The effects of Trolox, a water-soluble vitamin E analogue, in regionally ischemic, reperfused porcine hearts.
Myocardial protection by the water-soluble vitamin E analogue, Trolox, was investigated in 18 regionally ischemic, reperfused porcine hearts. The left anterior descending coronary artery was distally ligated for 45 min and was reperfused for three days. Five grams of Trolox (n = 9) were infused intravenously before coronary occlusion. Treatment was continued with an intravenous dose of 5 grams Trolox/24 hours until the end of the experiment. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was assessed by sonomicrometry. Generation of free radicals by stimulated neutrophils was evaluated by luminol-enhanced chemiluminescence. Plasma concentrations of Trolox were measured by high-performance liquid chromatography. Aside from heart rate before ischemia, global hemodynamic values including calculated left ventricular oxygen consumption did not differ significantly between the two groups. Plasma concentrations of Trolox measured 1.8 +/- 0.3 mmol/l (before ischemia), 0.96 +/- 0.13 mmol/l (before reperfusion), 0.77 +/- 0.1 mmol/l (40 min of reperfusion), and 0.08 mmol/l (end of the experiment). Generation of free radicals by stimulated neutrophils was reduced by about 30% in the treatment group before ischemia and immediately before reperfusion, but was not reduced at the end of the experiment. Risk regions (control group 19.4 +/- 6 g, treatment group 19.3 +/- 7 g) and infarct sizes (control group 69.3 +/- 8%, treatment group 69.3 +/- 12%) were almost identical. Regional systolic shortening of a control segment and of the risk region were similar in both groups before ischemia, before reperfusion, and after 45 min of reperfusion. After 3 days of reperfusion, regional systolic shortening of the reperfused myocardium of the treated group had recovered to a significantly greater extent (P = 0.027). This parameter amounted to 9 +/- 6% in the treated group and to 3 +/- 3% in the control group. Improved functional recovery was not accompanied by higher tissue concentrations of adenosine triphosphate. It is concluded that the chosen treatment with Trolox does not reduce infarct size but accelerates functional recovery. This finding suggests that the mechanisms resulting in myocardial necrosis during ischemia/reperfusion and in post-ischemic myocardial dysfunction may differ.
Klein
H H
HH
Department of Cardiology, University of Marburg, F.R.G.
Pich
S
S
Schuff-Werner
P
P
Niedmann
P
P
Blattmann
U
U
Nebendahl
K
K
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*; D002839:Chromans / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005609:Free Radicals / Q000097:blood / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008163:Luminescent Measurements; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D013552:Swine; D013610:Tachycardia / Q000503:physiopathology
D000975:Antioxidants; D002839:Chromans; D005609:Free Radicals; D000255:Adenosine Triphosphate; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid