Midazolam versus propofol for reducing contractility of fatigued canine diaphragm

The effects of midazolam and propofol on the contractility offatigued canine diaphragm were examined. Diaphragmatic fatiguewas induced by intermittent supramaximal bilateral electrophrenicstimulation at a frequency of 20 Hz applied for 30 min.After fatigue had been induced, group I (n=10) receivedno study drug, group II (n=10) was given a propofol infusion(0.1 mg kg^–1 loading dose plus 1.5 mg kg^–1 h^–1maintenance dose) and group III (n=10) was given a midazolaminfusion (0.1 mg kg^–1 loading dose plus 0.1 mg kg^–1 h^–1maintenance dose). Diaphragmatic contractility was assessedby measuring transdiaphragmatic pressure (P_di). After the fatigue-inducingperiod in each group, P_di at low-frequency (20 Hz) stimulationwas lower than the baseline values (P<0.05), whereas no changein P_di at high-frequency (100 Hz) stimulation was observed.In group II, P_di at 20 Hz stimulation was lower than fatiguedvalues (P<0.05); P_di at 100 Hz stimulation did not change.In group III, P_di at both stimulation frequencies was lowerthan fatigued values (P<0.05). Compared with group I, P_diat 20 Hz stimulation was lower than fatigued values (P<0.05)during administration of the study drug in groups II and III.The decrease in P_di was greater in group III than in group II(P<0.05). In conclusion, midazolam compared with propofolis associated with an inhibitory effect on contractility inthe fatigued canine diaphragm. Br J Anaesth 2001; 86: 879–81     

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.     

Milrinone enhances the contractility of fatigued diaphragm in dogs: a dose-ranging study.

The dose-related effects of milrinone, a phosphodiesterase (PDE) III inhibitor, on the contractility of fatigued diaphragm were studied in dogs. Animals were divided into three groups of eight each. Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. After the production of fatigue, Group I received no study drug; Group II was infused with milrinone (50 mg kg-1 loading dose plus 0.2 mg kg-1 min-1 maintenance dose); Group III was infused with milrinone (50 mg kg-1 loading dose plus 0.5 mg kg-1 min-1 maintenance dose). Diaphragmatic contractility was assessed by measurement of transdiaphragmatic pressure. After the fatigue-producing period, transdiaphragmatic pressure at low-frequency stimulation (20-Hz) decreased from the prefatigued values in all groups (P < 0.05), whereas transdiaphragmatic pressure at high-frequency (100-Hz) stimulation did not change. Compared with Group I, transdiaphragmatic pressure to each stimulus increased during milrinone infusion in Groups II and III (P < 0.05). The increase in trans-diaphragmatic pressure was greater in Group III than in Group II (P < 0.05). It is concluded that milrinone is associated with a dose-related effect on the contractility of fatigued diaphragm in dogs.     

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: Amrinone improves contractility of fatigued diaphragm in dogs

The effects of amrinone, a bipyridine derivative, on diaphragmatic contractility and fatigue were examined in 36 anaesthetized, mechanically ventilated dogs divided into four groups. In Group Ia (n = 8), dogs without diaphragmatic fatigue were given a bolus injection (0.75 mg · kg^?1) followed by continuous infusion (10 μg · kg^?1 · min^?1) of amrinone iv. In Group Ib (n = 8), animals without fatigue received infusion only of maintenance fluid. In Group IIa (n = 10) and Group IIb (n = 10), diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. After producing fatigue, amrinone (0.75 mg · kg^?1 loading dose plus 10 μg · kg^?1 · min^?1 maintenance dose) iv were administered in Group IIa. Only maintenance fluids were administered in Group IIb during this period. Diaphragmatic contractility was assessed in each group by measuring transdiaphragmatic pressure (Pdi). Compared with Group Ib, Pdi at any stimuli in Group Ia did not differ. After producing fatigue, in Group IIa and Group IIb, Pdi decreased at low-frequency (10–30 Hz) stimulation (P < 0.05), whereas no change in Pdi was observed at high-frequency (50–100 Hz) stimulation. In Group IIa, Pdi to each stimulus increased during amrinone infusion compared with Group IIb (P < 0.05). In Group IIb, the speed of recovery from fatigue was relatively slower at low-frequency stimulation. The integrated diaphragmatic electric activity (Edi) did not change throughout the experiment. These results indicate that amrinone improves contractility in the fatigued diaphragm.     

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: 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.     

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.     

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.     

Inhaled olprinone improves contractility of fatigued canine diaphragm

Background. Diaphragmatic fatigue is implicated as a cause ofrespiratory failure. This study was undertaken to evaluate theeffects of inhaled olprinone, a newly developed phosphodiesteraseIII inhibitor, on the contractility of fatigued diaphragm indogs. Methods. Diaphragmatic fatigue was induced by intermittent supramaximalbilateral electrophrenic stimulation at a frequency of 20 Hzstimulation applied for 30 min. When fatigue was established,group I (n=8) received inhaled vehicle; group II (n=8) receivedinhaled olprinone 1 mg; group III (n=8) received inhaled olprinone2 mg. Diaphragmatic contractility was assessed by transdiaphragmaticpressure (Pdi, cm H₂O). Results. In the presence of fatigue, in each group, Pdi at low-frequency(20 Hz) stimulation decreased from baseline values (P<0.05),whereas Pdi at high-frequency (100 Hz) stimulation did not change.In groups II and III, during olprinone administration, Pdi atboth stimuli increased from fatigued values (20 Hz stimulation:group II (mean (SD)) 10.8 (1.0) to 12.5 (1.3), group III 10.9(1.7) to 15.0 (3.0); 100 Hz stimulation: group II 20.1 (1.9)to 22.6 (1.3), group III 20.6 (2.0) to 24.5 (2.0), P<0.05).The increase in Pdi was larger in group III than in group II(P<0.05). Conclusions. Inhaled olprinone produces a dose-dependent improvementin contractility of fatigued canine diaphragm. Br J Anaesth 2002; 88: 408–11     

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.     

