Induction of 72-kDa heat shock protein does not produce second window of ischemic preconditioning in rat heart

Abstract

Ischemic preconditioning (PC) induces delayed phase of protection, known as the second window of protection (SWOP). We investigated this phenomenon in rat and correlated it with the expression of 72-kDa heat shock protein (HSP 72). Rats were preconditioned with 1, 2, and 3 cycles of 5-min left anterior descending artery occlusions, each separated by a 10-min reperfusion (PC × 1, PC × 2 and PC × 3, respectively). Another group of rats was preconditioned with heat shock (HS) by raising temperature to 42°C for 15 min. Twenty-four hours later, rats were given sustained ischemia for 30 min and 90 min of reperfusion. Infarct sizes (%risk area) were 40.0 ± 7.5, 37.6 ± 5.6, and 47.6 ± 2.4 (mean ± SE) for PC × 1, PC × 2, and PC × 3 hearts, respectively, which were not different from the sham (49.9 ± 3.9, P > 0.05). In contrast, infarct size was reduced from 47.5 ± 3.8% in sham to 4.7 ± 2.3% ( P < 0.01) 24 h after HS. Additionally, early PC significantly reduced infarct size from 47.5 ± 3.8% in controls to 6.0 ± 1.2 and 5.0 ± 1.1% with PC × 1 and PC × 3. Repeated PC cycles induced over a threefold increase in HSP 70 mRNA after 2 h compared with sham ( P < 0.05). HSP 72, which increased 24 h after PC or HS, was not significantly different between the two PC stimuli. We conclude that PC does not induce SWOP in rat heart despite enhanced expression of HSP 72. In contrast, HS-induced delayed protection was associated with enhanced accumulation of HSP 72. It is possible that SWOP and HS have distinct mechanisms of protection that may not be exclusively related to HSP 72 expression.

HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts

“…Moreover, two previous studies suggest that expression of inducible HSP70 following IP does not provide protection against ischemia, as assessed by a reduction in infarct size. Using a rat model of myocardial I/R, Qian et al (32) reported that IP, despite enhancing expression of myocardial HSP72, did not provide late protection against infarction following regional ischemia. Also, Tanaka et al (39) observed that IP failed to reduce infarction after prolonged ischemia in rabbits despite increased expression of HSP72-73 induced by IP.…”

Gene Transfer of Heat-Shock Protein 70 Reduces Infarct Size In Vivo After Ischemia/Reperfusion in the Rabbit Heart

“…There is now compelling genetic and biochemical evidence that these proteins belong to a family of ATP-dependent "unfoldases" implicated in protein assembly/dissociation of multimeric complexes, translocation, and import/export processes across membranes. 3 It is well established that preconditioning with brief episodes of ischemia, 4 -6 as well as other forms of stress, such as heat shock, [5][6][7][8] result in increased production of HSP 70 in the heart. The amount of HSP 70 synthesis correlates with the extent of myocardial protection after ischemia/reperfusion injury.…”

Attenuation of heat shock-induced cardioprotection by treatment with the opiate receptor antagonist naloxone

“…Qian et al (23) have shown that in rats ischemic preconditioning does not induce delayed cardioprotection, even though levels of HSP70 are comparable with those observed after whole body hyperthermia. In addition, Taylor et al (31) show that exercise alone without HSP induction confers protection.…”