Remote ischemic preconditioning improves tissue oxygenation in a porcine model of controlled hemorrhage without fluid resuscitation

Gal Yaniv,Yuval Heled,Gil Shimon,Shimon Firman,Elon Glassberg,Matan J Cohen ,A Berman ,Dean Nachman,Daniel Rimbrot,Baruch Batzofin ,Michael Hartal,Ruth Shaylor,Amir Shlaifer,Yitshak Kreiss,Linn Wagnert-Avraham,Ben Simon,Arik Eisenkraft,Lilach Gavish,Jacob Megreli,David Kushnir,S David Gertz

doi:10.1038/s41598-021-90470-6

Abstract

Remote ischemic preconditioning (RIPC) involves deliberate, brief interruptions of blood flow to increase the tolerance of distant critical organs to ischemia. This study tests the effects of limb RIPC in a porcine model of controlled hemorrhage without replacement therapy simulating an extreme field situation of delayed evacuation to definitive care. Twenty-eight pigs (47 ± 6 kg) were assigned to: (1) control, no procedure (n = 7); (2) HS = hemorrhagic shock (n = 13); and (3) RIPC + HS = remote ischemic preconditioning followed by hemorrhage (n = 8). The animals were observed for 7 h after bleeding without fluid replacement. Survival rate between animals of the RIPC + HS group and those of the HS group were similar (HS, 6 of 13[46%]-vs-RIPC + HS, 4 of 8[50%], p = 0.86 by Chi-square). Animals of the RIPC + HS group had faster recovery of mean arterial pressure and developed higher heart rates without complications. They also had less decrease in pH and bicarbonate, and the increase in lactate began later. Global oxygen delivery was higher, and tissue oxygen extraction ratio lower, in RIPC + HS animals. These improvements after RIPC in hemodynamic and metabolic status provide essential substrates for improved cellular response after hemorrhage and reduction of the likelihood of potentially catastrophic consequences of the accompanying ischemia.

Highlights

Remote ischemic preconditioning (RIPC) involves deliberate, brief interruptions of blood flow to increase the tolerance of distant critical organs to ischemia
In a previous study of controlled hemorrhagic shock in a large animal model, we reported that maladaptive responses across a range of cardiovascular parameters that begin early after hemorrhage may be predictive of impending death, in situations where early resuscitative treatment may be d elayed[22]
The percentages of animals that survived to the end of the 7-h follow-up period between those of the RIPC + HS group and those of the HS only group were similar (#died of total pigs: RIPC + hemorrhagic shock (HS), 4 of 8 [50%] -vs- HS, 6 of 13 [46%], p = 0.86 by chi-square)

Summary

Introduction

Remote ischemic preconditioning (RIPC) involves deliberate, brief interruptions of blood flow to increase the tolerance of distant critical organs to ischemia. Animals of the RIPC + HS group had faster recovery of mean arterial pressure and developed higher heart rates without complications They had less decrease in pH and bicarbonate, and the increase in lactate began later. DBP Diastolic blood pressure DO2 Global oxygen delivery ER Tissue oxygen extraction ratio FU Follow-up period GGT γ-Glutamyl transferase HCO3 Bicarbonate HR Heart rate HS Hemorrhagic shock INR International normalized ratio LCI Lower Confidence Interval LDH Lactic dehydrogenase MAP Mean arterial pressure MST Mean survival time PCWP Pulmonary capillary wedge pressure PT Prothrombin time PTT Partial thromboplastin time RCTs Randomized clinical trials RIFLE Risk, injury, and failure; and loss; and end-stage kidney RIPC Remote ischemic preconditioning SV Stroke volume SBP Systolic blood pressure UCI Upper confidence interval VSaO2 Mixed venous saturation WBC White blood cells. In all of these animal studies, the induced shock was followed by fluid resuscitation

Methods

Results

Conclusion