The Isolated, Perfused Pseudo-Working Heart Model

Increased interest in cardiac safety and renewed interest in drugs for treating myocardial ischemia and congestive heart failure have led to increased use of cardiovascular models. Unfortunately, many molecular or cell-based screens are not perfect predictors of activity in vivo. One rapid means to test “proof of principle” in hearts is the isolated or Langendorff perfused heart system. This allows direct measurement of cardiac contractile function and coronary flow without interference from changes in the systemic circulation. The setup basically is a heart whose coronary arteries are retrogradely perfused through the aortic root with heated and oxygenated buffer solutions. We will describe the constant pressure technique as this is the most commonly used and allows us to directly measure changes in coronary flow without changes in turgor noted with constant flow methods. Instead of a classical working heart preparation, we describe the use of a balloon properly fitted into the left ventricle to measure end diastolic and peak systolic pressure making this a much simpler and less expensive technique without loss of scientific quality. Such a setup can be used to measure effects of compounds or treatments on coronary flow, contractile function either in the normal or pathological states.