Form Of Myocardial Protection Research Articles

Effect on the Brain of Two Techniques of Myocardial Protection

This study compared the occurrence of intraoperative microemboli and postoperative changes in neuropsychological performance in 195 patients undergoing coronary artery bypass grafting who were randomized to intermittent crossclamp fibrillation or cardioplegic arrest. Cerebral microemboli were recorded from cannulation to 15 min after decannulation, using transcranial Doppler in 166 patients. Microemboli in relation to 9 surgical events were also noted. Neuropsychological change scores were obtained by comparing cognitive performance preoperatively with that at 6-8 weeks after surgery. The median number of microemboli detected was 105 (range, 9-1,757) in the fibrillation group, and 110 (range, 1-1,306) in the cardioplegia group, with no significant difference between groups. There was also no significant difference between groups in the generation of microemboli during any of the surgical events. Neuropsychological tests were completed postoperatively by 177 participants, with no significant differences in performance found between the 2 groups. Given the equivalence of the effect of intermittent crossclamp fibrillation and cardioplegic arrest on microemboli and neuropsychology, consideration of which form of myocardial protection to employ should perhaps focus more on which method affords most protection to the heart.

The role of K+ATP channels in the control of pre- and post-ischemic left ventricular developed pressure in septic rat hearts

Myocardial function is impaired 24 h after the induction of sepsis, however, recovery of left ventricular (LV) function after 35 min of global ischemia is complete. The mechanisms by which this protection occurs are unknown. Ischemic preconditioning, another form of myocardial protection from ischemia/reperfusion (I/R) injury, has been shown to be modulated by ATP-sensitive potassium (K+ATP) channels. To investigate the role of K+ATP channels in the regulation of coronary flow (CF) and protection from I/R injury in septic rat hearts, we assessed the effects of the K+ATP channel antagonist glibenclamide (GLIB) and the agonist cromakalim (CROM) on pre- and post-ischemic CF and left ventricular developed pressure (LVDP). Although GLIB decreased pre-ischemic CF in both control and septic rat hearts, LVDP was unaffected. After I/R, CF was decreased in GLIB-treated control and septic rat hearts and LVDP was more severely depressed in control rat hearts than in septic rat hearts. CROM increased pre-ischemic CF in the septic group although LVDP was unaltered in both groups. After I/R, control rat heart CF was depressed but LVDP completely recovered. Post-ischemic CF in septic rat hearts was elevated compared with vehicle-treated septic rat hearts, but the recovery of LVDP was not improved. These results suggest that K+ATP channels modulate CF in septic rat hearts, but do not mediate cardioprotection as observed in control rat hearts.

Ischemic preconditioning: the endogenous power--a review of the literature.

With the re-emergence of surgery on a beating heart, it is important to examine the unique phenomenon of ischemic preconditioning (IPC) and its role as a form of myocardial protection under these circumstances. Ischemic preconditioning is defined as a short period of ischemia, regional or global, imposed before a more prolonged period of ischemia, which increases the myocardium's tolerance to ischemia by endogenous adaptive mechanism. Until recently, it was generally held that repeated ischemic episodes would have a cumulative adverse effect and could lead to a "stuttering infarction."

New strategies in myocardial preservation.

Myocardial protection seems to be evolving toward simplified techniques, among which the use of minimally diluted tepid blood cardioplegia delivered retrograde or in a combined fashion is gaining wider clinical acceptance. In the future, agents that can duplicate the cardioprotective effects of ischemic preconditioning, prevent the cell-damaging calcium overload by inhibition of the sodium-hydrogen exchanger, and preserve endothelial function hold the greatest promises. The concept of hyperpolarized arrest (as opposed to the conventional potassium-induced depolarized arrest) also might be a breakthrough if it becomes clinically feasible. Finally, beating-heart (coronary) surgery without aortic cross-clamping possibly could be the ultimate form of myocardial protection, in particular if the inflammatory effects of cardiopulmonary bypass that adversely affect cardiac function can be mitigated by new developments in biomaterials and appropriate drug therapies.

