreased during PHP (from 8.5+/-.6 pg/mL to 5.9+/-.6*, p<.05). Bosentan increased ET-1 levels 2.7 times higher in septic than in nonseptic sheep. We conclude that during sepsis, the NO scavenger PHP unmasks an underlying ET-1 mediated vasoconstriction, and its effect is antagonized by L-arginine and bosentan.     

Mechanical ventilation with permissive hypercapnia increases intrapulmonary shunt in septic and nonseptic patients with acute respiratory distress syndrome

OBJECTIVE: To compare the effects of conventional mechanical ventilation with low-volume, pressure-limited ventilation (LVPLV) and permissive hypercapnia on ventilation-perfusion (V/Q) distributions in patients with acute respiratory distress syndrome. We hypothesized that the advantageous cardiopulmonary effects of LVPLV would be greater in patients with sepsis than in those without sepsis. PATIENTS AND INTERVENTIONS: Twenty-two patients with acute respiratory distress syndrome were studied (group 1: 12 patients with hyperdynamic sepsis; group 2: 10 nonseptic patients). Intrapulmonary shunt (Qsp/Qt) (percentage of cardiac output), perfusion of "low" V/Q areas (percentage of cardiac output), ventilation of "high" V/Q areas (percentage of total ventilation [VE]), and deadspace ventilation (percentage of VE) were calculated from the retention/excretion data of six inert gases. Data were obtained during conventional mechanical ventilation and during LVPLV. MEASUREMENTS AND MAIN RESULTS: In group 1, LVPLV increased PaCO(0)rom 38 +/- 6 torr (5.1 +/- 0.8 kPa) to 61 +/- 12 torr (8.1 +/- 1.6 kPa). Qsp/Qt increased from 28 +/- 16% to 36 +/- 17%, whereas Pao2 (84 +/- 15 torr [11.1 +/- 2.0 kPa] vs. 86 +/- 21 torr [11.5 +/- 2.8 kPa]) and Qt (10.6 +/- 2.3 vs. 11.5 +/- 2.5 L x -1) remained unchanged and PVO(2) (40 +/- 4 [5.3 +/- 0.5 kPa] vs. 49 +/- 6 torr [6.5 +/- 0.3]) increased. In group 2, LVPLV increased PaCO(2) from 38 +/- 6 torr (5.1 +/- 0.8 kPa) to 63 +/- 11 torr (8.4 +/- 1.5 kPa). For Qsp/Qt (24 +/- 9% to 34 +/- 16%), the increase was not significant, whereas Qt (7.4 +/- 1.8 vs. 10.2 +/- 2.2 L x -1), PVO(2)(38 +/- 4 torr [5.1 +/- 0.5 kPa] vs. 50 +/- 6 mm Hg [6.7 +/- 0.8 kPa]), and PaO(2) (89 +/- 16 torr [11.9 +/- 2.1 kPa] vs. 98 +/- 19 torr [13.1 +/- 2.5 kPa]) increased. In both groups, the scatter of perfusion distribution (log SDQ) was greater than expected for normal subjects but was not different between the groups or altered by the treatments. CONCLUSIONS: In patients with acute respiratory distress syndrome, LVPLV with permissive hypercapnia, tended to increase Qsp/Qt, without a concomitant decrease of PaO(2). This occurs because, although atelectasis and increased shunt result from the low ventilatory volume, the effects on PaO(2) are offset by increased PVO(2) resulting from the hypercapnic stimulation of cardiac output. This result was independent of the presence or absence of sepsis.     

Low-dose intravenous glucagon has no effect on myocardial contractility in normal man. An echocardiographic study

In order to investigate the pathophysiological background for the increased cardiac performance described in short-term insulin-dependent diabetes, we infused glucagon intravenously in 8 healthy men at a dose of 5 ng/kg/min for 1 h and at a dose of 10 ng/kg/min for a further hour. Heart rate and blood pressure were measured and myocardial contractility assessed by echocardiography as the fractional shortening of the left ventricle and as the mean circumferential shortening velocity before the glucagon infusion (first base-line level), after the first glucagon infusion period, after the second glucagon infusion period and at 1 h after stopping the glucagon infusion (second base-line level). Plasma levels of glucagon were 79 +/- 15 ng/l, 123 +/- 76 ng/l, 381 +/- 179 ng/l and 77 +/- 22 ng/l, respectively. Heart rate decreased significantly during the first (8%, p less than 0.05) and second (6%, p less than 0.01) glucagon infusion period compared to the mean of the first and the second base-line value. Mean arterial blood pressure, fractional shortening of the left ventricle and mean circumferential shortening velocity were unchanged. We conclude that increments in plasma concentrations of glucagon to levels seen in poorly controlled diabetes does not change myocardial contractility in normal man.     

