RETRACTED ARTICLE: Dobutamine increases contractility of fatigued diaphragm in dogs: The relationship between dose and diaphragmatic contractility

The dose-related effects of dobutamine (DOB) on the contractility of fatigued diaphragm were studied in 16 anesthetized, mechanically ventilated dogs. The animals were divided into two groups of eight: the control (group C) and the DOB (group D). Diaphragmatic fatigue was induced by intermittent supramaximal electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed from changes in transdiaphragmatic pressure (P_di). After the induction of diaphragmatic fatigue, P_di at low-frequency (20-Hz) stimulation decreased significantly compared with the prefatigue values (P<0.05), whereas no change in P_di was observed at high-frequency (100-Hz) stimulation. In group D, after producing fatigue, P_di at 20-Hz stimulation increased significantly with a continuous infusion of DOB (5 and 10 μg·kg⁻¹·min⁻¹) i.v. (P<0.05). The P_di at 100-Hz stimulation increased significantly with administration of DOB 10 μg·kg⁻¹·min⁻¹ i.v. (P<0.05). There was a significant correlation between dose of DOB and P_di at both stimuli (P<0.05). In group C, the speed of P_di recovery at 20-Hz stimulation was relatively slower. The integrated diaphragmatic electric activity (E_di) in each group did not change at any frequency of stimulation throughout the study. It is concluded that DOB increases the contractility of fatigued diaphragm in a dose-dependent manner.     

High-dose colforsin daropate increases diaphragmatic contractility in dogs

PURPOSE: To evaluate the effects of colforsin daropate, a water-soluble derivate known to improve contractility in fatigued canine diaphragm, at two different doses (low-dose and high-dose) on contractility of the non-fatigued diaphragm of dogs. METHODS: Twenty-four pentobarbitone-anesthetized dogs were divided into three groups of eight each: Group I received no study drug; Group II received low-dose (0.2 microg x kg-1 x min-1) colforsin daropate; Group III received high-dose (0.5 microg x kg-1 x min-1) colforsin daropate. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). RESULTS: In Group III, with an infusion of high-dose colforsin daropate, Pdi at low-frequency (20 Hz) and high-frequency (100 Hz) stimulation increased from baseline values (P < 0.05). Compared with Group I, Pdi at both stimuli increased during colforsin daropate administration in Group III (P < 0.05). In Group II, with an infusion of low- dose colforsin daropate, Pdi to each stimulus did not change. CONCLUSION: Colforsin daropate, only when administered at high-dose, increases contractility of non-fatigued diaphragm in dogs.     

Propofol decreases diaphragmatic contractility in dogs

Volatile anesthetics depress diaphragmatic muscle function; however, no data are available regarding the effect of propofol on diaphragmatic contractility. We therefore studied this effect in dogs. Pentobarbital-anesthetized animals were divided into three groups of 10 each. Group I received only maintenance fluid; Group II was infused with a subhypnotic dose of propofol (0.1-mg/kg initial dose plus 1.5-mg x kg(-1) x h(-1) maintenance dose); Group III was infused with an anesthetic dose of propofol (0.1-mg/kg initial dose plus 6.0-mg x kg(-1) x h(-1) maintenance dose). We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). With an infusion of propofol in Groups II and III, Pdi at low-frequency (20-Hz) stimulation decreased from the baseline values (P < 0.05), whereas Pdi at high-frequency (100-Hz) stimulation did not change. Compared with Group I, Pdi at 20-Hz stimulation decreased during propofol administration in Groups II and III (P < 0.05). The decrease in Pdi was more in Group III than in Group II (P < 0.05). We conclude that propofol is associated with a dose-related inhibitory effect on diaphragmatic contractility in dogs. IMPLICATIONS: Propofol is an effective IV anesthetic for the induction and maintenance of anesthesia. Subhypnotic and anesthetic doses of propofol decrease diaphragmatic contractility in dogs.     

Effect of sevoflurane on diaphragmatic contractility in dogs.

