Intermittent warm blood cardioplegia does not provide adequate myocardial resuscitation after global ischaemia.

OBJECTIVE: Intermittent warm blood cardioplegia is controversial, and many surgeons consider it inadequate for myocardial protection. The purpose of this study was to compare intermittent and continuous warm blood cardioplegia as resuscitation in hearts exposed to global ischaemia. METHODS: Pigs were put on cardiopulmonary bypass (CPB) and subjected to 30 min of warm, "unprotected", global ischaemia, followed by continuous (n = 7) or intermittent (n = 10, 12 ml/kg every 10 min) warm (34 degrees C) antegrade blood cardioplegia for 45 min (delivery pressure 75-80 mmHg) and weaned from CPB 45 to 60 min later. Indices of left ventricular function were acquired with the conductance catheter technique and pressure-volume loops at baseline and after 90 min of reperfusion. RESULTS: Cardioplegia was delivered during 17% of the cross-clamp time. Global left ventricular function, evaluated by preload recruitable stroke work (PRSW), was unchanged after continuous cardioplegia; 95 (76-130) (median (quartile interval)) to 91 (90-104) erg/ml x 10(3), but decreased after intermittent cardioplegia; 122 (100-128) to 64 (23-93) erg/ml x 10(3). Two pigs in the intermittent group weaned from CPB, but died before post-bypass measurement. A 95% confidence interval for the difference in post-bypass mean PRSW was estimated as 32 +/- 30 erg/ml x 10(3) (corresponding to P = 0.04 for comparison between treatments). The end-diastolic pressure-volume relation (EDPVR) increased from 0.17 (0.14-0.20) (continuous) and 0.15 (0.12-0.22) (intermittent) mmHg/ml to 0.27 (0.22-0.33) (P = 0.018) and 0.39 (0.25-0.66) (P = 0.005) mmHg/ml, respectively, indicating deterioration in diastolic function. No difference between groups was found in EDPVR, stiffness constant, troponin T release or myocardial water content. CONCLUSION: Following acute global ischaemia left ventricular global function was, in this model, less preserved using warm intermittent compared to warm continuous cardioplegia.     

Cardiac interleukin-6 release and myocardial recovery after aortic crossclamping. Crystalloid versus blood cardioplegia

BACKGROUND: Pro-inflammatory cytokines may play an important role in patient response to cardiopulmonary bypass (CPB). Since the myocardium is proposed to be a major source of cytokines, we studied the influence of the cardiolpegia type on interleukin-6 release and early myocardial recovery. METHODS: Experimental design: prospective, randomized study. Setting: university hospital, operative and intensive care. Patients: 20 consecutive patients (3 females) scheduled for elective coronary artery bypass grafting (CABG), mean age 62.8+/-5 years, history of myocardial infarction 11/20, left ventricular ejection fraction 62.9+/-15%. Interventions: patients were operated on using randomly either cold blood cardioplegia (B, n = 10) or cold crystalloid cardioplegia (C, n = 10). Measures: plasma levels of interleukin-6 (IL-6) were measured prior to CPB, after aortic declamping, after CPB, 1 hour, 6 hours and 12 hours postoperatively. RESULTS: Groups were comparable with respect to demographic data, left ventricular function, number of grafts, CPB and aortic crossclamp time. Group B patients demonstrated significant lower IL-6 levels after 1 hour (210+/-108 vs. 578+/-443 pg/ml), 6 hours (204+/-91 vs. 1210+/-671 pg/ml) and 12 hours (174+/-97 vs. 971+/-623 pg/ml). Post-CPB cardiac index was superior in group B (3.9+/-0.3 vs. 3.2+/-0.3 l/min/m2, p<0.05) with similar doses of inotropes. Group B patients could earlier be weaned off respirator (10+/-4 vs. 13+/-4 hours, p<0.05) and showed minor blood loss (635+/-211 vs. 918+/-347 ml, p<0.05). CONCLUSIONS: Inflammatory response to CPB is associated with delayed myocardial recovery. The use of blood cardioplegia may attenuate inflammatory reactions.     

Superior myocardial protection with nicorandil cardioplegia.

