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PROPOFOL PROVIDES CARDIOPROTECTION IN ISCHEMIC REPERFUSED RAT HEARTS AND ENHANCES THE PROTECTION OF THE Na-H EXCHANGE INHIBITOR HOE 642

Mathur, Sanjiv MD; Karmazyn, Morris PhD

doi: 10.1097/00000539-199802001-00085
Abstracts of Posters Presented at the International Anesthesia Research Society; 72nd Clinical and Scientific Congress; Orlando, FL; March 7-11, 1998: Cardiovascular Anesthesia
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Depts. of Pharmacology/Toxicology and Anaesthesia, University of Western Ontario, London, Ontario, CANADA.

Abstract S85

INTRODUCTION: Na-H exchange (NHE) inhibitors have been identified as effective cardioprotective agents against myocardial ischemic reperfusion injury [1]. The cardiac selective NHE inhibitor HOE 642 (Cariporide) is currently undergoing clinical evaluation in patients suffering myocardial ischemic episodes including those receiving coronary artery bypass. There is evidence that suggests that propofol may be cardioprotective possibly related to its antioxidant properties [2] and/or reducing calcium [3] overload in the reperfused myocardial cell. The purpose of this study is to examine the effects of propofol (35 [micro sign]M) on the ischemic reperfused rat heart alone or in combination with HOE 642 (5 [micro sign]M).

METHODS: Experiments were carried out in isolated rat hearts perfused by the Langendorff method at a constant flow rate and electrically paced at 300 beats/minute. Functional evaluation included continuous recording of left ventricular developed pressure (LVDP), left ventricular end diastolic pressure (EDP), coronary perfusion pressure and rates of LV pressure development and relaxation. At the conclusion of the experiment, hearts were freeze clamped for metabolite assays.

Isolated hearts were exposed either to control buffer, HOE 642 (5 [micro sign]M), propofol (35 [micro sign]M) alone or in combination with HOE 642, and were then subjected to 1 hour global ischemia followed by 1 hour of reperfusion with the same drug protocol as the preischemic period. Six rat hearts were used in each group.

RESULTS: Hearts treated with propofol exhibited complete recovery of LVDP (109.9% of preischemic value after 60 min reperfusion) compared to 62.5% in control hearts (p<0.05). HOE 642 also provided complete recovery of LVDP (107.3 %) as expected, however in the presence of propofol the cardioprotection with HOE 642 was enhanced (LVDP 136.7% of preischemic values at 60 min reperfusion, p<0.05 versus other groups). Propofol significantly attenuated the dramatic rise in reperfusion-induced EDP (EDP at 15min: 1166% of preischemic value in controls; propofol 490%, p<0.05), but all groups treated with HOE 642 exhibited a reduced EDP compared to untreated groups (283% HOE alone; 263% HOE+propofol).

CONCLUSIONS: This study reveals that a clinically relevant concentration of propofol (35 [micro sign]M) provides cardioprotection in the ischemic reperfused rat heart and enhances the recovery of function associated with HOE 642.

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REFERENCES

1. Can J Cardiol. 1996:12(10): 1074-82.
2. Anesthesiology 1996:84(1): 117-27.
3. Anesthesiology 1996:85(5): 1092-99.
© 1998 International Anesthesia Research Society