Hospital Cardioplegia Research Articles

Safety and Effectiveness of Del Nido Cardioplegia in Comparison to Blood-Based St. Thomas Cardioplegia in Congenital Heart Surgeries: A Prospective Randomized Controlled Study.

To compare the safety and effectiveness of del Nido cardioplegia with blood-based St Thomas Hospital (BSTH) cardioplegia in myocardial protection in congenital heart surgery. It is a prospective, open-labeled, randomized controlled study conducted at National Heart Institute, Kuala Lumpur from July 2018 to July 2019. All patients with simple and complex congenital heart diseases (CHD) with good left ventricular function (left ventricular ejection fraction [LVEF] >50%) were included while those with LVEF <50% were excluded. A total of 100 patients were randomized into two groups of 50 each receiving either del Nido or BSTH cardioplegia. Primary end points were the spontaneous return of activity following aortic cross-clamp release and ventricular function between two groups. Secondary end point was myocardial injury as assessed by troponin T levels. Cardiopulmonary bypass and aortic cross-clamp time, return of spontaneous cardiac activity following the aortic cross-clamp release, the duration of mechanical ventilation, and intensive care unit stay were comparable between two groups. Statistically significant difference was seen in the amount and number of cardioplegia doses delivered (P < .001). The hemodilution was significantly less in the del Nido complex CHD group compared to BSTH cardioplegia (P = .001) but no difference in blood usage (P = .36). The myocardial injury was lesser (lower troponin T release) with del Nido compared to BSTH cardioplegia (P = .6). Our study showed that both del Nido and BSTH cardioplegia are comparable in terms of myocardial protection. However, single, less frequent, and lesser volume of del Nido cardioplegia makes it more suitable for complex repair.

The Use of del Nido Cardioplegia for Myocardial Protection in Isolated Coronary Artery Bypass Surgery

The del Nido (DN) cardioplegia solution has been widely used in paediatric open-heart surgery for years; however, its application in adult open-heart surgery has not yet gained sufficient popularity. We investigated the safety and efficiency of the DN cardioplegia solution versus the traditional crystalloid cardioplegia solution [St. Thomas' Hospital (STH) cardioplegia solution] in adult patients undergoing coronary artery bypass grafting (CABG). A retrospective comparative analysis of 200 consecutive patients undergoing isolated on-pump CABG between April 2016 and September 2017 was performed. Patients were divided into two groups: DN group (n = 100) and STH group (n = 100). Groups were compared with regard to perioperative clinical outcomes, and the safety and efficiency of the DN cardioplegia solution in CABG surgery were evaluated. In the DN group, mean aortic cross-clamp, cardiopulmonary bypass, and total operation times were significantly shorter than in the STH group. After the release of the aortic cross-clamp, the requirement for intraoperative defibrillation was significantly less in the DN group. There were no significant differences between the groups in terms of the levels of perioperative cardiac biomarkers (including creatine kinase-myocardial band and troponin I), major postoperative adverse events, and in-hospital mortality. This study revealed that the use of the DN cardioplegia solution in adult patients undergoing isolated CABG provides significantly shorter aortic cross-clamp, cardiopulmonary bypass, and total operation times compared with the traditional cardioplegias solution. The DN solution could be used as a safe and efficient alternative to the traditional cardioplegia solutions in CABG surgery.

Efficacy of esmolol cardioplegia during hypothermic ischaemia

Cardioplegic arrest using a polarizing solution has been shown to have beneficial advantages for cardioprotection compared with depolarizing (potassium-based) arrest; most studies, however, have looked at normothermic ischaemia with short infusion intervals (every 10-15 min). This study examines the protective efficacy of an esmolol-based cardioplegia during hypothermic arrest, together with a prolonged infusion interval (30 min) for increased clinical feasibility. Isolated Langendorff-perfused hearts were subjected to arrest with St Thomas' Hospital cardioplegia (STH2), or esmolol cardioplegia (single- or multidose infusion at 32°C) for 60-min, 90-min or 120-min global ischaemia at 32°C, and recovery of function (left ventricular developed pressure) measured. A further study examined the protective efficacy of multidose esmolol cardioplegia compared with hypothermia alone at temperatures of 20°C, 28°C and 32°C compared with 37°C for 120 min of ischaemia. Esmolol cardioplegic arrest with multidose infusion at 32°C significantly improved recovery of function (left ventricular developed pressure) compared with 32°C STH2, at each ischaemic duration (88 ± 3 vs 66 ± 3% at 60 min, 82 ± 3 vs 51 ± 3% at 90 min and 73 ± 6 vs 49 ± 4% at 120 min; P < 0.05). At various hypothermic temperatures, esmolol cardioplegia significantly improved protection compared with hypothermia alone (88 ± 4%, 88 ± 3% and 72 ± 3% vs 60 ± 3%, 30 ± 2% and 15 ± 1% at 20°C, 28°C and 32°C, respectively; P < 0.05); however, at 37°C, there was no difference in protection. Contracture during ischaemia mirrored the effects of left ventricular developed pressure recovery. Esmolol cardioplegia (a polarizing solution), used as a multidose infusion during hypothermia, significantly improved cardioprotection compared with the depolarizing STH2. An increased infusion interval of 30 min indicates improved clinical feasibility.