The effect of sevoflurane on diaphragmatic contractility was investigated in 12 anesthetized, mechanically ventilated dogs with the thorax opened. Animals were divided into two groups of six each: the sevoflurane and time control groups. We assessed contractility by the transdiaphragmatic pressure (Pdi) during supramaximal stimulation of the phrenic nerve at frequencies of 0.5, 10, 20, 50, and 100 Hz under quasiisometric conditions. The integrated electrical activity (Edi) of the crural and costal parts of the diaphragm (Edi cru, Edi cost) was also measured. In the sevoflurane group, diaphragmatic contractility was determined during three levels of anesthesia, specifically 0, 1.0, and 1.5 minimum alveolar anesthetic concentration (MAC). Measurements were made at the start of the stimulation (initial) and at the end of the 2-s period (2-s). Increasing the depth of sevoflurane anesthesia did not cause any significant differences in Pdi and Edi at 0.5-, 10-, and 20-Hz stimulation. By contrast, at 50- and 100-Hz stimulation, initial Pdi during 1.0 and 1.5 MAC sevoflurane exposure decreased significantly compared with the 0 MAC value (P less than 0.05). In addition, there was a statistical difference in 2-s Pdi between 1.0 and 1.5 MAC at 100-Hz stimulation (P less than 0.05). The Edi cru showed similar changes in Pdi at both measurements, whereas there was no remarkable change in Edi cost. There was no significant change either in Pdi or in Edi with respect to time in the time control group. We conclude from these results that sevoflurane impairs diaphragmatic contractility through its inhibitory effect on neuromuscular transmission, predominantly of the crural part.     

RETRACTED ARTICLE: Effect of xenon on diaphragmatic contractility in dogs

PURPOSE: This study was undertaken to examine the effect of xenon on diaphragmatic contractility in pentobarbitone- anesthetized, mechanically ventilated dogs. METHODS: Twenty-one dogs were randomly allocated to three groups (n=7 of each): Group I received oxygen 100%; Group II received xenon 30% in oxygen; Group III received xenon 60% in oxygen. Diaphragmatic contractility was assessed by measuring transdiaphragmatic pressure (Pdi) generated during supramaximal stimulation of phrenic nerves at the neck at low-frequency (20-Hz) and high-frequency (100-Hz) stimulation, after maintaining 60 min of stable condition. RESULTS: With inhalation of xenon at two different concentration (30% and 60%), no changes were observed in Pdi at either concentration. There was no difference in Pdi among the three groups. CONCLUSION: Increasing the concentration of xenon to 60% has no effect on diaphragmatic contractility in dogs. This suggests that xenon may be used safely as an anesthetic with respect to respiratory muscle function.     

Comparative effects of xenon and nitrous oxide on diaphragmatic contractility in dogs

BACKGROUND: Xenon at two different concentrations (30%, 60%) has no effect on diaphragmatic contractility. This study was undertaken to compare the effects of xenon and nitrous oxide (N2O), a commonly used and well-established gas anesthetic, on diaphragmatic contractility in dogs. METHODS: Twenty-one pentobarbitone-anesthetized dogs were randomly divided into three groups of seven each: group 1 received xenon 30% (0.25 MAC) in oxygen; group 2 received N2O 47% (0.25 MAC) in oxygen; and group 3 received N2O 60% (0.32 MAC) in oxygen. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at low- (20-Hz) and high-frequency (100-Hz) stimulation, after maintaining 60 min of stable condition. The integrated electrical activity of diaphragm (Edi) to each stimulus was measured. RESULTS: With an inhalation of xenon 30%, N2O 47%, or N2O 60%, Pdi and Edi at both stimuli did not change. No difference in Pdi or Edi was observed among the groups. CONCLUSION: When used at clinical concentration, xenon or N2O does not affect contractility and electrical activity of the diaphragm in dogs.     

The recovery profile of reduced diaphragmatic contractility induced by propofol in dogs

Propofol decreases contractility of the diaphragm, but no data are available for its effects on recovery. We studied the recovery profile of reduced diaphragmatic contractility induced by propofol in dogs. Animals were divided into 4 groups of 7 each. Group I, without fatigue, received only maintenance fluid; Group II, without fatigue, was infused with propofol; Group III, with fatigue, received no study drug; Group IV, with fatigue, was infused propofol. Propofol at an anesthetic dose (0.1 mg/kg initial dose plus 6.0 mg x kg(-1) x h(-1)) was administered for 60 min. In Groups III and IV, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at 20-Hz for 30 min. We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). In group II, Pdi at low-frequency (20-Hz) stimulation decreased to less than baseline (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. At 10 min after the end of propofol administration, Pdi at 20-Hz stimulation returned to baseline. When fatigue was established, in Groups III and IV, Pdi at 20-Hz stimulation decreased to less than baseline (P < 0.05), whereas Pdi at 100-Hz stimulation did not change. After administering propofol in Group IV, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05). At 20 min after the end of propofol administration, Pdi at 20-Hz stimulation returned to fatigued values. We conclude that reduced contractility in nonfatigued and fatigued canine diaphragm induced by propofol recovers within 20 min after the cessation of administration.     

