BRETSCHNEIDER SOLUTION AND TWO ANTIANGINAL DRUGS PROTECT PERIPHERAL TISSUE IN AN ANIMAL MODEL OF HEMORRHAGIC SHOCK

Abstract: Shock and subsequent resuscitation provoke ischemia-reperfusion injury. Trimetazidine (TMZ), allopurinol (ALO), and Histidine-tryptophan-ketoglutarate (HTK) solution, can protect from ischemia-reperfusion injury in chronic coronary syndromes and in transplantation. The objective of the current study is to compare, in an hemorrhagic shock and standard resuscitation animal model, organ damage parameters between placebo and treatment with TMZ, ALO or HTK. Shock was induced in Wistar rats by controlled arterial bleeding, maintaining mean arterial pressure between 38 and 42 mmHg for 60 minutes; then, drawn blood was reinfused. Animals were divided into: Sham (n=4), Control (n=6), TMZ (n=7), ALO (n=9), and HTK (n=7). At the end of the experiment, animals were sacrificed and tissue harvested. TMZ, ALO and HTK decreased histopathological damage in heart [Control: 1.72 (1.7-1.77); TMZ: 1.75 (1.72-1.79); ALO: 1.75 (1.74-1.8); HTK: 1.82 (1.78-1.85); all p<0,05], kidney [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1(1-1); all p<0,05] and intestine [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1 (0-2); all p<0,05]. Also, treatment with TMZ, ALO and HTK increased immunohisthochemical expression of thioredoxin-1 in heart [Control: 6.6 (5.6-7.4); TMZ: 9.5 (8.1-9.7); ALO: 9.1 (8.4-10.2); HTK: 14.2 (12.6-15); all p<0,05]; and kidney [Control: 4.6 (4-5.1); TMZ: 9.7 (9.3-9.9); ALO: 9.6 (9-9.9); HTK: 16.7 (16.1-17); all p<0,05]. In an experimental model of hemorrhagic shock, TMZ, ALO and HTK Solution attenuated cell damage in multiple parenchyma and increased antioxidant defenses.