Ischaemic postconditioning: does cardioplegia influence protection?

Ischaemic postconditioning attenuates reperfusion injury and may be a useful adjunct to cardiac surgery. We examined the efficacy of postconditioning following ischaemic protection with cardioplegic arrest and the importance of index ischaemia and cardioplegia formulation. Isolated Langendorff-perfused rat hearts were subjected to varying durations (30, 45 or 60 min) of global (37°C) ischaemia and then reperfused; functions such as left ventricular developed pressure, left ventricular end-diastolic pressure and heart rate and coronary flow were assessed throughout reperfusion, and infarct size measured after 120 min of reperfusion. Two studies were conducted. Study 1 compared recovery of function and infarct size after varying durations (30, 45 or 60 min) of ischaemia alone and ischaemia preceded by protection with St Thomas' Hospital cardioplegic solution, with or without a postconditioning protocol (six cycles of 10-s reperfusion and 10-s ischaemia). Study 2 investigated the importance of magnesium in cardioplegia [low magnesium (1.2 mmol/l) or zero magnesium (0 mmol/l)] on postconditioning protection after varying durations of ischaemia (30, 45 or 60 min). Postconditioning enhanced protection after 30-min ischaemia alone [left ventricular developed pressure at 60-min reperfusion recovered to 34 ± 1% after ischaemia alone and 45 ± 2% after postconditioning (P < 0.05); infarct size was 21 ± 4 and 11 ± 1%, respectively (P < 0.05)], but there were no differences after 45 or 60 min of ischaemia. Increasing ischaemic durations reduced recovery, and cardioplegia was protective during shorter ischaemia but protection diminished as ischaemic duration increased. Postconditioning was ineffective after cardioplegia protection at all ischaemic durations. However, postconditioning after cardioplegia containing zero magnesium was efficacious for 60 min of ischaemia [left ventricular developed pressure at 60-min reperfusion was 41 ± 2% (P < 0.05) vs. 31 ± 3%; infarct size was 30 ± 7 vs. 56 ± 6%, respectively (P < 0.05)], but was ineffective for shorter periods of ischaemia. We conclude that postconditioning does not enhance the protective effect of St Thomas' Hospital cardioplegia (under these strict experimental conditions); however, the efficacy of postconditioning correlates with the magnesium concentration of the cardioplegic solution, which may imply involvement of magnesium on mitochondria during ischaemia. There is a limited window of postconditioning protection dependent on the duration of the index ischaemia.

Myocardial protection and neutrophil elastase inhibitor: Additive effect of the sivelestat on reperfusion injury

Objective: We have previously shown that sivelestat sodium hydrate (sivelestat), a novel synthesized neutrophil elastase inhibitor, affords a cardioprotective effect against 30 min global ischemia. In this study, we examined whether myocardial protection by sivelestat may be additive to that provided by cardioplegic arrest (St Thomas' Hospital cardioplegia; STH2) in crystalloid perfused rat hearts. Methods: Isolated rat hearts were aerobically Langendorff-perfused with bicarbonate buffer and function (left ventricular developed pressure; LVDP) was measured.

