Protection by Plasma Proteins of the Isolated Lamb Heart Perfused with Stroma-free Hemoglobin at 38°

Abstract

Isolated lamb hearts were perfused for eight hours at 38 degrees with stroma-free hemoglobin solution (SFHS). The preservation of cardiac structure and function was studied. Control hearts perfused with blood (N = 6) developed no ventricular failure or significant weight gain (13% +/- 5), showed no alteration of cellular ultrastructure, and little interstitial edema. Hearts perfused with 7% (N = 7) or 11% (N = 5) SFHS contracted less well, became edematous (22% and 44% weight gain) and showed altered mitochondria, capillary endothelial swelling and hemoglobin extravasation into the interstitial space. The addition of 5-7% albumin to SFHS (N = 9) markedly reduced interstitial edema (weight gain 11% +/- 13), preserved mitochondria, prevented endothelial swelling, and limited transcapillary escape of hemoglobin. Thus isolated hearts perfused with SFHS develop vascular endothelial damage and an increase in capillary permeability. The addition of plasma proteins to the perfusate protects against this injury.

Prolonged (≥24 Hours) Normothermic (≥32 °C) Ex Vivo Organ Perfusion: Lessons From the Literature

“…Weight gain was also consistently reported to illustrate organ edema as a consequence of inflammation and cellular damage. Suaudeau et al 19 reported that 20% of hearts survived with stable ventricular function and observed a 13% increase in organ weight. Gamble et al 20 reported routine survival ≥24 hours with thorough measurement of ventricular function but also observed a 28% increase in organ weight.…”

“…All used cross-circulation of whole blood or plasma from secondary animals (termed paracorporeal animals) that provided a continuous supply of metabolic substrates, endocrine signaling, and clearance of toxic metabolites. [17][18][19][20] Crosscirculation designates a closed circuit that inserts the ex vivo organ in parallel with the paracorporeal systemic circulation. Within each EVHP cross-circulation system, perfusate was returned to the live animal circulation and toxins accumulating in the perfusate were therefore removed by the live animal's renal or hepatic metabolism.…”

“…Although there are 3 reports of prolonged EVHP, none demonstrated graft viability with transplantation. [17][18][19][20] Instead, left ventricular systolic pressure, heart rate, and coronary blood flow were measured as surrogates for cardiac function. Weight gain was also consistently reported to illustrate organ edema as a consequence of inflammation and cellular damage.…”

“…These yet unidentified perfusate factors are humoral constituents, as cross-circulation of plasma alone has been shown to be as beneficial as whole blood cross-circulation in other organs. 19,69,120 Until the changing plasma proteome during perfusion can be precisely detailed, successful perfusion must rely on use of continuously refreshed plasma or the isolated liver as the source of proteins.…”

“…Although she successfully preserved kidneys for 48 hours with graft viability demonstrated by transplantation, 48 others could not replicate her success using acellular hemoglobin-based oxygen carrier during ex vivo perfusion of hearts. 18,19,112 This may be explained, in part, by the finding that erythrocytes attenuate endothelial injury by scavenging xanthine oxidase-dependent hydrogen peroxide in hyperoxic environments. 113 Hemoglobin levels high enough to provide normal oxygen delivery at normothermia was common to all successful EVP.…”