不同晶体停搏液对幼兔心肌作用的比较

目的比较四种停搏液[改良托马氏液1号-MST,台氏液（Tyers）,布氏液（Bretshneider—HTK）,罗氏液（Roe）]对未成熟心肌的作用。方法观察不同停搏液模型幼兔心在Langendorff离体灌注装置14℃缺血2h后血流动力学、冠脉流出液心肌酶和心肌生化的变化。结果与Krebs—Henseleit重碳酸盐缓冲（KH）液比较,MST和Tyers停搏液可明显提高幼兔心功能的恢复（P〈0．05）,心肌酶的漏出较少（P〈0．05）,ATP储存较好（P〈0．05）。与KH液比较,HTK和Roe停搏液模型幼兔心功能恢复差（P〈0．05）,心肌酶漏出明显增多（P〈0．05）。结论MST和Tyers停搏液对未成熟心肌可提供较满意的心肌保护,HTK和Roe停搏液不能对未成熟心肌提供良好的心肌保护。     

Protection of the myocardium during global ischemia. Is crystalloid cardioplegia effective in the immature myocardium?

In pediatric cardiac operations, a high proportion of hospital deaths are believed to result from inadequate myocardial protection during the period of global ischemia. To investigate whether this may be due to an inherently lower resistance to myocardial ischemia or to the failure of conventional cardioplegia to afford adequate protection in the immature heart, we have conducted a series of studies with isolated hearts from neonatal (3 to 5 days old, body weight 6.3 to 13.4 gm) and adult (84 to 112 days old, 260 to 340 gm) rats. The efficacy of cardioplegia was assessed in neonatal hearts (n = 6 per group) subjected to various durations of normothermic ischemia, with and without a 2-minute preischemic infusion of the St. Thomas' Hospital cardioplegic solution. At all times studied, the use of cardioplegia resulted in a greater postischemic recovery of left ventricular developed pressure and first derivative of left ventricular pressure. After periods of ischemia lasting 30, 60, 90, 120, and 150 minutes in the absence of cardioplegia, left ventricular developed pressure recovered to 80% +/- 10%, 66% +/- 11%, 53% +/- 7%, 33% +/- 6%, and 21% +/- 4% of preischemic values, respectively; in the presence of cardioplegia, the values were 89% +/- 6%, 83% +/- 8%, 74% +/- 6% (p less than 0.05), 58% +/- 5% (p less than 0.05), and 41% +/- 7% (p less than 0.05), respectively. The corresponding values for first derivative of left ventricular pressure were 78% +/- 9%, 67% +/- 12%, 54% +/- 7%, 30% +/- 5%, and 19% +/- 3% in the absence of cardioplegia and 92% +/- 7%, 88% +/- 8%, 75% +/- 8%, 56% +/- 5% (p less than 0.05) and 39% +/- 6% (p less than 0.05) in the presence of cardioplegia. In the noncardioplegia groups, 90% of hearts exhibited ischemic contracture (mean time to onset = 24.7 +/- 1.1 minutes), whereas in the cardioplegia groups, only 63% exhibited contracture, and of a significantly delayed onset (37.0 +/- 1.5 min, p less than 0.05). Adult hearts (n = 5) subjected to 30 minutes of normothermic ischemic arrest, in the absence of cardioplegia, recovered 36% +/- 7% of the preischemic left ventricular developed pressure and 37% +/- 9% of the preischemic first derivative of left ventricular pressure on reperfusion; 100% of these hearts exhibited some degree of contracture (mean time to onset = 15.4 +/- 1.1 minutes) by the end of the ischemic period.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparison of the protective properties of four clinical crystalloid cardioplegic solutions in the rat heart

