Regional myocardial interstitial norepinephrine kinetics during coronary occlusion and reperfusion

Abstract

We investigated myocardial interstitial norepinephrine kinetics in both the ischemic and nonischemic regions during reperfusion after 40 min of coronary occlusion in anesthetized cats. By use of a cardiac dialysis technique, dialysate norepinephrine contents from both regions were monitored as an index of myocardial interstitial norepinephrine levels. For vehicle perfusate (n = 8), the accumulated dialysate norepinephrine level in the postischemic region decreased from 3,010 +/- 923 pg/ml at 30-40 min of occlusion to 957 +/- 178 pg/ml at 0-10 min of reperfusion and returned to near control level at 30-40 min of reperfusion. After 40 min of reperfusion, there were no significant differences in tyramine (100 micrograms/ml, norepinephrine-releasing sympathomimetic amine)-induced norepinephrine release between both regions. For perfusate containing 100 microM desipramine (neural uptake inhibitor, n = 6), at 0-10 min of reperfusion, the dialysate norepinephrine in the postischemic region did not significantly decrease. The dialysate norepinephrine then returned to near preocclusion level at 30-40 min of reperfusion. These data suggest that reperfusion rapidly returns accumulated myocardial norepinephrine to the preischemic level and neuronal norepinephrine uptake greatly contributes to this return in the early phase of reperfusion. Forty minutes of coronary occlusion cause neither norepinephrine exhaustion nor irreversible impairment of norepinephrine uptake function in nerve terminals.

Cardiac epinephrine synthesis and ischemia-induced myocardial epinephrine release

“…NE that was taken up by extraneuronal cells was metabolized mainly to normetanephrine (NMN) or 3-methoxy-4-hydroxyphenylglycol (MHPG) by catechol O-methyltransferase (COMT) [19], but high NE was partly available for EPI synthesis with PNMT. These elevated NE levels were similar to the levels of myocardial ischemic regions in our previous studies [6,24]. Therefore, EPI synthesis with PNMT may gain relevance during myocardial ischemia.…”

Microdialysis separately monitors myocardial interstitial myoglobin during ischemia and reperfusion

“…Recently, a cardiac dialysis technique has provided a powerful method for monitoring myocardial interstitial levels of low-molecular-weight compounds in the cardiac ischemic region (2,6,14,31). Furthermore, this method is suitable for distinguishing between ischemia and reperfusion responses (32). By improving the microdialysis probes with a highmolecular-mass cutoff membrane, we have extended the molecular target to high-molecular-weight peptides and proteins and monitored myocardial interstitial protein levels.…”

Determination of myocardial norepinephrine in freely moving rats using in vivo microdialysis sampling and liquid chromatography with dual-electrode amperometric detection

“…A marked increase in myocardial NE has been observed after acute myocardial ischemia [1][2][3]. A decrease in myocardial NE has been shown to accompany long-term ischemia, cardiomyopathy, and various forms of heart failure [4][5][6]. The decrease of myocardial NE appears to be not only a consequence of pathologic processes in the myocardium, but may also be a factor responsible for the increased propensity for arrhythmias [5] and for the negative effect on left ventricular contractility in congestive heart failure [7].…”

“…The use of microdialysis sampling to monitor NE in the myocardial interstitium has been previously reported [2,6,[8][9][10][11][12][13]. Most of these studies were performed in comparatively large experimental animals: cats, rabbits or pigs.…”