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Biomedical subjects

M V Braimbridge

Publications and source records attributed to M V Braimbridge.

At least 73 records · Page 4Linked to original sources

Nifedipine and cardioplegia: rat heart studies with the St Thomas' cardioplegic solution.

The ability of nifedipine to enhance myocardial protection was assessed using an isolated rat heart model of cardiopulmonary bypass and ischaemic cardiac arrest. With normothermic ischaemic arrest (35 min, 37 degrees C), nifedipine addition improved the protective properties of the St Thomas' cardioplegic solution. Optimal protection was observed with 0.075 mumol nifedipine X litre-1, where post-ischaemic recovery of aortic flow was improved from 47.9 +/- 5.2% to 76.7 +/- 2.9% (P less than 0.001) and creatine kinase leakage was reduced by approximately 50%. Despite the marked additional protection under normothermic conditions the drug was unable to improve contractile recovery after a period of hypothermic ischaemic arrest (150 min, 20 degrees C) although it did allow a significant reduction (22%) in creatine kinase leakage. In other studies, the ability of nifedipine to replace the cardioplegic solution was examined. Under normothermic conditions, it showed a good ability to protect against ischaemia, but this protection did not match that afforded by the St Thomas' cardioplegic solution. Under hypothermic conditions the drug failed to substitute for the cardioplegic solution, suggesting that a common modality between hypothermia and nifedipine-induced protection.

Animals↗

Cardioplegia and slow calcium-channel blockers. Studies with verapamil.

The ability of dl-verapamil to enhance myocardial protection when given before, during, or after myocardial ischemia was assessed with the use of an isolated working rat heart model of cardiopulmonary bypass and ischemic cardiac arrest. Under conditions of normothermic ischemic arrest (30 minutes at 37 degrees C), the addition of verapamil enhanced the protective properties of the St. Thomas' Hospital cardioplegic solution. Optimal protection was observed with verapamil concentrations of 0.5 mg/L (1.09 mumol/L) of cardioplegic solution. Under these conditions, postischemic enzyme leakage was reduced by 32.2% and the postischemic recovery of aortic flow was improved by 18.7%. Despite the additional protection at normothermia, the drug at several concentrations appeared unable to improve functional recovery after an extended period of hypothermic arrest (150 minutes at 20 degrees C), although under these conditions its inclusion in the cardioplegic solution could substantially reduce enzyme leakage. In other studies, the ability of various doses of verapamil alone as a substitute for the cardioplegic solution was examined. At the optimal dose (again 0.5 mg/L), and under normothermic conditions, verapamil alone was a good protection against ischemic injury, although this protection did not match that afforded by the St. Thomas' Hospital cardioplegic solution. In similar studies under hypothermic conditions, the drug failed to afford tissue protection, perhaps indicating some common modality between hypothermia and verapamil-induced protection. Pretreatment with verapamil (0.1 mg/L) prior to ischemia offered moderate additional protection, but its use during reperfusion failed to enhance overall recovery.

Animals↗

A quantitative cytochemical method for the measurement of beta-hydroxyacyl CoA dehydrogenase activity in rat heart muscle.

Although cytochemical methods exist for measuring dehydrogenases that act on substrates involved in the production of chemical energy from sugars, virtually no methods exist for measuring the dehydrogenases that act on fatty acids. Yet the oxidation of fatty acids accounts for over 60% of the oxidative activity of cardiac muscle. Consequently a new quantitative cytochemical method, based on a new substrate (DL-S-beta-hydroxybutyryl-N-acetyl cysteamine), has been developed for measuring the activity of hydroxy-acyl coenzyme A dehydrogenase, which is the penultimate step of the beta-oxidation of fatty acids to acetyl-coenzyme A that is used in the Krebs' cycle. Menadione or phenazine methosulphate is used as the intermediate hydrogen-acceptor, with neotetrazolium chloride as the final acceptor. The medium contains nitroprusside, ostensibly to react with any cysteamine liberated by hydrolysis of the substrate. As a control, cysteamine is substituted for the substrate. The concentrations of reactants have been optimized for cardiac muscle; the reaction is linear with thickness of the sections and with time of reaction from 15 to 60 min.

3-Hydroxyacyl CoA Dehydrogenases↗

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.

Adult↗

Comparison between irrigation and conventional treatment for empyema and pneumonectomy space infection.

A new method of treating pleural empyema or pneumonectomy space infection by irrigation was evaluated in 11 patients. The infected cavities were filled with an antibiotic or antiseptic solution for three hours, and allowed to drain for one hour. This cycle was repeated every four hours for seven to 10 days. When cultures of the infected cavity became sterile the irrigation tube was removed and the wound sealed. Using this method, infection was eradicated after an average of 11 days in five of six patients with pleural empyema and in all five patients treated for an infected pneumonectomy space, including one with a bronchopleural fistula. The results of treating 58 similar cases of intrapleural sepsis over a 10-year period by the standard methods of aspiration, open drainage, decortication, or thoracoplasty were compared with the results of irrigation. In general, cyclical irrigation resulted in a shorter hospital stay and a shorter period of wound drainage than other methods.

Adolescent↗

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.

Animals↗

Protection of the myocardium during ischemic arrest. Dose-response curves for procaine and lignocaine in cardioplegic solutions.

