Adenosine-lidocaine Cardioplegia Research Articles

Effects of Graft Preservation Conditions on Coronary Endothelium and Functional Recovery in a Rat Model of Donation after Circulatory Death

Purpose Donation after circulatory death (DCD) could significantly improve cardiac graft availability. However, DCD hearts are subjected to potentially damaging conditions prior to circulatory arrest and during warm ischemia and reperfusion. Although the feasibility of DCD heart transplantation has been demonstrated, protocols for graft preservation and storage require optimization to ensure graft quality. Therefore, we aimed to compare the current clinical conditions used for heart preservation (St. Thomas n°2) with a potentially more suitable solution for DCD hearts, evaluating endothelial and cardiac function to investigate differences in cardioprotective effects. Methods Following anaesthesia, diaphragm transection, and circulatory arrest in male Wistar rats to simulate DCD conditions, hearts were subjected to either 0 or 18 minutes of warm, in-situ ischemia. At end-ischemia, hearts were perfused with either: St. Thomas n°2 cardioplegia at 4°C as in current clinical practice, or normokalemic, adenosine-lidocaine cardioplegia (A-L) at 4°C or 22°C. Afterwards, hearts were stored for 15 min in their respective solutions, and then reperfused ex-situ for either 30 min (to assess endothelial function) or 60 min (to assess cardiac function and biochemical parameters). Results A-L cardioplegia at 22°C better preserves vascular function as compared to cold A-L or St. T cardioplegia, as demonstrated by greater eNOS coupling (p Conclusion Use of A-L and avoidance of profound hypothermia and hyperkalemic cardioplegia could improve endothelial and contractile function, potentially through the promotion of eNOS dimerization and activation of the RISK pathway; these approaches should help to optimize clinical protocols in DCD heart transplantation and facilitate its widespread adoption in clinical practice.

Enhanced myocardial protection in cardiac donation after circulatory death using Intralipid® postconditioning in a porcine model.

Intralipid® (ILE), a clinically used lipid emulsion, reduces ischemia-reperfusion (IR) injury in healthy and infarct-remodelled rat hearts. We tested whether ILE is also cardioprotective in large porcine hearts in the context of the donation after circulatory death (DCD) model, where human hearts are procured for transplantation after cardiac arrest and thus are exposed to significant IR injury. After induction of anesthesia, surgical preparation, termination of ventilator support, and cardiac arrest, hearts of female pigs were procured following a 15 min standoff period, with an optimized normokalemic crystalloid adenosine-lidocaine cardioplegia. Hearts were then randomly allocated to ex vivo reperfusion (38°C) in the absence (control) or presence of 1% ILE. All hearts were perfused with blood and Krebs-Henseleit solution (1:1) for 30 min in Langendorff mode and for an additional 30 min in working mode to assess mechanical function. Left ventricular (LV) biopsies were obtained after five minutes of reperfusion and LV tissue was preserved at the end of reperfusion for biochemical analyses and immunohistochemistry. Intralipid® postconditioning reduced cell membrane damage as assessed by the mean (standard deviation) leakage of myocardial glutathione disulfide (39 (9) nmol·mg-1 protein vs 19 (7) nmol·mg-1 protein; P = 0.006), protected LV tissue from protein carbonylation (3.4 [0.6] nmol·mg-1 protein vs 5.3 [0.9] nmol·mg-1 protein; P = 0.006), decreased myeloperoxidase activity (35 [8] nmol·min-1·mg-1 protein vs 75 [11] nmol·min-1·mg-1 protein; P < 0.001), and increased inotropy (maximum rate of rise of LV pressure 2001 [345] mmHg·sec-1vs 1584 [192] mmHg·sec-1; P = 0.044). Intralipid® postconditioning triggered reactive oxygen species signalling at early reperfusion and activated protection signalling (Akt, signal transducer and activator of transcription 3, and glycogen synthase kinase 3β) in LV tissue, recapitulating all features of ILE-mediated protection reported in small rodent hearts. Our data show that ILE postconditioning elicits protection signalling in large mammalian hearts while mimicking clinical conditions, and is capable of enhancing protection of DCD hearts.

