Cardiotrophin-1 (CT-1) can protect the adult heart from injury when added both prior to ischaemia and at reperfusion

• Published in: Cardiovascular research 2002-03, Vol.53 (4), p.902-910
• Main Authors: ZHIHONG LIAO, BRAR, Bhawanjit K, QING CAI, STEPHANOU, Anastasis, O'LEARY, Rhona M, PENNICA, Diane, YELLON, Derek M, LATCHMAN, David S
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Apoptosis - drug effects; Biological and medical sciences; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Cardiology. Vascular system; Cell Hypoxia - physiology; Cell Survival - drug effects; Cells, Cultured; Coronary heart disease; Cytokines - administration & dosage; Cytokines - therapeutic use; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme Inhibitors - pharmacology; Female; Flavonoids - pharmacology; Heart; Hemodynamics - drug effects; Male; Medical sciences; Myocardial Reperfusion; Myocardial Reperfusion Injury - prevention & control; Myocardium - cytology; Rats; Rats, Sprague-Dawley
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/s0008-6363(01)00531-4

To determine whether the cytokine cardiotrophin-1 (CT-1) can protect the adult heart against ischaemia/reperfusion when added either prior to ischaemia or at reperfusion. CT-1 has previously been shown to protect cultured embryonic or neonatal cardiocytes from cell death. To assess the therapeutic potential of CT-1, it is necessary to determine whether this effect can be observed in adult cardiac cells both in culture and most importantly in the intact heart. We examined the protective effect of CT-1 both in cultured adult rat cardiocytes and in the rat intact heart. In both cases, the cardiac cells were exposed to hypoxia/ischaemia followed by reoxygenation/reperfusion and CT-1 was administered either prior to hypoxia/ischaemia or at reoxygenation/reperfusion. CT-1 has a protective effect in reducing ischaemic damage in the intact heart ex vivo as assayed by infarct size to area at risk ratio (20% compared to 35%). Similar protective effects against cell death were noted in adult cells in vitro. Both in vitro and ex vivo CT-1 can exert a protective effect when added at the time of reoxygenation/reperfusion as well as prior to the hypoxic/ischaemic stimulus (cell death reduced from 50 to 20% in TUNEL assay, infarct size to zone at risk ratio reduced from 35 to 20%). These protective effects are blocked by an inhibitor of the p42/p44 MAPK pathway. CT-1 can protect adult cardiac cells both in vitro and in vivo when added both prior to or after the hypoxic/ischaemic stimulus. The potential therapeutic benefit of CT-1 when added at the time of reperfusion following ischaemic damage is discussed.