NEGATIVE AND SELECTIVE EFFECTS OF PROPOFOL ON ISOLATED SWINE MYOCYTE CONTRACTILE FUNCTION IN PACING-INDUCED CONGESTIVE-HEART-FAILURE

Background: Although propofol (2-6 di-isopropylphenol) is commonly use d to induce and maintain anesthesia and sedation for surgery, systemat ic hypotension and reduced cardiac output can occur in patients with o r without intrinsic cardiac disease. The effect of propofol on myocyte contractility after the development of congestive heart failure (CHF) remains unknown. This study tested the hypothesis that propofol would have direct effects on myocyte contractile function in both healthy a nd CHF cardiac myocyte preparations. Methods: Isolated left ventricula r (LV) myocyte contractile function (shortening velocity, mu m/s) was examined in myocytes from five control pigs and in five pigs with paci ng-induced CHF (240 beats/min, for 3 weeks) in the presence of propofo l concentrations ranging from 1-6 mu g/ml. In addition, myocyte contra ctility in response to beta-adrenergic receptor stimulation (isoproter enol, 10-50 nM) in the presence of propofol (3 mu g/ml) was examined. Results: Three weeks of pacing caused LV dysfunction consistent with C HF as evidenced by increased LV end-diastolic diameter (control 3.3 +/ - 0.1 cm vs. CHF 5.6 +/- 0.2 cm; P < 0.05) and reduced LV fractional s hortening (control 34 +/- 3% vs CHF 12 +/- 2%, P < 0.05). Propofol (6 mu g/ml) caused a concentration-dependent negative effect on velocity of shortening from baseline in both control (67 +/- 2 mu m/s vs. 27 +/ - 3 mu m/s; P < 0.05) and CHF myocytes (29 +/- 1 mu m/s vs. 15 +/- 1 m u m/s; P < 0.05). Importantly, CHF myocytes were more sensitive than c ontrol myocytes to the negative effects of propofol on velocity of sho rtening at the lower concentration (1 mu g/ml). beta-adrenergic respon siveness was reduced by propofol (3 mu g/ml) in control myocytes only. Conclusions: Propofol has a direct and negative effect on basal myocy te contractile processes in the setting of CHF, which is more pronounc ed than that on healthy myocytes at reduced propofol concentrations.