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Biomedical subjects

M V Braimbridge

Publications and source records attributed to M V Braimbridge.

At least 55 records · Page 3Linked to original sources

The management of empyema thoracis by thoracoscopy and irrigation.

A technique of irrigation for the management of empyema is described. Initial thoracoscopy under general anesthesia enabled full debridement and division of loculi within the empyema cavity under direct vision. Irrigation with two tubes was instituted until three consecutive cultures of irrigation fluid became sterile; then the chest drains were removed. The results in 12 patients are presented. Using this method, irrigation was required for an average of 14 days and chest drains were removed after an average of 20 days. Patients remained in the hospital for an average of 4.8 weeks. Tuberculous empyema was not found to be a contraindication to the irrigation technique.

Adult↗

Calcium antagonists and myocardial protection: a comparative study of the functional, metabolic and electrical consequences of verapamil and nifedipine as additives to the St. Thomas' cardioplegic solution.

Using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest, a comparative study has been undertaken in order to characterize the functional, metabolic and electrophysiological consequences resulting from the addition of dl-verapamil or nifedipine to the St. Thomas' Hospital cardioplegic solution. Hearts (n = 6 in each group) were subjected to cardioplegic infusion with the St. Thomas' solution with or without added verapamil (1.1 micromoles/liter) or nifedipine (0.075 micromoles/liter). After 35 minutes of normothermic (37 degrees C) ischemic arrest, reperfusion was initiated and functional recovery was measured and expressed as a percent of its pre-ischemic control value. Inclusion of nifedipine in the cardioplegic solution improved the post-ischemic recovery of cardiac output from its control value of 59.8 +/- 3.0% to 80.0 +/- 2.5%. The temporal characteristics for the post-ischemic recovery of electrical activity and contractile performance were uncomplicated and similar to control hearts. Inclusion of verapamil also improved the protective properties of the St. Thomas' solution with cardiac output recovering to 76.8% +/- 2.8%. However, in contrast to the control and nifedipine groups, the profile for functional recovery was complex. After an early initial recovery, pressure development declined for 0.5 to 6.0 minutes. This occurred despite the recovery of electrical activity. Hearts then exhibited a second phase of recovery where pressure development returned to normal and this was sustained for the duration of the experiment. Analysis of electrocardiographic characteristics revealed a significant prolongation of the P-P and P-Q interval during the first 10 minutes of reperfusion in the verapamil group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Particle-induced coronary vasoconstriction during cardioplegic infusion. Characterization and possible mechanisms.

We have characterized an isolated rat heart preparation in which particles induce transient coronary vasoconstriction. Exploiting the fact that all commercially available intravenous solutions contain permissible levels of contaminant particles (usually 2 to 20 micron in diameter), we investigated whether these particles have any adverse effect upon coronary flow. A commercially available intravenous solution was modified to produce the St. Thomas' Hospital cardioplegic solution. Constant-pressure infusion of this solution over a 20 minute period caused a 46.2% +/- 5.1% reduction in coronary flow. This flow impairment could be limited to 13.3% +/- 3.5% by the incorporation of a 0.8 micron in-line filter. In hearts perfused with particle-containing solution followed by ultrafiltered solutions, the impairment of coronary flow was reversed within 1 minute. This quick reversal indicates that the particles were impairing flow not by physical occlusion of vessels but by triggering some form of transient vasoconstriction. In studies with filters of varying porosity (between 0.8 and 15.0 micron), the phenomenon was shown to be attributable to relatively small numbers of particles greater than 10.0 micron in diameter. In studies of myocardial protection, it was shown that the impairment of solution delivery and distribution caused by particles could severely reduce the protective properties of a chemical cardioplegic solution; hearts subjected to 180 minutes of hypothermic (20 degrees C) ischemic arrest with multidose (3 minutes every 30 minutes) cardioplegia recovered almost completely upon reperfusion if a filtered (0.8 micron) solution was used, but failed to recover when unfiltered, commercially prepared solutions were used. In an attempt to define the mechanisms underlying the particle-induced vasoconstriction, we conducted dose-response studies in which various vasoactive agents were used in an attempt to combat the effects of the particles. At their optimal concentrations, procaine (10.0 mmol/L), nifedipine (0.1 mumol/L), and adenosine triphosphate (1.0 mmol/L) completely prevented the problem; lidocaine and dipyridamole partially alleviated the effect; verapamil and isosorbide dinitrate were ineffective. These results indicate that several mechanisms acting at a small vessel level might contribute to the particle-induced vasoconstriction.