Although few surgeons dispute the benefits of high-potassium crystalloid cardioplegia, objective comparison of the efficacy of various formulations is difficult in clinical practice. We compared four commonly used cardioplegic solutions in the isolated rat heart (N = 6 for each solution) subjected to 180 minutes of hypothermic (20 degrees C) ischemic arrest with multidose cardioplegia (3 minutes every half-hour). The clinical solutions studied were St. Thomas' Hospital solution, Tyers' solution, lactated Ringer's solution with added potassium, and a balanced saline solution with glucose and potassium. Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of creatine kinase during reperfusion was measured as an additional index of protection. St. Thomas' Hospital solution provided almost complete recovery of all indexes of cardiac function following ischemia including 88.1 +/- 1.6% recovery of aortic flow, compared with poor recovery for the Tyers', lactated Ringer's, and balanced saline solutions (20.6 +/- 6.5%, 12.5 +/- 6.4%, and 9.6 +/- 4.2%, respectively) (p less than 0.001). Spontaneous defibrillation was rapid (less than 1 minute) and complete (100%) in all hearts in the St. Thomas' Hospital solution group, but much less satisfactory with the other formulations. Finally, St. Thomas' Hospital solution had a low postischemic level of creatine kinase leakage, contrasting with significantly higher enzyme release in the other solutions tested (p less than 0.001). Although differences in composition are subtle, all potassium crystalloid cardioplegic solutions are not alike in the myocardial protection they provide. Comparative studies under controlled conditions are important to define which formulation is superior for clinical application.     

Imidazole-buffered cardioplegic solution. Improved myocardial preservation during global ischemia

Progressive acidosis is a constant finding in global myocardial ischemia and is associated with reduced myocardial contractility after ischemia. The hypothesis tested in these experiments was that imidazole (pKa = 6.7 at 37 degrees C), a commonly used buffer in physiology and microbiology, would provide superior buffering capacity when used in lieu of bicarbonate (pKa = 6.1 at 37 degrees C) in a cardioplegic solution. Twenty-eight isolated, working rabbit hearts were perfused, and preischemic and postischemic determinants of performance were measured. The 30 minute interval of normothermic global ischemia was altered by the injection at 0 and 15 minutes of 2 ml/gm wet weight of a buffered cardioplegic solution. Control hearts received a bicarbonate-buffered cardioplegic solution and experimental hearts received a solution buffered with imidazole. In the imidazole-buffered group, there was a superior recovery of coronary flow, developed left ventricular pressure, peak rate of rise of left ventricular pressure, peak rate of relaxation, and stroke work indices (p less than 0.05). Recovery of mechanical parameters was coincident with an improved acid-base status of the coronary sinus effluent at the end of ischemia. Coronary sinus effluents in the imidazole group had significantly higher pH values and lower partial pressures of carbon dioxide than coronary sinus effluents in the bicarbonate-buffered group (p less than 0.001). The data suggest that improved buffering of the extracellular and possibly intracellular space during global ischemia with a nonbicarbonate buffer is beneficial and provides improved postischemic myocardial recovery.     

Effect of four crystalloid cardioplegias on immature rabbit hearts during global ischaemia

OBJECTIVE: Controversy surrounds the reported beneficial effects of crystalloid cardioplegic solutions in the immature myocardium. In the present study, we investigated the efficacy of four clinical cardioplegic solutions in the immature myocardium to determine if cardioplegic protection could be demonstrated and, if yes, the relative efficacy of the four solutions. METHODS: Isolated, working hearts (n=6 per group) from neonatal rabbits (age, 7-14 days) were perfused aerobically (37 C) for 15 minutes in the Langendorff mode and 30 minutes in the working mode before a 2-minute infusion of one of four cardioplegic solutions: the modified St. Thomas' Hospital no. 1 cardioplegic solution, Tyers solution, Bretschneider solution or Roe solution. Hearts were then rendered globally ischaemic for 120 minutes at 14C before reperfusion for 15 minutes in the Langendorff mode and 30 minutes in the working mode. The post-ischaemic recovery of cardiac function and leakage of myocardial enzymes (GOT, CK, CK-MB, LDH, LDH1) were compared with results in non-cardioplegic control hearts. RESULTS: Good protection was observed with modified St. Thomas' Hospital and Tyers solutions: postischaemic recovery of cardiac output was increased from 80.43+/-3.62% in the non-cardioplegic group to 85.19+/-3.12% and 70.66+/-3.48% in the St. Thomas' Hospital and Tyers groups (p<0.05), respectively. In contrast, no obvious protection was observed with either the Bretschneider or Roe solutions: cardiac output recovered to 45.08+/-3.16% and 30.06+/-2.59%, respectively. Post-ischaemic CK leakage was 19.83+/-2.14 IU/mL and 21.17+/-2.32 IU/mL in the St. Thomas' Hospital and Tyers groups (p>0.05). In the Bretschneider group, CK leakage increased to 30.00+/-3.16 IU/mL (p<0.01 vs. non-cardioplegic control hearts), and in the Roe group, CK leakage was 31.00+/-5.10 IU/mL (p<0.05 vs. cardioplegic-free hearts). Post-ischaemic ATP was 1.98+/-0.54 micromol/g*dry weight and 1.35+/-0.39 micromol/g*dry weight in the St. Thomas' Hospital and Tyers groups (p<0.01 vs. non-cardioplegic control group), respectively. In the Bretschneider group, ATP decreased to 0.91+/-0.16 micromol/g*dry weight (p<0.05 vs. non-cardioplegic control hearts), and in the Roe group to 0.88+/-0.10 micromol/g*dry weight (p<0.01 vs.cardioplegic-free hearts). CONCLUSION: In conclusion, cardioplegic protection can be achieved in the immature rabbit myocardium with both St. Thomas' Hospital and Tyers solutions, but acalcaemic solutions such as Bretschneider and Roe solutions increased damage. The reported lack of cardioplegic efficacy in the immature myocardium may, therefore, reflect the choice of cardioplegic solution rather than a greater vulnerability to injury in the neonatal heart.     