OBJECTIVE: The ATP-sensitive potassium channel (K(ATP)) activator nicorandil used as cardioplegic agent may protect the left ventricle during cardiac arrest. Nicorandil in cold blood was compared with standard hyperkalemic blood and crystalloid cardioplegia. METHODS: Twenty-one pigs were randomly assigned to three groups: (1) cold hyperkalemic crystalloid (n=7); (2) cold hyperkalemic blood (n=7); and (3) nicorandil as cardioplegia in cold blood (n=7). Left ventricular mechanical performance, pressure-volume area (PVA) and myocardial oxygen consumption (MVO(2)) were measured before and at 1 and at 2 h after 60 min of cold global ischemia on cardiopulmonary bypass using intraventricular pressure-volume conductance catheters, coronary flow probes and O(2)-content difference. RESULTS: The slope (M(w)) of the stroke work end-diastolic volume relationship, the preload recriutable stroke work relationship, was unchanged after ischemia in the nicorandil group, but was reduced to averaged 62.5% (standard deviation 14) of baseline values in both hyperkalemic perfusions (P<0.05). The slope of the MVO(2)-PVA relationship was unchanged after nicorandil cardioplegia while the slope after hyperkalemic blood and crystalloid cardioplegia increased with 33% (P<0.02) and 52% (P<0.02) of baseline values, respectively. CONCLUSIONS: Nicorandil as sole cardioplegic agent in cold blood given intermittently preserves left ventricular contractility and myocardial energetics significantly better than traditional forms of cardioplegia after cardiac arrest.     

Myocardial protection with high-dose beta-blockade in acute myocardial ischemia.

OBJECTIVE: The risk of postoperative cardiac dysfunction is markedly increased by emergency coronary artery bypass grafting in the presence of acute myocardial ischemia. High dose beta-blockade during continuous coronary perfusion has been suggested as an alternative to conventional cardioplegia and this technique has been applied successfully in high risk patients for coronary artery bypass grafting (CABG) surgery. This study compared high dose beta-blockade with esmolol to continuous warm blood cardioplegia in a clinically oriented model of acute left ventricular (LV) ischemia and reperfusion. METHODS: Twelve dogs were subjected to 60 min of regional LV ischemia by left anterior descending branch (LAD) ligation. Cardiopulmonary bypass (CPB) and aortic crossclamp were applied after 45 min of ischemia. Thereafter, high dose beta-blockade during continuous coronary perfusion (ESMO, n = 6) or antegrade continuous warm blood cardioplegia (WBC, n = 6) were maintained for 60 min. Myocardial water content (measured from endomyocardial biopsies using a microgravimetric technique), global LV function (preload recruitable stroke work: PRSW), and regional LV function (echocardiographic wall motion score) were determined at baseline and after weaning from CPB. RESULTS: During aortic crossclamp interstitial edema formation was significantly higher in the WBC group with an average water gain of 2.2 +/- 0.49 vs. 0.76 +/- 0.12% in the ESMO group. Thereafter, edema resolved in both groups, but myocardial water gain remained significantly higher in the WBC group at 60 and 120 min post CPB (0.98 +/- 0.19 and 1.13 +/- 0.32% vs. 0.07 +/- 0.25 and 0.04 +/- 0.08%). Global LV function was significantly higher in the ESMO group at 60 and 120 min post CPB (PRSW 103 +/- 6 and 94.7 +/- 4.6% of baseline vs. 85.3 +/- 4.9 and 74.7 +/- 7.6% of baseline). However, regional LV function showed no significant difference between groups. CONCLUSIONS: High-dose beta-blockade during continuous coronary perfusion may allow the surgeon to utilize the advantages of warm heart surgery, while avoiding the interstitial edema formation and temporary cardiac dysfunction associated with continuous warm blood cardioplegia. In high risk patients such as patients with unstable angina or after failed PTCA, high-dose beta-blockade may be an applicable alternative to cardioplegic arrest.     

