Prevention of the “no reflow” phenomenon in the canine heart by mioflazine

Abstract

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.

Protective activity of nifedipine and R 58735 upon damage caused by global ischemia in the guinea pig heart-lung preparation

“…Compounds like R 58735 and flunarizine exert a selective calcium overload blocking activity, as demonstrated by prevention of digitalis-induced calcium overload (16,23,27). Since excessive calcium uptake is an important feature of irreversible cellular injury (7,20,24) it is tempting to assume that a similar calcium overload blocking effect plays an important role in the protective effect of compounds like R 58735 ischemia, and this is supported by other investigators (6). Such a mechanism may prevent calcium-induced irreversible injury and cell necrosis during reperfusion.…”