Adenosine Triphosphate↗

Impairment of myocardial function induced by particulate contamination of cardioplegic solutions.

The U.S. Pharmacopoeia defines acceptable limits of particle contamination for intravenous solutions. Used conventionally, these solutions are filtered by the lungs, and there are few reports of particle-induced tissue injury to the systemic circulation. We have used an isolated rat heart model to assess whether unfiltered direct intraarterial administration of cardioplegic solutions, as in open-heart surgery, can be damaging to the myocardium. An intravenous solution of U.S. commercial manufacture was selected for evaluation. Particle-counting revealed this solution to be well within the U.S.P. limits. Direct intracoronary infusion of this solution at 20 degrees C and at constant pressure led to an approximate 75% reduction in coronary flow over 20 min. Filtration through a membrane of 0.8-micron porosity largely prevented this reduction of coronary flow. In studies with multidose cardioplegia (3-min infusions every 30 min), hearts given filtered solution recovered almost 90% of their preischemic functional capacity after 3 hr of hypothermic (20 degrees C) ischemic arrest. Hearts given an identical unfiltered solution essentially failed to recover despite the particle counts having conformed to the U.S.P. limit. This functional result was supported by measurement of creatine kinase leakage, which was significantly higher in the unfiltered group. These studies provide an argument for revision of U.S.P. particle limits when applied to intraarterially administered solutions; in particular, we believe that equipment for cardioplegic infusion into coronary arteries should incorporate a 0.8-micron in-line filter.

Animals↗

Calcium antagonists and myocardial protection during cardioplegic arrest.

The ability of nifedipine, verapamil, and diltiazem to enhance cardioplegic protection has been assessed using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest. With normothermic ischemia (30 or 35 min at 37 degrees C), the addition of these compounds enhanced the protective properties of the St. Thomas' cardioplegic solution. All these compounds showed bell-shaped dose-response characteristics, with the optimal concentrations in terms of functional recovery and enzyme leakage of verapamil being 1.0 mumole/liter; nifedipine, 0.075 mumole/liter; and diltiazem, 0.5 mumole/liter. However, under conditions of hypothermia (150 or 180 min at 20 degrees C), none of these compounds improved postischemic functional recovery, although there was some reduction in enzyme leakage. From these results, further experiments were undertaken to investigate the relationship between calcium antagonists and temperature. Verapamil improved functional recovery at 34, 31 and 29 degrees C, but not at 27, 25, and 20 degrees C. These results suggest a common site of action between hypothermia and calcium antagonists in promoting functional recovery after ischemia.

Animals↗

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.

Adolescent↗

Use of microscopic interferometry for measuring changes in water content of small samples of tissue.

Oedema following periods of ischaemic arrest and subsequent reperfusion has been shown experimentally and clinically to affect the functional state of the heart. Tissue water content has been measured in myocardial sections by microscopic interferometry and densitometry, and the results correlated with those obtained by wet and dry weight analysis (r = 0.87; p less than 0.001). Microscopic interferometry also revealed the distribution of the water in the tissue. Experimentally induced ischaemic arrest in isolated rat hearts resulted in predominantly intra-fibrillar oedema, whilst subsequent reperfusion resulted in interfibrillar oedema. Microscopic interferometry facilitates accurate measurement of water content in tissue samples as small as 2 mg wet weight and shows (as conventional wet/dry weight analysis cannot) the distribution of the water in the tissue.

Animals↗

Comparison of the protective properties of four clinical crystalloid cardioplegic solutions in the rat heart.

