Title: Muscarinic receptor stimulation by carbachol improves functional recovery in isolated, blood perfused rabbit heart
Authors: Hendrikx, M ×
Toshima, Y
Mubagwa, Kanigula
Flameng, Willem #
Issue Date: Jun-1993
Series Title: Cardiovascular Research vol:27 issue:6 pages:980-9
Abstract: OBJECTIVE: The aim was to test whether, besides adenosine A1 receptors, other receptors coupled to the "inhibitory" GTP binding protein Gi confer protection against ischaemic and reperfusion injury. METHODS: Isolated hearts were Langendorff perfused at 37 degrees C with blood and were divided into five groups, all subjected to 45 min zero flow normothermic ischaemia, followed by 1 h reperfusion. Group 1 consisted of control untreated hearts (n = 5). Group 2 consisted of hearts treated with the muscarinic agonist carbachol (CCh, 10 microM; n = 5). In group 3 (CCh+atropine, n = 5) 5 microM atropine was given as well as CCh. Groups 1, 2, and 3 were paced at 3 Hz except during ischaemia. Groups 4 (n = 5) and 5 (n = 6) were similar to groups 1 and 2, except that pacing was continued throughout ischaemia. RESULTS: In group 1, left ventricular end diastolic pressure increased during ischaemia, from 7.2(SEM 1.2) mm Hg to 57(5.6) mm Hg, and remained increased during reperfusion, whereas in group 2, it increased moderately during ischaemia, from 9.2(0.9) mm Hg to 21.6(4.9) mm Hg and returned to preischaemic levels during reperfusion. In hearts paced during ischaemia, contracture developed faster than in unpaced hearts, but CCh still delayed contracture. Postischaemic recovery of isovolumetric left ventricular pressure or its first derivative (dP/dt) and reactive hyperaemia were significantly greater in CCh treated hearts [left ventricular pressure = 69.8(4.9)% of preischaemic value after 60 min reperfusion] than in control hearts [29.3(6.8)%]. Recovery of left ventricular pressure and dP/dt was worsened by pacing, but CCh still improved this recovery [left ventricular pressure = 13.1(8.4)% in control, 46.7(5.3)% in CCh treated hearts]. The CCh effect could be prevented by atropine. ATP breakdown and lactate accumulation during the first minute of ischaemia were lower in non-paced CCh treated hearts than in controls. ATP recovered better at the end of reperfusion in both non-paced [7.1(0.72) mumol.g-1] and paced [4.4(0.77) mumol.g-1] CCh treated hearts, as compared with non-paced [1.8(0.58) mumol.g-1] and paced [1.2(0.39) mumol.g-1] control hearts. In paced hearts, less creatine kinase and lactate dehydrogenase were released in the CCh treated group throughout the reperfusion phase. CONCLUSIONS: Carbachol improves functional recovery and confers cellular protection, and this protection depends mainly but not entirely on its bradycardic effect.
ISSN: 0008-6363
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Experimental Cardiac Surgery (-)
× corresponding author
# (joint) last author

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