The potential benefits of 1.5% hetastarch as a cardioplegia additive

Introduction: Myocardial edema is a clinically relevant problem found in post-ischemic reperfused hearts. The objective of this study was to understand the effects of hetastarch-supplemented cardioplegia on post-ischemic edema and cardiac function. Materials and methods: Swine hearts were arrested with either St. Thomas Hospital cardioplegia with ( n = 6) or without ( n = 7) 1.5% hetastarch. Following hypothermic global ischemia, hearts were crystalloid reperfused in a four-chamber isolated working mode. Results: Hetastarch decreased myocardial water content gains after three hours of reperfusion (control versus hetastarch, hour 0: 67 ± 5% versus 67 ± 3%, NS; hour 3: 82 ± 2% versus 78 ± 1%, p = 0.1). Post-ischemic control group left ventricular end-diastolic pressures were elevated after 1 h (in mm Hg, hour 0: 13 ± 2, hour 1: 19 ± 3, hour 2: 19 ± 3, hour 3: 20 ± 2) but remained stable (<16 mm Hg) in the hetastarch group. Post-reperfusion creatine phosphokinase perfusate levels in the hetastarch treated hearts were decreased (control: 1.6 IU/l/g versus hetastarch: 0.6 IU/l/g, p = 0.15). Discussion/conclusions: Hetastarch treatment delayed myocardial edema development and attenuated myocardial creatine kinase efflux, thereby preserving diastolic function.

St. Thomas Hospital Cardioplegia #2 fails to suppress slow reaction pacemaker cell electrical activity 1

Background Inadequate right atrial myocardial preservation during cardioplegic arrest may promote postoperative supraventricular arrhythmias (SVA). We determined (1) if oxygenated St. Thomas Hospital Cardioplegia #2 (STH2) alone causes slow reaction pacemaker cell (SR) quiescence; and (2) if hypothermia, higher [K +], lower [Ca 2+], and verapamil in STH2 suppresses SR electrical activity. Materials and methods A glass microelectrode recorded SA node SR membrane action potentials (AP) in rabbits ( n = 23, 1.93 ± 0.45 kg) randomized to normothermic STH2 (33°C, n = 6), hypothermia (20°C, n = 4), hypothermic STH2 (22°C, n = 3), lower calcium STH2 ( n = 3), higher potassium STH2 ( n = 4), and STH2 plus Verapamil ( n = 3). Results Normothermic STH2 depressed SR action potential amplitude and action potential duration (APD), but did not completely suppress action potential generation. Hypothermia alone prolonged APD and sinus cycle length and suppressed SR AP. STH2 with hypothermia (to 20°C) completely suppressed propagating AP and STH2 plus 0.04 Ca 2+ mEq/L inhibited SR AP generation. STH2 plus 30 mEq K + and STH2 plus 2.5 mmol/L verapamil failed to generate SR AP. Conclusion STH2 cannot prevent SA node SR myocardial cells from low-amplitude AP autogeneration above 21°C. STH2 with 30 mEq/L K +, STH2 with 0.02mEq/L Ca 2+, and STH2 plus 2.5 mmol/L verapamil can arrest AP generation in SR and potentially prevent postoperative SVA.

Replacing potassium with nicorandil in cold St. Thomas' Hospital cardioplegia improves preservation of energetics and function in pig hearts

Background To determine whether the adenosine triphosphate-sensitive potassium channel opener nicorandil, instead of potassium in cold crystalloid cardioplegia, may enhance cardioprotection, crystalloid cardioplegia with nicorandil, magnesium, and procaine was compared with standard crystalloid cardioplegia in terms of left ventricular performance and efficiency. Methods Sixteen pigs were randomly assigned to receive cold hyperkalemic crystalloid cardioplegia (n = 8) or nicorandil in cold saline (n = 8). Cold (4°C) cardioplegic solutions were given antegradely and intermittently, with a cross-clamp time of 60 minutes. The preload recruitable stroke work relationship (PRSW), pressure-volume area (PVA), and myocardial oxygen consumption (MVO 2) were calculated at baseline and at one and two hours following cross-clamp release, using combined pressure-volume conductance catheters, coronary flow probes, and O 2-content differences. Results The left ventricular contractility expressed in PRSW was reduced to 58% (standard deviation [SD]: 20) of baseline in the crystalloid group and to 89% (SD: 20) in the nicorandil group two hours after cross-clamp release ( p = 0.044). The slope of the MVO 2-PVA relationship increased in the crystalloid group from 1.59 (SD: 0.22) before cardioplegia to 2.55 (SD: 0.73) afterwards, significantly more than in the nicorandil group, where the slope changed from 1.69 (SD: 0.30) to 1.95 (SD: 0.47) ( p = 0.027). Conclusions Nicorandil in a crystalloid cardioplegic solution was easily employed and contractility was significantly better than after standard hyperkalemic cardioplegia. The smaller shift of the slope in the MVO 2-PVA relationship in the nicorandil group shows improved efficiency in oxygen to mechanical transfer compared with the crystalloid group.

