Infarct size and the protection of ischemic myocardium in pig, dog and human.

Fujiwara, Hisayoshi; Matsuda, Mitsuo; Fujiwara, Yasunori; Ishida, Moriharu; Kawamura, Atsushi; Takemura, Genzou; Kida, Mitsugu; Uegaito, Takashi; Tanaka, Masahiro; Horike, Kiyoshi; Fujiwara, Takako; Kawai, Chuichi

doi:10.1253/jcj.53.1092

Cited by 13 publications

(13 citation statements)

References 8 publications

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“…A linear and logarithmic time scale is presented in the left and right panel, respectively. A: Data from previous studies in pigs (black circle = Fujiwara et al [ 9 ], white circle = Näslund et al [ 6 ]. B: Data from previous studies in rats (black circle = Hale et al [ 8 ], white circle Arheden et al [ 11 ]).…”

Section: Resultsmentioning

confidence: 99%

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Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage

Hedström

Engblom

Frogner

et al. 2009

Journal of Cardiovascular Magnetic Resonance

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BackgroundThe time course of infarct evolution, i.e. how fast myocardial infarction (MI) develops during coronary artery occlusion, is well known for several species, whereas no direct evidence exists on the evolution of MI size normalized to myocardium at risk (MaR) in man. Despite the lack of direct evidence, current literature often refers to the "golden hour" as the time during which myocardial salvage can be accomplished by reperfusion therapy. Therefore, the aim of the present study was to investigate how duration of myocardial ischemia affects infarct evolution in man in relation to previous animal data. Consecutive patients with clinical signs of acute myocardial ischemia were screened and considered for enrollment. Particular care was taken to assure uniformity of the patients enrolled with regard to old MI, success of revascularization, collateral flow, release of biochemical markers prior to intervention etc. Sixteen patients were ultimately included in the study. Myocardium at risk was assessed acutely by acute Myocardial Perfusion Single photon emission computed tomography (MPS) and by T2 imaging (T2-STIR) cardiovascular magnetic resonance (CMR) after one week in 10 of the 16 patients. Infarct size was measured by late gadolinium enhancement (LGE) at one week.ResultsThe time to reach 50% MI of the MaR (T50) was significantly shorter in pigs (37 min), rats (41 min) and dogs (181 min) compared to humans (288 min). There was no significant difference in T50 when using MPS compared to T2-STIR (p = 0.53) for assessment of MaR (288 ± 23 min vs 310 ± 22 min, T50 ± standard error). The transmural extent of MI increased progressively as the duration of ischemia increased (R2 = 0.56, p < 0.001).ConclusionThis is the first study to provide direct evidence of the time course of acute myocardial infarct evolution in relation to MaR in man with first-time MI. Infarct evolution in man is significantly slower than in pigs, rats and dogs. Furthermore, infarct evolution assessments in man are similar when using MPS acutely and T2-STIR one week later for determination of MaR, which significantly facilitates future clinical trials of cardioprotective therapies in acute coronary syndrome by the use of CMR.

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Section: Resultsmentioning

confidence: 99%

“…Therefore, it is important to compare the findings from the present study in man with earlier results from animal studies. For this purpose, analysis of MI size normalized to MaR for rats [ 8 , 11 ], pigs [ 6 , 9 ], and dogs [ 3 , 7 , 9 , 10 ] was performed and compared with the human data in the present study.…”

Section: Methodsmentioning

confidence: 99%

Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage

Hedström

Engblom

Frogner

et al. 2009

Journal of Cardiovascular Magnetic Resonance

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“…Interestingly, these transcripts were increased not only after the period of acute cell loss with infiltration of inflammatory cells (≈1 week in mice) but also during the fibrotic proliferation of scar maturation that ensues over the next 2 to 4 weeks in mice. Analogy to the postinfarct time course in humans would suggest that this period corresponds to 3 months after MI (ie, scar stabilization) . Although clinical evidence supporting myocardial responsiveness to IGF‐1 is limited, the variable amount of IGF‐1 produced by first‐generation CSC products may provide a portion of benefits seen after transplantation, despite the treatment gap from MI to therapy dictated by the realities of autologous cell culture (weeks to months) .…”

