Myocardial Protection In Cardiac Surgery Research Articles

Postconditioning the Human Heart with Adenosine in Heart Valve Replacement Surgery

The effect of adenosine postconditioning on myocardial protection in cardiac surgery remains uncertain. The present study evaluated the safety, feasibility, and beneficial effect of adenosine postconditioning as an adjunct to predominantly used cold-blood cardioplegic myocardial protection method in the setting of heart valve replacement operations. Sixty patients with rheumatic heart valve disease undergoing heart valve replacement operations were randomized to an adenosine (1.5 mg/kg) or saline (as control) bolus injection through an arterial catheter immediately after the aorta cross-clamp was removed. The surgical indications were similar in both groups, and heart valve replacement was successful in all patients. The extubation time and postoperative hospital time were similar in both groups. Compared with the control group, however, the inotrope scores in the intensive care unit (ICU) were much lower (p < 0.01), and the ICU time was significantly shorter (p < 0.05) in adenosine group. More important, cardiac troponin I release was less in the adenosine group, especially at 12 and 24 hours after reperfusion (p < 0.01), and total cardiac troponin I release estimated with the area under curve was also significantly reduced during the first 24 hours after reperfusion (p < 0.01). A 1.5-mg/kg bolus administration of adenosine through an arterial catheter immediately after the aorta cross-clamp is removed is feasible and well tolerated in patients undergoing heart valve replacement. An adenosine postconditioning adjunct to high potassium cold blood myocardial protection is related to less troponin I release, less inotropic drug use, and shorter ICU stay.

Caffeic acid phenethyl ester (CAPE) supplemented St. Thomas’ hospital cardioplegic solution improves the antioxidant defense system of rat myocardium during ischemia-reperfusion injury

Background and aim of study: Cardioplegic arrest remains the method of choice for myocardial protection in cardiac surgery. Caffeic acid phenethyl ester (CAPE) prevents lipid peroxidation induced by ischemia-reperfusion injury and has a potent antioxidant property. We investigated the advantages of CAPE supplemented cardioplegic solution (St. Thomas’ Hospital cardioplegic solution No.: 2) on the antioxidant defense system of myocardium against ischemia-reperfusion injury. Material and methods: Isolated rat hearts were mounted on a nonrecirculating type of Langendorff apparatus. The hearts were arrested for 60 min with cardioplegic solution given at 20-min intervals and then reperfused for 15 min. The hearts were divided into three groups. Cold saline (0.9%, 4 °C) in group 1, St. Thomas’ Hospital solution in group 2 and CAPE added St. Thomas’ Hospital solution in group 3 were used as the cardioplegic solution. Krebs–Henseleit buffer solution was used for reperfusion. The tissues were examined biochemically for oxidative stress. Results: Significant differences among the three groups existed in tissue myeloperoxidase (MPO), catalase (CAT), Na +–K + ATPase activity and in the concentrations of malonydealdehyde (MDA) and 3-nitrotyrosine (3-NT). Group 2 showed significant changes in MPO ( P = 0.04), Na +–K + ATPase enzyme activity ( P = 0.02) and the levels of MDA ( P = 0.004) and 3-NT ( P = 0.01) in comparison with group 1. Group 3 efficiently reduced MDA levels ( P = 0.004) and also led to significant decrease in levels of MPO ( P = 0.006), 3-NT ( P = 0.01) and Na +–K + ATPase activity ( P = 0.01) and increase in the level of CAT ( P = 0.004) in comparison with group 1. Significant changes were also found in the levels of MDA ( P = 0.03), MPO ( P = 0.04) and CAT ( P = 0.009) in comparison between groups 2 and 3. Conclusions: We demonstrated that the administration of CAPE into cardioplegic solutions improves the antioxidant defense system of rat heart during the ischemia-reperfusion injury.

Pre? and postconditioning during cardiac surgery

In spite of improved myocardial protection, postoperative arrhythmias and cardiac failure are still important problems causing morbidity and mortality in cardiac surgery. Ischemic preconditioning has been widely investigated experimentally with the purpose of identifying new therapeutic agents, but we have not unraveled the underlying mechanisms and we are not able yet to exploit them pharmacologically in clinical practice. Studies of preconditioning in cardiac surgery provide conflicting results, but the majority of studies show that ischemic preconditioning is an effective adjunct to myocardial protection in cardiac surgery. Interventions aimed at modifying reperfusion, or postconditioning, have the advantage that they also can be used after the ischemic insult has occurred, i.e. also in situations with "non-scheduled" ischemia. Postconditioning, as preconditioning, needs pharmacological mimics to be used routinely in settings of cardiac surgery or other human interventions. Possible common signaling pathways of the two phenomena are discussed, and suggested directions for clinical studies are outlined.