Safety of prolonged aortic clamping with blood cardioplegia. I. Glutamate enrichment in normal hearts

This study compares the protection provided by prolonged (4 hours) aortic clamping with glutamate-enriched potassium blood cardioplegia (n = 8) to (1) prolonged (4 hours) aortic clamping with multidose potassium blood cardioplegia without glutamate (n = 4), (2) 4 hours of continuous perfusion of the beating empty heart (n = 7), and (3) 15 minutes of normothermic ischemia (n = 10). According to measurements of myocardial oxygen uptake, left ventricular compliance, left ventricular contractility, and stroke work performance, no statistical difference could be detected between those hearts receiving blood cardioplegia either with or without glutamate enrichment. In both of these groups, myocardial protection was excellent, as demonstrated by the following: postischemic myocardial oxygen uptake 43% (p less than 0.05) above control, 95% +/- 6% recovery of the left ventricular compliance, a 97% +/- 5% return of the left ventricular contractility, and a 91% +/- 6% recovery of stroke work index. Contrary to the excellent recovery of those hearts receiving blood cardioplegic protection, those hearts undergoing 4 hours of continuous perfusion showed a 45% +/- 16% (p less than 0.05) loss of left ventricular compliance and a 72% +/- 8% (p less than 0.05) recovery of stroke work index; those hearts experiencing 15 minutes of normothermic ischemia showed a 74% +/- 6% (p less than 0.05) return of left ventricular compliance, a 30% +/- 5% (p less than 0.05) decrease in contractility, and a 56% +/- 5% (p less than 0.05) recovery of postischemic left ventricular stroke work.     

Electroplegia: an alternative to blood cardioplegia for arresting the heart during conventional (on-pump) cardiac operation

BACKGROUND: Aortic cross-clamping is contraindicated in patients with severe atherosclerosis of the ascending aorta, and administration of chemical cardioplegia may be cumbersome in these patients. In this study, we demonstrate an alternative method of achieving cardioplegia by electrical stimulation of the vagus nerve. METHODS: In anesthetized canines, the left anterior descending coronary artery was reversibly ligated for 90 minutes, followed by cardiopulmonary bypass (CPB) and randomization to three groups (n = 8 each): (1) BCP group: 1 hour of intermittent hypothermic (4 degrees C) blood cardioplegia infusion; (2) CPB group: 1 hour of CPB alone; (3) EP group (group receiving electroplegia): 1 hour of intermittent vagal stimulation (total of 60 20-second electrical stimuli at 40 Hz, 6 to 10 V) with adjunctive pyridostigmine (0.5 mg/kg), verapamil (50 microg/kg), and propranolol (80 microg/kg) to potentiate hyperpolarization and suppress ectopic escape beats. RESULTS: The EP group achieved consistent intervals of arrest with 3.8 +/- 1.2 escape beats per 20-second stimulation period. After 2 hours of reperfusion off CPB, the left anterior descending coronary artery segmental shortening was reduced from baseline in all groups, but the segmental shortening recovered to a greater extent in the EP group than in either the CPB or BCP group (2.4% +/- 1.4% versus -1.3% +/- 1.3% versus -4.0% +/- 0.8%, p < 0.05). Infarct size (TTC stain, percentage of area at risk) was comparable among groups (EP: 20.9% +/- 4.7%; CPB: 29.6% +/- 3.2%; BCP: 25.1% +/- 5.7%). Postischemic left anterior descending coronary artery endothelial function (percent maximum relaxation to acetylcholine) was depressed in the EP group (68.6% +/- 7.6% versus 102.3% +/- 6.4%, p < 0.05), but was comparable versus nonischemic circumflex function in the BCP group (77.1% +/- 11.9% versus 100.4% +/- 10.0%, p = 0.15) and the CPB group (93.8% +/- 6.6% versus 93.3% +/- 6.6%). CONCLUSIONS: Electroplegia achieves elective intermittent cardiac arrest, avoids hypothermia, chemical cardioplegia, and aortic cross-clamping, with physiological outcomes comparable to blood cardioplegia.     

Cold continuous antegrade blood cardioplegia: high versus low hematocrit.