Procaine in Cardioplegia: Does It Affect the Endothelial Function?

Objective: Cardioplegic solutions are widely used in cardiac surgery and hyperkelemia in cardioplegia has been demonstrated to impair the endothelium-derived hyperpolarizing factor (EDHF)-mediated endothelial function. The present study examined the effect of procaine in St. Thomas Hospital Cardioplegia on the EDHF-mediated response in porcine coronary arteries. Methods: Isometric force study: Porcine coronary micro-arteries were studied in a myograph. Two rings taken from the same artery (diameter 200–450 μm, n = 8) were incubated with Kreb's solution as control or Kreb's solution plus procaine (1 mM) at 37 °C for 1 h, respectively. The EDHF-mediated relaxation was induced by bradykinin (BK, −10 ∼−6.5 log M) in the presence of indomethacin (Indo, 7 μM), NG-nitro-L-arginine (L-NNA, 300 μM), and hemoglobin (HbO, 20 μM) after U46619-precontraction (−8 log M). Electrophysiological study: The membrane potential of a single smooth muscle cell in coronary arteries was measured by a microelectrode after superfusion with Kreb's solution or Kreb's containing procaine (1 mM) for 1 h. Results: Procaine had little effect on the resting force of porcine coronary micro-arteries (0.94 ± 0.74 mN vs. 0.67 ± 0.23 mN in control, P > 0.05) and did not alter the U46619-induced precontraction (10.7 ± 1.7 mN vs. 12.0 ± 1.7 mN, P > 0.05). The BK-induced, EDHF-mediated relaxation was increased by the treatment with procaine with the EC50 shifted leftward (97.3 ± 0.6% vs. 83.0 ± 5.1% at −7 log M and 99.4 ± 0.6% vs. 96.7 ± 1.6% at −6.5 log M, P 0.05) and decreased the BK-induced hyperpolarization from −70.3 ± 0.4 mV to −68.0 ± 0.8 mV (−7 log M, P < 0.05) and from −72.3 ± 0.7 mV to −68.8 ± 0.8 mV (−6.5 log M, P < 0.01). Conclusions: In the coronary arteries, procaine has depolarizing effect but it enhances the EDHF-mediated relaxation. Therefore, addition of procaine in cardioplegia may preserve the EDHF-mediated endothelial function.

Myocardial protection with oxygenated esmolol cardioplegia during prolonged normothermic ischemia in the rat

Objective: We previously showed that arrest with multidose infusions of high-dose (1 mmol/L) esmolol (an ultra-short-acting β-blocker) in oxygenated Krebs-Henseleit buffer (esmolol cardioplegia) provided complete myocardial protection after 40 minutes of normothermic (37°C) global ischemia in isolated rat hearts. In this study we investigated the importance of oxygenation for protection with esmolol cardioplegia, compared it with that of St Thomas' Hospital cardioplegia, and determined the protective efficacy of multidose esmolol cardioplegia for extended ischemic durations. Methods: Isolated rat hearts (n = 6/group) were perfused in the Langendorff mode at constant pressure (75 mm Hg) with oxygenated Krebs-Henseleit bicarbonate buffer at 37°C. The first part of the first study had four groups: (i) multidose (every 15 minutes) oxygenated (95% oxygen/5% carbon dioxide) Krebs-Henseleit buffer during 60 minutes of global ischemia, (ii) multidose deoxygenated (95% nitrogen/5% carbon dioxide) Krebs-Henseleit buffer during 60 minutes of global ischemia, (iii) multidose oxygenated esmolol cardioplegia during 60 minutes of global ischemia, and (iv) multidose deoxygenated esmolol cardioplegia during 60 minutes of global ischemia. The second part of the first study had three groups: (v) multidose St Thomas' Hospital solution during 60 minutes of global ischemia, (vi) multidose oxygenated St Thomas' Hospital solution during 60 minutes of global ischemia, and (vii) multidose oxygenated esmolol cardioplegia during 60 minutes of global ischemia. In the second study, hearts were randomly assigned to 60, 75, 90, or 120 minutes of global ischemia and at each ischemic duration were subjected to multidose oxygenated constant flow or constant pressure infusion of (i) Krebs-Henseleit buffer (constant flow), (ii) Krebs-Henseleit buffer (constant pressure), (iii) esmolol cardioplegia (constant flow), or (iv) esmolol cardioplegia (constant pressure). All hearts were reperfused for 60 minutes, and recovery of function was measured. Results: Multidose infusion of oxygenated esmolol cardioplegia completely protected the hearts (97% ± 5%) after 60 minutes of 37°C global ischemia. Deoxygenated esmolol cardioplegia was significantly less protective (45% ± 8%). Oxygenation of St Thomas' Hospital solution did not alter its protective efficacy in this study (70% ± 4% vs 69% ± 7%). Infusion of esmolol cardioplegia at constant pressure provided complete protection for 60, 75, and 90 minutes (104% ± 5%, 95% ± 5%, and 95% ± 3%, respectively), whereas protection with constant-flow esmolol cardioplegic infusion was significantly decreased at ischemic durations longer than 60 minutes. This decrease in efficacy of constant-flow esmolol cardioplegia was associated with increasing coronary perfusion pressure leading to myocardial injury. Conclusions: Oxygenation of esmolol cardioplegia (Krebs-Henseleit buffer plus 1.0 mmol/L esmolol) was essential for optimal myocardial protection. Multidose infusion of oxygenated esmolol cardioplegia provided good myocardial protection during extended periods of normothermic ischemia. Esmolol cardioplegia may provide an efficacious alternative to hyperkalemia.J Thorac Cardiovasc Surg 2002;124:340-51