BH4 peptide derivative from Bcl-xL attenuates ischemia/reperfusion injury thorough anti-apoptotic mechanism in rat hearts

To prevent apoptosis is thought to be promising for myocardial protection in cardiac surgery. Recently, we showed that BH4 domain of Bcl-xL is essential for the prevention of apoptosis, and that BH4 fused to HIV TAT protein (TAT-BH4) prevented apoptotic cell death. Then, we hypothesized TAT-BH4 may attenuate ischemia/reperfusion injury in rat hearts. The isolated rat hearts in the TAT-BH4 preconditioning group (BH4 group, n=8) or control group (C group, n=8) were subjected to warm ischemia (37 degrees C) for 30 min followed by 60 min of reperfusion using Langendorff perfusion system. Left ventricular developed pressure and maximum dP/dt after reperfusion were significantly improved in the BH4 group than those in the C group (P<0.01). Recovery of mitochondrial respiration was significantly better in the BH4 group (P<0.05). Moreover, expression of caspase-3 and TUNEL-positive myocardium were decreased in the BH4 group than those in the C group. These results demonstrated that TAT-BH4 attenuates myocardial ischemia/reperfusion injury through preventing myocardial apoptosis. Thus, TAT-BH4 may be a novel therapeutic agent for myocardial protection in cardiac surgery.

Prevention of myocardial reperfusion injury by poly(ADP-ribose) synthetase inhibitor, 3-aminobenzamide, in cardioplegic solution: in vitro study of isolated rat heart model.

Cardioplegic arrest remains the method of choice for myocardial protection in cardiac surgery. Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury in myocardial infarction by preventing energy depletion associated with oxidative stress. We investigated the efficacy of a cardioplegic solution containing a PARS inhibitor, 3-aminobenzamide (3-AB), for myocardial protection against ischemia-reperfusion injury caused by cardioplegic arrest. Isolated hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution given at 30-min intervals and then reperfused for 20 min. The hearts of rat in the 3-AB(-) group (n = 8) were perfused with a standard cardioplegic solution and terminal warm cardoplegia, whereas the 3-AB(+) group (n = 8) received these solutions supplemented with 3-AB (100 microM). Left ventricular function and release of cardiac enzymes were monitored before and after cardioplegic arrest. After reperfusion, NAD+ (nicotinamide-adenine dinucleotide) levels were assessed, and the tissues were examined immunohistochemically for oxidative stress and apoptosis. During reperfusion, the 3-AB(+) group showed significantly higher (P = 0.005)dp/dt and lower creatine phosphokinase (CPK) level and glucotamic-oxaloacetic transaminase (GOT) in the effluent (CPK; P = 0.003 GOT; P < 0.001) The cardiomyocytes of the 3-AB(+) group also preserved a higher NAD+ level (P < 0.001). Immunohistochemical study of oxidative stress revealed a lesser extent (P = 0.007) of nuclear staining and a lower fraction of apoptosis in the 3-AB(+) group. Cardioplegic solution supplemented with 3-AB provides efficient myocardial protection in cardioplegic ischemic reperfusion by suppressing oxidative stress and overactivation of PARS.

Ischemia alone is sufficient to induce TNF-alpha mRNA and peptide in the myocardium.

Over-production of tumor necrosis factor-alpha (TNF-alpha) following myocardial ischemia-reperfusion contributes to cardiac dysfunction, and anti-TNF-alpha has therapeutic potential for myocardial protection in cardiac surgery with obligatory ischemia. It remains unclear, however, whether myocardial TNF-alpha production occurs during ischemia and whether cardiac myocytes constitute a source of myocardial TNF-alpha. Ischemia alone has been shown to activate myocardial NF-kappaB. We hypothesized that ischemia alone is sufficient to induce myocardial TNF-alpha gene expression and peptide synthesis. We examined TNF-alpha production and NF-kappaB activation in the isolated rat heart subjected to global normothermic ischemia. Myocardial ischemia resulted in rapid IkappaB-alpha degradation and NF-kappaB activation. Immunofluorescence staining detected NF-KB intranuclear translocation primarily in myocardial interstitial cells. Ischemia alone induced a time-dependent increase in myocardial TNF-alpha. TNF-alpha peptide increased to 20.3+/-3.0 pg/mg after 25 min of ischemia (P < 0.05 vs 8.9+/-2.0 pg/mg in perfusion control). TNF-alpha was also localized to myocardial interstitial cells. Increased TNF-alpha peptide level correlated with TNF-alpha mRNA expression. We conclude that ischemia alone induces TNF-a gene expression and peptide synthesis in the myocardium that are associated with NF-kappaB activation. Non-myocytes constitute the main source of myocardial TNF-alpha following ischemia. The results suggest that therapeutic strategies attempting to decrease myocardial TNF-alpha production need to be applied before or in the early phase of ischemia.

Assessment of the myocardial protective effect of antegrade warm blood cardioplegia by measuring the release of biochemical markers.

