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  • Title: The effect of beta blockers on cardiac neural discharge associated with coronary occlusion in the cat.
    Author: Lathers CM, Spivey WH.
    Journal: J Clin Pharmacol; 1987 Aug; 27(8):582-92. PubMed ID: 2888794.
    Abstract:
    The effect of timolol on postganglionic cardiac sympathetic neural discharge, blood pressure, heart rate, and rhythm changes associated with acute coronary occlusion of the left anterior descending artery was examined and compared with the effects of the beta blockers practolol and metoprolol. Timolol (5 mg/kg, IV) was infused 15 minutes prior to coronary occlusion in cats anesthetized with alpha-chloralose. Control heart rate fell from 129 +/- 10 to 106 +/- 2 one minute prior to coronary occlusion and remained at 106 +/- 2 beats/minute in the minute prior to arrhythmia. Control blood pressure fell from 126 +/- 20 to 91 +/- 19 and stabilized at 99 +/- 19 mm Hg one minute prior to coronary occlusion. Mean time to arrhythmia and death was 4.7 +/- 2.3 and 68.0 +/- 51.0 minutes (P greater than .05 vs no drug), respectively. Three cats died and two were sacrificed six hours after coronary occlusion. Blood pressure fell to 86 +/- 20 mm Hg two minutes after coronary occlusion, rose to 95 +/- 23 mm Hg at ten minutes, and remained there for ten minutes. Timolol did not alter postganglionic cardiac sympathetic neural discharge prior to coronary occlusion. Two minutes after coronary occlusion, mean postganglionic cardiac sympathetic neural discharge was 128 +/- 27 and increased to 139 +/- 36 impulses/second (% control) 4 minutes after coronary occlusion. A similar trend was found for the data recorded in 15 nerves (eight cats) in which coronary occlusion was initiated without timolol. The data suggest that a difference exists among beta blockers because prior to coronary occlusion, the cardioselective drugs metoprolol (1, 5, and 10 mg/kg, IV) and practolol (8 mg/kg, IV) depressed postganglionic cardiac sympathetic neural discharge whereas noncardioselective timolol did not. Because all three beta blockers increased the times to arrhythmia and death (although the increase was significant only after metoprolol and practolol), the acute protective mechanism does not appear to be due primarily to a depression of spontaneous sympathetic neural discharge.
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