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PROPOFOL ENHANCES ISCHEMIC TOLERANCE OF MIDDLE-AGED RAT HEARTS

Centre for Anesthesia & Analgesia, Depts. of Anesthesia and Pharmacology & Therapeutics and Facultry of Pharmaceutical Sciences. Univ. of British Columbia, Vancouiver, BC, Canada

INTRODUCTION

Ageing is associated with increased myocardial susceptibility to ischemia-reperfusion injury (IRI) and enhanced oxidative stress. Myocardium becomes more vulnerable to IRI during middle-age ⁽¹⁾. We investigated the protective effect of propofol on IRI in isolated hearts of middle-aged rats.

METHODS

After ethical approval, we studied the hearts of young adult (10 weeks old, Y) and middle-aged rats (20 weeks old, M) assigned to propofol (P-Y, P-M) and control (C-Y, C-M) groups (n=6 each). We perfused hearts in Langendorff preparation with Krebs-Henseleit Solution(KH) at a constant flow rate of 10 ml/min (P-Y, C-Y) or 15 ml/min (P-M, C-M); with comparable initial perfusion pressures. After 10 min equilibration, we applied propofol (P-Y, P-M) for 10 min at 12 ug/ml before inducing 40 min global ischemia. During ischemia, saline(C-Y, C-M) or Propofol (P-Y, P-M) in saline was perfused through aorta at 60 µl/min. KH was perfused during 90 min of reperfusion in control groups. Propofol in KH was perfused at 12 µg/ml for the first 15 min of reperfusion, reduced to 5 µg/ml thereafter in P-Y and P-M groups. Left ventricular functions and coronary perfusion pressure was assessed. Perfusate was assayed for F₂- isoprostane after equilibration, during ischemia after the first 30 min period(T1) and during reperfusion. After 90 min reperfusion(T4), heart tissue isoprostane was measured in P-M and C-M.

RESULTS

We observed an increased latency to ischemic-contracture in P-Y, (24±4 vs C-Y, 15±2; C-M, 17.7±3 min, P<0.05) and a significantly reduced contracture after 35 min ischemia (LVEDP, 14±8 vs C-Y, 32±11; C-M, 29±9mmHg, P<0.01). No ischemic contracture was observed in P-M. There were significantly lower [isoprostane] in P-M and P-Y (24±5; 30±9pg/ml) than in C-M and C-Y (53±21; 63±26 pg/ml) at T1. At T4, the recovery of left ventricular developed pressure in P-M was greater than in P-Y (P=0.012); both were greater than in C-M and C-Y (P<0.05). Heart tissue free [isoprostane] was lower in P-M than in C-M (24±5 vs 37±6 pg/100 mg tissue, P<0.05).

DISCUSSION

Propofol enhanced ischemic tolerance of middle-aged hearts, by inhibiting the formation of isoprostane, marker of lipid peroxidation and potent vasoconstrictor.

REFERENCE

1 Circulation 95:2559-2566.

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