Prevention of cell swelling with low chloride St. Thomas' Hospital solution improves postischemic myocardial recovery

Objective: In isolated myocytes cardioplegia-induced cell swelling can be prevented by lowering the KCl product by replacing Cl - with an impermeant ion. This study tested the hypothesis that Cl - substitution in St. Thomas' Hospital cardioplegic solution would result in superior myocardial protection in the intact, blood-perfused heart. Methods: Using a parabiotic, isolated rabbit heart Langendorff model, hearts were exposed to 1 hour of hypothermic (10° to 12° C), global ischemia followed by 30 minutes of reperfusion. Isosmotic cardioplegia was administered as a single 50 ml bolus of either standard St. Thomas' Hospital solution ([K +] o × [Cl -] o = 2566.4 (mmol/L) 2) or low Cl - St. Thomas' Hospital solution ([K +] o × [Cl -] o = 700 (mmol/L) 2). Chloride was replaced by a large, impermeant ion, methanesulfonate. Postreperfusion systolic function and atrioventricular conduction times were measured before ischemia and after reperfusion. Results: Hearts receiving low Cl St. Thomas' Hospital cardioplegia demonstrated significantly better postischemic functional recovery (74% ± 3%) compared with those treated with standard high Cl St. Thomas' Hospital solution (55% ± 4%, p = 0.003). In addition, atrioventricular conduction times remained normal in the low Cl group but were significantly prolonged in the St. Thomas' Hospital group. Conclusions: Lowering the KCl product of St. Thomas' Hospital solution makes it isotonic with plasma and prevents cellular edema. This ameliorates the detrimental functional and electrophysiologic sequelae of hypothermic, hyperkalemic cardioplegia. (J Thorac Cardiovasc Surg 1998;115:1196-202)

Calcitonin Gene-Related Peptide-Induced Preconditioning Improves Preservation With Cardioplegia

