Failure to precondition pathological human myocardium
Sudip Ghosh, FRCS*,
Nicholas B. Standen, PhD and
Manuel Galiñanes, MD, PhD*
* Division of Cardiac Surgery, Department of Surgery, University Hospitals Leicester, Glenfield Campus, Leicester, United Kingdom
Department of Cell Physiology and Pharmacology, University Hospitals Leicester, Glenfield Campus, Leicester, United Kingdom
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Figure 1 Experimental protocols for study 1. All groups were equilibrated for 30 min in aerobic conditions (37°C). Then the right atrial slices were randomly assigned to one of the study groups (n = 6/group): Aerobic Control = aerobically incubated for the entire experimental time. Ischemia Alone = subjected to 90 min simulated ischemia followed by 120 min reoxygenation. PC = preconditioning with 5 min ischemia followed by 5 min reoxygenation before undergoing 90 min ischemia. Diazoxide = incubation in 0.1 mm of the drug for 10 min before exposure to 90 min ischemia. Glibenclamide = pretreatment in 10 µm of the drug for 10 min before preconditioning was applied.
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Figure 2 Experimental protocols for study 2. All groups were equilibrated for 30 min in aerobic conditions (37°C). Following this, the right atrial slices were randomly assigned to one of the following study groups (n = 6/group): Aerobic Control = aerobically incubated for the entire experimental time course. Ischemia Alone = subjected to 90 min simulated ischemia followed by 120 min reoxygenation. PC = preconditioning with 5 min ischemia followed by 5 min reoxygenation before undergoing 90 min ischemia. Diazoxide = incubation in 0.1 mM of the drug for 10 min before exposure to 90 min ischemia.
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Figure 3 Creatine kinase (CK) leakage (A) during the 120 min reoxygenation period (last 120 min in the aerobic control group) and MTT reduction (B) at the end of the reoxygenation period in study 1 (for protocol see Fig. 1). Data are expressed as mean ± standard error of mean of six experiments. *p < 0.05 versus corresponding group subjected to ischemia alone. White bar = nondiabetics; black bar = diet-controlled diabetes; striped bar = noninsulin-dependent diabetes; hatched bar = insulin-dependent diabetes; PC = preconditioning.
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Figure 4 Creatine kinase (CK) leakage (A) during the 120 min reoxygenation period (last 120 min in the aerobic control group) and MTT reduction (B) at the end of the reoxygenation period in study 2 (for protocol see Fig. 2). Data are expressed as mean ± standard error of mean of six experiments. *p < 0.05 versus corresponding group subjected to ischemia alone; p < 0.05 versus corresponding group subjected to preconditioning (PC). White bar: left ventricular ejection fraction (LVEF) >50%; striped bar: LVEF = 30% to 50%; black bar: LVEF <30%.
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