Intracoronary hypothermia before reperfusion to reduce reperfusion injury in acute myocardial infarction:a novel hypothesis and technique

\u3cp\u3eBecause current reperfusion strategies in acute myocardial infarction (AMI) seem to be exhausted in terms of additional mortality benefit, there remains a need for new methods to attenuate reperfusion injury and, thereby, further reduce myocardial infarct size and improve long-term survival. Therapeutic hypothermia (32-35°C) diminishes reperfusion injury and reduces infarct size in a variety of animal models of AMI if provided before reperfusion. In human studies this reduction has not been confirmed so far, most likely because systemic cooling acts slowly, and therefore, the target temperature is not reached in time or at all in a substantial number of patients. Furthermore, systemic cooling can cause adverse effects such as severe shivering, volume overload, and an enhanced adrenergic state. In most randomized clinical trials, however, subgroups of patients with anterior myocardial infarction that reached the target temperature before reperfusion did show a reduction in infarct size. To transform therapeutic hypothermia into a clinically feasible treatment for AMI, its method must be modified. An ideal technique should be quick enough to achieve sufficient myocardial hypothermia before reperfusion, without significant delay and without the adverse effects of systemic cooling. In this review, we propose a novel, potentially feasible method of selective intracoronary hypothermia to overcome the problems encountered with prior techniques.\u3c/p\u3

Usefulness of intra-aortic balloon pump counterpulsation

\u3cbr/\u3eIntra-aortic balloon pump (IABP) counterpulsation is the most widely used mechanical circulatory support device because of its ease of use, low complication rate, and fast manner of insertion. Its benefit is still subject of debate, and a considerable gap exists between guidelines and clinical practice. Retrospective nonrandomized studies and animal experiments show benefits of IABP therapy. However, recent large randomized trials do not show benefit of IABP therapy, which has led to a downgrading in the guidelines. In our view, this dichotomy between trials and practice might be the result of insufficient understanding of the prerequisites needed for effective IABP therapy, that is, exhausted autoregulation, and of not including the right patient population in trials. The population included in recent large randomized trials has been heterogeneous, also including patients in whom benefit of IABP could not be expected. The clinical condition in which most benefit is expected, that is persistent ischemia in acute ST-elevation myocardial infarction, is discussed in this review. In conclusion, this review aims to explain the physiological principles needed for effective IABP therapy, to reflect critically on the large randomized trials, and to solve some of the controversies in this field.\u3cbr/\u3e\u3cbr/\u3e\u3cbr/\u3e\u3cbr/\u3eAppropriate use of intra-aortic balloon pump (IABP) counterpulsation has been subject to heavy debate over the past years.1, 2, 3 and 4 Use of IABP is generally confined to 3 groups of patients, that is, high-risk percutaneous coronary intervention (PCI), acute myocardial infarction, and cardiogenic shock. There have been large randomized trials for all 3 indications, which will be discussed in the following sections. However, before analyzing these trials in detail, it is mandatory to better understand the presumed physiological principles of IABP counterpulsation and the prerequisites needed for adequate effect (or absence of effect) of IABP.\u3cbr/\u3

Safety and feasibility of local myocardial hypothermia

\u3cp\u3eBackground In ST-elevation myocardial infarction (STEMI), reduction in time to reperfusion of the occluded coronary artery reduces infarct size. In animal models, an additional reduction of infarct size was observed when hypothermia was induced before reperfusion, despite a longer ischemic time. However, several human studies did not corroborate this positive effect, which is believed to be in part due to the inability of systemic induced hypothermia to induce sufficient decrease of local myocardial temperature before reperfusion. Providing rapid local myocardial hypothermia by intracoronary infusion of saline before reperfusion in patients with STEMI may overcome this problem. In this study, we evaluate the safety and feasibility of providing rapid intracoronary myocardial hypothermia in patients undergoing intracoronary blood flow measurements based on thermodilution with continuous infusion of saline at room temperature. Methods and Results In 53 patients with stable angina (SA) and 20 patients with STEMI, a total of 215 measurements were performed. The measurements consisted of continuous selective intracoronary infusion of saline at room temperature with rates between 10 ml/min and 30 ml/min. Temperature changes compared to initial blood temperature (T\u3csub\u3eb\u3c/sub\u3e) were measured at the tip of the infusion catheter (T\u3csub\u3ei\u3c/sub\u3e) and distally in the coronary artery (T\u3csub\u3ed\u3c/sub\u3e). In patients with SA, T\u3csub\u3ei\u3c/sub\u3e was -5.65 ± 1.41°C (range -9.27 to -2.28) and T\u3csub\u3ed\u3c/sub\u3e was -0.78 ± 0.51°C (range -3.27 to -0.23°C). In patients with STEMI, T\u3csub\u3ei\u3c/sub\u3e was -7.45 ± 0.51°C (range -8.21 to -6.56) and T\u3csub\u3ed\u3c/sub\u3e was -1.37 ± 0.82°C (range -4.62 to -0.74°C). In all patients, steady-state intracoronary hypothermia was achieved within 15 sec and could be maintained without noticeable complications. Conclusion This study demonstrates the safety and feasibility of inducing intracoronary hypothermia by selective infusion of saline at room temperature in patients with SA and STEMI. Steady-state hypothermia could be achieved and maintained quickly, easily, and safely using common PCI techniques. Therefore, our findings warrant further studies to the use of intracoronary hypothermia to enhance myocardial salvage in acute myocardial infarction.\u3c/p\u3