The effect of sedative drugs on diaphragmatic contractility in dogs: propofol versus midazolam

Implications: a sedative dose (0.1 mg x kg(-1) x h(-1)) of midazolam, compared with a subhypnotic dose (1.5 mg x kg(-1) x h(-1)) of propofol, decreases the contractility of the diaphragm in dogs.     

RETRACTED ARTICLE: Dibutyryl cyclic AMP increases the contractility of fatigued diaphragm in dogs

The effects of dibutyryl cyclic AMP (DBcAMP) on the contractility of nonfatigued and fatigued diaphragms were studied in 36 anesthetized and mechanically ventilated dogs. The animals were divided into four groups. In group C₁ (n=8), dogs without fatigue received only Ringer's lactate solution. In group D₁ (n=8), dogs without fatigue were given a continuous infusion of DBcAMP 0.2 mg·kg⁻¹·min⁻¹. In groups C₂ and D₂ (n=10 each), diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. In group D₂, after producing fatigue, DBcAMP 0.2 mg·kg⁻¹·min⁻¹ was administered. In groups C₂, only Ringer's solution was administered during this period. Diaphragmatic contractility was assessed by measuring the transdiaphragmatic pressure (P_di, cmH₂O). No difference in P_di was observed in groups C₁ and D₁. After diaphragmatic fatigue in groups C₂ and D₂, P_di at low-frequency (20-Hz) stimulation decreased significantly compared with the prefatigue values (group C₂; 9.3±1.9vs 12.5±2.4, group D₂; 9.3±2.1vs 12.5±2.6; mean±SD;P<0.05), whereas no change in P_di was observed at high-frequency (100-Hz) stimulation. In group D₂, P_di at both stimuli increased significantly with an infusion of DBcAMP compared with the fatigue values (20 Hz; 13.3±3.3vs 9.3±2.1, 100 Hz; 23.4±3.6vs 21.3±3.2;P<0.05). In group C₂, the speed of recovery from fatigue was relatively slower at 20-Hz stimulation than at 100-Hz stimulation. It is concluded that DBcAMP increases the contractility of fatigued diaphragm, but that this agent does not affect the contractility of nonfatigued diaphragm.     

Dose-response characteristics of midazolam for reducing diaphragmatic contractility

A sedative dose of midazolam decreases contractility of the diaphragm, but no data are available concerning the relationship between dose and diaphragmatic contractility. We studied the dose-response characteristics of midazolam for reducing the diaphragmatic contractility in dogs. Animals were divided into three groups of eight each: Group 1 received no study drug, Group 2 was infused with a sedative dose of midazolam (0.1 mg/kg initial dose plus 0.1 mg x kg(-1) x h(-1) maintenance dose), and Group 3 was infused with an anesthetic dose of midazolam (0.1 mg/kg initial dose plus 0.5 mg x kg(-1) x h(-1) maintenance dose). We assessed the diaphragmatic contractility by transdiaphragmatic pressure (Pdi). With an infusion of midazolam in Groups 2 and 3, Pdi at low-frequency (20 Hz) and high-frequency (100 Hz) stimulation decreased from the baseline values (P < 0.05), and the integrated electrical activity of diaphragm (Edi) at 100-Hz stimulation decreased from the baseline values, whereas Edi at 20-Hz stimulation did not change. Compared with Group 1, Pdi and Edi for each stimulus decreased during midazolam infusion in Groups 2 and 3 (P < 0.05). The decrease in Pdi and Edi was more in Group 3 than in Group 2 (P < 0.05). We conclude that midazolam decreases, in a dose-dependent manner, contractility of the diaphragm in dogs.     

Dobutamine increases oxygen consumption during constant flow cardiopulmonary bypass

We have studied the effects of flow and dobutamine on systemic haemodynamic variables, oxygen delivery (DO2) and oxygen consumption (VO2) in 20 patients during cardiopulmonary bypass (CPB) with mild hypothermia (34 degrees C). In a subgroup of seven patients, we also studied the effects on gastric microcirculatory blood flow (MCF) using laser Doppler flowmetry. During CPB, measurements were made before and after two interventions: the first consisted of increasing flow from 2.4 to 3.0 litre min-1 m-2 for 10 min; the second consisted of an infusion of dobutamine at a rate of 6 micrograms kg-1 min-1 for 10 min during constant flow CPB. There were no significant differences in DO2, VO2 or haemodynamic variables between the two baseline measurements. The increase in flow raised DO2 (27%, P < 0.001), mean arterial pressure (P < 0.01) and MCF (P < 0.01), but failed to increase VO2. In contrast, dobutamine infusion increased VO2 (11%, P < 0.001) during constant flow CPB without significant changes in DO2, systemic haemodynamic variables or MCF. These results indicate that increases in VO2 during dobutamine may be flow-independent.      

