Hemodynamic pathogenesis of ischemic hepatic injury following cardiogenic shock/resuscitation

Post-ischemic hepatic injury is observed commonly following cardiogenic or hypovolemic shock. We evaluated the putative roles of the alpha -adrenergic sympathetic nervous system and the renin-angiotensin axis in the pathogene sis of hepatic injury following cardiogenic shock. Previous studies have ch aracterized the hepatic hemodynamic response to shock, while the relationsh ip of these hemodynamic changes to ischemic hepatic injury has not been def ined. Sustained (4 h) periods of pericardial tamponade (after mild hemorrha ge) followed by 2 h of resuscitation generated a reproducible model of card iogenic shock and consequent post-ischemic hepatic injury in anesthetized p igs. In a separate group of pigs, the alpha -adrenergic component of the sy mpathetic nervous system was ablated with phenoxybenzamine or, in other gro ups, the renin-angiotensin axis was ablated by either prior nephrectomy or, separately, by confirmed angiotensin converting enzyme inhibition with tep rotide. The hepatic injury response in each case was reevaluated. Compared to sham-shocked pigs, those subjected to tamponade alone manifested selecti ve splanchnic vasospasm and consequent biochemical and histological evidenc e of classic post-ischemic liver injury (centrilobular necrosis involving a bout a third of each hepatic lobule). These manifestations of splanchnic va sospasm and the consequent ischemic injury were not ameliorated by confirme d alpha -adrenergic blockade, but significantly attenuated by either method of prior ablation of the renin-angiotensin axis. This model of sustained c ardiogenic shock and resuscitation generates the manifestations of ischemic hepatic injury associated with selective splanchnic vasospasm, findings co nsistent with previous, short-term, hemodynamic studies, The major mediator of this response, and the consequent hepatic injury, is the selective hype rsensitivity of the mesenteric vasculature to the renin-angiotensin axis.