Metabolic effects of beta-adrenergic receptor blockade in advanced alcoholic cirrhosis.
It has been postulated that the adverse metabolic effects of beta-adrenergic blockade with propranolol in cirrhosis may be related to altered delivery and utilisation of oxygen, particularly in patients with advanced alcoholic liver disease (ALD). Consequently, in 10 patients with decompensated ALD, we assessed (a) systemic and hepatic oxygen delivery (DO2), extraction ratio (%O2E) and consumption (VO2), (b) myocardial VO2 (assessed by the rate-pressure product [RPP], together with full systemic and splanchnic haemodynamics) and (c) hepatic redox state (HRS), measured indirectly by the arterial ketone body ratio (KBR i.e. ratio of acetoacetate/beta-hydroxybutyrate), prior to and following intravenous propranolol (0.1-2 mg/kg). Results are expressed as mean +/- S.E.M. Propranolol reduced DO2 (700 +/- 33 vs. 583 +/- 32 ml/min/m2, p < 0.05) and myocardial VO2 (RPP 72 vs. 58, p < 0.05). The %O2E increased however, (18.5 +/- 1.3 vs. 22.6 +/- 1.6%, p < 0.05), resulting in unaltered systemic VO2 (127 +/- 7.3 vs. 131 +/- 6.9 ml/min/m2, p > 0.10). Similarly hepatic VO2 did not change. KBR was not altered (0.44 +/- 0.08 vs. 0.48 +/- 0.07), and in fact improved in two patients (Child C12 and C13) from 0.17 to 0.34 and 0.12 to 0.27, respectively. In conclusion, the results of this study suggest that an underlying O2 debt exists in patients with advanced alcoholic cirrhosis and that beta-adrenergic blockade with propranolol 'normalises' the O2 supply-consumption relationship resulting in more efficient O2 utilisation without adversely affecting HRS. The mechanism of this action may be related to the antagonism of beta 2-mediated arteriovenous shunting resulting in appropriate blood redistribution.
Liver Unit, King's College School of Medicine and Dentistry, Denmark Hill, London, United Kingdom.
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MacMathuna
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Vlavianos
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Wendon
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CD
Gove
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Westaby
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Williams
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007657:Ketone Bodies / Q000097:blood; D008102:Liver Circulation / Q000187:drug effects; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010313:Partial Pressure; D011433:Propranolol / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects
D007657:Ketone Bodies; D011943:Receptors, Adrenergic, beta; D002245:Carbon Dioxide; D011433:Propranolol