Local cardiac hypothermia for myocardial protection

Profound local cardiac hypothermia was used as the method of myocardial protection during cardiac anoxia in 190 patients, with an overall operative mortality of 4.7%. Local cardiac hypothermia avoids the complications and complexities of coronary perfusion, allows for a decreased operating time, and promotes satisfactory postoperative cardiac performance. The technique is recommended for cardiac operations in which cardiac anoxia is desirable or required.     

Local cardiac hypothermia for myocardial protection during correction of congenital heart disease.

Eighty-eight operations for correction of intracardiac congenital heart defects were performed using local cardiac hypothermia for protection of the ischemic myocardium. Twenty-six patients underwent repair of tetralogy of Fallot, 23 had patch closure of ventricular septal defect, 24 had correction of various types of congenital aortic stenosis, and 15 were operated upon for other complex lesions. The overall operative mortality was 5.6%. Ischemia times ranged from 9 to 119 minutes (mean, 48 minutes). Ischemic arrest protected by local cardiac hypothermia provides an optimal operative field, permitting repair of uncomplicated intracardiac defects in a precise, unhurried manner. No hemodynamic abnormalities attributable to the technique were encountered.     

Uneven myocardial hypothermia among cardiac chambers during hypothermic myocardial preservation

During the development of methods to protect the heart from ischaemic injury, attention has been focused on protection of the left ventricle. In an attempt to assess right heart preservation. 55 consecutive patients undergoing open heart surgery were studied. Mean aortic cross-clamp time was 59.3 +/- 29.4 min. Temperature probes were inserted into the right atrium (RA), right ventricle (RV), and left ventricle (LV). During cardioplegia, the mean myocardial temperatures of RA, RV and LV were 19.1 degrees +/- 4.1 degrees C, 12.7 degrees +/- 4.8 degrees C and 7.3 degrees +/- 3.4 degrees C, respectively. Of the LV temperature measurements, 67.2% were 10 degrees C or lower. By contrast, 94.1% of RA measurements and 58.5% of RV measurements were above 10 degrees C. The inhomogeneity of chamber temperatures was observed irrespective of the patient's disease or age and whether the atrium or right ventricle were open or not. Hearts with mitral regurgitation (MR), in contrast to mitral stenosis and stenoinsufficiency, had higher LV temperatures, similar to those in the RV. We conclude that there is uneven hypothermia among the three cardiac chambers during hypothermic cardioplegic arrest, regardless of disease states except MR and regardless of age and procedure performed.     

Interactions between pharmacological cardioplegia and hypothermia for intraoperative myocardial protection

Cold cardioplegia is currently the method of choice for providing myocardial protection during open-heart surgical procedures. Two components of protection, perfusion cooling and pharmacological cardiac arrest, were investigated in the guinea pig heart-lung model. The effects of two cardioplegic solutions, the University of Alabama Hospital solution and the St. Thomas' Hospital solution, and a control perfusate were compared. The results confirmed the efficacy of hypothermia as a protective agent and the additional protection afforded by pharmacological cardioplegia. Infusion temperature critically influenced the cardioprotective action of the Alabama solution: Striking protection was afforded only under hypothermic conditions, whereas myocardial damage was exacerbated by the infusion at 37 degrees C. The St. Thomas' Hospital solution provided substantial protection independent of infusion temperature. Thus, the safety margin of the Alabama solution was narrower than that of the St. Thomas' solution. It is suggested that the difference between the two cardioplegic solutions partially depends on their coronary vasoactivity, since the administration of the Alabama solution at 37 degrees C increased coronary perfusion pressure. It would seem worthwhile to use a temperature-independent cardioplegic solution devoid of coronary vasoconstricting action.     

Enhanced myocardial protection by systemic deep hypothermia in children undergoing total correction of tetralogy of Fallot

The effectiveness of systemic deep hypothermia for myocardial protection was evaluated retrospectively in 36 consecutive children who underwent total correction of tetralogy of Fallot in the four-year period 1980 to 1984. Moderate hypothermia combined with potassium-induced cold cardioplegia and topical cardiac cooling was employed in 16 patients (Group A), and deep hypothermia together with cold cardioplegia and topical cooling was used in 20 patients (Group B). A higher incidence of spontaneous defibrillation, a higher postoperative right ventricular cardiac index, a significant decrease in the maximal requirement of isoproterenol hydrochloride, a significant increase in the mean urinary output, and much better operative results were obtained in Group B compared with Group A. Postmortem histopathological examination of the heart in 3 patients in Group A disclosed various degrees of hypoxic change in the myocardium, which were more pronounced in the right ventricle than in the left ventricle. It is concluded that the myocardial protection obtained with cold cardioplegia and topical cooling under moderate hypothermia may well be insufficient for repair of tetralogy of Fallot, a condition characterized by increased non-coronary blood flow to the myocardium and abundant collateral bronchial flow. However, when combined with systemic deep hypothermia, such myocardial protection is quite safe and effective.     