Although few surgeons dispute the benefits of high-potassium crystalloid cardioplegia, objective comparison of the efficacy of various formulations is difficult in clinical practice. We compared four commonly used cardioplegic solutions in the isolated rat heart (N = 6 for each solution) subjected to 180 minutes of hypothermic (20 degrees C) ischemic arrest with multidose cardioplegia (3 minutes every half-hour). The clinical solutions studied were St. Thomas' Hospital solution, Tyers' solution, lactated Ringer's solution with added potassium, and a balanced saline solution with glucose and potassium. Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of creatine kinase during reperfusion was measured as an additional index of protection. St. Thomas' Hospital solution provided almost complete recovery of all indexes of cardiac function following ischemia including 88.1 +/- 1.6% recovery of aortic flow, compared with poor recovery for the Tyers', lactated Ringer's, and balanced saline solutions (20.6 +/- 6.5%, 12.5 +/- 6.4%, and 9.6 +/- 4.2%, respectively) (p less than 0.001). Spontaneous defibrillation was rapid (less than 1 minute) and complete (100%) in all hearts in the St. Thomas' Hospital solution group, but much less satisfactory with the other formulations. Finally, St. Thomas' Hospital solution had a low postischemic level of creatine kinase leakage, contrasting with significantly higher enzyme release in the other solutions tested (p less than 0.001). Although differences in composition are subtle, all potassium crystalloid cardioplegic solutions are not alike in the myocardial protection they provide. Comparative studies under controlled conditions are important to define which formulation is superior for clinical application.

Animals↗

Hormonal and electrolyte responses during and after open heart surgery.

Maintenance of the balance of electrolytes and hormones within their normal range is necessary for normal myocardial metabolism. Open heart surgery involving cardiopulmonary bypass produces metabolic disturbances which affect normal metabolic homeostasis. Several studies have suggested that pulsatile cardiopulmonary bypass causes less severe metabolic disturbance than non-pulsatile bypass and that non-pulsatile bypass causes hypofunction of the anterior pituitary and adrenal glands. The present study, however, with non-pulsatile flow showed that there was no evidence of hypothalamo-pituitary-adrenal axis hypofunction when the hormonal values of corticotrophin (ACTH), cortisol and cortisone were corrected for the hemodilution involved in cardiac surgery. Electrolytes, particularly calcium, play an important role in myocardial contractility. The levels of ionized calcium are normally controlled by parathyroid hormone (PTH) with a negative feedback of calcium controlling the system. However, this study showed that significant increases in bioactive PTH during cardiopulmonary bypass were not related to the calcium concentration, but appeared to be influenced by low blood pH values and by the degree of hypothermia.

Adrenocorticotropic Hormone↗

Myocardial catecholamines following cold cardioplegic arrest during open-heart surgery.

Preservation of both right and left ventricular subendocardial and subepicardial muscle was assessed using quantitative polarization microscopy (birefringence measurements) with preservation of myocardial catecholamines measured by fluorescence microscopy in biopsies from 20 consecutive patients who underwent open heart surgery with cold cardioplegic arrest (St. Thomas' Solution). Six of the 7 patients with clinical complications were predicted from the birefringence results. One developed left ventricular deterioration during bypass, two patients right ventricular deterioration, one patient both left and right ventricular deterioration and two patients had poor left ventricular function before bypass. Birefringence measurements were thus reliable in predicting post-operative cardiac outcome. There were no significant changes during the bypass period in the catecholamine scores, even in those patients who had clinical complications. Fluorescence microscopy showed that the "free" myocardial nerve net and the pericoronary nerve plexuses retained their catecholamine stores equally well. This indicated that St. Thomas' cardioplegia preserves myocardial catecholamine stores, depletion of which would remove a potentially important compensatory mechanism in cardiac pump failure. There may however be a temporary blockade in the release of endogenous cardiac catecholamine (noradrenaline) stores from the adrenergic nerve terminals following cold cardioplegic arrest despite myocardial pump failure.

Adult↗

The potential hazard of particulate contamination of cardioplegic solutions.