Intermittent warm blood cardioplegia has been reported as a valuable alternative for myocardial protection in cardiac surgery; however, conflicting experimental data have been published. To assess the clinical effectiveness of intermittent warm cardioplegia, we measured the release of troponin-T (Tn-T), a highly sensitive and specific marker of myocardial damage, and creatine kinase MB isoenzyme (CK-MB), in 12 patients who underwent elective coronary artery bypass grafting (CABG) with antegrade intermittent warm blood cardioplegia (37 degrees C) being the warm group, in comparison with 16 patients who underwent CABG with antegrade intermittent cold blood cardioplegia (4 degrees C) being the cold group. Blood samples were taken to determine the serum concentrations of CK-MB and Tn-T, at the induction of anesthesia, then 3, 6, 12, and 24h after the termination of cardiopulmonary bypass (CPB). The peak increase in serum CK-MB levels, 3h after CPB, was significantly lower in the warm group than in the cold group, at 27.8+/-7.8 IU/l vs. 40.8+/-12.6 IU/l, respectively (P = 0.0042). The serum Tn-T 12 h after CPB was significantly lower in the warm group than in the cold group, at 1.40+/-0.71 ng/ml vs. 2.06+/-0.95 ng/ml, respectively (P = 0.049). In conclusion, intermittent antegrade warm blood cardioplegia showed effective myocardial protection in elective CABG.

Protection of the myocardium with sodium-hydrogen exchange inhibitors: A cardiac surgical perspective.

Strategies for myocardial protection in cardiac surgery are directed at the prevention of procedure-induced ischemia/reperfusion injury as well as metabolic resuscitation in acute ischemic syndromes. Postreperfusion myocardial dysfunction remains a significant clinical problem, most importantly in certain high-risk patient groups. The large body of experimental evidence demonstrating a significant role for sodium-hydrogen exchange activation in myocardial ischemia/reperfusion injury suggests that the ability to pharmacologically inhibit the exchanger presents a promising new approach to current myocardial preservation techniques.

Alterations in the beta-adrenergic receptor system after hypothermic ischemia in hearts with preischemic beta-receptor desensitization.

Although hypothermic cardioplegic arrest is a basic method of myocardial protection in cardiac surgery, the beta-adrenergic receptor (BAR) system has been little investigated in the heart subjected to hypothermic ischemia. Additionally, although the hypothermic arrest is often induced in hearts with preischemic desensitization of the BAR system by preceding congestive heart failure, the functional state of the BAR system after ischemia has not been studied in these hearts. We investigated alterations in the BAR system after hypothermic ischemia in normal rat hearts and in those with preischemic desensitization of the BAR system produced with isoproterenol (ISP: 400 micrograms/kg/hr for 24 hr). Both normal and BAR-desensitized hearts were isolated and subjected either to 40 min of hypothermic (10 degrees C) global ischemia followed by 40 min of reperfusion or subjected to time-matched aerobic perfusion with modified Krebs-Henseleit solution. At the end of perfusion (1) BAR binding properties with [3H]CGP-12177 and adenylate cyclase activity were measured in crude membrane fraction and (2) the inotropic response to ISP (delta LV + dP/dtmax) was evaluated in an isovolumetric contracting heart preparation. Following reperfusion, normal hearts without desensitized BAR showed a higher Bmax value than those of nonischemic time-matched hearts (41.8 +/- 3.1 vs 35.4 +/- 2.4 fmole/mg protein, P less than 0.05), whereas the Kd value was in a similar range in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial protection in cardiac surgery: Experimental evaluation and clinical assessment of leukocyte-depleted terminal blood cardioplegia

Myocardial protection in cardiac surgery: Experimental evaluation and clinical assessment of leukocyte-depleted terminal blood cardioplegia

Preventive insulin administration for myocardial protection in cardiac surgery.

The object of this study was to determine whether high doses of insulin administered preventively in combination with glucose and potassium exert a protective effect upon the myocardium. This approach should result in a preoperative accumulation of the myocardial glycogen stores with an increased anaerobic provision of energy-rich substrates (ATP) during coronary ischemia. Two comparable groups of seven dogs each, undergoing experimental extracorporeal circulation (ECC) with 90-min aortic cross-clamping were examined. Cardiac output (CO), systolic left ventricular blood pressure (pventr), left ventricular enddiastolic pressure (LVEDP), mean central venous pressure (CVP), and heart rate (HR) were recorded at left atrial (LA) pressures of 5, 10, 15, and 20 mmHg in order to construct ventricular function curves. These data were registered prior to the onset of ECC (preischemic value), after termination of ECC and after two 10-min periods of reperfusion. The first group served as control and the second group received high iv doses of insulin (total 25 U/kg) within 60 min prior to the onset of the ECC. In the control group, pventr and CO after termination of the ECC and after the first reperfusion were significantly (P less than 0.05) less than the preischemic values; after the second reperfusion they reached the preischemic range. In contrast, pventr and CO in the insulin group already were within the preischemic range at the termination of the ECC. After the first and the second reperfusion, CO was even greater than the preischemic value. LVEDP changed inversely, while CVP and HR showed no significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)