title: Hemodynamic pathogenesis of ischemic hepatic injury following cardiogenic shock/resuscitation.
abstract: 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 pathogenesis of hepatic injury following cardiogenic shock. Previous studies have characterized the hepatic hemodynamic response to shock, while the relationship of these hemodynamic changes to ischemic hepatic injury has not been defined. Sustained (4 h) periods of pericardial tamponade (after mild hemorrhage) followed by 2 h of resuscitation generated a reproducible model of cardiogenic shock and consequent post-ischemic hepatic injury in anesthetized pigs. In a separate group of pigs, the alpha-adrenergic component of the sympathetic nervous system was ablated with phenoxybenzamine or, in other groups, the renin-angiotensin axis was ablated by either prior nephrectomy or, separately, by confirmed angiotensin converting enzyme inhibition with teprotide. The hepatic injury response in each case was reevaluated. Compared to sham-shocked pigs, those subjected to tamponade alone manifested selective splanchnic vasospasm and consequent biochemical and histological evidence of classic post-ischemic liver injury (centrilobular necrosis involving about a third of each hepatic lobule). These manifestations of splanchnic vasospasm and the consequent ischemic injury were not ameliorated by confirmed alpha-adrenergic blockade, but significantly attenuated by either method of prior ablation of the renin-angiotensin axis. This model of sustained cardiogenic shock and resuscitation generates the manifestations of ischemic hepatic injury associated with selective splanchnic vasospasm, findings consistent with previous, short-term, hemodynamic studies. The major mediator of this response, and the consequent hepatic injury, is the selective hypersensitivity of the mesenteric vasculature to the renin-angiotensin axis.
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Bailey
authors.forename: M L
authors.initials: ML
authors.lastname: Brengman
authors.forename: K C
authors.initials: KC
authors.lastname: Fuh
authors.forename: S R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: H F
authors.initials: HF
authors.lastname: Herlong
authors.forename: G B
authors.initials: GB
authors.lastname: Bulkley
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000641:Ammonia / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002305:Cardiac Tamponade / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D006439:Hemodynamics; D007511:Ischemia / Q000209:etiology* / Q000503:physiopathology; D008099:Liver / Q000098:blood supply* / Q000293:injuries*; D012084:Renin-Angiotensin System / Q000502:physiology; D012151:Resuscitation; D012770:Shock, Cardiogenic / Q000150:complications* / Q000503:physiopathology / Q000628:therapy; D013152:Splanchnic Circulation; D013552:Swine
chemical_list: D000641:Ammonia; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase