Cardiac dysfunction is a common problem in the surgical intensive care unit (SICU). It occurs in settings of sepsis and hypermetabolism, frequently requiring drug, fluid and ventilator support. Cardiac failure is also a common component of multiple systems organ failure (MSOF), the cause of death in 90% of SICU patients. Malnutrition is present in SICU patients and is a primary manifestation of chronic hypermetabolism - MSOF. Both sepsis and malnutrition can depress ventricular performance (Frank- Starling performance; power output) and contractility in in-vivo models. This depression of ventricular function is frequently refractory to inotropic agents. In the clinical setting, it is difficult to identify whether sepsis, malnutrition, or both are responsible for the depression in myocardial function. Nutrition support is commonly used in these settings. The effects of acute nutrition support on cardiac function in these SICU settings is largely unstudied and it can cause sudden death when used in conditions of moderate to severe malnutrition. The present studies will allow the quantitative assessment of diastolic and systolic cardiac function under conditions of malnutrition alone, sepsis alone, malnutrition and sepsis, and neither malnutrition nor sepsis. A chronic, awake canine model will be employed, utilizing sonomicrometry to assess systolic/diastolic cardiac function; caloric deprivation to induce malnutrition; and cecal infarction to induce sepsis. In addition, the effects of acute nutrition support (TPN) on ventricular function will be determined in the same four states. The altered pharmacodynamics could be due to beta receptor malfunction or altered pharmacokinetics of endogenous chemical agents, e.g. catecholamines, or administered drugs. Altered drug clearance and protein binding with altered drug dynamics have been observed in malnutrition, sepsis, organ failure and with nutrition support. Drug kinetics and beta receptor function will be evaluated in the same control and experimental groups as a cause of the altered cardiac dynamics that are observed. The insight derived will be applicable in the clinical setting and in deriving new drug and nutrition regimens for support of the altered cardiac function in SICU patients.
