Protection from diaphragmatic fatigue by nitric oxide synthase inhibitor in dogs

The role of endogenous nitric oxide (NO) in producing diaphragmatic fatigue was examined in 26 anaesthetized, mechanically ventilated dogs divided into four groups. In Group Ia (n = 5), dogs without fatigue received only Ringer's lactate solution. In Group Ib (n = 5), dogs without fatigue were given i.v. L-arginine analog N omega-nitro-L-arginine methyl ester (L-NAME) 10 mg.kg-1 to inhibit NO synthase (NOS). Groups IIa and IIb (n = 8 of each) received the same doses of i.v. lactate and L-NAME as Groups Ia and Ib effectively. Following administration of the i.v. solution, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed in each group by measuring transdiaphragmatic pressure (Pdi). No difference in Pdi was observed between Groups Ia and Ib. After the fatigue-producing period, in Group IIa, Pdi at low-frequency (20 Hz) stimulation decreased from the pre-fatigued values (P < 0.05), whereas Pdi at high-frequency (100 Hz) stimulation did not change. In Group IIb, given L-NAME before producing fatigue, Pdi at both stimuli did not change. In conclusion, L-NAME inhibits the production of diaphragmatic fatigue. This finding suggests that endogenous NO plays an important role in producing diaphragmatic fatigue.     

RETRACTED ARTICLE: Nicardipine enhances diaphragmatic fatigue

The effects of nicardipine, a calcium channel blocker, on diaphragmatic fatigue were studied in 20 anaesthetized, mechanically ventilated dogs divided into two groups: control group (Group C, n = 10) and nicardipine group (Group N, n -10). Diaphragmatic fatigue was induced by intermittent supramaximal electric stimulation to bilateral phrenic nerves at a frequency of 20 Hz for 30 min. In Group N, 5 μg · kg^?1· min^?1 nicardipine iv was infused continuously during this fatigueproducing period. Transdiaphragmatic pressure (Pdi) produced by electrical stimulation (10–100 Hz) of the phrenic nerves was used as an index of diaphragmatic contractility. After a fatigueproducing period, the Pdi in both groups decreased at low frequency (10–30 Hz) stimulation compared with pre-fatigue values (P < 0.05), whereas no change in Pdi was observed at high-frequency (50–100 Hz) stimulation. The decrease of Pdi at low-frequency stimulation was larger in Group N (P < 0.05). The integrated diaphragmatic electric activity (Edi) in both groups did not change at any frequency of stimulation throughout the experiment. We conclude that nicardipine enhances diaphragmatic fatigue.     

RETRACTED ARTICLE: Different effects of olprinone on contractility in nonfatigued and fatigued diaphragm in dogs

PURPOSE: To evaluate the effects of low-dose olprinone, a phosphodiesterase III inhibitor, on contractility and its mechanism in nonfatigued and fatigued diaphragm in dogs. METHODS: Thirty six pentobarbitone-anesthetized dogs were studied. In Group Ia (n=6), animals without fatigue, received no study drug. In Group Ib (n=6), dogs were given a bolus injection (10 ug x kg(-1)) followed by continuous infusion (0.1 microg x kg(-1) x min(-1)) of olprinone. In Groups IIa, IIb, and IIc (n=8 each), diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz applied for 30 min. After producing fatigue, Group IIa received no study drug; Group IIb was infused with olprinone (10 ug x kg(-1) loading dose plus 0.1 microg-kg(-1) min(-1) maintenance dose); Group IIc was infused with nicardipine (5 microg x kg(-1) x min(-1)) during olprinone administration. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). RESULTS: No difference in Pdi was observed between Groups Ia and Ib. After fatigue, in Groups IIa, IIb, and IIc, Pdi at low-frequency (20-Hz) stimulation decreased from prefatigued (baseline) values (P < 0.05), whereas there was no change in Pdi at high-frequency stimulation (100-Hz). In Group IIb, during olprinone administration, Pdi at both stimuli increased from fatigued values (P < 0.05). In Group IIc, the augmentation of Pdi to each stimulus in fatigued diaphragm by olprinone was abolished with an infusion of nicardipine. CONCLUSION: Low-dose olprinone does not affect contractility in nonfatigued diaphragm, but increases contractility in fatigued diaphragm via its effect on transmembrane calcium movement in dogs.     

