Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.

Abstract

We have previously shown that a brief episode of ischemia slows the rate of ATP depletion during subsequent ischemic episodes. Additionally, intermittent reperfusion may be beneficial to the myocardium by washing out catabolites that have accumulated during ischemia. ' Thus, we proposed that multiple brief ischemic episodes might actually protect the heart from a subsequent sustained ischemic insult. To test this hypothesis, two sets of experiments were performed. In the first set, one group of dogs (n = 7) was preconditioned with four 5 min circumflex occlusions, each separated by 5 min of reperfusion, followed by a sustained 40 min occlusion. The control group (n = 5) received a single 40 min occlusion. In the second study, an identical preconditioning protocol was followed, and animals (n = 9) then received a sustained 3 hr occlusion. Control animals (n = 7) received a single 3 hr occlusion. Animals were allowed 4 days of reperfusion thereafter. Histologic infarct size then was measured and was related to the major baseline predictors of infarct size, including the anatomic area at risk and collateral blood flow. In the 40 min study, preconditioning with ischemia paradoxically limited infarct size to 25% of that seen in the control group (p < .001). Collateral blood flows were not significantly different in the two groups. In the 3 hr study, there was no difference between infarct size in the preconditioned and control groups. The protective effect of preconditioning in the 40 min study may have been due to reduced ATP depletion and/or to reduced catabolite accumulation during the sustained occlusion. These results suggest that the multiple anginal episodes that often precede myocardial infarction in man may delay cell death after coronary occlusion, and thereby allow for greater salvage of myocardium through reperfusion therapy. Circulation 74, No. 5, 1124-1136, 1986 OCCLUSION of a major coronary artery in the dog induces injury that is reversible for the first 15 to 20 min, in that complete tissue recovery ensues after reperfusion. However, if the occlusion is maintained beyond this time, the injury becomes irreversible; some cells die despite reperfusion. Ischemic cell death begins first in the subendocardial region and then progresses with time toward the subepicardium.2 A previous study from our laboratory' has shown that repeated brief episodes of ischemia do not have a cumulative deleterious effect. Four 10 min occlusions produced no more ATP depletion than a single occlusion, and did not cause necrosis, although 40 min of sustained ischemia has been associated with severe

Caveolin-3 expression and caveolae are required for isoflurane-induced cardiac protection from hypoxia and ischemia/reperfusion injury

“…Protection of the heart from ischemia/reperfusion injury can be induced by multiple stimuli (e.g., ischemia [1], opioids [2] and volatile anesthetics [3,4]). Though many volatile anesthetics, including isoflurane [3,4], sevoflurane [5,6], and desflurane [6] show cardiac protection in vivo, the precise mechanism for volatile anesthetic-induced cardiac protection has not been elucidated.…”

Cardioprotection and mitochondrial S-nitrosation: Effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia–reperfusion injury

“…These events lead to opening of the mitochondrial permeability transition (PT) pore, cytochrome c release, and subsequent apoptosis or necrosis [2][3][4]. The extent of cellular damage in IR is dependent on the length of ischemia, and interestingly brief periods of ischemia are known to trigger signaling pathways that protect against longer ischemic insults; a phenomenon known as ischemic preconditioning (IPC) [5]. Despite numerous studies the precise mechanisms of IPC are still under debate, but the preservation of mitochondrial function is believed to be an important end-point in IPC signaling.…”

Cannabinoids, the Heart of the Matter

“…2‐AG, but not anandamide, provides protection in isolated perfused rat hearts by reducing infarct size and myocardial damage 31. The activation of CB2 receptors confers immediate protection against a subsequent prolonged and injurious period of ischemia 31, 32. Furthermore, ischemic preconditioning has a protective effect on diabetic and aging hearts 33…”