(735) - Impact of Initial Acidic Reperfusion on the Functional Recovery of DCD Hearts During Ex Vivo Heart Perfusion

s S251 normothermic beating state and transitioned into working mode for assessment of myocardial function by measuring the cardiac index (mL/minute/gram heart tissue) achieved at a left atrial pressure of 8 mmHg and an aortic diastolic pressure of 40 mmHg. RESULTS: Hearts sustained an equivalent period of warm ischemia (5 C1⁄428 1, 25 C1⁄429 1, 35 C1⁄427 1 minutes, p1⁄40.50) prior to IR. During IR coronary blood flow (5 C1⁄4483 53, 25 C1⁄4722 60, 35 C1⁄4906 36 mL/min, p<0.01) and coronary sinus lactate concentration (5 C1⁄4 0.73 0.06, 25 C1⁄41.33 0.03, 35 C1⁄41.75 0.15 umol/L, p<0.01) differed among treatment groups. Greater preservation of endothelial cell integrity (electron microscopy endothelial injury score: 5 C1⁄43.2 0.5, 25 C1⁄41.8 0.2, 35 C1⁄41.7 0.3, p1⁄40.01) and less myocardial injury (troponin I: 5 C1⁄491 6, 25 C1⁄464 16, 35 C1⁄457 7 pg/ mL/gram, p1⁄40.04) were evident in hearts reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of indexed cardiac output (5 C1⁄43.9 0.8, 25 C1⁄46.2 0.4, 35 C1⁄46.5 0.0.6 mL/min/ gram, p<0.01). CONCLUSION: Avoidance of profound hypothermia during IR with a normokalemic adenosine-lidocaine cardioplegia minimizes injury and improves the functional recovery of DCD hearts. 384 GENDER SPECIFIC INFLUENCES ON EFFECTOR T-CELL FUNCTION AND PROLIFERATION: 2-METHOXYESTRADIOL MODULATES CELLULAR REJECTION JG Luc, JY Zhao, ED Michelakis, DH Freed, J Nagendran

AVOIDANCE OF PROFOUND HYPOTHERMIA DURING INITIAL REPERFUSION IMPROVES THE FUNCTIONAL RECOVERY OF DCD HEARTS

s S251 normothermic beating state and transitioned into working mode for assessment of myocardial function by measuring the cardiac index (mL/minute/gram heart tissue) achieved at a left atrial pressure of 8 mmHg and an aortic diastolic pressure of 40 mmHg. RESULTS: Hearts sustained an equivalent period of warm ischemia (5 C1⁄428 1, 25 C1⁄429 1, 35 C1⁄427 1 minutes, p1⁄40.50) prior to IR. During IR coronary blood flow (5 C1⁄4483 53, 25 C1⁄4722 60, 35 C1⁄4906 36 mL/min, p<0.01) and coronary sinus lactate concentration (5 C1⁄4 0.73 0.06, 25 C1⁄41.33 0.03, 35 C1⁄41.75 0.15 umol/L, p<0.01) differed among treatment groups. Greater preservation of endothelial cell integrity (electron microscopy endothelial injury score: 5 C1⁄43.2 0.5, 25 C1⁄41.8 0.2, 35 C1⁄41.7 0.3, p1⁄40.01) and less myocardial injury (troponin I: 5 C1⁄491 6, 25 C1⁄464 16, 35 C1⁄457 7 pg/ mL/gram, p1⁄40.04) were evident in hearts reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of indexed cardiac output (5 C1⁄43.9 0.8, 25 C1⁄46.2 0.4, 35 C1⁄46.5 0.0.6 mL/min/ gram, p<0.01). CONCLUSION: Avoidance of profound hypothermia during IR with a normokalemic adenosine-lidocaine cardioplegia minimizes injury and improves the functional recovery of DCD hearts. 384 GENDER SPECIFIC INFLUENCES ON EFFECTOR T-CELL FUNCTION AND PROLIFERATION: 2-METHOXYESTRADIOL MODULATES CELLULAR REJECTION JG Luc, JY Zhao, ED Michelakis, DH Freed, J Nagendran

An experimental study on the endothelium protective effect of adenosine-lidocaine cardioplegia on canine coronary artery