RETRACTED ARTICLE: Contractility of fatigued diaphragm is improved by dobutamine

The effects of dobutamine (DOB) on diaphragmatic fatigue were examined in 20 anaesthetized, mechanically ventilated dogs. Animals were divided into two groups: the DOB group (n = 10) and the control group (n = 10). Diaphragmatic fatigue was induced by intermittent supramaximal electric stimulation applied to bilateral phrenic nerves at a frequency of 20 Hz for 30 min. Diaphragmatic contractility was assessed with transdiaphragmatic pressure (Pdi). After diaphragmatic fatigue, Pdi decreased at low-frequency (20 Hz) stimulation (P < 0.05), whereas the decrease was minimal at high-frequency (100 Hz) stimulation. In the DOB group, after producing fatigue, the continuous administration of 10 μg · kg^?1 · min^?1 dobutamine iv for 30 min produced an increased Pdi at both frequencies of stimulation (P < 0.05). The Pdi returned to pre-fatigue values after cessation of dobutamine administration. In the control group, the speed of recovery from fatigue was much slower at low-frequency stimulation. The integrated diaphragmatic electric activity (Edi) in the two groups did not change throughout the experiment at any frequency of stimulation. We conclude that dobutamine improves contractility in fatigued diaphragm.     

RETRACTED ARTICLE: Nicardipine inhibits amrinone-enhanced contractility in fatigued diaphragm

The purpose of this study was to examine the effect of amrinone, a bipyridine derivative, with and without nicardipine, a calcium channel blocker, on the contractility of fatigued diaphragm in dogs. Twenty dogs were divided into two groups of ten each: amrinone group (group A) and combined amrinone and nicardipine group (group AN). Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed from changes in transdiaphragmatic pressure (P_di). In group A, after producing fatigue, amrinone (0.75 mg·kg⁻¹ loading dose plus 10 μg·kg⁻¹·min⁻¹ maintenance dose) was administered iv. In group AN, nicardipine 5 μg·kg⁻¹·min⁻¹ was infused iv simultaneously with amrinone during this period. After diaphragmatic fatigue, P_di at low-frequency (10–30 Hz) stimulation decreased compared with the prefatigue values (P<0.05), whereas no change in P_di was observed at high-frequency (50–100 Hz), stimulation. The P_di at each stimulus were increased compared with the fatigued values (P<0.05) by administering amrinone, and returned to these values after this agent was discontinued. The P_di values at any frequency of stimulation did not change when amrinone was administered with nicardipine. Our results suggest that amirinone may enhance contractility in fatigued diaphragm via its effect on transmembrane calcium movement.     

RETRACTED ARTICLE: The dose-response relationship of amrinone in increasing the contractility of fatigued diaphragm in dogs

We studied the dose-related effects of amrinone on the contractility of a fatigued diaphragm in 16 anesthetized, mechanically ventilated dogs. The animals were divided into two groups: the control group (Group C,n=8) and the amrinone group (Group A,n=8). Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. The contractility of the diaphragm was assessed from changes in transdiaphragmatic pressure (P _di). After inducing fatigue,P _di at low-frequency (20 Hz) stimulation decreased significantly compared with the pre-fatigue values (P<0.05), whereas no change was observed at high-frequency (100 Hz) stimulation. In Group A, after producing fatigue,P _di at 20 Hz stimulation increased significantly with a bolus injection (0.75 mg·kg⁻¹) followed by continuous infusion of amrinone (2.5, 5 and then 10μg·kg⁻¹min⁻¹) IV (P<0.05).P _di at 100 Hz stimulation increased significantly with an administration of amrinone (10μg·kg⁻¹min⁻¹ IV (P<0.05). There was a significant positive correlation betweenP _di at both stimuli and amrinone dose (P<0.01). In Group, C, the speed of recovery ofP _di at 20 Hz stimulation was relatively slower. The integrated electric activity of the diaphragam (E _di) in each group did not change at any frequency of stimulation throughout the experiment. We conclude that amrinone exerts a dose-dependent enhancement of the contractility of a fatigued diaphragm in dogs.     

