Responses to ischaemia and reperfusion in the mouse isolated perfused heart and the phenomenon of 'contractile cycling'.
1. The aims of the present study were to examine the response of the murine heart to ischaemia and reperfusion and to determine whether these responses are influenced by the strain of mouse. 2. Isolated, paced (600 b.p.m.) murine (T/O mice) hearts were perfused aerobically (2.6 mL/min) with buffer for 40 min before being subjected to whole-heart (global) ischaemia (37 degrees C) for 20, 30, 35, 40 or 50 min prior to 90 min reperfusion. Contracture was measured during ischaemia and the reperfusate was collected and assayed for creatine kinase. 3. With increasing durations of ischaemia, there was a progressive decline in postischaemic recovery such that left ventricular developed pressure (LVDP) after 20, 30, 35, 40 or 50 min ischaemia was 75 +/- 4, 65 +/- 4, 38 +/- 6, 18 +/- 2 and 18 +/- 2% of pre-ischaemic controls, respectively. 4. There was a reciprocal increase in creatine kinase leakage, indicative of a time-dependent increase in tissue injury. 5. To compare the ischaemic vulnerability of different strains, hearts from Swiss and C57BL/6 mice were perfused for 20 min, followed by 40 min global ischaemia (37 degrees C) and 60 min reperfusion. Functional recovery of LVDP in Swiss mouse hearts was significantly higher than in C57BL/6 mouse hearts (39 +/- 7 vs 20 +/- 4%, respectively; P < 0.04, t-test; 10 d.f.). 6. During our investigations, we encountered and characterized the phenomenon of 'contractile cycling' (cyclical patterns of declining and increasing left ventricular systolic pressure of variable severity and duration). 7. We have shown that this confounding phenomenon is a manifestation of an underlying metabolic disturbance of unknown origin that can be attenuated by the addition of substrates, such as pyruvate or acetate, to the standard glucose-containing perfusion buffer.
Sutherland
Fiona J
FJ
Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, London, UK. fiona.sutherland@kcl.ac.uk
Baker
Kathryn E
KE
Shattock
Michael J
MJ
Hearse
David J
DJ
D000818:Animals; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D013045:Species Specificity; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology