Infusion Of Cardioplegic Solution Research Articles

Effects of histidine load on ammonia, amino acid, and adenine nucleotide concentrations in rats.

The unique capability of proton buffering is the rationale for using histidine (HIS) as a component of solutions for induction of cardiac arrest and myocardial protection in cardiac surgery. In humans, infusion of cardioplegic solution may increase blood plasma HIS from ~ 70 to ~ 21,000µM. We examined the effects of a large intravenous dose of HIS on ammonia and amino acid concentrations and energy status of the body. Rats received 198mM HIS intravenously (20ml/kg) or vehicle. Samples of blood plasma, urine, liver, and soleus (SOL) and extensor digitorum longus (EDL) muscles were analysed at 2 or 24h after treatment. At 2h after HIS load, we found higher HIS concentration in all examined tissues, higher urea and ammonia concentrations in blood and urine, lower ATP content and higher AMP/ATP ratio in the liver and muscles, higher concentrations of almost all examined amino acids in urine, and lower glycine concentration in blood plasma, liver, and muscles when compared with controls. Changes in other amino acids were tissue dependent, markedly increased alanine and glutamate in the blood and the liver. At 24h, the main findings were lower ATP concentrations in muscles, lower concentrations of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in blood plasma and muscles, and higher carnosine content in SOL when compared with controls. It is concluded that a load of large HIS dose results in increased ammonia levels and marked alterations in amino acid and energy metabolism. Pathogenesis is discussed in the article.

Optimizing cardioplegia in cardiopulmonary bypass surgeries

Aim. To investigate the influence of intentional cardiac arrest before cardioplegic solution infusion on cardioplegia quality and myocardial protection. Methods. We propose a method for optimizing cardioplegia, allowing to achieve asystole and pharmacologically prepare the myocardium to aortic clamping. The developed method uses systemic and intracoronary administration of adenosine triphosphate and lidocaine to cause asystole, which gives rapid and effective cardioplegic effect without threatening hypertension in coronary arteries. The described method was used in 724 patients who underwent surgery in the period from 2008 to 2013. Normothermic perfusion mode - without myocardial cooling with ice-slush - was used in all cases. Results. Cardiac activity restored spontaneously in 89.7% of cases, manifestations of reperfusion syndrome were negated, frequency and duration of inotropic support were significantly reduced, no serious arrhythmias, like AV block, ventricular tachyarrhythmias and extrasystoles were registered. The described method creates the conditions for sinus rhythm reversion in patients with atrial fibrillation, given the favorable anatomical and physiological conditions (heart chambers volume, duration and type of atrial fibrillation). Conclusion. The described method allows optimizing the surgical stage after standard pharmacological cardioplegia, provides more efficient cardioplegic solution delivery to the myocardium, which is especially important in patients with coronary artery disease, as well as parmacological preconditioning of myocardium before a long period of ischemia and thus to improve the clinical course of post-ischemic period

Aortic Surgery without Infusion of Cardioplegic Solution at Total Circulatory Arrest

BackgroundMinimal infusion of cardioplegic solution (CPS) during aortic surgery using total circulatory arrest (TCA) may reduce several potential side effects: clamping on a diseased aorta, insult of coronary ostia, and edema.Materials and MethodsFrom 2006 to 2009, 72 patients underwent aortic surgery without infusion of cardioplegic solution at the initiation of circulatory arrest. The diagnoses were acute aortic dissection (44), aneurysm (22), and intramural hematoma (6).ResultsThe duration of TCA, the lowest nasopharyngeal temperature, bypass time, and aortic clamp time was 45 minutes, 16.4℃, 162 minutes, and 100 minutes, respectively. The amount of CPS was 1,050 mL, and 15 patients underwent surgery without CPS. The average inotrope score was 113 points (range, 6.25 to 5,048.5 points) corresponding to the dopamine infusion of 5 mcg/kg/min for 1 day. Seven patients showed a level of creatine kinase-MB above 50 ng/mL, postoperatively, compared with the average of 12.75 ng/mL. The ischemic change was found on electrocardiogram in 5 patients, postoperatively. There was no cardiac morbidity requiring mechanical assist. The average of intensive care unit stay and postoperative hospital stay was 40 hours (range, 15 to 482 hours) and 11 days, respectively.ConclusionMinimal infusion of only retrograde CPS during rewarming without initial infusion at TCA in aortic surgery is feasible and can be used with acceptable results.

Associated factors with survivals in patients undergoing orthotopic heart transplant using retrograde blood microcardioplegia

Several techniques and cardioplegic solutions have been used for heart preservation during transplant procedures. Unfortunately, there is a lack of ideal method for myocardial preservation in the clinical practice. The use of retrograde cardioplegia provides continuous infusion of cardioplegic solution during the graft implantation. This strategy may provide better initial recovery of the graft. The objective of this study is to describe the experience of a single center where all patients received the same solution for organ preservation and were subjected to continuous retrograde blood microcardioplegia during implantation of the graft and to evaluate factors associated to early and late mortality with this technique.This is a retrospective, observational and descriptive study of a single center.During the study period were performed 35 heart transplants. Fifteen (42.9%) patients were in cardiogenic shock. The probability of survival was 74.8±7.8%, 60.4±11.3% and 15.1±13.4% at 1 year, 5 years and 10 years of follow-up, respectively. The median survival time was 96.6 months.The use of myocardial protection with retrograde cardioplegic solution may reduce the risks associated morbidity due to cold ischemia time during the heart transplant, and we suggest that this benefit may be even greater in cases of cold ischemia time longer ensuring protection to the myocardium.

Direct Optical Measurement of Intraoperative Myocardial Oxygenation During Congenital Heart Surgery

This study demonstrates use of novel technology to measure cellular oxygenation during corrective congenital heart surgery. Cellular oxygenation was measured using a custom-designed optical probe placed on the free wall of the right ventricle. Cellular oxygenation, determined from myoglobin saturation, was calculated using multiwavelength analysis. Timing of bypass, aortic cross-clamp, infusion of cardioplegic solution, and length of intensive care unit (ICU) stay were recorded. Baseline cellular oxygenation was approximately 50% just before aortic cross-clamp and decreased to approximately 20% during cardioplegia. Cellular oxygenation remained low throughout cardioplegia and returned toward baseline after bypass. In four cases, cellular oxygenation did not return as quickly to baseline as in the other three cases. Among the four patients demonstrating slow recovery, the average ICU length of stay was 2.25 days compared with an average stay of 1.33 days for those patients exhibiting rapid cellular oxygenation recovery (p = 0.06). The slow recovery group had an average cross-clamp time of 40.1 ± 28.4 minutes, compared with 26.0 ± 8.5 minutes for the fast recovery group (p = 0.34). This study demonstrates for the first time that myocyte cellular oxygenation can be measured intraoperatively during cardiac surgery. Measurement of cellular oxygenation may be useful for improving myocardial preservation techniques.

Anesthetic management of apicoaortic bypass in patients with severe aortic stenosis

Apicoaortic bypass (AAB), or apicoaortic conduit insertion, is a conventional surgical method that has been regaining attention due to the aging population and the increasing number of repeat surgeries. The indication for the procedure has been extended as an alternative for aortic stenosis when the usual sternotomy or aortic clamping is considered to be difficult, e.g., in patients with severe calcification of the ascending aorta (porcelain aorta), or in patients with a patent coronary artery bypass graft located adjacent to the posterior surface of the sternum. Herein, we report our recent anesthetic management of three patients undergoing AAB. Once the apicoaortic conduit is inserted, blood from the left ventricle is ejected via two routes, the narrowed native aortic valve and the apicoaortic conduit. Thus, it is necessary to elucidate any change in blood flow after the withdrawal of the extracorporeal circulation, by using intraoperative transesophageal echocardiography. Furthermore, if a rigid apical connector is not used, anastomosis of the cardiac apex and conduit is conducted under ventricular fibrillation without the infusion of cardioplegic solution; thus, patients are deemed likely to suffer increased myocardial damage. As a rigid apical connector was not used in the three present patients, the administraction of adequate catecholamines was needed for the withdrawal of the extracorporeal circulation. In addition, because those undergoing AAB often have extremely poor cardiac reserve preoperatively owing to the administration of adequate catecholamines was needed for the withdrawal of the extracorporeal circulation. In the three present patients, anesthetic management was successful, and there were no intraoperative or immediate postoperative complications.

Reliability of temperatures measured at standard monitoring sites as an index of brain temperature during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction

It is essential to estimate the brain temperature of patients during deliberate deep hypothermia. Using jugular bulb temperature as a standard for brain temperature, we evaluated the accuracy and precision of 5 standard temperature monitoring sites (ie, pulmonary artery, nasopharynx, forehead deep-tissue, urinary bladder, and fingertip skin-surface tissue) during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction. In 20 adult patients with thoracic aortic aneurysms, the 5 temperature monitoring sites were recorded every 1 minute during deep hypothermic (<20 degrees C) cardiopulmonary bypass. The accuracy was evaluated by the difference from jugular bulb temperature, and the precision was evaluated by its standard deviation, as well as by the correlation with jugular bulb temperature. Pulmonary artery temperature and jugular bulb temperature began to change immediately after the start of cooling or rewarming, closely matching each other, and the other temperatures lagged behind these two temperatures. During either situation, the accuracy of pulmonary artery temperature measurement (0.3 degrees C-0.5 degrees C) was much superior to the other measurements, and its precision (standard deviation of the difference from jugular bulb temperature = 1.5 degrees C-1.8 degrees C; correlation coefficient = 0.94-0.95) was also best among the measurements, with its rank order being pulmonary artery > or = nasopharynx > forehead > bladder > fingertip. However, the accuracy and precision of pulmonary artery temperature measurement was significantly impaired during and for several minutes after infusion of cold cardioplegic solution. Pulmonary artery temperature measurement is recommended to estimate brain temperature during deep hypothermic cardiopulmonary bypass, even if it is conducted with the sternum opened; however, caution needs to be exercised in interpreting its measurements during periods of the cardioplegic solution infusion.

The Na+/H+ exchange inhibitor cariporide is washed out from the myocardium by crystalloid cardioplegia

Objectives: Experimentally, inhibition of the Na+/H+-exchanger [NHE] has been shown to be cardioprotective. However, a clinical benefit could not be demonstrated unequivocally, most likely because of difficulties to deliver the correct dose of NHE-inhibitor at the right time. Whether the infusion of cardioplegic solutions has the potential to affect the myocardial concentration of NHE-inhibitors has not been evaluated so far.

A Technique for Infusion of Cardioplegic Solution in Coronary Artery Bypass with Aortic Regurgitation

Complications such as heart failure due to insufficient cardioplegia may develop in on-pump coronary artery bypass (CAB) with mild-to-moderate aortic regurgitation (AR). A technique for administration of cardioplegic solution was carried out to avoid such complications. Cardiopulmonary bypass was established. After aortic cross-clamping, cardioplegic solution was administered from aortic root. Because complete cardiac arrest was not rapidly achieved, the aortic root was incised. Three cusps of the aortic valve were sutured. The aorta was closed; cardioplegic solution was administered from the aortic root. Then, cardiac arrest was rapidly achieved. After distal anastomosis of quadruple bypass was completed, the suture of the cusps was removed. There was no exacerbation of AR due to this method compared to the preoperative state. When off-pump coronary artery bypass is impossible and retrograde cardioplegia cannot be performed for a certain reason, this method may be set to one of the choices.

Is coma an absolute contraindication for emergency central aortic operation?

Clinical Summary The patient was a 79-year-old man. Left hemiplegia and loss of consciousness developed suddenly, and he was transferred to our emergency center under suspicion of brain infarction. On admission, his Glasgow coma scale was E1 V1 M1. Although brain computed tomography (CT) revealed no abnormal finding except for atrophy, body enhanced CT confirmed acute Stanford type A aortic dissection complicated with brain malperfusion caused by extension of the dissected flap to the innominate artery. Four hours after development of coma, an emergency operation was performed. Extracorporeal circulation was established by means of infusion into the left axillary artery and drainage from the right atrium. At a bladder temperature of 28°C, the aorta was clamped between the innominate and left carotid arteries. After incision of the ascending aorta, chemical arrest was induced by means of direct infusion of cardioplegic solution into the bilateral coronary artery, and selective innominate artery perfusion was performed by means of direct cannulation into the true lumen from the orifice with a balloon cannula. Graft replacement of the aorta was performed from above the sinotubular junction to the aortic arch proximal to the left carotid artery. The entire length of the dissected portion of the innominate artery was resected and reconstructed with a branched graft from the aortic graft. Fourteen hours after the operation, the patient awakened clearly with mild muscle weakness of the left upper limb, and the endotracheal tube was removed. Two days after the operation, he was able to walk. Fifteen days after the operation, he was discharged from our hospital. The brain CT scan during the follow-up period at another hospital revealed infarction at the right putamen. Brain magnetic resonance imaging (Figure 1) 25 days after the operation revealed hemorrhage at the infarction site; however, no significant paralysis developed. Three months after the operation, the patient returned to his life as a farmer.

Nitric oxide attenuates cardiomyocytic apoptosis via diminished mitochondrial complex I up-regulation from cardiac ischemia-reperfusion injury under cardiopulmonary bypass

Objective This study tested the hypothesis that cardioplegic solution supplemented with a nitric oxide donor agent attenuates postischemic cardiomyocytic apoptosis by reduction of mitochondrial complex I up-regulation during global cardiac arrest under cardiopulmonary bypass. Methods Twenty-four anesthetized dogs supported by total vented bypass were divided evenly into 4 groups (n = 6) and subjected to 60 minutes of hypothermic ischemia followed by 4°C multidose crystalloid cardioplegic solution infusion. Hearts received either standard crystalloid cardioplegic solution (control), crystalloid cardioplegic solution supplemented with 2 mmol/L l-arginine ( l-Arg group), crystalloid cardioplegic solution supplemented with 400 μmol/L N G-monomethyl- l-arginine ( l-NMMA group), or crystalloid cardioplegic solution supplemented with 100 μmol/L of NO donor compound (3-morpholinosydnonimine; SIN-1 group). After 60 minutes of cardioplegic arrest, the heart was reperfused for a total of 240 minutes after discontinuation of bypass. The occurrence of cardiomyocytic apoptosis was assessed by terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling and Western blot analysis of caspase-3. Results The occurrence of cardiomyocytic apoptosis was significantly reduced in SIN-1 and l-Arg groups compared with the control group. Mitochondrial complex I mRNA was up-regulated in the control group, and its expression was significantly higher in the l-NMMA group but significantly reduced in the SIN-1 and l-Arg groups. Western blot analysis of Bcl-2 and cytochrome c, an index of mitochondrial damage in postischemic myocardium, revealed a similar pattern. Conclusion Nitric oxide–supplemented crystalloid cardioplegic solution diminished postischemic cardiomyocytic apoptosis after global cardiac arrest under cardiopulmonary bypass, possibly via prevention of mitochondrial complex I up-regulation.

Recombinant human complement C5a receptor antagonist reduces infarct size after surgical revascularization

Objectives: This study tested the hypothesis that a recombinant human C5a antagonist, CGS 32359, attenuates neutrophil activation and reduces infarct size in a porcine model of surgical revascularization. Methods: CGS 32359 (0.16-16 μmol/L) dose-dependently inhibited superoxide production by human C5a-activated porcine neutrophils (18 ± 3.7 vs 1.6 ± 0.5 nmol/5 min/5 × 106 neutrophils; P <.05) and reduced neutrophil adherence to coronary endothelium from 194 ± 9 to 43 ± 6 neutrophils/mm2 (P <.05). The left anterior descending coronary artery was occluded for 50 minutes, after which saline solution (n = 8), mannitol-buffer vehicle (n = 9, 102 mg/kg bolus, 102 mg · kg–1 · h–1), or CGS 32359 (CGS, n = 7, 60 mg/kg bolus, 60 mg · kg–1 · h–1) was infused. After ischemia, 1-hour arrest was achieved by means of multidose hypothermic (4°C) blood cardioplegia, followed by 2.5 hours of off-bypass reperfusion. The ligature on the left anterior descending artery was released before the second infusion of cardioplegic solution. Results: Area at risk was similar in all groups (saline solution, 27% ± 2%; mannitol-buffer vehicle, 26% ± 2%; CGS, 26% ± 2% left ventricular mass). Infarct size (area necrosis/area at risk) was significantly reduced by CGS (18% ± 6%, P <.05) versus saline solution (52% ± 3%) and mannitol-buffer vehicle (60% ± 4%). Postischemic systolic shortening (sonomicrometry) in the area at risk was significantly improved with CGS (0.8% ± 0.9%) compared with saline solution (–3.7% ± 1.1%) and mannitol-buffer vehicle (–6.4% ± 1.0%). Myeloperoxidase activity from accumulated neutrophils was less in the ischemic zone of CGS (0.014 ± 0.002 U/100 mg tissue; P <.05) than mannitol-buffer vehicle (0.133 ± 0.012 U/100 mg tissue). Conclusions: We conclude that the recombinant human C5a receptor antagonist CGS 32359 inhibits surgical ischemia-reperfusion injury after coronary occlusion. (J Thorac Cardiovasc Surg 2000;120:350-8)

Induktion hyperzirkulatorischer Kreislaufreaktionen nach aortokoronarem Bypass durch systemische Wirksamkeit der Bretschneider-Kardioplegie bei atriokavaler Kanülierung

Introduction: The use of extracorporeal circulation (ECC) in cardiac surgery can cause hypercirculatory cardiac failure (HCF). ECC induced release of inflammatory mediators is one mechanism responsible for HCF. Additionally, hemodilution itself can cause a decrease in systemic vascular resistance. Therefore, we prospectively studied the effects of different venous drainage techniques on the incidence of hypercirculatory cardiac failure.¶Methods: After ethical approval and written informed consent, 120 patients scheduled for CABG surgery were randomized into three groups: group A: single atrial cannulation; group B: single atrial cannulation combined with intraoperative hemofiltration to zero fluid balance, and group C: bicaval cannulation with complete venous drainage of cardioplegic solution. Cardioplegia was performed with 2 L of Bretschneider HTK solution into the aortic root. Bypass grafting was performed in moderate hypothermia (32°C). Hemodynamics, use of vasoactive drugs, plasma electrolytes, body temperature, and hemoglobin/hematocrit ratio were recorded. HCF was defined as cardiac output (CO) >6 l min–1, systemic vascular resistance (SVR) <800 dyn sec cm–5 and mean arterial pressure (MAP) <60 mm Hg. Statistical analysis was performed using multiple analysis of variance for repeated measures (MANOVA). A level of p≤0.05 was considered significant.¶Results: No perioperative mortality was observed in the three groups. The incidence of HCF was significantly higher in group A (32%, n=13) and B (40%, n=16) compared to group C (10%, n=4) (p<0.05). Cardiac output in patients with HCF was significantly higher than in patients with No-HCF (Gr.A: 8.2±1.1 vs. 6.0±1.3, Gr.B: 7.8±0.8 vs. 4.7±0.9, Gr.C: 7.4±4.6; p<0.05). In correlation systemic vascular resistance was decreased in patients with HCF (Gr.A: 575±86 vs. 992±232, Gr.B: 603±157 vs. 1134±257 vs. 725±172 vs. 1325±297; p<0.05). Statistical analysis revealed no interaction between HCF and hematocrit, body temperature, plasma levels of sodium and calcium or other hemodynamic parameters like pulmonary artery pressure, pulmonary vascular resistance or heart rate.¶ Conclusions: The results of the present study suggest that single atrial cannulation results in a significantly higher incidence of HCF when compared to bicaval cannulation. A possible explanation for the higher incidence of HCF in group A and B might be the inevitable infusion of cardioplegic solution into the systemic circulation. Perioperative zero flow balanced hemofiltration does not prevent HCF.

Dose dependency of l-arginine in neonatal myocardial protection: The nitric oxide paradox

Objectives: Recent experimental studies have suggested that enriching cardioplegic solution with L-arginine improves myocardial protection by increasing nitric oxide production. Nitric oxide, however, also generates the toxic oxygen-derived free radical peroxynitrite; thus these beneficial effects may be dose dependent, especially in vulnerable (stressed) hearts. Methods: Fifteen neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8%-10%) followed by 20 minutes of normothermic ischemia on cardiopulmonary bypass (stress). They were then protected for 70 minutes with multiple doses of blood cardioplegic solution. In 5 (group 1), the cardioplegic solution contained no L-arginine, in 5 (group 2), it was enriched with a 4 mmol/L concentration of L-arginine, and in 5 (group 3), a 10 mmol/L concentration of L-arginine. Myocardial function was assessed by means of pressure volume loops and expressed as a percentage of control, and coronary vascular resistance and conjugated diene production were measured during infusions of cardioplegic solution. Results: Compared with the protection afforded by blood cardioplegic solution without L-arginine (group 1), the addition of a 4 mmol/L concentration of L-arginine (group 2) significantly improved myocardial protection, resulting in complete return of systolic function (end-systolic elastance 38% vs 100%; P < .001 vs 4 mmol/L L-arginine) and preload recruitable stroke work (40% vs 100%; P < .001 vs 4 mmol/L L-arginine); minimal increase in diastolic stiffness (239% vs 158%; P < .001 vs 4 mmol/L L-arginine); and lower coronary vascular resistance, conjugated diene production, and myeloperoxidase activity ( P < .001 vs 4 mmol/L L-arginine in each case). Conversely, supplementing the cardioplegic solution with a 10 mmol/L dose of L-arginine (group 3) negated these beneficial effects, resulting in depressed systolic function (end-systolic elastance 41% ± 2%; P < .001 vs 4 mmol/L L-arginine) and preload recruitable stroke work (40% ± 2%; P < .001 vs 4 mmol/L L-arginine); increased diastolic stiffness (246% ± 7%; P < .001 vs 4 mmol/L L-arginine); and higher conjugated diene production, myeloperoxidase activity, and coronary vascular resistance ( P < .001 vs 4 mmol/L L-arginine in each case). Conclusions: Enriching cardioplegic solution with a 4 mmol/L concentration of L-arginine significantly improves myocardial protection by reducing oxygen-derived free radical formation by white blood cells, thus preserving vascular and myocardial function. However, these beneficial effects are dose dependent because 10 mmol/L concentrations of L-arginine increase oxygen-derived free radical production, resulting in vascular and myocardial dysfunction. (J Thorac Cardiovasc Surg 1999;118:655-64)

Multi-dose Crystalloid Cardioplegia Preserves Intracellular Sodium Homeostasis in Myocardium

The goal of this study was to assess the effect of multi-dose St Thomas» cardioplegia on intracellular sodium homeostasis in a rat heart model. A new magnetic resonance method was applied which enable us to detect intracellular Na changes without chemical shift reagents. Three groups of isolated rat hearts were subjected to 51 min of ischemia and 51 min of reperfusion at 37°C: Group 1—three infusions of St Thomas» cardioplegia every 17 min for 2 min (n=7); Group 2—single-dose infusion of cardioplegia at the beginning of stop-flow ischemia (n=8); and Group 3—clamp ischemia (n=3) without cardioplegia administration. Performance of the heart was assessed by rate–pressure product relative to the pre-ischemic level (RPP). An NMR method was applied which continuously detects the Naiconcentration in the heart, using the ability of bound sodium to exhibit triple-quantum transitions and the growth of the corresponding signal when sodium ions pass from extracellular to intracellular space. Clamp ischemia without cardioplegia and 50 min of reperfusion left the heart dysfunctional, with Naigrowth from the pre-ischemic level of 13.9±1.2 m m to 34.9±1.3 m m and 73.9±1.9 m m at the end of ischemia and reperfusion, respectively. During single-dose cardioplegia the corresponding values for Naiwere 30.2±1 m m and 48.5±1.7 m m (RPP=29%). Multiple infusions of cardioplegic solution resulted in a remarkable preservation of the heart's intracellular Na concentration with a non-significant increase in Naiduring ischemia and only 16.7±1 m m, (P=0.01), after subsequent reperfusion (RPP=85%). The time course of Naichanges in the rat heart model demonstrates a prominent potential of multi-dose St Thomas» cardioplegia in preserving intracellular sodium homeostasis at 37°C. The growth of Naiconcentration during ischemia, as an indicator of the viability of the myocytes, can have a prognostic value for the heart's performance during reperfusion.

Retrograde Coronary Perfusion: Effects on Iatrogenic Edema and Diastolic Properties

Background. The relative merits of antegrade infusion and retrograde infusion of cardioplegic solution in terms of heart weight, myocardial water content, and ventricular diastolic properties are undefined. Accordingly, we compared antegrade and retrograde flow of hemodiluted blood in isolated, hypothermic porcine hearts. Methods. After cardiectomy, 1 L of cold heparinized blood diluted with lactated Ringer’s solution to concentrations ranging from 100% lactated Ringer’s to 50% lactated Ringer’s and 50% blood was perfused in an antegrade (n = 6) or retrograde (n = 6) fashion at mean pressures of 62 ± 2 mm Hg (± standard error of the mean) and 49 ± 2 mm Hg, respectively. Heart weight, myocardial water content, and left ventricular pressure–volume relationships were obtained before and after perfusion. Results. In the comparison of measurements before and after perfusion, changes in heart weight (36 ± 4 g versus 5 ± 2 g; p < 0.05), myocardial water content (6.9% ± 1.0% versus 2.5% ± 0.4%; p < 0.01), and ventricular filling measured by normalized left ventricular volume at 10, 15, and 20 mm Hg were greater in the antegrade group. Conclusions. In the isolated porcine heart, retrograde flow is distinguished from antegrade flow by less change in heart weight and myocardial water content and no diastolic dysfunction.

Energy metabolism and mechanical recovery after cardioplegia in moderately hypertrophied rats.

It is well established that severe hypertrophy induces metabolic and structural changes in the heart which result in enhanced susceptibility to ischemic damage during cardioplegic arrest while much less is known about the effect of cardioplegic arrest on moderately hypertrophied hearts. The aim of this study was to elucidate the differences in myocardial high energy phosphate metabolism and in functional recovery after cardioplegic arrest and ischemia in mildly hypertrophied hearts, before any metabolic alterations could be shown under baseline conditions. Cardiac hypertrophy was induced in rats by constriction of the abdominal aorta resulting in 20% increase in heart weight/body weight ratio (hypertrophy group) while sham operated animals served as control. In both groups, isolated hearts were perfused under normoxic conditions for 40 min followed by infusion of St.Thomas' Hospital No. 1 cardioplegia and 90 min ischemia at 25 degrees C with infusions of cardioplegia every 30 min. The changes in ATP, phosphocreatine (PCr) and inorganic phosphate (Pi) were followed by 31P nuclear magnetic resonance (NMR) spectroscopy. Systolic and diastolic function was assessed with an intraventricular balloon before and after ischemia. Baseline concentrations of PCr, ATP and Pi as well as coronary flow and cardiac function were not different between the two groups. However, after cardioplegic arrest PCr concentration increased to 61.8+/-4.9 micromol/g dry wt in the control group and to 46.3+/-2.8 micromol/g in hypertrophied hearts. Subsequently PCr, pH and ATP decreased gradually, concomitant with an accumulation of Pi in both groups. PCr was transiently restored during each infusion of cardioplegic solution while Pi decreased. PCr decreased faster after cardioplegic infusions in hypertrophied hearts. The most significant difference was observed during reperfusion: PCr recovered to its pre-ischemic levels within 2 min following restoration of coronary flow in the control group while similar recovery was observed after 4 min in the hypertrophied hearts. A greater deterioration of diastolic function was observed in hypertrophied hearts. Moderate hypertrophy, despite absence of metabolic changes under baseline conditions could lead to enhanced functional deterioration after cardioplegic arrest and ischemia. Impaired energy metabolism resulting in accelerated high energy phosphate depletion during ischemia and delayed recovery of energy equilibrium after cardioplegic arrest observed in hypertrophied hearts could be one of the underlying mechanisms.