Short-term effects of phenylephrine on systemic and regional hemodynamics in patients with septic shock: a crossover pilot study

Clinical studies evaluating the use of phenylephrine in septic shock are lacking. The present study was designed as a prospective, crossover pilot study to compare the effects of norepinephrine (NE) and phenylephrine on systemic and regional hemodynamics in patients with catecholamine-dependent septic shock. In 15 septic shock patients, NE (0.82 +/- 0.689 microg x kg(-1) x min(-1)) was replaced with phenylephrine (4.39 +/- 5.23 microg x kg(-1) x min(-1)) titrated to maintain MAP between 65 and 75 mmHg. After 8 h of phenylephrine infusion treatment was switched back to NE. Data from right heart catheterization, acid-base balance, thermo-dye dilution catheter, gastric tonometry, and renal function were obtained before, during, and after replacing NE with phenylephrine. Variables of systemic hemodynamics, global oxygen transport, and acid-base balance remained unchanged after replacing NE with phenylephrine except for a significant decrease in heart rate (phenylephrine, 89 +/- 18 vs. NE, 93 +/- 18 bpm; P < 0.05). However, plasma disappearance rate (phenylephrine, 13.5 +/- 7.1 vs. NE, 16.4 +/- 8.7% x min(-1)) and clearance of indocyanine green (phenylephrine, 330 +/- 197 vs. NE, 380 +/- 227 mL x min(-1) x m(-2)), as well as creatinine clearance (phenylephrine, 81.3 +/- 78.4 vs. NE, 94.3 +/- 93.5 mL x min(-1)) were significantly decreased by phenylephrine infusion (each P < 0.05). In addition, phenylephrine increased arterial lactate concentrations as compared with NE infusion (1.7 +/- 1.0 vs. 1.4 +/- 1.1 mM; P < 0.05). After switching back to NE, all variables returned to values obtained before phenylephrine infusion except creatinine clearance and gastric tonometry values. Our results suggest that for the same MAP, phenylephrine causes a more pronounced hepatosplanchnic vasoconstriction as compared with NE.     

多巴胺合用去甲肾上腺素对内毒素休克犬血流动力学的影响

目的：观察多巴胺（DA）及去甲肾上腺素（NE）对内毒素休克犬血流动力学的影响。方法：静脉内注射脂多糖（LPS）复制犬内毒素休克模型，监测血流动力学各项指标。结果：内毒素休克后平均动脉压（MAP）、心脏指数（CI）、每搏指数（SVI）、外周血管阻力指数（SVRI）、左室作功指数（LVSWI）和以作功指数（RVSWI）均降低；NE治疗后LVSWI和RVSWI则均增高；DA治疗后LWSWI和RVSWI进一步降低；DA合用NE治疗后LVSWI和RVSWI则均增加。内毒素休克后血乳酸普遍增加，各组药物治疗后血乳酸均无显著影响。结论：LPS对外周阻力血管有直接作用；内毒素休克时DA不能提高心脏的作功能力及改善休克犬受抑制的血流动力学状态，而DA合用NE对改善休克犬心脏作功能力是一个最佳的组合。     

Brain pH effects of NaHCO3 and Carbicarb in lactic acidosis

The effects of iv sodium bicarbonate (NaHCO3) and Carbicarb, an experimental buffer, were compared in a rat model of lactic acidosis induced by controlled hemorrhage and asphyxia. Although both NaHCO3 and Carbicarb were effective at alkalinizing the arterial blood in this model, NaHCO3 administration resulted in a rise in PaCO2 where Carbicarb did not (+9 +/- 2 vs. +2 +/- 2 torr at 2 min after infusion, p less than .01). Moreover, NaHCO3 resulted in a small decrease in intracellular brain pH as measured with P-31 nuclear magnetic resonance where Carbicarb afforded intracellular brain alkalinization (-0.03 +/- 0.01 vs. +0.08 +/- 0.02 pH units at 2 min, p less than .01). If these data are confirmed clinically, Carbicarb may offer advantages over NaHCO3 under conditions of fixed or limited ventilation.