Myocardial protection and cardioplegia

Over the past year there has been a tremendous enthusiasm for the novel technique of warm heart surgery. In contradistinction to hypothermic myocardial preservation, warm cardiac surgery provides for operative repair in a nonischemic heart. Warm cardioplegia can be administered in an antegrade or retrograde manner, continuously, and perhaps even intermittently. It may have beneficial effects on systemic perfusion and may be a useful adjunct in the setting of acute cardiac ischemia. There likewise has been a burgeoning enthusiasm for the retrograde cardioplegic delivery route. Many reviews of clinical work using both warm and cold retrograde cardioplegia have identified the advantage of this technique, particularly in the setting of valve replacement and reoperation for coronary revascularization. Finally, new avenues of investigation in ischemia and reperfusion including inquiry into the role of neutrophils in reperfusion injury and modification of the reduced thiol pool to modulate the postischemic burst of oxygen-free radical production.     

改良式温血停搏液在心脏瓣膜置换术中心肌保护作用的研究

为探讨改良式温血停搏液（WBC）持续灌注在心脏瓣膜置换术中的心肌保护作用。随机将103例患者分为两组，观察组（43例）术中采用WBC、对照组（60例）应用冷晶体停搏液（CCC）行心肌保护，结果观察组血清心肌肌钙蛋白T（cTnT）水平明显低于对照组，随缺血时间延长差别更加明显：心脏自动复跳率明显高于对照组（P＜0．01），观察组无死亡，对照组围术期死亡2例，均为低心排。术后观察组多巴胺用量明显低于对照组（P＜0．01），补钾量明显减少，认为心脏瓣膜置换术中WBC持续灌注较CCC间断灌注具更好的心肌保护作用。     

Myocardial protection: the rebirth of potassium-based cardioplegia

The introduction of open-heart surgery more than 4 decades ago signaled a new era in medicine. For the 1st time, previously untreatable cardiac anomalies became amenable to surgical therapy. The use of the heart-lung machine seemed to grant the surgeon unlimited time in which to operate inside the heart. Still frustrated by poor operating conditions and the threat of air embolism, Denis Melrose introduced elective cardiac arrest in 1955. His use of a potassium citrate solution seemed to offer a safe method to effect a quiet, bloodless field. However, a few years after its inception, numerous reports began to question the safety of this approach, and the Melrose technique was abandoned in the early 1960s. Nearly 15 years elapsed before potassium-based cardioplegia regained popularity. During this period, topical hypothermia, coronary perfusion with intermittent aortic occlusion, and normothermic ischemia were evaluated and discarded. A few European investigators like Hoelscher, Bretschneider, and Kirsch had maintained their interest in chemical cardioplegia, and it was through their efforts that future researchers like Hearse and Gay spearheaded the return to potassium-based cardioplegia, which today forms the core of the cardiac surgeon's myocardial protective armamentarium and has contributed towards lowering operative mortality rates.     

改良式氧合血停搏液对未成熟心肌的保护作用

目的:证实氧合血停搏液对未成熟心肌的保护作用。方法:以18例婴幼儿复杂先心病患者为对象.分为晶体组和氧合血停搏液组,观察转流中及术后各项指标,并进行比较。结果:两组患者术前情况都比较接近,转流时间,阻断时间、复跳情况,术后并发症均未见明显差异,但晶体组预充总量大,停跳液晶体回收量大,转中多应用超滤.利尿剂等,血球压积变化较大和库血用量多(P均<0.05)。结论:氧合血停搏液可为婴幼儿提供良好的心肌保护条件。     

自体冷血停跳液对未成熟心肌保护机制的研究

目的:研究婴幼儿心内直视手术灌注不同停跳液心肌细胞丙二醛(MDA)和超氧化物歧化酶(SOD)的变化,探讨自体冷血停跳液对婴幼儿心肌保护的作用机制.方法:婴幼儿(体重≤8 Kg)非发绀先天性心脏病30例,随机分为自体冷血(A组)、冷血(B组)和晶体(C组)停跳液组,每组10例.分别于心脏停跳前、复跳后取右心耳心肌,检测心肌MDA和SOD含量.结果:3组术后心肌细胞MDA明显升高,SOD明显降低,与术前比较差异有统计学意义(P＜0.05);其中A组MDA较低,SOD较高,与B、C组比较差异有统计学意义(P＜0.05).结论:自体冷血停跳液通过降低心肌细胞氧自由基的产生对婴幼儿心内直视手术心肌具有保护作用.     