Background. Our recent work has shown that calcitonin gene-related peptide (CGRP) may play an important role in mediation of ischemic preconditioning. Therefore, we tested the hypothesis that CGRP-induced preconditioning protects against myocardial damage after prolonged cardioplegic arrest in isolated rat hearts. Methods. Six groups were studied: the control, ischemic preconditioning, and CGRP-pretreated groups for both 4- and 8-hour hypothermic ischemia. All hearts were arrested using St. Thomas Hospital cardioplegia, and then reperfused with normothermic Krebs-Henseleit solution for 60 minutes after the 4- or 8-hour hypothermic ischemic period. Hearts were subjected to two cycles of 5-minute ischemia and 10-minute reperfusion in the ischemic preconditioning group. In the CGRP-pretreated group, Krebs-Henseleit solution containing CGRP (5 × 10 −9 mol/L) was substituted for the ischemic period. Results. At 30 minutes of reperfusion after 4-hour storage, left ventricular pressure (mm Hg) and its first derivative (dp/dt max, mm Hg/s) in the control, ischemic preconditioning, and CGRP groups were 65.2 ± 5.93 and 1,170 ± 119, 94.13 ± 4.93 and 1,825 ± 145.83, and 85.47 ± 4.17 and 1,900 ± 123.13, respectively ( p < 0.01). After 8-hour storage, left ventricular pressure (mm Hg) and dp/dt max (mm Hg/s) in the same groups were 51.07 ± 5.83 and 815 ± 107.17, 83.47 ± 6.54 and 1,480 ± 120.91, and 84.8 ± 8.49 and 1,396 ± 126.16 ( p < 0.01). Ischemic preconditioning and CGRP-induced preconditioning also significantly reduced the release of myocardial enzymes. Conclusions. The present studies suggest that ischemic preconditioning protects against ischemia-reperfusion injury even after 8 hours of hypothermic preservation in isolated rat hearts, and that CGRP exerts preconditioning-like cardioprotection.

St. Thomas' Hospital cardioplegia: Enhanced protection with exogenous creatine phosphate

Experimentally, creatine phosphate (CP) improves postischemic recovery of function and reduces postischemic arrhythmias. We studied 50 patients undergoing valve replacement. They were randomized into either a control group, who received St. Thomas' Hospital cardioplegic solution No. 1, or a CP-treated group, receiving the same cardioplegic solution plus CP (10 mmol/L). There were no preoperative clinical differences between groups. Assessment was by electrocardiographic analysis, inotropic drug requirement, quantitative birefringence, myocardial high-energy phosphate content, function, and semiquantitative ultrastructural assessment. Direct-current shocks were reduced in the CP-treated group (0.88 +/- 0.15) compared with the control group (1.40 +/- 0.14; p < 0.02), as was the total number of joules (22.0 +/- 3.5 versus 34.4 +/- 3.7, respectively; p <0.02). The incidence of spontaneous sinus rhythm was higher in the CP-treated group (40% versus 8%; p < 0.05) and the incidence of postoperative arrhythmias, lower (8% versus 32%; p < 0.05). Prolonged inotropic administration (12 hours or longer) occurred in fewer patients in the CP-treated group (4% versus 28%; p < 0.05). Response to inotropic support (in the subset of patients requiring this treatment) was significantly greater in the CP-treated group than in the control group. There were no differences in recovery of function, birefringence changes, myocardial high-energy phosphate content, or ultrastructure between groups. St. Thomas' Hospital cardioplegic solution No. 1 plus CP enhanced myocardial protection and conferred a direct benefit to the patient by reducing postoperative arrhythmias and need of prolonged inotropic support.

Exogenous creatine phosphate, added to St Thomas' Hospital cardioplegia no 1 (STH1), enhances myocardial protection in valve surgery patients

Exogenous creatine phosphate, added to St Thomas' Hospital cardioplegia no 1 (STH1), enhances myocardial protection in valve surgery patients

Interactions between preischemic hypothermia and cardioplegic solutions in the neonatal lamb heart