OBJECTIVE: Cold continuous antegrade blood cardioplegia (CCABCP) is used with different hematocrit values. We investigated the consequences of CCABCP with low hematocrit (LH: 20-25%) versus high hematocrit (HH: 40-45%). METHODS: Anesthetized open chest pigs (25 kg) were placed on cardiopulmonary bypass (CPB). The hearts were arrested for 30 min by 6 degrees C CCABCP with either LH or HH (n=8, each): After an initial 3 min application of high potassium (20 mEq) BCP the hearts were arrested for subsequent 27 min by normokalemic 6 degrees C cold blood delivered continuously antegradely. Thereafter the hearts underwent perfusion with warm systemic blood for an additional 30 min on CPB. Biochemical cardiac data (MVO(2) (ml min(-1)100 g(-1)), release of creatine kinase (CK; units min(-1)100 g(-1))) and lactate (mg min(-1)100 g(-1))) and the coronary vascular resistance index (CVRI (mmHg ml(-1)ming)) were measured during CPB. Total tissue water content (%) and left and right ventricular stroke work indices (LV-and RV-SWI (g m kg(-1))) were assessed 30 min after discontinuation of CPB and compared to pre-CPB controls. RESULTS: The hearts of the LH group had no biochemical or functional disturbance. The HH group showed marked CK leakage (0.6+/-0.2* vs. 0.1+/-0.1, *P<0.05 for comparison of LH vs. HH with Student's t-test for unpaired data), impaired initial oxygen consumption (4+/-1* vs. 7+/-1) after cardiac arrest, an increased CVRI (82+/-12* vs. 50+/-8), the formation of myocardial edema (81.0+/-1.3* vs. 77.5+/-1.2), and poor functional recovery (LVSWI 0.2+/-0.1* vs. 1.0+/-0.1; RVSWI 0.1+/-0.1* vs. 0.5+/-0.1). The absence of lactate production in both groups was in accord with the non-ischemic protocol. CONCLUSIONS: CCABCP with a low hematocrit of 20-25% is cardioprotective. In contrast, CCABCP with a high hematocrit of 40-45% jeopardizes the heart despite avoiding ischemic periods, and should be avoided.     

Whole blood cardioplegia (minicardioplegia) reduces myocardial edema after ischemic injury and cardiopulmonary bypass

While blood:crystalloid cardioplegia is the clinical standard for patients undergoing cardiopulmonary bypass (CPB), it has been postulated that whole blood minicardioplegia may benefit the severely injured heart by reducing cardioplegic volume, thereby reducing myocardial edema. To test this hypothesis, we compared the cardioprotection of a popular 4:1 blood:crystalloid cardioplegia to whole blood minicardioplegia (WB) in a porcine model of acute myocardial ischemia. Yorkshire pigs (n = 20) were placed on atriofemoral bypass and subjected to 30 minutes of global normothermic ischemia. Animals were randomized to receive either 4:1 cold cardioplegia (n = 10) or WB cold cardioplegia (n = 10) delivered antegrade continuously for 90 minutes. Baseline (BL) echocardiographic determination of left ventricular mass (LVM) was compared within groups for cardiac edema (%) measured by histologic morphometrics. All (100%) animals receiving WB were successfully weaned off CPB, whereas only 40% of animals receiving 4:1 were successfully weaned off CPB. Cardiac edema percentage (p < .004) and LVM (p < .05) were significantly decreased in the WB group compared with 4:1. WB cardioplegia increases the number of hearts successfully weaned from CPB and decreases cardiac edema in our porcine model of acute myocardial ischemia. This finding implies whole blood cardioplegia may be more protective in a select group of patients undergoing extended CPB time by decreasing myocardial edema.     

Myocardial recovery: Perfusion of the fibrillating heart versus cold chemical cardioplegia

Recovery of left ventricular function (LVF) in the immediate post bypass period was studied in 14 patients undergoing coronary revascularization. In 5 patients recovery after normothermic perfusion of the fibrillating heart was studied and compared to recovery in 9 patients following the use of cold chemical cardioplegia. Ventricular function was evaluated by stepwise volume loading just prior to, and at 5 and 20 min after, cardiopulmonary bypass (CPB). In the perfused fibrillating group there was a 50% increase in left ventricular end diastolic pressure (LVEDP) and an 18% decrease in left ventricular stroke work index (LVSWI) 5 min after CPB compared to 25 and 16% in the cardioplegia group. Twenty minutes after CPB, the LVF of the cardioplegia group had returned to prebypass levels while the fibrillating group showed an additional 5% increase in LVEDP and a 5% decrease in LVSWI. Changes in contractility and relaxation indices paralleled the changes in ventricular function curves. We conclude that recovery of LVF was not perfect with either technique. Volume loading was not well tolerated by either group 5 min after CPB; however, the cardioplegia group demonstrated good recovery of function 20 min after CPB.     