心脏瓣膜手术中冷氧合血与冷晶体停跳液保护心肌作用的比较(附20例报告)

将20例行心脏瓣膜置换术的患者随机分为两组，分别在体外循环期间采用冷氧合血停跳液及冷晶体停跳液。通过监测围术期，术后24h的血流动力学变化，心脏自动复跳率及复跳时间，开放主动脉后6h心肌肌钙蛋白T（cTnT)的变化，术后标准Ⅱ导联心电图变化和临床强心药物使用及患者在危重监测病房（ICU）停留时间等，对比观察两组的心肌保护效果。结果：冷氧合血停跳液组（氧合血组）的心脏自动复跳率及自动复跳时间优于冷晶体停跳液组（冷晶体组）；开放主动脉后6h cTnT含量少于冷晶体组，两组术中及术后24h内血流动力学变化无差异。认为冷氧合血停跳液的心肌保护效果优于冷晶体停跳液。     

Myocardial protection during coronary surgery. Getting the maximum advantage of both cardioplegia and hypothermia

The author presents a specially timed protocol of a combination of cold cardioplegic arrest and deep total body hypothermia designed to include the best features and to eliminate some of the principal short-comings of these 2 commonly used methods of myocardial preservation. According to this protocol, the operations were divided into 3 periods: (1) About half the number of the peripheral anastomoses are done in the first period while the body is cooled to 20 degrees C and the during which the heart is in cold ischemic cardioplegic arrest. (2) Most or all proximal anastomoses are done in the second period during which body temperature is kept at 20 degrees C and the heart is in a per vias naturales perfused cold arrest. (3) During the third period, the remaining anastomoses are completed while the heart is again in cold ischemic cardioplegic arrest and the body is rewarmed. This method was used in excess of 100 myocardial revascularization procedures with satisfactory clinical results.     

20℃低温稀释血停搏液心肌保护效果的实验研究

目的：研究20℃低温稀释血停搏液（20℃HBC）灌注结合体循环自然降温在心脏直视手术中的心肌保护效果。方法：将14条15－20kg成年杂种犬随机分成对照组和实验组（n=7)，雌雄不拘，实验组采用间断20℃HBC灌注，体温自然降至32－35摄氏度，对照组采用体循环主动降温：间断8－10摄氏度稀释血停搏液（CBC）灌注。于主动脉阻断前、后抽取右房血测乳酸脱氢酶（LDH），肌酸激酶同工酶（CK－MB）、肌钙蛋白I（cTn-I)，取左心室心内膜下心肌观察超微结构变化，于主动脉阻断前、后监测心功能。结果：两组停搏液灌注后LDH，CK－MB,cTn-I均升高，实验组变化幅度小（P＜0．05）；实验组与对照组相比，灌注液对心功能影响较小，心肌超微结构损伤性变化不明显。结论：在体外循环过程中，与CBC相比，在心肌酶，cTn-I、心肌超微结构方面20℃HBC灌注对心肌有较好的保护作用。     

晶体心脏停搏液优于血液心脏停搏液对风湿性心脏病患者的心肌保护

目的比较血液心脏停搏液和晶体停搏液对风湿性心脏病患者心肌保护的效果,为临床选择提供依据。方法将75例择期手术的风湿性心脏病患者分为两组:血液心脏停搏液组(B-rh)和晶体心脏停搏液组(C-rh)。分别于术前1d,术后1,3,5,8d晨分别取静脉血,测定血清天门冬氨酸氨基转氨酶(AST),肌酸激酶(CK)及同工酶MB(CK-MB),乳酸脱氢酶(LDH)及同工酶1(LDH-1)。结果术前除B-rh的LDH略高于正常水平外其它心肌酶的测定结果均在正常范围;术后1d两组的心肌酶分别升高到术前的3~19倍(P<0.05);术后3d两组的CK-MB虽说已恢复到正常值,但五种心肌酶仍明显高于术前水平(P<0.05);术后5dC-rh的CK和CK-MB,B-rh的CK,CK-MB和AST与术前相比已无明显差别(P>0.05);术后8d两组的LDH与LDH-1仍未恢复正常(P<0.05)。两组间有显著差异的心肌酶释放均是B-rh的高。心肌酶的释放量与主动脉阻断时间(CCT)和体外循环时间(ECCT)呈良好的正相关。两组患者的年龄,体重和ECCT无明显差异(P>0.05),CCT以B-rh为短[(77.2±34.6)min比(61.7±26.7)min,P<0.05]。结论从心肌酶的释放来判断,晶体心脏停搏液优于血液心脏停搏液对风湿性心脏病患者的心肌保护效果。     

