Effects of rolipram, pimobendan and zaprinast on ischaemia-induced dysrhythmias and on ventricular cyclic nucleotide content in the anaesthetized rat.

BACKGROUND AND OBJECTIVE: This study was designed to compare the haemodynamic, electrophysiological and pharmacodynamic effects of three selective inhibitors of the different isoenzyme forms of phosphodiesterase (PDE) on ischaemia-induced dysrhythmias in the anaesthetized rat. The drugs used were pimobendan, a selective PDE III inhibitor, rolipram, a selective PDE IV inhibitor, and zaprinast, a selective PDE V inhibitor. METHODS: The coronary artery was occluded 15 min after commencing drug administration, and myocardial ischaemia was maintained for 30 min during which the heart rate and mean arterial pressure were recorded. cAMP and cGMP were determined by radioimmunoassay. RESULTS: Pretreatment with rolipram decreased the duration of ventricular tachycardia without any change in the incidences of dysrhythmias or the mortality rate. This drug did not modify ventricular content of adenosine 3',5'-cyclic monophosphate (cAMP) or guanosine 3',5'-cyclic monophosphate (cGMP). Pimobendan (1 mg kg(-1) + 0.1 mg kg(-1) min) decreased the duration of ventricular tachycardia. This dose of pimobendan and zaprinast (1 mg kg(-1) + 0.1 mg kg(-1) min(-1)) increased the incidence rate of ventricular fibrillation following coronary artery ligation and the mortality rate. Moreover, both drugs increased cGMP in the ventricle. CONCLUSIONS: The results demonstrated that pimobendan and zaprinast increased the incidence of dysrhythmias and the mortality rate, which was accompanied by an increase in the ventricular content of cGMP. Rolipram decreased the duration of ventricular tachycardia without a change in the cyclic nucleotide content or in the mortality rate.

Combined phosphodiesterase inhibition and beta-blockade in the GI104313, decreases ischemia-induced arrhythmias in the rat.

PURPOSE: The purpose of the present study was to evaluate the effects of GI104313, a chimeric molecule containing a phosphodiesterase inhibiting pyradazinone and a blocking phenoxpropanolamine, on ischemia-induced arrhythmias in anesthetized rats. METHOD: The coronary artery was occluded 15 min after commencing drug administration and myocardial ischemia was maintained for 30 min during which the heart rate and mean blood pressure were recorded. Cyclic AMP and GMP were determined by radio-immunoassay. RESULTS: GI104313 (0.1 micromol x kg(-1) plus 0.01 micromol x kg(-1) x min(-1) or 1 micromol x kg(-1) plus 0.1 micromol x kg(-1) x min(-1)) decreased the incidence of ventricular tachycardia (86% and 75%), ventricular fibrillation (28%, P <0.01 and 12%, P <0.001) and premature ventricular beats (164 +/- 27.0 and 114 +/- 28.5, P <0.05) following coronary artery ligation, resulting in a decrease in mortality (29% and 12%, P <0.05). Changes in cyclic nucleotide concentrations have been implicated in the genesis of ischemia-induced arrhythmias. However, in the present study GI104313 did not change the concentrations of adenosine 3':5'-cyclic monophosphate (cyclic AMP) (1.0 +/- 0.07 pmol x mg(-1), 1.0 +/- 0.05 pmol x mg(-1)) or guanosine 3':5'-cyclic monophosphate (cyclic GMP) (0.025 +/- 0.008 pmol x mg(-1) protein, 0.017 +/- 0.004 pmol x mg(-1) protein) in the left ventricle during ischemia-induced arrhythmias in anesthetized rats compared to saline (0.9 +/- 0.1 pmol x mg(-1) and 0.013 +/- 0.002 pmol x m(-1), respectively). CONCLUSION: Our results demonstrate that, in rats, GI104313 induced a decrease in both incidence of arrhythmias and mortality which was not associated with changes in ventricular cyclic nucleotide content.

[Analgesic effectiveness and repercussions on the progress of labor of small doses of bupivacaine and fentanyl in continuous peridural perfusion]. / Eficacia analgésica y repercusión sobre la evolución del parto de bajas dosis de bupivacaína y fentanilo en perfusión peridural continua.

OBJECTIVES: To compare the analgesic efficacy and repercussion on labor of early administration of two different concentrations of bupivacaine/fentanyl in continuous epidural perfusion, in comparison with a control group receiving no epidural anesthesia. PATIENTS AND METHODS: One hundred fifty patients were distributed among 3 groups. Group I (n = 50) received no epidural analgesia. Group II (n = 50) and III (n = 50) received test doses of 3 ml of bupivacaine plus adrenalin 1/200,000. After 5 minutes each patient in the study groups received 13 ml of the solution assigned (group II: 0.04% bupivacaine plus adrenalin 1/2,500,000 and fentanyl 2.5 micrograms/ml; group III: 0.0625% bupivacaine plus adrenalin 1/1,600,000 and fentanyl 2 micrograms/ml). Five minutes later a perfusion of 12 ml/h-1 of the same solution was delivered until dilation was complete. RESULTS: Epidural perfusion was started at 2.5 +/- 0.93 cm of dilation (group II) and 2.3 +/- 0.92 cm (group III). There were no statistically significant differences in either duration of labor until full dilation or expulsion among the groups. Pain assessed on a visual analog scale evolved from a baseline mean of 4.5 to 5 in the three groups, reaching 8.9 +/- 0.74 (group I), 0.24 +/- 0.89 (group II) and 0.28 +/- 0.57 (group III). There were no significant differences in fetal presentation or Apgar scores among the three groups at the end of delivery. CONCLUSION: Both solutions provide good analgesia during labor with minimum undesirable side effects. Low epidural doses of bupivacaine and fentanyl started early do not affect the course of labor.