Left ventricular function and chronotropic responses after normothermic cardiopulmonary bypass with intermittent antegrade warm blood cardioplegia in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Recent studies indicate that normothermic cardiopulmonary bypass (CPB) with intermittent antegrade warm blood cardioplegia (IAWBC) may have metabolic and clinical advantages, but limited data exist on its effects on myocardial function. Therefore, we investigated the acute effects of this approach on systolic and diastolic left ventricular function and on chronotropic responses. METHODS: In 10 patients undergoing isolated CABG we obtained on-line left ventricular pressure-volume loops using the conductance catheter before and after normothermic CPB with IAWBC. Steady state and load-independent indices of left ventricular function derived from pressure-volume relations were obtained during right atrial pacing (80-100-120 beats/min) to determine baseline systolic and diastolic function and chronotropic responses. RESULTS: The mean time of CPB was 105+/-36 min (median 103, range 60-167 min) with a mean aortic cross-clamp time of 75+/-27 min (median 69, range 43-129 min). Baseline (80 beats/min) end-systolic elastance (E(ES)) did not change after CPB (1.22+/-0.53 to 1.12+/-0.28 mm Hg/ml, P>0.2), while the diastolic chamber stiffness constant (k(ED)) significantly increased (0.014+/-0.005 to 0.040+/-0.007 ml-1, P=0.018) and relaxation time constant (tau) significantly decreased (61+/-3 to 49+/-2 ms, P=0.004). Before CPB, incremental atrial pacing had no significant effects on E(ES) and tau but significant negative effects on kED (0.014+/-0.005 to 0.045+/-0.012 ml-1, P=0.013). After CPB, atrial pacing had significant positive effects on E(ES), tau and kED (E(ES): 1.12+/-0.28 to 2.60+/-1.54 mm Hg/ml, P=0.021; tau: 49+/-2 to 45+/-2 ms, P=0.009; kED: 0.040+/-0.007 to 0.026+/-0.005 mm Hg, P=0.010), indicating improved systolic and diastolic chronotropic responses. CONCLUSION: On-pump normothermic CABG with IAWBC preserved systolic function, increased diastolic stiffness, and improved systolic and diastolic chronotropic responses. Normalization of the chronotropic responses post-CPB is likely due to effects of successful revascularization and subsequent relief of ischemia.     

冷温血停搏液联合灌注对瓣膜置换术中炎性细胞因子和自由基的影响

目的　评价冷温血停搏液联合灌注在瓣膜置换术中对血浆促炎性细胞因子和自由基代谢水平的影响 ,探讨更有效的心肌保护方法。方法　将 30例瓣膜病病人随机分为两组 :温血组 (A组 ,n =15 ) ,采用温血诱导心脏停搏、冷血维持与终末温血灌注心肌保护方法 ;冷血组 (B组 ,n =15 ) ,采用冷氧合血停搏液进行心肌保护。分别于心肺转流 (CPB)前 (T1)、CPB 30min(T2 )、CPB结束后30min(T3 )、4h(T4)、2 4h(T5)测定血浆白细胞介素 6 (IL 6 )、IL 8和MDA浓度及SOD活性。结果B组IL 6于T2 即升高 ,持续至T5;A组无明显变化 ,于T3 明显低于B组 (P <0 0 5 )。B组IL 8于T2升高 (P <0 0 1) ,至T3 达峰值 (P <0 0 1) ,于T5下降至基础值水平 ;A组在T3 ～T4较基础值明显升高 (P <0 0 5 ) ,于T2 ～T4均显著低于B组 (P <0 0 5 )。两组MDA均在T2 升高 ,持续至T4,但A组于T3 、T4显著低于B组 (P <0 0 5 )。B组SOD活性自T2 开始降低 ,持续至T4(P <0 0 1) ;A组无明显变化 ,且在T3 与B组比较有显著性差异 (P <0 0 5 )。结论　冷温血停搏液联合灌注对瓣膜病病人的心肌再灌注损伤的抑制效应优于冷血心脏停搏液。     

Warm retrograde blood cardioplegia saves more ischemic myocardium but may cause a functional impairment compared to cold crystalloid.