Coxsackie virus heart disease: 15 years after

From 1969 to 1973, 68 patients were admitted to the 4th Divisionof Medicine of the Brescia Civil Hospital with the diagnosisof viral myocarditis. The patients were divided into two groupsaccording to the results of the Coxsackie virus complement fixingantibodies test: Group 1 (42 patients) with a fourfold or greaterrising antibody titre: Group 2 (26 patients) with a negativeserum test. Both groups were examined after a follow-up period of 15 years.Ten patients from Group 1 died. The diagnoses were chronic myocarditis(three cases): chronic cardiomyopathy — pulmonary embolism(one case); chronic cardiomyopathy — liver cirrhosis (onecase); dialted cardiomyopathy—sudden death (two cases);congestive cardiomyopathy (three cases). No Group 2 patientsdied. The 15-year mortality rate of Group I was significantlyhigher than that of Group 2 (Fisher Test;p<0.005). In conclusion, the natural history of Coxsackie virus heartdisease is characterized by two possibilities: a complete recoveryfrom a clinical point of view, in some cases with only minorT wave abnormalities, or evolution into a chronic disease (dilatedcardiomyopathy) having a high mortality rate within 10 yearsof the onset of the acute disease.     

一体化综合性心肌保护对婴幼儿心肌超微结构的保护

目的：观察一体化综合性心肌保护方法对婴幼儿心肌超微结构的影响以评价其心肌保护效果。方法：30例复杂先天性心脏病患儿随机分成一体化综合性心肌保护组（综合组，含温血停搏液诱导停搏，冷血停搏液间歇灌注和终末温血灌注液复苏）、冷血停搏液间断灌注组（冷血组），及冷晶体停搏液间断灌注组（冷晶组），各10例。于心脏停跳即刻、缝合右心房切口前分别取小块右心房肌肉作光镜及电镜观察，并对线粒体、细胞核、肌纤维进行定量评估。结果：三组心肌均存在不同程度的损伤，冷晶组最重，综合组最轻。心肌超微结构评分在三组之间两两比较较有统计学意义（P〈0．01或P〈0．05）。结论：一体化综合性心肌保护作用优于冷血停搏液和冷晶体停搏液。     

Evidence that continuous normothermic blood cardioplegia offers better myocardial protection than intermittent hypothermic cardioplegia.

OBJECTIVES--To compare transmyocardial ischaemia and oxidative stress, as well as non-infarction myocardial injury, in patients randomised to intermittent hypothermic cardioplegia or continuous normothermic blood-potassium cardioplegia. DESIGN--Prospective randomised trial. SETTING--Tertiary cardiac referral centre. METHODS--24 patients undergoing elective coronary artery bypass surgery were randomised to hypothermic (13 patients, mean (SEM) age 59.5 (2.6) years) or normothermic (11 patients, mean (SEM) age 59.7 (3.3) years) cardioplegia. Transmyocardial oxidative stress and ischaemia were assessed by the difference in plasma concentrations of oxidised glutathione and lactate respectively, from samples taken simultaneously from the coronary sinus and aortic root. Blood samples were taken just before cross clamp application and at intervals up to 15 min after cross clamp release. Non-infarction myocardial injury was assessed by measurement of creatine kinase MB isoenzyme activity from peripheral venous blood taken 2 and 18 h after surgery. RESULTS--Intermittent hypothermic cardioplegia resulted in a significant increase in transmyocardial ischaemia (P < 0.001) and oxidative stress (P < 0.001). Evidence of significantly increased myocyte damage was also present (P < 0.01). No significant corresponding changes were present with normothermic cardioplegia. CONCLUSIONS--Normothermic blood cardioplegia seems to avoid significant changes in myocardial ischaemic status and consequent oxidative stress. This study provides direct evidence that normothermic cardioplegia offers enhanced myocardial protection compared with that of hypothermic cardioplegia. Certain subsets of patients may derive more benefit from normothermic cardioplegia, although it is unclear whether this would be the case for all patients.     

