Mild hypothermia has been shown to reduce heart tissue damage resulting from acute myocardial infarction (AMI). In previous work we developed a trilumen cooling catheter to deliver cooled blood rapidly to the heart during emergency angioplasty. This paper describes two alternative designs that seek to maintain tissue cooling capability and improve “ease of use.” The first design was an autoperfusion design that uses the natural pressure difference between the aorta and the coronary arteries to move blood through the trilumen catheter. The second design used an external cooling system, where blood was cooled externally before being pumped to the heart through a commercially available guide catheter. Heat transfer and pressure drop analyses were performed on each design. Both designs were fabricated and tested in both in vitro and in vivo settings. The autoperfusion design did not meet a cooling capacity target of 20 W. Animal tests, using swine with healthy hearts, showed that the available pressure difference to move blood through the trilumen catheter was approximately 5–10 mmHg. This differential pressure was too low to motivate sufficient blood flow rates and achieve the required cooling capacity. The external cooling system, however, had sufficient cooling capacity and reasonable scalability. Cooling capacity values varied from 14 to 56 W over a flow range of 30–90 ml/min. 20 W and 30 W were achieved at 38 ml/min and 50 ml/min, respectively. Animal testing showed that a cooling capacity of 30 W delivered to the left anterior descending (LAD) and left circumflex arteries (LCX) of a healthy 70 kg swine can reduce heart tissue temperatures rapidly, approximately 3 °C in 5 min in some locations. Core temperatures dropped by less than 0.5 °C during this cooling period. An autoperfusion design was unable to meet the target cooling capacity of 20 W. An external cooling design met the target cooling capacity, providing rapid (1 °C/min) localized heart tissue cooling in a large swine model. Future animal testing work, involving a heart attack model, will investigate if this external cooling design can save heart tissue.