Bradykinin protects the rabbit heart after cardioplegic ischemia via NO-dependent pathways

Background. Depressed myocardial performance is an important clinical problem after open heart surgery. We hypothesized pretreating with bradykinin would pharmacologically precondition the heart and improve postischemic performance, and induce myocardial preconditioning by activating nitric oxide synthase.

Methods. Thirty-three rabbit hearts underwent retrograde perfusion with Krebs-Henseleit buffer (KHB) followed by 50 minutes of 37°C cardioplegic ischemia with St. Thomas’ cardioplegia solution (StTCP). Ten control hearts received no pretreatment. Ten bradykinin-pretreated hearts received a 10-minute infusion of 0.1 μMol/L bradykinin-enriched KHB and cardioplegic arrest with 0.1 μMol/L bradykinin-enriched StTCP. Six other hearts received 0.1 μMol/L HOE 140, a selective B2 receptor antagonist, added to both the 0.1 μMol/L bradykinin-enriched KHB and 0.1 μMol/L bradykinin-enriched StTCP solutions. Finally, six other hearts received 100 μMol/L of N-Ω-nitro- -arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, added to both the 0.1 μMol/L bradykinin-enriched KHB and 0.1 μMol/L bradykinin-enriched StTCP solutions.

Results. Bradykinin pretreatment significantly improved postischemic performance and coronary flow (CF) compared with control (LVDP: 53 ± 5* vs 27 ± 4 mm Hg; +dP/dt_max: 1,025 ± 93* vs 507 ± 85 mm Hg/s; CF: 31 ± 3* vs 22 ± 2 mL/min; *p < 0.05). Both HOE 140 and L-NAME abolished bradykinin-induced protection, resulting in recovery equivalent to untreated controls.

Conclusions. Bradykinin pretreatment improves recovery of ventricular and coronary vascular function via nitric oxide-dependent mechanisms. Pharmacologic preconditioning by bradykinin pretreatment may be an important new strategy for improving myocardial protection during heart surgery.     

Improved myocardial preservation with short hyperthermia prior to cold cardioplegic ischemia in immature rabbit hearts.

OBJECTIVE: Recent observations have been shown that the induction and accumulation of heat shock proteins (HSPs) by short exposure to nonlethal whole-body hyperthermia with normothermic recovery are closely associated with transient resistance to subsequent ischemia-reperfusion challanges. Here, this study was performed to investigate whether a shortly heat shock pretreatment affects the left ventricular (LV) function after cold cardioplegic ischemia in reperfused neonatal rabbit hearts. METHODS: Hearts from neonatal New Zealand White rabbits were isolated perfused (working heart preparation) and exposed to 2 h of cold cardioplegic ischemia followed by reperfusion for 60 min. To induce the heat shock response neonatal rabbits (n=5, HT-group) were subjected to whole-body hyperthermia at 42.0-42.5 degrees C for 15 min, followed by a normothermic recovery period of 60 min, before harvesting and the onset of global hypothermic cardioplegic arrest. Another set of hearts (n=5, control group) without a heat treatment underwent a similar perfusion and ischemia protocol served as control. The postischemic recovery was assessed by measuring several parameters of LV function. LV biopsies from all control and heat treated animals were taken before ischemia and at the end of reperfusion to examine myocardial HSP levels by Western blot analysis. RESULTS: At 60 min of reperfusion the HT-group showed significant better recovery of ventricular function such as LV developed pressure (DP) (74.6+/-10 vs. 52.1+/-8.5%, P<0.05), LV positive dP/dt (910+/-170 vs. 530+/-58 mmHg/s, P<0.01) and LV end-diastolic pressure (LVEDP) (8+/-2 vs. 18.4+/-5 mmHg, P<0.05) than control. Myocardial oxygen consumption (MVO(2)) was significantly higher in the HT-group compared with control (0.054+/-0.006 vs. 0.041+/-0.002 ml/g per min, P<0.05). Significant postreperfusion lower level in lactate production was observed in the HT-group (0.83+/-0.11 vs. 1.67+/-0.8 mmol/l, P<0.05). Also, the recovery of hemodynamic parameters such as aortic flow, coronary flow and cardiac output was significantly superior (P<0.05) in the HT-group. Furthermore, high expression of HSP72(+)/73(+) were detected in the myocardial tissue samples of heat-treated rabbits by immunoblotting, appearing even at 60 min of normothermic recovery after heat stress. CONCLUSIONS: These data in the immature rabbit heart indicate that previous shortly heat treatment with high level expression of heat shock proteins (HSP72(+)/73(+)) before hypothermic cardioplegic ischemia provides transient tolerance against myocardial injury and could be an improvement for the postischemic functional recovery of neonatal hearts.     