The effect of olprinone compared with milrinone on diaphragmatic muscle function in dogs.

We compared the effect of olprinone with milrinone on the contractility of fatigued diaphragms in dogs. Animals were divided into four groups of 10 each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. After producing fatigue, Group I received only maintenance fluids; Group II was given a bolus injection (50 microg/kg) followed by continuous infusion (0.5 microg x kg(-1) x min(-1)) of milrinone; Group III was infused with olprinone (10 microg/kg initial dose plus 0.3 microg x kg(-1) x min(-1) maintenance dose); Group IV was infused with nicardipine (5 microg x kg(-1) x min(-1)) during olprinone administration. After the fatigue-producing period in each group, transdiaphragmatic pressure (Pdi) at low-frequency (20 Hz) stimulation decreased from the prefatigued values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups II and III, during study drug infusion, Pdi at both stimuli increased from fatigued values (P < 0.05). The increase in Pdi was larger in Group III than in Group II (P < 0.05). In Group IV, the augmentation of Pdi by olprinone was abolished in the fatigued diaphragm with an infusion of nicardipine. We conclude that olprinone is more effective than milrinone for the improvement of contractility in he fatigued diaphragm and that the potentiating mechanism of olprinone may be closely related to the transmembrane calcium movement. IMPLICATIONS: Diaphragmatic fatigue may contribute to the development of respiratory failure. Compared with milrinone, olprinone improves the contractility in fatigued diaphragm in dogs.     

The dose-related efficacy of diltiazem for enhancing diaphragmatic fatigability in dogs

Nicardipine, a calcium channel blockade, enhances the production of diaphragmatic fatigue. We studied the dose-related effects of diltiazem, another calcium channel blockade, on diaphragmatic fatigability in dogs. Animals were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. During this fatigue-producing period, Group I received no study drug, Group II was infused with diltiazem 0.1 mg. kg(-1). h(-1), and Group III was infused with diltiazem 0.5 mg. kg(-1). h(-1). We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After the fatigue-producing period, in Group I, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups II and III, with an infusion of diltiazem, Pdi at both stimuli decreased from baseline values (P < 0.05). The decrease in Pdi to each stimulus was more in Group III than in Group II (P < 0.05). We conclude that diltiazem causes a dose-related augmentation of fatigability in the diaphragm of dogs. IMPLICATIONS: Diaphragmatic muscle fatigue is implicated as a cause of respiratory failure. Diltiazem, a calcium channel blockade, enhances diaphragmatic fatigability in dogs in a dose-related manner.     

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.     

RETRACTED ARTICLE: Effects of dobutamine on the fatigued diaphragm: A comparison with dopamine

We examined the effects of dopamine (DOA) 10 μg·kg⁻¹·min⁻¹ I.V. and dobutamine (DOB) 10 μg·kg⁻¹. min⁻¹ I.V. on the contractility of the fatigued diaphragm in 26 anesthetized, mechanically ventilated dogs. Animals were divided into two groups of 13 each: the DOA and DOB groups. Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed from changes in transdiaphragmatic pressure (P_di). After diaphragmatic fatigue, P_di at low-frequency (20 Hz) stimulation decreased significantly compared with the prefatigue value (P<0.05), whereas no change in P_di was observed at high-frequency (100 Hz) stimulation. In the fatigued diaphragm, P_di at both stimuli increased with an infusion of either DOA (P<0.05) or DOB (P<0.05). The increase of P_di at 20 Hz stimulation was significantly larger in the DOB group compared with that of the DOA group (P<0.05). In each group, P_di at both stimuli decreased after the cessation of administration. The integrated diaphragmatic electric activity (E_di) in the two groups did not change at any frequency of stimulation throughout the study. We conclude that DOB in comparison with DOA is more effective in improving the contractility of the fatigued diaphragm.     

