Long-term survival rates after prolonged aortic cross-clamping with St. Thomas' Hospital cardioplegia.

Prolonged aortic cross-clamping (in excess of 120 min) was necessary in 154 cardiac surgical patients. St. Thomas' Hospital cardioplegia was used for myocardial preservation. Quantitative polarization microscopy enabling quantitative birefringence measurements to assess the change in birefringence of the muscle fibres in response to the addition of buffer containing ATP and calcium (i.e. myocardial contractility) was used to detect whether there had been any deterioration in right or left ventricular myocardium during the bypass period. 30 day survival was 90%, long-term (60 months) survival was 80%. In single valve replacements, patients with aortic valvular replacement had 100% survival up to 92 months, whereas patients with mitral valvular replacement had survival rates of 83% after 12 months and 27% after 60 months. Survival rates after 60 months were 89% for coronary artery bypass grafting, 80% for multiple valve replacements, and 74% for combined valvular and coronary artery bypass grafting surgery. Quantitative birefringence assessment of function showed that in the surviving patients 5% had functional deterioration during bypass whereas in the non-surviving patients 70% had functional deterioration. It may be concluded that after cardiac surgery necessitating prolonged aortic cross-clamping--once the initial operative problems are overcome--reasonable long-term results can be obtained by using St. Thomas' Hospital cardioplegia.

St. Thomas' Hospital cardioplegia for myocardial preservation during prolonged aortic cross-clamping.

The effectiveness of St. Thomas' Hospital cardioplegia for myocardial preservation during prolonged aortic cross-clamping was analyzed in a clinical series of 100 consecutive cardiac surgical patients identified as having aortic cross-clamp times greater than 120 minutes. Hospital mortality from all causes was 8%, but only one of these 8 patients succumbed from immediate primary failure of the myocardial preservation protocol. Severe but reversible low cardiac output syndrome occurred in 5 patients, and in 4 of them there had obviously been a primary failure in cardiac protection. Peri-operative, clinically "silent" myocardial infarction could be demonstrated in retrospect by electrocardiographic criteria in 3 other patients. Post-operative complications occurred in 26 patients, many of them having several complications at the same time. Paired left ventricular and right ventricular prebypass and post-bypass biopsies processed for cytochemical and biophysical investigation were available from one third of the patients. Only 2 cases showed a severe deterioration. There was lack of correlation between the duration of aortic occlusion and operative mortality rate, incidence of peri-operative infarction, and occurrence of low cardiac output syndrome post-operatively. The results thus indicate that St. Thomas' Hospital cardioplegia is a very effective means of myocardial protection during prolonged periods of aortic cross-clamping.

Biopsy assessment of preservation during open-heart surgery with cold cardioplegic arrest.

The efficacy of cold cardioplegic arrest as a method of myocardial preservation has been evaluated by cytochemical and biophysical assessments made on needle biopsies taken from 150 patients undergoing open-heart surgery (e.g., aortic valve replacement, aortic and mitral valve replacement, mitral valve replacement, coronary artery bypass graft, repair of atrial or ventricular septal defects). Comparison of endo- and epicardial preservation showed improved endocardial preservation with cardioplegia compared with that achieved with the previous method used--continuous coronary perfusion at 32 degrees C; however, care had to be taken to ensure adequate cooling of the epicardium. Biopsies also showed the need for repeated infusions of cardioplegic solution if the aorta was occluded for more than 70 min. Preservation of right and left ventricle has also been compared.

Cardioplegia versus intermittent ischaemic arrest in coronary bypass surgery.

No definitive method of myocardial preservation has been established and conclusions based on experimental data may not be applicable to patients with coronary artery disease. Fifty patients undergoing coronary bypass grafting were randomly assigned to one of two groups for myocardial preservation. In group A cold cardioplegia with external cardiac cooling was used and in group B ischaemic arrest with mild systemic cooling to 32 degrees C. Myocardial preservation was assessed by analysis of enzymes specific to the heart, left ventricular biopsy, and electrocardiography. Equal protection of the myocardium was provided in both groups but the mean cross-clamp time in group A was significantly longer than in group B. This implies that cardioplegia confers greater protection than intermittent ischaemic arrest.

Cellular chemical indices of right ventricular protection in children.

