Preconditioning during warm blood cardioplegia

Objective: Preconditioning describes the cardioprotective effects of multiple brief episodes of warm ischemia. The purpose of the study was to determine whether warm ischemia, during the intermittent delivery of warm blood cardioplegia, would induce preconditioning during cardioplegia arrest. Methods: Dogs, 15, were randomized to a preconditioning protocol or to serve as controls. The control group received 60 min of continuous warm blood cardioplegia (WBC) followed by 30 min of warm arrested ischemia. The preconditioned group were arrested with WBC and then underwent three consecutive cycles consisting of 10 min of warm ischemia followed by 10 min of reperfusion. Reperfusion was provided by a continuous infusion of WBC. The preconditioning protocol was followed by 30 min of warm arrested ischemia. Myocardial functional recovery was assessed before cardiopulmonary bypass and cardioplegia arrest and again 30, 60 and 90 min after the arrest. Pressure-volume loops were used to measure the maximum elastance of the left ventricle (E_max), diastolic compliance, and used to calculate preload recruitable stroke work area. Results: Myocardial functional recovery was better preserved after 30 min of warm arrested ischemia in those animals that had been preconditioned. Conclusion: Preconditioning may be induced when warm blood cardioplegia is delivered intermittently during cardioplegia arrest.     

Effects of supplemental L-arginine during warm blood cardioplegia.

OBJECTIVES: Effects of supplemental L-arginine, nitric oxide precursor, during warm blood cardioplegia were assessed in the blood perfused isolated rat heart. METHODS: The isolated hearts were perfused with blood at 37 degrees C from a support rat. After 20 minutes of aerobic perfusion, the hearts were arrested for 60 minutes with warm blood cardioplegia given at 20-minute intervals. This was followed by 60 minutes of reperfusion. The hearts were divided into the following three groups according to the supplemental drugs added to the cardioplegic solution. The control group (n = 10) received standard warm blood cardioplegia. The L-ARG group (n = 10) received warm blood cardioplegia supplemented with L-arginine (3 mmol/l). The L-NAME group (n = 10) received warm blood cardioplegia supplemented with L-arginine (3 mmol/l) and L-nitro-arginine methyl ester, a competitive inhibitor of nitric oxide synthase (1 mmol/l). After 60 minutes of cardioplegic arrest, cardiac function, myocardial metabolism and myocardial release of circulating adhesion molecules were measured during reperfusion. RESULTS: Left ventricular end-diastolic pressure was significantly lower (p<0.05) in the L-ARG group than in the control group and the L-NAME group during reperfusion. Isovolumic left ventricular developed pressure, dp/dt and coronary blood flow were significantly greater (p< 0.05) in the L-ARG group during reperfusion. The L-ARG group resulted in early recovery of lactate metabolism during reperfusion. Myocardial release of circulating intercellular adhesion molecule-1 (ICAM-1) and E-selectin were significantly less (p<0.05) in the L-ARG group at 15 minutes of reperfusion. CONCLUSIONS: The results suggest that augmented nitric oxide by adding L-arginine to warm blood cardioplegia can preserve left ventricular function and ameliorate endothelial inflammation. The technique can be a novel cardioprotective strategy in patients undergoing cardiac surgery.     

Intermittent antegrade warm blood cardioplegia for CABG: extended interval of cardioplegia

BACKGROUND: Intermittent delivery of warm cardioplegia provides a bloodless surgical field, but it is clinically important to evaluate the periods of normothermic ischemia. The aims of this study are to compare intermittent antegrade warm blood cardioplegia (IAWBC) with intermittent antegrade cold blood cardioplegia (IACBC) groups in terms of myocardial protection, and also to evaluate whether the length of ischemic time in the IAWBC group has an effect on myocardial dysfunction. METHODS: This study is based on a retrospective review of patients who underwent elective coronary artery bypass surgery: 162 consecutive patients with IAWBC and 107 consecutive patients with IACBC. RESULTS: The creatinine kinase peak was smaller in the IAWBC group compared with the IACBC group (p<0.0001). The cardiac index after cardiopulmonary bypass was higher in the IAWBC group (p<0.02), and the amount of inotropic support required to wean from cardiopulmonary bypass was less in the IAWBC group compared with the IACBC group (p<0.0001). CONCLUSIONS: IAWBC with 30 minutes of ischemia provides to be clinically acceptable myocardial protection for coronary bypass surgery.     