Objective By observing the changes in levels of nitric oxide (NO),endothelin (ET) and circulating endothelial cells (CEC),and that in functions of coronary vasomotor,the author discusses the protective effects of adenosine-Lidocaine cardioplegia on endothelial cells of canine coronary artery and its possible mechanism.Methods 12 mongrel dogs were randomly divided into two groups:experimental group with Adenosine-lidocaine cardioplegia (AL group,n =6) and the control group with ST.Thomas Ⅱ cardioplegia (K group,n =6).Measured the changes in levels of NO,ET and CEC on three time points:before operation (T1),1 h after heart re-beat (T2) and 2 h after heart re-beat (T3),observed the changes in functions of coronary vasodilation,and analyzed the coronary ultrastructure by using electron microscope.Results There were no statistical differences between the two groups in T1.On the time point of T3,NO in plasma of group K has been significantly decreased than that of group AL (P ＜ 0.05).ET has been increased significantly (P ＜ 0.05),so as CEC (P ＜ 0.05).The maximum percentage of coronary vasodilation in group K is (29.13 ± 8.24)％ which is lower than that of AL group (68.52 ± 11.32)％ (P ＜ 0.01).Electron microscopy results show that the damage of coronary vascular endothelial cell ultrastructure of group K is more serious than that of group AL.Conclusion The protective effect of Adenosine-Lidocaine cardioplegia on canine coronary vascular endothelial cell is superior to that of ST.Thomas Ⅱ cardioplegia. Key words: Adenosine ; Lidocaine; Cardiopulmonary bypass; Coronary artery ; Circulating endothelial cell

Initial Reperfusion of DCD Hearts Under Hypothermic Conditions Impairs Myocardial Functional Recovery During Ex Vivo Heart Perfusion.

Objective: Initial reperfusion (IR) of donor hearts following circulatory death (DCD) with cardioplegia may facilitate restoration of ion homeostasis prior to myocardial contraction, minimize ischemia-reperfusion injury, and optimize functional recovery. We investigated the impact of IR temperature on the recovery of myocardial function during ex vivo heart perfusion. Methods: Eighteen pigs were anesthetized, mechanical ventilation was discontinued, and cardiac arrest ensued. A 15-minute standoff period was observed and then hearts were procured and reperfused with a normokalemic adenosine-lidocaine crystalloid cardioplegia for 3 minutes at 3 different temperatures (5°C; N=6, 25°C; N=5, and 35°C; N=7). Hearts were then perfused ex vivo in a normothermic beating state and transitioned into working mode (left atrial pressure: 8 mmHg) at 1, 3, and 5 hours for assessment of myocardial function using a conductance catheter. Results: Hearts sustained an equivalent period of warm ischemia (5°C=28±1, 25°C=29±1, 35°C=27±1 minutes, p=0.50) prior to IR. IR coronary blood flow (5°C=483±53, 25°C=722±60, 35°C=906±36 mL/min, p<0.01) and coronary sinus lactate concentration (5°C=0.73±0.06, 25°C=1.33±0.03, 35°C=1.75±0.15 umol/L, p<0.01) differed among treatment groups. IR under hypothermic conditions impaired systolic (dP/dt max) and diastolic (dP/dt min) functional recovery (Figure 1). Electron microscopy revealed greater preservation of endothelial cell integrity in hearts reperfused at warmer temperatures (injury score 5°C=3.2±0.5, 25°C=1.8±0.2, 35°C=1.7±0.3 minutes, p=0.01). Conclusions:Avoidance of profound hypothermia during IR with an adenosine-lidocaine cardioplegia preserves endothelial integrity and improves the functional recovery of DCD hearts.Figure: No Caption available.

