Cardioplegia is an important method of providing myocardial protection during cardiac surgeries such as heart transplantation, evolving from systemic hypothermia in the 1950s to modern pharmacological arrest techniques. Melrose et al. first introduced high-potassium cardioplegia in 1955, aiming to achieve elective, reversible cardiac arrest, though early formulations caused focal myocardial necrosis and were temporarily abandoned.¹ Later, researchers refined cardioplegic solutions to optimize myocardial preservation, leading to the development of Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) solution in Germany, which added procaine but was low in sodium and calcium free. This solution was more successful in inducing arrest while maintaining a polarized membrane.² In the mid-1970s, St. Thomas’ Hospital solution, developed by Hearse and Braimbridge, became the predominant crystalloid cardioplegia worldwide, characterized by moderately elevated potassium levels, magnesium supplementation, and near-physiologic calcium concentrations.³ By the 1970s, researchers such as Jynge et al. demonstrated that crystalloid cardioplegic solutions could significantly reduce ischemic injury by inducing a controlled and reversible cardiac arrest, allowing operations on still and bloodless hearts while preserving myocardial viability.⁴ In 1977, Buckberg and colleagues pioneered blood cardioplegia.⁵ This method uses blood as a substrate for cardioprotective and arresting agents and is currently the most common method of cardioplegia.⁶ These solutions, along with several other notable solutions, are summarized in Table 1. Despite these advancements, current clinical practice varies widely, with some centers favoring a single dose during procurement and others administering supplemental doses at implantation. These differences reflect not only institutional preferences, but also a lack of standardized guidelines or consensus on optimal cardioplegia strategy. As a result, key questions remain unanswered—such as whether the benefits of supplemental dosing outweigh potential risks in various complex donor and recipient contexts, or how evolving perfusion techniques and cardioplegia formulations should be integrated into practice. These unresolved issues highlight the ongoing relevance of debate on the topic and the need for further evidence to guide decision-making. This article will discuss the Cons of administering additional doses, while another Pro article will review its potential benefits.⁷