The efficiency of intermittent antegrade warm blood cardioplegia

We studied the effects of modified Calafiore technique that is intermittent antegrade warm blood cardioplegia including potassium solution and oxygenated with normothermic cardiopulmonary bypass. From January 1996 to March 1997, 45 patients who had undergone elective coronary artery bypass grafting were assigned retrospectively to two groups. Warm group: 25 patients received intermittent antegrade warm blood cardioplegia with normothermic cardiopulmonary bypass. Cold group: 20 patients received intermittent antegrade cold blood cardioplegia with slight hypothermic cardiopulmonary bypass. Preoperative variables were similar in both groups. The rate of sinus rebeating after aorta declamping with DC was lower in warm group than in cold group [warm group 2/25 (8%) versus cold group 8/20 (40%); P < 0.05]. The levels of CK and CK-MB were significantly lower in warm group than in cold group on postoperative day 0. On postoperative day 0 and day 1, the dosage of cathecholamines were significantly less for the warm group than in the cold group. Perioperative events of IABP, PMI and neurological dysfunction were not statistically different. These results show that intermittent antegrade warm blood cardioplegia is a safe and effective method for myocardial protection. But it requires further assessment.     

Myocardial oxygen consumption and lactate production during antegrade warm blood cardioplegia.

Continuous warm blood cardioplegia has recently been recommended as an alternative to multidose cold blood cardioplegia for myocardial protection during coronary bypass operations. Cardioplegia may have to be interrupted in order to provide a bloodless operating field during coronary anastomosis. To determine the effects of ischemia at normothermia on myocardial oxygen consumption and lactate production we randomized 17 dogs to receive either warm blood cardioplegia (37 degrees C) or cold blood cardioplegia combined with systemic and topical cooling. After initiating arrest, cardioplegia was interrupted for periods of 1, 2, 3, 4, 5, 6, and 10 min. Myocardial oxygen debt occurred after 3.5 min of ischemia in the 9 animals receiving warm blood cardioplegia. In contrast, myocardial oxygen consumption never exceeded oxygen availability during cold blood cardioplegia (P less than 0.001). Lactate production increased linearly in both groups but was much greater in those animals receiving warm blood cardioplegia (P less than 0.001). Spontaneous electromechanical activity was much more common during warm blood cardioplegia which required frequent infusions of cardioplegia to maintain cardiac arrest (P less than 0.0003). Conclusions: (1) Oxygen debt occurred after 3.5 min of warm ischemia; (2) spontaneous electromechanical activity is more common during warm heart protection which necessitates the use of larger volumes of cardioplegia to maintain cardiac arrest.     

脱白细胞温血心脏停搏液对心脏瓣膜置换术患者心肌的保护作用

目的研究脱白细胞温血心脏停博液微流量连续灌注对体外循环下瓣膜置换术患者心肌的保护效果。方法拟行心脏瓣膜置换术患者4JD例,随机分为对照组和试验组,每组20例。对照组:采用温血心脏停博液微流量连续顺行灌注;试验组:采用脱白细胞的温血心脏停博液微流量连续顺行灌注。采集术中不同时间点静脉血标本,检测血浆类脂肪酸结合蛋白、丙二醛及右心房心肌内髓过氧化物酶水平。结果试验组主动脉开放30、60min血浆类脂肪酸结合蛋白、丙二醛均较主动脉阻断前升高,但均低于对照组(P<0.05)。试验组心肌内髓过氧化物酶在主动脉开放后与阻断前相比差异无统计学意义(P>0.05),而对照组与阻断前相比增加(P<0.05),两组之间比较,差异有统计学意义。结论脱白细胞温血心脏停博液微流量连续灌注,可有效减轻心肌缺血再灌注损伤。     

The intermittent "warm" blood cardioplegia]

Even today, a plethora of cardioplegic solutions are in clinical use. In the study presented here, sixty-six consecutive coronary bypass procedures received normothermic (37 degrees C) blood cardioplegia (NBC) intermittently. This group of patients was compared to an historical group of 68 patients having received cold crystalloid cardioplegia (CCC), and a second group of 41 patients having received cold blood (10 degrees C) cardioplegia (CBC). The number of patients, as well as their age, sex, functional class, ejection fraction and urgency of intervention were comparable between the three groups. The preoperative use of inotropic drugs was less prevalent in the normothermic blood cardioplegia group (NBC 24% v. CCC 52% and CBC 51%, p < 0.05), as was the use of a pacemaker (NBC 8% v. CCC 52% and CBC 51%, p < 0.02). Finally, the rates of myocardial infarction and mortality were comparable between the three groups. These results suggest that normothermic blood cardioplegia is efficient in reducing the demand in O2, by inducing the electromechanical arrest of the heart and, that intermittent normothermic blood cardioplegia can be safe and effective.     