Different effects of halothane and enflurane on diaphragmatic contractility in vivo

We examined the effects of halothane and enflurane on diaphragmatic contractility in 12 anesthetized, mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Animals were randomly assigned to two groups, a halothane group (n = 6) and an enflurane group (n = 6). The Pdi stimulus-frequency relationship was compared at anesthetic levels of 1, 1.5, and 2 MAC (minimum alveolar concentration) in each group. The sequence of changing anesthetic concentration was randomized. In addition, the Pdi-frequency relationship was also compared between 1 MAC of halothane and enflurane in 8 of 12 dogs. In animals anesthetized with enflurane, Pdi significantly decreased with 50- and 100-Hz stimulation in the presence of increasing MAC values, whereas Pdi at 10-Hz stimulation was not affected by the depth of anesthesia. Pdi with 20-Hz stimulation during 2 MAC enflurane also decreased significantly below Pdi levels seen at 1 and 1.5 MAC. By contrast, with halothane there was no difference in Pdi at any of the stimulation frequencies during any of the three levels of anesthesia. There was no statistical difference, however, between Pdi-frequency relationships during 1 MAC of halothane and enflurane in eight animals. From these results, we conclude that halothane does not impair diaphragmatic contractility any more than enflurane does, but enflurane decreases force generation of the diaphragm at high stimulation frequencies in a dose-related fashion. This depressant effect of enflurane occurs mainly through the impairment of neuromuscular transmission and/or membrane excitability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recovery of costal and crural diaphragmatic contractility from partial paralysis

Since the two muscles (costal and crural) that constitute the diaphragm are separate and histologically different, their individual recovery pattern from neuromuscular blockade also may be different. Therefore, we studied the recovery of force and shortening in the in vivo diaphragm from atracurium-induced neuromuscular blockade in seven pentobarbital anesthetized dogs to assess segmental differences. Transdiaphragmatic pressure (Pdi), shortening of costal and crural segments, integrated electromyogram (EMG), and tidal volume (VT) were measured during spontaneous breathing. After atracurium had reduced VT to 30% of control, breathing parameters were followed until recovered to 90% of control values. In addition, force-frequency curves generated by supramaximal tetanic stimuli of the phrenic nerve were measured. Recovery times for tidal Pdi, tidal EMG, tidal shortening, low-frequency shortening, and twitch Pdi were twice as fast as for VT (40 +/- 4 min), reflecting a slower rate of recovery of accessory inspiratory muscles. High-frequency recovery was typically slower than that of VT. During tidal breathing and tetanic stimulation, costal and crural shortening recovered simultaneously. On the other hand, comparison between costal and crural by analysis of pressure-shortening relationships showed a segmental difference (crural shortened 30% more than costal at the same Pdi), which implied reduced afterload on the crural segment. However, since shortening and pressure were linearly related during paralysis and recovery, measurements of Pdi alone can accurately reflect changes in contractile mass when heterogeneity and afterload are controlled.     

Olprinone improves diaphragmatic contractility and fatigability during abdominal sepsis in a rat model

BACKGROUND: Respiratory failure with diaphragmatic fatigability is common in patients suffering sepsis or septic shock. However, the development and progress of diaphragmatic fatigability remains poorly understood, and no method has been established to treat fatigability. In this study, we hypothesize that neutrophil activation contributes to the development of diaphragmatic fatigability. We also sought to investigate whether a phosphodiesterase inhibitor, olprinone, improves diaphragmatic fatigability associated with abdominal sepsis and inhibits an increase in myeloperoxidase activity in diaphragmatic muscle. METHODS: Male Wistar rats were randomly assigned to a sham group, coecal legation perforation group (CLP), and a phosphodiesterase inhibitor (PDE) pretreated group. At 16 h after surgical procedure, the left hemidiaphragm was removed for the measurement of diaphragmatic contractility and fatigability. In addition, for the measurement of serial changes in myeloperoxidase activity, the right hemidiaphragm was also removed at 4, 8 or 16 h after the surgical procedure in each group. RESULTS: In a septic model involving rats, we observed that diaphragmatic muscles were fatigable and myeloperoxidase activity increased. We also demonstrated that intraperitoneal administration of olprinone improves diaphragmatic fatigability and inhibits an increase in myeloperoxidase activity induced by abdominal sepsis. CONCLUSION: Olprinone represents a potential therapy for cases of respiratory failure with diaphragmatic fatigability resulting from inhibition of neutrophil activation.