High-energy phosphate changes in the normal and hypertrophied heart during cardioplegic arrest and ischemia.

The profile of metabolic changes in the ischemic heart following repeated infusions of cardioplegic solution has not been well characterized in cardiac hypertrophy. In this study we evaluated the effect of mild cardiac hypertrophy on the changes in phosphocreatine (PCr) and ATP throughout a cardioplegic arrest/ischemia/reperfusion experimental protocol (see Fig. 1). In addition to metabolic status, mechanical recovery of systolic and diastolic function was evaluated in the same hearts.

Myocardial protection in normal and hypoxically stressed neonatal hearts: The superiority of blood versus crystalloid cardioplegia

Objectives: Blood cardioplegia predominates in the adult because it provides superior myocardial protection, especially in the ischemically stressed heart. However, the superiority of blood over crystalloid cardioplegia in the pediatric population is unproved. Furthermore, because many pediatric hearts undergo a preoperative stress such as hypoxia, it is important to compare the different methods of protection in both normal and hypoxic hearts. Methods: Twenty neonatal piglets were supported by cardiopulmonary bypass and subjected to 70 minutes of cardioplegic arrest. Of 10 nonhypoxic hearts, five (group 1) were protected with blood cardioplegia and five (group 2) with crystalloid cardioplegia (St. Thomas' Hospital solution). Ten other piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen concentration 8% to 10%) before cardioplegic arrest. Five (group 3) were then protected with blood cardioplegia and the other five (group 4) with crystalloid cardioplegia. Myocardial function was assessed by means of pressure volume loops and expressed as a percentage of control. Coronary vascular resistance was measured with each infusion of cardioplegic solution. Results: No difference waas noted between blood (group 1) or crystalloid cardioplegia (group 2) in nonhypoxic hearts regarding systolic function (end-systolic elastance 104% vs 103%), diastolic stiffness (156% vs 159%), preload recruitable stroke work (102% vs 101%), or myocardial tissue edema (78.9% vs 78.9%). Conversely, in hearts subjected to a hypoxic stress, blood cardioplegia (group 3) provided better protection than crystalloid cardioplegia (group 4) by preserving systolic function (end-systolic elastance 106% vs 40%; p < 0.05) and preload recruitable stroke work (103% vs 40%; p < 0.05); reducing diastolic stiffness (153% vs 240%; p < 0.05) and myocardial tissue edema (79.6% vs 80.1%); and preserving vascular function, as evidenced by unaltered coronary vascular resistance ( p < 0.05). Conclusion: This study demonstrates that (1) blood or crystalloid cardioplegia is cardioprotective in hearts not compromised by preoperative hypoxia and (2) blood cardioplegia is superior to crystalloid cardioplegia in hearts subjected to the preoperative stress of acute hypoxia. (J Thorac Cardiovasc Surg 1997;113:994-1005)

High-energy phosphate changes in the normal and hypertrophied heart during cardioplegic arrest and ischemia

The profile of metabolic changes in the ischemic heart following repeated infusions of cardioplegic solution has not been well characterized in cardiac hypertrophy. In this study we evaluated the effect of mild cardiac hypertrophy on the changes in phosphocreatine (PCr) and ATP throughout a cardioplegic arrest/ischemia/reperfusion experimental protocol (see Fig. 1). In addition to metabolic status, mechanical recovery of systolic and diastolic function was evaluated in the same hearts.