Studies of myocardial protection in the immature heart. I. Enhanced tolerance of immature versus adult myocardium to global ischemia with reference to metabolic differences

This study compares the metabolism and functional responses of adult and immature hearts to a standard ischemic insult. Ten adult dogs (25 to 27 kg) and 10 puppies (6 to 10 weeks old) underwent 45 minutes of aortic clamping on bypass. Preoperative and postoperative ventricular performance (Starling curves), biochemical factors, and water content were measured. Global ischemia in adults produced a 30% mortality rate (3/10) and low output syndrome in survivors (33% recovery of stroke work index). Conversely, all puppies survived and stroke work index returned to 85% of control, with less edema developing (0.4% versus 2% water gain, p less than 0.05). Puppies expended comparable glycogen stores but used more glutamate (15.4 versus 8.6 mumol/gm dry weight), produced more alanine (18.9 versus 6.4 mumol, p less than 0.05), succinate (19 versus 8.2 mumol, p less than 0.05), and malate (2.6 versus 0.15 mumol, p less than 0.05) during ischemia, and recovered better postischemic aerobic metabolism (410 versus 255 nmol tissue pyruvate, p less than 0.05). We conclude that tolerance of immature hearts to ischemia is related to amino acid utilization by transamination and increased substrate level phosphorylation, as occurring in diving mammals, suggesting retention of intrautero adaptive mechanisms.     

Effect of anoxia, flow-stop and cardioplegic solutions on the liberation of noradrenaline from the isolated rabbit heart in comparison to clinical findings

Experiments with isolated hearts. The results include the effects of anoxia, flow-stop and cardioplegic solutions (CPL) on the efflux of noradrenaline (NA) from isolated rabbit hearts preperfused with 3H-noradrenaline. 1.) Anoxic Tyrode solution did not enhance 3H-NA efflux into the perfusion medium. 2.) 3H-NA efflux was greatly enhanced after a flow-stop period of 20 min in normothermia (34 degrees C), but only to a small amount after a flow-stop period of 30 min in hypothermia (10 degrees C). 3.) In flow-stop experiments in hypothermia all CPL solutions enhanced the 3H-NA efflux. This effect is due to sodium deprivation (most CPL) or to high potassium concentration.--Studies on cardiosurgical patients. NA-concentration was determined in blood samples from vena cava superior (zv), radial artery (art) and coronary sinus (cv). 1.) cv NA-level continuously rose from 0.27 ng/ml after induction of anaesthesia to 0.77 ng/ml at onset of complete extracorporeal circulation. 2.) In 19 patients cardioplegia was induced by CPL HTP Bretschneider. Immediately after the cardioplegic period art und cv samples were collected at short intervals. NA-concentrations were not elevated in cv samples. 3.) An increase of NA in cv blood was distinct in two patients with extremely long periods of cardioplegia. In summary, after perfusion of isolated rabbit hearts with hypothermic CPL and subsequent flow-stop, an enhanced NA efflux is evident during reperfusion with Tyrode's solution. The effect of CPL on the NA release seems of minor importance in patients undergoing cardiosurgical procedures.     

Protection of the neonatal myocardium during hypothermic ischemia. Effect of cardioplegia on left ventricular function in the rabbit

The protective effect of cardioplegia upon neonatal myocardium during ischemia has not been clearly established. This study evaluated the effects of cardioplegia on left ventricular function in isolated working neonatal rabbit hearts (aged 1 week) subjected to 120 minutes of global ischemia at 28 degrees C. Four groups were studied: Group 1, hypothermia alone; Group 2, intermittent washout with an oxygenated noncardioplegic solution; Group 3, multidose cardioplegia; Group 4, single-dose cardioplegia. After ischemia, cardiac output was reduced to 72% +/- 5% (mean +/- standard error of the mean) of control (p less than 0.02) in Group 1 and to 56% +/- 4% in Group 2 (p less than 0.001). In contrast, there was no significant reduction from baseline cardiac output in those animals receiving cardioplegic solution (Group 3, 93% +/- 6%, and Group 4, 97% +/- 4%). Group 2 hearts demonstrated significantly worse recovery of cardiac output and stroke volume than all other groups. After ischemia, the first derivative of left ventricular pressure fell to 73% +/- 13% of control in Group 1 (p less than 0.1) and to 89% +/- 5% in Group 2 (p less than 0.05). However, the first derivative of left ventricular pressure was restored to control values in Group 3 (118% +/- 11%) and Group 4 (114% +/- 9%). When compared to baseline, creatine kinase was higher 30 minutes after reperfusion in Group 1 (40 +/- 8 versus 143 +/- 32 IU/L/gm, p less than 0.05) and in Group 2 (39 +/- 7 versus 163 +/- 33 IU/L/gm, p less than 0.05). Creatine kinase remained unchanged from baseline in Groups 3 and 4. This study demonstrates excellent preservation of left ventricular function in the neonatal rabbit heart protected with cardioplegic solution. In contrast, neither hypothermia alone nor intermittent washout with an oxygenated noncardioplegic solution was effective in preventing myocardial dysfunction. As in adults, the administration of cardioplegic solution preserves ventricular function during ischemia in neonatal hearts.     

Myocardial protection in the neonatal heart. A comparison of topical hypothermia and crystalloid and blood cardioplegic solutions

Myocardial protection achieved during 2 hours of ischemic arrest was evaluated in 45 isolated, blood perfused, neonatal (1 to 5 days) piglet hearts. Comparisons were made among five methods of myocardial protection: Group I, topical cooling; Group II, hyperosmolar (450 mOsm) low-calcium (0.5 mmol/L) crystalloid cardioplegia; Group III, St. Thomas' Hospital cardioplegia; Group IV, cold blood cardioplegia with potassium (21 mmol/L), citrate-phosphate-dextrose (calcium level 0.6 mmol/L), and tromethamine; and Group V, cold blood cardioplegia with potassium alone (16 mmol/L) (calcium level 1.2 mmol/L). Hemodynamic recovery (percent of the preischemic stroke work) after 30 and 60 minutes of reperfusion was 82.9% and 86.7% in Group I, 35.7% (p less than 0.0001) and 43.7% (p less than 0.0001) in Group II, 76.1% and 77.7% in Group III, 67.4% (p less than 0.05) and 60.6% (p less than 0.05) in Group IV, and 110.7% and 100.6% in Group V. Conclusions: Topical cooling is an effective method of myocardial protection in the neonate. Cold blood cardioplegia with potassium alone and a normal calcium level provides optimal functional recovery. The improved protection obtained with both crystalloid and blood cardioplegia with normal calcium levels suggests an increased sensitivity of the neonatal heart to the calcium level of the cardioplegic solution.     

Cardioplegia for the immature myocardium. A comparative study in the neonatal rabbit

This study examined the effect of hypothermia (15 degrees C) alone or combined with various cardioplegic solutions on functional recovery of the neonatal heart after 120 minutes of global ischemia in an isolated working rabbit heart model. Control hearts were preserved with hypothermia alone, and groups 1 to 6 were given different hyperkalemic crystalloid cardioplegic solutions. Each cardioplegic solution differed in Na+ and Ca++ content. Aortic flow, coronary flow, cardiac output, heart rate, peak systolic pressure, and stroke work were measured before ischemia and after 35 and 45 minutes of reperfusion. There were no statistical differences in hemodynamic recovery in the six groups in which cardioplegia was used. However, hearts preserved with multidose hyperkalemic cardioplegia showed significantly better recovery of cardiac output (86% versus 75%; p less than 0.05), coronary flow (88% versus 72%; p less than 0.05), and stroke work (86% versus 75%; p less than 0.05) than those preserved with hypothermia alone. These results suggest that hypothermic hyperkalemic cardioplegia improves preservation of the neonatal rabbit heart but that variations in Ca++ and Na+ content appear not to provide further myocardial protection.     