温血停搏液持续与间断灌注在冠状动脉搭桥术中的比较研究

目的 比较温血持续与间断灌注心脏停搏液在冠状动脉搭桥术中心肌保护效应。方法将30例冠状动脉搭桥手术随机分为温血持续灌注组（n=15）;温血间断灌注组（n=15）,灌注心脏停搏液,在常温体外循环下分别于切皮前、转流60min、停机6、12h采集动脉血,以ELISA法测定血浆心肌肌钙蛋白T（cTnT）浓度。分别取主动脉阻断前、开放后心肌组织,观察三磷酸腺苷（ATP）含量及心肌超微结构。结果 温血间断组 cTnT在停机6h时点比温血持续组有显著性差异（P<0.05）。两组术中60min、停机6hcTnT升高,停机24h逐渐恢复术前水平。两组ATP含量比主动脉阻断前有显著性差异（P<0.05）。温血间断组线粒体计分主动脉阻断开放后比主动脉阻断开放前有显著性差异（P<0.05）,温血持续组略升高（P<0.05）。结论 常温体外循环中温血持续灌注停搏液优于温血间断灌注停搏液的心肌保护作用。     

Experience with warm blood cardioplegia in 480 patients

From 1 March 1992 too 31 July 1993 (17 months), 480 consecutive patients underwent various open-heart procedures under anterograde (83 patients) or retrograde (397 patients) continuous warm blood cardioplegia. Some 352 patients (73.3%) had isolated coronary artery bypass grafts (CABG) and 117 (24.3%) had valve replacement either isolated (96) or in combination with other operations (21). Two patients had CABG and ventricular aneurysmectomy, eight had correction of congenital defects, and one had resection of left atrial myxoma. The 30-day postoperative mortality rate was 2.9% (14 deaths). In four patients the cause of death was not cardiogenic. An intra-aortic balloon was used in 11 patients following CABG (3.1%) with six survivors. Perforation of the coronary sinus occurred in one patient. Perioperative myocardial infarction was observed in 5.6% of patients after CABG. No myocardial infarction occurred after valve replacement. Phrenic nerve injury and wound infection were not observed. These results indicate that warm blood cardioplegia, especially when delivered retrogradely, provides excellent myocardial protection of both ventricles during various open-heart procedures.     

Technique and pitfalls of retrograde continuous warm blood cardioplegia

The recent development of normothermic myocardial preservation and systemic perfusion during bypass has questioned the fundamental need for hypothermia during cardiac operations. The antegrade technique of almost continuous perfusion by the aortic root and vein grafts has been supplemented by continuous normothermic blood cardioplegia through the coronary sinus. Recently, great interest has been shown in this technique. It is important to describe the method in detail along with its potential shortcomings and dangers. This communication describes the technical details, pitfalls, and shortcomings of retrograde continuous warm blood cardioplegia.     

Continuous monitoring of myocardial acid–base status during intermittent warm blood cardioplegia

Objective: Intermittent warm blood cardioplegia (IWBC) is a well-established technique for myocardial protection during cardiac operations. According to standardized protocols, IWBC administration is currently performed every 15–20 min regardless of any individual variable and in the absence of any instrumental monitoring. We devised a new system for continuous measurement of the acid–base status of coronary sinus blood for on-line evaluation of myocardial oxygenation during IWBC. Methods: In 19 patients undergoing cardiac surgery for coronary artery bypass graft and/or valve surgery and receiving IWBC (34–37°C) by antegrade induction (3 min) and retrograde or antegrade maintenance (2 min) every 15 min, continuous monitoring of myocardial oxygenation and acid/base status was performed by means of a multiparameter PO₂, PCO₂, pH, and temperature sensor (Paratrend7 ®, Philips Medical System) inserted into the coronary sinus. Results: Mean cross-clamping time was 76±26 min; ischemic time was 13±0.2 min. pH decline was not linear, showing an initial fast decline, a point of flexus, and a progressive slow decline. After every ischemic period, the pH adaptation curve showed a complex pattern reaching step-by-step lower minimum levels (7.28±0.14 during the first ischemic period, to 7.16±0.19 during the third ischemic period – P=0.003). PO₂ decreased rapidly at 90% in 5.0±1.2 min after every reperfusion. During ischemia, PCO₂ increased steadily at 1.6±0.1 mmHg per minute, with progressively incomplete removal after successive reperfusion, and progressive increase of maximal level (42±12 mmHg during the first ischemic period, to 53±23 mmHg during the third ischemic period – P=0.05). Conclusions: Myocardial oxygen, carbon dioxide, and pH show marked changes after repeated IWBC. Myocardial ischemia is not completely reversed by standardized reperfusions, as reflected by steady deterioration of PCO₂ and pH after each reperfusion. Progressive increase of reperfusion durations or direct monitoring of myocardial oxygenation could be advisable in cases of prolonged cross-clamping time.     