Hypothermia is believed to improve the tolerance to both ischemia and cardiopulmonary bypass and is commonly used during heart operations, particularly in the neonate. However, hypothermia also causes calcium to accumulate in the myocyte experimentally, and an increase in intracellular calcium during ischemia may worsen the effect of ischemia and impair the postischemic recovery of function. This effect of hypothermia on intracellular calcium has generally not been considered in experiments that attempt to optimize the composition of cardioplegic solutions. We have evaluated the impact of hypothermia before cardioplegic ischemia on the efficacy of two common cardioplegic solutions, one with calcium (St. Thomas’ Hospital cardioplegia) and the other without calcium (glucose-potassium cardioplegia), in 37 isolated blood-perfused neonatal lamb hearts. Left ventricular maximal developed pressure, positive maximum of the first derivative of left ventricular pressure, left ventricular stiffness constant at 10 mm Hg end-diastolic pressure, coronary blood flow, and myocardial oxygen consumption were measured before and 30 minutes after 2 hours of cold ischemia. After baseline measurements were made, two groups of hearts (ST-C and GK-C) had perfusion-cooling for 10 minutes to 17° C myocardial temperature, and two other groups (ST-NC and GK-NC) had the same period of normothermic perfusion. Then the hearts were arrested with 4° C St. Thomas’ cardioplegia in groups ST-C and ST-NC and with glucose-potassium cardioplegia in groups GK-C and GK-NC. In the groups without preischemic cooling, both St. Thomas’ (group ST-NC) and glucose-potassium (group GK-NC) cardioplegia resulted in a similar recovery of function compared with baseline levels (group ST-NC: developed pressure = 91.3% ± 9.2%, dP/dt = 88.1% ± 8.9%, left ventricular stiffness constant = 96.1% ± 3.3%; group GK-NC: developed pressure = 89.3% ± 6.9%, dP/dt = 82.6% ± 8.8%, left ventricular stiffness constant = 99.4% ± 2.0%; data are mean plus or minus the standard deviation). However, with preischemic cooling, St. Thomas’ cardioplegia (group ST-C) resulted in a significantly reduced recovery of both systolic and diastolic function (developed pressure = 81.6% ± 6.2%, dP/dt = 75.1% ± 8.4%, left ventricular stiffness constant = 103.7% ± 2.7%) compared with that for both glucose-potassium cardioplegia (group GK-C: developed pressure = 92.4% ± 8.7%, dP/dt = 83.7% ± 6.0%, left ventricular stiffness constant = 100.5% ± 2.1%) and St. Thomas’ cardioplegia without preischemic cooling (group ST-NC) ( p < 0.05). The results suggest that hypothermia before cardioplegia has a significant impact on postischemic recovery, but that this effect is dependent on the composition of the cardioplegic solution. These effects may be related to the effects of hypothermia and ischemia on intracellular calcium homeostasis although the precise mechanisms remain unclear. However, these results emphasize the importance of considering the interactions between myocardial hypothermia before ischemia and the ischemic episode itself when the optimal composition of cardioplegic solutions for the neonatal heart is being investigated. (J T HORAC C ARDIOVASC S URG 1994;107:822-8)

Developmental differences in myocardial protection in response to 5′-nucleotidase inhibition

Age-related differences in the activity of 5'-nucleotidase, an enzyme responsible for conversion of high-energy phosphates to their the diffusible precursors, may help to explain age-related differences in tolerance of global myocardial ischemia. Postischemic function and high-energy phosphate content were measured in the hearts of rabbits 7 to 10 days old (neonate), 30 to 40 days old (1 month), and 6 to 12 months old (adult). Hearts in each age group were subjected to 60 minutes of ischemia at 34 degrees C either with no cardioplegia, with unmodified St. Thomas' Hospital cardioplegic solution, or with St. Thomas' Hospital cardioplegic solution with pentoxifylline, a 5'-nucleotidase inhibitor. These groups were compared with one another and with control hearts that were continuously perfused for 1 hour. In adults, addition of pentoxifylline to St. Thomas' Hospital cardioplegic solution restored adenosine triphosphate and total nondiffusible nucleotide levels to control values and improved recovery of cardiac output and developed pressure compared with results with unmodified St. Thomas' Hospital cardioplegic solution. In contrast, biochemical and functional parameters in neonatal hearts were not affected by either unmodified St. Thomas' Hospital cardioplegic solution cardioplegia or St. Thomas' Hospital cardioplegic solution with pentoxifylline. Functional recovery in neonatal hearts subjected to unprotected ischemia was superior to that in the older age groups. In 1-month-old hearts, St. Thomas' Hospital cardioplegia improved recovery compared with recovery after unprotected ischemia, but no incremental improvement in function or high-energy stores was seen with addition of pentoxifylline. The lack of effect of pentoxifylline on neonatal hearts suggest that there is a relative deficiency of 5'-nucleotidase in this age group. This may contribute to the improved functional recovery observed in unprotected hearts. Furthermore, addition of pentoxifylline to adult hearts appears to confer the benefits of low 5'-nucleotidase activity occurring naturally in the neonate.

Haemodynamic Evaluation of Retrograde versus Anterograde Delivery of Cardioplegic Solution in Aortic Valve Replacement

A total of 44 patients undergoing isolated aortic valve replacement received either anterograde (20 patients) or retrograde (24 patients), cold St Thomas's Hospital cardioplegia. The patients were similar with respect to age, sex, left ventricular ejection fraction, left ventricular-aortic pressure gradient, cross-clamping time and mean dose of cardioplegia. After surgery, there were no differences in enzyme release, low cardiac output syndrome, rhythm disturbances or clinical outcome between the two groups. Analysis of the postoperative haemodynamic data, however, suggests better preservation of left ventricular contractility with retrograde delivery of cardioplegic solution.

