Histidine as a protective agent in cardiac surgery and myocardia

Details Histidine as a protective agent in cardiac surgery and myocardia Histidine as a protective agent in cardiac surgery and myocardia

1992-03-13

1994-01-18

Cintins, Marianne M.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

A01N 4350, A61K 31415

Patent

active

052800385

ABSTRACT:
Histidine has been found to be efficacious in preventing ischemic/reperfusion induced myocardial injury both functionally and ultrastructurally. Isolated perfused rat hearts (n=8/group) were subjected to 30 minutes of global ischemia and 20 minutes of reperfusion. Histidine concentrations ranging from 10 to 50 mM were given throughout the experiment. During ischemia and reperfusion without histidine the contractile function and coronary flow were 59.+-.10% and 78.+-.6% of control, respectively. Perfusion with histidine (25 mM and above) resulted in significant increases in contractility (94.+-.4%) and coronary flow (92.+-.4) levels. The incidence of arrhythmias (ventricular tachycardia and ventricular fibrillation) during reperfusion was 100 percent (8/8) in the ischemic/reperfused group with an average duration of 13.23.+-.4.48 min. The addition of 25 mM histidine to the perfusion medium reduced the incidence and duration of arrhythmias significantly (mean.+-.SEM 2.25.+-.0.98 min) (P<0.01). The protective effects of histidine (25 mM and 50 mM) were significantly better than SOD/catalase/mannitol. Histidine has also been found to significantly reduce the infarct size and the occurrence of arrhythmias in vivo.

REFERENCES:
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Niall MacFarlane et al., "Rapid Communication Synergism of Histidyl . . . ," J. Moll Cell Cardiol, 23, pp. 1205-1207. 1991.
Karen P. Burton et al., "Alterations in Membrane Phospholipids . . . ", Kluwer Publishers, (1988).
Roberto Bolli et al., "Role of Oxy-Radicals in Postischemic Myocardial . . . ", Kluwer Publishers (1988).
Myung-Suk Kim et al., "O.sub.2 Free Radicals: Cause of Ischemia-reperfusion . . . ", Am. Psy. Soc., 0388-6135/1987.
CA 94(6):363498, Bretschneider et al., Protective solutions for heart and kidneys 1980.

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