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.     

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.     

Comparative effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility in dogs

Purpose. The present study was carried out to determine the direct effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility, and whether fentanyl would enhance the myocardial depression caused by propofol. Method. The anesthetics were injected directly into the circuit that supplied blood to the left circumflex coronary artery (LCX) in anesthetized open-chest dogs. Myocardial contractility was evaluated from measurements of percent segmental shortening (%SS). Results. Etomidate, ketamine, and propofol significantly reduced %SS in a dose-dependent manner. The %SS values with 1.6 and 3.2 mg of etomidate were similar to those with 3.2 and 6.4 mg of ketamine, respectively, and the %SS value with 6.4 mg of propofol was similar to those with 3.2 and 6.4 mg of ketamine. Fentanyl alone had no effects on myocardial performance and did not influence the effect of propofol on %SS. Conclusion. On the basis of clinical doses, the direct myocardial depressant effect of ketamine is more than twice as potent as that of etomidate and slightly more than that of propofol. Fentanyl has no inotropic effect and does not enhance the direct myocardial depressant effect of propofol. Received for publication on June 22, 1998; accepted on October 14, 1998     

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.     

The effects of propofol and midazolam on canine left ventricular contractility

Pronounced decrease in arterial blood pressure during propofol or midazolam infusion for sedation of critically ill patients, has raised the possibility that they have a direct negative inotropic action. Accordingly, in the current study, changes in the left ventricular (LV) contractility were examined during i.v. infusion of these two sedatives in anesthetized dogs. Myocardial contractility was assessed with the slope (Ees) of the LV end-systolic pressure-volume relationship and the slope (Msw) of the LV end-diastolic volume-stroke work relationship. Propofol was administered at 5, 10 and 20 mg.kg-1.h-1, and midazolam at 0.3, 0.6 and 1.2 mg.kg-1.h-1 over 60 min. Propofol caused dose-dependent decrease in Ees (55 +/- 7 during the low dose to 27 +/- 3 mmHg.ml-1 during the high dose, P < 0.05) and in Msw (91 +/- 8 during the low dose to 67 +/- 6 erg.cm-3 x 10(-3) during the high dose, P < 0.05). Midazolam, also, decreased in Ees and Msw significantly. No significant differences were observed between three different doses of midazolam. It is concluded that propofol shows the dose-dependent inhibition of myocardial contractility, but midazolam induces dose-independent inhibition.     

Direct effects of propofol on myocardial contractility in in situ canine hearts.

The pronounced decrease in arterial blood pressure evident during anesthetic induction with propofol has raised the possibility that propofol has a direct negative inotropic effect. Previous attempts to evaluate this mechanism in vivo have been inconclusive because of confounding variables associated with intravenous administration of propofol. Accordingly, in the current study, steady-state changes in myocardial contractility and related hemodynamic parameters were assessed during intracoronary infusions of propofol in seven open-chest dogs anesthetized with fentanyl and midazolam. The left anterior descending coronary artery (LAD) was cannulated and perfused at controlled pressure (100 mmHg) with normal arterial blood. In LAD-perfused myocardium, contractility was evaluated from measurements of percent segmental shortening (%SS) obtained with ultrasonic crystals. Coronary blood flow in LAD was measured electromagnetically and used to calculate myocardial oxygen consumption (MVO2; Fick principle) and coronary propofol concentration. Propofol was infused into the LAD at 150, 300, 600, and 1,200 micrograms/min (P-150, P-300, P-600, P-1,200). These infusion rates yielded calculated blood concentrations of 7 +/- 1, 15 +/- 1, 26 +/- 2, and 50 +/- 5 micrograms.ml-1, respectively. The calculated blood concentrations at P-150 were in the clinical range, whereas those at P-300, P-600, and P-1,200 were supratherapeutic. P-150 had no effect on %SS, whereas higher infusion rates caused decreases in %SS. Changes in MVO2 by propofol generally paralleled changes in %SS. At P-150 and P-300, coronary blood flow was proportional to MVO2, whereas at P-600 and P-1,200, coronary blood flow was in excess of the prevailing MVO2, resulting in increased coronary venous oxygen tension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of diltiazem on contractility and electromyographic activity of non-fatigued diaphragm in dogs

BACKGROUND: No data are available for diltiazem on muscle function (contractility and electomyographic activity) of non-fatigued diaphragm. METHODS: Eighteen pentobarbital-anesthetized dogs were divided into 3 groups of 6 each: Group I received no drug; Group II received small-dose of diltiazem (0.1 mg.kg-1.h-1); Group III received large-dose of diltiazem (0.5 mg.kg-1.h-1). Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi), the difference between esophageal and gastric pressures. Diaphragmatic electromyographic activity (Edi) was measured by means of electrodes placed at the anterior portion of the crural and costal parts of the diaphragm. After measuring baseline values of Pdi and Edi at 20 Hz and 100 Hz stimulation, the study drug was administered for 30 min. RESULTS: With infusion of diltiazem, Pdi and Edi to each stimulus did not change in Groups II and III. In Group I, these variables also showed no change. CONCLUSIONS: Diltiazem, at doses below 0.5 mg.kg-1.h-1, does not affect contractility and electromyographic activity of non-fatigued canine diaphragm.