What question did this study set out to answer?

To determine whether myocardial apoptosis during heart failure occurs primarily in myocytes or nonmyocytes in primates and humans.

May 22, 2009AJP Heart and Circulatory Physiology

Apoptosis predominates in nonmyocytes in heart failure

Q: What is the clinical evidence from this study?

Study design: Other. Population: Heart Failure (n=24). Intervention: Heart failure following myocardial infarction vs. Sham-operated controls. Primary outcome: TUNEL-positive apoptotic cells in nonmyocytes versus myocytes in adjacent myocardium (MI+HF monkeys) (p=<0.05).

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Key result

In both a primate model of heart failure and human cardiomyopathy biopsies, apoptosis occurred predominantly in nonmyocytes, with rates eight- to ninefold greater than in myocytes.

Authors

MPMisun ParkTheragen YSYou-Tang ShenBrunswick (United States)VGVinciane GaussinRutgers New Jersey Medical School

Discussion

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Implication

Questions primacy of myocyte apoptosis in heart failure; leaves open whether nonmyocyte targeting alters progression.

Key Points

To determine whether myocardial apoptosis during heart failure occurs primarily in myocytes or nonmyocytes in primates and humans.
Examined a nonhuman primate model of chronic heart failure induced by rapid pacing 2–6 months after myocardial infarction.
Analyzed myocardial biopsy specimens from patients with ischemic cardiomyopathy using dual-labeling techniques to differentiate myocytes from nonmyocytes.
Total apoptosis increased from 0.62 cells/mm² post-myocardial infarction to 1.91 cells/mm² during heart failure as left ventricular ejection fraction decreased from 78% to 35% (P < 0.05).
Apoptosis in nonmyocytes was eight- to ninefold greater than in myocytes in both animal models and human heart failure biopsies across adjacent and remote myocardial regions.
Macrophages represented 41% of all apoptotic nonmyocytes, compared to 25% endothelial and other cells, 18% neutrophils, and 16% fibroblasts.

PICO

Population

20 male monkeys with induced myocardial infarction and heart failure, and 4 patients with cardiomyopathy, evaluated for the distribution of myocardial apoptosis.

Exposure / Comparator

Heart failure following myocardial infarction vs Sham-operated controls

Primary Outcome

TUNEL-positive apoptotic cells in nonmyocytes versus myocytes in adjacent myocardium (MI+HF monkeys), p=<0.05

Main Result

Absolute Event Rate: 1.69% vs 0.22%

p-value: p=<0.05

Limitations

Small sample size of human biopsies
Insufficient human tissue available to permit identification of specific nonmyocyte cell types

Cite This Study

Park et al. (2009) studied Heart Failure (n=24). Heart failure following myocardial infarction vs. Sham-operated controls was evaluated on TUNEL-positive apoptotic cells in nonmyocytes versus myocytes in adjacent myocardium (MI+HF monkeys) (p=<0.05). In both a primate model of heart failure and human cardiomyopathy biopsies, apoptosis occurred predominantly in nonmyocytes, with rates eight- to ninefold greater than in myocytes.

synapsesocial.com/papers/6a8f07b88cfc62bc787d90b9 https://doi.org/10.1152/ajpheart.00310.2009

Topics

Heart failure HFrEF treatment Cardiomyopathy Bremelanotide

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Apoptosis predominates in nonmyocytes in heart failure

Discussion

Member takes

Implication

Key Points

PICO

Main Result

Limitations

Cite This Study

Topics

Apoptosis predominates in nonmyocytes in heart failure

Discussion

Member takes

Implication

Key Points

PICO

Main Result

Limitations

Cite This Study

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Topics

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