Calcium content of St. Thomas' II cardioplegic solution damages ischemic immature myocardium

Clinical application of hypothermic pharmacologic cardioplegia in pediatric cardiac surgery is less than satisfactory, despite its well known benefits in adults. Protection of the ischemic immature rabbit heart with hypothermia alone is better than with hypothermic St. Thomas' II cardioplegic solution. Control of cellular calcium is a critical component of cardioplegic protection. We determined whether the existing calcium content of St. Thomas' II solution (1.2 mmol/L) is responsible for suboptimal protection of the ischemic immature rabbit heart. Modified hypothermic St. Thomas' II solutions (calcium content, 0 to 2.4 mmol/L) were compared with hypothermic Krebs bicarbonate buffer in protecting ischemic immature (7- to 10-day-old) hearts. Hearts (n = 6 per group) underwent aerobic "working" perfusion with Krebs buffer, and cardiac function was measured. The hearts were then arrested with a 3-minute infusion of either cold (14 degrees C) Krebs buffer (1.8 mmol calcium/L) as hypothermia alone or cold St. Thomas' II solution before 6 hours of hypothermic (14 degrees C) global ischemia. Hearts were reperfused, and postischemic enzyme leakage and recovery of function were measured. A bell-shaped dose-response profile for calcium was observed for recovery of aortic flow but not for creatine kinase leakage, with improved protection at lower calcium concentrations. Optimal myocardial protection occurred at a calcium content of 0.3 mmol/L, which was better than with hypothermia alone and standard St. Thomas' II solution. We conclude that the existing calcium content of St. Thomas' II solution is responsible, in part, for its damaging effect on the ischemic immature rabbit heart.     

Cooling of the myocardium: clinical comparison of 2 methods of administering the cardioplegic solution

The authors studied the dynamics of changes in myocardial temperature in injection of an oxygenated cardioplegic solution through the root of the aorta (group 1 of patients) and through the right atrium (group 2) during prosthetic repair of the heart valves. Retrograde injection of the cardioplegic solution through the right atrium ensured adequate cooling of the hypertrophied myocardium of both ventricles and did not yield to antegrade infusion. It proved possible to attain a safe level of right-atrial hypothermia only when the cardioplegic solution was infused through the right atrium. This is due to the fact that the method combined the features of perfusion and local hypothermia.     

Studies of myocardial protection in the immature heart. IV. Improved tolerance of immature myocardium to hypoxia and ischemia by intravenous metabolic support

Thirteen immature puppies (2 to 4 kg) underwent 1 hour of acute hypoxia (oxygen tension 25 to 30 mm Hg), followed by 45 minutes of normothermic global ischemia on total vented bypass with normal blood reperfusion. Ventricular function was assessed by inscribing Starling function curves and measuring stroke work indices before hypoxia and after reperfusion. Seven puppies (control) received normal saline infusion at 4 ml/kg/hr. Six other puppies received a 4 ml/kg/hr intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, mercaptopropionyl glycine, carnitine, and catalase during hypoxia and reperfusion. In control hearts, acute hypoxia depleted myocardial glutamate and aspartate by 52% (p less than 0.05 versus prehypoxia) and 48% (p less than 0.05 versus prehypoxia) and caused severe hemodynamic deterioration (55% decrease of stroke work index) (p less than 0.05 versus prehypoxia); three of seven (43%) required premature institution of bypass. Postischemic left ventricular function recovered to only 40% of control levels (p less than 0.05 versus prehypoxia). In contrast, intravenous metabolic infusions maintained tissue glutamate (p less than 0.05 versus control group) and aspartate (p less than 0.05 versus control group) in treated hearts during hypoxia and allowed cardiac index to rise 20% (p less than 0.05 versus prehypoxia); all treated hearts tolerated 1 hour of hypoxia, and stroke work recovered 70% (p less than 0.05 versus control group) of stroke work index after subsequent ischemia. Impaired tolerance of immature hearts to acute hypoxia and subsequent ischemia is due to substrate depletion. This impairment can be reduced by intravenous metabolic support during hypoxia and reperfusion and leads to improved recovery of postischemic function.     

