The effects of oral pretreatment with mioflazine (2.5 mg X kg-1) on regional myocardial reflow, infarct size reduction and hemodynamic recovery were studied in 24 anesthetized open-chest dogs undergoing 90 minutes of acute left anterior descending coronary artery (LAD) occlusion followed by 150 minutes of reperfusion. Regional myocardial blood flow was measured with tracer microspheres, and infarct size was determined by triphenyl tetrazolium chloride staining. Pretreatment with mioflazine resulted in a reduced diastolic aortic pressure (p less than 0.05) and an elevated cardiac output and LV dpdt max (p less than 0.05). These effects persisted throughout the experiment. In control animals (n = 12) a hyperemic reflow response was found in the perfusion area of the LAD during the first minutes of reperfusion. After 150 min of reperfusion, however, the viable myocardium of the LAD area became underperfused, and almost no reflow was found in the infarcted zones. In the animals pretreated with mioflazine (n = 12) the hyperemic response persisted throughout the reperfusion phase and the no-reflow phenomenon was prevented. Infarct size (expressed as percentage of perfusion area) tended to be smaller in this group: 23.7 +/- 12.4% versus 33.7 +/- 19.2% (p greater than 0.05). Left atrial pressure increased during LAD occlusion in both groups but normalized completely in the drug-pretreated animals (p less than 0.05). It is concluded that pretreatment with mioflazine prevents the no-reflow phenomenon after reperfusion of an evolving infarction, tends to reduce infarct size and improves hemodynamic recovery.

Animals↗

PubMedDate not supplied

A comparison of two methods for estimating the area at risk in experimental myocardial infarction.

In a canine model of coronary artery occlusion and reperfusion, we assessed the amount of myocardium at risk for necrosis using both post-mortem perfusion staining with triphenyltetrazolium-chloride (TTC) and autoradiography following in vivo injection of 141Ce microspheres. Twenty-four transverse slices of 5 dog hearts were analyzed. In the same heart slice planimetry was performed both on the calibrated colour picture taken after TTC staining (A) and on the autoradiogram (B). The values for the area at risk, as determined by both methods, were very closely correlated and almost identical: A = 0.977 B + 31.4 mm2, r = 0.99, p less than 0.001. This is in contrast to an earlier report where a different autoradiographic technique was used. In short-term experimental models of coronary artery occlusion, autoradiography delineates an area at risk, matching very closely the area at risk obtained after TTC staining.

Animals↗

PubMedDate not supplied

Oral pretreatment with mioflazine completely changes the pattern and remarkably prolongs the accumulation of nucleosides in ischemic and reperfused myocardium.

In dog myocardium, the changes in the levels of creatine phosphate, inorganic phosphate, ATP, ADP, AMP, adenosine and inosine with 8 min of ischemia and subsequent reperfusion for 2, 4, 8, 16 and 32 min have been followed. Creatine phosphate and inorganic phosphate recovered completely within a few minutes as did the energy charge. However, total nucleotides remained depressed, the decrease being compensated for by the increase in inosine levels during ischemia. There was a rapid removal of the latter with reperfusion. Low oral doses of mioflazine (2.5 mg X kg-1), given 2.5 h before LAD occlusion, did not affect the pattern of changes seen in control animals, except for the nucleosides. The drug induced a complete reversal of the adenosine to inosine ratio during ischemia and a remarkable prolongation of the accumulation within the tissue of mainly adenosine during early reperfusion and inosine afterwards. Assuming that the main action of mioflazine is through inhibition of nucleoside transport, the present results provide interesting information about the mechanism of release, metabolism and final washout of adenosine.

Adenosine↗

PubMedDate not supplied

Blood hyperviscosity in spontaneously hypertensive rats.

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Animals↗

PubMedDate not supplied

Cardiac and hemodynamic effects of intravenous R 80122, a new phosphodiesterase III inhibitor, in anesthetized and awake dogs.

R 80122 is a newly synthesized, selective phosphodiesterase III inhibitor. The cardiac and hemodynamic effects of this compound following intravenous administration were studied in closed-chest anesthetized as well as in conscious chronically instrumented dogs. The findings in the closed-chest anesthetized dogs indicate that R 80122 has positive inotropic and possibly moderate vasodilating properties [maximum increase in LV dp/dtmax/pd: 61%, and maximum decrease in systemic vascular resistance: 29% (a 12.5% decrease for the solvent)]. As a result, cardiac output maximally increased to 149% of the control value. The most striking effect of R 80122 was its positive lusitropic effect (maximal decrease in the time constant of relaxation [T] of 46%). This pronounced lusitropic effect of R 80122 can be regarded as beneficial, because of the increasing evidence that lusitropic defects play an important role in disorders related to heart failure. These effects of R 80122 were associated with only slight changes in arterial blood pressure. The effects of R 80122 lasted about 75 min after stopping the infusion. No ventricular arrhythmias were noted during and after infusion of the compound. The positive inotropic effects seen in anesthetized dogs were confirmed in conscious nonsedated dogs. It may be concluded that R 80122 has a clinically favorable cardiovascular profile for acute applications in heart failure, because its combined positive inotropic and positive lusitropic effects, and moderate vasodilating properties lead to a pronounced increase in cardiac output and only minimal changes in aortic blood pressure.

Anesthesia↗