Enhancing outcomes in Langendorff-perfused rodent hearts through perfusion parameter optimization

Despite important advancements in addressing cardiovascular diseases (CVDs), there has been an overall lack of progress in the field, leading to a slower decline in the rate of CVDs related deaths, and even an increase for some risk groups (e.g. increase in stroke mortality) exacerbated by an aging and obese population. While a multi-faceted problem, this deceleration may be influenced by the preferred model systems utilized in translation research. Cardiac cell lines, although easier to handle, lack biological accuracy due to the unnatural modifications required for successful culture and may not recapitulate complex 3-dimensional structural and environmental factors. At the same time, whole animal experimentation provides unwanted complexity during initial scientific development. Alternatively, ex vivo perfusion of isolated rodent hearts provides the needed biological accuracy with decreased organismal complexity. This platform facilitates the evaluation of the isolated heart, without neuro-reflexes and/or humoral contributions, unveiling the direct effects of stimuli in heart function/homeostasis. This manuscript leverages the wide array of perfusion parameters (i.e. perfusate, flow rate, coronary pressures), to demonstrate the capability of ex vivo heart perfusion protocols to accommodate a large range of experimental needs. Through this work, it was determined that the use of physiological perfusion pressures leads to increased left ventricular (LV) pressures but results in a loss of function over time, making it ideal conditions for organ assessment. Conversely, lower-than-physiological perfusion pressures lead to decreased LV pressures but prevent loss of function over time, which is preferable when longer perfusion times are relevant to experimental needs. Similarly, the use of adenosine as a pharmacological intervention was found to decrease both edema formation and inflammatory responses. In contrast, the use of packed red blood cells as oxygen carriers appears to induce a pro-inflammatory response and cause greater cardiac damage, particularly when combined with low perfusion pressures.