A cardioprotective preservation strategy employing ex vivo heart perfusion facilitates successful transplant of donor hearts after cardiocirculatory death

Ex vivo heart perfusion (EVHP) has been proposed as a means to facilitate the resuscitation of donor hearts after cardiocirculatory death (DCD) and increase the donor pool. However, the current approach to clinical EVHP may exacerbate myocardial injury and impair function after transplant. Therefore, we sought to determine if a cardioprotective EVHP strategy that eliminates myocardial exposure to hypothermic hyperkalemia cardioplegia and minimizes cold ischemia could facilitate successful DCD heart transplantation. Anesthetized pigs sustained a hypoxic cardiac arrest and a 15-minute warm ischemic standoff period. Strategy 1 hearts (S1, n = 9) underwent initial reperfusion with a cold hyperkalemic cardioplegia, normothermic EVHP, and transplantation after a cold hyperkalemic cardioplegic arrest (current EVHP strategy). Strategy 2 hearts (S2, n = 8) underwent initial reperfusion with a tepid adenosine-lidocaine cardioplegia, normothermic EVHP, and transplantation with continuous myocardial perfusion (cardioprotective EVHP strategy). At completion of EVHP, S2 hearts exhibited less weight gain (9.7 ± 6.7 [S2] vs 21.2 ± 6.7 [S1] g/hour, p = 0.008) and less troponin-I release into the coronary sinus effluent (4.2 ± 1.3 [S2] vs 6.3 ± 1.5 [S1] ng/ml; p = 0.014). Mass spectrometry analysis of oxidized pleural in post-transplant myocardium revealed less oxidative stress in S2 hearts. At 30 minutes after wean from cardiopulmonary bypass, post-transplant systolic (pre-load recruitable stroke work: 33.5 ± 1.3 [S2] vs 19.7 ± 10.9 [S1], p = 0.043) and diastolic (isovolumic relaxation constant: 42.9 ± 6.7 [S2] vs 65.2 ± 21.1 [S1], p = 0.020) function were superior in S2 hearts. In this experimental model of DCD, an EVHP strategy using initial reperfusion with a tepid adenosine-lidocaine cardioplegia and continuous myocardial perfusion minimizes myocardial injury and improves short-term post-transplant function compared with the current EVHP strategy using cold hyperkalemic cardioplegia before organ procurement and transplantation.

Abstract 255: A Normokalemic Nondepolarizing Cardioplegia Minimizes Myocardial Injury and Improves Cardiac Function in a Large Animal Model of Donation After Cardiocirculatory Death

Background: Procurement of donor hearts is typically preceded by delivery of a cold hyperkalemic cardioplegia (CP) that achieves arrest by depolarization of the membrane potential. This method has no intrinsic cardioprotective properties and may exacerbate ischemia-reperfusion (IR) injury. A tepid adenosine-lidocaine (AL) non-depolarizing CP has been shown to limit IR injury and improve myocardial functional recovery in a small animal model of orthotopic heart transplantation. We sought to determine the impact of AL CP on myocardial injury and function, in a porcine model of donation after cardio-circulatory death (DCD). Methods: Female Yorkshire pigs (60 kg) were subjected to a hypoxic cardiac arrest. Following a 15-minute standoff period donor hearts were procured, resuscitated ex-vivo, and transplanted into a recipient animal. Hearts in group 1 (N=7) were protected with a cold blood-Plegisol CP, perfused with a blood-crystalloid solution during ex-vivo assessment, and arrested with a cold blood-Plegisol CP prior to transplantation. Hearts in group 2 (N=5) were protected with a tepid AL-STEEN CP and perfused with a blood-STEEN solution in a continuous fashion during ex-vivo assessment and transplantation. Results: Animals in group 2 had a significantly longer ex-vivo perfusion time compared to those in group 1 (174±29 vs. 135±45 min, p&lt;0.05), yet they demonstrated significantly less weight gain (14±4 vs. 25±8 grams/hour, p&lt;0.05). Further, animals in group 2 exhibited less troponin I release during ex-vivo perfusion and had significantly better diastolic function following wean from cardiopulmonary bypass (left ventricular end-diastolic pressure volume relationship 0.115±0.052 vs. 0.508±0.223, p&lt;0.05). However, there was no significant difference in level of calpain activity between groups (171.3±68.6 vs. 140.12±50.6, p=0.36). Conclusion: A tepid non-depolarizing AL CP results in less myocardial edema during ex-vivo perfusion, minimizes myocardial injury, and improves diastolic function following transplantation of DCD hearts, but fails to eliminate the activation of calcium-dependent proteases. Further studies should investigate if a calpain inhibitor delivered at reperfusion could further minimize IR injury in DCD hearts.