Adenosine in myocardial protection in on-pump and off-pump cardiac surgery

Adenosine is most well known for its potent vasodilation of the vasculature. However, it also promotes glycolysis, and activates potassium-sensitive adenosine triphosphate (K(ATP)) channels. Adenosine also strongly inhibits neutrophil function such as superoxide anion production, protease release, and adherence to coronary endothelial cells. Hence adenosine attenuates ischemic injury as well as neutrophil-mediated reperfusion injury. Adenosine has also been implicated in the cardioprotective phenomenon of ischemic preconditioning. Accordingly experimental evidence shows that adenosine reduces postischemic injury when administered before ischemia and at the onset of reperfusion. Clinical studies in cardiology and cardiac surgery show cardioprotective trends with adenosine treatment but the effects are not as dramatic as those reported by experimental studies.     

Preventive insulin administration for myocardial protection in cardiac surgery

The object of this study was to determine whether high doses of insulin administered preventively in combination with glucose and potassium exert a protective effect upon the myocardium. This approach should result in a preoperative accumulation of the myocardial glycogen stores with an increased anaerobic provision of energy-rich substrates (ATP) during coronary ischemia. Two comparable groups of seven dogs each, undergoing experimental extracorporeal circulation (ECC) with 90-min aortic cross-clamping were examined. Cardiac output (CO), systolic left ventricular blood pressure (pventr), left ventricular enddiastolic pressure (LVEDP), mean central venous pressure (CVP), and heart rate (HR) were recorded at left atrial (LA) pressures of 5, 10, 15, and 20 mmHg in order to construct ventricular function curves. These data were registered prior to the onset of ECC (preischemic value), after termination of ECC and after two 10-min periods of reperfusion. The first group served as control and the second group received high iv doses of insulin (total 25 U/kg) within 60 min prior to the onset of the ECC. In the control group, pventr and CO after termination of the ECC and after the first reperfusion were significantly (P less than 0.05) less than the preischemic values; after the second reperfusion they reached the preischemic range. In contrast, pventr and CO in the insulin group already were within the preischemic range at the termination of the ECC. After the first and the second reperfusion, CO was even greater than the preischemic value. LVEDP changed inversely, while CVP and HR showed no significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)     

Optimal level of hypothermia for prolonged myocardial protection assessed by 31P nuclear magnetic resonance.

The optimal level of hypothermia during myocardial preservation for cardiac transplantation is not known. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess the effect of different preservation temperatures (15 degrees C in group 1, 4 degrees C in group 2) on the myocardial high-energy phosphate profiles during prolonged global ischemia and subsequent reperfusion of isolated rat hearts. Adenosine triphosphate depletion during ischemia was more gradual in group 2, leading to significant differences in myocardial adenosine triphosphate concentrations between the two groups after 3 hours of ischemia. The fall in intracellular pH during ischemia was significantly less pronounced in hearts preserved at 4 degrees C as compared with those at 15 degrees C. The postischemic recovery of both the left ventricular peak systolic pressure and the maximum rate of increase of left ventricular pressure was enhanced in group 2, although the ischemic period was 3 hours longer than in group 1. Hypothermia at 4 degrees C as compared with 15 degrees C appears to prolong myocardial protection with respect to adenosine triphosphate preservation, prevention of the fall in intracellular pH, and the enhancement of postischemic hemodynamic recovery.     

Ultrastructural artefacts in biopsied normal myocardium and their relevance to myocardial biopsy in man.

Biopsy specimens, as a source of myocardial tissue, are being used increasingly in the appraisal of various myocardial diseases. A study of myocardial tissue, biopsied and processed in various ways, and obtained from normal healthy experimental animals, showed that a variety of artefacts may be found. These artefacts develop in reactive, beating myocardium but not in non-reactive hearts. The artefacts are in many instances similar to, or mimic, changes previously described as pathological in origin. This is most unsatisfactory, and if valid pathological appraisals of myocardial biopsies are to be made, a technique allowing the recovery of tissue, free of biopsy artefact, is required. Such a technique is described.     

Cardiac hypothermia evaluated by ultrastructural studies in man.

Transmural left ventricular biopsies from 13 patients undergoing cardiopulmonary bypass were studied. The hypertrophic myocardium was protected by deep hypothermia (15 degrees C.) during ischemic arrest for a maximal period of 96 minutes. Biopsies were taken at the start of bypass, at the end of aortic cross-clamping, and after 20 minutes of reperfusion. The structure of the mitochondria remained normal, whereas cellular alterations in the form of widened intercalated discs, interstitial and intracellular edema, myelin figures, and slight myofibrillar lysis were observed in all stages. As no clear correlation between these structural injuries and aortic cross-clamping time was seen, they are a result of cardiac hypertrophy rather than intraoperative ischemia.     

Cold cardioplegia versus hypothermia for myocardial protection. Randomized clinical study.