The potential hazard of particulate debris in unfiltered cardioplegic solutions was assessed using the isolated rat heart preparation. Five intravenous solutions were evaluated: These were manufactured by three pharmaceutical firms (two United States and one British) and are commonly used as bases for preparing clinical cardioplegic solutions. Particles were counted in each solution, and each fell well within the limits for particle contamination defined by both the United States and the British Pharmacopoeias. Intracoronary continuous infusion of each solution over 20 minutes at constant temperature and pressure (20 degrees C, 60 cm H2O) resulted in a progressive reduction in coronary flow (mean reduction 55.7% +/- 6.6%) due to a rise in coronary vascular resistance; filtration of these same solutions through a 0.8 micron filter just prior to their entry into the heart largely prevented these coronary vascular changes. The filter was examined by scanning electron microscopy and showed amorphous and crystalline debris. Nifedipine (0.1 mumol/L) added to the cardioplegic solution reduced by almost 50% the impairment in coronary flow seen in the unfiltered group. In more clinically relevant studies of 180 minutes of hypothermic (20 degrees C) ischemia using multidose cardioplegia (3 minutes every 30 minutes), hearts infused with filtered solution recovered almost 90% of their preischemic functional capacity. Hearts receiving identical but unfiltered solution, however, essentially failed to recover (p less than 0.001) and had significantly higher levels of creatine kinase leakage. These results suggest that commercially produced solutions conforming to limits of particulate contamination acceptable for intravenous administration may prove harmful if given unfiltered directly into coronary arteries, with the likely mechanism of action being particle-induced coronary vasoconstriction.

Animals↗

Creatine phosphate: an additive myocardial protective and antiarrhythmic agent in cardioplegia.

The potential for enhancing myocardial protection by adding high-energy phosphates to cardioplegic solutions was investigated in a rat heart model of cardiopulmonary bypass and ischemic arrest. Creatine phosphate (CP) was evaluated as an additive to the St. Thomas' Hospital cardioplegic solution. Dose-response studies (CP 0 to 50 mmol/L) revealed 10.0 mmol/L as the optimal concentration which improved recovery of aortic flow and cardiac output after a 40 minute period of normothermic (37 degrees C) ischemic arrest from 21.2% +/- 5.4% and 32.8% +/- 4.6% in the CP-free control group to 82.5% +/- 3.7% and 82.6% +/- 4.2% (p less than 0.001), respectively. Creatine kinase (CK) leakage was reduced by 68.7% (p less than 0.001) in the CP group. With hypothermic (20 degrees C) ischemia (240 minutes) and multidose (every 30 minutes) cardioplegia, recoveries of aortic flow and cardiac output were improved from 33.1% +/- 8.4% and 42.2% +/- 7.7% in the CP-free control group to 77.9% +/- 4.2% and 79.6% +/- 4.3% (p less than 0.001), respectively, in the drug group. In addition to improving function and decreasing CK release, CP reduced reperfusion arrhythmias, significantly decreasing the time between cross-clamp removal and return of regular rhythm and also completely obviating the need for electrical defibrillation. 51Chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), an extracellular space marker, was used to study the disappearance of CP from the cardioplegic solution during its stasis in the heart. Upon reperfusion, two thirds of the infused dose appeared unchanged in the coronary effluent; the remainder was either degraded or accumulated by the myocardium. Despite its alleged inability to enter the myocardial cell, exogenous CP exerts potent protective and antiarrhythmic effects when added to the St. Thomas' Hospital cardioplegic solution. Although the mechanism of action remains to be elucidated, it may involve binding or uptake of the drug.

Adenosine Triphosphate↗

Calcium and cardioplegia. The optimal calcium content for the St. Thomas' Hospital cardioplegic solution.

The relationship between the calcium content of the St. Thomas' Hospital cardioplegic solution and the degree of tissue protection it affords has been characterized by means of an isolated working rat heart preparation subjected to normothermic ischemic arrest. With a 3 minute period of preischemic infusion of solutions containing calcium chloride concentrations of 0, 0.6, 1.0, 1.1, 1.2, 1.3, 1.4, and 2.4 mmol/L and 35 minutes of normothermic ischemic arrest, postischemic creatine kinase leakage was 562.3 +/- 26.7, 64.8 +/- 12.1, 63.3 +/- 9.9, 37.5 +/- 5.4, 33.4 +/- 3.1, 41.2 +/- 4.1, 58.6 +/- 7.4, and 65.7 +/- 9.1 IU/15 min/gm dry weight, respectively. The postischemic recovery of aortic flow was 0%, 29.2% +/- 6.8%, 29.0% +/- 3.3%, 45.8% +/- 4.9%, 55.5% +/- 1.4%, 38.5% +/- 2.7%, 27.8% +/- 8.6%, and 19.5 +/- 7.1%, respectively. The results indicate optimal protection with a calcium concentration of 1.2 mmol/L and a rapid decline in protection with even small changes in concentration either side of the optimum. The hazard of total absence of calcium was confirmed by the induction of the calcium paradox. This study shows that under normothermic conditions a calcium concentration of 1.2 mmol/L is optimal for the St. Thomas' Hospital solution. This study reinforces the importance of undertaking dose-response studies for all components of all cardioplegic solutions.