Fatal gastrointestinal histoplasmosis 15 years after orthotopic liver transplantation

We report a case of ileo-colonic Histoplasmosis without apparent respiratory involvement in a patient who had previously undergone an orthotopic liver transplant(OLT) for primary biliary cholangitis 15 years earlier. The recipient lived in the United Kingdom,a non-endemic region for Histoplasmosis. However,she had previously lived in rural southern Africa prior to her OLT. The patient presented with iron deficiency anaemia,diarrhoea,abdominal pain and progressive weight loss. She reported no previous foreign travel,however,it later became known that following her OLT she had been on holiday to rural southern Africa. On investigation,a mild granulomatous colitis primarily affecting the right colon was identified,that initially improved with mesalazine. Her symptoms worsened after 18 mo with progressive ulceration of her distal small bowel and right colon. Mycobacterial,Yersinia,cytomegalovirus and human immunodeficiency virus infections were excluded and the patient was treated with prednisolone for a working diagnosis of Crohn's disease. Despite some early symptom improvement following steroids,there was subsequent deterioration with the patient developing gram-negative sepsis and multi-organ failure,leading to her death. Post-mortem examination revealed that her ileo-colonic inflammation was caused by Histoplasmosis.     

Multiple metastases from renal carcinoma 15 years after nephrectomy

A 72-year-old man was admitted to our hospital complaining of an axillary mass. He underwent left total nephrectomy for renal cell carcinoma (RCC) 15 years previously (in 1990). Since further evaluation yielded no evidence of extra renal metastases, he was followed up in the outpatient clinic. On admission, there was a hard tumor in the right axilla. Ultrasonography demonstrated a vascular tumor with a smooth surface, 26 by 24mm. Laboratory findings were generally close to normal, including tumor markers. Chest contrast-enhanced dynamic CT showed that the tumor was enhanced. Furthermore, abdominal contrast-enhanced dynamic CT revealed some enhancing lesions within the right side of the rectus muscle of abdomen and pancreas head as well. Open simple axillary mass biopsy was performed on August 2 and the tumor was histologically confirmed as a metastasis of the RCC to the axillary. His overall status was normal, and he underwent an operation for the pancreas tumor and the tumor in the rectus muscle of the abdomen. On histological examination, both excised specimens were found to be metastases of RCC. During 2 years follow-up period in the outpatient clinic, additional metastasis has not been observed in any organ. Since this case confirms the potential of RCC for late and multiple distant metastases, careful long-term follow-up after radical nephrectomy is needed.     

Myocardial protection with preconditioning

Myocardial preconditioning with brief coronary artery occlusions before a sustained ischemic period is reported to reduce infarct size. To determine the number of occlusive episodes required to produce the preconditioning effect, we performed single or multiple occlusions of the left circumflex coronary artery (LCx) followed by a sustained occlusion (60 minutes) of the LCx. Anesthetized dogs underwent one (P1), six (P6), or 12 (P12) 5-minute occlusions of the LCx. Each occlusion period was followed by a 10-minute reperfusion period. A 60-minute occlusion of the LCx followed the preconditioning sequences. A control group received a 60-minute occlusion of the LCx without preconditioning. All groups were subjected to 6 hours of reperfusion after which the heart was removed for calculating infarct size (IS), area at risk (AR), and left ventricular mass (LV). The IS/AR ratio for the control group was 29.8 +/- 4.4% (n = 17), which was substantially greater (p less than 0.001) than that of the preconditioned groups: P1, 3.9 +/- 1.3% (n = 14); P6, 0.4 +/- 0.3% (n = 5); and P12, 2.9 +/- 2.8% (n = 5). There were no significant differences in the IS/AR ratio among the three preconditioned groups. The AR/LV ratio was comparable among all groups and did not differ statistically: control, 40.4 +/- 1.3%; P1, 36.2 +/- 1.7%; P6, 36.1 +/- 1.7%; and P12, 37.3 +/- 2.1%. Collateral blood flow to the inner two thirds of the risk region determined with radiolabeled microspheres during ischemia did not differ significantly between the control group (0.03 +/- 0.01 ml/min/g, n = 8) and single occlusion group (0.06 +/- 0.02 ml/min/g, n = 8), indicating that the marked disparity in infarct size could not be attributed to differences in collateral blood flow. The data indicate that preconditioning with one brief ischemic interval is as effective as preconditioning with multiple ischemic periods.