Transplantation of exogenous mitochondria mitigates myocardial dysfunction after cardiac arrest

Reviewer #1 (Public Review):

Summary:

In this study, the authors investigate the effect of mitochondrial transplantation on post-cardiac arrest myocardial dysfunction (PAMD), which is associated with mitochondrial dysfunction. The authors demonstrate that mitochondrial transplantation enhances cardiac function and increases survival rates after the return of spontaneous circulation (ROSC). Mechanistically, they found that myocardial tissues with transplanted mitochondria exhibit increased mitochondrial complex activity, higher ATP levels, reduced cardiomyocyte apoptosis, and lower myocardial oxidative stress post-ROSC.

Strengths:

Previous studies have reported that mitochondrial transplantation can improve myocardial recovery after regional ischemia, but its potential for treating myocardial injury following cardiac arrest has not been tested yet. Therefore, the findings are somewhat novel. Remarkably, the increased survival in mitochondria treated group post-ROSC is very promising and highlights its translational potential.

Weaknesses:

The organization of the paper, along with the analysis and interpretation of the results, requires significant revision.

Reviewer #2 (Public Review):

Summary:

The authors address an important question in cardiovascular science that is very topical. The use of exogenous mitochondrial transplantation is assessed after cardiac arrest to determine if these exogenous mitochondria can enhance cardiac function. Given the role of mitochondria in the energy expenditure of the heart, this is an important question to study.

Strengths:

The strength lies mainly in the hypothesis being addressed as it is highly relevant in the quest for more strategies to enhance cardiac function.

Weaknesses:

There is further refinement needed in experimental details and transparency. Also, additional experiments need to be performed such as the seahorse experiment for oxygen consumption. Improvements in the text and in figures are needed and these comments are directed to the authors in our recommendations to the authors.

Reviewer #3 (Public Review):

In this manuscript titled "Transplantation of exogenous mitochondria mitigates myocardial dysfunction after cardiac arrest", Zhen Wang et al. report that exogenous mitochondrial transplantation can enhance myocardial function and survival rates. It limits mitochondrial morphology impairment, boosts complexes II and IV activity, and increases ATP levels. Additionally, mitochondrial therapy reduces oxidative stress, lessens myocardial injury, and improves PAMD after cardiopulmonary resuscitation. The results of this manuscript clearly demonstrate that mitochondrial transplantation can effectively improve PAMD after cardiopulmonary resuscitation, highlighting its significant scientific and clinical value. The findings shown in this manuscript are interesting to the readers. However, further experiments are needed to confirm this conclusion. In addition, the results should be rewritten to describe and discuss the relevant data in detail.

Major comments:

(1) Can isolated mitochondria be transported to cultured cardiomyocytes, such as H9C2 cells, in vitro?

(2) The description of results in the manuscript is too simple. It lacks detail on the rationale behind the experiments and the significance of the data.

(3) The authors demonstrate that mitochondrial transplantation reduces cardiomyocyte apoptosis. Therefore, Western blot analysis of apoptosis-related caspases could be provided for further confirmation.

(4) Do donor mitochondria fuse with recipient mitochondria? Relevant experiments and data should be provided to address this question.

(5) In Figure 5A, the histograms are not labeled with the specific experimental groups.