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Using different subtypes of cyclic nucleotide phosphodiesterase (PDE) isoenzymes isolated from canine left ventricle, we identified R 80122, a 1,2,3,5-tetrahydro2-oxoimidazo[2,1-b]quinazoline derivative that was a more selective and potent inhibitor of PDE type III than milrinone or enoximone. Such substances improve cardiac contraction and relaxation, elicit vasodilation, and increase cardiac output (CO). To determine the extent to which these compounds affect the contractile force of stunned myocardium, the effects of enoximone, milrinone, and R 80122 on cardiac function were compared in anesthetized dogs subjected to 15-min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion, and treated beginning 30 min after reperfusion, with the compound being studied. During occlusion, all dogs exhibited passive systolic ventricular wall bulging in the ischemic area. Thirty minutes after reperfusion, systolic wall thickening was significantly decreased in the reperfused LAD segments and remained low (at 36% of baseline) in control animals. After enoximone administration, global left ventricular (LV) function was improved with i.v. doses greater than or equal to 0.64 mg/kg. Systolic wall thickening in the ischemic myocardium was restored less than or equal to 70% of baseline at 1.25 mg/kg i.v., but this dose also induced a marked decrease in arterial pressure and an increase in heart rate (HR). Milrinone and R 80122 significantly increased global LV function and systolic wall thickening in ischemic areas at doses greater than or equal to 0.16 mg/kg i.v. At the highest doses, HR increased slightly with both compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Sexual behavior, follicular development and ovulation, and concentrations of circulating gonadotropins during the estrous cycle were studied during the summer in 7 jennies. Mean behavioral estrous length was 6.4 +/- 0.6 days (mean +/- SEM, n=19; 5.6 +/- 0.5 days preovulatory and 0.8 +/- 0.2 days post-ovulatory). Mean diestrous length was 19.3 +/- 0.6 days (n=14). Females in estrus typically showed posturing, mouth clapping, clitoral winking, urinating and tail raising. Mouth clapping began approximately one day sooner and lasted approximately one day longer than winking and tail raising, so that the total duration of clapping was significantly greater than for the other two signs. Follicular changes and concentrations of gonadotropins were determined for 14 estrous cycles (2 per jenny). The follicular end points [diameter of the largest follicle and number of large (>25 mm), medium (20-24 mm), and small follicles (<20 mm)] showed a significant day effect. The diameter of the largest follicle and the number of large follicles began to increase significantly 7 days prior to ovulation with a maximum value the day before ovulation. Medium follicles reached a maximum number 4 days prior to ovulation, and small follicles decreased significantly prior to ovulation. After ovulation, all follicular end points, except the number of small follicles, remained low for the next 12 days. Mean values of FSH were low during estrus and high during diestrus with 2 significant peaks, one 3 days and one 9 days after ovulation. In contrast, mean levels of LH were low during diestrus and high during estrus with a maximum value the day after ovulation. The LH profile showed a more prolonged gradual increase prior to ovulation, than that which has been reported for ponies and horses.