Colforsin daropate improves contractility in fatigued canine diaphragm

We studied the effects of colforsin daropate, a water-soluble forskoline derivative, on contractility in fatigued canine diaphragm. Dogs were randomly divided into 4 groups of 8 each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Immediately after the end of a fatigue-producing period, Group 1 received no study drug, Group 2 was infused with small-dose colforsin daropate (0.2 microg. kg(-1). min(-1)), Group 3 was infused with large-dose colforsin daropate (0.5 microg. kg(-1). min(-1)), and Group 4 was infused with nicardipne (5 microg. kg(-1). min(-1)) during colforsin daropate (0.5 microg. kg(-1). min(-1)) administration. After the fatigue-producing period, in each group transdiaphragmatic pressure (Pdi) at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, during colforsin daropate administration, Pdi to each stimulus increased from fatigued values (P < 0.05). The increase in Pdi was larger in Group 3 than in Group 2 (P < 0.05). In Group 4, the augmentation of Pdi by colforsin daropate was abolished in fatigued diaphragm with an infusion of nicardipine. The integrated diaphragmatic electric activity did not change in any of the groups. We conclude that colforsin daropate improves, in a dose-dependent manner, contractility in fatigued canine diaphragm via its effect on transmembrane calcium movement. IMPLICATIONS: Diaphragmatic fatigue is implicated as a cause of respiratory failure in normal subjects and in patients with chronic obstructive lung disease. Colforsin daropate improves contractile properties during diaphragmatic fatigue.     

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.     

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.     

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.     

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.     

The dose-range effects of propofol on the contractility of fatigued diaphragm in dogs.

Diaphragmatic fatigue may contribute to the development of respiratory failure. We studied the dose-range effects of propofol on the contractility of fatigued diaphragm in dogs. Animals were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation for 30 min. Immediately after the end of a fatigue-producing period, Group 1 received no study drug; Group 2 was infused with small-dose propofol (0.1 mg/kg initial dose plus 1.5 mg x kg(-1) x h(-1) maintenance dose); Group 3 was infused with large-dose 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). After the fatigue-producing period, in each group, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, with an infusion of propofol, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05). Compared with Group 1, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05) during propofol administration in Groups 2 and 3. The decrease in Pdi was more in Group 3 than in Group 2 (P < 0.05). We conclude that propofol decreases the contractility of fatigued canine diaphragm in a dose-related fashion. IMPLICATIONS: Propofol is a widely used IV anesthetic for the induction and maintenance of general anesthesia and sedation. It decreases, in a dose-related fashion, the contractility of fatigued diaphragm in dogs.     

The effect of inhaled colforsin daropate on contractility of fatigued diaphragm in dogs

We studied the effect of inhaled colforsin daropate, a water-soluble forskolin derivative, on the contractility of fatigued diaphragm in dogs. Animals were divided into 3 groups of 8. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation applied for 30 min. Immediately after the end of the fatigue-producing period, Group 1 received inhaled vehicle, Group 2 received inhaled colforsin daropate 0.1 mg/mL, and Group 3 received inhaled colforsin daropate 0.2 mg/mL. We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After fatigue was produced, in each group, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), and there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, during colforsin daropate inhalation, Pdi at both stimuli increased from fatigued values (P < 0.05). The increase in Pdi was significantly larger in Group 3 than in Group 2. The integrated electrical activity of the diaphragm did not change in any group. We conclude that inhaled colforsin daropate causes an increase in contractility of fatigued canine diaphragm in a dose-related fashion. IMPLICATIONS: Diaphragmatic fatigue may contribute to the development of respiratory failure. Inhaled colforsin daropate improves, in a dose-dependent manner, the contractility of fatigued diaphragm in dogs.     