Continuous warm blood cardioplegia preserves cardiac autonomic function.

We studied in anesthetized dogs, the effects of cardiopulmonary bypass with normothermic whole blood, crossclamping of the aortic root, and continuous warm blood cardioplegia on the ability of the efferent sympathetic nervous system to augment the heart and that of the efferent parasympathetic nervous system to depress the heart. In control states, heart rate, atrial force of contraction, and right and left ventricular wall systolic pressures were augmented by stimulation of the intrathoracic efferent sympathetic nervous system and by administration of isoproterenol into the systemic circulation. After 1 hour of normothermic cardiopulmonary bypass that utilized aortic crossclamping and continuous perfusion of the coronary arteries with normothermic blood (20 mEq/L potassium), cardiac-augmenting effects induced by the efferent sympathetic nervous system and by isoproterenol were similar. Depressive responses elicited by the efferent parasympathetic nervous system were also unaffected by these procedures. Continuous warm blood cardioplegia does not result in impairment of the efferent sympathetic nervous system regulating the heart.     

Accelerated myocardial metabolic recovery with terminal warm blood cardioplegia

Although blood cardioplegia provides excellent protection, myocardial metabolic recovery is delayed. To evaluate the benefits of a terminal warm cardioplegic infusion after cold blood cardioplegia, we performed a prospective randomized trial in 20 patients undergoing elective coronary bypass grafting. Eleven patients received cold blood cardioplegia and nine patients received cold blood cardioplegia and warm blood cardioplegia before cross-clamp removal (hot shot). The hot shot provided oxygen and removed excess lactate from the arrested heart. After the hot shot lactate was extracted by the heart and tissue adenosine triphosphate and glycogen concentrations were preserved. Atrial pacing and volume loading 3 and 4 hours postoperatively decreased myocardial lactate extraction after cold blood cardioplegia but increased lactate extraction after the hot shot. Left atrial pressures were higher at similar end-diastolic volumes (by nuclear ventriculography), which suggested decreased diastolic compliance after cold blood cardioplegia. Terminal warm blood cardioplegia accelerated myocardial metabolic recovery, preserved high-energy phosphates, improved the metabolic response to postoperative hemodynamic stresses, and reduced left atrial pressures.     

Intermittent warm blood cardioplegia —An experimental study—

The influence of intermittent warm blood cardioplegia (WBCP) on myocardial function and metabolism was studied. Fourty-two adult mongrel dogs were used. The isolated heart of one dog was perfused by the cross circulation method with another support dog. The dogs then were divided into three groups. In group I (n=6), the empty beating heart was perfused with warm blood (WB) kept at 36°C for 100 minutes. In group II (n = 7), the arrested heart was perfused with continuous WBCP using modified Fremes solution for 100 minutes. In group III (n=8), the arrested heart was perfused with WBCP for 10 minutes following a 15-minute non-perfusion period. This perfusion method was repeated four times. The E max, LV developed pressure, ± LV dp/dt and LVEDP were all measured to evaluated the myocardial function. In addition, the coronary venous blood pH, myocardial oxygen consumption, myocardial lactate extraction, coronary blood flow, myocardial high energy phosphate content and myocardial water content were also studied in order to elucidate the myocardial metabolism. Regarding the myocardial function, no significant difference was observed between the three groups. The results of chemical studies on the myocardial metabolism were as follows: (1) the coronary venous blood pH in group III decreased at the end of the no perfusion period of WBCP. But it thereafter gradually returned to the normal physiological range; (2) the myocardial oxygen consumption in group III increased just after each interruption, but then gradually decreased toward following intermittent WBCP; (3) the myocardial lactate extraction decreased at the end of the non-perfusion period. However, it gradually returned to the control value by the end of each period of WBCP perfusion; (4) after 60 minutes of reperfusion, the coronary venous blood pH, myocardial oxygen consumption and myocardial lactate extraction showed no significant differences between the groups; (5) the coronary blood flow in group III increased significantly after 1 minute of reperfusion; (6) the ATP value in group III decreased significantly after 60 minutes of reperfusion. The ADP and AMP values demonstrated no significant difference between the groups during the same period; and (7) no significant difference was seen in the myocardial water content between the groups after 60 minutes of reperfusion. It is thus concluded that 10 minutes of intermittent WBCP followed by a 15-minute interruption appeared to have no deleterious effect on the myocardial funciton and metabolism.     