Eight hours of cold static storage with adenosine and lidocaine (Adenocaine) heart preservation solutions: Toward therapeutic suspended animation

Most cardiac preservation solutions provide safe cold ischemic storage times for 4 to 5 hours. Our aim was to investigate the effects of 8 hours of cold static storage (4°C) using 2 normokalemic, polarizing adenosine-lidocaine (Adenocaine; Hibernation Therapeutics Global Ltd, Kilquade, Ireland) solutions and to compare their functional recovery with hearts preserved in gold standard histidine-tryptophan-ketoglutarate (Custodiol-HTK; Essential Pharma, Newtown, Pa) and Celsior (Genzyme, Cambridge, Mass) solutions. Male Sprague-Dawley rats (350-450 g) were randomly assigned to 1 of 4 groups (n=8): (1) adenosine-lidocaine cardioplegia with low Ca(2+)/high Mg(2+); (2) 2× adenosine-lidocaine cardioplegia, low Ca(2+)/high Mg(2+), melatonin, and insulin (2× adenosine, lidocaine, melatonin, and insulin); (3) histidine-tryptophan-ketoglutarate solution; or (4) Celsior. Hearts were perfused in working mode, arrested (37°C), removed, stored for 8 hours at 4°C, reattached in Langendorff mode and rewarmed for 5 minutes (37°C), and switched to working mode for 60 minutes. Myocardial oxygen consumption, effluent lactates, and troponin T levels were measured. Hearts preserved for 8 hours in adenosine-lidocaine and 2× adenosine, lidocaine, melatonin, and insulin returned 50% and 76% of aortic flow and 70% and 86% of coronary flow, respectively, at 60 minutes of reperfusion. In contrast, Custodiol-HTK and Celsior hearts returned 2% and 17% of aortic flow and 11% and 48% of coronary flow, respectively, at 60 minutes of reperfusion. Hearts preserved in adenosine-lidocaine and 2× adenosine, lidocaine, melatonin, and insulin returned 90% and 100% of developed pressures and 101% and 104% of heart rate, respectively. Hearts preserved in histidine-tryptophan-ketoglutarate failed to increase systolic pressure greater than 14 mm Hg (11% baseline) and diastolic pressure greater than 10 mm Hg (17% baseline), and recovered only 16% of heart rate. Hearts preserved in Celsior developed 70% of baseline systolic pressures and 86% recovery of heart rate. At 5 minutes of rewarming after cold storage, the myocardial oxygen consumption for hearts preserved in adenosine-lidocaine, 2× adenosine, lidocaine, melatonin, and insulin, Custodiol-HTK, and Celsior was 23.0 ± 5, 20 ± 4, 15 ± 1, and 10 ± 2 μmol O(2)/min/g dry wt, respectively, with corresponding lactate outputs of 1.8 ± 0.8, 1.5 ± 0.7, 2.6 ± 0.7, and 3.2 ± 1.4 μmol lactate/min/g dry weight. Troponin T was not detected in the coronary effluent of adenosine-lidocaine or 2× adenosine, lidocaine, melatonin, and insulin hearts, whereas Custodiol-HTK and Celsior hearts had troponin T levels of 0.08 and 0.24 μg/mL, respectively. We report a 78% return of cardiac output, 90% to 100% return of developed pressures, and 101% to 104% return of heart rate after 8 hours of cold static storage using normokalemic, adenosine, lidocaine, melatonin, and insulin preservation solution in the isolated rat heart compared with 55% cardiac output with polarizing adenosine-lidocaine cardioplegia alone, 4% cardiac output with Custodiol-HTK, and 25% cardiac output in Celsior preservation solutions.