OBJECTIVES: Ongoing ischemia, or even ischemia in progress, is regularly encountered in today's patients amenable to cardiac surgery. We set out to assess the effect of 'active resuscitation' during cardioplegia with warm continuous retrograde blood cardioplegia (WB) in a protocol simulating a clinical situation. METHODS: After 60 min with a regional ischemic injury to the left ventricle, 21 pigs were randomized to receive no treatment (control), cold retrograde intermittent crystalloid cardioplegia (CC) or WB. All animals were put on cardiopulmonary bypass. After 1h of cardioplegia and 1 h of reperfusion the perfused left ventricle was colored with methylene blue. After excision of the hearts a standard planimetri technique was used to determine the area at risk and amount of necrosis (triphenyltetrazolium). Heart rate, mean arterial pressure (MAP), cardiac output and myocardial blood flow were recorded as well as myocardial oxygen consumption, plasma levels of free fatty acids, glucose, lactate and Troponin T from the coronary sinus. RESULTS: The area at risk of the left ventricle was 13.6+/-1.2%. We found 71+/-2, 61+/-3 and 30+/-2% necrosis of the area at risk in the controls, CC and WB, respectively (P<0.001, CC versus control and P<0.0001, WB against CC and control). Troponin T release was highest in the CC group in the reperfusion period. Glucose levels increased significantly after ischemia in the controls and WB. In accordance with the amount of saved myocardium in the WB group which also had a normal coronary sinus lactate level as opposed to the fourfold increase in the CC group after ischemia. After standstill cardiac output and MAP were significantly lower than baseline values in the WB group only (P<0.05). CONCLUSIONS: CC did reduce the size of the infarction by about 10% compared to control animals, whereas WB reduced the infarction by more than 50% of that seen after CC. Both modalities are, however, associated with a functional reduction during the first 60 min of reperfusion, WB being the worst.     

Polarized arrest with warm or cold adenosine/lidocaine blood cardioplegia is equivalent to hypothermic potassium blood cardioplegia

BACKGROUND: Hypothermic depolarizing hyperkalemic (K + 20 mEq/L) blood cardioplegia is the "gold standard" in cardiac surgery. K + has been associated with deleterious consequences, eg, intracellular calcium overload. This study tested the hypothesis that elective arrest in a polarized state with adenosine (400 micromol/L via adenosine triphosphate-sensitive potassium channel opening) and the Na + channel blocker lidocaine (750 micromol/L) as the arresting agents in blood cardioplegia provides cardioprotection comparable to standard hypothermic K + -blood cardioplegia. METHODS: Anesthetized dogs were placed on cardiopulmonary bypass and assigned to 1 of 3 groups receiving antegrade cardioplegia delivered every 20 minutes for 1 hour of arrest: cold (10 degrees C) K + -blood cardioplegia (n = 6), cold (10 degrees C) adenosine/lidocaine blood cardioplegia (n = 6), or warm (37 degrees C) adenosine/lidocaine blood cardioplegia (n = 6). After an hour of arrest, cardiopulmonary bypass was discontinued, and reperfusion was continued for 120 minutes. RESULTS: Time to arrest was longer with cold and warm adenosine/lidocaine blood cardioplegia (175 +/- 19 seconds and 143 +/- 19 seconds, respectively) compared with K + -blood cardioplegia (27 +/- 2 seconds; P < .001). Postcardioplegia left ventricular systolic function (slope of the end-systolic pressure/dimension relationship) was comparable among the 3 groups (K + -blood cardioplegia, 15.2 +/- 2.1 mm Hg/mm; cold adenosine/lidocaine blood cardioplegia, 15.9 +/- 3.4 mm Hg/mm; warm adenosine/lidocaine blood cardioplegia, 14.1 +/- 2.8 mm Hg/mm; P = .90). Plasma creatine kinase activity in cold and warm adenosine/lidocaine blood cardioplegia was similar to that in K + -blood cardioplegia at 120 minutes of reperfusion (cold adenosine/lidocaine blood cardioplegia, 11.5 +/- 2.1 IU/g protein; warm adenosine/lidocaine blood cardioplegia, 10.1 +/- 0.9 IU/g protein; K + -blood cardioplegia, 7.6 +/- 0.8 IU/g protein; P = .17). Postcardioplegia coronary artery endothelial function was preserved in all groups. CONCLUSIONS: Intermittent polarized arrest with warm or cold adenosine/lidocaine blood cardioplegia provided the same degree of myocardial protection as intermittent hypothermic K + -blood cardioplegia in normal hearts.     

