Stunning, preconditioning, and functional recovery after global myocardial ischemia

• Published in: The Annals of thoracic surgery Vol. 58; no. 3; pp. 822 - 827
• Main Authors: Bolling, Steven F., Olszanski, Douglas A., Childs, Keith F., Gallagher, Kim P., Ning, Xue-Han
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.1994; Elsevier Science
• Subjects: Animals; Bicarbonates - pharmacology; Biological and medical sciences; Blood Pressure; Calcium Chloride - pharmacology; Cardiology. Vascular system; Cardioplegic Solutions - pharmacology; Coronary heart disease; Heart; Heart Arrest, Induced; Heart Rate; In Vitro Techniques; Magnesium - pharmacology; Male; Medical sciences; Models, Biological; Myocardial Contraction - drug effects; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocardial Stunning - etiology; Myocardial Stunning - metabolism; Myocardial Stunning - physiopathology; Oxygen Consumption; Potassium Chloride - pharmacology; Rabbits; Sodium Chloride - pharmacology; Time Factors; Ventricular Function, Left; Biochemical analysis; Rat; Rodentia; Cardiovascular disease; Exploration; Metabolism; Myocardial disease; Vertebrata; Mammalia; Reperfusion; Ischemia; Animal; Myocardium
• ISSN: 0003-4975; 1552-6259
• DOI: 10.1016/0003-4975(94)90759-5

Stunning (reversible myocardial ischemia without necrosis) occurs with induced global ischemia during cardiac operation and depresses the ability of the heart to utilize oxygen efficiently because less contractile work is developed per unit of oxygen utilized. Interestingly, regional studies have demonstrated dramatic infarct size reduction with stunning episodes before prolonged ischemia, a phenomenon known as myocardial preconditioning. It is postulated that the postischemic contractile dysfunction noted after stunning causes reduced energy demands, which “preconditions” myocardium to withstand a subsequent longer ischemic episode. Some evidence from regional studies suggests that preconditioning may improve functional recovery after ischemia. This study examined the complex relationship between stunning and preconditioning to functional recovery in a surgical setting of global ischemia. To study the effect of stunning, myocardial oxygen consumption, oxygen extraction, and functional indices of contractility were measured before and after isolated rabbit hearts were subjected to 10, 20, or 45 minutes of normothermic 37 °C global ischemic stun intervals. This demonstrated that while oxygen consumption and extraction quickly recover to prestun levels, contractility remains depressed well beyond the stun interval. To study the effect of preconditioning using stunning, isolated hearts were then subjected to 120 minutes of 34°C cardioplegic-induced ischemia after preconditioning. Hearts received either modified St. Thomas cardioplegic solution as a control or cardioplegia administered after preconditioning with 37 °C ischemic stunning for 5, 10, 15, 20, or 45 minutes or multiple 5- or 10-minute stuns, with reperfusion before cardioplegic-induced ischemia. Additionally, two groups of hearts were subjected to “graded” stunning (low or intermediate coronary flow for 10 minutes) before cardioplegia-induced ischemia. In all groups, contractility and metabolic recovery were all significantly worsened with preconditioning stunning. In contrast with the benefit of myocardial preconditioning upon necrosis and infarct size in regional ischemia, the present study suggests that preconditioning by stunning does not enhance postischemic myocardial functional recovery in a simple model of global ischemia.