Retrograde continuous warm blood cardioplegia reduces oxidative stress during coronary artery bypass grafting.

Myocardial oxidative stress during retrograde continuous blood cardioplegia (RCBC) was evaluated in 22 patients undergoing elective aortocoronary bypass surgery. The patients were divided into two groups: Group C (n=11) received cold RCBC, and Group W (n=11) received warm RCBC. Myocardial oxidative stress was assessed by measuring the release of oxidized glutathione (GSSG), malondialdehyde (MDA), and myeloperoxidase (MPO) in the coronary sinus plasma before aortic clamping, at 1, 5, and 10 minutes after unclamping. Both the hemodynamic recovery and the creatine kinase MB (CKMB) activity were measured perioperatively until 24 hours after unclamping. In Group C, a significant coronary sinus release of GSSG was found in the early reperfusion period in comparison to Group W. No significant difference in the release of MDA nor MPO was noted in the two groups. The recoveries in the left and right ventricular functions, and the peak CK-MB activity were similar in both groups. In conclusion, warm blood cardioplegia is thus considered to protect the myocardium from ischemia-reperfusion injury better than cold blood cardioplegia under retrograde continuous perfusion.     

Myocardial metabolism and efficiency after warm continuous blood cardioplegia

Background. Warm continuous blood cardioplegia (WCBCP) has been recommended during prolonged cardiac arrest to minimize functional deterioration. Myocardial metabolism and efficiency after this cardioplegic modality are not well described.

Methods. Substrate oxidation, blood flow, and myocardial function were measured before, during, and after 3 hours of WCBCP in 7 pigs.

Results. Free fatty acid and glucose oxidation decreased by 60% ± 3.8% and 94% ± 1.2%, respectively, during cardioplegia (both p < 0.05) and increased to 62% ± 28% and 122% ± 62% of baseline during the early recovery phase (p < 0.05 for glucose). One hour after WCBCP oxidation rates were similar to baseline. The transient postcardioplegic increase in substrate oxidation was associated with a 43% ± 23% elevation of oxygen consumption (MVO₂) compared with baseline and a 62% ± 18% increase in myocardial blood flow. Cardiac output and mean arterial pressure did not change significantly after WCBCP, although myocardial function (stroke work, left ventricular end-systolic pressure, end-diastolic pressure, contractility, and efficiency) was depressed (p < 0.05). End-diastolic pressure and contractility improved from early to late phase of recovery, whereas the other indicators of ventricular function remained depressed.

Conclusions. Myocardial substrate oxidation was preserved after 3 hours of WCBCP, although ventricular function was moderately impaired. Thus, WCBCP with a seemingly normal substrate and oxygen supply was associated with a reduced cardiac efficiency.     

Does warm blood retrograde cardioplegia preserve right ventricular function?

BACKGROUND: Efficacy of warm blood retrograde cardioplegia in preserving right heart function remains controversial. The current study was conducted to gauge the preservation of right ventricular function after warm blood retrograde cardioplegia. METHODS: We studied 75 consecutive patients undergoing isolated heart valve procedures with warm blood retrograde cardioplegia as the exclusive mode of preservation. Right ventricular radionuclide ejection fraction and hemodynamic measurements using a pulmonary artery catheter were calculated before and within 3 days after operation. RESULTS: Postoperative radionuclide right ventricular ejection fraction was well preserved at 0.4686 +/- 0.0122 compared with 0.4327 +/- 0.0255 preoperatively (p = 0.7064). Right ventricular systolic work index improved from 5.82 +/- 0.52 to 8.97 +/- 0.60 g x m/m2 (p < 0.0001) and cardiac index increased from 2.40 +/- 0.09 to 2.92 +/- 0.11 L/m2 (p < 0.0001). When right ventricular systolic work index was correlated with preload, 30 patients moved up and down on the same ventricular function curve and 42 moved to a higher inotropic curve postoperatively. Only 3 patients demonstrated decreased inotropy. CONCLUSIONS: In the clinical setting warm blood retrograde cardioplegia used as the exclusive mode of myocardial preservation provides adequate protection of the right heart.