Myocardial preservation during open heart surgery in children was studied using biopsies of the right ventricle taken at the beginning and end of a bypass with a Tru-Cut biopsy needle. Three assessments were used: (1) semi-quantitative cytochemical grading of Baker's acid haematein reaction, and the distribution of succinate dehydrogenase and myosin ATPase; (2) microdensitometry of the succinate dehydrogenase activity; and (3) quantitative birefringence measurements to assess the response of the myocardial fibres to ATP and calcium. For each assessment, the values at the beginning and end of the bypass were compared. In a series of 42 children, two died in low cardiac output and three others required substantial inotropic support. No patient showed deterioration in the overall cytochemical assessment. Two patients showed deterioration in birefringence, one died and one had low cardiac output. The remaining three patients who had post-operative problems had low birefringence values at the beginning of bypass. Thirty-two patients were used for the microdensitometric assays, one died and three required substantial inotropic support. Succinate dehydrogenase activity decreased significantly during bypass in only two patients. One of these died and the other required substantial inotropic support.

The St. Thomas' hospital cardioplegic solution: a characterization in two species.

Following detailed investigation and definition of some of the critical factors relating to the composition and use of cardioplegic protective solutions, we have formulated the St. Thomas' Hospital cardioplegic solution number 2. This cardioplegic solution (NaCl 110.0 mM, NaHCO3 10.0 mM, KCl 16.0 mM, MgCl2 16.0 mM, CaCl2 1.2 mM, pH 7.8) is designed for routine clinical use combining optimal protection with simplicity of formulation and administration/infusion. In order to characterize the efficacy of this modified solution, experiments have been carried out in two species: the isolated rat heart and the in-situ dog heart. In parallel protocols, hearts were subjected to ischemic arrest of up to 4 hours. Multidose (every 40 minutes) cardioplegic infusion of the St. Thomas' solution combined with topical hypothermia extended the tolerable period of ischemia from less than 30 minutes to about 120 minutes in the rat and from less than 60 minutes to more than 180 minutes in the dog. These conclusions were based on the measurement of functional indices together with biochemical, cellular chemical and ultrastructural assessments. The studies confirmed the additive protective properties of hypothermia and chemical cardioplegia and the utility of the rat heart model in the assessment of protective interventions.

The additive protective effects of hypothermia and chemical cardioplegia during ischemic cardiac arrest in the dog.

In clinical use cardioplegia is usually combined with local cardiac hypothermia, whose powerful protective effects make it difficult to assess the contributions made by the cardioplegic solution. The additive protective effects of hypothermia and of an experimental cardioplegic infusate were studied in 20 dogs which were subjected to 120 minutes of myocardial ischemia at 20 degrees C. In the hypothermic group 10 hearts were infused with a noncardioplegic solution at 20 degrees C at the onset and after 60 minutes of ischemia. In the cardioplegia plus hypothermia group of 10 hearts identical infusion conditions were followed, with the cardioplegia solution at 20 degrees C. Measurements of ventricular function before and after bypass revealed significantly better recoveries in the cardioplegic group than in the hypothermic group. Recoveries of cardiac output, left ventricular minute work, and dP/dt in the cardioplegia group were 92%, 62% and 91%, respectively, whereas in the hypothermia group the values were 38%, 17%, and 43%, respectively. Parallel biochemical assessments from biopsies revealed that postischemic myocardial adenosine triphosphate (ATP) content was unchanged from control in the cardioplegia group but fell significantly to 56% of control in the hypothermia group. Assessment of myocardial integrity by birefringence showed no change in the cardioplegia group but a deterioration in the hypothermia group. These results demonstrate that chemical cardioplegia when combined with hypothermia affords additional protection to the ischemic heart.

Biopsy evidence of left ventricular myocardial abnormality in patients with mitral-leaflet prolapse and chest pain.

Left ventricular endomyocardial biopsy specimens were obtained at cardiac catheterisation in 11 patients with mitral-leaflet prolapse, chest pain, and normal coronary arteries. Specimens were examined for birefringence before and after contraction induced by adenosine triphosphate and were also subjected to histochemical analysis. Biopsy specimens from a control group of patients with rigorously defined normal left ventricular function and another control group with poor left ventricular function were also studied. Biopsy specimens from patients with mitral-leaflet prolapse showed a markedly subnormal birefringence response to adenosine triphosphate, with the group mean value intermediate between values for controls with normal and poor left ventricular function. Histochemical studies in the prolapse group also revealed an abnormal pattern, particularly for monoamine-oxidase activity. This is further evidence of a cardiomyopathy in this symptomatic subgroup of patients with mitral-leaflet prolapse.