Early reperfusion with warm, polarizing adenosine–lidocaine cardioplegia improves functional recovery after 6 hours of cold static storage

Rewarming and reanimating the donor heart from cold static storage predisposes the organ to injury and graft dysfunction. Our main aim was to investigate the effects of 5 minutes of continuous rewarming with a normokalemic, oxygenated, polarizing adenosine-lidocaine arrest solution after 6 hours of cold static storage (4°C) in adenosine-lidocaine or Celsior (Genzyme Corp, Cambridge, Mass) solutions. Male Sprague-Dawley rats (350-450 g, n = 40) were randomly assigned to one of 5 groups: (1) adenosine-lidocaine cold arrest with modified Krebs-Henseleit rewarming, (2) adenosine-lidocaine cold arrest with adenosine-lidocaine rewarming, (3) Celsior cold arrest with Celsior rewarming, (4) Celsior cold arrest with Krebs-Henseleit, and (5) Celsior cold arrest with adenosine-lidocaine arrest rewarming. Hearts were perfused in working mode, arrested (37°C), removed and stored for 6 hours at 4°C, reattached in Langendorff mode, and rewarmed for 5 minutes (37°C). Hearts were switched to working mode, and function was compared with prestorage values. Myocardial oxygen consumption and effluent lactate and pH values were measured during rewarming and recovery. Cold adenosine-lidocaine hearts rewarmed with Krebs-Henseleit recovered 40% aortic flow and 58% coronary flow at 60 minutes of reperfusion. Rewarming with adenosine-lidocaine arrest solution led to significantly higher aortic flow (63%) and coronary flow (77%) at 60 minutes. Cold Celsior hearts rewarmed with Celsior had 9 times higher effluent lactate values with acidosis (pH 6.5) during the last minute of rewarming compared with all groups, and this was associated with early myocardial, vascular, and electrical stunning. At 5 and 10 minutes of recovery, the aortic flow was 1.0 and 8 mL/min, respectively. If cold Celsior hearts were rewarmed with adenosine-lidocaine, they generated 18-fold higher aortic flow and 16-fold higher coronary flow at 5 minutes. At 60 minutes, cold Celsior with Celsior-rewarmed hearts recovered 35% aortic flow and 50% coronary flow compared with 44% aortic flow and 67% coronary flow (P < .05) for Celsior with adenosine-lidocaine-rewarmed hearts. Celsior with Krebs-Henseleit-rewarmed hearts recovered 39% aortic flow and 51% coronary flow and were not significantly different from Celsior-rewarmed hearts. The myocardial oxygen consumption in the last minute of rewarming was 1.6 times higher for cold adenosine-lidocaine hearts rewarmed with adenosine-lidocaine compared with cold Celsior and Celsior hearts (19 vs 12 μmol O(2)/min/g dry weight) along with low lactate values and no acidosis. Rewarming the rat heart after cold static storage in polarizing adenosine-lidocaine arrest solution resulted in significantly higher aortic flow, coronary flow, and cardiac output compared with that seen after Krebs-Henseleit or Celsior rewarming. Rewarming cold Celsior hearts with adenosine-lidocaine solution reduced stunning. Adenosine-lidocaine cardioplegia might offer a new reperfusion strategy after cold static storage.

Normokalemic adenosine–lidocaine cardioplegia: Importance of maintaining a polarized myocardium for optimal arrest and reanimation