The dose-response curve of procaine or lignocaine (lidocaine) added to the St. Thomas' Hospital cardioplegic solution was investigated with an isolated working rat heart preparation. In the absence of any cold cardioplegic protection, hearts failed to recover after as little as 30 minutes of ischemia. A single infusion (20 degrees C) of the basic St. Thomas' Hospital cardioplegic solution allowed hearts to recover to 60% or more of their preischemic control aortic flow after a 120 minute period of ischemia. Addition of procaine to the cardioplegic solution either increased or reduced the apparent protective properties of the solution with a bell-shaped dose-response curve being obtained. The optimum procaine concentration was 0.05 mM/L. At this concentration the protection afforded by the St. Thomas' Hospital solution was increased by up to two thirds. Substitution of lignocaine for procaine resulted in a similar dose-response curve with its optimum also at 0.05 mM/L. If a similar optimum exists for the human heart, the doses in current clinical use would appear to be too high. These results argue for determining the dose-response characteristics of all substances used in cardioplegic solutions.

Animals↗

Protection of the myocardium during ischemic arrest: possible toxicity of carnitine in cardioplegic solutions.

Carnitine has been suggested as an agent for the protection of the myocardium during regional ischemia and it might therefore be able to reduce tissue injury during surgically induced global ischemia. Using an isolated working rat heart model we have assessed the way in which various concentrations of carnitine infuence the efficacy of the St. Thomas' Hospital Cardioplegic Solution. Carnitine was found to exert a dose-dependent detrimental effect upon the ischemic myocardium, with high concentrations abolishing all the protective properties of the cardioplegic solution. Furthermore, this compound appeared to promote the occurrence of reperfusion dysrhythmias.

Animals↗

Sequential brush biopsy and conventional biopsy: direct comparison of diagnostic sensitivity in lung malignancy.

One hundred and sixteen patients with suspected lung malignancy who were referred for bronchoscopy were examined using both the flexible fibreoptic bronchoscope and the rigid bronchoscope. Both instruments were used sequentially under the same general anaesthetic. Brush biopsies were obtained through the fibreoptic bronchoscope and conventional biopsies, for histological examination, through the rigid bronchoscope. Both specimens were taken from the same area. Eighty-two per cent of those in whom there was a final clinical diagnosis of malignancy were found to have abnormal cytology via the fibreoptic bronchoscope, while abnormal histology was found in 50% by means of the rigid bronchoscope. For those in whom malignancy was confirmed, 16.9% showed disagreement between the two methods in cell typing. Brush biopsy through the flexible fibreoptic bronchoscope under general anaesthesia is confirmed as a sensitive method for diagnosing lung malignancy.

Adolescent↗

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.

Adenosine Triphosphate↗

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

In a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest the potential additive protective effects of hypothermia and chemical cardioplegia have been investigated. Isolated rat hearts were subjected to a 2 minute period of coronary infusion with a cardioplegic or a noncardioplegic solution immediately before and also at the midpoint of a 2 hour period of hypothermic (20 degrees C) ischemic cardiac arrest. In the hypothermia plus cardioplegia group postischemic aortic flow recovered to more than 50% of its preischemic control value, myocardial energy phosphate content returned to near preischemic control levels, and creatine kinase leakage was moderate. By contrast, in the hypothermia alone group (coronary infusion with non cardioplegic solution) the postischemic functional recovery was less than 30% of its preischemic control value, cellular high-energy phosphate content was considerably reduced, and creatine kinase leakage was more than twice that observed in the hypothermia plus cardioplegia group. In addition to illustrating the additive nature and powerful protective properties of hypothermia and cardioplegia these studies serve to illustrate the utility of the isolated rat heart model for the primary assessment of procedures designed to protect the myocardium during ischemic cardiac arrest. The results and conclusions derived from this study were quantitatively and qualitatively similar to those obtained in a parallel study in the dog.

Adenosine Triphosphate↗

Inotropic agents and functional recovery from ischemic cardiac arrest.

Short periods of ischemic arrest may cause myocardial cell damage so that reperfusion does not result in an immediate return to normal metabolic and contractile activity. Studies have been carried out using a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest in order to determine whether the use of inotropic agents (isoprenaline and dobutamine) to augment contractile activity during the early phase of post-ischemic reperfusion extends pre-existing damage and results in ultimate impairment of contractile activity. The results indicated the existance of a substantial metabolic reserve, capable of providing sufficient energy for a marked increase in dP/dt and heart rate, without inducing tissue damage. However, in this isolated rat heart preparation the use of these agents had relatively little effect upon cardiac output and could be shown to induce a dose-dependent reduction in stroke volume.

Animals↗

Echocardiographic findings in prolapsed aortic cusp with vegetation.

A patient with severe aortic regurgitation showed abnormal echoes in the left ventricular outflow tract compatible with aortic vegetation or flail aortic cusp. At operation, a pedunculated vegetation on a prolapsed aortic cusp was found. The case illustrates some of the pitfalls in the echocardiographic distinction of the two conditions.

Adult↗

Cost of a cardiac surgical and a general thoracic surgical patient to the National Health Service in a London teaching hospital.

The cost of the inpatient stay for a typical aortic valve replacement and for an oesophagectomy were determined by recording and costing every aspect of the patients' care from admission until discharge. This method of cost calculation was found to be satisfactory and could be used by other centres to allow comparisons between hospitals or countries. At St Thomas's Hospital in 1977 the cost of a cardiac operation was 2755 pounds, an oesophagectomy 1870 pounds, and a general surgical operation 564 pounds.

Aortic Valve↗

Equipment for inducing cold cardioplegic arrest.

A technique for the infusion of the cardioplegic solution used at St. Thomas' Hospital is described. A flanged aortic root needle is used for patients with competent aortic valves and hand-held metal cannulas for those with aortic regurgitation.

Aortic Valve↗