Cold cardioplegia or continuous coronary perfusion? Report on preliminary clinical experience as assessed cytochemically.

Myocardial preservation by continuous coronary perfusion is compared with cold cardioplegia. The 1 L. of St. Thomas' cardioplegic protective solution used for infusion into the coronary arteries was at 4 degrees C. and had a normal electrolyte content except for raised concentrations of magnesium and potassium and the addition of procaine. Myocardial preservation was assessed by cytochemical grading of myocardial biopsy specimens and also by the requirement for significant inotropic support postoperatively. In aortic valve replacements with an aortic occlusion time of 1 1/2 hours, both techniques afforded a similar degree of preservation, except that the inner half of the myocardium was markedly better preserved by cold cardioplegia. After 2 hours in double valve replacements, a single cardioplegic infusion was not as effective as continuous coronary perfusion, but this could be corrected by a second infusion of the cardioplegic solution after an hour.

Myocardial preservation during aortic valve surgery. Assessment of five techniques by cellular chemical and biophysical methods.

Five different types of myocardial protection were employed in this series of 168 patients undergoing aortic valve replacement. Two methods of assessing myocardial preservation were used: cellular biological estimations and quantitative polarization measurements. Both parameters showed that either of two methods, continuous perfusion at 32 degrees C. with a beating heart or cardioplegic hypothermic arrest, protected the myocardum best. Intermittent perfusion at 30 degrees C. with a fibrillating heart was the worst means of preservation. Our investigations (both clinical and experimental) have also shown that changes in birefringence, indicative of deteriorating myocardial function, are often detectable before parallel cytochemical changes are apparent.

Left ventricular endomyocardial biopsy. III: ultrastructural characteristics of cardiomyopathy and cardiac hypertrophy with good or poor ventricular function.

Left ventricular endomyocardial biopsies have been obtained from patients with cardiomyopathy and hypertrophy due to aortic valve disease. These biopsies have been examined by electron microscopy and the ultrastructural abnormalities compared. In congestive cardiomyopathy no specific abnormalities were found although myofibrillary degeneration and membrane-bound vacuoles were more commonly present. Crossing of whole groups of sarcomeres was found only in asymmetric septal hypertrophy, but was not present in all cases. Amyloid deposits were demonstrated easily by electron microscopy in patients with restrictive cardiomyopathy. In the patients with hypertrophy due to aortic valve disease, no specific features were found and ultrastructural abnormalities did not differentiate between normal and impaired left ventricular functions.

Left ventricular endomyocardial biopsy. II: the value of light microscopy.

Histological sections of left ventricular endomyocardial biopsies have been examined by light microscopy. The biopsies were taken from patients with congestive, hypertrophic, or restrictive cardiomyopathy and from patients with either aortic stenosis or regurgitation. In congestive cardiomyopathy no specific features were found and similar abnormalities were seen in aortic valve disease. In only one of six cases of asymmetric septal hypertrophy were the characteristic histological appearances noted. In four out of five patients with a restrictive type of cardiomyopathy, amyloid was demonstrated. The muscle fibres in aortic stenosis had a greater cross-sectional area than those in aortic regurgitation. A greater degree of fibrosis was present in aortic stenosis than in aortic regurgitation. In aortic stenosis the amount of fibrous tissue was inversely related to function.

Evaluation of perfusion conditions in cardiopulmonary bypass.

Fresh sections of left ventricular drill biopsies, taken at the beginning and end of cardiopulmonary bypass in 164 patients undergoing aortic valve replacement, have been analyzed for myocardial function. This has been assessed by changes in biochemical function, measured by semi-quantitative histochemical methods, and by changes in birefringence, measured quantitatively by polarization microscopy. It has been shown that continuous perfusion at 32 degrees C with the heart beating provided better preservation than did the other three perfusion procedures, in all of which the heart was fibrillating. More recently, in a small number of cases, cardioplegic arrest has been found to given even better preservation.