Depolarizing potassium cardioplegia does not afford optimal cardioprotection in pediatric or adult patients requiring complicated operative procedures. Polarizing adenosine-lidocaine cardioplegia has been shown to be cardioprotective without hyperkalemia. Our aim was to examine the effects of changing extracellular potassium levels in adenosine-lidocaine cardioplegia on arrest and reanimation properties. Isolated-perfused rat hearts (n = 96) were arrested at 32 degrees C to 33 degrees C for 1 or 2 hours with intermittent 200 mumol/L adenosine and 500 mumol/L lidocaine in modified Krebs-Henseleit buffer with 0.1, 3.0, 5.9, 10, and 16 mmol/L potassium or with 16 or 25 mmol/L potassium in Krebs-Henseleit buffer (n = 8 for each group). Membrane potentials were estimated in the arrested ventricular myocardium (n = 42), and recovery function was measured in working mode during 60 minutes' reperfusion. Arrest was interrupted by breakout beats in the adenosine-lidocaine hypokalemic (0.1 and 3 mmol/L potassium) and non-adenosine-lidocaine hyperkalemic (16 and 25 mmol/L potassium) groups. The membrane potentials for the non-adenosine-lidocaine 16 and 25 mmol/L potassium groups were -51 and -39 mV, and those for the adenosine-lidocaine groups (0.1, 3.0, 5.9, 10, and 16 mmol/L potassium) were -183, -94, -75, -65, and -49 mV, respectively. After 1 hour of arrest, coronary vascular resistance increased linearly in adenosine-lidocaine cardioplegia with increasing potassium levels (5.9, 10, and 16 mmol/L), and the slope increased more than 2-fold after 2 hours. Nearly 40% of hearts in the adenosine-lidocaine (0.1 mmol/L potassium) and non-adenosine-lidocaine 25 mmol/L potassium groups failed to recover after 1 hour arrest. After 2 hours, hearts in the polarizing (5.9 mmol/L potassium) adenosine-lidocaine group increased coronary vascular resistance by only 30% and spontaneously recovered 107% heart rate, 92% systolic pressure, 81% aortic flow, and 113% coronary flow (all metrics returned 85% to 100% at 15 minutes) with no reperfusion arrhythmias. In contrast, hearts in the adenosine-lidocaine (3, 10, and 16 mmol/L potassium) groups were all slow to recover (15% to 40% return at 15 minutes) and experienced arrhythmias. Increasing potassium levels in adenosine-lidocaine cardioplegia from 5.9 to 16 mmol/L resulted in a 67% loss of left ventricular contractility. Polarizing adenosine-lidocaine cardioplegia (5.9 mmol/L potassium) administered intermittently at 33 degrees C provides superior arrest and reanimation profiles under normokalemic conditions when the myocardial cell membrane potential is close to its resting state.

Warm nondepolarizing adenosine and lidocaine cardioplegia: Continuous versus intermittent delivery

Continuous infusion of warm to normothermic cardioplegia may limit the surgeon's visual field, increase coronary vascular resistance, and lead to potassium-exacerbated ischemia-reperfusion damage. Our aim was to examine the versatility of a new normokalemic, nondepolarizing adenosine-lidocaine cardioplegia during continuous or intermittent infusion at 33 degrees C and compare it with lidocaine cardioplegia. Isolated, perfused rat hearts (n = 6 each group) were arrested at 33 degrees C for 40 or 60 minutes with 200 microm of adenosine and 500 microm of lidocaine in Krebs-Henseleit buffer (10 mmol/L glucose, pH 7.6-7.7 at 37 degrees C) or 500 microm of lidocaine in Krebs-Henseleit buffer for 60 minutes delivered at 60 mm Hg. Times to arrest were 7 to 10 seconds for the adenosine-lidocaine groups and 102 seconds for the lidocaine group (P < .05). Total cardioplegia volumes for intermittent (2 minutes every 18 minutes) and continuous deliveries were 122 to 159 mL and 699 to 922 mL for the 40- and 60-minute adenosine-lidocaine arrest protocols, respectively, and 136 mL for the 60-minute intermittent lidocaine group. In the last 2 minutes of the 40- and 60-minute arrest protocols, the coronary vascular resistance was not significantly different for the hearts arrested with adenosine and lidocaine (0.27-0.32 megadyne/sec/cm(-5)). Significantly higher coronary vascular resistance was found in the lidocaine cardioplegia group (0.38 megadyne/sec/cm(-5)). No significant differences were found between the continuous or intermittent adenosine-lidocaine delivery protocols. Hearts arrested with adenosine and lidocaine recovered 88% to 89% of aortic flow and 109% of coronary flow at 60 minutes of reperfusion after 40-minute arrest, and 77% to 86% of aortic flow and 98% to 109% of coronary flow at 60 minutes of reperfusion after 60-minute arrest. Lidocaine cardioplegia led to significantly lower aortic and coronary flows after 60-minute arrest compared with the intermittent adenosine-lidocaine group. We conclude that adenosine-lidocaine cardioplegia can be delivered intermittently or continuously with similar functional recoveries after a 40- or 60-minute arrest at 33 degrees C. Hearts receiving lidocaine cardioplegia took a significantly longer time to arrest, showed higher coronary vascular resistance, and achieved lower functional recovery than the 60-minute adenosine-lidocaine cardioplegia groups. Intermittent or continuous delivery of adenosine-lidocaine cardioplegia may offer an alternative to current surgical hyperkalemic cardioplegia at warm to normothermic temperatures.