Attenuation of Severity of Myocardial Ischemia During Repeated Daily Ischemic Episodes

Objectives. The purpose of this study was to assess whether the severity of myocardial ischemia would be attenuated by repeated daily ischemic episodes, recorded by ambulatory electrocardiographic monitoring (AEM).Background. Repetitive ischemic episodes induced by brief coronary occlusions in animal experiments and in humans during balloon coronary angioplasty produce preconditioning. We wanted to assess whether this phenomenon also exists during daily ischemic episodes.Methods. Twenty-one patients with known coronary artery disease and ischemia on exercise testing and AEM were requested to walk a distance known to have previously caused myocardial ischemia on three consecutive occasions. Walking time was ∼15 min and was followed by 5 min of rest.Results. Mean maximal heart rate during the three walks was similar; however, the mean maximal ST segment depression decreased significantly from 2.21 mm during the first walk to 1.61 mm and 1.43 mm, respectively, on the second and third walks (p = 0.001). Ischemia duration was also significantly reduced on the second and third walks by 56% from 514 to 228 and 254 s, respectively (p = 0.012). The heart rate at onset of ischemia (ischemic threshold) increased from 99 beats/min on the first walk to 101 beats/min on the second walk and to 106 beats/min on the third walk (p = 0.058).Conclusions. This study demonstrated attenuation of myocardial ischemia with an associated increase in ischemic threshold in patients with repeated and adjacent ischemic episodes. This form of myocardial protection is likely to be encountered in patients during ordinary activity and may represent the clinical counterpart of myocardial preconditioning.(J Am Coll Cardiol 1997;30:119–24)

Elective cardiac arrest with a hyperpolarizing adenosine triphosphate–sensitive potassium channel opener: A novel form of myocardial protection?

Hyperkalemic depolarized cardiac arrest has been the cornerstone of myocardial protection during cardiac surgery for more than 30 years. Many of the advances in myocardial protection seek to minimize the cellular damage and to reduce the ongoing metabolic processes occurring as a direct consequence of the depolarized state. Ideally, cardiac arrest at hyperpolarized cellular membrane potentials--the natural resting state of the heart--will meet all the requirements of modern cardioplegia, namely, electromechanical asystole and cardiac relaxation, while preserving the vital integrity of the heart itself. To determine whether activation of adenosine triphosphate-sensitive potassium channels by pharmacologic agents could produce hyperpolarized cardiac arrest, we tested the ability of aprikalim, a known adenosine triphosphate-sensitive potassium channel opener, to arrest the intact beating heart. In a normothermic (37 degrees C) isolated rabbit heart preparation, aprikalim was found to rapidly shorten the action potential duration and produce cardiac asystole that was maintained during 20 minutes of "no-flow" global ischemia without a rise in end-diastolic pressure. Cardiac rhythm and function were fully restored by reperfusion alone (developed pressure was 100.6% +/- 7.9% of prearrest value after 30 minutes of reperfusion). In contrast, 20 minutes of unprotected normothermic global ischemia resulted in a 2.7 +/- 0.55 mmHg rise in end-diastolic pressure and only 58.2% +/- 3.8% recovery of developed pressure after 30 minutes of reperfusion. By way of comparison, 20 minutes of standard hyperkalemic depolarized normothermic rest was accompanied by a 1.2 +/- 0.6 mmHg rise in end-diastolic pressure and only 80.8% +/- 2.6% recovery of developed pressure after 30 minutes of reperfusion. To directly compare hyperkalemic depolarized cardiac arrest to hyperpolarized cardiac arrest induced by potassium channel openers and to better define the characteristics of such hyperpolarized arrest, we studied a fixed (4 mmHg rise in end-diastolic pressure--contracture) ischemic injury model. The time to development of the contracture was prolonged by hyperkalemic arrest (35.8 +/- 1.7 minutes) and significantly more so by hyperpolarized arrest (47.0 +/- 3.3 minutes) when compared with that of unprotected hearts (24.0 +/- 1.2 minutes). Moreover, aprikalim resulted in significantly better postischemic recovery of function (developed pressure was 69.0% +/- 6.7% of prearrest value after 30 minutes of reperfusion) than after no cardioplegia (45.4% +/- 7.5%) or standard hyperkalemic cardioplegia (44.3% +/- 5.7%). Pharmacologic activation of adenosine triphosphate-sensitive potassium channels can result in predictable and sustainable hyperpolarized cardiac arrest that is reversible by reperfusion. This method of myocardial protection was found to fully preserve cardiac electromechanical function after a 20-minute period of global normothermic ischemia. Furthermore, hyperpolarized arrest induced by potassium channel openers significantly prolonged the period to the development of contracture and afforded a significantly better postischemic recovery of function than obtained in either hearts protected with hyperkalemic depolarized arrest or those not protected by any form of cardioplegia.