Protection of the immature heart. Temperature-dependent beneficial or detrimental effects of multidose crystalloid cardioplegia in the neonatal rabbit heart

There are conflicting reports of the detrimental or beneficial effects of hypothermic cardioplegia in the immature heart. We therefore investigated the temperature-dependence of myocardial protection and the ability of single-dose and multidose infusions of cardioplegic solution to protect the immature heart during hypothermic ischemia. Isolated, working hearts (n = 6 per group) from neonatal rabbits (aged 7 to 10 days) were perfused aerobically (37.0 degrees C) for 20 minutes before infusion (2 minutes) with either perfusion fluid (noncardioplegia control) or St. Thomas' Hospital cardioplegic solution and ischemic arrest (for 4, 6, and 18 hours) at various temperatures between 10.0 degrees and 30.0 degrees C. Hearts arrested with cardioplegic solution received either one preischemic infusion only (single-dose cardioplegia) or repeated infusions at intervals of 60 or 180 minutes (multidose cardioplegia). Ischemic arrest with single-dose cardioplegia for 4 hours at 10.0 degrees, 20.0 degrees, 22.5 degrees, 25.0 degrees, 27.5 degrees, and 30.0 degrees C resulted in 96.0% +/- 4.3%, 96.6 +/- 2.5%, 87.0% +/- 3.8%, 71.8% +/- 10.0% (p less than 0.05 versus 10.0 degrees C group), 35.1% +/- 10.3% (p less than 0.01 versus 10.0 degrees C group), and 3.0% +/- 1.9% (p less than 0.04 versus 10.0 degrees C group) recovery of preischemic cardiac output, respectively. With 6 hours of ischemia at 20.0 degrees C, single-dose cardioplegia significantly (p less than 0.01) increased the recovery of cardiac output from 20.9% +/- 13.1% (control) to 76.4% +/- 4.4%, whereas multidose cardioplegia (infusion every 60 minutes) further increased recovery to 97.8% +/- 3.8% (p less than 0.01 versus control and single-dose cardioplegia). In contrast, after 6 hours of ischemia at 10.0 degrees C, cardiac output recovered to 93.4% +/- 1.2% (control) and 92.3% +/- 3.1% (single-dose cardioplegia), whereas multidose cardioplegia reduced recovery to 76.9% +/- 2.2% (p less than 0.01 versus both groups). This effect was confirmed after 18 hours of ischemia at 10.0 degrees C; single-dose cardioplegia significantly increased the recovery of cardiac output from 24.5% +/- 10.9% (control) to 62.9% +/- 13.3% (p less than 0.05), whereas multidose cardioplegia reduced recovery to 0.8% +/- 0.4% (p less than 0.01 versus single-dose cardioplegia) and elevated coronary vascular resistance from 8.90 +/- 0.56 mm Hg.min/ml (control) to 47.83 +/- 9.85 mm Hg.min/ml (p less than 0.01). This effect was not reduced by lowering the infusion frequency (from every 60 to every 180 minutes).(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparison of three cardioplegic solutions during hypothermic ischemic arrest in neonatal blood-perfused rabbit hearts

Inadequate myocardial preservation continues to be an important cause of postoperative morbidity and mortality after pediatric cardiac operations. To investigate methods of improving preservation in neonatal myocardium, we compared three cardioplegic solutions with topical hypothermia during 120 minutes of ischemic arrest in isolated, blood-perfused, neonatal rabbit hearts. Topical hypothermia (15 degrees C) without cardioplegia resulted in 71% +/- 5% recovery of preischemic contractile function. A high potassium (30 mEq/L) cardioplegic solution resulted in a 76% +/- 6% recovery of function, not significantly different from that obtained with hypothermia alone. In contrast, the St. Thomas' Hospital and H?pital Lariboisiere cardioplegic solutions resulted in recoveries of 89% +/- 6% and 88% +/- 7%, respectively, both of which were significantly greater (p less than 0.001) than recoveries obtained with the high potassium solution or hypothermia alone. Thus the cardioplegic solutions used at St. Thomas' Hospital and H?pital Lariboisiere provided excellent protection during 2 hours of hypothermic ischemic arrest in neonatal rabbit hearts and resulted in functional recovery superior to that achieved with hypothermia alone or with the high potassium cardioplegic solution.