Midazolam-induced muscle dysfunction and its recovery in fatigued diaphragm in dogs

Midazolam, widely used for sedation and anesthesia, decreases contractility in nonfatigued diaphragm; however, its effects on contractility in fatigued diaphragm that are implicated as a cause of respiratory failure have not been established. We therefore studied the effects of midazolam on diaphragm muscle function and recovery in fatigued diaphragm. Dogs were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation for 30 min. When fatigue was established, Group I received no study drug; Group II was infused with a sedative dose (0.1 mg x kg(-1) x h(-1)) of midazolam; and Group III was infused with an anesthetic dose (0.5 mg x kg(-1) x h(-1)) of midazolam. We assessed diaphragm muscle function (contractility and electrical activity) by transdiaphragmatic pressure (Pdi) and integrated electrical activity of the diaphragm (Edi). In the presence of fatigue, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), Pdi at high-frequency (100-Hz) stimulation did not change, and Edi to each stimulus did not change. With an infusion of midazolam, in Groups II and III, Pdi at both stimuli and Edi at 100-Hz stimulation decreased from fatigued values (P < 0.05). The decrease in Pdi and Edi was more in Group III than in Group II (P < 0.05). At 60 min after the cessation of midazolam administration, in Group II, Pdi and Edi recovered from midazolam-induced values (P < 0.05) and returned to fatigued values. In Group III, Pdi and Edi did not change from midazolam-induced values. We conclude that midazolam causes, in a dose-related manner, diaphragm muscle dysfunction in fatigued canine diaphragm and that at a sedative dose, but not at an anesthetic dose, midazolam does not delay its recovery.     

Dobutamine increases diaphragmatic contractility in dogs

The effects of dobutamine on diaphragmatic contractility were studied in 24 dogs anaesthetized with secobarbital and receiving mechanical lung ventilation. The phrenic nerves were stimulated supramaximally for two seconds with electrodes placed around the fifth and sixth cervical roots when the airway was closed at the level of FRC. The stimulating frequency ranged from 10 to 100 Hz. Transdiaphragmatic pressure gradient (Pdi) generated by the electrophrenic stimulation was used as an index of diaphragmatic contractility. The electrical activity of the diaphragm during the stimulation (Edi) was also measured with needle electrodes inserted in the right hemidiaphragm percutaneously. During an infusion of dobutamine (10 micrograms.kg-1.min-1 for 20 min), Pdi increased by 15 +/- 2.1% of control value at 20 Hz stimulation (P less than 0.01), and by 13 +/- 1.2% at 100 Hz stimulation (P less than 0.01). The Edi was not altered by dobutamine infusion. This enhancement of Pdi by dobutamine was abolished by simultaneous infusion of nicardipine, a Ca-channel blocker, but was not affected by prostaglandin E1. These results suggest that dobutamine has a stimulating effect on canine diaphragmatic contraction, and this action may be related to the increased inward movement of extracellular calcium.     

RETRACTED ARTICLE: Effects of nicardipine on diaphragmatic fatigue in the dog: The relationship between dosage and fatigability

We examined the dose-related effects of nicardipine on the diaphragmatic fatigability in 24 anesthetized, mechanically ventilated dogs. Animals were divided into three groups of eight each: the control group (group C), the nicardipine 3 μg·kg⁻¹ I.V. group (group N₁) and the nicardipine 5 μg·kg⁻¹·min⁻¹ I.V. group (group N₂). Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. In groups N₁ and N₂, nicardipine was continuoulsy infused intravenously during this fatigueproducing period. Diaphragmatic contractility was assessed by changes in transdiaphragmatic pressure (P_di). After induction of diaphragmatic stimulation at low-frequency (20 Hz), P_di decreased significantly in all groups compared with the prefatigue value (P<0.05), whereas no change was observed in P_di at high-frequency (100 Hz) stimulation. The P_di at 20 Hz stimulation was significantly lower in groups N₁ and N₂ compared with that in group C (P<0.05). The decrease in P_di at 20 Hz stimulation was significantly larger in group N₂ than in group N₁ (P<0.05). The speed of recovery of P_di at 20 Hz stimulation was dose dependent. The integrated diaphragmatic electric activity (E_di) in each group did not change at any frequency of stimulation throughout the study. Our results demonstrate that nicardipine causes a dose-dependent reduction of the contractility of the fatigued diaphragm.