Effects of cardiopulmonary bypass and cardioplegia on regional and global cardiac actions of halothane in dogs

Cardiopulmonary bypass (CPB) with aortic cross-clamping represents a controlled period of global cardiac ischemia. We hypothesized that CPB (asanguineous prime), with aortic cross-clamping and repeated cardioplegia, alters myocardial function, which would be manifested as an exaggerated myocardial depression caused by halothane after CPB. In nine dogs anesthetized with fentanyl and midazolam, halothane dose-response curves (0.0%-2.0%) were compared before and after CPB. A reduced mean arterial blood pressure (46.4 +/- 3.7 vs 85.8 +/- 5.9 mm Hg), associated with a marked hemodilution (hematocrit, 19% +/- 1% vs 41% +/- 2%), was observed after CPB. Cardiac output and systolic shortening were not significantly different after versus before CPB during fentanyl-midazolam anesthesia. Normalized to fentanyl-midazolam hemodynamics, halothane dose-response curves before and after CPB were identical for all variables except cardiac output, where halothane caused a slight but statistically significantly more pronounced decrease after CPB compared with before CPB. The effect of halothane on left ventricular function, therefore, is relatively unaffected by CPB with cardioplegia.     

Preventive effect of post-ischemic reperfusion injury by terminal Nicorandil-Mg cardioplegia

In this study, we evaluated the preventive effect of post-ischemic reperfusion injury by Nicorandil-Mg cardioplegia (Nic: 8 mg/l, Mg: 20 mEq/l) given just prior to reperfusion as "terminal cardioplegia". Nineteen dogs were placed on cardiopulmonary bypass and the aorta was cross-clamped for 90 min under hypothermic (17-19 degrees C) cardioplegic arrest. The hearts of ten dogs were reperfused without terminal cardioplegia (Group A). In the other nine dogs, terminal cardioplegia was given for 2 min prior to reperfusion (Group B). During and after a period of ischemia, myocardial tissue calcium ion (t-Ca) and PCO2 (t-PCO2) were continuously monitored by ISFET (ion sensitive filed effective transistor) sensor. Myocardial tissue blood flow, oxygen consumption and lactate flux were calculated at 5, 10, 20, 40 min of reperfusion. And myocardial function was evaluated at 45 min of reperfusion. In the initial reperfusion period, Group B showed an improved myocardial tissue blood flow compared to group A (at 5 min of reperfusion in group A: 29.4% of control, in group B: 42.7% of control, p less than 0.025). T-Ca and T-PCO2 in Group B were rapidly and significantly decreased at 5 min of reperfusion (t-Ca in group A: 2.8 +/- 0.5 mM----1.7 +/- 0.5 mM, in group B: 3.1 +/- 0.6----1.2 +/- 0.4, p less than 0.05; t-PCO2 in group A: 117.5 +/- 23.0 mmHg----82.5 +/- 17.4 mmHg, in group B: 127.5 +/- 22.5----42.5 +/- 9.7, p less than 0.001), and group B had better metablic recovery evaluated by myocardial oxygen consumption and lactate flux.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Orthotopic transplantation of pig hearts harvested after 30 min of normothermic ischemia: controlled reperfusion with blood cardioplegia containing the Na-H-exchange inhibitor HOE 642