Animals↗

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.

Biopsy↗

The effect of ionized calcium, pH, and temperature on bioactive parathyroid hormone during and after open-heart operations.

Normal myocardial function is dependent on the metabolic balance of a number of electrolytes and hormones. The calcium ion plays a major role in muscle contraction and is rigorously controlled within narrow limits. Open-heart surgery imposes metabolic disturbances on both electrolytes and hormones, especially ionized calcium. Normally, ionized calcium levels are controlled by parathyroid hormone with a negative feedback from the ionized calcium controlling the system, but the results from this study suggest that during open-heart procedures, ionized calcium does not impose its normal negative feedback on bioactive parathyroid hormone secretion. The low blood pH levels that occurred during the operative conditions of the patients studied and the level of hypothermia imposed on the circulating blood during cardiopulmonary bypass appeared to influence the control of parathyroid hormone secretion, causing high levels of hormone to be secreted during this period.

Adult↗

Clinical and quantitative birefringence assessment of 100 patients with aortic clamping periods in excess of 120 minutes after hypothermic cardioplegic arrest.

At St. Thomas' Hospital the first 100 patients with prolonged aortic cross-clamp times in excess of 120 minutes have been analyzed clinically (low cardiac output and mortality) and 49 of these patients from which left and right ventricular biopsies were taken, have been analyzed by quantitative birefringence (biophysical measurement of myocardial deterioration). A total of 8 patients died (8%) and 11 had low cardiac output syndrome (11%). The patients were divided into those given only a single infusion (n = 18) and those given hourly infusions (n = 82) of hypothermic cardioplegic solution. These were then subdivided into those with single (n = 37) or multiple (n = 63) corrective surgical procedures. In the patients who had a single corrective surgical procedure there was no difference at all, but in those patients who had multiple corrective surgical procedures, hourly infusion reduced low cardiac output from 12.5% to 9.4% in multiple valve patients and from 50% to 19% in bypass graft combined with valve replacement patients. In this latter group mortality fell from 50% to 4.8% but there were only 2 patients given a single infusion. There was no statistically significant advantage in hourly infusions compared with single infusions, either clinically or cytochemically. Twenty-six patients had aortic cross-clamp periods in excess of 150 minutes. Mortality and low cardiac output increased compared with the 120 to 150 minute group, rising from 3% to 19% and from 7% to 23% respectively. As a result of these analyses, surgical practice has been changed to 30-minute reinfusion intervals with currently improved results.

Birefringence↗

Calcium antagonists and myocardial protection: diltiazem during cardioplegic arrest.

Using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest, the effects of the addition of the calcium antagonist, diltiazem, to St. Thomas' cardioplegic solution were investigated. Under conditions of normothermic ischemic arrest (37 degrees C, 35 min), the addition of diltiazem improved the protective properties of the St. Thomas' cardioplegic solution. Moreover, studies with varying concentrations produced a bell-shaped dose-response curve for diltiazem with its optimal concentration at 0.5 mumoles/liter (0.21 mg/liter) when postischemic recovery of aortic flow was improved from 53.2 +/- 4.3% to 79.2 +/- 4.4% (p less than 0.01) and postischemic creatine kinase leakage was reduced by approximately 40%. Despite this marked additional protection when ischemic arrest was normothermic, diltiazem afforded no improvement in protection under conditions of hypothermic (20 degrees C, 180 min) ischemic arrest.

Animals↗