Retrograde coronary sinus cardioplegia in myocardial revascularization: hemodynamic evaluation of the influence on the right-ventricular function.

The problem of the efficacy of right-ventricular protection with retrograde coronary sinus cardioplegia is studied. Sixty patients undergoing myocardial revascularization were prospectively assigned to receive cold St. Thomas' Hospital cardioplegia into the aortic root (30 patients) or retrogradely in the coronary sinus (30 patients). The two groups were similar concerning preoperative and operative data. The hemodynamic recovery postoperatively was good in both groups, the increase of the heart rate, the decrease of the mean aortic pressure and the right-ventricular stroke-work index were not significantly different in the two groups. However, right atrial pressure increased significantly (p less than 0.001) in patients who received cardioplegia anterogradely and decreased, but not significantly, in the retrograde group. The data suggest that the decrease of the right-ventricular stroke-work index in the anterograde group is related to a depressed contractility and in the group with retrograde delivery of cardioplegia to a decreased preload. There were no differences between the groups with respect to clinical outcome. We conclude that retrograde delivery of cardioplegia results in an excellent protection of the right-ventricular function in elective myocardial revascularization.

Ischaemic endothelial dysfunction after single or multidose cardioplegia.

The effect of ischaemia, either alone or after a single or multidose infusion of St Thomas' Hospital cardioplegia solution (ST), on endothelial function was studied by examining its influence on 5-Hydroxytryptamine- (5-HT-) and nitroglycerine- (GTN-) induced coronary vasodilation in the isolated rat heart. Eighty rat hearts were perfused on a modified Langendorff preparation. Thirty minutes of unprotected ischaemia (N = 16) abolished the vasodilatory response to 5-HT but maintained the response to GTN (expressed as % of the control value 5-HT, pre 45.0 +/- 3.5, post 2.3 +/- 3.2, GTN, pre 42.3 +/- 4.4, post 39.8 +/- 4.0). The increase in coronary flow induced by either agent was unaltered following 30 or 60 min of ischaemia protected by a single dose of ST (N = 16 in each). Ninety minutes of ischaemia preceded by a single infusion of ST (N = 16) markedly reduced the 5-HT response but maintained the vasodilation induced by GTN (5-HT, pre 37 +/- 2.6, post 6.9 +/- 2.6, GTN, pre 40.1 +/- 2.5, post 37 +/- 2.8). During 90 min of ischaemia, infusion of an additional dose of ST after 45 min (N = 8) or two extra doses every 30 min (N = 8) maintained the 5-HT-induced increase in coronary flow (pre 39.5 +/- 3.9, post 36.4 +/- 3.5). It can be concluded that coronary vascular endothelium is more susceptible to ischaemic damage when compared with vascular smooth muscle. This results in early loss of endothelium-dependent vasodilation. Multidose infusion of St Thomas' Hospital cardioplegia solution is superior to a single infusion in protecting endothelial function following prolonged cardiac ischaemia.

Age-related changes in the efficacy of crystalloid cardioplegia

Recent work has shown that multi-dose St. Thomas' Hospital cardioplegia solution (STHC) may not provide reliable protection of the neonatal myocardium. We have used an isolated working heart model to study the age-related development of this observation. Sets of eight hearts from 2-, 4-, 6-, and 8-week-old rabbits were subjected to 90 min of ischemia at 10°C. STHC was infused at 30-min intervals in a dose of 10 ml/kg. There were no differences in the preservation of ATP stores during ischemia among the groups. The percentage recovery of preischemic mean aortic pressure, left atrial pressure, and heart rate were not different among groups, but the percentage recovery of aortic flow (AF) (expressed as means ± standard error of the mean) was significantly lower in the 2- and 4-week hearts (44.1 ± 8.2 and 66.2 ± 7.7%) than in the 6- and 8-week hearts (93.0 ± 6.4 and 97.6 ± 4.7%). We have confirmed that the use of multi-dose STHC impairs recovery of ventricular function in the neonatal rabbit heart. This effect, however, diminishes rapidly as the immature animal develops and is not present by 6 weeks of age. Additional experimentation is necessary to identify those aspects of the developing myocardium that account for these observations.