Seventeen of 34 consecutive patients undergoing coronary artery bypass grafting were randomly assigned to one of two methods of myocardial preservation. With the cold cardioplegic method (Group A), a 4 degrees C. asanguineous solution with 30 mEq. of potassium per liter was infused into the aortic root for about 2 minutes immediately after aortic cross-clamping and again after about 45 minutes or when myocardial temperature rose above 19 degrees C. External cardiac cooling was provided by constant infusion of 4 degrees C. Ringer's solution into the pericardium. Seventeen patients were assigned to simple cardiac cooling by hypothermic systemic perfusion before aortic cross-clamping plus external cardiac cooling (Group B). Electromechanical activity ceased within 1 to 2 minutes in Group A but continued throughout the ischemic period in 14 patients in Group B. Myocardial temperature (mean for all observations) during aortic cross-clamping was 17.2 +/- 0.44 degrees C. In Group A and 24.0 +/- 0.70 degrees C. in Group B. Operating conditions were better in Group A. Card-ac function early postoperatively was good in both groups clinically and according to measurements, but only in the cold cardioplegic group (A) was cardiac index not adversely affected by longer cross-clamp time. Myocardial necrosis occurred in both groups but was probably less in the cold cardioplegic group. Thirteen patients (76 percent) in Group A had no electrocardiographic evidence of myocardial injury, compared with eight (47 percent) in Group B (p = 0.08). Eleven (65 percent of Group A had no or short-lived appearance of ceatine phosphokinase isoenzyme (CK-MB), compared with six (35 percent) of Group B (p = 0.08). Time-related CK-MB and SGOT mean levels were consistently lower in Group A.     

Right ventricular myocardial protection through intracavitary cooling in cardiac operations

In an attempt to protect the right ventricle, we designed and tested a closed cooling system that circulates cold saline through a double-lumen, balloon-tipped catheter positioned in the right ventricular cavity. Fourteen sheep were randomly assigned to two groups. In group A (n = 7), the right ventricular cooling catheter system was used in addition to coronary cardioplegic perfusion and systemic hypothermia for myocardial protection. Group B (n = 7) served as a control group. In group A, the right ventricular temperatures were significantly lower than those of the control group (16.1 degrees +/- 0.3 degrees C versus 23.9 degrees +/- 0.4 degrees C; p less than 0.0001, Student's t test). The most common temperature range was 12 degrees to 18 degrees C (67.1%, frequency distribution analysis), and 63.2% of temperatures were below 16 degrees C. The catheter system also maintained the temperatures of the interventricular septum at a lower level than those recorded in the control group and prevented septal rewarming, which was significant in group B (from 16.5 degrees +/- 1.5 degrees C to 25.0 degrees +/- 0.9 degrees C; p less than 0.04, Mann-Whitney U test). Left ventricular temperatures were not changed by the catheter system. By better cooling the right ventricle and the septum, the right ventricular cooling catheter system should decrease the prevalence of right ventricular failure and allow more time to safely complete multiple coronary anastomoses in coronary artery bypass graft operations.     

Resection of the ascending aorta using profound local hypothermia for myocardial protection.

Resection of the ascending aorta with or without aortic valve replacement requires prolonged interruption of myocardial blood flow. Profound local cardiac hypothermia was used in 8 patients, 5 of whom had simultaneous aortic valve replacement. Three patients with acute dissections were encountered, one with cardiac tamponade secondary to intrapericardial rupture. The duration of aortic cross-clamp time varied from 43 to 122 minutes. There were no complications related to the cooling technique. There were no operative or hospital deaths. One patient died of myocardial infarction at 6 weeks. These results coupled with the experience of others suggest that coronary perfusion during periods of obligatory anoxia in unnecessary. Local cardiac hypothermia offers a satisfactory alternative for myocardial protection during prolonged aortic crossclamping.     

Ultrastructural and cytochemical studies on cell death of osteoclasts induced by bisphosphonate treatment.

The process of apoptosis and fate of osteoclasts are not well elucidated because dying osteoclasts are rarely seen in normal bone. Histological, cytochemical, and ultrastructural features of osteoclasts undergoing apoptosis were studied in the femur and tibia of rats treated with a third-generation bisphosphonate (disodium dihydrogen (cycloheptylamino)-methylene-1, 1-bisphosphonate). After the bisphosphonate administration, osteoclasts decreased significantly in number. Initially, they became devoid of ruffled borders and detached from the bone surface. In such osteoclasts, the Golgi apparatus was degraded, or dispersed in the cytoplasm. Later, osteoclasts revealed typical features of apoptosis, with pyknotic nuclei showing condensation and margination of heterochromatins and DNA fragmentation. They were often convoluted to give rise to apoptotic bodies. In addition, enlargement and fusion of nuclear envelopes and subsequent disruption leading to leakage of nuclear contents into the cytoplasm were observed in osteoclasts in the late stage of apoptosis. These osteoclasts as well as apoptotic bodies were surrounded by cytoplasmic processes of macrophages, which often contained degenerated cytoplasmic fragments of osteoclasts. Apoptotic osteoclasts migrating into or present in capillaries were also observed in some areas. In conclusion, bisphosphonate induces apoptosis of osteoclasts, which was characterized by ultrastructural changes of the nucleus typical of apoptosis accompanied by degradation of cell organelles. The majority of them are eliminated by macrophages, but there are some that escape into blood vessels.