Measurement of pH in the heart

C-sodium acetate is produced by the reaction of the Grignard reagent, methylmagnesium bromide in diethyl ether, with cyclotron-produced nC-carbon dioxide at -15°C (Oberdorfer et al, 1996). After reaction, the product is allowed to react with O-phthaloyl dichloride to produce nC-acetyl chloride, which is then hydrolyzed to 11C-acetate with saline. The solution is filtered through a 0.22-pm membrane filter. 11C-acetate has been found to be stable at pH between 4.5 and 8.5 for up to 2 h at room temperature. The overall yield is about 10-50%. It is used for the measurement of oxygen consumption (oxidative metabolism) in the heart, since acetyl CoA synthetase converts 11C-acetate to acetyl coenzyme A after myocardial uptake, which is metabolized to 11C-C02 in the tricarboxylic acid cycle. 

Figure 2 Time course of changes in intracellular pH ( ), ATP(D) and PCr ( ) in a rat heart subjected to 25 min of total global ischaemia followed by 30 min of reperfusion. pH was determined from the chemical shift of Pj. Changes in ATP and PCr are expressed as percentage change from the basal levels measured prior to ischaemia. Total global ischaemia was achieved by stopping all flow of perfusate to the heart.

These early observations have evolved into the branch of chemistry called electrochemistry. This subject deals not only with the use of spontaneous chemical reactions to produce electricity but also with the use of electricity to drive non-spontaneous reactions forward. Electrochemistry also provides techniques for monitoring chemical reactions and measuring properties of solutions such as the pK, of an acid. Electrochemistry even allows us to monitor the activity of our brain and heart (perhaps while we are trying to master chemistry), the pH of our blood, and the presence of pollutants in our water supply. 

Furthermore, pH determination has been used in other clinical research, both alone and in combination with other measurements. This research includes studies into the relationship between extracellular and intracellular pH in an ischemic heart [6, 7], the pH of airway lining fluid in respiratory disease [8], the study of pH as a marker for pyloric stenosis [9], malnutrition in alkalotic peritoneal dialysis patients [10], pH modulation of heterosexual HIV transmission [11, 12], and wound prevention and treatment [13], In addition, pH changes due to blood acidosis have been used to trigger and pace the ventricular rate of an implanted cardiac pacemaker [14], Research using pH measurements... 

Simultaneous and continuous measurements of extracellular pH, potassium K+, and lactate in an ischemic heart were carried out to study lactic acid production, intracellular acidification, and cellular K+ loss and their quantitative relationships [6, 7], The pH sensor was fabricated on a flexible kapton substrate and the pH sensitive iridium oxide layer was electrodeposited on a planar platinum electrode. Antimony-based pH electrodes have also been used for the measurement of myocardial pH in addition to their application in esophageal acid reflux detection. 

Although P MRS can be used to measure pH in isolated, perfused hearts, it is not suitable in vivo because 2,3-diphosphoglycerate in ventricular blood interferes with the myocardial Pi resonance. Schroeder et al. have developed a possible alternative method for in vivo use based on the carbonic-anhydrase-catalyzed, pH-dependent equilibrium of CO2 and HCO3. Infusion of h)q)erpolarized 1- C-pyruvate generates strong signals of metabolically produced C02 and H COJ to yield pH by the Henderson-Hasselbalch equation. Applicability of the method in humans remains to be demonstrated. 

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