Early myocardial injury is an integral component of experimental acute liver failure – a study in two porcine models

Abstract

IntroductionThere is accumulating clinical evidence that acute liver failure may be regularly associated with myocardial injury. To test this hypothesis in a standardized experimental setting, we used two porcine models of ALF.Material and methodsIn 14 domestic pigs ALF was induced by either a) surgical devascularization of the liver (DV group, n = 7), or b) partial (70-75%) hepatectomy and ischaemia/reperfusion of the liver remnant for 150 min (I/R group, n = 7). Four additional animals constituted the sham operation group. All animals were monitored for a 12-h period, at the end of which their hearts were harvested. Plasma troponin I (cTnI) and malondialdehyde (MDA) were measured before the operation (baseline) and at 6 h and 12 h postoperatively. The harvested hearts were histologically analysed, appointing a score from 0 (no injury) to 3 (maximum injury) to selected injury indicators.ResultsIn the sham group, all cTnI measurements and total myocardial injury score were zero in all animals. In both ALF groups, plasma cTnI levels increased by the 6th and remained elevated up to the 12th postoperative hour (p < 0.01 vs. sham animals). Total myocardial injury score and total histological score revealed some extent of myocardial injury. The rise of MDA levels suggests an underlying oxidative mechanism.ConclusionsOur study provides direct evidence of early myocardial injury in the setting of acute liver failure in pigs. The mechanism of injury remains to be elucidated.

Myocardial Involvement During Ischemia-Induced Acute Liver Failure in the Pig

“…A possible subclinical injury as a result of cardiac involvement in the ALF-induced multiple organ dysfunction process cannot be excluded. Our findings support this hypothesis and are in agreement with those recently reported by Papoutsidakis et al, who detected early cTnI elevations along with histopathological findings indicative of myocardial injury in an analogous experimental model [6]. Our results are also in accordance with the clinical findings of Parekh et al, who reported that 74% of patients with ALF due to a variety of causes had elevated cTnI levels, which were associated with increased complications and a poorer outcome [5].…”

“…To our knowledge, there are limited data on the impact of ALF syndrome on myocardium [5,6]. A possible subclinical injury as a result of cardiac involvement in the ALF-induced multiple organ dysfunction process cannot be excluded.…”

“…This mechanism could also be present in ALF-associated myocardial insult, since in patients with ALF resulting from paracetamol overdose, administration of acetylcysteine increased oxygen delivery, oxygen utilization by tissue, CI, and MAP, with a positive effect on survival [17]. Oxidative mechanisms may also be involved in ALF-associated myocardial injury, according to the increased levels of malondialdehyde found in experimental models of ALF [6].…”

“…More than 60% of patients with ALF may develop systemic inflammatory syndrome progressing to multiple organ failure associated with high mortality rates [4]. Even though the multiple organ failure induced by ALF has attracted the interest of many investigators, the involvement of myocardial tissue has not received much attention [5,6], except from reports on myocardiac insult following paracetamol poisoning [7,8].…”

Acute Liver Failure Complicated with Severe Heart Failure

“…It has been previously reported that most ALF patients had significantly high levels of serum troponin I regardless of the etiology (16,17). Troponin is a specific marker of myocardial cell injury (18).…”