Section: Discussionmentioning

confidence: 99%

“…Analogy to the postinfarct time course in humans would suggest that this period corresponds to 3 months after MI (ie, scar stabilization). 37 Although clinical evidence supporting myocardial responsiveness to IGF-1 is limited, the variable amount of IGF-1 produced by firstgeneration CSC products may provide a portion of benefits seen after transplantation, despite the treatment gap from MI to therapy dictated by the realities of autologous cell culture (weeks to months). 1 In this study, the peri-infarct area in mice was maximally responsive to IGF-1 at 7 days after left anterior descending artery ligation, justifying the timing of a cytokinebased therapy (%1 month after MI in humans).…”

Section: Discussionmentioning

confidence: 99%

“…1 In this study, the peri-infarct area in mice was maximally responsive to IGF-1 at 7 days after left anterior descending artery ligation, justifying the timing of a cytokinebased therapy (%1 month after MI in humans). 37,38 Like the myocardium, ex vivo proliferated c-Kit+ cells have been shown to be responsive to IGF-1 signaling, suggesting a role in autocrine/paracrine prosurvival effects. 39 In this study, we found that within the heterogeneous EDCs, IGF-1R and IR colocalized with all subpopulations, with a strong tendency to favor the cardiac (c-Kit+) and mesenchymal (CD90+) progenitor fractions.…”

Section: Discussionmentioning

confidence: 99%

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Paracrine Engineering of Human Cardiac Stem Cells With Insulin‐Like Growth Factor 1 Enhances Myocardial Repair

Jackson

Tilokee

Latham

et al. 2015

JAHA

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BackgroundInsulin-like growth factor 1 (IGF-1) activates prosurvival pathways and improves postischemic cardiac function, but this key cytokine is not robustly expressed by cultured human cardiac stem cells. We explored the influence of an enhanced IGF-1 paracrine signature on explant-derived cardiac stem cell–mediated cardiac repair.Methods and ResultsReceptor profiling demonstrated that IGF-1 receptor expression was increased in the infarct border zones of experimentally infarcted mice by 1 week after myocardial infarction. Human explant-derived cells underwent somatic gene transfer to overexpress human IGF-1 or the green fluorescent protein reporter alone. After culture in hypoxic reduced-serum media, overexpression of IGF-1 enhanced proliferation and expression of prosurvival transcripts and prosurvival proteins and decreased expression of apoptotic markers in both explant-derived cells and cocultured neonatal rat ventricular cardiomyocytes. Transplant of explant-derived cells genetically engineered to overexpress IGF-1 into immunodeficient mice 1 week after infarction boosted IGF-1 content within infarcted tissue and long-term engraftment of transplanted cells while reducing apoptosis and long-term myocardial scarring.ConclusionsParacrine engineering of explant-derived cells to overexpress IGF-1 provided a targeted means of improving cardiac stem cell–mediated repair by enhancing the long-term survival of transplanted cells and surrounding myocardium.

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Ischemic postconditioning: experimental models and protocol algorithms

et al. 2009

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Ischemic postconditioning, a simple mechanical maneuver at the onset of reperfusion, reduces infarct size after ischemia/reperfusion. After its first description in 2003 by Zhao et al. numerous experimental studies have investigated this protective phenomenon. Whereas the underlying mechanisms and signal transduction are not yet understood in detail, infarct size reduction by ischemic postconditioning was confirmed in all species tested so far, including man. We have now reviewed the literature with focus on experimental models and protocols to better understand the determinants of protection by ischemic postconditioning or lack of it. Only studies with infarct size as unequivocal endpoint were considered. In all species and models, the duration of index ischemia and the protective protocol algorithm impact on the outcome of ischemic postconditioning, and gender, age, and myocardial temperature contribute.

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Infarct size and the protection of ischemic myocardium in pig, dog and human.

Cited by 13 publications

References 8 publications

Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage

Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage

Paracrine Engineering of Human Cardiac Stem Cells With Insulin‐Like Growth Factor 1 Enhances Myocardial Repair

Ischemic postconditioning: experimental models and protocol algorithms

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