Objectives: The aim of our study was to develop a surgical technique for a successful transplantation of hearts harvested after 30 min of normothermic ischemia without donor pretreatment. Successful transplantation of ischemic compromised hearts could help to expand the severely limited donor pool. We used the pig model because this species is very susceptible to myocardial ischemia. Na⁺-H⁺-exchange (NHE) inhibitors have shown excellent protective properties in several in vitro and in vivo models of myocardial ischemia and reperfusion. Methods: In group I (n=12) hearts were harvested after 30 min of normothermic ischemia following cardiac arrest induced by exsanguination. Hearts were perfused with warm blood cardioplegia and transplanted orthotopically. In group II (n=9) controlled reperfusion with cold leucocyte-depleted blood cardioplegia was performed after 30 min of normothermic ischemia. In group III (n=8) the same procedure was performed as in group II but blood cardioplegia contained 1 mmol/l HOE 642. Results: In group I massive myocardial oedema was observed and none of the animals could be weaned from cardiopulmonary bypass (CPB). In contrast, all animals in groups II and III could be weaned from CPB with low dose inotropic support. In groups II and III the contractility of the hearts, expressed as maximal left and right ventricular stroke work index was significantly impaired after transplantation as compared with the preoperative value. Supplementation of blood cardioplegia with HOE 642 resulted in a significantly better recovery of the LVSWImax (Group II vs. III). Conclusions: Successful transplantation of pig hearts is possible after 30 min of normothermic ischemia without donor pretreatment if a controlled reperfusion with cold leucocyte-depleted blood cardioplegia is performed. HOE 642 given during reperfusion only improves posttransplant left ventricular function.     

Continuous cold blood cardioplegia improves myocardial protection: a prospective randomized study

BACKGROUND: To assess the influence on myocardial protection of the rate of infusion (continuous vs intermittent) of cold blood cardioplegia administered retrogradely during prolonged aortic cross-clamping. The end-points were ventricular performance and biochemical markers of ischemia. METHODS: Seventy patients undergoing myocardial revascularization for three-vessel disease were prospectively randomized to receive intermittent or continuous retrograde cold blood cardioplegia. Hemodynamic measurements were obtained using a rapid-response thermodilution catheter and included right ventricular ejection fraction, cardiac output, left and right ventricular stroke work index, and systemic and pulmonary vascular resistance. Blood samples were obtained from the coronary sinus before cross-clamp application and immediately after cross-clamp removal for determinations of lactate and hypoxanthine. RESULTS: The left ventricular stroke work index trend was significantly superior (p = 0.038) by repeated-measures analysis in continuous cardioplegia. Other hemodynamic measurements revealed a similar trend. The need for postoperative inotropic drugs support was reduced in continuous cardioplegia. The release of lactate in the coronary sinus after unclamping was 2.30 +/- 0.12 mmol/L after intermittent cardioplegia and 1.97 +/- 0.09 mmol/L after continuous cardioplegia (p = 0.036). The release of hypoxanthine was 20.47 +/- 2.74 micromol/L in intermittent cardioplegia and 11.77 +/- 0.69 micromol/L in continuous cardioplegia (p = 0.002). CONCLUSIONS: Continuous cold blood cardioplegia results in improved ventricular performance and reduced myocardial ischemia in comparison with intermittent administration.     

Myocardial preservation using lidocaine blood cardioplegia

Prevention of ventricular fibrillation after aortic unclamping using lidocaine hydrochloride as an additive to cold potassium blood cardioplegia was studied prospectively in 46 patients undergoing elective myocardial revascularization. Patients were similar with respect to age, ventricular function, severity of coronary artery disease, cross-clamp time, completeness of revascularization, frequency of internal thoracic artery grafting, systemic temperature at the time of cross-clamp removal, and mean infusate volume and temperature. Patients receiving lidocaine blood cardioplegia (group 1, 23 patients) had a significant reduction in the incidence of ventricular fibrillation (22% versus 74%; p less than 0.0005) and in the mean number of cardioversion attempts required to defibrillate the heart (0.5 +/- 1.3 versus 1.9 +/- 0.97; p less than 0.0005) after cross-clamp removal compared with controls (group 2, 23 patients). There were no differences between the two groups postoperatively with regard to cardiac enzyme release, hemodynamic measurements, or clinical outcome. Patients receiving lidocaine blood cardioplegia tended to have a lower incidence of new postoperative atrial fibrillation (9% versus 26%). Ventricular function was preserved equally in both groups. We conclude that lidocaine is a safe additive to potassium blood cardioplegia and significantly reduces the incidence of ventricular fibrillation after aortic unclamping.     

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.