Low-flow perfusion of guinea pig isolated hearts with 26 degrees C air-saturated Lifor solution for 20 hours preserves function and metabolism

Abstract

Background: Donor human hearts cannot be preserved for >5 hours between explantation and recipient implantation. A better approach is needed to preserve transplantable hearts for longer periods, ideally at ambient conditions for transport. We tested whether Lifor solution could satisfactorily preserve guinea pig isolated hearts perfused at low flow with no added oxygen at room temperature for 20 hours.

Methods: Hearts were isolated from 18 guinea pigs and perfused initially with oxygenated Krebs-Ringer (KR) solution at 37 degrees C. Hearts were then perfused with recirculated Lifor or cardioplegia (CP) solution (K(+) 15 mmol/liter) equilibrated with room air at 20% of control flow at 26 degrees C for 20 hours. Hearts were then perfused at 100% flow with KR for 2 hours at 37 degrees C.

Results: Lifor and CP arrested all hearts. During the 20-hour low-flow perfusion with Lifor coronary pressure increased by 6 +/- 2 mm Hg and percent oxygen extraction by 29 +/- 2%, whereas oxygen consumption (MVo(2)) decreased by 74 +/- 4%. Similar changes were noted for CP, except that MVo(2) was decreased by 86 +/- 7%. After 20-hour low-flow perfusion with Lifor and 2 hours of warm reperfusion with KR solution, diastolic left ventricular pressure (LVP), maximal dLVP/dt and percent oxygen extraction returned completely to baseline values, whereas heart rate returned to 80 +/- 3%, developed LVP to 76 +/- 3%, minimal dLVP/dt (relaxation) to 65 +/- 4%, coronary flow to 80 +/- 4%, oxygen consumption to 82 +/- 4% and cardiac efficiency to 85 +/- 4% of baseline values. Flow responses to adenosine and nitroprusside after Lifor treatment were 65 +/- 3% and 64 +/- 3% of their baseline values. After cardioplegia, treatment there was no cardiac activity, with a diastolic pressure of 35 +/- 14 mm Hg and a return of coronary flow to only 45 +/- 3% of baseline value.

Conclusions: Compared with a cardioplegia solution at ambient air and temperature conditions, Lifor solution is a much better medium for long-term cardiac preservation in this model.

Figure 1

(A) Cardiac temperature before, during and after treatment with air-equilibrated, recirculated CP or Lifor solution for 20 hours at 20% baseline flow. (B) Both treatment-arrested hearts; after treatment, CP treated hearts did not beat. Heart rate in the Lifor-treated group was lower than before treatment.

Figure 2

(A) Developed (systolic–diastolic) left ventricular pressure (LVP) was near zero after CP treatment and reduced after Lifor treatment. (B) Diastolic LVP was not altered during or after Lifor treatment but was markedly increased after CP treatment.

Figure 3

(A) Minimal dLVP/dt was lower after treatment with air-equilibrated, re-circulated Lifor for 20 h at 26°C at 20% baseline coronary flow. (B) Maximal dLVP/dt was fully restored after Lifor treatment. CP-treated hearts exhibited no contractility or relaxation.

Figure 4

(A) Coronary flow was natural at constant pressure (55 mm Hg) before and after treatment, and pump perfused at 20% of the natural flow during treatment. Natural coronary flow was lower than baseline after Lifor treatment but even lower after CP treatment. (B) During either treatment, perfusion pressure gradually increased at the constant coronary flow of 20% baseline, indicating increased flow resistance.

Figure 5

(A) Before Lifor treatment (0.5 hours), coronary flow increased with nitroprusside (NP) and adenosine (ADE) compared with baseline (BL). After treatment (22 hours), vasodilator responses were attenuated. After CP treatment, there were no flow responses to ADE or NP (data not shown). (B) Percent oxygen extraction increased during Lifor treatment when Po₂ was reduced from 97% to 20% (room air), but returned to baseline levels after treatment. After CP treatment, percent oxygen extraction remained high.

Figure 6

(A) Oxygen consumption decreased markedly during Lifor or CP treatment, while hearts were arrested and Po₂ was lower, but was less decreased during Lifor than during CP treatment. After treatment, oxygen consumption was lower than baseline in both groups. (B) Cardiac efficiency (heart rate · systolic — diastolic LVP/O₂ consumption) was zero during CP and Lifor treatments and was zero after CP treatment and lower than baseline after Lifor treatment.